bluuebunny/crossref_metadata_2025_split huggingface dataset:
How many lives do COVID vaccines save? Evidence from Israel
Authors: Arbel Ronen , Moore Candace Makeda , Sergienko Ruslan , Pliskin Joseph 
Published: October 2021

AbstractBackgroundIn December 2020, Israel began a mass vaccination program with the rapid rollout of the Pfizer-BioNTech COVID-19 BNT162b2 vaccine for adults in Israel. The campaign vaccinated fewer people than necessary for herd immunity. However, at the same time, government stringency measures in terms of closing public life were decreased. Real-world observational data were used to examine the effect of mass vaccination on Covid-19 mortality.MethodsThe study period to examine the effect of vaccination on mortality was chosen to capture when at least 90% of the population over age 70 were vaccinated for less than seven months. Projected deaths as expected from vaccine efficacy and actual mortality data were compared for the study population with examination of potential confounding effects of government stringency. Average government stringency (Oxford Stringency Index) was calculated in the study period and the preceding period of the pandemic. Potential confounding effects of an age shift in the distribution of deaths were examined by analyzing the distributions of deaths and cases before and after the study period.ResultsConfirmed deaths from COVID-19 in the population over 70 after mass vaccination were recorded as 370, versus 408 expected from applying person-days of vaccine efficacy, and 5,120 estimated without vaccinations.ConclusionsVaccines against COVID-19 saved more lives than expected by simply applying individual vaccine efficacy to the vaccinated population in Israel, despite a loosening of government stringency.
NHR-23 activity is necessary forC. elegansdevelopmental progression and apical extracellular matrix structure and function
Authors: Johnson Londen C. , Vo An A. , Clancy John C. , Myles Krista M. , Pooranachithra Murugesan , Aguilera Joseph , Levenson Max T. , Wohlenberg Chloe , Rechtsteiner Andreas , Ragle James Matthew , Chisholm Andrew D. , Ward Jordan D. 
Published: October 2021

SUMMARY STATEMENTThis work shows how aC. eleganstranscription factor controls remodeling of the apical extracellular matrix during development and in which tissues it acts.ABSTRACTNematode molting is a remarkable process where animals must repeatedly build a new apical extracellular matrix (aECM) beneath a previously built aECM that is subsequently shed. The nuclear hormone receptor NHR-23/NR1F1 is an important regulator ofC. elegansmolting. NHR-23 expression oscillates in the epidermal epithelium, and soma-specific NHR-23 depletion causes severe developmental delay and death. Tissue-specific RNAi suggests thatnhr-23acts primarily in seam and hypodermal cells. NHR-23 coordinates the expression of factors involved in molting, lipid transport/metabolism, and remodeling of the aECM. NHR-23 depletion causes dampened expression of anas-37promoter reporter and a loss of reporter oscillation. The cuticle collagen ROL-6 and zona pellucida protein NOAH-1 display aberrant annular localization and severe disorganization over the seam cells following NHR-23 depletion, while the expression of the adult-specific cuticle collagen BLI-1 is diminished and frequently found in patches. Consistent with these localization defects, the cuticle barrier is severely compromised when NHR-23 is depleted. Together, this work provides insight into how NHR-23 acts in the seam and hypodermal cells to coordinate aECM regeneration during development.
Mechanisms Governing Target Search and Binding Dynamics of Hypoxia-Inducible Factors
Authors: Chen Yu , Cattoglio Claudia , Dailey Gina , Zhu Qiulin , Tjian Robert , Darzacq Xavier 
Published: October 2021

AbstractTranscription factors (TFs) are classically attributed a modular construction, containing well-structured sequence specific DNA-binding domains (DBDs) paired with disordered activation domains (ADs) responsible for protein-protein interactions targeting cofactors or the core transcription initiation machinery. However, this simple division of labor model struggles to explain why TFs with identical DNA binding sequence specificity determined in vitro exhibit distinct binding profiles in vivo. The family of Hypoxia-Inducible Factors (HIFs) offer a stark example: aberrantly expressed in several cancer types, HIF-1α and HIF-2α subunit isoforms recognize the same DNA motif in vitro – the hypoxia response element (HRE) – but only share a subset of their target genes in vivo, while eliciting contrasting effects on cancer development and progression under certain circumstances. To probe the mechanisms mediating isoform-specific gene regulation, we used live cell single particle tracking (SPT) to investigate HIF nuclear dynamics and how they change upon genetic perturbation or drug treatment. We found that HIF-α subunits and their dimerization partner HIF-1β exhibit distinct diffusion and binding characteristics that are exquisitely sensitive to concentration and subunit stoichiometry. Using domain-swap variants, mutations, and a HIF-2α specific inhibitor, we found that although the DBD and dimerization domains are important, a major determinant of chromatin binding and diffusion behavior is the AD-containing intrinsically disordered region (IDR). Using Cut&Run and RNA-seq as orthogonal genomic approaches we also confirmed IDR-dependent binding and activation of a specific subset of HIF-target genes. These findings reveal a previously unappreciated role of IDRs in regulating the TF search and binding process that contribute to functional target site selectivity on chromatin.
Colloidal physics modeling reveals how per-ribosome productivity increases with growth rate inE. coli
Authors: Maheshwari Akshay J. , Sunol Alp M. , Gonzalez Emma , Endy Drew , Zia Roseanna N. 
Published: October 2021

SummaryFaster growing cells must synthesize proteins more quickly. Increased ribosome abundance only partly accounts for increases in total protein synthesis rates. The productivity of individual ribosomes must increase too, almost doubling by an unknown mechanism. Prior models point to diffusive transport as a limiting factor but surface a paradox: faster growing cells are more crowded, yet crowding slows diffusion. We suspected physical crowding, transport, and stoichiometry, considered together, might reveal a more nuanced explanation. To investigate, we built a first-principles physics-based model ofE. colicytoplasm in which Brownian motion and diffusion arise directly from physical interactions between individual molecules of finite size, density, and physiological abundance. Using our microscopically-detailed model, we predict that physical transport of individual ternary complexes accounts for ~80% of translation elongation latency. We also find that volumetric crowding increases at faster growth even as cytoplasmic mass density remains relatively constant. Despite slowed diffusion, we predict that improved proximity between ternary complexes and ribosomes wins out, illustrating a simple physics-based mechanism for how individual elongating ribosomes become more productive. We speculate how crowding imposes a physical limit on growth rate and undergirds cellular behavior more broadly. Unfitted colloidal-scale modeling offers systems biology a complementary “physics engine” for exploring how cellular-scale behaviors arise from physical transport and reactions among individual molecules.
Biochemical characterization of a glycoside hydrolase family 43 β-D-galactofuranosidase from the fungus Aspergillus niger
Authors: Bulmer Gregory S. , Yuen Fang Wei , Begum Naimah , Jones Bethan S. , Flitsch Sabine L. , Munster Jolanda M. van 
Published: October 2021

Abstractβ-D-Galactofuranose (Galf) and its polysaccharides are found in bacteria, fungi and protozoa but do not occur in mammalian tissues, and thus represent a specific target for anti-pathogenic drugs. Understanding the enzymatic degradation of these polysaccharides is therefore of great interest, but the identity of fungal enzymes with exclusively galactofuranosidase activity has so far remained elusive. Here we describe the identification and characterization of a galactofuranosidase from the industrially important fungus Aspergillus niger. Phylogenetic analysis of glycoside hydrolase family 43 subfamily 34 (GH43_34) members revealed the occurrence of three distinct clusters and, by comparison with specificities of characterized bacterial members, suggested a basis for prediction of enzyme specificity. Using this rationale, in tandem with molecular docking, we identified a putative β-D-galactofuranosidase from A. niger which was recombinantly expressed in Escherichia coli. The Galf-specific hydrolase, encoded by xynD demonstrates maximum activity at pH 5, 25 °C towards 4-Nitrophenyl-β-galactofuranoside (pNP-β-Galf), with a Km of 17.9 ± 1.9 mM and Vmax of 70.6 ± 5.3 μmol min−1. The characterization of this first fungal GH43 galactofuranosidase offers further molecular insight into the degradation of Galf-containing structures and may inform clinical treatments against fungal pathogens.
Impact of protein conformational diversity on AlphaFold predictions
Authors: Saldaño Tadeo , Escobedo Nahuel , Marchetti Julia , Zea Diego Javier , Mac Donagh Juan , Velez Rueda Ana Julia , Gonik Eduardo , Melani Agustina García , Novomisky Nechcoff Julieta , Salas Martín N. , Peters Tomás , Demitroff Nicolás , Fernandez Alberti Sebastian , Palopoli Nicolas , Fornasari Maria Silvina , Parisi Gustavo 
Published: October 2021

AbstractAfter the outstanding breakthrough of AlphaFold in predicting protein 3D models, new questions appeared and remain unanswered. The ensemble nature of proteins, for example, challenges the structural prediction methods because the models should represent a set of conformers instead of single structures. The evolutionary and structural features captured by effective deep learning techniques may unveil the information to generate several diverse conformations from a single sequence. Here we address the performance of AlphaFold2 predictions under this ensemble paradigm. Using a curated collection of apo-holo conformations, we found that AlphaFold2 predicts the holo form of a protein in 70% of the cases, being unable to reproduce the observed conformational diversity with an equivalent error than in the estimation of a single conformation. More importantly, we found that AlphaFold2’s performance worsens with the increasing conformational diversity of the studied protein. This impairment is related to the heterogeneity in the degree of conformational diversity found between different members of the homologous family of the protein under study. Finally, we found that main-chain flexibility associated with apo-holo pairs of conformers negatively correlates with the predicted local model quality score plDDT, indicating that plDDT values in a single 3D model could be used to infer local conformational changes linked to ligand binding transitions.
Map7D2 and Map7D1 facilitate microtubule stabilization through distinct mechanisms in neuronal cells
Authors: Kikuchi Koji , Sakamoto Yasuhisa , Uezu Akiyoshi , Yamamoto Hideyuki , Ishiguro Kei-ichiro , Shimamura Kenji , Saito Taro , Hisanaga Shin-ichi , Nakanishi Hiroyuki 
Published: October 2021

AbstractMicrotubule (MT) dynamics are modulated through the coordinated action of various MT-associated proteins (MAPs). However, the regulatory mechanisms underlying MT dynamics remain unclear. We show that the MAP7 family protein Map7D2 stabilizes MTs to control cell motility and neurite outgrowth. Map7D2 directly bound to MTs through its N-terminal half and stabilized MTs in vitro. Map7D2 localized prominently to the centrosome and partially on MTs in mouse N1-E115 neuronal cells, which expresses two of the four MAP7 family members, Map7D2 and Map7D1. Map7D2 loss decreased the resistance to the MT-destabilizing agent, nocodazole without affecting acetylated/detyrosinated stable MTs, suggesting that Map7D2 stabilizes MTs via direct binding. In addition, Map7D2 loss increased the rate of random cell migration and neurite outgrowth, presumably by disturbing the balance between MT stabilization and destabilization. Map7D1 exhibited similar subcellular localization and gene knock-down phenotypes to Map7D2. However, in contrast to Map7D2, Map7D1 was required for the maintenance of acetylated stable MTs. Taken together, our data suggest that Map7D2 and Map7D1 facilitate MT stabilization through distinct mechanisms in cell motility and neurite outgrowth.
Hoop-like role of the cytosolic interface helix in Vibrio PomA, an ion-conducting membrane protein, in the bacterial flagellar motor
Authors: Nishikino Tatsuro , Sagara Yugo , Terashima Hiroyuki , Homma Michio , Kojima Seiji 
Published: October 2021

AbstractVibrio has a polar flagellum driven by sodium ions for swimming. The force-generating stator unit consists of PomA and PomB. PomA contains four-transmembrane regions and a cytoplasmic domain of approximately 100 residues which interacts with the rotor protein, FliG, to be important for the force generation of rotation. The three-dimensional structure of the stator shows that the cytosolic interface (CI) helix of PomA is located parallel to the inner membrane. In this study, we investigated the function of CI helix and its role as stator. Systematic proline mutagenesis showed that residues K64, F66, and M67 were important for this function. The mutant stators did not assemble around the rotor. Moreover, the growth defect caused by PomB plug deletion was suppressed by these mutations. We speculate that the mutations affect the structure of the helices extending from TM3 and TM4 and reduce the structural stability of the stator complex. This study suggests that the helices parallel to the inner membrane play important roles in various processes, such as the hoop-like function in securing the stability of the stator complex and the ion conduction pathway, which may lead to the elucidation of the ion permeation and assembly mechanism of the stator.ImportanceBacteria have a motor embedded in the membrane to rotate flagella as screw for swimming. The motor is composed rotor and stator complexes. The interaction between the rotor and stator converts the electrochemical potential gradient across the membrane into motor torque. The stator functions as an ion channel and is composed of two membrane proteins, MotA and MotB for proton or PomA and PomB for sodium ion. Based on the structural data of stator, we systematically introduce the proline replacement mutations and found that the cytosolic interface (CI) helix which is located parallel to the inner membrane between the second and third transmembrane (TM) segments, performs a hoop-like function in securing the stability of the stator complex and the ion conduction pathway. The results of this study provide novel insights into the energy conversion mechanism of the flagellar motor and the general mechanism of the ion channel function.
Polycomb Repressive Complexes occupancy reveals PRC2-independent PRC1 critical role in the control of limb development
Authors: Guerard-Millet Fanny , Gentile Claudia , Paul Racheal , Mayran Alexandre , Kmita Marie 
Published: October 2021

AbstractThe Polycomb Repressive Complexes (PRC) are key players in the regulation of tissue-specific gene expression through their ability to epigenetically silence developmental genes. They are subdivided into two multicomponent complexes, PRC1 and PRC2, functioning through post-translational modifications of histone tails. A large body of work revealed functional interactions between PRC1 and PRC2, whereby trimethylation of lysine 27 on histone H3 (H3K27me3) by PRC2 contributes to the recruitment of canonical PRC1 (cPRC1). In parallel, a PRC2-independent binding of PRC1 has been uncovered and referred to as non-canonical PRC1 or variant PRC1 (vPRC1), in which PRC1-dependent ubiquitination of lysine 119 on histone H2A is involved in recruiting PRC2/propagating PRC2-dependent H3K27 trimethylation. While it was initially assumed that cPRC1 and vPRC1 bind distinct targets, subsequent evidence pointed to cPRC1 and vPRC1 sharing a significant subset of targets. How the functional interplay between PRC2, cPRC1 and vPRC1 contributes to gene regulation remains partially understood. Here, we show that, in the developing limb, PRC2 inactivation barely affects PRC1 occupancy, as the majority of PRC2- bound loci are bound by vPRC1 (RYBP-PRC1), both in wild type and PRC2 mutant limbs. Consistent with this, we found that loci bound by CBX2, a PRC1 subunit involved in the recognition of H3K27me3 and thereby recruitment of cPRC1, are, for the vast majority, also bound by vPRC1. Intriguingly, analysis of PRC2 mutant limbs revealed that while a large part of CBX2 occupancy is lost in absence of PRC2 function, as expected from the absence of H3K27me3, there is a significant number of genes retaining CBX2 occupancy as well as a few genes with apparent gain of CBX2 binding. Importantly, among these genes, 56 of them correspond to developmental genes known for playing a key role in limb morphogenesis. Based on the importance of vPRC1 in gene silencing, our findings emphasize the primary role of PRC2-independent PCR1 function in regulating developmental genes and questions the role of PRC2/cPRC1 in controlling developmental programs.
The effect of borax addition to aluminum alloy produced by powder metallurgy on mechanical and thermophysical properties
Authors: Mutlu Rasiha Nefise , Acar Ayşe Nur , Gizir Ahmet Murat 
Published: October 2021

Purpose
Lightweight, durable and economical materials production has gained considerable importance according to the needs of developing technology. The purpose of this paper is to develop an new aluminum alloy by powder metalurgy.

Design/methodology/approach
Powder metallurgy, which provides controllably on desired end product, method was applied. Aluminum alloy was created with Al, Zn, Mg, Cu powders and 1.5% Na2[B4O5(OH)4].8H2O added. It was pressed under high pressure and sintered at 600 °C under N2 gas atmosphere. Density, hardness behaviors and thermal properties were determined. Surfaces and crystal structures of samples were characterized.

Findings
The addition of borax made easier grains coming to together, acting as binders and the AlB2 crystal phase was formed. It was also observed that MgZn2, Al2CuMg phases were formed. In this way, the pores between the particles of the material were reduced from 35% to 5% total porosity and the hardness of the material was increased 29 N/mm2 to 45 N/mm2 (Brinell Hardness, HB). The surface properties improved and the hydrophobicity of the surface (from 63° to 102° contact angle with borax) increased. Thus, the heat transfer among atoms get easier and the borax addition decreased specific heat capacity and enthalpy of aluminum–borax samples. This situation was also simulated with the heat transfer module of COMSOL. As result, the energy required reduced. In the other word, sintering process occurred at low temperature and more efficient.

Originality/value
New aluminum alloy has been created from different amounts of Zn, Mg, Cu elemental powders. In addition to literature, relationship of borax and aluminum and other alloying elements on the mechanical, thermophysical and surface properties of new obtained aluminum alloy has been investigated.
Biomass as a means of achieving rural energy self-sufficiency: a concept
Authors: Vijay Vandit , Chandra Ram , Subbarao P.M.V. 
Published: October 2021

PurposeTo better understand bioenergy's role in sustainable rural development and cleaner environment, it is necessary to place it in a local regional context. This paper aims to provide a conceptual approach for biomass-based energy self-sufficiency in rural areas of developing and underdeveloped countries having a strong agricultural sector. It further provides a framework for the estimation of surplus biomass and bioenergy potential and the biomass power emissions in a rural area.Design/methodology/approachA detailed approach is laid out to attain energy self-sufficiency in rural areas encompassing identification of surplus biomass resources in a selected area, suitable conversion technologies, consideration of local end-use priorities, skill development and monitoring of the project.FindingsFollowing the novel approach proposed in this paper a case study analysis for Thanagazi block (Alwar District, India) is done, and it is observed that locally available biomass in the block can substitute more than 75% of the conventional energy demand and save 78% emissions vis-à-vis equivalent coal power. This indicates that creating local bioenergy production system as a means of substituting/complementing fossil energy can contribute to a cleaner self-sufficient ecosystem.Originality/valueBiomass is a spatio-temporal resource. Prior works have looked at bioenergy potential for national or state levels; however, granular data to reveal a more realistic outlook in a rural area is the novelty of this work. Furthermore, biomass assessment studies largely focus on crop residual biomass, whereas the present study also includes livestock manure assessment which is a major resource in rural areas. This paper highlights the need and the approach for exploring locally available biomass to meet the local energy demands for clean energy security while considering the involvement of the local population in bioenergy planning and implementation.
Performance indicators for lifecycle process of public private partnership (PPP) projects in Malaysia
Authors: Ismail Suhaiza , Mohamad Rosnani , Mohd Said Julia 
Published: October 2021

PurposeThis paper has two objectives. The first objective is to examine the important performance indicators of the lifecycle process of public private partnership (PPP) projects. The second objective is to investigate the difference in the perception of the importance of the performance indicators between the public and private sectors.Design/methodology/approachTo achieve the research objectives, the study used a questionnaire survey. The questionnaire was distributed via postal mail to officers of government departments and private sector companies who may have been involved in PPP projects. A total of 237 completed questionnaires were received, representing a 51.52% response rate. To examine the importance of performance indicators, the descriptive statistical tests of mean, standard deviation and mean score ranking were used. Independent t-tests were conducted to investigate the differences in the perceptions of the importance of performance indicators between the two respondent groups.FindingsThe findings show that all the 16 performance indicators are perceived as important and very important. The top five important performance indicators for a PPP project lifecycle process are “Time management”, “Contractual management”, “Cost management”, “Safety management” and “Effective risk management system”, while “stress or conflicts management” is the least important. In terms of the differences in the perception of the public and private sector groups, the results indicate that four indicators (“environment protection”, “cost management”, “effective risk management system” and “good work environment”), show a significant statistical difference between the perception of the public and the private sector respondents.Originality/valueThis study offers empirical evidence on key performance indicators for a PPP project that are crucial throughout its lifecycle as perceived by two key parties in a PPP contract, i.e. the public and the private sectors.