Australian baby’s head reattached to severed spinal cord in ‘miracle’ surgery .

Sixteen-month-old Jaxon Taylor is laughing, walking and playing again after just a few weeks after being internally decapitated.

In mid-September, Jaxon, his mother Rylea and nine-year-old sister Shayne were travelling on a highway to move into their new home in Queensland when a speeding car driven by a teen crashed into them.
“For a split second I saw dust and then the force hit,” Rylea wrote in a petition after the crash.

Shayne suffered a fractured vertebrae and had to undergo a three-and-a-half surgery to stop internal bleeding.

But when Rylea picked up her baby, she knew something was seriously wrong.

“The second I pulled him out, I knew that his neck was broken,” she told 7 News Australia.
His head had internally detached from the vertebrae of his spine.

Jaxon was airlifted to a Brisbane hospital where orthopedic surgeon Dr. Geoff Askin and his team performed a six-hour surgery on the baby.

A metal halo brace was attached to Jaxon’s skull and his vertebrae were reattached using a piece of wire, then grafted together with a piece of his rib.

Askin said it was one of the worst injuries he had ever seen and that most children would not have survived it.

“It is a miracle,” Rylea said.
Jaxon will have to wear his halo brace for two months, but is on the path to recovery.

Similar Nucleotide Excision Repair Capacity in Melanocytes and Melanoma Cells

Sunlight UV exposure produces DNA photoproducts in skin that are repaired solely by nucleotide excision repair in humans. A significant fraction of melanomas are thought to result from UV-induced DNA damage that escapes repair; however, little evidence is available about the functional capacity of normal human melanocytes, malignant melanoma cells, and metastatic melanoma cells to repair UV-induced photoproducts in DNA. In this study, we measured nucleotide excision repair in both normal melanocytes and a panel of melanoma cell lines. Our results show that in 11 of 12 melanoma cell lines tested, UV photoproduct repair occurred as efficiently as in primary melanocytes. Importantly, repair capacity was not affected by mutation in the N-RAS or B-RAF oncogenes, nor was a difference observed between a highly metastatic melanoma cell line (A375SM) or its parental line (A375P). Lastly, we found that although p53 status contributed to photoproduct removal efficiency, its role did not seem to be mediated by enhanced expression or activity of DNA binding protein DDB2. We concluded that melanoma cells retain capacity for nucleotide excision repair, the loss of which probably does not commonly contribute to melanoma progression. Cancer Res; 70(12); 4922–30. ©2010 AACR.


UV light from the sun causes a variety of lesions in the genome that distort the structure of DNA, resulting in blocks to gene transcription and DNA replication. Epidemiologic evidence strongly indicates that UV-induced DNA damage is a primary cause of skin cancer, including melanoma (1, 2), an aggressive form of skin cancer that arises from specialized pigmented cells called melanocytes. Although comprising only 5% to 10% of human skin, melanocytes synthesize the pigment melanin, which provides skin tone, hair color, and protection from UV radiation. The significant increase in melanoma cases in the past half-century and the poor survival rates among patients with metastatic melanoma (3, 4) therefore merit thorough investigations of the underlying causes of melanoma initiation and progression.

Among the lesions induced by UV, cyclobutane pyrimidine dimers (CPD; 80–90%) and [6-4] pyrimidine-pyrimidone photoproducts ([6-4] PP; 10–20%) are most abundant, although both can be accurately removed from the genome by nucleotide excision repair (henceforth termed “excision repair”). This well-characterized repair system responds to a variety of environmental and chemotherapeutic agents that form bulky adducts in DNA and, in humans, is the sole mechanism for removal of CPDs and [6-4] PPs from DNA (5). Importantly, reconstitution of excision repair in vitro with the six essential factors (XPA, RPA, XPC, TFIIH, XPG, and XPF-ERCC1) has provided a significant understanding of the individual steps of repair and allowed a clear determination of the minimal set of factors necessary and sufficient for the complete removal of UV photoproducts from DNA (6, 7). The importance of the excision repair system to human health is most obvious in xeroderma pigmentosum (XP), a disease in which most patients lack one of the essential excision repair factors (8). One consequence of this loss is a 2,000-fold higher incidence of metastatic melanoma compared with normal individuals (9).

Melanomas display complex genetic profiles but often show activating mutations in the oncogenes B-RAF (50–75%) and N-RAS (10–15%; refs. 10, 11), resulting in enhanced cell growth through signaling of the mitogenic extracellular signal-regulated kinase 1/2 pathway (12, 13). Similarly, although the tumor suppressor p53 is disrupted in nearly half of all cancers and is known to promote repair of UV photoproducts in many cell types (14), studies indicate that p53 mutations are rare in primary melanoma (<1%; ref. 15) but do increase in frequency in metastatic melanoma (5%; ref. 16). Although the p53 gene is not commonly altered in melanoma, disruption of the tumor suppressor ARF, which regulates p53 protein stability, is a common occurrence in metastatic melanoma through genetic deletion of the CDKN2A locus (1719). Therefore, alterations of p53-dependent pathways have the potential to influence melanoma progression.

In contrast, although there is some evidence linking a polymorphism in the excision repair gene XPD and susceptibility to cutaneous melanoma (20), there is little available data indicating that altered expression of excision repair genes contributes to melanoma, and indeed, a recent microarray analysis of mRNA expression profiles in metastatic melanomas did not find changes in excision repair genes (21). Although analyses of mRNA transcript and protein expression profiles have the potential to be informative, it may be more relevant to test for functional excision repair capacity to make proper correlations of DNA repair and carcinogenesis. Along these lines, although early work initially indicated that melanoma cells did not show enhanced repair rates (22), other work suggested that subclones of a metastatic melanoma line did indeed show elevated repair rates in comparison with nonmelanoma cells, and this repair correlated with increased survival after UV (23). An additional study similarly concluded that DNA repair capacity in mouse melanoma cell lines correlated with metastatic potential (24). However, more recent in situ work indicated that cutaneous melanoma patients show normal repair kinetics (25). It is therefore unclear whether excision repair capacity is altered in melanoma cells relative to normal melanocytes or whether genetic background (B-RAF/N-RAS/p53 status) or metastatic potential is directly correlated with excision repair capacity.

In this study, we used normal human melanocytes (NHM) and a variety of melanoma cell lines to characterize excision repair capacity as a function of genetic and metastatic states. Our results show that in nearly all melanoma cell lines tested, excision repair occurred as efficiently as in NHMs, irrespective of mutations in the N-RAS and B-RAF oncogenes. In addition, we found no change in excision repair capacity in a highly metastatic melanoma cell line (A375SM) compared with its parental melanoma cell line (A375P), which has a low metastatic potential. Lastly, we observed that melanoma cell lines containing functional p53 repair UV photoproducts more efficiently than lines with inactive p53 but that this difference seems to be not due to enhanced levels of the UV photoproduct binding protein DDB2.

Materials and Methods

Cell lines

Description of the sources, culture method, and UV irradiation of the melanoma cell lines is provided in Supplementary Table S1. All of the cell lines used in our study are authenticated by microarray analysis as described previously (13). Secondary cultures of NHMs were derived as reported previously (26). Briefly, these cells (NHM16 and NHM21) were grown in Medium 254 (Life Technologies) containing Human Melanocyte Growth Supplement (HMGS-1; Life Technologies) at 37°C in a cell culture incubator with 5% CO2. A375P and A375SM cell lines were a gift from Dr. Richard O. Hynes (Massachusetts Institute of Technology, Cambridge, MA).

UV irradiation

Culture medium was removed from exponentially growing cells and set aside, and then cells were washed once with warm PBS before placement under a GE germicidal lamp emitting primarily 254-nm UV light (UV-C) connected with a digital timer. After receiving the indicated dose of UV (typically 5–20 J/m2, as indicated), culture medium was added back to the cells, which were subsequently placed back into the cell culture incubator for the indicated length of time. A UV-C sensor (UV Products) was used to calibrate the fluence rate of the incident light.

Immunoslot blot assay for measurement of CPD and [6-4] PP repair in vivo

Repair of CPDs and [6-4] PPs by immunoslot blot was performed essentially as reported previously (27).

Fluorescence microscopy

Immunofluorescence microscopy was performed as described previously (28). Briefly, cells were cultured in 35-mm glass-bottom dishes (MatTek) for 24 hours before UV irradiation (10 J/m2). Cells harvested at various time points after irradiation were fixed with 4% formalin and further treated with ice-cold detergent (0.5% Triton X-100) for 5 minutes. After denaturation of DNA with 2 mol/L HCl for 30 minutes at room temperature, CPDs were detected with the mouse monoclonal anti-CPD antibody (Kamiya Biomedical) and Alexa Fluor 488 goat anti-mouse IgG conjugate (Invitrogen). Nuclear DNA was counterstained with propidium iodide, and CPD signals were observed with a Leica inverted DMIRB fluorescence microscope.

Measurement of [6-4] PP repair activity in cell-free extracts

Preparation of radiolabeled substrate and the in vitro excision repair assay was essentially as previously described (27, 29). Cell-free extracts for use in the excision assay were prepared as reported (30).

Immunoblot analyses

Protein lysates from exponentially growing cultures of cells were harvested and analyzed by SDS-PAGE and immunoblotting as described elsewhere (26). The following antibodies were used to detect the respective proteins: XPA, XPC, RPA70, TFIIH (p62 subunit, XPB), p53, and actin (Santa Cruz Biotechnology); p21, DDB2, and GAPDH (Cell Signaling Technology, Inc.); RPA34 (Calbiochem); and XPF and XPG (Abcam).

siRNA transfection

Exponentially growing cells of SK-Mel-103 or SK-Mel-187 were transfected with either p53 siRNA (Santa Cruz Biotechnology) or nontargeting siRNA (Dharmacon) using Lipofectamine RNAiMAX (Invitrogen) transfection reagent. Cells were UV irradiated 48 hours after transfection and then harvested at the indicated time points to assay for CPD repair.

Electrophoretic mobility shift assay for UV-DDB binding activity

UV-DDB binding activity was performed using cell-free extracts from both SK-Mel-103 and SK-Mel-187 cell lines as reported previously (3033). Briefly, 5 fmol of 136-bp dsDNA containing a [6-4] PP were incubated with the indicated amount of proteins or cell-free extract in 12.5 μL of reaction mixtures. After a 30-minute incubation at 30°C, glycerol was added to ∼8%, and reaction mixtures were resolved using 5% native PAGE at room temperature with a constant current (25 mA). DNA binding was visualized by autoradiography and quantified using ImageQuant 5.2 software (Molecular Dynamics). Recombinant UV-DDB protein was used as a positive control for DDB binding activity (31).

Matrigel invasion assay

Cellular invasion assays were performed using 8.0-μm pore size Biocoat Matrigel Invasion chambers (BD Biosciences) as described by the manufacturer. Each data point represents the average of three independent experiments and error bars represent the SD of the mean.


Measurement of [6-4] PP repair in vitro

Epidemiologic evidence suggests a strong correlation between exposure to UV from the sun and development of melanoma in humans (22, 34, 35), and we therefore sought to investigate whether the capacity to repair UV photoproducts differed between NHMs and melanoma cell lines. Our initial approach used an in vitro, cell-free excision assay to measure excision repair. Our laboratory has used this assay extensively to study the mechanism of nucleotide excision repair and to measure repair capacity in mammalian cell lines and tissues (29, 36). The assay involves incubation of an internally 32P-labeled oligonucleotide containing a site-specific [6-4] PP in cell-free extract and then electrophoresis of the purified DNA on a denaturing gel, which allows visualization and quantitation of the small 24- to 32-nucleotide oligomers that are generated during the repair reaction (Fig. 1A). Although the assay has been used with extracts from a variety of mammalian cell types and tissues, it has not previously been applied to measure repair in melanocytes or melanoma cells, a physiologically relevant and medically important target of UV-induced DNA damage.

Figure 1.

[6-4] PP repair in cell-free extracts. A, schematic of the in vitro excision assay. An internally 32P-labeled (black square), 136-bp dsDNA containing a centrally located [6-4] PP (gray triangle) is incubated with cell-free extract for 90 min. The damaged DNA is removed through dual incisions of the DNA at sites bracketing the lesion, resulting in release of 24- to 32-nucleotide-long oligomers (excised products) that are visualized by denaturing PAGE and phosphorimager analysis. B, excision repair in cell-free extracts. Cell lines examined included two NHM lines and two cell lines each that lack (WT) or contain mutations in either N-RAS or B-RAF. C, quantitative analyses of excision repair in cell-free extracts. The percent of total radiolabeled material released as excision products represents the amount of excision repair (% excision). Excision assays were performed thrice with three independent preparations of cell-free extract for each cell line. Columns, average from these assays; bars, SD.

Our initial studies focused on two NHM lines (NHM16 and NHM21) and two cell lines each from melanoma cells containing normal or mutant forms of the B-RAF and N-RAS oncogenes [wild-type (WT): SK-Mel-187 and RPMI8322; N-RAS: SK-Mel-103 and VMM39; B-RAF: A2058 and A375]. Using cell-free extracts prepared from the indicated cell lines, we observed variable amounts of [6-4] PP removal among the different melanoma lines (Fig. 1B), ranging from ∼1% in the RPMI8332 line and up to ∼12.5% in A375 cells (Fig. 1C). This variation is consistent with previous reports showing that human melanomas show a high degree of interindividual variability in excision repair in situ (25). Importantly, immunoblot analyses of these extracts showed no clear correlation between excision repair capacity and expression level of any specific excision repair protein (Supplementary Fig. S1).

Interestingly, we observed very little excision activity in the extracts from the NHMs. To better understand this lack of excision repair activity with this assay, we supplemented extracts from excision-competent A375 and Chinese hamster ovary (CHO) cells, which do not contain detectable level of melanin (Supplementary Table S2), with either NHM16 or NHM21 extract. As shown in Supplementary Fig. S2A, both NHM extracts inhibited the excision activity of A375 and CHO extracts, indicating the presence of an inhibitory factor in the NHM extract. We considered that the presence of melanin in the NHM extracts might interfere with the in vitro excision activity. To test for the effect of melanin, we titrated CHO cell-free extract with increasing amounts of synthetic melanin and observed a concentration-dependent inhibition of excision repair (Supplementary Fig. S2B). This inhibition was not specific to excision repair, however, as the ability of restriction enzymes to digest the substrate was also inhibited by melanin (Supplementary Fig. S2C), indicating that melanin may nonspecifically bind to DNA and inhibit the action of multiple nucleases. We conclude, however, that although the excision assay is a convenient and reliable tool for measuring repair capacity in many cell lines, including melanoma cells, it cannot be used for all cell types, such as melanocytes.

Measurement of [6-4] PP repair in vivo

We next used an immunoslot blot assay to monitor removal of [6-4] PPs in NHMs and melanoma cell lines. This assay involves the immobilization of genomic DNA from cells at various times after UV irradiation onto a nitrocellulose membrane and then immunoblotting with antibodies that specifically recognize either CPDs or [6-4] PPs (37). As shown in Fig. 2A, we observed a time-dependent reduction in anti–[6-4] PP antibody reactivity in genomic DNA from both the NHMs and the melanoma cell lines, at rates near those previously reported for other cell types (38), with typically 50% to 80% of [6-4] PPs removed within 2 hours in the various cell lines (Fig. 2B). Importantly, we observed very similar [6-4] PP signals in the UV-irradiated melanocytes and melanoma cells before repair, indicating that similar numbers of photoproducts were induced by UV. Cell lines lacking or containing mutations in the B-RAFand N-RAS oncogenes repaired [6-4] PPs at similar rates, indicating that mutation of these oncogenes does not significantly affect excision repair. Interestingly, when we compared the relative amount of [6-4] PP repair in the immunoslot blot assay (Fig. 2A and B) with repair in the in vitro excision assay (Fig. 1) among the six melanoma cell lines tested, we observed a strong correlation (R2 = 0.91) between the two assays (Fig. 2C), indicating that the two approaches are reliable measures of [6-4] PP repair capacity.

Figure 2.

Immunoslot blot assay for [6-4] PP repair. A, an immunoslot blot assay was used to measure [6-4] PP repair at various time points after irradiation in NHMs and melanoma cell lines exposed to 10 J/m2 of UV-C. The image shows the [6-4] PP signal detected with an anti–[6-4] PP antibody and SYBR Gold staining to show equal loading of total genomic DNA. B, quantitative analysis of the repair assay. Points, average from two independent experiments; bars, SD. C, correlation between [6-4] PP repair levels using the immunoslot blot and in vitrocell-free excision assays. For each of the six melanoma cell lines examined, the level of [6-4] PP repair as measured at the 2-h time point by immunoslot blot assay (in vivo repair) was plotted along with the amount of [6-4] PP substrate repaired for 90 min in the excision assay inFig. 1 (in vitro repair).

Measurement of CPD repair in vivo

We next measured CPD repair in the same set of cell lines. CPDs constitute the majority of UV photoproducts in DNA and are recognized and repaired by the excision repair machinery more slowly than for [6-4] PPs and inefficiently in the in vitro excision assay, making quantitative comparison of CPD repair with the excision assay difficult. Therefore, we solely relied on the slot blot assay for in vivo repair. As displayed and quantified in Fig. 3A, with the exception of RPMI8332 cells, which repaired CPDs very inefficiently, all the other cell lines removed 40% to 80% of CPDs within 12 hours. Importantly, the two NHM lines showed very similar CPD repair kinetics with three of these melanoma lines, indicating that melanocytes and melanoma cells repair UV photoproducts with similar kinetics. The RPMI8332 melanoma line, which repaired [6-4] PPs least efficiently in both the in vitro excision assay (Fig. 1) and thein vivo slot blot assay (Fig. 2), seemed to lack any CPD repair capacity, with only ∼4% of CPDs removed within 12 hours (Fig. 3A). To confirm this inefficient repair phenotype, we used immunofluorescence microscopy to detect CPD formation and removal in the repair-deficient RPMI8332 line and the repair-proficient line SK-Mel-187. Very little CPD removal was observed in RPMI8332 cells by immunofluorescence (Fig. 3B), consistent with the results of the immunoslot blot assay.

Figure 3.

CPD repair in melanocytes and melanoma cell lines. A, cells were exposed to UV-C (10 J/m2) and harvested at the indicated time points for immunoslot blot analysis of CPD repair. The top image shows a representative experiment. CPD repair assays were performed thrice for each cell line. Points, average CPD repair; bars, SD. B, immunofluorescence analyses of CPD repair in SK-Mel-187 and RPMI8332 cells. C, CPD repair in six additional melanoma cell lines with WT N-Ras and B-Raf. The graph (bottom) includes SK-Mel-187 and RPMI cells analyzed in A.

Because we observed a significant difference in CPD repair in RPMI8332 and SK-Mel-187 cells, both of which are WT for both B-RAF and N-RAS, we decided to measure CPD removal in six additional melanoma lines with WT forms of these genes. As shown in Fig. 3C, all six lines displayed CPD removal rates comparable with SK-Mel-187 and the other cell lines and were unlike that seen in the RPMI8332 cells. Although the cause of the inefficient CPD and [6-4] PP removal in RPMI8332 cells is not known, we conclude that the repair deficiency is not characteristic of melanoma cells that are WT for both B-Raf and N-Ras. Interestingly, RPMI8332 cells were also significantly more sensitive to UV than the other cell lines in a colony formation assay (Supplementary Fig. S3). This line has high level of chromosomal instability and some unusual growth properties as the cells undergo massive cell death on reaching confluency, suggesting that inefficient repair is secondary to gross dysregulation of many pathways.

p53 contributes to CPD repair efficiency in melanoma cells

Although the tumor suppressor p53 has been shown to contribute to CPD repair rates and UV survival in human skin fibroblasts and other cell types (14, 38), other work has indicated no effect of p53 deficiency on UV photoproduct repair in keratinocytes (39). We therefore sought to examine p53 functionality in normal melanocytes and melanoma cell lines to determine whether p53 status may influence CPD repair in melanoma. Because p53 mutation status has only been characterized in a subset of these lines (13, 40), we tested p53 functionality by immunoblotting extracts from nonirradiated or UV-irradiated cells for UV-induced expression of p53 and its transactivation targets p21 and DDB2. As shown in Fig. 4A, p53 functionality varied among the different cell lines but exhibited normal responses in the normal melanocytes and in four of the melanoma lines (SK-Mel-103, A375, SK-Mel-5, and Mel-537). With this information, we then reexamined the CPD repair data for the melanoma cell lines presented in Fig. 3 by combining the repair data among the cell lines based on p53 status. Interestingly, we observed significantly more CPD repair in cells with WT, functional p53 compared with cells with mutant or inactive p53 (Fig. 4B). Although less pronounced, [6-4] PP repair also correlated with p53 functionality (Supplementary Fig. S4). To confirm the positive role for p53 in excision repair, we transfected p53-positive SK-Mel-103 and p53-inactive SK-Mel-187 cells with either a nontargeting control siRNA or a siRNA targeting p53 and then measured CPD repair. Consistent with the pooled cell line data shown in Fig. 4B, knockdown of p53 in SK-Mel-103 cells, which did not have measurable effect on DDB2 level (Supplementary Fig. S5), resulted in less CPD removal near the level observed in p53-inactive SK-Mel-187 cells (Fig. 4C). Based on these results, we conclude that p53 contributes to UV photoproduct removal in human melanoma cell lines.

Figure 4.

Analysis of p53 and DDB2 functionality and in melanoma cells and melanocytes. A, Western blot analyses were performed with extracts from the indicated cell lines harvested at various times after UV irradiation (12.5 J/m2) to monitor p53 functionality, as determined by induction of p21 and DDB2 protein expression. B, based on p53 functionality determined in A, CPD repair measurements for the individual cell lines (Fig. 3) were pooled and reanalyzed as a function of p53 status. Columns, average of CPD repair for the seven p53 mutant cell lines (RPMI was excluded) and four p53 WT cell lines; bars, SD. Asterisks indicate a statistically significant difference (P < 0.01, two-tailed Student’s t test) in CPD repair between p53 mutant and WT cell lines. C, knockdown of p53 in SK-Mel-103 cells inhibits CPD repair. SK-Mel-103 (p53 WT) and SK-Mel-187 (p53 mutant) cells were transfected with nontargeting or p53 siRNAs and exposed to UV, and CPD repair was measured at the indicated time points. D, electrophoretic mobility shift assay of UV-DDB binding to damaged DNA. Cell-free extract from SK-Mel-103 (p53 WT) and SK-Mel-187 (p53 mutant) cells was incubated with radiolabeled [6-4] PP substrate DNA, and complexes were separated on a 5% nondenaturing gel. Purified UV-DDB complex was used as a positive control and CHO-AA8 extract as a negative control. The cell-free extract protein concentrations ranged from 0.5, 1.0, 2.0, or 4.0 μg per reaction. The experiment was repeated thrice, and the average percent binding is indicated.

A role for p53 in excision repair has been reported to be due to transcriptional induction of the XPE gene encoding the DDB2 protein (41), which in the form of UV-DDB (DDB1-DDB2 heterodimer) directly binds to UV photoproducts. We therefore used an electrophoretic mobility shift assay (32, 33) to examine UV-DDB functionality in SK-Mel-103 and SK-Mel-187 cell extracts. As shown in Fig. 4D, we observed similar levels of binding to an oligonucleotide containing a [6-4] PP in both extracts, but not in extract from CHO cells, in which the XPE (DDB2) gene is transcriptionally repressed (14). The levels of UV-DDB activities in SK-Mel-103 and SK-Mel-187 were similar 6 hours after UV but slightly higher in SK-Mel-103 24 hours after UV (Supplementary Fig. S6), by which time all of the CPDs were removed in both cell lines. Thus, we conclude that although p53 contributes to the removal of UV lesions in DNA, UV-DDB does not seem to be a major contributor through which p53 promotes repair in melanoma cells.

Excision repair in highly metastatic melanoma cells

We next wished to address whether metastatic state in melanoma contributes to the efficiency of nucleotide excision repair because a previous report indicated that UV photoproduct removal occurred more rapidly in highly metastatic murine melanoma cells (24). However, because the repair assay used in that study did not directly measure repair of UV-damaged genomic DNA, we reexamined whether excision repair capacity is altered in melanoma cells of different metastatic states by comparing [6-4] PP and CPD removal in A375 cells and a derivative line with a higher metastatic potential (A375SM). As previously reported (42), we confirmed that A375SM cells are more invasive than its parental A375 line (A375P; Fig. 5A). We then examined the protein expression levels of excision repair factors and found no significant difference between the two lines (Fig. 5B). Consistent with the similar expression levels, both A375P and A375SM cells repaired [6-4] PPs and CPDs at similar rates (Fig. 5C). We conclude from these results that metastatic state does not necessarily alter nucleotide excision repair capacity in melanoma cell lines.

Figure 5.

Excision repair in highly metastatic melanoma cells. A, Matrigel invasion assay of the highly metastatic cell line (A375SM) compared with its parent cell line (A375P). Columns, average of three independent experiments; bars, SD. B, Western blot analyses of the DNA excision repair protein levels of both A375P and A375SM cell lines. C, immunoslot blot analysis of CPD and [6-4] PP repair after UV irradiation (10 J/m2) of A375P and A375SM cells. Points, average from two independent experiments; bars, SD.


Melanoma is the most deadly form of skin cancer and in industrialized countries is rapidly growing in prevalence (43). Based on the high rates of melanoma in patients with XP, most of whom lack one of the essential excision repair factors, the development or progression of melanoma may be associated with a reduced capacity for excision repair. However, here, we show that excision repair capacity in NHMs is very similar to that in melanoma cells (Figs. 2 and 3), irrespective of B-RAF and N-RAS status, suggesting that altered repair capacity may not be a predominant cause of melanoma initiation or progression.

Tumors from metastatic melanoma patients are characterized by significant resistance to DNA-damaging agents, such as cisplatin, decarbazine, and melphalan (23), suggesting a broad underlying resistance to the effects of DNA damage. Although one report indicated that mouse melanoma cells with high metastatic potential exhibited elevated excision repair capacity (24), the study used an indirect measure of DNA repair. By monitoring the direct removal of CPDs and [6-4] PPs from genomic DNA in human A375 cells and a supermetastatic derivative cell line (A375SM), here, we observed no difference in nucleotide excision repair efficiency (Fig. 5). We conclude that metastatic potential and excision repair capacity are not directly related to one another.

In contrast, our results do show that the functionality of the tumor suppressor p53 is an important determinant of UV photoproduct repair efficiency in melanoma cells (Fig. 4; Table 1). These results are consistent with a variety of data from other cell types, including normal human fibroblasts (38, 39), although, importantly, our results provide the first evidence that p53 status affects excision repair specifically in melanoma cells. Although only 1% of primary melanomas and 5% of metastatic melanomas show mutations in the p53 gene (15, 16,44), the common loss of ARF function in metastatic melanomas with deletion of the CDKN2A locus (1719) suggests that p53-dependent processes may contribute to melanoma development. Because p53 regulates many components of the cellular response to DNA damage induced by UV irradiation, including DNA repair, cell cycle checkpoint, and apoptosis, it is not clear how its many diverse functions ultimately control cell fate in melanoma. Similarly, although our data do not indicate that p53 regulation of DDB2 influences excision repair in melanoma cells, DDB2 may contribute to other aspects of the UV response in melanocytes or melanoma, such as cell survival and apoptosis (45, 46).

Table 1.

Summary of N-Ras, B-Raf, and p53 status and excision repair capacity in 12 melanoma cell lines and 2 NHM lines used in our study

Inefficient UV photoproduct repair has also been shown in cells with mutations in the melanocortin 1 receptor (MC1R), which acts upstream in the microphthalmia-associated transcription factor (MITF) signaling pathway of eumelanin biosynthesis (47), and in cells with deletion of the CDKN2A locus that encodes the tumor suppressor genes p16 and ARF (48). Although the repair-deficient RPMI8332 cell line shows reduced expression of MITF and loss of p16, many of the other melanoma cell lines we examined also show reduced MITF levels (Mel505, SK-Mel-187, and PMWK) or p16 loss (SK-Mel-103; refs. 13, 26), indicating that other factors are responsible for the lack of excision repair in RPMI8332 cells.

In summary, 11 of 12 melanoma cell lines displayed normal rates of repair of UV-induced DNA photoproducts in comparison with normal melanocytes, indicating that functional inactivation of the excision repair pathway is uncommon in sporadic melanoma.

First-borns likely to be short-sighted because parents make them study harder.

But a new study by UK researchers suggests the weight of parental expectation on first-borns is harming eyesight

A little girl does her homework at a desk

First borns are more likely to be short-sighted because they are kept indoors to study

First-born children are more likely to be short sighted because their parents force them to study more, research has suggested.

Order of birth has long been seen as crucial to personality, with the oldest child often growing up to be more conservative, academic and law-abiding than their more reckless young siblings.

But a new study by Cardiff University suggests that the weight of parental expectation on first-borns is also having a grave impact on eye health. Older children are 10 per cent more likely to be short sighted, and 20 per cent more likely to be severely short-sighted than younger brothers and sisters.

Scientists suggest that over-anxious parents who keep their children indoors, hunched over text books are to blame for the problems.

Short-sightedness, or myopia, is increasing in prevalence in younger generations because children do not play outside as much as previous generations.

“Greater educational exposure in earlier-born children may expose them to a more myopiagenic (factors causing myopia) environment, for example, more time doing near work and less time spent outdoors,” said lead author Dr Jeremy Guggenheim

“Reduced parental investment in children’s education for offspring of later birth order contributed to the observed birth order vs myopia association.”

kid with glassesThe number of children with myopia is rising

Researchers looked at nearly 90,000 people between 40 and 69 years old and cross-referenced their birth order with their eyesight.

They found that those who were first born were far more likely to suffer eye problems. But the correlation disappeared when academic achievement was taken into account. For example, if all children attained the same results their eyesight was similar, suggesting that the differences was linked to studying.

In people with myopia, the typically spherical eyeball becomes elongated, resembling the shape of a grape or an olive.

In April, a study published by Ulster University found that the rate of short-sightedness in Britain has doubled over the past 50 years, because children no longer spend enough time outdoors.

Twenty-three per cent of British 12 and 13-year-olds now suffer from myopia which causes distant objects to appear blurred, while close objects can be seen clearly – compared to 10 per cent in the 1960s.

Trust found children today spend fewer than ten per cent of their playtime in wild placesChildren need to spend time outside to protect their vision  Photo: Alamy

Experts have recently called on schools to begin teaching children outdoors to save their vision.

The problem is so bad in China that the Beijing Institute of Ophthalmology, have been trialling glass box school classrooms.

Previous studies have shown that hunter gatherer societies which live mainly outdoors, such as tribes in Gabon, were found to have the smallest levels of myopia, just one in 200 members suffering from the condition.

Previous studies have shown that first-borns are often thirsty for approval after having the exclusive attention of their parents interrupted by a new baby. They also have better language skills because of the focussed attention before a new sibling arrives and do better in school.

In contrast middle born children are likely to be creative, sporty and unconventional. They are also likely to be the first to leave home. The last born are creative, rebellious and outgoing, while only children tend to be perfectionists.

The world’s on track to get 26% of its power from renewables by 2020.

It’s no secret that renewable energy sources such as solar and wind are getting cheaper and more efficient by the day, and as a result, countries around the world are increasingly beginning to embrace the technology. In fact, there’s now more capacity for renewable energy being added each year than coal, natural gas, and oil combined, which is a really huge deal.

Even better, a new report by the International Energy Agency (IEA) suggests that this trend isn’t going to slow down any time soon. Taking into account projections for the global economy, energy market and fossil fuel prices over the next five years, the study predicts that the planet will get 26 percent – more than a quarter! – of its energy from renewable sources by 2020.

At the moment, the planet gets around 22 percent of its energy from clean sources, predominantly solar, hydro and wind energy. So getting up to just over a quarter isn’t a huge leap in the grand scheme of things, but the IEA calls it “a remarkable shift in a very limited period of time”. And if nothing else, it’s proof that incentives to install renewable energy around the world are working.

The prediction is based on the assumption that the world will add 700 gigagwatts – which is a billion watts – of renewable energy capacity by the end of the decade. To put that into perspective, the IEA notes: “By 2020, the amount of global electricity generation coming from renewable energy will be higher than today’s combined electricity demand of China, India and Brazil.” It’s also enough energy to power the entire nation of Japan twice over.

The agency came up with this figure after studying the trends over the past decade, and then closely monitoring future expectations, as well as already proposed renewable installations.


And just in case you were wondering, the IEA – which was formed after the 1973 oil crisis to offer independent advice to governments – is known for being conservative, so it’s highly unlikely that these predictions are inflated.

The new renewable energy will make up more two thirds of all new additions to the world’s generation capacity, which means that fossil fuels are slowly dying out. Finally.

Even in the US, which has been notoriously slow to get behind renewables, the writing’s on the wall. Brian Merchant reports for Motherboard that 40 percent of the coal plants that were running in the US five years ago have now been closed down. And countries like Sweden are moving towards weaning themselves off fossil fuels entirely.


But despite the progress, there’s still a long way to go before we’ve added enough renewable energy to mitigate the effects of climate change. Getting a quarter of our energy needs from renewables is great, but that still means 75 percent of our electricity will come from burning fossil fuels and releasing CO2.

Scientists have shown that we have the potential and the technology to reach close to 100 percent reliance on renewable energy by 2050 if we made some huge policy changes worldwide. But as the IEA projections show, even though our renewable capacity is rapidly increasing, it’s not growing fast enough just yet to reach that goal.

“Renewables are poised to seize the crucial top spot in global power supply growth, but this is hardly time for complacency,” IEA Executive Director Fatih Birol said at a press conference. “Governments must remove the question marks over renewables if these technologies are to achieve their full potential, and put our energy system on a more secure, sustainable path.”

Futuristic Device Fixes Holes In The Heart Without Invasive Surgery

Scientists in Boston have come up with an ingenious new way to repair life-threatening holes in patients’ hearts and other organs.

Instead of invasive surgery and the risk that entails, the new technique makes use of an ultraviolet-light-enabled catheter that patches the holes using a plug made of abiodegradable, light-activated adhesive . The experimental device may prove useful in fixing stomach ulcers and abdominal hernias as well as hearts.

“Currently, to repair wounds or holes in the body, a second large hole made by incision must be created in order to give clinicians access to the affected area for suturing,” Conor Walsh, a Wyss Institute Core Faculty member and assistant professor at Harvard University’s John A. Paulson School of Engineering and Applied Sciences (SEAS), who co-authored a paper describing the research, told The Huffington Post in an email.

With the new device, a tissue patch can be delivered and adhered to the area in a minimally invasive manner — either through the original wound opening itself or through another small incision depending on the location in the body,” he said. “This can all be done within a matter of minutes — it is certainly our goal and belief that this could revolutionize wound repair.”

The device is snaked into the body via a vein into the hole in the heart or other body part to be repaired. The device deploys the patch at just the right spot, and then two balloon-like chambers — one positioned on either side of the hole — are inflated to keep the patch in place.

Then the catheter emits UV light that causes the biodegradable patch to harden and form a tight seal with body tissues. Just check out the GIF below.

“The catheter can be removed, leaving only the adhesive and patch behind,” Ellen Roche, a scientist at Harvard University’s SEAS and Wyss Institute and co-author of the paper, told The Huffington Post in an email. “These act as a bridge for tissue ingrowth, and will eventually disappear once the defect has healed.”

In other words, since the patch and adhesive are biodegradable, they dissolve into the body as the tissue heals. The researchers plan additional study to fine-tune the rate at which the patch degrades, New Scientist reported.

The patch hasn’t been tried on humans, but the scientists have successfully tested it on rat tissue and in the hearts of living pigs.

“Although the catheter is in early research stages, it represents a step along the translational path to closing tissue defects less invasively,” Roche said.

Microsoft’s new smart battery ‘learns’ how to last longer based on your activity.

It knows when you need power and when you don’t.

Our computers and mobile devices are getting noticeably faster and more sophisticated with the passing of every year, but the same can’t be said for the batteries that power them. You’d be hard-pressed to find anyone who’s particularly happy about the life of their iPhone battery, and who among us can say you don’t wish your laptop could stay unplugged for just a little longer between charge cycles?

The fact is it’s taken more than a decade to double the performance of our batteries, and researchers at Microsoft say it’s time to tackle the problem from a completely different angle – instead of trying to squeeze a bunch of conflicting properties into one battery, they’re developing an entire system of batteries that combines different types of batteries for a more ‘personalised’ charge.

“No single battery type can deliver the ever-growing list of requirements of modern devices: fast charging, high capacity, low cost, less volume, light in weight, less heating, better longevity, and high peak discharge rates,” they write in the Journal of the ACM.

“A growing range of battery chemistries are under development, each of which delivers a different set of benefits in terms of performance. We believe that combining multiple of these heterogeneous batteries instead of using a single battery chemistry can allow a mobile system to dynamically trade between their capabilities and thereby offer attractive tradeoffs.”

Named the Software Defined Battery (SDB), the system would work by having the hardware control the amount of that power that passes in and out of each battery via what the team describes as “smart switching circuitry”. Figuring out how much power to draw from each battery, and how to recharge each battery, lies with the SDB software that runs through the computer’s operating system.

That’s where the system starts to get really clever – the team proposes that this software would track how an individual uses their laptop day-to-day, so it can anticipate periods of high and low power usage. This means each battery can be optimised for the specific task it’s been designed to perform by going into stand-by when it’s not needed so it’s fully charged and ready to go when it is.

smart-battery-iconAnirudh Badam et al.

For example, if you typically just run a word processing program and Internet browser on your laptop during the day and spend the night doing something more demanding, such as video editing or gaming, the SDB would learn that during the day it needs to conserve charge on the battery in the system that’s best at handling a high workload.

“The algorithms implemented by this software use various metrics for increasing the single charge-discharge duration of the device, and the longevity of the batteries, and thereby decide the ratios in which to discharge each battery, and the ratios in which to charge them,” the researchers explain.

They envisage the battery system to be suited to everything from long-lived wearable devices and computer ‘turbo modes’ to 2-in-1 laptops with detachable keyboards, claiming the efficiency of the latter could be improved by 22 percent.

The system is just a concept at this stage, but it’s an intriguing glimpse into how we might solve the rather significant problem we have with batteries right now. Because why have one battery working for you, when you can have an entire team?

New method facilitates research on fuel cell catalysts.

Faster design -- better catalysts
The different number of similar neighbors has an important influence on the catalytic activity of surface atoms of a nanoparticle. Scientists from the Technical University of Munich and the Ruhr University Bochum (Germany), the Ecole normale superieure (ENS) de Lyon, Centre national de la recherche scientifique (CNRS), Universite Claude Bernard Lyon 1 (France) and Leiden University (Netherlands) developed a new method which elegantly correlates geometric and adsorption properties of catalysts. 

While the cleaning of car exhausts is among the best known applications of catalytic processes, it is only the tip of the iceberg. Practically the entire chemical industry relies on catalytic reactions. Therefore, catalyst design plays a key role in improving these processes. An international team of scientists has now developed a concept, that elegantly correlates geometric and adsorption properties. They validated their approach by designing a new platinum-based catalyst for fuel cell applications.

Hydrogen would be an ideal energy carrier: Surplus wind power could split water into its elements. The hydrogen could power fuel cell-driven electric cars with great efficiency. While the only exhaust would be water, the range could be as usual. But are still a rare exception. The required platinum (Pt) is extremely expensive and the world’s annual output would not suffice for all cars.

A key component of the fuel cell is the that is used to reduce oxygen. It is well known that not the entire surface but only a few particularly exposed areas of the platinum, the so-called active centers, are catalytically active.

A team of scientists from the Technical University of Munich and the Ruhr University Bochum (Germany), the Ecole normale superieure (ENS) de Lyon, Centre national de la recherche scientifique (CNRS), Universite Claude Bernard Lyon 1 (France) and Leiden University (Netherlands) have set out to determine what constitutes an active center.

Studying the model

A common method used in developing catalysts and in modeling the processes that take place on their surfaces is computer simulation. But as the number of atoms increases, quantum chemical calculations quickly become extremely complex.

Faster design -- better catalysts
Not the complete platinum surface is catalytically active, but only some especially exposed areas, so-called active centers. Measurement of a platinum electrode with a hanging meniscus configuration. 

With their new methodology called “coordination-activity plots” the research team presents an alternative solution that elegantly correlates geometric and adsorption properties. It is based on the “generalized coordination number” (GCN), which counts the immediate neighbors of an atom and the coordination numbers of its neighbors.

Calculated with the new approach, a typical Pt (111) surface has a GCN value of 7.5. According to the coordination-activity plot, the optimal catalyst should, however, achieve a value of 8.3. The required larger number of neighbors can be obtained by inducing atomic-size cavities into the platinum surface, for example.

Successful practical test

In order to validate the accuracy of their new methodology, the researchers computationally designed a new type of platinum catalyst for applications. The model catalysts were prepared experimentally using three different synthesis methods. In all three cases, the catalysts showed up to three and a half times greater catalytic activity.

“This work opens up an entirely new way for catalyst development: the design of materials based on geometric rationales which are more insightful than their energetic equivalents,” says Federico Calle-Vallejo. “Another advantage of the method is that it is based clearly on one of the basic principles of chemistry: coordination numbers. This significantly facilitates the experimental implementation of computational designs.”

“With this knowledge, we might be able to develop nanoparticles that contain significantly less platinum or even include other catalytically active metals,” says Professor Aliaksandr S. Bandarenka, tenure track professor at Technical University of Munich. “And in future we might be able to extend our method to other catalysts and processes, as well.”

How DNA Database Statistics Can Lead To Questionable Convictions.

The “match statistics” generated by analyzing large troves of DNA information are easy to misinterpret.
In 2001, an analyst in the DNA unit of Arizona’s state crime laboratory noticed something interesting. Two seemingly unrelated individuals—one white and one black—shared the same two markers at nine of the 13 places in the standard DNA profile. Yet that particular genetic profile should have been exceedingly rare.

According to the standard method of computing how often one might expect to encounter a particular DNA profile in the population at large—what is known as the “random match probability”—if you plucked a non-Hispanic white person at random from the population, there would be only a 1 in 754 million chance of finding that profile. For African Americans, the number was 1 in 561 billion. And yet here, in a database of less than 100,000 people, it was appearing twice—and in people of different races.

The DNA-unit analyst wrote up a quick summary of her findings and submitted the results to a major international forensic-DNA conference. Her observations came to the attention of a public defender in San Francisco, who held a master’s degree in genetics and was in midst of defending a California man, John Puckett, accused of a rape and murder from decades earlier. Police had collected forensic evidence in 1972, when a nurse was found sexually assaulted and fatally stabbed, but DNA typing was still decades away. The case sat open until, more than 30 years later, investigators dusted off the badly degraded DNA samples, tested them, and ran the results through the state database. A partial match linked then 70-year-old, wheelchair-bound John Puckett to the only testable evidence—sperm found on the body. On the basis of this match, prosecutors charged Puckett with murder.
Puckett’s defense lawyer contacted the Arizona lab for more information about their findings, but the head of the lab denied the request. After a court issued a subpoena to compel the lab to disclose its findings, the analyst who had found the matching nine-locus pair testified that she had actually found ninety others within the database. When the lab offered no explanation for why 1 in 1 trillion events were happening regularly, the court ordered them to conduct a full search of the known-offender database and report back all matching pairs.

Ultimately, the lab’s report showed that there were actually quite a large number of these matches. The Arizona database had only 65,493 people in it, each identified by the two markers at 13 places that constituted his or her DNA profile. Yet 122 sets of people shared the same genetic markers at nine places of the 13, and some even shared markers at 10, 11, or 12 places. It’s like assuming that you have a fairly unique identifier—such as 26 digits that represent birthday, bank account, and social-security numbers all combined together—only to learn that a significant number of people share most of those numbers, and in the same order, as you.

The FBI called the Arizona results “misleading” and “meaningless,” and suppressed the findings.
As news of these unexpected pairings swept the nation, lawyers in other cities pressed for similar searches. If there were 122 matches in a 65,000-person sized database, how many such matches might be found in the 11 million-person national database? But rather than embrace the inquiry, the FBI called the Arizona results “misleading” and “meaningless,” and suppressed the findings. FBI leaders reprimanded the Arizona lab, claiming that disclosing the results violated its agreement with the FBI. They further threatened to cut off access to the national database to any lab that independently conducted their own such studies.

Why were the findings from the Arizona lab so explosive? The answer turns half on an understanding of math, and half on an understanding of law. And as is so often the case with forensic evidence, the gap between those two worlds proved critical.

At the time of the Arizona findings, state and national DNA databases had started to blossom. In its early days, most people thought of DNA testing as a tool to confirm the identity of a person that police had identified as a suspect in a crime. But it was on the brink of becoming something much more significant. The idea of “big data”—using vast networks of computers to churn unprecedented amounts of information—was on the cusp of taking off. For instance, although law-enforcement agencies had an incredible trove of fingerprint data, computerized searching didn’t become commonplace until 1999.

The FBI built a computerized network for its large national repository of DNA profiles—known as the Combined DNA Index System, or CODIS—and then built software to look for associations between all the profiles it contained. This meant that a new kind of “cold hit” case—one, like John Puckett’s, that was prompted by genetic identity rather than conventional investigative leads—came to the fore.

Some cold hit cases become “hot” immediately upon investigation, with the non-genetic evidence falling into place. But some cold hit cases, like Puckett’s, stay cold. None of the many fingerprints found at the scene matched him.
Yet prosecutors were willing to press for conviction based on the DNA match alone. Puckett mostly matched the description given by the sole eyewitness—he was the right age, gender, and race, and had been in the area at that time. He had also previously sexually assaulted three women around the same time, the convictions that had landed him in the database in the first place.

This case illustrates the importance of the 2001 Arizona findings, and the resulting national debate among mathematicians, lawyers, and forensic scientists. The simple explanation for the seemingly improbable matches—which a forensic or statistical expert would see straight away, but police, prosecutors, and testifying lab analysts would not—lies in a mathematical parable known as the birthday problem: How many people must there be in a group to have more than a 50 percent chance that two of them will have the same birthday? Despite the intuitive answer (a very large group), the correct answer is that it takes only 23 people.

It’s key to note that the question of the birthday problem is different than asking what the likelihood is that, picking a person at random on the street, that person would have a particular birthday. Similarly, the difference between “Does anyone in the database match anyone else?” and “Does anyone in the database match this evidence?” explains why nine-locus matches were likely to be common in a large database like Arizona’s.

Even so, cases around the country routinely proceeded on the basis of only a nine-locus database match, treated by lawyers and courts alike as conclusive proof of guilt.

In John Puckett’s case, that’s exactly what happened. Before the trial, the prosecutor proposed to tell the jury the random match probability, which was calculated as 1 in 1.1 million. His defense lawyer pressed the court to allow her to present an alternative match statistic, one in three.

Each of these statistics has a very different interpretation of the significance of the DNA-database match.
The defense’s alternative statistic, known as the “database match probability” (DMP), accounts for the difference between a truly random match, and a match made among a finite pool of candidates, like those contained within the database. DMP was put forward in 1996 as the proper method by a blue-ribbon panel of experts at the National Academy of Sciences in what is considered the single most authoritative report on DNA evidence in criminal cases. But there were other ways that the statistical significance of Puckett’s match could have been presented. Another approach—and probably the one most helpful to the jury—would have been to ask, “Of all the men who lived in the metropolitan area at the time of the killing, and who were the right age to have committed the offense, how many would likely match the crime scene evidence?” In Puckett’s case, the result of this approach, nicknamed the “n*p” statistic, was that at least two other people living in the area at that time matched the evidence.

Each of these statistics has a very different interpretation of the significance of the DNA-database match. Yet all are legitimate in one way or another, and there remains a lack of consensus among statisticians as to which one deserves priority within the criminal-justice system. Some defense lawyers have argued that this disagreement requires courts to reject database-match cases altogether. Others have sought additional confirming testing, or at the very least, presentation of conflicting statistics.
What Your DNA Says About Medieval History

As U.S. databases continue to expand, and cold-hit searches continue, this disagreement becomes increasingly important. A 2014 report by the European Network of Forensic Science Institutes spelled it out in plain language: “[a]s DNA-databases become larger, the chance of finding adventitious matches also increases, especially with partial and mixed profiles and DNA-profiles of relatives, which have higher random match probabilities.” The organization recommended last year that additional DNA testing be done in cases where a database match is the only thing linking someone to a crime. They also recommended that database managers keep a record of the number of adventitious matches, along with the conditions under which they were found (such as size of the database, number of searches) for future analysis.

Right now, the only “bad” cold hits that receive attention are those in which law enforcement seriously blunders—cases in which the suspects are fortunate enough to have ironclad alibis. For example, in 2000 in the U.K., police used a six-locus match to arrest a 49-year-old man for a burglary that occurred 200 miles away. One account placed the rarity of that profile as 1 in 37 million. Trouble was, the man was severely disabled by late-stage Parkinson’s disease, and physically incapable of committing the crime. Additional testing eventually exonerated him.

The judge in Puckett’s case ruled that the jury should hear only part of the story recounted here. Jurors heard only the prosecution’s probability statistic—that there was a 1 in 1.1 million chance that a person picked at random would match the crime-scene DNA. But the jurors never heard that Puckett had been picked as a result of a nonrandom trawl through a police database. They also never heard about the Arizona matches, or the fact that sharing alleles at nine loci is not uncommon. They did not learn that, even using the government’s own probability statistic, around 40 other people in California matched that crime scene evidence, or that, according to the database-match statistic endorsed by that 1996 report—the bible of forensic DNA—the probability of a match in the database searched by the government was 1 in 3. They never learned that it was likely that two other people in the area also matched the same evidence.

Indeed, just over five years after the trial, the FBI announced that the tables it created to compute DNA statistics—the data that the Arizona matches had called into question—contained errors. In a case with high quality and quantity DNA, the mistakes appear negligible. But in cases involving incomplete results like Puckett’s, the error’s effects are dramatic. Last month, one jurisdiction in Texas reported that a DNA-match probability computed according to the erroneous table was 1 in a billion; when corrected, the accurate figure was 1 in 100.

But the news came too late for Puckett: By the time the FBI admitted its mistake, he had already begun serving his sentence of life without parole.

Your Brain Isn’t a Computer. It’s a Quantum Field.

The irrationality of how we think has long plagued psychology. When someone asks us how we are, we usually respond with “fine” or “good.” But if someone followed up about a specific event — “How did you feel about the big meeting with your boss today?” — suddenly, we refine our “good” or “fine” responses on a spectrum from awful to excellent.


In less than a few sentences, we can contradict ourselves: We’re “good” but feel awful about how the meeting went. How then could we be “good” overall? Bias, experience, knowledge, and context all consciously and unconsciously form a confluence that drives every decision we make and emotion we express. Human behavior is not easy to anticipate, and probability theory often fails in its predictions of it.

Enter quantum cognition: A team of researchers has determined that while our choices and beliefs don’t often make sense or fit a pattern on a macro level, at a “quantum” level, they can be predicted with surprising accuracy. In quantum physics, examining a particle’s state changes the state of the particle — so too, the “observation effect” influences how we think about the idea we are considering.

The quantum-cognition theory opens the fields of psychology and neuroscience to understanding the mind not as a linear computer, but rather an elegant universe.

In the example of the meeting, if someone asks, “Did it go well?” we immediately think of ways it did. However, if he or she asks, “Were you nervous about the meeting?” we might remember that it was pretty scary to give a presentation in front of a group. The other borrowed concept in quantum cognition is that we cannot hold incompatible ideas in our minds at one time. In other words, decision-making and opinion-forming are a lot like Schrödinger’s cat.

The quantum-cognition theory opens the fields of psychology and neuroscience to understanding the mind not as a linear computer, but rather an elegant universe. But the notion that human thought and existence is richly paradoxical has been around for centuries. Moreover, the more scientists and scholars explore the irrational rationality of our minds, the closer science circles back to the confounding logic at the heart of every religion. Buddhism, for instance, is premised on riddles such as, “Peace comes from within. Do not seek it without it.” And, in Christianity, the paradox that Christ was simultaneously both a flesh-and-blood man and the Son of God is the central metaphor of the faith.

[D]ecision-making and opinion-forming are a lot like Schrödinger’s cat.

For centuries, religious texts have explored the idea that reality breaks down once we get past our surface perceptions of it; and yet, it is through these ambiguities that we understand more about ourselves and our world. In the Old Testament, the embattled Job pleads with God for an explanation as to why he has endured so much suffering. God then quizzically replies, “Where were you when I laid the foundations of the earth?” (Job 38:4). The question seems nonsensical — why would God ask a person in his creation where he was when God himself created the world? But this paradox is little different from the one in Einstein’s famous challenge to Heisenberg’s “Uncertainty Principle”: “God does not play dice with the universe.” As Stephen Hawking counters, “Even God is bound by the uncertainty principle” because if all outcomes were deterministic then God would not be God. His being the universe’s “inveterate gambler” is the unpredictable certainty that creates him.

The mind then, according to quantum cognition, “gambles” with our “uncertain” reason, feelings, and biases to produce competing thoughts, ideas, and opinions. Then we synthesize those competing options to relate to our relatively “certain” realities. By examining our minds at a quantum level, we change them, and by changing them, we change the reality that shapes them.

Surgeons restore hand, arm movement to quadriplegic patients.

A pioneering surgical technique has restored some hand and arm movement to patients immobilized by spinal cord injuries in the neck, reports a new study. The researchers assessed outcomes of nerve-transfer surgery in nine quadriplegic patients with spinal cord injuries in the neck. Every patient in the study reported improved hand and arm function.

Washington University physician Michael Bavlsik, MD, shows surgeon Ida Fox, MD, how he can now grip an otoscope, which he uses in his practice. He is one of nine quadriplegic patients who regained some hand and arm movement after nerve-transfer surgery, a procedure pioneered at Washington University School of Medicine. Fox, an assistant professor of surgery, operated on Bavlsik.

A pioneering surgical technique has restored some hand and arm movement to patients immobilized by spinal cord injuries in the neck, reports a new study at Washington University School of Medicine in St. Louis.

Like railroad switchmen, the focus is on rerouting passageways; however, instead of trains on a track, the surgeons redirect peripheral nerves in a quadriplegic’s arms and hands by connecting healthy nerves to the injured nerves. Essentially, the new nerve network reintroduces conversation between the brain and the muscles that allows patients, once again, to accomplish tasks that foster independence, such as feeding themselves or writing with a pen.

The researchers assessed outcomes of nerve-transfer surgery in nine quadriplegic patients with spinal cord injuries in the neck. Every patient in the study reported improved hand and arm function.

The study is published in the October issue of the American Society of Plastic Surgeons’ journal Plastic and Reconstructive Surgery.

“Physically, nerve-transfer surgery provides incremental improvements in hand and arm function. However, psychologically, these small steps are huge for a patient’s quality of life,” said the study’s lead author, Ida K. Fox, MD, assistant professor of plastic and reconstructive surgery. “One of my patients told me he was able to pick up a noodle off his chest when he dropped it.’ Before the surgery, he couldn’t move his fingers. It meant a lot for him to clean off that noodle without anyone helping him.”

Soft nerve bundles form the human spinal cord, which acts as the body’s control tower by communicating to the brain physical activities both large and small. The cervical spinal cord, in the neck, is comprised of seven vertebra denoted as C1 through C7.

Ultimately, medical professionals hope to discover a way to restore full movement to the estimated 250,000 people in the United States living with spinal cord injuries. More than half of such injuries involve the neck. However, until a cure is found, progress in regaining basic independence in routine tasks is important.

Indeed, one of the most humbling effects of spine damage is the inability to manage bladder or bowel functions. “People with spinal cord injuries cannot control those functions because their brains can’t talk to the nerves in the lower body, and they often can’t feel the need to go to the bathroom,” said Fox, who performs surgeries at Barnes-Jewish Hospital​. “Patients often can’t insert a catheter to empty their bladders or insert a suppository for bowel movement and have to rely on help from a caregiver. But after this surgery, one of my patients was able to independently catheterize himself, which he hadn’t been able to do since his accident over a decade ago. This boost in privacy and personal space restores a significant amount of dignity.”

The procedure allowed a St. Louis primary care physician and a father of eight to feed himself with a fork, write with a pen, look into patients’ ears with an otoscope and drive his kids to activities. In 2012, Michael D. Bavlsik, MD, lost the ability to use his left hand and extend his left elbow while he, his son and other Boy Scouts were on a trip in Minnesota and his van collided with a boat and a trailer. None of the boys was severely injured, but the accident left Bavlsik a quadriplegic. He now moves about in a motorized wheelchair.

“Nerve-transfer surgery has been very successful in helping me because it restored triceps function and improvement in my grip,” said Bavlsik, an assistant professor of clinical medicine at the School of Medicine. “I am extremely grateful for this surgery.”

Surgeons at Washington University pioneered nerve-transfer surgery. Developed about 25 years ago by the study’s senior author, Susan E. Mackinnon, MD, director of the Division of Plastic and Reconstructive Surgery at the School of Medicine, the technique initially was performed to restore movement in the extremities of patients who had injured peripheral nerves and lost the ability to move a foot or an arm.

But in the past five years, the same technique has been used to restore limited movement to patients with spinal cord injuries. Quadriplegics from Colorado, Michigan and Arizona, among other states, have traveled to St. Louis for the surgery.

The operation can be performed even years after a spinal cord injury. It usually takes four hours, and most patients go home the next morning.

Since surgeons connect working nerves in the upper arms to a patient’s damaged nerves in their arms and hands, the technique targets patients with injuries at the C6 or C7 vertebra, the lowest bones in the neck. It typically does not help patients who have lost all arm function due to higher injuries in vertebrae C1 through C5.

Bypassing the spinal cord, surgeons reroute healthy nerves sitting above the injury site, usually in the shoulders or elbows, to paralyzed nerves in the hand or arm. Once a connection is established, patients undergo extensive physical therapy to train the brain to recognize the new nerve signals, a process that takes about 6-18 months.

“The gains after nerve-transfer surgery are not instantaneous,” said Mackinnon, director of the School of Medicine’s Center for Nerve Injury and Paralysis, and the Sydney M. Shoenberg Jr. and Robert H. Shoenberg Professor of Surgery. “But once established, the surgery’s benefits provide a way to let individuals with spinal cord injuries improve their daily lives.”

Another patient benefiting from the nerve-transfer technique is a 72-year-old right-handed man who had the surgery two years after he suffered a cervical spinal cord injury. The doctors took healthy tissue from the patient’s upper arm, connected it to a paralyzed nerve that controlled his ability to pinch and then plugged it into a working nerve that restored the man’s ability to flex his thumb and index finger. This allowed him to feed himself and to hold a water bottle to maintain hydration, which, in turn, reduced his risk of developing urinary tract infections and has bolstered his overall health.

“Our innovations to address spinal cord injuries came directly from a quarter century of nerve-transfer work in nerve injury,” Mackinnon said. “We want to continue building our expertise in this area very carefully. While the surgery itself can be relatively straightforward, the decision-making is complicated. We want to encourage people with spinal cord injury to consider this option when so little is often offered or made available.”