bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tegument ultrastructure in mother sporocysts ofBunocotyle progenetica(Markowski, 1936) Chabaud & Buttner, 1959 (Digenea: Hemiuridae)
Authors: Podvyaznaya I.M. , Filimonova S.A. 
Published: April 2023

ABSTRACTThis investigation is devoted to the fine structure of mother sporocysts, the least studied stage of the digenean life cycle. The ultrastructure of the tegument of mature mother sporocysts ofBunocotyle progeneticawas examined by transmission electron microscopy and described in detail. The tegument of these parthenitae is represented by an outer anucleate syncytium connected with the deeper-lying tegumental cells by cytoplasmic bridges. Its outer plasma membrane forms minute leaf-like outgrowths and numerous deep invaginations in the shape of interconnected channels. These channels, which pass in various directions and permeate almost the entire outer syncytium, considerably amplify its surface area. The cytoplasm of the outer layer of the tegument contains large mitochondria, microtubules and rare dense secretory granules, whose contents are discharged into the lumen of the channels. Numerous pinocytotic vesicles originate from the plasma membrane of the channels. Small endocytic vesicles are transported along the cytoplasmic bridges to the tegumental cells, where endocytosed food material is sorted and broken down. These cells are characterized by a well-developed Golgi apparatus, which is represented by multiple stacks of cisternae, and the presence of numerous endosomes at different stages of maturity and residual bodies. Some steps of endosomal maturation in the tegumental cells were traced. In addition to their digestive activity, tegumental cells produce secretory granules, which are transported to the outer syncytium after their maturation. It was shown for the first time that in mature parthenitae, the population of tegumental cells could be renewed at the expense of a reserve pool of undifferentiated cells. The ultrastructural features of the tegument of mother sporocysts ofB. progeneticaare discussed in the light of the concept of the enhanced trophic function of the tegument in sporocysts lacking the alimentary canal.
Atomistic Modeling of Liquid-Liquid Phase Equilibrium Explains Dependence of Critical Temperature on γ-Crystallin Sequence
Authors: Qin Sanbo , Zhou Huan-Xiang 
Published: April 2023

AbstractLiquid-liquid phase separation of protein solutions has regained heightened attention for its biological importance and pathogenic relevance. Coarse-grained models are limited when explaining residue-level effects on phase equilibrium. Here we report phase diagrams for γ-crystallins using atomistic modeling. The calculations were made possible by combining our FMAP method for computing chemical potentials and Brownian dynamics simulations for configurational sampling of dense protein solutions, yielding the binodal and critic temperature (Tc). We obtain a higherTcfor a known high-Tcγ-crystallin, γF, than for a low-Tcparalog, γB. The difference inTcis corroborated by a gap in second virial coefficient. Decomposition of inter-protein interactions reveals one amino-acid substitution between γB and γF, from Ser to Trp at position 130, as the major contributor to the difference inTc. This type of analysis enables us to link phase equilibrium to amino-acid sequence and to design mutations for altering phase equilibrium.
Not one, but multiple radiations underlie the biodiversity of Madagascar’s endangered lemurs
Authors: Everson Kathryn M. , Pozzi Luca , Barrett Meredith A. , Blair Mary E. , Donohue Mariah E. , Kappeler Peter M. , Kitchener Andrew C. , Lemmon Alan R. , Lemmon Emily M. , Pavón-Vázquez Carlos J. , Radespiel Ute , Randrianambinina Blanchard , Rasoloarison Rodin M. , Rasoloharijaona Solofonirina , Roos Christian , Salmona Jordi , Yoder Anne D. , Zenil-Ferguson Rosana , Zinner Dietmar , Weisrock David W. 
Published: April 2023

AbstractLemurs are a well-known example of adaptive radiation. Since colonizing Madagascar, more than 100 extant lemur species have evolved to fill the variety of ecological niches on the island. However, recent work suggests that lemurs do not exhibit one of the hallmarks of adaptive radiations: explosive speciation rates that decline over time. We test this idea using a phylogenomic dataset with broad taxonomic sampling of lemurs and their sister group, the lorisiforms of Asia and continental Africa. We find higher rates of speciation in Madagascar’s lemurs compared to lorisiforms and we confirm that lemurs did not experience an “early burst” of speciation after colonizing Madagascar. Instead, we identify three independent bursts of speciation approximately 15 million years ago that underly much of today’s lemur diversity. We demonstrate that the lemur clades with exceptionally high diversification rates have higher rates of introgression. This suggests that hybridization in these primates is not an evolutionary dead- end, but a driving force for diversification. Considering the conservation crisis affecting strepsirrhine primates, with approximately 95% of species being threatened with extinction, this phylogenomic study offers a new perspective for explaining Madagascar’s exceptional primate diversity and reveals patterns of speciation, extinction, and gene flow that will help inform future conservation decisions.
Tau Filaments from Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex (ALS/PDC) adopt the CTE Fold
Authors: Qi Chao , Verheijen Bert M. , Kokubo Yasumasa , Shi Yang , Tetter Stephan , Murzin Alexey G. , Nakahara Asa , Morimoto Satoru , Vermulst Marc , Sasaki Ryogen , Aronica Eleonora , Hirokawa Yoshifumi , Oyanagi Kiyomitsu , Kakita Akiyoshi , Ryskeldi-Falcon Benjamin , Yoshida Mari , Hasegawa Masato , Scheres Sjors H.W. , Goedert Michel 
Published: April 2023

ABSTRACTThe amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) of the island of Guam and the Kii peninsula of Japan is a fatal neurodegenerative disease of unknown cause that is characterised by the presence of abundant filamentous tau inclusions in brains and spinal cords. Here we used electron cryo-microscopy (cryo-EM) to determine the structures of tau filaments from the cerebral cortex of three cases of ALS/PDC from Guam and eight cases from Kii, as well as from the spinal cord of two of the Guam cases. Tau filaments had the chronic traumatic encephalopathy (CTE) fold, with variable amounts of Type I and Type II filaments. Paired helical tau filaments were also found in two Kii cases. We also identified a novel Type III CTE tau filament, where protofilaments pack against each other in an anti-parallel fashion. ALS/PDC is the third known tauopathy with CTE-type filaments and abundant tau inclusions in cortical layers II/III, the others being CTE and subacute sclerosing panencephalitis. Because these tauopathies are believed to have environmental causes, our findings support the hypothesis that ALS/PDC is caused by exogenous factors.SIGNIFICANCEA neurodegenerative disease of unknown cause on the island of Guam and the Kii peninsula of Japan has been widely studied, because patients can suffer from the combined symptoms of motor neuron disease, parkinsonism and dementia. Abnormal filamentous inclusions made of tau protein characterise this amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) and their formation closely correlates with neurodegeneration. Here we have used electron cryo-microscopy (cryo-EM) to show that tau filaments from ALS/PDC are identical to those from chronic traumatic encephalopathy (CTE), a disease caused by repetitive head impacts or blast waves. CTE tau filaments are also found in subacute sclerosing panencephalitis, which is a rare consequence of measles infection. ALS/PDC may therefore also be caused by environmental factors.
Evolutionarily-conserved behavioral plasticity enables context-dependent performance of mating behavior inC. elegans
Authors: Susoy Vladislav , Samuel Aravinthan D.T. 
Published: April 2023

SummaryBehavioral plasticity helps humans and animals to achieve their goals by adapting their behaviors to different environments. Although behavioral plasticity is ubiquitous, many innate species-specific behaviors, such as mating, are often assumed to be stereotyped and unaffected by plasticity or learning, especially in invertebrates. Here, we describe a novel case of behavioral plasticity in the nematodeC. elegans– under a different set of naturalistic conditions the male uses a unique, previously undescribed set of behavioral steps for mating. Under standard lab conditions (agar plates with bacterial food), the male performs parallel mating, a largely two-dimensional behavioral strategy where his body and tail remain flat on the surface and slide alongside the partner ‘s body from initial contact to copulation. But when placed in liquid medium, the male performs spiral mating, a distinctly three-dimensional behavioral strategy where he winds around the partner ’s body in a helical embrace. The performance of spiral mating does not require a long-term change in growing conditions but it does improve with experience. This experience-dependent improvement involves a critical period – a time window around the L4 to early adult stage, which coincides with the development of most male-specific neurons. We tested several wild isolates ofC. elegansand otherCaenorhabditisspecies and found that most were capable of parallel mating on surfaces and spiral mating in liquids. We suggest that two- and three-dimensional mating strategies inCaenorhabditisare plastic, conditionally expressed phenotypes conserved across the genus, and which can be genetically “fixed ” in some species.
Computational Mechanobiology Model Evaluating Healing of Postoperative Cavities Following Breast-Conserving Surgery
Authors: Harbin Zachary , Sohutskay David , Vanderlaan Emma , Fontaine Muira , Mendenhall Carly , Fisher Carla , Voytik-Harbin Sherry , Tepole Adrian Buganza 
Published: April 2023

AbstractBreast cancer is the most commonly diagnosed cancer type worldwide. Given high survivorship, increased focus has been placed on long-term treatment outcomes and patient quality of life. While breast-conserving surgery (BCS) is the preferred treatment strategy for early-stage breast cancer, anticipated healing and breast deformation (cosmetic) outcomes weigh heavily on surgeon and patient selection between BCS and more aggressive mastectomy procedures. Unfortunately, surgical outcomes following BCS are difficult to predict, owing to the complexity of the tissue repair process and significant patient-to-patient variability. To overcome this challenge, we developed a predictive computational mechanobiological model that simulates breast healing and deformation following BCS. The coupled biochemical-biomechanical model incorporates multi-scale cell and tissue mechanics, including collagen deposition and remodeling, collagen-dependent cell migration and contractility, and tissue plastic deformation. Available human clinical data evaluating cavity contraction and histopathological data from an experimental porcine lumpectomy study were used for model calibration. The computational model was successfully fit to data by optimizing biochemical and mechanobiological parameters through the Gaussian Process. The calibrated model was then applied to define key mechanobiological parameters and relationships influencing healing and breast deformation outcomes. Variability in patient characteristics including cavity-to-breast volume percentage and breast composition were further evaluated to determine effects on cavity contraction and breast cosmetic outcomes, with simulation outcomes aligning well with previously reported human studies. The proposed model has the potential to assist surgeons and their patients in developing and discussing individualized treatment plans that lead to more satisfying post-surgical outcomes and improved quality of life.
Dynamic saccade context triggers more stable object-location binding
Authors: Lu Zitong , Golomb Julie D. 
Published: April 2023

AbstractOur visual systems rapidly perceive and integrate information about object identities and locations. There is long-standing debate about how we achieve world-centered (spatiotopic) object representations across eye movements, with many studies reporting persistent retinotopic (eye-centered) effects even for higher-level object-location binding. But these studies are generally conducted in fairly static experimental contexts. Might spatiotopic object-location binding only emerge in more dynamic saccade contexts? In the present study, we investigated this using the Spatial Congruency Bias paradigm in healthy adults. In the static (single saccade) context, we found purely retinotopic binding, as before. However, robust spatiotopic binding emerged in the dynamic (multiple frequent saccades) context. We further isolated specific factors that modulate retinotopic and spatiotopic binding. Our results provide strong evidence that dynamic saccade context can trigger more stable object-location binding in ecologically-relevant spatiotopic coordinates, perhaps via a more flexible brain state which accommodates improved visual stability in the dynamic world.Significance StatementOne of the most fundamental challenges for human behavior is how we integrate and stabilize perceptual information in our ever-changing sensory environments. In particular, we make multiple eye movements every second, constantly displacing and distorting our visual input. Yet despite receiving visual input in these disjointed, eye-centered (retinotopic) coordinates, we perceive the world as stable, based on objects’ world-centered (spatiotopic) locations. Our study provides strong evidence for a previously unstudied cue – dynamic saccade context – in triggering more stable object-location binding, which offers a novel step forward in understanding how we form a stable perception of the dynamic world. More broadly, these findings suggest the importance of considering dynamic saccade context in visual perception and cognitive neuroscience studies.
Psychedelic Concentrations of Nitrous Oxide Reduce Functional Differentiation in Frontoparietal and Somatomotor Cortical Networks
Authors: Dai Rui , Huang Zirui , Larkin Tony E. , Tarnal Vijay , Picton Paul , Vlisides Phillip E. , Janke Ellen , McKinney Amy , Hudetz Anthony G. , Harris Richard E. , Mashour George A. 
Published: April 2023

AbstractDespite the longstanding use of nitrous oxide and descriptions of its psychological effects more than a century ago, there is a paucity of neurobiological investigation of associated psychedelic experiences. Identifying the impact of nitrous oxide on functional brain networks would advance understanding and contribute to the growing body of research in psychedelic neuroscience. Based on human resting-state fMRI data acquired before and during the administration of 35% nitrous oxide, we measured the brain’s functional geometry (through analysis of cortical gradients) and temporal dynamics (through analysis of co-activation patterns). Both analyses show that nitrous oxide reduces functional differentiation in frontoparietal and somatomotor networks. Importantly, the subjective psychedelic experience induced by nitrous oxide is inversely correlated with the degree of functional differentiation. Thus, like classical psychedelics acting on 5-HT2 receptors, nitrous oxide flattens the functional geometry of the cortex and disrupts temporal dynamics in association with psychoactive effects.
Broadly neutralizing antibodies targeting a conserved silent face of spike RBD resist extreme SARS-CoV-2 antigenic drift
Authors: Song Ge , Yuan Meng , Liu Hejun , Capozzola Tazio , Lin Ryan N. , Torres Jonathan L. , He Wan-ting , Musharrafieh Rami , Dueker Katharina , Zhou Panpan , Callaghan Sean , Mishra Nitesh , Yong Peter , Anzanello Fabio , Avillion Gabriel , Vo Anh Lina , Li Xuduo , Makhdoomi Muzamil , Feng Ziqi , Zhu Xueyong , Peng Linghang , Nemazee David , Safonova Yana , Briney Bryan , Ward Andrew B , Burton Dennis R. , Wilson Ian A. , Andrabi Raiees 
Published: April 2023

SummaryDeveloping broad coronavirus vaccines requires identifying and understanding the molecular basis of broadly neutralizing antibody (bnAb) spike sites. In our previous work, we identified sarbecovirus spike RBD group 1 and 2 bnAbs. We have now shown that many of these bnAbs can still neutralize highly mutated SARS-CoV-2 variants, including the XBB.1.5. Structural studies revealed that group 1 bnAbs use recurrent germline encoded CDRH3 features to interact with a conserved RBD region that overlaps with class 4 bnAb site. Group 2 bnAbs recognize a less well-characterized "site V" on the RBD and destabilize spike trimer. The site V has remained largely unchanged in SARS-CoV- 2 variants and is highly conserved across diverse sarbecoviruses, making it a promising target for broad coronavirus vaccine development. Our findings suggest that targeted vaccine strategies may be needed to induce effective B cell responses to escape resistant subdominant spike RBD bnAb sites.
Identification of a new Corin atrial natriuretic peptide-converting enzyme substrate: Agouti-signaling protein (ASIP)
Authors: MacDonald Bryan T. , Elowe Nadine H. , Garvie Colin W. , Kaushik Virendar K. , Ellinor Patrick T. 
Published: April 2023

AbstractCorin is a transmembrane tethered enzyme best known for processing the hormone atrial natriuretic peptide (ANP) in cardiomyocytes to control electrolyte balance and blood pressure. Loss of function mutations in Corin prevent ANP processing and lead to hypertension. Curiously, Corin loss of function variants also result in lighter coat color pigmentation in multiple species. Corin pigmentation effects are dependent on a functional Agouti locus encoding the agouti-signaling protein (ASIP) based on a genetic interaction. However, the nature of this conserved role of Corin has not been defined. Here we report that ASIP is a direct proteolytic substrate of the Corin enzyme.
Network analysis for identifying potential anti-virulence targets through whole transcriptome analysis ofPseudomonas aeruginosaandStaphylococcus aureusexposed to certain anti-pathogenic polyherbal formulations
Authors: Ruparel Feny , Shah Siddhi , Patel Jhanvi , Thakkar Nidhi , Gajera Gemini , Kothari Vijay 
Published: April 2023

AbstractTranscriptome of two important pathogens,Pseudomonas aeruginosaandStaphylococcus aureusexposed to two different quorum-modulatory polyherbal formulations were subjected to network analysis to identify the most highly networked differentially expressed genes (hubs) as potential anti-virulence targets. Genes associated with denitrification and sulfur metabolism emerged as the most important targets inP. aeruginosa. Increased build-up of nitrite (NO2) inP. aeruginosaculture exposed to the polyherbal formulationPanchvalkalwas confirmed throughin vitroassay too. Generation of nitrosative stress and inducing sulfur starvation seems to be effective anti-pathogenic strategies against this notorious gram-negative pathogen. Important targets identified inS. aureuswere the transcriptional regulatorsarA, immunoglobulin-binding protein Sbi, serine proteaseSplA, thesaeR/Sresponse regulator system, and gamma-haemolysin componentshlgBandhlgC. Further validation of the potential targets identified in these pathogens is warranted through appropriatein vitroandin vivoassays in model hosts. Such validated targets can prove vital to many antibacterial drug discovery programmes globally.
Migratory pattern of zoonoticToxocara catiandT. canisin experimentally infected pigs
Authors: Poulsen Casper Sahl , Yoshida Ayako , Wellbrant Tinna Thordardottir , Leifsson Pall Skuli , Skallerup Per , Thamsborg Stig Milan , Nejsum Peter 
Published: April 2023

AbstractOver a billion people are infected withToxocara canisorT. cati, the roundworms of dogs and cats. Historically,T. canishas been considered the main responsible of human toxocarosis but as serodiagnosis cannot discriminate the two species, this remains unresolved. We assessed the migratory pattern ofT. catiandT. canisin a pig model and found them to be equally infective. Overall, they had a similar migration pattern reaching multiple organs and tissues, including mesenteric lymph nodes, liver, lungs and diaphragm. We recovered larvae of both species in the brain, suggesting thatT. catialso can cause neurological toxocarosis in humans. Both species induced systemic eosinophilia and histopathological changes in lungs, livers and mesenteric lymph nodes. This study emphasizes the importance ofT. catias a zoonotic agent and the need to develop diagnostic methods that can differentiate between sources of infection in humans.
Investigating Spatiotemporal Dynamics of Cortical Activity During Language Production in the Healthy and Lesioned Brain
Authors: Mesnildrey Quentin , Aksenov Alexandre , D’Ambra Malo Renaud , Hartwigsen Gesa , Volpert Vitaly , Beuter Anne 
Published: April 2023

AbstractEfficient language production requires rapid interactions between different brain areas. These interactions can be severely affected by brain lesions. However, the neurophysiological correlates of the spatiotemporal dynamics during language production are not well understood. The current pilot study explores differences in spatiotemporal cortical dynamics between five subjects with post-stroke aphasia and five control subjects. Electroencephalography was recorded during picture naming in both groups.Average-based analyses (event-related potential (ERP), frequency-specific Global Field Power (GFP)), reveal a strong synchronization of cortical oscillations, especially within the first 600ms post-stimulus, with a time shift between participants with aphasia and control subjects. ERPs and the corresponding brain microstates indicate coordinated brain activity alternating mainly between frontal and occipital zones. This behavior can be described as standing waves between two main sources.At the single-trial scale, traveling waves (TW) were identified from both phase and amplitude analyses. The spatiotemporal distribution of amplitude TW reveals subject-specific organization of several interconnected hubs. In patients with aphasia this spatial organization of TW reveals zones with no TW notably in the vicinity of stroke lesions.The present results provide important hints for the hypothesis that TW contribute to the synchronization and communication between different brain areas especially by interconnecting cortical hubs. Moreover, our findings show that cortical dynamics is affected by brain lesions.Contribution to the FieldSpatiotemporal cortical dynamics of individual trials reveals the presence of phase and amplitude traveling waves.Exploration of traveling waves on the 2D cortical surface reveals the presence of interconnected epicenters or hubs in all subjects.The spatiotemporal distribution of traveling waves shows a higher density in the prefrontal area for people with aphasia than for healthy subjects.For subjects with aphasia, a sparser density of traveling waves is observed in the approximated lesion area.Event-related potential analyses reveal a consistent alternating activity between the frontal and occipital regions.Subjects with aphasia present a larger and/or delayed contribution in the delta range in the GFP patterns compared to control subjects.