Miracle-dz/UniFAR-FTUs huggingface dataset:
Genomic signals of diversification along ecological gradients in a tropical lizard

Studies of rainforest diversification that simultaneously consider the effects of genetic drift and natural selection are rare. We use Amplified Fragment Length Polymorphism genome scans of the African rainforest lizard Trachylepis affinis from Cameroon to examine the spatial patterns and environmental associations of both neutrally evolving loci and those thought to be under selection. Bayesian selection scans revealed that approximately 7% of the genome may be under divergent selection. Using non‐linear environmental modelling techniques, we fit patterns of genetic differentiation recovered from the pooled neutral data and from individual loci showing a signature of natural selection. Neutral differentiation occurred along a cline from coastal lowland rainforest inland toward the gallery forests‐savanna mosaic (ecotone), and was associated with both geographic distance and changing precipitation patterns. Loci under selection were differentiated predominantly along the forest–ecotone gradient—in concordance with morphological divergence in traits related to fitness. A second set of these loci was differentiated between lowland and montane habitats. A third set of loci was indicative of divergent selection between rainforest refugia. Niche models and demographic signals in mitochondrial sequence data support a population expansion out of a core rainforest area into savanna since the last glacial maximum. Our findings indicate adaptive diversification in T. affinis may be taking place along the forest–ecotone gradient during range expansions or contractions, and that refugial isolation augmented by divergent adaptation to different rainforest environments appears to play a less significant role.
Gateway to genetic exchange? DNA double‐strand breaks in the bdelloid rotifer Adineta vaga submitted to desiccation

The bdelloid rotifer lineage Adineta vaga inhabits temporary habitats subjected to frequent episodes of drought. The recently published draft sequence of the genome of A. vaga revealed a peculiar genomic structure incompatible with meiosis and suggesting that DNA damage induced by desiccation may have reshaped the genomic structure of these organisms. However, the causative link between DNA damage and desiccation has never been proven to date in rotifers. To test for the hypothesis that desiccation induces DNA double‐strand breaks (DSBs), we developed a protocol allowing a high survival rate of desiccated A. vaga. Using pulsed‐field gel electrophoresis to monitor genomic integrity, we followed the occurrence of DSBs in dried bdelloids and observed an accumulation of these breaks with time spent in dehydrated state. These DSBs are gradually repaired upon rehydration. Even when the genome was entirely shattered into small DNA fragments by proton radiation, A. vaga individuals were able to efficiently recover from desiccation and repair a large amount of DSBs. Interestingly, when investigating the influence of UV‐A and UV‐B exposure on the genomic integrity of desiccated bdelloids, we observed that these natural radiations also caused important DNA DSBs, suggesting that the genome is not protected during the desiccated stage but that the repair mechanisms are extremely efficient in these intriguing organisms.
Significance of C-Reactive Protein and Transcranial Doppler in Cerebral Vasospasm Following Aneurysmal Subarachnoid Hemorrhage

Objective Cerebral vasospasm is a common and potentially devastating complication of aneurysmal subarachnoid hemorrhage (aSAH). Inflammatory processes seem to play a major role in the pathogenesis of vasospasm. C-reactive protein (CRP) constitutes a highly sensitive inflammatory marker. Elevation of serum CRP levels has been demonstrated in patients with aSAH. The purpose of the current study was to evaluate the possible relationship between CRP levels in the serum and transcranial Doppler (TCD) and the development of vasospasm in patients with aSAH. Methods A total of 61 adult patients in whom aSAH was diagnosed were included in the study from November 2008 to May 2011. The patients' demographics, Hunt and Hess grade, Fisher grade, CT scans, digital subtraction angiography studies, and daily neurological examinations were recorded. Serial serum CRP measurements were obtained on days 1, 3, 5, 7, 9, 11 and 13 and TCD was measured on days 3, 5, 7, 9, 11 and 13. All patients underwent either surgical or endovascular treatment within 24 hours of their hemorrhagic attacks. Results Serum CRP levels peaked on the 3rd postoperative day. There were significant differences between the vasospasm group and the non-vasospasm group on the 1st, 3rd and 5th day. There were significant differences between the vasospasm group and the non-vasospasm group on the 3rd day in the mean middle cerebral artery velocities on TCD. Conclusion Patients with high levels of CRP on the 1st postoperative day and high velocity of mean TCD on the 3rd postoperative day may require closer observation to monitor for the development of vasospasm.
Rich Pickings Near Large Communal Roosts Favor ‘Gang’ Foraging by Juvenile Common Ravens, Corvus corax

Ravens (Corvus corax) feed primarily on rich but ephemeral carcasses of large animals, which are usually defended by territorial pairs of adults. Non-breeding juveniles forage socially and aggregate in communal winter roosts, and these appear to function as ‘information centers’ regarding the location of the rare food bonanzas: individuals search independently of one another and pool their effort by recruiting each other at roosts. However, at a large raven roost in Newborough on Anglesey, North Wales, some juveniles have been observed recently to forage in ‘gangs’ and to roost separately from other birds. Here we adapt a general model of juvenile common raven foraging behavior where, in addition to the typical co-operative foraging strategy, such gang foraging behavior could be evolutionarily stable near winter raven roosts. We refocus the model on the conditions under which this newly documented, yet theoretically anticipated, gang-based foraging has been observed. In the process, we show formally how the trade off between search efficiency and social opportunity can account for the existence of the alternative social foraging tactics that have been observed in this species. This work serves to highlight a number of fruitful avenues for future research, both from a theoretical and empirical perspective.
Monosegmental Transpedicular Fixation for Selected Patients With Thoracolumbar Burst Fractures

Study Design A prospective cohort study on selected consecutive patients. Objective To evaluate the efficacy of an innovative operative technique called monosegmental transpedicular fixation for the treatment of some thoracolumbar burst fractures. Summary of Background Data Short-segment pedicle screw instrumentation is accepted by many spinal surgeons as an acceptable technique for the treatment of thoracolumbar burst fractures. Preoperative evaluation using the spinal load-sharing makes this technique more reliable. To preserve more motion segments, some authors have advocated using monosegmental pedicle screw instrumentation (MSPI) to treat thoracolumbar fractures. However, up until now this kind of maneuver is only performed in cases of flexion distraction injuries. Methods A cohort of 20 patients with thoracolumbar burst fractures fulfilling the inclusion criteria were prospectively submitted to surgical treatment of monosegmental transpedicular fixation plus posterior fusion. All instrumentations were performed with pedicle screws inserted bilaterally into the fractured level and 1 adjacent level, either superior or inferior depending on the locating side of the intact endplate. All patients were followed up. The preoperative radiographs, the postoperative radiographs within 1 week of operation, and the radiographs of the most recent follow-up were evaluated for kyphosis correction recorded in the Sagittal Index and Load-Sharing Classification (LSC) index. The postoperative functional outcomes were evaluated using the Frankel Performance Scale together with the Denis Pain Scale. Results Eighteen patients were followed up successfully with an average final follow-up of 24.7±8.0 months. The focal kyphotic angulations were corrected satisfactorily with the mean Sagittal Index of preoperative 16.5±6.6 degrees, initial postoperative 4.0±2.4 degrees, and latest follow-up 4.8±4.0 degrees. No obvious loss of correction occurred except for 2 patients who both scored 8 points on the LSC Score. Postoperatively, most patients attained both functional neurologic improvement and pain relief, and only a few complications were noted. Conclusions For selected thoracolumbar burst fractures, MSPI can provide the same or better fixation and preserve more motion segments than other methods of posterior pedicle instrumentation. With preoperative evaluation using the spinal LSC system, MSPI is effective and reliable for the treatment of thoracolumbar burst fractures when properly indicated.
Analysis of GTPase-activating proteins: Rab1 and Rab43 are key Rabs required to maintain a functional Golgi complex in human cells

Rab GTPases control vesicle movement and tethering membrane events in membrane trafficking. We used the 38 human Rab GTPase activating proteins (GAPs) to identify which of the 60 Rabs encoded in the human genome function at the Golgi complex. Surprisingly, this screen identified only two GAPs, RN-tre and TBC1D20, disrupting both Golgi organization and protein transport. RN-tre is the GAP for Rab43, and controls retrograde transport into the Golgi from the endocytic pathway. TBC1D20 is the ER-localized GAP for Rab1, and is the only GAP blocking the delivery of secretory cargo from the ER to the cell surface. Strikingly, its expression causes the loss of the Golgi complex, highlighting the importance of Rab1 for Golgi biogenesis. These effects can be antagonized by reticulon, a binding partner for TBC1D20 in the ER. Together, these findings indicate that Rab1 and Rab43 are key Rabs required for the biogenesis and maintenance of a functional Golgi structure, and suggest that other Rabs acting at the Golgi complex are likely to be functionally redundant.
TETRODOTOXIN RESISTANCE IN GARTER SNAKES: AN EVOLUTIONARY RESPONSE OF PREDATORS TO DANGEROUS PREY

The use of the “arms race” analogy as a conceptualization of evolutionary predator‐prey interactions has been criticized because of the lack of evidence that predators can and do adapt to increased antipredator ability of prey. We present evidence that the garter snake Thamnophis sirtalis has evolved resistance to tetrodotoxin (TTX) in response to the toxicity of the newt Taricha granulosa on which the snake feeds. A bioassay (locomotor performance before and after injection of TTX) was used to obtain repeated measures of resistance for individual snakes. We studied interpopulation and interspecific variation by comparing resistance in Thamnophis sirtalis from populations occurring sympatrically and allopatrically with Taricha granulosa, and in Thamnophis ordinoides (which does not feed on the newt) occurring sympatrically with Taricha granulosa. We also examined intrapopulation variation in TTX resistance using snakes from a population known to feed on Taricha granulosa. Resistance differed significantly among individuals and litters; repeatability and heritability estimates of the assay were significantly different from zero, demonstrating the potential for response to selection. The population of Thamnophis sirtalis that occurs with Taricha granulosa exhibited levels of resistance much greater than either of the other groups. These results suggest that the predator‐prey arms race analogy may be applicable to this system.
Evaluation of the ASPIRANT trial

Several pathophysiological, clinical, and therapeutic features of resistant hypertension are far from being clearly defined. This is the case also for the efficacy of aldosterone receptor antagonists as an add-on treatment of resistant hypertension. The Addition of Spironolactone in Patients with Resistant Arterial Hypertension (ASPIRANT) trial evaluated, with a double-blind, placebo-controlled design, the effects of low-dose (25 mg/day) spironolactone as compared with placebo on clinic and ambulatory blood pressure in 117 resistant hypertensive obese patients, already under treatment with at least four antihypertensive drugs. The primary study endpoint was the achievement of a statistically significant difference in the systo-diastolic blood pressure reduction during the daytime period between the spironolactone-treated and the placebo-treated group. The results show that aldosterone blockade was associated with a significant reduction in clinic, 24-h and daytime systolic (but not in diastolic) blood pressure as compared with the placebo-treated group, the systo-diastolic blood pressure difference between the two treatment regimens amounting to 5.4/1.0 mmHg. Although a number of limitations weaken some of the study conclusions, ASPIRANT trial provides the first controlled evidence on the blood pressure-lowering effects of low-dose spironolactone in resistant hypertensive patients.
Depolarization promotes GAD 65‐mediated GABA synthesis by a post‐translational mechanism in neural stem cell‐derived neurons

Neuronal activity regulates neurogenesis and neuronal differentiation in the mammalian brain. The commencement of neurotransmitter expression establishes the neuronal phenotype and enables the formation of functional connectivity between neurons. In addition, release of neurotransmitters from differentiating neurons may modulate the behaviour of neural precursors. Here, we show that neuronal activity regulates γ‐aminobutyric acid (GABA) expression in neurons generated from stem cells of the striatum and adult subventricular zone (SVZ). Differentiating neurons display spontaneous Ca2+ events, which are voltage‐gated calcium channel (VGCC) dependent. Depolarization increases both the frequency of Ca2+ transients and the amount of Ca2+ influx in differentiating neurons. We show that depolarization‐dependent GABA expression is regulated by the amplitude and not by the frequency of Ca2+ influx. Brief activation of VGCCs leads to Ca2+ influx that in turn promotes a rapid expression of GABA. Depolarization‐dependent GABA expression does not require changes in gene expression. Instead, it involves cAMP‐dependent protein kinase (PKA) and Ca2+ and phospholipid‐dependent protein kinase (PKC) signalling. Activity increases the number of glutamic acid decarboxylase (GAD) 65‐immunoreactive neurons in a PKA‐dependent manner, without altering the expression of GAD 65, suggesting that depolarization promotes recruitment of GAD 65 by a post‐translational mechanism. In line with this, depolarization does not permanently increase the expression of GABA in neurons derived from neural stem cells of the embryonic striatum, cortex and adult SVZ. Thus, neuronal activity does not merely accelerate neuronal differentiation but it may alter the mechanism of GABA synthesis in newly generated neurons.
GDNF family receptors in the embryonic and postnatal rat heart and reduced cholinergic innervation in mice hearts lacking Ret or GFRα2

Members of the GDNF family, which are important during peripheral nervous system development and kidney organogenesis, signal via Ret and GFRα receptors. Here we have studied their possible role in heart development. Gfra1 was expressed in the endocardial cushion mesenchyme at E12 and later, in the developing and mature valves, and in the walls of the aorta and the pulmonary trunk. Gfra2 was expressed in the outer layers of the aorta and pulmonary trunk and in the valves at E18–P60. Endocardial cells showed moderate Gfra2 mRNA and protein expression between E12 and E15. Gfra3 mRNA was detected, mainly postnatally, in scattered cells of the atria and the great vessels. In embryonic and postnatal rat cardiac ganglia, Ret and Gfra2 transcripts were seen in the neurons, whereas Gfra1 and Gfra3 mRNA were preferentially found in non‐neuronal cells within the ganglia. GFRα2 immunoreactivity was seen in both cardiac ganglion neurons and their nerve fibers. There were no obvious non‐neuronal defects in hearts of Ret‐, GFRα1‐, or GFRα2‐deficient mice, suggesting that these receptors are not essential for gross cardiac development. However, E18 Ret‐deficient mice exhibited a reduced volume of cardiac ganglia and cholinergic innervation of the ventricular conduction system. Moreover, adult Gfra2−/− mice showed reduced cholinergic innervation by 40% in their ventricles and by 60% in the ventricular conduction system. These findings indicate that GFRα2/Ret signaling is required for normal cholinergic innervation of heart. © 2000 Wiley‐Liss, Inc.
Impaired Glucose Tolerance in the R6/1 Transgenic Mouse Model of Huntington’s Disease

Previous reports have highlighted a possible link between Huntington’s disease (HD) and diabetes mellitus (DM), but the association has not been characterised in detail. A transgenic mouse model for HD, the R6/2 mouse, also develops diabetes. In the present study, we examined the R6/1 mouse, which carries a shorter CAG repeat than the R6/2 mouse, and found that, although not diabetic, the mice showed several signs of impaired glucose tolerance. First, following i.p. glucose injection, the blood glucose concentration was approximately 30% higher in young R6/1 mice (10 weeks) compared to wild‐type mice (P = 0.004). In older mice (38 weeks), glucose tolerance was further impaired in both R6/1 and wild‐type animals. Second, during glucose challenge, the R6/1 mice reached higher plasma insulin levels than wild‐type mice, but the peripheral insulin sensitivity was normal as measured by injection of human or mouse insulin or when evaluated by the quantitative insulin sensitivity check index (QUICKI). Third, the beta cell volume was 17% and 39% smaller at 10 and 38 weeks of age, respectively, compared to age‐matched wild‐type littermates and the reduction was not caused by apoptosis at either age. Finally, we demonstrated the presence of the HD gene product, huntingtin (htt), in both alpha‐ and beta‐cells in R6/1 islets of Langerhans. Since pancreatic beta cells and neurons share several common traits, clarification of the mechanism associating neurodegenerative diseases with diabetes might improve our understanding of the pathogenic events leading to both groups of diseases.
Transient improvement in sensorimotor conversion during post-anoxic encephalopathy with bilateral medial temporal ischemia

We report the case of a patient with sensorimotor conversion that improved transiently during post-anoxic medial temporal ischemia inducing anterograde and retrograde amnesia. Symptoms reappeared in parallel with mnesic recovery. This case raises a hypothesis concerning the role of hippocampi and amygdalae, which are involved in emotionally-associated memory. The amnesia may have modified the patient’s “self,” giving her a “distant” point of view. Another hypothesis is that cerebral anoxic stress may have “reset” the cerebral network that controls behavior. These findings give clues about the mechanisms of somatoform disorder and highlight the possibility of specific therapeutic strategies to induce cognitive reappraisal of emotionally-associated experiences.
Survival impact of epidermal growth factor receptor overexpression in patients with non-small cell lung cancer: a meta-analysis

Background: It is thought that overexpression of epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) might compromise patient survival, presumably by promoting tumour growth by an autocrine mechanism. However, conflicting results have been reported from various laboratories, and the clinical importance of EGFR overexpression remains unsettled. Methods: A meta-analysis of previous studies was performed to quantitatively review the effects of EGFR overexpression on survival in patients with NSCLC using a DerSimonian-Laird random effects model. Eighteen studies including 2972 patients were subjected to final analysis. Results: Overall, positivity for EGFR overexpression differed between histological types: 39% in adenocarcinomas, 58% in squamous cell carcinomas, 38% in large cell carcinomas, and 32% in cancers in a miscellaneous category (p<0.0001). The combined hazard ratio (HR) was 1.14 (95% CI 0.97 to 1.34; p = 0.103), indicating that EGFR overexpression has no significant impact on survival. When only the 15 immunohistochemistry based studies were considered, the combined HR was 1.08 (95% CI 0.92 to 1.28; p = 0.356), again suggesting that EGFR overexpression has no impact on survival. Heterogeneity testing indicated that there was heterogeneity between studies but publication bias was absent, which suggests that the summary statistics obtained may approximate the actual average. Conclusions: EGFR overexpression was not associated with poorer survival in patients with NSCLC. Specific mutations of the EGFR gene will need further study in terms of survival implications.
Blind deconvolution of Gaussian blurred images containing additive white Gaussian noise

Image restoration algorithms are used to reconstruct the information that is suppressed when an observed image is subjected to blurring. These algorithms generally assume that knowledge of the nature of the distortion and noise contained in an observed image is available. When this information is not available and has to be directly estimated from the image being processed the problem becomes one of blind deconvolution. This paper makes use of a novel blur identification technique and a noise identification technique to perform blind deconvolution on single images that have been degraded by a Gaussian blur and contain additive white Gaussian noise.
NFAT-3 Is a Transcriptional Repressor of the Growth-associated Protein 43 during Neuronal Maturation*

Transcription is essential for neurite and axon outgrowth during development. Recent work points to the involvement of nuclear factor of activated T cells (NFAT) in the regulation of genes important for axon growth and guidance. However, NFAT has not been reported to directly control the transcription of axon outgrowth-related genes. To identify transcriptional targets, we performed an in silico promoter analysis and found a putative NFAT site within the GAP-43 promoter. Using in vitro and in vivo experiments, we demonstrated that NFAT-3 regulates GAP-43, but unexpectedly, does not promote but represses the expression of GAP-43 in neurons and in the developing brain. Specifically, in neuron-like PC-12 cells and in cultured cortical neurons, the overexpression of NFAT-3 represses GAP-43 activation mediated by neurotrophin signaling. Using chromatin immunoprecipitation assays, we also show that prior to neurotrophin activation, endogenous NFAT-3 occupies the GAP-43 promoter in PC-12 cells, in cultured neurons, and in the mouse brain. Finally, we observe that NFAT-3 is required to repress the physiological expression of GAP-43 and other pro-axon outgrowth genes in specific developmental windows in the mouse brain. Taken together, our data reveal an unexpected role for NFAT-3 as a direct transcriptional repressor of GAP-43 expression and suggest a more general role for NFAT-3 in the control of the neuronal outgrowth program.