Nel positively regulates the genesis of retinal ganglion cells by promoting their differentiation and survival during development

Peer reviewedPublisher PD

Born Knowing: Tentacled Snakes Innately Predict Future Prey Behavior

Background: Aquatic tentacled snakes (Erpeton tentaculatus) can take advantage of their prey’s escape response by startling fish with their body before striking. The feint usually startles fish toward the snake’s approaching jaws. But when fish are oriented at a right angle to the jaws, the C-start escape response translates fish parallel to the snake’s head. To exploit this latter response, snakes must predict the future location of the fish. Adult snakes can make this prediction. Is it learned, or are tentacled snakes born able to predict future fish behavior? Methods and Findings: Laboratory-born, naïve snakes were investigated as they struck at fish. Trials were recorded at 250 or 500 frames per second. To prevent learning, snakes were placed in a water container with a clear transparency sheet or glass bottom. The chamber was placed over a channel in a separate aquarium with fish below. Thus snakes could see and strike at fish, without contact. The snake’s body feint elicited C-starts in the fish below the transparency sheet, allowing strike accuracy to be quantified in relationship to the C-starts. When fish were oriented at a right angle to the jaws, naïve snakes biased their strikes to the future location of the escaping fish’s head, such that the snake’s jaws and the fish’s translating head usually converged. Several different types of predictive strikes were observed. Conclusions: The results show that some predators have adapted their nervous systems to directly compensate for the future behavior of prey in a sensory realm that usually requires learning. Instead of behavior selected during their lifetime

Facial Cosmetics and Attractiveness: Comparing the Effect Sizes of Professionally-Applied Cosmetics and Identity

Forms of body decoration exist in all human cultures. However, in Western societies, women are more likely to engage in appearance modification, especially through the use of facial cosmetics. How effective are cosmetics at altering attractiveness? Previous research has hinted that the effect is not large, especially when compared to the variation in attractiveness observed between individuals due to differences in identity. In order to build a fuller understanding of how cosmetics and identity affect attractiveness, here we examine how professionally-applied cosmetics alter attractiveness and compare this effect with the variation in attractiveness observed between individuals. In Study 1, 33 YouTube models were rated for attractiveness before and after the application of professionally-applied cosmetics. Cosmetics explained a larger proportion of the variation in attractiveness compared with previous studies, but this effect remained smaller than variation caused by differences in attractiveness between individuals. Study 2 replicated the results of the first study with a sample of 45 supermodels, with the aim of examining the effect of cosmetics in a sample of faces with low variation in attractiveness between individuals. While the effect size of cosmetics was generally large, between-person variability due to identity remained larger. Both studies also found interactions between cosmetics and identity-more attractive models received smaller increases when cosmetics were worn. Overall, we show that professionally- applied cosmetics produce a larger effect than self-applied cosmetics, an important theoretical consideration for the field. However, the effect of individual differences in facial appearance is ultimately more important in perceptions of attractiveness

Adaptations to Climate-Mediated Selective Pressures in Humans

Humans inhabit a remarkably diverse range of environments, and adaptation through natural selection has likely played a central role in the capacity to survive and thrive in extreme climates. Unlike numerous studies that used only population genetic data to search for evidence of selection, here we scan the human genome for selection signals by identifying the SNPs with the strongest correlations between allele frequencies and climate across 61 worldwide populations. We find a striking enrichment of genic and nonsynonymous SNPs relative to non-genic SNPs among those that are strongly correlated with these climate variables. Among the most extreme signals, several overlap with those from GWAS, including SNPs associated with pigmentation and autoimmune diseases. Further, we find an enrichment of strong signals in gene sets related to UV radiation, infection and immunity, and cancer. Our results imply that adaptations to climate shaped the spatial distribution of variation in humans

Sequential Assembly of Centromeric Proteins in Male Mouse Meiosis

The assembly of the mitotic centromere has been extensively studied in recent years, revealing the sequence and regulation of protein loading to this chromosome domain. However, few studies have analyzed centromere assembly during mammalian meiosis. This study specifically targets this approach on mouse spermatocytes. We have found that during prophase I, the proteins of the chromosomal passenger complex Borealin, INCENP, and Aurora-B load sequentially to the inner centromere before Shugoshin 2 and MCAK. The last proteins to be assembled are the outer kinetochore proteins BubR1 and CENP-E. All these proteins are not detected at the centromere during anaphase/telophase I and are then reloaded during interkinesis. The loading sequence of the analyzed proteins is similar during prophase I and interkinesis. These findings demonstrate that the interkinesis stage, regularly overlooked, is essential for centromere and kinetochore maturation and reorganization previous to the second meiotic division. We also demonstrate that Shugoshin 2 is necessary for the loading of MCAK at the inner centromere, but is dispensable for the loading of the outer kinetochore proteins BubR1 and CENP-E

Synergistic effects of various Her inhibitors in combination with IGF-1R, C-MET and Src targeting agents in breast cancer cell lines

Introduction: Overexpression of the receptor tyrosine kinase HER2 has been reported in around 25% of human breast cancers, usually indicating a poor prognosis. As a result, HER2 has become a popular target for therapy. However, despite recent advances in HER2 targeted therapy, many patients still experience primary and secondary resistance to such treatments. It is therefore important to understand the underlying mechanism of resistance and to develop more effective therapeutic interventions for breast cancer. Methods: The sensitivity of a panel of seven breast cancer cell lines to treatment with various types HER-family inhibitors alone, or in combination with a selection of other tyrosine kinase inhibitors (TKIs) or chemotherapeutic agents was determined using the Sulforhodamine B colorimetric assay. Receptor expression, cell-cycle distribution, cell signalling and cell migration were determined using flow cytometry, Western blot and Incucyte Zoom Live-Cell Analysis System respectively. Results: Overall, breast cancer cells were more sensitive to treatment with the irreversible pan-HER family inhibitors, particularly afatinib and neratinib, than treatment with the first-generation reversible inhibitors. Of three HER-2 overexpressing cell lines in this panel, SKBr3 and BT474 were highly sensitive to treatment with HER-family inhibitors (IC50s as low as 3 nM), while MDA-MB-453 was relatively resistant (lowest IC50 = 0.11 μM). When the HER-family inhibitors were combined with other agents such as NVP-AEW541 (an IGF-1R inhibitor), dasatinib (a Src inhibitor) or crizotinib (a c-Met/ALK inhibitor), such combination produced synergistic effects in some of the cell lines examined. Interestingly, co-targeting of Src and HER-family members in MDA-MB-453 cells led to synergistic growth inhibition, suggesting the importance of Src in mediating resistance to HER2-targeting agents. Finally, treatment with the irreversible HER family blockers and dasatinib were also most effective at inhibiting the migration of breast cancer cells. Conclusion: We concluded that the irreversible inhibitors of HER-family members are generally more effective at inhibiting growth, downstream signalling and migration compared with reversible inhibitors, and that combining HER-family inhibitors with other TKIs such as dasatinib may have therapeutic advantages in certain breast cancer subtypes and warrants further investigation

The evolution of the upright posture and gait—a review and a new synthesis

During the last century, approximately 30 hypotheses have been constructed to explain the evolution of the human upright posture and locomotion. The most important and recent ones are discussed here. Meanwhile, it has been established that all main hypotheses published until the last decade of the past century are outdated, at least with respect to some of their main ideas: Firstly, they were focused on only one cause for the evolution of bipedality, whereas the evolutionary process was much more complex. Secondly, they were all placed into a savannah scenario. During the 1990s, the fossil record allowed the reconstruction of emerging bipedalism more precisely in a forested habitat (e.g., as reported by Clarke and Tobias (Science 269:521–524, 1995) and WoldeGabriel et al. (Nature 412:175–178, 2001)). Moreover, the fossil remains revealed increasing evidence that this part of human evolution took place in a more humid environment than previously assumed. The Amphibian Generalist Theory, presented first in the year 2000, suggests that bipedalism began in a wooded habitat. The forests were not far from a shore, where our early ancestor, along with its arboreal habits, walked and waded in shallow water finding rich food with little investment. In contrast to all other theories, wading behaviour not only triggers an upright posture, but also forces the individual to maintain this position and to walk bipedally. So far, this is the only scenario suitable to overcome the considerable anatomical and functional threshold from quadrupedalism to bipedalism. This is consistent with paleoanthropological findings and with functional anatomy as well as with energetic calculations, and not least, with evolutionary psychology. The new synthesis presented here is able to harmonise many of the hitherto competing theories