Hindlimb and pelvic anatomy of Caiman yacare (Archosauria, Pseudosuchia): Myology and osteological correlates with emphasis on lower leg and autopodial musculature.

The anatomy of the archosaurian pelvis and hindlimb has adopted a diversity of successful configurations allowing a wide range of postures during the evolution of the group (e.g., erect, sprawling). For this reason, thorough studies of the structure and function of the pelvic and hindlimb musculature of crocodylians are required and provide the possibility to expand their implications for the evolution of archosaurian locomotion, as well as to identify potential new characters based on muscles and their bony correlates. In this study, we give a detailed description of the pelvic and hindlimb musculature of the South American alligator Caiman yacare, providing comprehensive novel information regarding lower limb and autopodial muscles. Particularly for the pedal muscles, we propose a new classification for the dorsal and ventral muscles of the autopodium based on the organisation of these muscles in successive layers. We have studied the myology in a global background in which we have compared the Caiman yacare musculature with other crocodylians. In this sense, differences in the arrangement of m. flexor tibialis internus 1, m. flexor tibialis externus, m. iliofibularis, mm. puboischiofemorales internii 1 and 2, between Ca. yacare and other crocodylians were found. We also discuss the muscle attachments that have different bony correlates among the crocodylian species and their morphological variation. Most of the correlates did not exhibit great variation among the species compared. The majority of the recognised correlates were identified in the pelvic girdle; additionally, some bony correlates associated with the pedal muscles are highlighted here for the first time. This research provides a wide framework for future studies on comparative anatomy and functional morphology, which could contribute to improving the character definition used in phylogenetic analyses and to understand the patterns of musculoskeletal hindlimb evolution.

"African" acral keratoderma: Further evidence for a single entity. A retrospective study of 42 patients.

BACKGROUND: Several phenotypes of non-inflammatory palmar and plantar keratoderma (PPK) have been described in patients of Sub-Saharan African descent. They include keratosis punctata of the palmar creases, marginal keratoderma, also known as acrokeratoelastoidosis or focal acral hyperkeratosis, knuckle pads, other forms of diffuse hyperkeratosis, the very rare "mosaic acral keratosis", and ainhum. A previous survey has shown that these various forms of PPK are particularly frequent in patients of Sub-Saharan African descent and that they commonly occur concurrently, suggesting that they could form part of a single entity called "African" Acral Keratoderma (AAK). AIM: To assess the validity of the concept of AAK and clarify its main characteristics. METHODS: A retrospective, descriptive, monocenter study was carried out on patients with AAK seen at our institution between 2009 and 2020. RESULTS: There were 42 patients (median age 38 years, range: 12-69 years), all of Sub-Saharan African descent. The male-female sex ratio was 0.3. Thirty-three (78%) had diffuse keratoderma, 25 (59%) had marginal keratoderma on their hands and/or feet, 20 (48%) had knuckle pads, 20 (48%) had keratosis punctata of the palmar creases, 3 had ainhum, and 2 had mosaic acral keratoderma. Mixed forms were seen in 76% of the patients (n = 32). Familial histories were reported by 17 patients (40%). Treatment was topical in over 90% of patients and systemic in 9 patients (21%). Ainhum was managed surgically. CONCLUSION: This retrospective study provides additional evidence for the concept of AAK. A genetic origin is suggested by the familial aggregation of cases.

DNA Sequences in Centromere Formation and Function.

Faithful chromosome segregation during cell division depends on the centromere, a complex DNA/protein structure that links chromosomes to spindle microtubules. This chromosomal domain has to be marked throughout cell division and its chromosomal localization preserved across cell generations. From fission yeast to human, centromeres are established on a series of repetitive DNA sequences and on specialized centromeric chromatin. This chromatin is enriched with the histone H3 variant, named CENP-A, that was demonstrated to be the epigenetic mark that maintains centromere identity and function indefinitely. Although centromere identity is thought to be exclusively epigenetic, the presence of specific DNA sequences in the majority of eukaryotes and of the centromeric protein CENP-B that binds to these sequences, suggests the existence of a genetic component as well. In this review, we will highlight the importance of centromeric sequences for centromere formation and function, and discuss the centromere DNA sequence/CENP-B paradox.

How obesity relates to socio-economic status: identification of eating behavior mediators.

BACKGROUND: Socio-economic status (SES) is a strong determinant of eating behavior and the obesity risk. OBJECTIVE: To determine which eating and lifestyle behaviors mediate the association between SES and obesity. METHODS: We performed a case-control study of 318 obese people and 371 non-obese people in northern France. Ten eating behavior traits were assessed using the Three-Factor Eating Questionnaire Revised 21-Item and an eating attitude questionnaire (on plate size, the number of servings, reasons for stopping eating and the frequency of eating standing up, eating in front of the television set (TV) and eating at night). The SES score (in three categories) was based on occupation, education and income categories. Mediation analysis was performed using the test of joint significance and the difference of coefficients test. RESULTS: The age- and gender-adjusted obesity risk was higher for individuals in the low-SES groups (odds ratio (OR) (95% confidence interval (CI)=1.82 (1.48-2.24), P<0.0001). Additional servings were associated with a higher obesity risk (OR=3.43, P<0.0001). Cognitive restraint (P<0.0001) and emotional eating (P<0.0001) scores were higher in obese participants than in non-obese participants but did not depend on SES. Of the 10 potential factors tested, eating off a large plate (P=0.01), eating at night (P=0.04) and uncontrolled eating (P=0.03) significantly mediated the relationship between SES and obesity. CONCLUSION: Our results highlighted a number of obesogenic behaviors among socially disadvantaged participants: large plate size, uncontrolled eating and eating at night were significant mediators of the relationship between SES and the obesity risk.

Structural and functional characterization of enamel pigmentation in shrews.

Pigmented tooth enamel occurs in several vertebrate clades, ranging from mammals to fish. Although an iron compound is associated with this orange to red colored pigmentation, its chemical and structural organization within the enamel is unknown. To determine the nature of the iron compound, we investigated heavily pigmented teeth of the northern short-tailed shrew Blarina brevicauda using combined characterization techniques such as scanning and transmission electron microscopy and synchrotron X-ray diffraction. We found that the pigmentation of the enamel with an iron content of around 8wt% results from a close to amorphous magnetite phase deposited around the nm-sized enamel crystals. Furthermore, the influence of the pigmentation on the enamel hardness was determined by nanoindentation measurements. Finally, the biomechanical function and biological context are discussed in light of the obtained results.

Contribution of above- and below-ground plant traits to the structure and function of grassland soil microbial communities.

BACKGROUND AND AIMS: Abiotic properties of soil are known to be major drivers of the microbial community within it. Our understanding of how soil microbial properties are related to the functional structure and diversity of plant communities, however, is limited and largely restricted to above-ground plant traits, with the role of below-ground traits being poorly understood. This study investigated the relative contributions of soil abiotic properties and plant traits, both above-ground and below-ground, to variations in microbial processes involved in grassland nitrogen turnover. METHODS: In mountain grasslands distributed across three European sites, a correlative approach was used to examine the role of a large range of plant functional traits and soil abiotic factors on microbial variables, including gene abundance of nitrifiers and denitrifiers and their potential activities. KEY RESULTS: Direct effects of soil abiotic parameters were found to have the most significant influence on the microbial groups investigated. Indirect pathways via plant functional traits contributed substantially to explaining the relative abundance of fungi and bacteria and gene abundances of the investigated microbial communities, while they explained little of the variance in microbial activities. Gene abundances of nitrifiers and denitrifiers were most strongly related to below-ground plant traits, suggesting that they were the most relevant traits for explaining variation in community structure and abundances of soil microbes involved in nitrification and denitrification. CONCLUSIONS: The results suggest that consideration of plant traits, and especially below-ground traits, increases our ability to describe variation in the abundances and the functional characteristics of microbial communities in grassland soils.

The minimally invasive MitraClip™ procedure for mitral regurgitation under general anaesthesia: immediate effects on the pulmonary circulation and right ventricular function.

A relatively new minimally invasive cardiological procedure, called the MitraClip(™), does not require sternotomy and may have a number of advantages compared with open mitral valve surgery, but its acute impact on the pulmonary circulation and right ventricular function during general anaesthesia is unclear. We prospectively assessed the effects of the MitraClip procedure in 81 patients with or without pulmonary hypertension (defined as mean pulmonary artery pressure > 25 mmHg), who were anaesthetised using fentanyl (5 µg.kg(-1)), etomidate (0.2-0.3 mg.kg(-1)), rocuronium (0.5-0.6 mg.kg(-1)) and isoflurane. Placement of the MitraClip led to a 60% increase in mean (SD) right ventricular stroke work index (from 512 (321) to 820 (470) mmHg.ml.m(-2), p < 0.0001), while mean (SD) pulmonary vascular resistance index decreased by 24% (522 (330) to 399 (244) dyn.s.cm(-5), p < 0.0001), and mean (SD) pulmonary artery pressure decreased by 10% (30 (8) to 27 (8) mmHg, p < 0.0001). Patients with pulmonary hypertension experienced a similar decrease in mean pulmonary artery pressure compared with those without, and they also had a slight reduction in mean (SD) pulmonary artery occlusion pressure (22 (6) down to 20 (6) mmHg, p = 0.044). We conclude that successful MitraClip treatment for mitral regurgitation acutely improves right ventricular performance by reducing right ventricular afterload, regardless of whether patients have pre-operative pulmonary hypertension.

Sleep and wake disturbances following traumatic brain injury.

Traumatic brain injury (TBI) is a major health concern in industrialised countries. Sleep and wake disturbances are among the most persistent and disabling sequelae after TBI. Yet, despite the widespread complaints of post-TBI sleep and wake disturbances, studies on their etiology, pathophysiology, and treatments remain inconclusive. This narrative review aims to summarise the current state of knowledge regarding the nature of sleep and wake disturbances following TBI, both subjective and objective, spanning all levels of severity and phases post-injury. A second goal is to outline the various causes of post-TBI sleep-wake disturbances. Globally, although sleep-wake complaints are reported in all studies and across all levels of severity, consensus regarding the objective nature of these disturbances is not unanimous and varies widely across studies. In order to optimise recovery in TBI survivors, further studies are required to shed light on the complexity and heterogeneity of post-TBI sleep and wake disturbances, and to fully grasp the best timing and approach for intervention.

Determining the likelihood and cost of detecting reductions of nitrate­nitrogen concentrations in groundwater across New Zealand.

Nitrate­nitrogen (NO3-N) is a contaminant of concern in groundwater worldwide. Stakeholders need information on the ability to detect changes in NO3-N concentrations to prove that land management practices are meeting water quality aims. We created a database of quarterly to monthly NO3-N measurements in 948 sites across New Zealand; 186 of those sites had mean residence time (MRT) data. New Zealand has set a target of sufficient land use mitigations in the next 30 years to ensure steady state surface water concentrations do not exceed 2.4 mg L-1. Here we assess whether the current monitoring network could identify the impacts of these mitigations, assuming that the mitigations are successfully implemented at the source. Only 41 % of the network could detect statistically significant reductions with the current standard quarterly sampling after 30 years of monitoring. The percentage of sites increased to 60 % with increased monitoring frequency (often weekly) but this required a 100-300 % increase in monitoring costs. However, policy makers and stakeholders typically require information on policy and mitigation effectiveness within 5-10 years. Detection within 5-10 years was very unlikely (0-20 % of sites) regardless of the sampling frequency. Importantly, these analyses include the impacts of groundwater lag and temporal dispersion on the likelihood of detecting change, ignoring these impacts, incorrectly, yields a much higher likelihood of detecting reductions. We conclude that the current monitoring network is unlikely to be fit for the purpose of detecting NO3-N reductions within practical timeframes or budgets. Furthermore, we conclude that lag and temporal dispersion effects must be included in detection power calculations; we therefore recommend that MRT data is regularly collected. We also provide a python package to enable easy detection power calculations with lag and temporal dispersion impacts, thereby supporting the development of robust change-detection monitoring networks.

A candidate prostate cancer susceptibility gene at chromosome 17p.

It is difficult to identify genes that predispose to prostate cancer due to late age at diagnosis, presence of phenocopies within high-risk pedigrees and genetic complexity. A genome-wide scan of large, high-risk pedigrees from Utah has provided evidence for linkage to a locus on chromosome 17p. We carried out positional cloning and mutation screening within the refined interval, identifying a gene, ELAC2, harboring mutations (including a frameshift and a nonconservative missense change) that segregate with prostate cancer in two pedigrees. In addition, two common missense variants in the gene are associated with the occurrence of prostate cancer. ELAC2 is a member of an uncharacterized gene family predicted to encode a metal-dependent hydrolase domain that is conserved among eukaryotes, archaebacteria and eubacteria. The gene product bears amino acid sequence similarity to two better understood protein families, namely the PSO2 (SNM1) DNA interstrand crosslink repair proteins and the 73-kD subunit of mRNA 3' end cleavage and polyadenylation specificity factor (CPSF73).

The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds.

Breast carcinoma is the most common malignancy among women in developed countries. Because family history remains the strongest single predictor of breast cancer risk, attention has focused on the role of highly penetrant, dominantly inherited genes in cancer-prone kindreds (1). BRCA1 was localized to chromosome 17 through analysis of a set of high-risk kindreds (2), and then identified four years later by a positional cloning strategy (3). BRCA2 was mapped to chromosomal 13q at about the same time (4). Just fifteen months later, Wooster et al. (5) reported a partial BRCA2 sequence and six mutations predicted to cause truncation of the BRCA2 protein. While these findings provide strong evidence that the identified gene corresponds to BRCA2, only two thirds of the coding sequence and 8 out of 27 exons were isolated and screened; consequently, several questions remained unanswered regarding the nature of BRCA2 and the frequency of mutations in 13q-linked families. We have now determined the complete coding sequence and exonic structure of BRCA2 (GenBank accession #U43746), and examined its pattern of expression. Here, we provide sequences for a set of PCR primers sufficient to screen the entire coding sequence of BRCA2 using genomic DNA. We also report a mutational analysis of BRCA2 in families selected on the basis of linkage analysis and/or the presence of one or more cases of male breast cancer. Together with the specific mutations described previously, our data provide preliminary insight into the BRCA2 mutation profile.

The nature of deep overturning and reconfigurations of the silicon cycle across the last deglaciation.

Changes in ocean circulation and the biological carbon pump have been implicated as the drivers behind the rise in atmospheric CO2 across the last deglaciation; however, the processes involved remain uncertain. Previous records have hinted at a partitioning of deep ocean ventilation across the two major intervals of atmospheric CO2 rise, but the consequences of differential ventilation on the Si cycle has not been explored. Here we present three new records of silicon isotopes in diatoms and sponges from the Southern Ocean that together show increased Si supply from deep mixing during the deglaciation with a maximum during the Younger Dryas (YD). We suggest Antarctic sea ice and Atlantic overturning conditions favoured abyssal ocean ventilation at the YD and marked an interval of Si cycle reorganisation. By regulating the strength of the biological pump, the glacial-interglacial shift in the Si cycle may present an important control on Pleistocene CO2 concentrations.

[Teratozoospermia at the time of intracytoplasmic morphologically selected sperm injection (IMSI)]. / La tératozoospermie à l'heure de l'intracytoplasmic morphologically selected sperm injection (IMSI).

Until now, the morphological sperm analysis (spermocytogram) allows to define sperm normality, but the relationship between sperm morphology and fertility is not yet assessed. Although several studies do not report any relationship between abnormal sperm morphology and ICSI results, nevertheless, the success rate of ICSI sems to be dependent on injected sperm morphological aspect. Detailed morphological sperm examination (especially sperm head) at high magnification (from x 6600 to x 12500) (MSOME) in real time allows to select the best spermatozoa before oocyte injection (IMSI). In some cases, implantation and ongoing pregnancy rates were improved with this sperm selection method. Ultramorphologic criteria were established and the most predictive factor of sperm quality is the presence of vacuoles in the sperm head. Those vacuoles appear to be related to DNA damage (fragmentation and/or denaturation) and affect embryo development. To standardize those observations, several authors tried to establish sperm MSOME classifications in order to be used in routine and to replace the conventional spermocytogram in the next future.

Nabothian cyst content: A potential pitfall for the diagnosis of invasive cancer on Pap test cytology.

Nabothian cysts are common, benign findings of the squamocolumnar junction of the adult cervix. These cysts are filled with mucus and can also contain proteinaceous material, neutrophils, or neutrophil debris. Nabothian cysts can be broken by the spatula during smear taking, may stick to the brush and be smeared onto slides in conventional cytology or dissolved in the preserving solution for liquid-based cytology (LBC) preparations. The granular content of Nabothian cysts may be mistaken for the tumor diathesis (TD) pattern associated with invasive carcinoma. In the case described, the patient presented a high-grade squamous intraepithelial lesion associated with granular material (Nabothian cyst content) that we considered erroneously on LBC to be TD-like material, thus, raising the suspicion of invasive carcinoma. To the best of our knowledge, this is the first report showing that Nabothian cyst content may present a potential pitfall in the diagnosis of invasive carcinoma on LBC.

Influence of mitochondrial enzyme deficiency on adult neurogenesis in mouse models of neurodegenerative diseases.

Mitochondrial defects including reduction of a key mitochondrial tricarboxylic acid cycle enzyme alpha-ketoglutarate-dehydrogenase complex (KGDHC) are characteristic of many neurodegenerative diseases. KGDHC consists of alpha-ketoglutarate dehydrogenase, dihydrolipoyl succinyltransferase (E2k), and dihydrolipoamide dehydrogenase (Dld) subunits. We investigated whether Dld or E2k deficiency influences adult brain neurogenesis using immunohistochemistry for the immature neuron markers, doublecortin (Dcx) and polysialic acid-neural cell adhesion molecule, as well as a marker for proliferation, proliferating cell nuclear antigen (PCNA). Both Dld- and E2k-deficient mice showed reduced Dcx-positive neuroblasts in the subgranular zone (SGZ) of the hippocampal dentate gyrus compared with wild-type mice. In the E2k knockout mice, increased immunoreactivity for the lipid peroxidation marker, malondialdehyde occurred in the SGZ. These alterations did not occur in the subventricular zone (SVZ). PCNA staining revealed decreased proliferation in the SGZ of E2k-deficient mice. In a transgenic mouse model of Alzheimer's disease, Dcx-positive cells in the SGZ were also reduced compared with wild type, but Dld deficiency did not exacerbate the reduction. In the malonate lesion model of Huntington's disease, Dld deficiency did not alter the lesion-induced increase and migration of Dcx-positive cells from the SVZ into the ipsilateral striatum. Thus, the KGDHC subunit deficiencies associated with elevated lipid peroxidation selectively reduced the number of neuroblasts and proliferating cells in the hippocampal neurogenic zone. However, these mitochondrial defects neither exacerbated certain pathological conditions, such as amyloid precursor protein (APP) mutation-induced reduction of SGZ neuroblasts, nor inhibited malonate-induced migration of SVZ neuroblasts. Our findings support the view that mitochondrial dysfunction can influence the number of neural progenitor cells in the hippocampus of adult mice.

[Embryo quality and selection]. / Qualité et sélection des embryons.

Embryo quality is routinely evaluated based on morphological and kinematic criteria, but it should also be founded on clinical and biological data from the ovulation induction treatments and the data from the SPZ test, with, if necessary, their genetic analysis. Zygote quality evaluation is based on the zygote score or the P0 profiles. Embryo cleavage kinetics is evaluated at D1 (early cleavage 25-27 h post-insemination), at D2 (four cells), and at D3 (eight cells), and their selection, particularly for eSET, is for the most part based on the cell number and regularity, the percentage of fragmentation (< or = 20 %) and the location of the fragments and the absence of blastomere polynucleation. Imaging software (Fertimorph) now facilitates the evaluation of embryo quality.

Immunoperoxidase localization of bile salts in rat liver cells. Evidence for a role of the Golgi apparatus in bile salt transport.

The mechanisms of intracellular transport of bile acids from the sinusoidal pole to the canalicular pole of the hepatocyte are poorly understood. There is physiological and autoradiographic evidence for a vesicular pathway. The purpose of this study was to determine the localization of natural bile acids in the liver using antibodies against cholic acid conjugates and ursodeoxycholic acid. An indirect immunoperoxidase technique was used on rat liver sections fixed either with paraformaldehyde (PF) and saponin, a membrane-permeabilizing agent that allows penetration of antibodies into the cell, or with PF alone. Retention of taurocholate in the liver after tissue processing was 26 +/- SD 15% of the bile acid initially present. When sections fixed with PF and saponin were incubated with the antibody against cholic acid conjugates, a granular cytoplasmic staining was observed by light microscopy in all hepatocytes. By electron microscopy, strong electron-dense deposits were observed mostly on vesicles of the Golgi apparatus (GA) and, sometimes, in the smooth endoplasmic reticulum (SER). After taurocholate infusion, the intensity of the reaction increased. When the liver was fixed with PF alone, almost no reaction was visible on light microscopy, but on electron microscopy the label was localized on the hepatocyte plasma membrane, mainly on the bile canalicular domain and to a lesser extent on the sinusoidal domain. With the antibody against ursodeoxycholic acid, no staining was observed in three of four livers, and a slight staining was observed in one. However, after infusion of ursodeoxycholic acid, staining of GA and SER vesicles was observed when the liver was fixed with PF and saponin. With PF alone, the reaction was intense on the canalicular membrane. These results support the view that, within the limits of the method, vesicles from the GA and possibly vesicles of the SER are involved in the intracellular transport of bile acids before canalicular secretion.

The modifications of the long-range temporal correlations of the sleep EEG due to major depressive episode disappear with the status of remission.

OBJECTIVE: The aim of the present study is to investigate the scaling properties of the sleep electroencephalogram (EEG) in remitted depressed men, and to evaluate if a past history of major depressive disorder (MDD) could modify significantly and definitively, as a "scar marker," the dynamics of the sleep EEG time series. METHODOLOGY: Whole night sleep electroencephalogram signals were recorded in 24 men: 10 untreated depressed men in full to partial remission (42.43+/-5.62 years) and 14 healthy subjects (42.8+/-8.55 years). Scaling properties in these time series were investigated with detrended fluctuation analysis (DFA) (time range: 0.16-2.00 s). The scaling exponent alpha was determined in stage 2, in slow wave sleep (stages 3 and 4), and during rapid eye movement (REM) sleep. Forty-five epochs of 20 s were chosen randomly in each of these stages for each subject in both groups. RESULTS: We did not observe a significant difference and deviation of the scaling exponents between the two groups during the three sleep stages of interest. CONCLUSION: In this study, we do not observe any functional sequelae of a past history of one or more unipolar major depressive episode on the fluctuation properties of the sleep EEG. This finding is a sign of similar underlying neuronal dynamics in healthy controls and patients with a lifetime history of MDD. This study gives an additional argument to the theory that depression does not modify definitively the dynamics of the neuronal networks and is therefore against the "depressive scar hypothesis," in which permanent residual deficit is created by the acute state of the depressive disease.