Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of EBV-mediated membrane fusion by anti-gHgL antibodies

Significance Herpesviruses infect a large percentage of the human population and are responsible for a significant human health disease burden. EBV, like other herpesviruses, expresses a set of glycoproteins—gH, gL, and gB—responsible for virus entry into cells, which are targets of protective antibody responses and potential candidates for vaccine development. Here we study the interactions and mechanisms of two anti-EBV antibodies that recognize the gHgL complex, providing a foundation for understanding herpesvirus neutralization. Herpesvirus entry into cells requires the coordinated action of multiple virus envelope glycoproteins, including gH, gL, and gB. For EBV, the gp42 protein assembles into complexes with gHgL heterodimers and binds HLA class II to activate gB-mediated membrane fusion with B cells. EBV tropism is dictated by gp42 levels in the virion, as it inhibits entry into epithelial cells while promoting entry into B cells. The gHgL and gB proteins are targets of neutralizing antibodies and potential candidates for subunit vaccine development, but our understanding of their neutralizing epitopes and the mechanisms of inhibition remain relatively unexplored. Here we studied the structures and mechanisms of two anti-gHgL antibodies, CL40 and CL59, that block membrane fusion with both B cells and epithelial cells. We determined the structures of the CL40 and CL59 complexes with gHgL using X-ray crystallography and EM to identify their epitope locations. CL59 binds to the C-terminal domain IV of gH, while CL40 binds to a site occupied by the gp42 receptor binding domain. CL40 binding to gHgL/gp42 complexes is not blocked by gp42 and does not interfere with gp42 binding to HLA class II, indicating that its ability to block membrane fusion with B cells represents a defect in gB activation. These data indicate that anti-gHgL neutralizing antibodies can block gHgL-mediated activation of gB through different surface epitopes and mechanisms.
Aspect controls the survival of ice cliffs on debris-covered glaciers

Significance Glaciers in High Mountain Asia (HMA) are important water sources for millions of people downstream. Ice cliffs on debris-covered glaciers act as hot spots for melt and may explain anomalously high glacier mass losses in HMA, but their temporal evolution remains unknown, hindering sound parameterizations of these features in glacier models. We simulate the evolution of cliff systems with different aspects, show that south-facing ice cliffs disappear within a few weeks in the Northern Hemisphere, and explain the processes driving this. Cliffs that persist melt 10 times faster than the surrounding glacier surfaces. These findings provide a basis for understanding the surface evolution of debris-covered glaciers with implications for their dynamics, mass balance, and hydrology. Supraglacial ice cliffs exist on debris-covered glaciers worldwide, but despite their importance as melt hot spots, their life cycle is little understood. Early field observations had advanced a hypothesis of survival of north-facing and disappearance of south-facing cliffs, which is central for predicting the contribution of cliffs to total glacier mass losses. Their role as windows of energy transfer suggests they may explain the anomalously high mass losses of debris-covered glaciers in High Mountain Asia (HMA) despite the insulating debris, currently at the center of a debated controversy. We use a 3D model of cliff evolution coupled to very high-resolution topographic data to demonstrate that ice cliffs facing south (in the Northern Hemisphere) disappear within a few months due to enhanced solar radiation receipts and that aspect is the key control on cliffs evolution. We reproduce continuous flattening of south-facing cliffs, a result of their vertical gradient of incoming solar radiation and sky view factor. Our results establish that only north-facing cliffs are recurrent features and thus stable contributors to the melting of debris-covered glaciers. Satellite observations and mass balance modeling confirms that few south-facing cliffs of small size exist on the glaciers of Langtang, and their contribution to the glacier volume losses is very small (∼1%). This has major implications for the mass balance of HMA debris-covered glaciers as it provides the basis for new parameterizations of cliff evolution and distribution to constrain volume losses in a region where glaciers are highly relevant as water sources for millions of people.
Joining forces: crosstalk between biochemical signalling and physical forces orchestrates cellular polarity and dynamics

Dynamic processes like cell migration and morphogenesis emerge from the self-organized interaction between signalling and cytoskeletal rearrangements. How are these molecular to sub-cellular scale processes integrated to enable cell-wide responses? A growing body of recent studies suggest that forces generated by cytoskeletal dynamics and motor activity at the cellular or tissue scale can organize processes ranging from cell movement, polarity and division to the coordination of responses across fields of cells. To do so, forces not only act mechanically but also engage with biochemical signalling. Here, we review recent advances in our understanding of this dynamic crosstalk between biochemical signalling, self-organized cortical actomyosin dynamics and physical forces with a special focus on the role of membrane tension in integrating cellular motility. This article is part of the theme issue ‘Self-organization in cell biology’.
Deception by Design: Evidence-Based Signaling Games for Network Defense

Deception plays a critical role in the financial industry, online markets, national defense, and countless other areas. Understanding and harnessing deception - especially in cyberspace - is both crucial and difficult. Recent work in this area has used game theory to study the roles of incentives and rational behavior. Building upon this work, we employ a game-theoretic model for the purpose of mechanism design. Specifically, we study a defensive use of deception: implementation of honeypots for network defense. How does the design problem change when an adversary develops the ability to detect honeypots? We analyze two models: cheap-talk games and an augmented version of those games that we call cheap-talk games with evidence, in which the receiver can detect deception with some probability. Our first contribution is this new model for deceptive interactions. We show that the model includes traditional signaling games and complete information games as special cases. We also demonstrate numerically that deception detection sometimes eliminate pure-strategy equilibria. Finally, we present the surprising result that the utility of a deceptive defender can sometimes increase when an adversary develops the ability to detect deception. These results apply concretely to network defense. They are also general enough for the large and critical body of strategic interactions that involve deception.
Spectrophotometric and Spectrofluorimetric Studies on Azilsartan Medoxomil and Chlorthalidone to Be Utilized in Their Determination in Pharmaceuticals

The recently approved angiotensin II receptor blocker, azilsartan medoxomil (AZL), was determined spectrophotometrically and spectrofluorimetrically in its combination with chlorthalidone (CLT) in their combined dosage form. The UV-spectrophotometric technique depends on simultaneous measurement of the first derivative spectra for AZL and CLT at 286 and 257 nm, respectively, in methanol. The spectrofluorimetric technique depends on measurement of the fourth derivative of the synchronous spectra intensities of AZL in presence of CLT at 298 nm in methanol. The effects of different solvents on spectrophotometric and spectrofluorimetric responses were studied. For, the spectrofluorimetric study, the effect of pH and micelle-assisted fluorescence enhancement were also studied. Linearity, accuracy, and precision were found to be satisfactory over the concentration ranges of 8–50 μg mL−1 and 2–20 μg mL−1 for AZL and CLT, respectively, in the spectrophotometric method as well as 0.01–0.08 μg mL−1 for AZL in the spectrofluorimetric method. The methods were successfully applied for the determination of the studied drugs in their co-formulated tablets. The developed methods are inexpensive and simple for the quality control and routine analysis of the cited drugs in bulk and in pharmaceuticals.
Where Is the Extended Phenotype in the Wild? The Community Composition of Arthropods on Mature Oak Trees Does Not Depend on the Oak Genotype

Through a series of common garden experiments, it has been shown that heritable phenotypic differences between individual trees can affect arthropod communities. However, field studies under heterogeneous environmental conditions remain rare. In the present study, we investigated the genetic constitution of 121 mature oak host trees at different trophic levels from 10 sites across Bavaria, southern Germany and their associated insect communities. A total of 23,576 individuals representing 395 species of beetles and true bugs were evaluated. In particular, we determined whether the composition of arthropod communities is related to the oak genotype and whether the strength of the relationships decreases from lower to higher trophic levels, such as for phytophagous, xylophagous, zoophagous, and mycetophagous species. The genetic differentiation of oaks was assessed using eight microsatellite markers. We found no significant influence of the oak genotype on neither the full beetle and true bug community nor on any of the analyzed trophic guilds. In contrast, the community composition of the insects was highly related to the space and climate, such that the community similarity decreased with increases in spatial distance and climatic differences. The relationship with space and climate was much stronger in beetles than in true bugs, particularly in mycetophagous species. Our results suggest that spatial processes override the genetic effects of the host plant in structuring arthropod communities on oak trees. Because we used neutral markers, we cannot exclude the possibility that trait-specific markers may reveal a genetic imprint of the foundation tree species on the composition of the arthropod community. However, based on the strength of the spatial patterns in our data set, we assume that genetic differences among oaks are less important in the structuring of arthropod communities. Future whole-genome studies are required to draw a final conclusion.
Experimental Investigation on Mechanical Characterization of Fiber Reinforced Foamed Concrete

With the increase in demand for structures which are light in weight, researcher and industrialist interest in foamed concrete to be used in structural applications is steadily increasing. Foamed concrete is currently believed to have a promising future. Foamed concrete was restricted to use as partition wall, thermal insulation, filling the void and rehabilitation work in the past. In the last two decades, with the understanding of the phenomenon underlying foamed concrete, researchers have studied various parameters that affects the performance of foamed concrete with and without fibers, and efforts have been made to use foamed concrete in structural application. The main objective of the research is to investigate the mechanical and structural properties of plain and fiber reinforced foamed concreteFoamed concrete also known as cellular concrete or lightweight concrete is a type of concrete with cementitious paste, fines, water and voids without coarse aggregate. The voids are created by using foam. The use of admixtures such as fly ash, silica fume and fibers in the foam concrete provide more strength than plain foamed concrete (PFC). Under this research program, three different mixes were made: plain foam concrete (PFC), polypropylene fiber reinforced foam concrete (PPFC) and basalt fiber reinforced foam concrete (BFC). Specimens were tested for compressive strength, splitting tensile strength, Young’s Modulus and Poisson’s ratio, Flexural strength and RFC (Reinforced Foamed Concrete) strength. This study showed that the use of optimum foam volume i.e. 20% gives a specific density of foam concrete 70 – 100 pcf and compressive strength of 3000 – 5500 psi. For the study of flexural application, eight different steel reinforced sandwich beams were tested. For study of compression application, sixteen compression columns, eight of them with reinforcement and eight without reinforcement were tested. Steel reinforced sandwich beams were divided into four different sets, two of each, normal concrete - Styrofoam R-13 rating combination, normal concrete - PFC combination, normal concrete - PPFC combination and normal concrete – BFC combination. Similarly, to study the structural behavior of the compression column, specimens were divided into different groups as that of sandwich beams. The flexural strength of BFC specimen was 10 times more than PFC specimen. Among the RFC beam specimens, BFC has shown maximum load carrying capacity. Also, experimental results show that normal concrete – BFC combination has shown the highest load carrying capacity under bending. Among the compression column normal concrete – PFC combination has shown the highest load carrying capacity.
Scale Impacts Elicited Gestures for Manipulating Holograms: Implications for AR Gesture Design

Because gesture design for augmented reality (AR) remains idiosyncratic, people cannot necessarily use gestures learned in one AR application in another. To design discoverable gestures, we need to understand what gestures people expect to use. We explore how the scale of AR affects the gestures people expect to use to interact with 3D holograms. Using an elicitation study, we asked participants to generate gestures in response to holographic task referents, where we varied the scale of holograms from desktop-scale to room-scale objects. We found that the scale of objects and scenes in the AR experience moderates the generated gestures. Most gestures were informed by physical interaction, and when people interacted from a distance, they sought a good perspective on the target object before and during the interaction. These results suggest that gesture designers need to account for scale, and should not simply reuse gestures across different hologram sizes.
Easy and fast extraction methods to determine organochlorine pesticides in sewage sludge, soil, and water samples based at low temperature

ABSTRACT Organochlorine pesticides present in sewage sludge can contaminate soil and water when they are used as either fertilizer or agricultural soil conditioner. In this study, the technique solid–liquid extraction with low temperature purification was optimized and validated for determination of ten organochlorine pesticides in sewage sludge and soil samples. Liquid–liquid extraction with low temperature purification was also validated for the same compounds in water. Analyses were performed by gas chromatography-mass spectrometry operating in the selective ion monitoring mode. After optimization, the methods showed recoveries between 70% and 115% with relative standard deviation lower than 13% for all target analytes in the three matrices. The linearity was demonstrated in the range of 20 to 70 µg L−1, 0.5 to 60 µg L−1, and 3 to 13 µg L−1, for sludge, soil, and acetonitrile, respectively. The limit of quantification ranged between 2 and 40 µg kg−1, 1 and 6 µg kg−1, and 0.5 µg L−1 for sludge, soil, and water, respectively. The methods were used in the study of pesticide lixiviation carried out in a poly vinyl chlorine column filled with soil, which had its surface layer mixed with sludge. The results showed that pesticides are not leached into soil, part of them is adsorbed by the sewage sludge (4–40%), and most pesticides are lost by volatilization.
Myofibril breakdown during atrophy is a delayed response requiring the transcription factor PAX4 and desmin depolymerization

Significance Muscle wasting as occurs with disuse, spinal injuries, aging, and many diseases (including cancer, sepsis, and renal failure) results primarily from the accelerated destruction of the myofibrillar apparatus, although the molecular mechanisms for this effect are largely unclear. To gain insight into the sequence of events leading to myofibril destruction, we studied the atrophy induced by denervation. We found that phosphorylation and ubiquitination of the desmin cytoskeleton precede its depolymerization, which eventually causes myofibril destruction. We further uncovered a delayed phase in the atrophy process, which involves the induction of genes that facilitate myofibril breakdown, including the AAA-ATPase p97/VCP, by the transcription factor paired box 4 (PAX4). Consequently, desmin phosphorylation, p97/VCP, and PAX4 may represent new therapeutic targets to reduce myofibril breakdown during atrophy. A hallmark of muscle atrophy is the excessive degradation of myofibrillar proteins primarily by the ubiquitin proteasome system. In mice, during the rapid muscle atrophy induced by fasting, the desmin cytoskeleton and the attached Z-band–bound thin filaments are degraded after ubiquitination by the ubiquitin ligase tripartite motif-containing protein 32 (Trim32). To study the order of events leading to myofibril destruction, we investigated the slower atrophy induced by denervation (disuse). We show that myofibril breakdown is a two-phase process involving the initial disassembly of desmin filaments by Trim32, which leads to the later myofibril breakdown by enzymes, whose expression is increased by the paired box 4 (PAX4) transcription factor. After denervation of mouse tibialis anterior muscles, phosphorylation and Trim32-dependent ubiquitination of desmin filaments increased rapidly and stimulated their gradual depolymerization (unlike their rapid degradation during fasting). Trim32 down-regulation attenuated the loss of desmin and myofibrillar proteins and reduced atrophy. Although myofibrils and desmin filaments were intact at 7 d after denervation, inducing the dissociation of desmin filaments caused an accumulation of ubiquitinated proteins and rapid destruction of myofibrils. The myofibril breakdown normally observed at 14 d after denervation required not only dissociation of desmin filaments, but also gene induction by PAX4. Down-regulation of PAX4 or its target gene encoding the p97/VCP ATPase reduced myofibril disassembly and degradation on denervation or fasting. Thus, during atrophy, the initial loss of desmin is critical for the subsequent myofibril destruction, and over time, myofibrillar proteins become more susceptible to PAX4-induced enzymes that promote proteolysis.
An amidase is required for proper intercellular communication in the filamentous cyanobacterium Anabaena sp. PCC 7120

Significance The filamentous cyanobacterium Anabaena has become a widely studied model to determine the molecular mechanisms involved in establishing and maintaining the pattern of heterocyst differentiation in response to the removal of fixed nitrogen from the environment. Heterocysts develop from vegetative cells, usually spaced about 10 cells apart, converting an oxic cell capable of division into an anoxic factory for nitrogen fixation that does not divide. Genetic analysis to elucidate the mechanisms of intercellular material exchange between heterocysts and vegetative cells is in an early phase. Here we show that an amidase is involved in the function of channels that penetrate the rigid peptidoglycan walls that separate cells in the filaments. Channels that cross cell walls and connect the cytoplasm of neighboring cells in multicellular cyanobacteria are pivotal for intercellular communication. We find that the product of the gene all1140 of the filamentous cyanobacterium Anabaena sp. PCC 7120 is required for proper channel formation. All1140 encodes an amidase that hydrolyses purified peptidoglycans. An All1140-GFP fusion protein is located at the Z-ring in the periplasmic space during most of the cell cycle. An all1140-null mutant (M40) was unable to grow diazotrophically, and no mature heterocysts were observed in the absence of combined nitrogen. Expression of two key genes, hetR and patS, was studied in M40 using GFP as a reporter. Upon nitrogen step-down, the patterned distribution of green fluorescent cells in filaments seen in the wild type were not observed in mutant M40. Intercellular communication in M40 was studied by measuring fluorescence recovery after photobleaching (FRAP). Movement of calcein (622 Da) was aborted in M40, suggesting that the channels connecting the cytoplasm of neighboring cells are impaired in the mutant. The channels were examined with electron tomography; their diameters were nearly identical, 12.7 nm for the wild type and 12.4 nm for M40, suggesting that AmiC3 is not required for channel formation. However, when the cell wall sacculi isolated by boiling were examined by EM, the average sizes of the channels of the wild type and M40 were 20 nm and 12 nm, respectively, suggesting that the channel walls of the wild type are expandable and that this expandability requires AmiC3.
Typical and subtle atypical presentations of endometriosis

Purpose of review To review the concept of typical, subtle and invisible endometriosis and analyze the evolution and progression of the disease, as well as some factors possibly involved in the pathogenesis. Recent findings Although rejected by Redwine, the concept of non-visible endometriosis has been proven to exist. Some new ideas on the implication of reactive oxygen species in the development of endometriosis and its early stages are described here. Summary The increased diagnosis of endometriosis can be explained not only by the increased experience and ability of the surgeon to detect typical and non-typical endometriotic lesions, but also by a better understanding of the pathogenesis.
Development of a core outcome set for clinical trials in childhood constipation: a study using a Delphi technique

Objective Patients, their parents and healthcare professionals (HCPs) have a different perception regarding the symptoms of functional constipation (FC). Consequently, a lack of agreement exists on definitions and outcomes used in therapeutic trials of FC. Therefore, our aim was to develop a core outcome set (COS) for FC for children aged 0–1 year and 1–18 years. Design and setting Prospective study design: primary, secondary and tertiary care settings. Methods This COS was developed using a Delphi technique. First, HCPs, parents of children with FC and patients aged ≥12–18 years were asked to list up to five outcomes they considered relevant in the treatment of FC. Outcomes mentioned by >10% of participants were included in a shortlist. In the next phase, outcomes on this shortlist were rated and prioritised by HCPs, parents and patients. Outcomes with the highest scores were included in a draft COS. In a face-to-face expert meeting, the final COS was determined. Results The first phase was completed by 109 HCPs, 165 parents and 50 children. Fifty HCPs, 80 parents and 50 children completed the subsequent phase. The response rate was between 63% and 100% in both steps. The final COS for all ages consisted of: defecation frequency, stool consistency, painful defecation, quality of life, side effects of treatment, faecal incontinence, abdominal pain and school attendance. Conclusion The use of this COS for FC will decrease study heterogeneity and improve comparability of studies. Therefore, researchers are recommended to use this COS in future therapeutic trials on childhood FC.