bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structures of SARS-CoV-2 B.1.351 neutralizing antibodies provide insights into cocktail design against concerning variants
Authors: Du Shuo , Liu Pulan , Zhang Zhiying , Xiao Tianhe , Yasimayi Ayijiang , Huang Weijin , Wang Youchun , Cao Yunlong , Xie Xiaoliang Sunney , Xiao Junyu 
Published: August 2021

AbstractThe spread of the SARS-CoV-2 variants could seriously dampen the global effort to tackle the COVID-19 pandemic. Recently, we investigated the humoral antibody responses of SARS-CoV-2 convalescent patients and vaccinees towards circulating variants, and identified a panel of monoclonal antibodies (mAbs) that could efficiently neutralize the B.1.351 (Beta) variant. Here we investigate how these mAbs target the B.1.351 spike protein using cryo-electron microscopy. In particular, we show that two superpotent mAbs, BD-812 and BD-836, have non-overlapping epitopes on the receptor-binding domain (RBD) of spike. Both block the interaction between RBD and the ACE2 receptor; and importantly, both remain fully efficacious towards the B.1.617.1 (Kappa) and B.1.617.2 (Delta) variants. The BD-812/BD-836 pair could thus serve as an ideal antibody cocktail against the SARS-CoV-2 VOCs.
Spike protein multiorgan tropism suppressed by antibodies targeting SARS-CoV-2
Authors: Brady Molly , Combs Abigail , Venkatraman Chethana , Solorzano Alexander , Johnson Angelique , McQuaid Conor , Rahman Akib , Leyva Hannah , Edmund Kwok Wing-Chi , Wood Ronald W , Deane Rashid 
Published: August 2021

AbstractWhile there is clinical evidence of severe acute respiratory syndrome coronavirus 2 multiorgan tropism in severely infected coronavirus 19 patients, it’s unclear if there is differential multiorgan biodistribution and organ uptake in healthy young individuals, a group that usually has asymptomatic to moderate coronavirus 19 symptoms. In addition, for antibody therapies and vaccines that target the spike protein, it’s unclear if these reduce severe acute respiratory syndrome coronavirus 2 or spike protein multiorgan tropism equally. We used fluorescently labeled spike protein near infrared fluorescence to study viral behavior, using an in vivo dynamic imaging system, in young mice. We found a spike protein body-wide biodistribution followed by a slow regional elimination, except for the liver, which showed an accumulation. Spike protein uptake was highest for the lungs, and this was followed by kidney, heart and liver, but, unlike the choroid plexus, it was not detected in the brain parenchyma or cerebrospinal fluid. Thus, the brain vascular barriers were effective in restricting the entry of spike protein into brain parenchyma in young healthy mice. While both anti-angiotensin converting enzyme 2 and anti-spike protein antibodies suppressed spike protein biodistribution and organ uptake, anti-spike protein antibody was more effective. By extension, our data support the efficacy of these antibodies on severe acute respiratory syndrome coronavirus 2 biodistribution kinetics and multiorgan tropism that could determine coronavirus 19 organ-specific outcomes.
The Effect of Incarceration on Tuberculosis Treatment Outcomes in Brazil: a Retrospective Cohort Study
Authors: O’Marr Jamieson , Gonçalves Crhistinne , Arakaki-Sanchez Denise , Pelissari Daniele Maria , Costa Fernanda Dockhorn , Croda Julio , Walter Katharine S. , Andrews Jason R. 
Published: August 2021

AbstractBackgroundTuberculosis notifications in Latin American prisons have more than doubled over the past two decades; however, treatment outcomes and their determinants among incarcerated individuals in this region are not well understood.MethodsNewly diagnosed drug-susceptible tuberculosis cases reported to Brazil’s Sistema de Informação de Agravos de Notificação (SINAN) between January 2015 and December 2017 were included. Multivariate logistic regression was used to assess socioeconomic and clinical factors associated with treatment success among incarcerated individuals.ResultsIncarcerated individuals (n=17,776) had greater treatment success than non-incarcerated individuals (n=160,728; 82.2% vs 75.1%, p<0.0001), including after adjusting for demographic and clinical risk factors (adjusted Odds Ratio [aOR]: 1.27; 95% CI: 1.19-1.34). These differences were partially mediated by increased use of directly observed therapy among incarcerated individuals (DOT) (61% vs 47%, p<0.001), which was associated with greater efficacy in the incarcerated population (aOR 2.56 vs aOR 2.17; p<0.001). DOT was associated with improved treatment success among incarcerated subpopulations at elevated risk of poor outcomes.ConclusionTuberculosis treatment success among incarcerated individuals in Brazil is higher than non-incarcerated individuals, but both fall below WHO targets. Expanding the use of DOT and services for socially and medically vulnerable individuals may improve outcomes in carceral settings.
STAT3 expression in dendritic cells protects mice from colitis by a gut microbiome-dependent mechanism
Authors: Liu Jianyun , Szilágyi Keely L. , Capitano Maegan L. , Iyer Abhirami K. , He Jiefeng , Olson Matthew R. , Du Jianguang , Van Der Pol William , Morrow Casey , Zhou Baohua , Kaplan Mark H. , Dent Alexander L. , Brutkiewicz Randy R. 
Published: August 2021

AbstractAn imbalance in gut homeostasis results in local and systemic pathogenesis. It is still not well-understood how the immune system interacts with the gut microbiome and maintains a delicate balance. Here, we utilized a mouse model in which STAT3 expression is deleted in CD11c+ (i.e., dendritic) cells (STAT3 cKO); these mice developed an ulcerative colitis-like disease, colon carcinoma and myelodysplastic syndrome-like disease. Circulating IgE levels in STAT3 cKO mice were significantly elevated. The gut microbiome was indispensable for the observed pathogenesis, as treatment with broad-spectrum antibiotics or cross-fostering STAT3 cKO pups with mothers harboring a different microbiome prevented disease development. Gut microbiome analyses suggested that decreased commensal bacteria and increased pathogenic bacteria most likely contributed to disease. Our data suggest that STAT3 controls the manifestation of inflammation in the gut caused by the microbiome. Therefore, we conclude that a deficiency of STAT3 in DCs is sufficient to trigger uncontrolled inflammation and the development of inflammatory bowel disease.
Human centromere formation activates transcription and opens chromatin fibre structure
Authors: Naughton Catherine , Huidobro Covadonga , Catacchio Claudia R. , Buckle Adam , Grimes Graeme R. , Nozawa Ryu-Suke , Purgato Stefania , Rocchi Mariano , Gilbert Nick 
Published: August 2021

AbstractHuman centromeres appear as constrictions on mitotic chromosomes and form a platform for kinetochore assembly in mitosis. Biophysical experiments led to a suggestion that repetitive DNA at centromeric regions form a compact scaffold necessary for function, but this was revised when neocentromeres were discovered on non-repetitive DNA. To test whether centromeres have a special chromatin structure we have analysed the architecture of a neocentromere. Centromere formation is accompanied by RNA pol II recruitment and active transcription to form a decompacted, negatively supercoiled domain enriched in ‘open’ chromatin fibres. In contrast, centromerisation causes a spreading of repressive epigenetic marks to surrounding regions, delimited by H3K27me3 polycomb boundaries and divergent genes. This flanking domain is transcriptionally silent and partially remodelled to form ‘compact’ chromatin, similar to satellite-containing DNA sequences, and exhibits genomic instability. We suggest transcription disrupts chromatin to provide a foundation for kine-tochore formation whilst compact pericentromeric heterochromatin generates mechanical rigidity.
Rational Design of Self-assembling Artificial Proteins Utilizing a Micelle-Assisted Protein Labeling Technology (MAPLabTech): Testing the Scope
Authors: Reddy Mullapudi Mohan , Bhandari Pavankumar , Sandanaraj Britto S 
Published: August 2021

AbstractSelf-assembling artificial proteins (SAPs) have gained enormous interest in recent years due to their applications in different fields. Synthesis of well-defined monodisperse SAPs is accomplished predominantly through genetic methods. However, the last decade witnessed the use of few chemical technologies for that purpose. In particular, micelle-assisted protein labeling technology (MAPLabTech) has made huge progress in this area. The first generation MAPLabTech focused on site-specific labeling of the active-site residue of serine proteases to make SAPs. Further, this methodology was exploited for labeling of N-terminal residue of a globular protein to make functional SAPs. In this study, we describe the synthesis of novel SAPs by developing a chemical method for site-specific labeling of a surface-exposed cysteine residue of globular proteins. In addition, we disclose the synthesis of redox- and pH-sensitive SAPs and their systematic self-assembly and dis-assembly studies using complementary biophysical studies. Altogether these studies further expand the scope of MAPLabTech in different fields such as vaccine design, targeted drug delivery, diagnostic imaging, biomaterials, and tissue engineering.
Individual-level specialisation and interspecific resource partitioning in bees revealed by pollen DNA metabarcoding
Authors: Klečka Jan , Mikát Michael , Koloušková Pavla , Hadrava Jiří , Straka Jakub 
Published: August 2021

ABSTRACTIt is increasingly recognised that intraspecific variation in traits, such as morphology, behaviour, or diet is both ubiquitous and ecologically important. While many species of predators and herbivores are known to display high levels of between-individual diet variation, there is a lack of studies on pollinators. It is important to fill in this gap because individual-level specialisation of flower-visiting insects is expected to affect their efficiency as pollinators with consequences for plant reproduction. Accordingly, the aim of our study was to quantify the level of individual-level specialisation and foraging preferences, as well as interspecific resource partitioning, across different temporal scales in three co-occurring species of bees of the genusCeratina(Hymenoptera: Apidae: Xylocopinae),C.chalybea,C.nigrolabiata, andC.cucurbitina. We conducted a field experiment where we provided artificial nesting opportunities for the bees and combined a short-term mark-recapture study with the dissection of the bees’ nests to obtain repeated samples from individual foraging females and complete pollen provisions from their nests. Hence, we could study variation of the composition of pollen collected by the bees at different temporal scales. We used DNA metabarcoding based on the ITS2 locus to identify the composition of the pollen samples. We found that the composition of pollen carried on the bodies of female bees and stored in the brood provisions in their nests significantly differed among the three co-occurring species. At the intraspecific level, individual females consistently differed in their level of specialisation and in the composition of pollen carried on their bodies and stored in their nests. Our study thus provides evidence of consistent individual-level specialisation in pollinators across multiple temporal scales. We also demonstrate that higher generalisation at the species level stemmed from larger among-individual variation in diets as observed in other types of consumers, such as predators. Our study thus reveals how specialisation and foraging preferences of bees change from the scale of individual foraging bouts to complete pollen provisions accumulated in their nests over their lifetime. Such multi-scale view of foraging behaviour is necessary to improve our understanding of the functioning of plant-flower visitor communities.
Downregulation of Neurodevelopmental Gene Expression in iPSC-Derived Cerebral Organoids Upon Infection by Human Cytomegalovirus
Authors: O’Brien Benjamin S. , Mokry Rebekah L. , Schumacher Megan L. , Pulakanti Kirthi , Rao Sridhar , Terhune Scott S. , Ebert Allison D. 
Published: August 2021

AbstractHuman cytomegalovirus (HCMV) is a beta herpesvirus that, upon congenital infection, can cause severe birth defects including vision and hearing loss, microcephaly, and seizures. Currently, no approved treatment options exist for in utero infections. We previously demonstrated that HCMV infection decreases calcium signaling responses and alters neuronal differentiation in induced pluripotent stem cell (iPSC) derived neural progenitor cells (NPCs). Here we aimed to determine the impact of infection on the transcriptome in developing human neurons using iPSC-derived 3-dimensional cerebral organoids. We infected iPSC-derived cerebral organoids with HCMV encoding eGFP and sorted cell populations based on GFP signal strength. Significant transcriptional downregulation was observed including in key neurodevelopmental gene pathways in both the GFP (+) and intermediate groups. Interestingly, the GFP (-) group also showed downregulation of the same targets indicating a mismatch between GFP expression and viral infection. Using a modified HCMV virus destabilizing IE 1 and 2 proteins, we still observed significant downregulation of neurodevelopmental gene expression in infected neural progenitor cells. Together, these data indicate that IE viral proteins are not the main drivers of neurodevelopmental gene dysregulation in HCMV infected neural tissues suggesting therapeutically targeting IE gene expression is insufficient to restore neural differentiation and function.
Classification and clustering of RNA crosslink-ligation data reveal complex structures and homodimers
Authors: Zhang Minjie , Fischer-Hwang Irena T. , Li Kongpan , Bai Jianhui , Chen Jian-Fu , Weissman Tsachy , Zou James Y. , Lu Zhipeng 
Published: August 2021

AbstractThe recent development and application of methods based on the general principle of “crosslinking and proximity ligation” (crosslink-ligation) are revolutionizing RNA structure studies in living cells. However, extracting structure information from such data presents unique challenges. Here we introduce a set of computational tools for the systematic analysis of data from a wide variety of cross-link-ligation methods, specifically focusing on read mapping, alignment classification and clustering. We design a new strategy to map short reads with irregular gaps at high sensitivity and specificity. Analysis of previously published data reveals distinct properties and bias caused by the crosslinking reactions. We perform rigorous and exhaustive classification of alignments and discover 8 types of arrangements that provide distinct information on RNA structures and interactions. To deconvolve the dense and inter-twined gapped alignments, we develop a network/graph-based tool CRSSANT (Crosslinked RNA Secondary Structure Analysis using Network Techniques), which enables clustering of gapped alignments and discovery of new alternative and dynamic conformations. We discover that multiple crosslinking and ligation events can occur on the same RNA, generating multi-segment alignments to report complex high level RNA structures and multi-RNA interactions. We find that alignments with overlapped segments are produced from potential homodimers and develop a new method for their de novo identification. Analysis of overlapping alignments revealed potential new homodimers in cellular noncoding RNAs and RNA virus genomes in the Picornaviridae family. Together, this suite of computational tools enables rapid and efficient analysis of RNA structure and interaction data in living cells.
Claudin-5 binder enhances focused ultrasound-mediated opening in anin vitroblood-brain barrier model
Authors: Chen Liyu , Sutharsan Ratneswary , Lee Jonathan LF , Cruz Esteban , Asnicar Blaise , Palliyaguru Tishila , Leinenga Gerhard , Götz Jürgen 
Published: August 2021

AbstractRationaleThe blood-brain barrier (BBB) while functioning as a gatekeeper of the brain, impedes cerebral drug delivery. An emerging technology to overcome this limitation is focused ultrasound (FUS). When FUS interacts with intravenously injected microbubbles (FUS+MB), the BBB opens, transiently allowing the access of therapeutic agents into the brain. However, the ultrasound parameters need to be tightly tuned: when the acoustic pressure is too low there is no opening, and when it is too high, bleeds can occur. We therefore asked whether BBB permeability can be increased by combining FUS+MBwith a second modality such that in a clinical setting lower acoustic pressures could be potentially used.MethodsGiven that FUS achieves BBB opening by the disruption of tight junction (TJ) proteins such as claudin-5 of brain endothelial cells, we generated a stable MDCK II cell line (eGFP-hCldn5-MDCK II) that expresses fluorescently tagged human claudin-5. Two claudin-5 binders, mC5C2 (a peptide) and cCPEm (a truncated form of an enterotoxin), that have been reported previously to weaken the barrier, were synthesized and assessed for their abilities to enhance the permeability of cellular monolayers. We then performed a comparative analysis of single and combination treatments.ResultsWe successfully generated a novel cell line that formed functional monolayers as validated by an increased transendothelial electrical resistance (TEER) reading and a low (< 0.2%) permeability to sodium fluorescein (376 Da). We found that the binders exerted a time- and concentration-dependent effect on BBB opening when incubated over an extended period, whereas FUS+MBcaused a rapid barrier opening followed by recovery after 12 hours within the tested pressure range. Importantly, preincubation with cCPEm prior to FUS+MBtreatment resulted in greater barrier opening compared to either FUS+MBor cCPEm alone as measured by reduced TEER values and an increased permeability to fluorescently labelled 40 kDa dextran (FD40).ConclusionThe data suggest that pre-incubation with clinically suitable binders to TJ proteins may be a general strategy to facilitate safer and more effective ultrasound-mediated BBB opening in cellular and animal systems and potentially also for the treatment of human diseases of the brain.
Scalable clustering with supervised linkage methods
Authors: Anibal James , Day Alexandre G. , Bahadiroglu Erol , O’Neill Liam , Phan Long , Peltekian Alec , Erez Amir , Kaplan Mariana , Altan-Bonnet Grégoire , Mehta Pankaj 
Published: August 2021

AbstractData clustering plays a significant role in biomedical sciences, particularly in single-cell data analysis. Researchers use clustering algorithms to group individual cells into populations that can be evaluated across different levels of disease progression, drug response, and other clinical statuses. In many cases, multiple sets of clusters must be generated to assess varying levels of cluster specificity. For example, there are many subtypes of leukocytes (e.g. T cells), whose individual preponderance and phenotype must be assessed for statistical/functional significance. In this report, we introduce a novel hierarchical density clustering algorithm (HAL-x) that uses supervised linkage methods to build a cluster hierarchy on raw single-cell data. With this new approach, HAL-x can quickly predict multiple sets of labels for immense datasets, achieving a considerable improvement in computational efficiency on large datasets compared to existing methods. We also show that cell clusters generated by HAL-x yield near-perfect F1-scores when classifying different clinical statuses based on single-cell profiles. Our hierarchical density clustering algorithm achieves high accuracy in single cell classification in a scalable, tunable and rapid manner. We make HAL-x publicly available at: https://pypi.org/project/hal-x/
Worldwide research tendencies on probiotics in food science: 1993 to 2021
Authors: Bulut Albayrak Çisem , Duran Mustafa 
Published: August 2021

PurposeThis study aimed to identify the main and emerging structural patterns in the growth of the literature on probiotic research in food science, analyze current trends and determine gaps and present future projections.Design/methodology/approachA total of 1,301 scientific documents retrieved from Scopus database dated from 1993 to 2021 were analyzed by using bibliometric and scientometric tools.FindingsThe most influencer journals, leading countries and hotspots were identified by scientometric mapping. “Lactic acid bacteria”, “lactobacillus”, “lactobacillus plantarum”, “viability”, “functional foods” and “microencapsulation” were the top keywords that indicate main emerging areas. After a clear understanding of the current situation, future directions can be better projected. Therefore, investigating new probiotic microorganisms with advanced health promoting properties, adapting the new organisms to various food formulations, identifying the probiotic potential of unexplored traditional fermented foods and developing of nondairy probiotic foods can be the studies of the future.Research limitations/implicationsProbiotic concept has been revised during years and valuable knowledge has been accumulated over past decades. The findings demonstrate the development and trends of probiotic related food science researches. This is the first study to address the limitations of prior systematic literature reviews by applying network analysis and guide future works to fill the identified gaps.Originality/valueThe probiotic concept has been revised for years and valuable knowledge has been accumulated. Within the expanding literature, scientometric and bibliometric analysis will provide valuable contribution for identifying the main patterns, analyzing current trends, determining gaps and presenting future projection. This work presents detailed analysis to determine tendencies in probiotic research in food science.
Electronically tunable mixed mode universal filter employing grounded capacitors utilizing highly versatile VD-DVCC
Authors: Faseehuddin Mohammad , Herencsar Norbert , Albrni Musa Ali , Shireen Sadia , Sampe Jahariah 
Published: August 2021

Abstract

Purpose
This paper aims to achieve two main objectives. First, to introduce to the literature a new versatile active building block, namely, voltage differencing differential voltage current conveyor (VD-DVCC) for analog signal processing applications. Second, to design a novel electronically tunable mixed-mode universal filter. The designed filter provides low-pass, high-pass, band-pass, band-reject and all-pass responses in voltage-mode (VM), current-mode (CM), trans-impedance-mode (TIM) and trans-admittance-mode (TAM).

Design/methodology/approach
The proposed filter uses two VD-DVCCs, three resistors and two capacitors. All the capacitors used are grounded, which is advantageous from the monolithic integration point of view. The VD-DVCC is designed and validated in Cadence software using CMOS 0.18 µm process design kit from Silterra Malaysia at a supply voltage of ±1 V.

Findings
The proposed novel filter enjoys many attractive features including as follows: the ability to operate in all four modes, no requirement of capacitive matching, tunability of quality factor (Q) independent of pole frequency, availability of both inverting and non-inverting outputs for VM and TIM mode, high output impedance explicit current output for CM and TAM, no requirement for double/negative input signals (voltage/current) for response realization and low active and passive sensitivities. The filter is designed for a pole frequency of 5.305 MHz. The obtained results bear a close resemblance with the theoretical findings.

Originality/value
The proposed novel filter structure requires a minimum number of active and passive components and provides operation in all four operating modes. The filter will find application in structures of mixed-mode systems.