bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Timeline of Bacterial and Archaeal Diversification in the Ocean
Authors: Martinez-Gutierrez Carolina A. , Uyeda Josef C. , Aylward Frank O. 
Published: October 2022

ABSTRACTMicrobial plankton play a central role in marine biogeochemical cycles, but the timing in which abundant lineages diversified into ocean environments remains unclear. Here, we reconstructed the timeline in which major clades of bacteria and archaea colonized the ocean using a high-resolution benchmarked phylogenetic tree that allows for simultaneous and direct comparison of the ages of multiple divergent lineages. Our findings show that the diversification of the most prevalent marine clades spans throughout a period of 2.2 Ga, with most clades colonizing the ocean during the last 800 million years. The oldest clades - SAR202, SAR324,Ca.Marinimicrobia, and Marine Group II - diversified around the time of the Great Oxidation Event (GOE), during which oxygen concentration increased but remained at microaerophilic levels throughout the Mid-Proterozoic, consistent with the prevalence of some clades within these groups in oxygen minimum zones today. We found the diversification of the prevalent heterotrophic marine clades SAR11, SAR116, SAR92, SAR86, and Roseobacter as well as the Marine Group I, to occur near to the Neoproterozoic Oxygenation Event (0.8-0.4 Ga). The diversification of these clades is concomitant with an overall increase of oxygen and nutrients in the ocean at this time, as well as the diversification of eukaryotic algae, consistent with the previous hypothesis that the diversification of heterotrophic bacteria is linked to the emergence of large eukaryotic phytoplankton. The youngest clades correspond to the widespread phototrophic cladesProchlorococcus, Synechococcus,andCrocosphaera, whose diversification happened after the Phanerozoic Oxidation Event (0.45-0.4 Ga), in which oxygen concentrations had already reached their modern levels in the atmosphere and the ocean. Our work clarifies the timing at which abundant lineages of bacteria and archaea colonized the ocean, thereby providing key insights into the evolutionary history of lineages that comprise the majority of prokaryotic biomass in the modern ocean.
Tracking the horizontal transfer of plasmids inShigella sonneiandShigella flexneriusing phylogenetics
Authors: Müller Nicola F. , Duchêne Sebastián , Williamson Deborah A. , Bedford Trevor , Howden Benjamin P. , Ingle Danielle J. 
Published: October 2022

AbstractAntimicrobial resistance (AMR) poses an ever-increasing challenge to the treatment of infections. AMR mechanisms are commonly associated with AMR genes that are carried on mobile elements, such as plasmids that can move between bacterial lineages. Here we introduce an approach that allows us to reconstruct how plasmids move between bacterial lineages. To do so, we model the co-evolution of chromosomal and plasmid DNA in a Bayesian phylogenetic network approach using a joint coalescent and plasmid transfer process. We apply this new approach to a five-year dataset ofShigellaisolates from Melbourne, Australia. Doing so, we reconstruct the gain and loss of small plasmids, and the recent dissemination of a multidrug-resistance plasmid betweenS. sonneiandS. flexnerilineages in multiple independent events and through steady growth in the prevalence since 2010. This approach has a strong potential to improve our understanding of where AMR-carrying plasmids are introduced and maintained.
FACTORs: a Novel R Package for Functional Data Reduction and Hypothesis Testing
Authors: Malamon John S. , Saben Jessica L. , Kaplan Bruce 
Published: October 2022

ABSTRACTTo extract biological meaning from transcriptomics analysis, investigators almost exclusively rely on biological annotation databases and the subsequent associations made between gene products and ontology terms (i.e., gene ontology analysis). Although there is ease and utility to this approach, multiple hypothesis testing methods such as differential expression analysis are performed in the absence ofin silicovalidation, and downstream gene ontology analysis methods lack precision and propagate Type I error. Therefore, we present a novel R package, Functional Association Vectors (FACTORs), that begins to address some of the common pitfalls associated with functional association studies in transcriptomics research. FACTORs are vectorized containers for directly comparing and testing congruent functional association statistics at the molecular level. Our goal was to develop novel methodology an R software package to allow for the experimental validation of differentially expressed genes that are conserved across studies and to reduce Type I error in the down-stream functional analysis of these signals. FACTORs are generalizable and flexible, allowing for any association statistic such as log fold change (logFC), t-statistic, p-value, or other functional significance score. To demonstrate utility of FACTORs in the cross-study validation of global mRNA expression profiling, we used differential expression analysis summary statistics obtained from two studies with publicly available transcriptomic data. Through this demonstration we show FACTORs provide a more precise and generalizable functional hypothesis testing methodology and data reduction approach that directly tests functional association statistics at the molecular level, across experiments.AUTHOR SUMMARYWe present a novel statistical methodology and software tool that can be used to validate transcriptomic data across studies. FACTORs is available as an R package and will aid in transcriptomic data reduction, identifying gene expression profiles that are conserved across studies, and improving the precision and generalizability of functional association studies. We propose FACTORs as a generalizable methodology for reducing Type I error and increasing the biological relevance of functional associations in transcriptomics studies.
Relatedness coefficients and their applications for triplets and quartets of genetic markers
Authors: Ritland Kermit 
Published: October 2022

ABSTRACTRelatedness coefficients which seek the identity-by-descent of genetic markers are described. The markers are in groups of two, three or four, and if four, can consist of two pairs. It is essential to use cumulants (not moments) for four-marker-gene probabilities, as the covariance of homozygosity, used in 4-marker applications, can only be described with cumulants. A covariance of homozygosity between pairs of markers arises when populations follow a mixture distribution. Also, the probability of four markers all identical-by-descent equals the normalized fourth cumulant. In this paper, a “genetic marker” generally represents either a gene locus or an allele at a locus.Applications of three marker coefficients mainly involve conditional regression, and applications of four marker coefficients can involve identity disequilibrium. Estimation of relatedness using genetic marker data is discussed. However, three- and four-marker estimators suffer from statistical and numerical problems, including higher statistical variance, complexity of estimation formula, and singularity at some intermediate allele frequencies.
Three-dimensional imaging and single-cell transcriptomics of the human kidney implicate perturbation of lymphatics in alloimmunity
Authors: Jafree Daniyal J , Stewart Benjamin , Kolatsi-Joannou Maria , Davis Benjamin , Mitchell Hannah , Russell Lauren G , Marinas del Rey Lucía , Mason William J , Lee Byung Il , Heptinstall Lauren , Pomeranz Gideon , Moulding Dale , Wilson Laura , Wickenden Tahmina , Malik Saif , Holroyd Natalie , Walsh Claire , Chandler Jennifer C , Cao Kevin X , Winyard Paul JD , Price Karen L , Woolf Adrian S , Busche Marc Aurel , Walker-Samuel Simon , Scambler Peter J , Motallebzadeh Reza , Clatworthy Menna R , Long David A 
Published: October 2022

ABSTRACTStudies of the structural and molecular features of the lymphatic vasculature, which clears fluid, macromolecules and leukocytes from the tissue microenvironment, have largely relied on animal models, with limited information in human organs beyond traditional immunohistochemical assessment. Here, we use three-dimensional imaging and single-cell RNA-sequencing to study lymphatics in the human kidney. We found a hierarchical arrangement of lymphatic vessels within human kidneys, initiating along specialised nephron epithelium in the renal cortex and displaying a distinct, kidney-specific transcriptional profile. In chronic transplant rejection we found kidney allograft lymphatic expansion alongside a loss of structural hierarchy, with human leukocyte antigen-expressing lymphatic vessels infiltrating the medulla, presenting a putative target for alloreactive antibodies. This occurred concurrently with lymphatic vessels invading and interconnecting tertiary lymphoid structures at early stages of lymphocyte colonisation. Analysis of intercellular signalling revealed upregulation of co-inhibitory molecule-mediated CD4+T cell-lymphatic crosstalk in rejecting kidneys, potentially acting to limit local alloimmune responses. Overall, we delineate novel structural and molecular features of human kidney lymphatics and reveal perturbations to their phenotype and transcriptome in the context of alloimmunity.SUMMARYLymphatics regulate fluid balance and immune cell accumulation but are under-studied in human organs such as the kidney. Jafree and colleagues profiled human kidney lymphatics using three-dimensional imaging and single-cell RNA-sequencing, revealing structural and transcriptional perturbations in rejecting kidney transplants.
DMDantisense oligonucleotide mediated exon skipping efficiency is affected by flanking intron retention time and target position within the exon
Authors: Goossens Remko , Verwey Nisha , Ariyurek Yavuz , Schnell Fred , Aartsma-Rus Annemieke 
Published: October 2022

AbstractMutations in theDMDgene are causative for Duchenne muscular dystrophy (DMD). Antisense oligonucleotide (AON) mediated exon skipping to restore disrupted dystrophin reading frame is a therapeutic approach that allows production of a shorter but functional protein. As DMD causing mutations can affect most of the 78 exons encoding dystrophin, a wide variety of AONs are needed to treat the patient population. Design of AONs is largely guided by trial-and-error, and it is yet unclear what defines the skippability of an exon.Here, we use a library of phosphorodiamidate morpholino oligomer (PMOs) AONs of similar physical properties to test the skippability of a large number ofDMDexons. TheDMDtranscript is non-sequentially spliced, meaning that certain introns are retained longer in the transcript than downstream introns. We tested whether the relative intron retention time has a significant effect on AON efficiency, and found that targeting an exon flanked at its 5’ by an intron that is retained in the transcript longer (‘slow’ intron) leads to overall higher exon skipping efficiency than when the 5’ intron is ‘fast’. Regardless of splicing speed of flanking introns, we find that positioning an AON closer to the 5’ of the target exon leads to higher exon skipping efficiency opposed to targeting an exons 3’-end.The data enclosed herein can be of use to guide future target selection and preferential AON binding sites for both Duchenne and other disease amenable by exon skipping therapies.
GENLIB: new function to simulate haplotype transmission in large complex genealogies
Authors: Rakesh Mohan , Vézina Hélène , Laprise Catherine , Freeman Ellen E , Burkett Kelly M , Roy-Gagnon Marie-Hélène 
Published: October 2022

AbstractSummaryFounder populations with deep genealogical data are well suited for investigating genetic variants contributing to diseases. Here, we present a new function added to the genealogical analysis R package GENLIB, which can simulate the transmission of haplotypes from founders to probands along very large and complex user-specified genealogies.Availability and implementationThe new function is available in the latest version of the GENLIB package (v1.1.6), available on the CRAN repository and fromhttps://github.com/R-GENLIB/GENLIB. Stand-alone scripts for analyzing the output of the function can be accessed athttps://github.com/R-GENLIB/simuhaplo_scripts.
SEMPAI: a Self-Enhancing Multi-Photon Artificial Intelligence for prior-informed assessment of muscle function and pathology
Authors: Mühlberg Alexander , Ritter Paul , Langer Simon , Goossens Chloë , Nübler Stefanie , Schneidereit Dominik , Taubmann Oliver , Denzinger Felix , Nörenberg Dominik , Haug Michael , Goldmann Wolfgang H. , Maier Andreas K. , Friedrich Oliver , Kreiss Lucas 
Published: October 2022

AbstractDeep learning (DL) shows notable success in biomedical studies. However, most DL algorithms work as a black box, exclude biomedical experts, and need extensive data. We introduce the Self-Enhancing Multi-Photon Artificial Intelligence (SEMPAI), that integrates hypothesis-driven priors in a data-driven DL approach for research on multiphoton microscopy (MPM) of muscle fibers. SEMPAI utilizes meta-learning to optimize prior integration, data representation, and neural network architecture simultaneously. This allows hypothesis testing and provides interpretable feedback about the origin of biological information in MPM images. SEMPAI performs joint learning of several tasks to enable prediction for small datasets.The method is applied on an extensive multi-study dataset resulting in the largest joint analysis of pathologies and function for single muscle fibers. SEMPAI outperforms state-of-the-art biomarkers in six of seven predictive tasks, including those with scarce data. SEMPAI’s DL models with integrated priors are superior to those without priors and to prior-only machine learning approaches.
How am I doing financially compared to expectations? An experimental comparison of messaging strategies in investor newsletters
Authors: Pulk Kristjan , Uusberg Andero , Riitsalu Leonore 
Published: October 2022

PurposeThis study aims to investigate which messaging strategies employed in personalised newsletters could be used for improving the propensity of individuals to save or invest and secure their financial well-being.Design/methodology/approachThe authors conducted a field experiment with 4,782 clients at an Estonian retail bank. For three months (after measuring baseline levels for a month), the participants received personalised monthly newsletters with either a praising or a scolding message based on comparing their recent investment decisions to their past decisions.FindingsTheir results suggest that newsletters could serve as an encouragement for those who already invest significant amounts each month and a reminder for those who have stopped regular investing for a month. The newsletters robustly increased investments in securities accounts for these groups.Research limitations/implicationsThe authors contribute to the marketing literature by examining praise and scolding messaging strategies within the same channel and company, focussing on the individual's past behaviour. They raise several hypotheses to be tested in future randomised controlled trials (RCTs).Practical implicationsThe authors’ results show the importance of investor behaviour analysis as the effectiveness of the newsletter intervention largely depended on the type of customer it was served to. This highlights the importance of personalisation.Originality/valueThe results show that a given message tends to influence only specific groups of investors. Identifying these groups is valuable information for messaging strategies.
A decade later: exploring managerial insights on millennials
Authors: Sessoms-Penny Sandra , Underwood Kimberly M. , Taylor Joy 
Published: October 2022

PurposeThe purpose of this research was to explore managers' perceptions related to the emerging needs, roles, values, responsibilities and commitments of millennials in the multi-generational workplace, and to determine how managers may effectively recognize and use millennial contributions to enhance the organizational culture and infrastructure.Design/methodology/approachThis qualitative, narrative inquiry study utilized semi-structured interviews to capture collective insights of managers who lead millennials within multi-generational teams. All researchers used an interview protocol with each participant to maintain integrity. Data analysis included the creation of a code manual which was developed utilizing the first five interviews. The code manual included definitions, descriptions and exemplar text and was then used to code all remaining interviews.FindingsData are presented through three key areas of exploration: The contributions of millennials in multi-generational workplaces, the evolution of managerial views of millennials and the tactics managers use for millennial management in multi-generational teams.Originality/valueScholarly literature has clearly presented perceived qualities millennials bring to the workplace, including poor communication, advanced technology skills, overconfidence, and a need for work–life balance. This study seeks to provide an understanding of the generation, through the lens of their managers.
Balance: Benefit or bromide?
Authors: Williams Emma 
Published: October 2022

AbstractThere seem to be obvious virtues to keeping a sense of balance. In this paper, I consider some examples from ordinary life and education where the pursuit of balance would appear to be a benefit. Yet I also draw upon lines of thinking from John Stuart Mill and Adam Phillips to examine whether the apparent good sense of balance can be disturbed. I show how Mill's and Phillips’ ideas extend into a consideration of the aesthetics of balance and the idea that there might be something deceptively alluring about balance. I seek to develop these lines of thinking in relation to a work of modernist literature that works to dissipate balance's beguiling allure.
Detection of hidden marks on Hwatu cards used in illegal gambling
Authors: Lee Joong , Kim Hongseok , Kang Tae‐Yi , Yook Simyub 
Published: October 2022

AbstractHwatu is a popular card game widely played in both Korea and Japan. This study examined hwatu cards used in the fraudulent gambling in Korea. Fraudsters used the hwatu cards, with hidden marks printed on the back using special ink to identify the cards so that they could deceive unknowing game players. These marks are invisible to the naked eye under normal conditions and are only visible when wearing special lenses. When suspicious hwatu cards are sent to the forensic laboratory, detection of the hidden mark conducted by the microscope, video spectral comparator (VSC), and radiography, which are laborious. In this study, we developed visualization of the hidden mark on the hwatu cards by utilizing a set of the algorisms including color splitting, histogram normalization, FFT denoising, These algorithms were applied to mobile applications affording convenience and accessibility to help prevent fraud or to help law enforcement conduct an immediate investigation. The proposed method was confirmed to be simple and effective in detecting hidden marks on hwatu cards without the need for costly equipment.
Vitamin D—A prominent immunomodulator to prevent COVID‐19 infection
Authors: Ashique Sumel , Gupta Kirti , Gupta Gaurav , Mishra Neeraj , Singh Sachin Kumar , Wadhwa Sheetu , Gulati Monica , Dureja Harish , Zacconi Flavia , Oliver Brian G. , Paudel Keshav Raj , Hansbro Philip M. , Chellappan Dinesh Kumar , Dua Kamal 
Published: October 2022

AbstractCOVID‐19 remains a life‐threatening infectious disease worldwide. Several bio‐active agents have been tested and evaluated in an effort to contain this disease. Unfortunately, none of the therapies have been successful, owing to their safety concerns and the presence of various adverse effects. Various countries have developed vaccines as a preventive measure; however, they have not been widely accepted as effective strategies. The virus has proven to be exceedingly contagious and lethal, so finding an effective treatment strategy has been a top priority in medical research. The significance of vitamin D in influencing many components of the innate and adaptive immune systems is examined in this study. This review aims to summarize the research on the use of vitamin D for COVID‐19 treatment and prevention. Vitamin D supplementation has now become an efficient option to boost the immune response for all ages in preventing the spread of infection. Vitamin D is an immunomodulator that treats infected lung tissue by improving innate and adaptive immune responses and downregulating the inflammatory cascades. The preventive action exerted by vitamin D supplementation (at a specific dose) has been accepted by several observational research investigations and clinical trials on the avoidance of viral and acute respiratory dysfunctions. To assess the existing consensus about vitamin D supplementation as a strategy to treat and prevent the development and progression of COVID‐19 disease, this review intends to synthesize the evidence around vitamin D in relation to COVID‐19 infection.
SIAH proteins regulate the degradation and intra‐mitochondrial aggregation of PINK1: Implications for mitochondrial pathology in Parkinson's disease
Authors: Abd Elghani Fatimah , Safory Hazem , Hamza Haya , Savyon Mor , Farhoud Malik , Toren‐Hershoviz Michal , Vitic Zagorka , Ebanks Kirsten , Shani Vered , Bisharat Sleman , Shaulov Lihi , Brodski Claude , Song Zhiyin , Bandopadhyay Rina , Engelender Simone 
Published: October 2022

AbstractParkinson's disease (PD) is characterized by degeneration of neurons, particularly dopaminergic neurons in the substantia nigra. PD brains show accumulation of α‐synuclein in Lewy bodies and accumulation of dysfunctional mitochondria. However, the mechanisms leading to mitochondrial pathology in sporadic PD are poorly understood. PINK1 is a key for mitophagy activation and recycling of unfit mitochondria. The activation of mitophagy depends on the accumulation of uncleaved PINK1 at the outer mitochondrial membrane and activation of a cascade of protein ubiquitination at the surface of the organelle. We have now found that SIAH3, a member of the SIAH proteins but lacking ubiquitin‐ligase activity, is increased in PD brains and cerebrospinal fluid and in neurons treated with α‐synuclein preformed fibrils (α‐SynPFF). We also observed that SIAH3 is aggregated together with PINK1 in the mitochondria of PD brains. SIAH3 directly interacts with PINK1, leading to their intra‐mitochondrial aggregation in cells and neurons and triggering a cascade of toxicity with PINK1 inactivation along with mitochondrial depolarization and neuronal death. We also found that SIAH1 interacts with PINK1 and promotes ubiquitination and proteasomal degradation of PINK1. Similar to the dimerization of SIAH1/SIAH2, SIAH3 interacts with SIAH1, promoting its translocation to mitochondria and preventing its ubiquitin‐ligase activity toward PINK1. Our results support the notion that the increase in SIAH3 and intra‐mitochondrial aggregation of SIAH3‐PINK1 may mediate α‐synuclein pathology by promoting proteotoxicity and preventing the elimination of dysfunctional mitochondria. We consider it possible that PINK1 activity is decreased in sporadic PD, which impedes proper mitochondrial renewal in the disease.