bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recent insights into Fc-mediated effector responses to HIV-1
Authors: Carpenter Margaret C. , Ackerman Margaret E. 
Published: July 2020

Purpose of review
Recent work defining Fc-mediated effector functions for both viral control and protection against infection is summarized and considered along with new strategies to drive robust Fc-mediated responses.

Recent findings
In new human and nonhuman primate (NHP) vaccine trials as well as studies of natural infection, Fc-mediated effector responses have sometimes been observed to correlate with decreased risk of infection or with better clinical outcomes, suggesting a potential role for these responses in HIV-1 prevention and therapy. Recent highlights include use of antibody-dependent cellular cytotoxicity-sensitizing CD4-induced mimetic compounds, novel V1V2 immunogens, passive transfer studies, and vaccine regimens that successfully elicited Fc-mediated responses and were reported to decrease risk of infection in challenge studies in NHPs. Lastly, detailed studies of IgG3 forms of HIV-specific antibodies have reported that both neutralizing and Fc-mediated responses can be increased relative to the more prevalent IgG1 subclass.

Summary
Successful harmonization of neutralizing and Fc-mediated responses may make key contributions to the goal of reducing HIV-1 infection via active and passive vaccination. New studies continue to highlight the importance of Fc-mediated antibody responses as correlates of decreased risk of infection and suggest enhanced phagocytosis is a potential mechanism of reduced risk of infection associated with human IgG3 responses. Results from recent studies may help guide the rational design of therapies and vaccines that aim to specifically leverage antibody effector function.
Efficacy and safety study of direct-acting oral anticoagulants for the treatment of chronic portal vein thrombosis in patients with liver cirrhosis
Authors: Ai Ming-hua , Dong Wei-guo , Tan Xiao-ping , Xu Ling , Xu Chao , Zhang Qing , Zhang Yan , Li Jie 
Published: July 2020

Aims
This study is designed to investigate the efficacy and safety of direct-acting oral anticoagulants (DOACs) for the treatment of chronic portal vein thrombosis (PVT) in liver cirrhosis patients.

Materials and methods
In a prospective cohort study, patients were divided into DOACs group (oral rivaroxaban tablets or dabigatran etexilate capsules) and control group (no anticoagulant treatment). Based on propensity score matching method, 40 patients with cirrhosis and chronic PVT in each of the groups were recruited for this study. CT portal venography was used to monitor the portal vein area. Color Doppler ultrasound was used to monitor the portal vein flow rate. Biochemical testing and thromboelastography (TEG) were also used for monitoring the status of PVT.

Results
After 3 months of DOACs treatment, the complete/partial recanalization rate of DOACs was 12.8% (5/39). After 6 months of DOACs treatment, the PVT complete/partial recanalization rate of DOACs was 28.2% (11/39). The recanalization rate and portal vein flow velocity improvement were higher than those in the control group (P < 0.05). Patients’ total bilirubin level and Child-Pugh scores were improved in the DOACs group. The TEG coagulation index was lower in the DOACs group than in the control group (P < 0.05). There was no statistically significant difference between the DOACs group and control group in the cases of bleeding (P > 0.05).

Conclusion
DOACs are effective and safe for chronic PVT in patients with liver cirrhosis. The TEG can predict the risk of bleeding in patients with chronic PVT in cirrhosis, which is more sensitive than conventional coagulation function test.
Neonatal Dengue With HLH: Perks of Early Diagnosis and Management
Authors: Krishnappa Archana , Munusamy Jeyaraj , Ray Somosri , Rameshbabu Monisha , Bhatia Prateek , Roy Pritam S. , Sundaram Venkataseshan , Kumar Praveen 
Published: July 2020

Background:
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening, aggressive syndrome. It can be primary, which involves genetic mutation with an early presentation, or secondary to infections, malignancies, etc., due to absence of immune downregulation. It is a very rare condition in newborns. Dengue is a potential virus causing HLH, but, in newborns, there are only few case reports and limited clinical literature.

Observation:
Herein, in this report, we highlight a case of neonatal HLH, triggered by perinatal dengue. The neonate manifested clinically within the first week of life, the earliest reported timeline so far in the literature.

Conclusion:
HLH should be excluded in neonates especially when multisystem involvement cannot be explained by sepsis alone.
Vascularized Composite Parietal Bone Flap for Immediate Reconstruction of a Hemi-Maxillectomy Defect in an Infant
Authors: Chandler Ludmila , Pourtaheri Navid , Maniskas Seija , Ahmad Maham , Lopez Joseph , Steinbacher Derek M. 
Published: July 2020

Background:
Surgical resection of maxillary tumors can result in defects that can be difficult to reconstruct by conventional means due to the complex functional and anatomic nature of the midface and lack of regional bone flap options in the head and neck. Many reconstructive methods have been used to repair maxillary defects, but the ideal technique for the reconstruction of hemi-maxillectomy defects in growing pediatric patients has yet to be determined.

Methods:
The authors present a rare pediatric patient with melanotic neuroectodermal tumor of infancy resulting in a hemi-maxillectomy defect after resection that was reconstructed using a pedicled vascularized composite flap consisting of temporalis muscle, pericranium, and parietal bone.

Results:
The patient achieved successful long-term bony reconstruction of his right maxilla with this flap. Stable skeletal fixation with adequate orbital support was maintained over a >3-year follow-up period.

Conclusion:
A vascularized composite parietal bone flap is a reliable reconstructive option for reconstruction of large maxillectomy defects providing low donor-site morbidity, adequate globe support, excellent long-term skeletal stability, and malar symmetry in rapidly growing pediatric patients. Successful reconstruction for a rare patient with maxillary melanotic neuroectodermal tumor of infancy requiring hemi-maxillectomy was demonstrated with >3-year follow-up.
A structural model of a Ras-Raf signalosome
Authors: Mysore Venkatesh P. , Zhou Zhi-Wei , Ambrogio Chiara , Li Lianbo , Kapp Jonas N. , Lu Chunya , Wang Qi , Tucker Maxwell R. , Okoro Jeffrey J. , Nagy-Davidescu Gabriela , Bai Xiaochen , Plückthun Andreas , Jänne Pasi A. , Westover Kenneth D. , Shan Yibing , Shaw David E. 
Published: July 2020

AbstractThe protein K-Ras functions as a molecular switch in signaling pathways regulating cell growth. In the MAPK pathway, which is implicated in many cancers, multiple K-Ras proteins are thought to assemble at the cell membrane with Ras-effector proteins from the Raf family. Here we propose an atomistic structural model for such an assembly. Our starting point was an asymmetric, GTP-mediated K-Ras dimer model, which we generated using unbiased molecular dynamics simulations and verified with mutagenesis experiments. Adding further K-Ras monomers in a head-to-tail fashion led to a compact helical assembly, a model we validated using electron microscopy and cell-based experiments. This assembly stabilizes K-Ras in its active state and presents composite interfaces to facilitate Raf binding. Guided by existing experimental data, we then positioned C-Raf, the downstream kinase MEK1, and accessory proteins (Galectin-3 and 14-3-3σ) on the helical assembly. The resulting Ras-Raf signalosome model offers an explanation for a large body of data on MAPK signaling.
Erythrocyte-targeted immunomodulatory antigens enabled by in vivo selection of D-peptides
Authors: Loftis Alexander R. , Zhang Genwei , Backlund Coralie , Quartararo Anthony J. , Pishesha Novalia , Schissel Carly K. , Garafola Daniel , Loas Andrei , Collier R. John , Ploegh Hidde , Irvine Darrell J. , Pentelute Bradley L. 
Published: July 2020

AbstractTargeting of antigens to erythrocytes can be used to selectively mitigate their immunogenicity, but the methods to equip a variety of cargoes with erythrocyte-targeting properties are limited. Here we identified a D-peptide that targets murine erythrocytes and decreases anti-drug antibody responses when conjugated to the protective antigen fromBacillus anthracis, a protein of therapeutic interest. The D-peptide likewise decreases inflammatory anti-ovalbumin (OVA) CD8+T cell responses when attached to a peptide antigen derived from OVA. To discover this targeting ligand, we leveraged mass spectrometry to decode a randomized D-peptide library selected in mice, extending the application of synthetic libraries to in vivo affinity selections.
The blood-brain barrier studiedin vitroacross species
Authors: Thomsen Maj Schneider , Humle Nanna , Hede Eva , Moos Torben , Burkhart Annette , Thomsen Louiza Bohn 
Published: July 2020

AbstractThe blood-brain barrier (BBB) is formed by brain capillary endothelial cells (BECs) supported by pericytes and astrocytes. The BBB maintains homeostasis and protects the brain against toxic substances circulating in the blood, which consequently means that only a few drugs can pass the BBB. Thus for drug screening, understanding cell interactions, and pathology,in vitroBBB models have been developed using BECs from various animal sources. When comparing models of different species, differences exist especially in regards to the transendothelial electrical resistance (TEER). Thus, in the present study, we compared primary mice, rat, and porcine BECs (mBECs, rBECs, and pBECs) cultured in mono- and co-culture with astrocytes, to identify potential species-dependent differences that could explain the variations in TEER and aid to the selection of models for futurein vitroBBB studies.Thein vitroBBB models based on primary mBECs, rBECs, and pBECs were evaluated and compared in regards to major BBB characteristics. The barrier integrity was evaluated by the expression of tight junction proteins and measurements of TEER and apparent permeability (Papp). Furthermore, the cell size, the functionality of the P-glycoprotein (P-gp) efflux transporter, and the expression of the transferrin receptor were evaluated and compared.pBECs exhibit the highest TEER followed by rBECs and mBECs, but surprisingly the Papp was not that different, which might be explained by a significantly larger cell size of pBECs than rBECs and mBECs. The expression and organization of many tight junction proteins were in all three species influenced by co-culturing, which supports the findings that the TEER increases after co-culturing with astrocytes. Furthermore, all models had functional polarised P-gp efflux transporters and expressed the transferrin receptor. In conclusion, the choice of species for in vitro BBB modeling should be based on the purpose of the study.
Astrocyte-neuron crosstalk through Hedgehog signaling mediates cortical circuit assembly
Authors: Xie Yajun , Kuan Aaron T. , Wang Wengang , Herbert Zachary T. , Mosto Olivia , Olukoya Olubusola , Adam Manal , Vu Steve , Kim Minsu , Gómez Nicolás , Tran Diana , Charpentier Claire , Sorour Ingie , Tolstorukov Michael Y. , Sabatini Bernardo L. , Lee Wei-Chung Allen , Harwell Corey C. 
Published: July 2020

SUMMARYNeuron-glia relationships play a critical role in the regulation of synapse formation and neuronal specification. The cellular and molecular mechanisms by which neurons and astrocytes communicate and coordinate are not well understood. Here we demonstrate that the canonical Sonic hedgehog (Shh) pathway is active in cortical astrocytes, where it acts to coordinate layer-specific synaptic connectivity and functional circuit development. We show that Ptch1 is a Shh receptor that is expressed by cortical astrocytes during development and that Shh signaling is necessary and sufficient to promote the expression of layer-specific astrocyte genes involved in regulating synapse formation and function. Loss of Shh in layer V neurons reduces astrocyte complexity and coverage by astrocytic processes in tripartite synapses, moreover, cell-autonomous activation of Shh signaling in astrocytes promotes cortical excitatory synapse formation. Together, these results suggest that Shh secreted from deep layer cortical neurons acts to specialize the molecular and functional features of astrocytes during development to shape circuit assembly and function.
Multi-scale predictions distinctively modulate tone perception in schizophrenia patients with auditory verbal hallucinations
Authors: Yang Fuyin , Zhu Hao , Yu Lingfang , Lu Weihong , Zhang Chen , Tian Xing 
Published: July 2020

AbstractsAuditory verbal hallucinations (AVHs) are one of the most pronounced symptoms that manifest the underlying mechanisms of deficits in schizophrenia. Cognitive models postulate that malfunctioned source monitoring incorrectly weights the top-down prediction and bottom-up sensory processing and causes hallucinations. Here, we investigate the featural-temporal characteristics of source monitoring in AVHs. Schizophrenia patients with and without AVHs, and healthy controls identified target tones in noise at the end of tone sequences. Predictions of different timescales were manipulated by either an alternating pattern in the preceding tone sequences, or a repetition between the target tone and the tone immediately before. The sensitivity index, d’, was obtained to assess the modulation of predictions on tone identification. We found that patients with AVHs showed higher d’ when the target tones conformed to the long-term regularity of alternating pattern in the preceding tone sequence than that when the targets were inconsistent with the pattern. Whereas, the short-term regularity of repetitions modulated the tone identification in patients without AVHs. Predictions did not influence tone identification in healthy controls. These findings suggest that malfunctioned source monitoring in AVHs heavily weights predictions to form incorrect perception. The weighting function in source monitoring can extend to the process of basic tonal features, and predictions at multiple timescales differentially modulate perception in different clinical populations. These collaboratively reveal the featural and temporal characteristics of weighting function in source monitoring of AVHs and suggest that the malfunctioned interaction between top-down and bottom-up processes might underlie the development of auditory hallucinations.HighlightsMalfunctioned source monitoring incorrectly weights the top-down prediction and bottom-up sensory processing underlie pathogenesis of auditory verbal hallucinations in schizophrenia.The weighting function in top-down predictions and bottom-up sensory processing can extend to tonal features.Predictions at multiple timescales differentially modulate perception in different clinical schizophrenia populations.
Evidence of SARS-CoV2 entry protein ACE2 in the human nose and olfactory bulb
Authors: Klingenstein M. , Klingenstein S. , Neckel P.H. , Mack A. F. , Wagner A. , Kleger A. , Liebau S. , Milazzo A. 
Published: July 2020

ABSTRACTUsually, pandemic COVID-19 disease, caused by SARS-CoV2, presents with mild respiratory symptoms such as fever, cough but frequently also with anosmia and neurological symptom. Virus-cell fusion is mediated by Angiotensin-Converting Enzyme 2 (ACE2) and Transmembrane Serine Protease 2 (TMPRSS2) with their organ expression pattern determining viral tropism. Clinical presentation suggests rapid viral dissemination to central nervous system leading frequently to severe symptoms including viral meningitis. Here, we provide a comprehensive expression landscape of ACE2 and TMPRSS2 proteins across human, post-mortem nasal and olfactory tissue. Sagittal sections through the human nose complemented with immunolabelling of respective cell types represent different anatomically defined regions including olfactory epithelium, respiratory epithelium of the nasal conchae and the paranasal sinuses along with the hardly accessible human olfactory bulb. ACE2 can be detected in the olfactory epithelium, as well as in the respiratory epithelium of the nasal septum, the nasal conchae and the paranasal sinuses. ACE2 is located in the sustentacular cells and in the glandular cells in the olfactory epithelium, as well as in the basal cells, glandular cells and epithelial cells of the respiratory epithelium. Intriguingly, ACE2 is not expressed in mature or immature olfactory receptor neurons and basal cells in the olfactory epithelium. Similarly ACE2 is not localized in the olfactory receptor neurons albeit the olfactory bulb is positive. Vice versa, TMPRSS2 can also be detected in the sustentacular cells and the glandular cells of the olfactory epithelium.Our findings provide the basic anatomical evidence for the expression of ACE2 and TMPRSS2 in the human nose, olfactory epithelium and olfactory bulb. Thus, they are substantial for future studies that aim to elucidate the symptom of SARS-CoV2 induced anosmia of via the olfactory pathway.
Moderate prenatal alcohol exposure increases total length of L1 axons in E15.5 mice
Authors: Kiss Shannon , Herrera Karen , McElroy Abigail , Blake Kelsey , Sicher Avery , Crocker Emily , Jacob Christa , Lefkove McKayla , Cramer Myla , Henriksen Allysen , Novacek Josef , Severa Jenna , Siberski Justin , Thomas Emily , Favero Carlita B. 
Published: July 2020

AbstractPublic health campaigns broadcast the link between heavy alcohol consumption during pregnancy and physical, cognitive, and behavioral birth defects; however, they appear less effective in deterring moderate consumption prevalent in women who are pregnant or of childbearing age. The incidence of mild Fetal Alcohol Spectrum Disorders (FASD) is likely underestimated because the affected individuals lack physical signs such as retarded growth and facial dysmorphology and cognitive/behavioral deficits are not commonly detected until late childhood. Sensory information processing is distorted in FASD, but alcohol effects on the development of axons that mediate these functions are not widely investigated. We hypothesize that alcohol exposure alters axon growth and guidance contributing to the aberrant connectivity that is a hallmark of FASD. To test this, we administered alcohol to pregnant dams from embryonic day (E) 7.5 to 14.5, during the time that axons which form the major forebrain tracts are growing. We found that moderate alcohol exposure had no effect on body weight of E15.5 embryos, but significantly increased the length of L1+ axons. Our findings support our hypothesis. Future studies will investigate cellular, molecular, and functional mechanisms that underlie these effects.
Characterizing receptor flexibility to predict mutations that lead to human adaptation of influenza hemagglutinin
Authors: Xu Huafeng , Palpant Timothy , Weinberger Cody , Shaw David E. 
Published: July 2020

AbstractA key step in the emergence of human pandemic influenza strains has been a switch in the binding preference of the viral glycoprotein hemagglutinin (HA) from avian to human sialic acid receptors (SAs). The conformation of the bound SA varies substantially with HA sequence, and crystallographic evidence suggests that the bound SA is flexible, so it is difficult to predict from crystal structures which mutations are responsible for the change in HA binding preference. We performed molecular dynamics (MD) simulations of SA analogs binding to various HAs, and observed a dynamic equilibrium among structurally diverse receptor conformations, including novel conformations that have not been experimentally observed. Using one such novel conformation, we predicted—and subsequently confirmed with microscale thermophoresis experiments—a set of mutations that substantially increased an HA’s affinity for a human SA analog. This prediction could not have been inferred from existing crystal structures, suggesting that MD-generated HA-SA conformational ensembles could help researchers predict human-adaptive mutations, aiding in the surveillance of emerging pandemic threats.
Dynamic spatiotemporal coordination of neural stem cell fate decisions through local feedback in the adult vertebrate brain
Authors: Dray Nicolas , Mancini Laure , Binshtok Udi , Cheysson Felix , Supatto Willy , Mahou Pierre , Bedu Sébastien , Ortica Sara , Krecsmarik Monika , Herbert Sébastien , Masson Jean-Baptiste , Tinevez Jean-Yves , Lang Gabriel , Beaurepaire Emmanuel , Sprinzak David , Bally-Cuif Laure 
Published: July 2020

SUMMARYNeural stem cell (NSC) populations persist in the adult vertebrate brain over a life time, and their homeostasis is controlled at the population level. The nature and properties of these coordination mechanisms remain unknown. Here we combine dynamic imaging of entire NSC populations in theirin vivoniche over weeks, pharmacological manipulations, mathematical modeling and spatial statistics, and demonstrate that NSCs use spatiotemporally resolved local feedbacks to coordinate their decision to divide. These involve a Notch-mediated inhibition from transient neural progenitors, and a dispersion effect from dividing NSCs themselves, exerted with a delay of 9-12 days. Simulations from a stochastic NSC lattice model capturing these interactions demonstrate that they are linked by lineage progression and control the spatiotemporal distribution of output neurons. These results highlight how local and temporally delayed interactions occurring between brain germinal cells generate self-propagating dynamics that maintain NSC population homeostasis with specific spatiotemporal correlations.
Endothelial reprogramming by disturbed flow revealed by single-cell RNA and chromatin accessibility study
Authors: Andueza Aitor , Kumar Sandeep , Kim Juyoung , Kang Dong-Won , Mumme Hope L , Perez Julian I , Jo Hanjoong 
Published: July 2020

SUMMARYDisturbed flow(d-flow)induces atherosclerosis by regulating gene expression in endothelial cells (ECs). For further mechanistic understanding, we carried out a single-cell RNA sequencing (scRNAseq) and scATACseq study using endothelial-enriched single-cells from the left- and right carotid artery exposed to d-flow (LCA) and stable-flow (s-flowin RCA) using the mouse partial carotid ligation (PCL) model. We found 8 EC clusters along with immune cells, fibroblasts, and smooth muscle cells. Analyses of marker genes, pathways, and pseudo-time revealed that ECs are highly heterogeneous and plastic.D-flowinduced a dramatic transition of ECs from atheroprotective phenotypes to pro-inflammatory, mesenchymal (EndMT), hematopoietic stem cells, endothelial stem/progenitor cells, and an unexpected immune cell-like (EndICLT) phenotypes. While confirming KLF4/KLF2 ass-flow-sensitive transcription factor binding site, we also found those sensitive to d-flow (RELA, AP1, STAT1, and TEAD1). D-flow reprograms ECs from atheroprotective to pro-atherogenic phenotypes including EndMT and potentially EndICLT.