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Résumé: Objectif: Les lymphomes sont des affections fréquentes et graves. Le but de ce travail était de décrire les aspects épidémiologiques et histopathologiques des lymphomes au Togo. Matériel et méthodes: Il s’agit d’une étude rétrospective et descriptive portant sur les lymphomes hodgkiniens et non hodgkiniens observés sur une période de 25 ans (1984 à 2008), au laboratoire d’anatomie pathologique du CHU Tokoin de Lomé, Togo. Résultats: Au cours de notre période d’étude, nous avons colligé 755 cas de lymphomes (92 hodgkiniens et 663 non hodgkiniens) représentant 14,4 % de l’ensemble des cancers. Le lymphome de Hodgkin était observé chez 62 hommes et 30 femmes à un âge moyen de 26,2 ans et les lymphomes non hodgkiniens (LNH) chez 387 hommes et 276 femmes avec un âge moyen de 32 ans. Le lymphome de Hodgkin était de siège ganglionnaire avec une prédominance des types à déplétion lymphocytaire (33,7 %) et scléronodulaire (28,2 %). Les LNH étaient extraganglionnaires dans 256 cas (38,7 %) avec à l’histologie une prédominance du lymphome centroblastique (27,1 %) et du lymphome de Burkitt (21,1 %). Conclusion: Les lymphomes sont fréquents au Togo, survenant le plus souvent chez des sujets relativement jeunes, avec une prédominance masculine.

This article illustrates requirement exchanges based on the STEP AP242 application protocol. These results are the outcomes of the systems engineering interoperability forum (SE‐IF) of the ATLAS program, a working group sponsored by the French industry and the French government. The SE‐IF is composed of manufacturers, who define use cases and assign priorities and solution providers, who implement the standard, carry out interoperability tests and establish recommended practices. The objective of this forum is to enable exchange of requirements and their attributes in a fluid and tool‐agnostic way, to facilitate collaborative work in the context of the extended enterprise. This work gives promising perspectives for standardized transfers of all other systems engineering data.

The characterization of the conformational landscape of the RNA backbone is rather complex due to the ability of RNA to assume a large variety of conformations. These backbone conformations can be depicted by pseudotorsional angles linking RNA backbone atoms, from which Ramachandran-like plots can be built. We explore here different definitions of these pseudotorsional angles, finding that the most accurate ones are the traditional η(eta) and θ(theta) angles, which represent the relative position of RNA backbone atoms P and C4′. We explore the distribution of η− θin known experimental structures, comparing the pseudotorsional space generated with structures determined exclusively by one experimental technique. We found that the complete picture only appears when combining data from different sources. The maps provide a quite comprehensive representation of the RNA accessible space, which can be used in RNA-structural predictions. Finally, our results highlight that protein interactions lead to significant changes in the population of the η− θspace, pointing toward the role of induced-fit mechanisms in protein–RNA recognition.

ABSTRACTLow-temperature conditioning (LTC) has been reported to effectively control post-harvest chilling injury (CI). Conspicuously, it has not been widely adopted by the industry. This is in part related to an incomplete understanding of the factors governing the treatment's efficacy and consistency along genotypes and maturities. Herein, we evaluated the effect of fruit type (stripedand purple)and harvest maturity (babyand large)on the effectiveness of LTC (10°C for 2 days) to control eggplant CI. Purpleeggplants showed a strong increase in chilling susceptibility between the babyand largematurity stages. In contrast, stripedfruit evidenced no major changes in chilling susceptibility along maturation. Susceptible purple largeeggplants benefited far more from LTC than babyfruit. Prestorage LTC not only controlled surface scaled development but also decreased pulp softening and browning. In addition, it substantially improved phenolic antioxidants, anthocyanin, and chlorogenic acid retention during storage at 4°C. Overall, results show, for the first time, that the efficacy of LTC in eggplant is deeply affected by the fruit's genotype and maturity. Low-temperature conditioning may be a valuable tool to improve the storage compatibility of commercial eggplant batches having different chilling injury sensitivity.

Efficient engagement with the envelope glycoprotein membrane-proximal external region (MPER) results in robust blocking of viral infection by a class of broadly neutralizing antibodies (bnAbs) against human immunodeficiency virus (HIV). Developing an accommodation surface that engages with the viral lipid envelope appears to correlate with the neutralizing potency displayed by these bnAbs. The nature of the interactions established between the antibody and the lipid is nonetheless a matter of debate, with some authors arguing that anti-MPER specificity arises only under pathological conditions in autoantibodies endowed with stereospecific binding sites for phospholipids. However, bnAb-lipid interactions are often studied in systems that do not fully preserve the biophysical properties of lipid bilayers, and therefore, questions on binding specificity and the effect of collective membrane properties on the interaction are still open. Here, to evaluate the specificity of lipid interactions of an anti-MPER bnAb (4E10) in an intact membrane context, we determine quantitatively its association with lipid bilayers by means of scanning fluorescence correlation spectroscopy and all-atom molecular dynamic simulations. Our data support that 4E10 establishes electrostatic and hydrophobic interactions with the viral membrane surface and that the collective physical properties of the lipid bilayer influence 4E10 dynamics therein. We conclude that establishment of peripheral, nonspecific electrostatic interactions with the viral membrane through accommodation surfaces may assist high-affinity binding of HIV-1 MPER epitope at membrane interfaces. These findings highlight the importance of considering antibody-lipid interactions in the design of antibody-based anti-HIV strategies.

Background: Primary carcinoid tumors are rare and constitute 0.23% of all testicular tumors. We report a case of primary carcinoid tumor of testicular localization, with a review of the literature.Case presentation: A 29-year-old man, without specific ascendants, consulted the urology department for progressive scrotal swelling of 6 months, associated with pain. After surgery, histology showed diffuse tumor proliferation composed of small round monotone cells with hyperchromatic nuclei evoking undifferentiated carcinoma. Immunohistochemistry showed that tumor cells were positive for chromogranin A and negative for placental alkaline phosphatase and α-fetoprotein.Conclusion: Primary neuroendocrine carcinoma of the testis is a very rare malignant tumor. Immunohistochemistry contributes to its diagnosis in relation to other metastatic neuroendocrine carcinomas, carcinoid tumor teratomas, seminoma, and Sertoli cells.

Les preuves d'une épidémie émergente de cancer du sein en Afrique subsaharienne (ASS) constituent une réalité épidémiologique dont l'ampleur n'a pas encore été évaluée à la mesure de sa gravité. Notre vision à long terme est de contribuer à l'amélioration de la santé de ces populations par une meilleure compréhension de l’épidémiologie et de la génétique du cancer du sein dans cette partie du monde.

We report on the fate of nucleic acids conformation in the gas phase as sampled using native mass spectrometry coupled to ion mobility spectrometry. On the basis of several successful reports for proteins and their complexes, the technique has become popular in structural biology, and the conformation survival becomes more and more taken for granted. Surprisingly, we found that DNA and RNA duplexes, at the electrospray charge states naturally obtained from native solution conditions (≥100 mM aqueous NH4OAc), are significantly more compact in the gas phase compared to the canonical solution structures. The compaction is observed for all duplex sizes (gas-phase structures are more compact than canonical B-helices by ∼20% for 12-bp, and by up to ∼30% for 36-bp duplexes), and for DNA and RNA alike. Molecular modeling (density functional calculations on small helices, semiempirical calculations on up to 12-bp, and molecular dynamics on up to 36-bp duplexes) demonstrates that the compaction is due to phosphate group self-solvation prevailing over Coulomb repulsion. Molecular dynamics simulations starting from solution structures do not reproduce the experimental compaction. To be experimentally relevant, molecular dynamics sampling should reflect the progressive structural rearrangements occurring during desolvation. For nucleic acid duplexes, the compaction observed for low charge states results from novel phosphate–phosphate hydrogen bonds formed across both grooves at the very late stages of electrospray.

Potassium channels are of paramount physiological and pathological importance and therefore constitute significant drug targets. One of the keys to rationalize the way drugs modulate ion channels is to understand the ability of such small molecules to access their respective binding sites, from which they can exert an activating or inhibitory effect. Many computational studies have probed the energetics of ion permeation, and the mechanisms of voltage gating, but little is known about the role of fenestrations as possible mediators of drug entry in potassium channels. To explore the existence, structure, and conformational dynamics of transmembrane fenestrations accessible by drugs in potassium channels, molecular dynamics simulation trajectories were analyzed from three potassium channels: the open state voltage-gated channel Kv1.2, the G protein-gated inward rectifying channel GIRK2 (Kir3.2), and the human two-pore domain TWIK-1 (K2P1.1). The main results of this work were the identification of the sequence identity of four main lateral fenestrations of similar length and with bottleneck radius in the range of 0.9–2.4 Å for this set of potassium channels. It was found that the fenestrations in Kv1.2 and Kir3.2 remain closed to the passage of molecules larger than water. In contrast, in the TWIK-1 channel, both open and closed fenestrations are sampled throughout the simulation, with bottleneck radius shown to correlate with the random entry of lipid membrane molecules into the aperture of the fenestrations. Druggability scoring function analysis of the fenestration regions suggests that Kv and Kir channels studied are not druggable in practice due to steric constraining of the fenestration bottleneck. A high (>50%) fenestration sequence identity was found in each potassium channel subfamily studied, Kv1, Kir3, and K2P1. Finally, the reported fenestration sequence of TWIK-1 compared favorably with another channel, K2P channel TREK-2, reported to possess open fenestrations, suggesting that K2P channels could be druggable via fenestrations, for which we reported atomistic detail of the fenestration region, including the flexible residues M260 and L264 that interact with POPC membrane in a concerted fashion with the aperture and closure of the fenestrations.

Transient receptor potential (TRP) ion channels constitute a notable family of cation channels involved in the ability of an organisms to detect noxious mechanical, thermal, and chemical stimuli that give rise to the perception of pain, taste, and changes in temperature. One of the most experimentally studied agonist of TRP channels is capsaicin, which is responsible for the burning sensation produced when chili pepper is in contact with organic tissues. Thus, understanding how this molecule interacts and regulates TRP channels is essential to high impact pharmacological applications, particularly those related to pain treatment. The recent publication of a three-dimensional structure of the vanilloid receptor 1 (TRPV1) in the absence and presence of capsaicin from single particle electron cryomicroscopy experiments provides the opportunity to explore these questions at the atomic level. In the present work, molecular docking and unbiased and biased molecular dynamics simulations were employed to generate a structural model of the capsaicin–channel complex. In addition, the standard free energy of binding was estimated using alchemical transformations coupled with conformational, translational, and orientational restraints on the ligand. Key binding modes consistent with previous experimental data are identified, and subtle but essential dynamical features of the binding site are characterized. These observations shed some light into how TRPV1 interacts with capsaicin, and may help to refine design parameters for new TRPV1 antagonists, and potentially guide further developments of TRP channel modulators.

Three bulls of the Montbéliarde breed that exhibited fertility rates lower than 30% following more than 400 artificial inseminations were examined. Semen quality (sperm motility and morphology) from these bulls was normal. Fertilizing ability estimated from in vitro embryo production results was studied for two of them. In vitro production rate was very low for one bull (A) and normal for the other (B). Cytogenetic analyses were carried out on the three bulls using chromosome banding techniques. These analyses revealed a reciprocal translocation (12;17)(q22;q14) in bull B. Based on family analyses, the hypothesis of a de novo origin of this rearrangement is proposed.

Four new chromosomal rearrangements are reported in the domestic pig: 3 reciprocal translocations, rcp(4;12)(p13;q13) in a crossbred boar, rcp(1; 7)(q 17;q26) in a Large White purebred boar, rcp(1;6)(q17;q35) in a purebred synthetic paternal line boar, and a pericentric inversion inv(2)(p13q11) in a crossbred boar. The 1/7 reciprocal translocation and the pericentric inversion were detected in animals that had sired small litters. The effect of the 1/7 translocation was accurately determined: –4.5 piglets born per litter, i.e. –36%. Both the 1/6 and 1/7 reciprocal translocations were of maternal origin. All the chromosomal rearrangements were highlighted using GTG and/or RBG banding techniques. Chromosome painting experiments were also carried out to confirm the proposed hypotheses for the three reciprocal translocations.

In combination with other spectroscopy, microscopy, and scattering techniques, neutron reflectivity is a powerful tool to characterize biological systems. Specular reflection of neutrons provides structural information at the nanometer and subnanometer length scales, probing the composition and organization of layered materials. Currently, analysis of neutron reflectivity data involves several simplifying assumptions about the structure of the sample under study, affecting the extraction and interpretation of information from the experimental data. Computer simulations can be used as a source of structural and dynamic data with atomic resolution. We present a novel tool to compare the structural properties determined by neutron reflectivity experiments with those obtained from molecular simulations. This tool allows benchmarking the ability of molecular dynamics simulations to reproduce experimental data, but it also promotes unbiased interpretation of experimentally determined quantities. Two application examples are presented to illustrate the capabilities of the new tool. The first example is the generation of reflectivity profiles for a 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) lipid bilayer from molecular dynamics simulations using data from both atomistic and coarse-grained models, and comparison with experimentally measured data. The second example is the calculation of lipid volume changes with temperature and composition from all atoms simulations of single and mixed 1,2-di-palmitoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine (DPPC) bilayers.

Voltage-gated potassium channels of the Kv1 family play a crucial role in the generation and transmission of electrical signals in excitable cells affecting neuronal and cardiac activities. Small-molecule blockage of these channels has been proposed to occur via a cooperative mechanism involving two main blocking sites: the inner-pore site located below the selectivity filter, and a side-pocket cavity located between the pore and the voltage sensor. Using 0.5 μs molecular dynamics simulation trajectories complemented by docking calculations, the potential binding sites of the PAP-1 (5-(4-phenoxybutoxy)psoralen) blocker to the crystal structure of Kv1.2 channel have been studied. The presence of both mentioned blocking sites at Kv1.2 is confirmed, adding evidence in favor of a cooperative channel blockage mechanism. These observations provide insight into drug modulation that will guide further developments of Kv inhibitors.

Modeling of macromolecular structures and interactions represents an important challenge for computational biology, involving different time and length scales. However, this task can be facilitated through the use of coarse-grained (CG) models, which reduce the number of degrees of freedom and allow efficient exploration of complex conformational spaces. This article presents a new CG protein model named SIRAH, developed to work with explicit solvent and to capture sequence, temperature, and ionic strength effects in a topologically unbiased manner. SIRAH is implemented in GROMACS, and interactions are calculated using a standard pairwise Hamiltonian for classical molecular dynamics simulations. We present a set of simulations that test the capability of SIRAH to produce a qualitatively correct solvation on different amino acids, hydrophilic/hydrophobic interactions, and long-range electrostatic recognition leading to spontaneous association of unstructured peptides and stable structures of single polypeptides and protein–protein complexes.

We report the use of dual-colour chromosome painting to determine the exact nature of certain chromosome rearrangements observed in the pig (Sus scrofa domestica). The chromosomal abnormalities were detected by GTG- and RBG-banding techniques. The initially proposed interpretations were: (1) rcp(6;13)(p1.5;q4.1); (2) rcp(11;16)(p1.4;q1.4); (3) rcp(6;16)(p1.1;q1.1); (4) rcp(13;17)(q4.1;q1.1); (5) rcp(6;14)(q2.7;q2.1); (6) rcp(3;5)(p1.3;q2.3); (7) rcp(2; 14)(q1.3;q2.7); (8) rcp(15;17)(q1.3;q2.1). Hybridizations were carried out with biotin- and digoxigenin-labelled probes obtained by priming authorizing random mismatches polymerase chain reaction (PARM-PCR) amplification of porcine flow-sorted chromosomes. In some cases, i.e. (1), (4), (5), (6), (7) and (8), the fluorescence in situ hybridization (FISH) results allowed confirmation of the interpretations proposed with classical cytogenetic methods. Chromosome painting proved the reciprocity of the translocation in cases (1), (6) and (8), whereas modifications of the formula were proposed for case (2). Primed in situ DNA labelling (PRINS) experiments have also been carried out in case (3) using a primer specific for the centromeres of acrocentric chromosomes (first experiment) or a primer specific for the centromeres of a subset of meta- and submetacentric chromosomes including chromosome 6 (second experiment). It allowed us to demonstrate that the breakpoints occurred in the centromeric region of chromosome 16 and in the p arm of chromosome 6, just above the centromere.

Accurate simulation of biomolecular systems requires the consideration of solvation effects. The arrangement and dynamics of water close to a solute are strongly influenced by the solute itself. However, as the solute–solvent distance increases, the water properties tend to those of the bulk liquid. This suggests that bulk regions can be treated at a coarse grained (CG) level, while keeping the atomistic details around the solute. Since water represents about 80% of any biological system, this approach may offer a significant reduction in the computational cost of simulations without compromising atomistic details. We show here that mixing the popular SPC water model with a CG model for solvation (called WatFour) can effectively mimic the hydration, structure, and dynamics of molecular systems composed of pure water, simple electrolyte solutions, and solvated macromolecules. As a nontrivial example, we present simulations of the SNARE membrane fusion complex, a trimeric protein–protein complex embedded in a double phospholipid bilayer. Comparison with a fully atomistic reference simulation illustrates the equivalence between both approaches.

Biological processes occur on space and time scales that are often unreachable for fully atomistic simulations. Therefore, simplified or coarse grain (CG) models for the theoretical study of these systems are frequently used. In this context, the accurate description of solvation properties remains an important and challenging field. In the present work, we report a new CG model based on the transient tetrahedral structures observed in pure water. Our representation lumps approximately 11 WATer molecules into FOUR tetrahedrally interconnected beads, hence the name WAT FOUR (WT4). Each bead carries a partial charge allowing the model to explicitly consider long-range electrostatics, generating its own dielectric permittivity and obviating the shortcomings of a uniform dielectric constant. We obtained a good representation of the aqueous environment for most biologically relevant temperature conditions in the range from 278 to 328 K. The model is applied to solvate simple CG electrolytes developed in this work (Na+, K+, and Cl−) and a recently published simplified representation of nucleic acids. In both cases, we obtained a good resemblance of experimental data and atomistic simulations. In particular, the solvation structure around DNA, partial charge neutralization by counterions, preference for sodium over potassium, and ion mediated minor groove narrowing as reported from X-ray crystallography are well reproduced by the present scheme. The set of parameters presented here opens the possibility of reaching the multimicroseconds time scale, including explicit solvation, ionic specificity, and long-range electrostatics, keeping nearly atomistic resolution with significantly reduced computational cost.

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Transient receptor potential (TRP) ion channels are important pharmacological targets because of their role in the perception of pain, and so, understanding their chemical regulation is essential for the development of analgesic drugs. Among the currently known TRP channel chemical agonists, capsaicin, the active compound of chili pepper, is probably the most exhaustively studied. The availability of the three-dimensional structure of the vanilloid receptor 1 (TRPV1) has fueled computational studies revealing the molecular details of capsaicin binding modes. Although this is a significant step, a comprehensible binding mechanism or pathway is invaluable for targeting TRP channels in modern pharmacology. In the present work, free-energy and enhanced sampling techniques have been used to explore a possible membrane-mediated pathway for capsaicin to enter the TRPV1 binding pocket where capsaicin accesses the protein starting at the extracellular milieu through the outer leaflet and into its binding site in the protein. The main states visited along this route have been characterized and include (i) a bound state in agreement with the binding mode “head-down, tail-up” and (ii) an alternative state corresponding to a “head-up, tail-down” binding mode. In agreement with previous reports, binding is mediated by both hydrogen bonds and van der Waals interactions, and residue Y511 is crucial for stabilizing the bound state and during the binding process. Together, these results provide a foundation to further understand TRPV channels, and they could be used to guide therapeutic design of selective inhibitors potentially leading to novel avenues for pharmacological applications targeting the TRPV1 channel.

Bruxism has been reported to exist in many children with cerebral palsy; however, only a few studies confirm this fact. The objective of this study was to determine the rate of bruxism in children with cerebral palsy and to relate its presence to the following factors: kind of cerebral palsy, gender, age, dentition, degree of malocclusion. oral mucous membrane trauma, trismus, and number of wear facets on specific teeth. The guardians of 121 children with cerebral palsy between the ages of 4 and 9 years were interviewed and the children were clinically examined. Bruxism was detected in 69.4% of the children and reported by 57% of the guardians. In 4‐and 5‐year‐old children, the rate of wear facets was small. Children with athetosis and spastic tetraplegia had a higher rate of bruxism than all others.

The purpose of this study was to evaluate the impact of enteral nutrition on early outcome of patients after myeloablative allogeneic stem cell transplantation (allo-SCT). From January 2001 to January 2003, 22 patients agreed to receive enteral nutrition via a nasogastric feeding tube; the remaining 23 patients received parenteral nutrition (n22) or standard oral feeding (n1). Early complications and factors influencing 100-day overall survival (OS) were investigated. Patients who received enteral nutrition developed less often acute-grade III/IV graft-versus-host disease (18%) than those who did not (35%) (P0.011). In addition, this group showed lower mortality from infection during the first 100 days after transplantation. In multivariate analyses, only the absence of enteral nutrition was found to adversely influence 100-day OS with a hazard ratio of 8.3. Enteral nutrition is a safe and effective method for feeding allo-SCT patients. A randomized trial is warranted to confirm its advantage on early patient outcome.

Drip loss from thawed, pressure-shift-frozen longissimus dorsi pork was not different from drip loss from fresh meat samples, while cryogen-frozen (using liquid nitrogen at -70 °C) and air-frozen (-20 °C) pork both had significantly higher drip loss (12%) upon thawing when compared to pressure-shift-frozen and fresh pork (4%). Pressure-shift-frozen pork was discolored, with a significant decrease in CIE redness parameter a*, and showed signs of denaturation upon visual inspection. A high molecular weight protein band (Mw 97,000) characteristic for gel electrophoresis (SDS-PAGE) for drip from fresh, air-frozen, and cryogen-frozen pork was not present in drip from pressure-shift-frozen pork. Ice crystals in the frozen pork, as evaluated by image analysis of cavities in digitized pictures from light microscopy of 14 µm-thick meat slices (cut transverse to the fiber direction) embedded in tissue wax following treatment with Carnoy’s fixative and ethanol, increased in the order: pressure-shift-frozen

Eight new cases of reciprocal translocation in the domestic pig are described. All the rearrangements were highlighted using GTG banding techniques. Chromosome painting experiments were also carried out to confirm the proposed hypotheses and to accurately locate the breakpoints. Three translocations, rcp(4;6)(q21;p14), rcp(2;6)(p17;q27) and rcp(5;17)(p12;q13) were found in boars siring small litters (8.3 and 7.4 piglets born alive per litter, on average, for translocations 2/6 and 5/17, respectively). The remaining five, rcp(5;8)(p12;q21), rcp(15;17)(q24;q21), rcp(7;8)(q24;p21), rcp(5;8)(p11;p23) and rcp(3;15)(q27;q13) were identified in young boars controlled before entering reproduction. A decrease in prolificacy of 22% was estimated for the 3/15 translocation after reproduction of the boar carrier. A parental origin by inheritance of the translocation was established for the (5;8)(p11;p23) translocation. The overall incidence of reciprocal translocations in the French pig populations over the 2000/2001 period was estimated (0.34%).

Extracts from preparations of partially purified Anaplasma marginalerevealed low levels of lactate dehydrogenase (LDH). Enzyme inhibition by immune sera further indicated that A. marginalepossesses a protein moiety the same as that of the normal red blood cell (RBC), although data suggested an alteration of LDH1from that observed in normal RBC. Bimodal isozyme distribution was detected after electrophoresis of the extracts. One isozyme approached the cathode and the other the anode, and both appeared to be nicotinamide adenine dinucleotide-dependent. Heterogeneity of parasite and host cell isozymes was established on the basis of zone electrophoresis on cellulose acetate strips.

Cholesterol is a major component of mammalian plasma membranes that not only affects the physical properties of the lipid bilayer but also is the function of many membrane proteins including G protein-coupled receptors. The oxytocin receptor (OXTR) is involved in parturition and lactation of mammals and in their emotional and social behaviors. Cholesterol acts on OXTR as an allosteric modulator inducing a high-affinity state for orthosteric ligands through a molecular mechanism that has yet to be determined. Using the ion channel-coupled receptor technology, we developed a functional assay of cholesterol modulation of G protein-coupled receptors that is independent of intracellular signaling pathways and operational in living cells. Using this assay, we discovered a stable binding of cholesterol molecules to the receptor when it adopts an orthosteric ligand-bound state. This stable interaction preserves the cholesterol-dependent activity of the receptor in cholesterol-depleted membranes. This mechanism was confirmed using time-resolved FRET experiments on WT OXTR expressed in CHO cells. Consequently, a positive cross-regulation sequentially occurs in OXTR between cholesterol and orthosteric ligands. The possibility to selectively stabilize the interaction of functional cholesterol molecules also offers new opportunities for the challenging identification of the functional cholesterol binding site(s) and for deeper understanding of the molecular mechanisms.

Bronze working is a nonnative technical craft which was incorporated relatively late in southern China and Southeast Asia. Debates about the origins of the Bronze Age in these regions hinge on finding the “missing” geographic linkages facilitating the cultural transfer of knowledge during the second millennium BCE. We provide the first series of AMS assays from Bronze Age sites in the Lake Dian basin in Yunnan and definitively connect the timing of tin-bronze metalworking in southwestern China with sites in Northeast Thailand to the 11th to 10th c. BC. Using Bayesian modeling to calibrate dates from stratified deposits, we propose a revised chronology for the Bronze Age and present a division spanning three phases (early, middle, and late). The findings indicate the establishment of settlements beginning in the early 12th c. BC, accompanied by the incorporation of copper-base metallurgy (1100/1000–800 BCE), a middle (800–600 BCE) and late ‘Dian’ period (600–250 BCE) that is identified with the emergence of a bronze drum culture. The revised chronology not only pushes back the timing of copper-base technology in central Yunnan by at least five centuries before the material medium was co-opted by elites as a means of wealth production. Temporal correspondences between the Dian sequence and other prehistoric complexes in the region also strengthen arguments for a potential technological link between Yunnan and Mainland Southeast Asia (MSEA) and the transfer of tin-bronze metallurgical knowledge across geographic regions.

Modern molecular and cellular biology profits from astonishing resolution structural methods, currently even reaching the whole cell level. This is encompassed by the development of computational methods providing a deep view into the structure and dynamics of molecular processes happening at very different scales in time and space. Linking such scales is of paramount importance when aiming at far-reaching biological questions. Computational methods at the interface between classical and coarse-grained resolutions are gaining momentum with several research groups dedicating important efforts to their development and tuning. An overview of such methods is addressed herein, with special emphasis on the SIRAH force field for coarse-grained and multi-scale simulations. Moreover, we provide proof of concept calculations on the implementation of a multi-scale simulation scheme including quantum calculations on a classical fine-grained/coarse-grained representation of double-stranded DNA. This opens the possibility to include the effect of large conformational fluctuations in chromatin segments on, for instance, the reactivity of particular base pairs within the same simulation framework.

Neuroendocrine carcinoma (NEC) of the breast is a rare disease and has been scarcely reported by African authors. The authors report a case of breast NEC in a 13-year-old African girl initially diagnosed as an atypical adenofibroma by ultrasonography. Ultrasound-guided biopsy and conventional histological examination indicated two potential diagnoses: primary malignant non-Hodgkin’s lymphoma and undifferentiated carcinoma. According to immunohistochemistry performed on paraffin blocks in France, infiltrating ductal carcinoma with a strong neuroendocrine component was confirmed by CD56, CD57, and chromogranin A markers.

We intend to implement the ALOHA at 1.55μm up-conversion interferometer on the CHARA Array. After a full laboratory investigation, a sensitivity evaluation is conducted on several stars using a single interferometric arm in a photometric mode. The on-sky photometric results allows us to calibrate a numerical simulation of the interferometric configuration, and to predict the future performance of ALOHA at 1.55μm as a function of the seeing conditions.

We report a case of poorly differentiated squamous cell carcinoma of the vulva induced by human papillomavirus in a 23-year-old woman, in whom we experienced diagnostic difficulties.

Three bulls of the Montbéliarde breed that exhibited fertility rates lower than 30% following more than 400 artificial inseminations were examined. Semen quality (sperm motility and morphology) from these bulls was normal. Fertilizing ability estimated from in vitroembryo production results was studied for two of them. In vitroproduction rate was very low for one bull (A) and normal for the other (B). Cytogenetic analyses were carried out on the three bulls using chromosome banding techniques. These analyses revealed a reciprocal translocation (12;17)(q22;q14) in bull B. Based on family analyses, the hypothesis of a de novoorigin of this rearrangement is proposed.