bluuebunny/crossref_metadata_2025_split huggingface dataset:
anndata: Annotated data
Authors: Virshup Isaac , Rybakov Sergei , Theis Fabian J. , Angerer Philipp , Wolf F. Alexander 
Published: December 2021

Summaryanndata is a Python package for handling annotated data matrices in memory and on disk (github.com/theislab/anndata), positioned between pandas and xarray. anndata offers a broad range of computationally efficient features including, among others, sparse data support, lazy operations, and a PyTorch interface.Statement of needGenerating insight from high-dimensional data matrices typically works through training models that annotate observations and variables via low-dimensional representations. In exploratory data analysis, this involvesiterativetraining and analysis using original and learned annotations and task-associated representations. anndata offers a canonical data structure for book-keeping these, which is neither addressed by pandas (McKinney, 2010), nor xarray (Hoyer & Hamman, 2017), nor commonly-used modeling packages like scikit-learn (Pedregosa et al., 2011).
Well-Lit: A programmable and customizable assistant for manual multi-well plate pipetting
Authors: Gómez-Sjöberg Rafael , Cabrera Joana P. , Cote Andrew T. 
Published: December 2021

AbstractA very large number of biology and biochemistry laboratory protocols require transferring liquid aliquots from individual containers into individual wells of a multi-well plate, from plates to individual containers, or from one plate to another. Doing this by hand without errors, such as skipping wells, placing two samples in the same well, or swapping sample locations, especially when using plates with 96 wells or more, is difficult and requires enormous operator focus and/or a tedious manual error checking system. We present here a device built to facilitate error-free pipetting of samples from individual barcoded tubes to a multi-well plate or between multi-well plates (both 96 and 384 wells are supported). The device is programmable, modular and easily customizable to accommodate plates with different form-factors, and different protocols. The main components are only a 12.3” touch screen, a small form-factor PC, and a barcode scanner, combined with custom-made parts can be easily fabricated with a laser cutter and a hobby-grade 3D printer. The total cost is between approximately US$550 and US$600, depending on the configuration.Specifications table
Pre-clinical evaluation of antiviral activity of nitazoxanide against Sars-CoV-2
Authors: Driouich Jean-Sélim , Cochin Maxime , Touret Franck , Petit Paul-Rémi , Gilles Magali , Moureau Grégory , Barthélémy Karine , Laprie Caroline , Wattanakul Thanaporn , Chotsiri Palang , Hoglund Richard M. , Tarning Joel , Escudié Fanny , Scandale Ivan , Chatelain Eric , de Lamballerie Xavier , Solas Caroline , Nougairède Antoine 
Published: December 2021

AbstractTo address the emergence of SARS-CoV-2, multiple clinical trials in humans were rapidly started, including those involving an oral treatment by nitazoxanide, despite no or limited pre-clinical evidence of antiviral efficacy. In this work, we present a complete pre-clinical evaluation of the antiviral activity of nitazoxanide against SARS-CoV-2. First, we confirmed the in vitro efficacy of nitazoxanide and tizoxanide (its active metabolite) against SARS-CoV-2. Then, we demonstrated nitazoxanide activity in a reconstructed bronchial human airway epithelium model. In a SARS-CoV-2 virus challenge model in hamsters, oral and intranasal treatment with nitazoxanide failed to impair viral replication in commonly affected organs. We hypothesized that this could be due to insufficient diffusion of the drug into organs of interest. Indeed, our pharmacokinetic study confirmed that concentrations of tizoxanide in organs of interest were always below the in vitro EC50. These preclinical results suggest, if directly applicable to humans, that the standard formulation and dosage of nitazoxanide is not effective in providing antiviral therapy for Covid-19.
Prediction of high-risk liver cancer patients from their mutation profile: Benchmarking of mutation calling techniques
Authors: Patiyal Sumeet , Dhall Anjali , Raghava Gajendra P. S. 
Published: December 2021

AbstractIdentification of somatic mutations with high precision is one of the major challenges in prediction of high-risk liver-cancer patients. In the past, number of mutation calling techniques have been developed that include MuTect2, MuSE, Varscan2, and SomaticSniper. In this study, an attempt has been made to benchmark potential of these techniques in predicting prognostic biomarkers for liver cancer. Initially, we extracted somatic mutations in liver-cancer patients using VCF and MAF files from the cancer genome atlas. In terms of size, the MAF files are 42 times smaller than VCF files and containing only high-quality somatic mutations. Further, machine learning based models have been developed for predicting high-risk cancer patients using mutations obtain from different techniques. The performance of different techniques and data files have been compared based on their potential to discriminate high and low risk liver-cancer patients. Finally, univariate survival analysis revealed the prognostic role of highly mutated genes. Based on correlation analysis, we selected 80 genes negatively associated with the overall survival of the liver cancer patients. Single-gene based analysis showed that MuTect2 technique based MAF file has achieved maximum HRLAMC3 9.25 with p-value 1.78E-06. Further, we developed various prediction models using selected genes for each technique, and the results indicate that MuTect2 technique based VCF files outperform all other methods with maximum AUROC of 0.72 and HR 4.50 (p-value 3.83E-15). Eventually, VCF file generated using MuTect2 technique performs better among other mutation calling techniques to explore the prognostic potential of mutations in liver cancer. We hope that our findings will provide a useful and comprehensive comparison of various mutation calling techniques for the prognostic analysis of cancer patients.
Unexpected arabinosylation after humanization of plant protein N-glycosylation
Authors: Bohlender Lennard L. , Parsons Juliana , Hoernstein Sebastian N. W. , Bangert Nina , Rodríguez-Jahnke Fernando , Reski Ralf , Decker Eva L. 
Published: December 2021

AbstractAs biopharmaceuticals, recombinant proteins have become indispensable tools in medicine. An increasing demand, not only in quantity but also in diversity, drives the constant development and improvement of production platforms. The N-glycosylation pattern on biopharmaceuticals plays an important role in activity, serum half-life and immunogenicity. Therefore, production platforms with tailored protein N-glycosylation are of great interest. Plant-based systems have already demonstrated their potential to produce pharmaceutically relevant recombinant proteins, although their N-glycan patterns differ from those in humans. Plants have shown great plasticity towards the manipulation of their glycosylation machinery, and some have already been glyco-engineered in order to avoid the attachment of plant-typical, putatively immunogenic sugar residues. This resulted in complex-type N-glycans with a core structure identical to the human one. Compared to humans, plants lack the ability to elongate these N-glycans with β1,4-linked galactoses and terminal sialic acids. However, these modifications, which require the activity of several mammalian enzymes, have already been achieved for Nicotiana benthamiana and the moss Physcomitrella. Here, we present the first step towards sialylation of recombinant glycoproteins in Physcomitrella, human β1,4-linked terminal N-glycan galactosylation, which was achieved by the introduction of a chimeric β1,4-galactosyltransferase (FTGT). This chimeric enzyme consists of the moss α1,4-fucosyltransferase transmembrane domain, fused to the catalytic domain of the human β1,4-galactosyltransferase. Stable FTGT expression led to the desired β1,4-galactosylation. However, additional pentoses of unknown identity were also observed. The nature of these pentoses was subsequently determined by Western blot and enzymatic digestion followed by mass spectrometric analysis and resulted in their identification as α-linked arabinoses. Since a pentosylation of β1,4-galactosylated N-glycans was reported earlier, e.g. on recombinant human erythropoietin produced in glyco-engineered Nicotiana tabacum, this phenomenon is of a more general importance for plant-based production platforms. Arabinoses, which are absent in humans, may prevent the full humanization of plant-derived products. Therefore, the identification of these pentoses as arabinoses is important as it creates the basis for their abolishment to ensure the production of safe biopharmaceuticals in plant-based systems.
Diversity and Divergence: Evolution of defense chemistry in the tropical tree genusInga
Authors: Forrister Dale L. , Endara María-José , Soule Abrianna J. , Younkin Gordon C. , Mills Anthony G. , Lokvam John , Dexter Kyle G. , Pennington R. Toby , Kidner Catherine A. , Nicholls James A. , Loiseau Oriane , Kursar Thomas A. , Coley Phyllis D. 
Published: December 2021

SummaryPlants are widely recognized as chemical factories, with each species producing dozens to hundreds of unique secondary metabolites. These compounds shape the interactions between plants and their natural enemies. Here we explore how plants generate chemical diversity, and what evolutionary processes have led to novel compounds and unique chemical profiles.We comprehensively characterized the chemical profile of one-third of the species of tropical rainforest trees in the genusInga(∼ 100, Fabaceae) and applied phylogenetic comparative methods to understand the mode of chemical defense evolution.We show that: 1) EachIngaspecies produces exceptionally high levels of phytochemical diversity, despite costs, tradeoffs and biosynthetic constraints. 2) Closely related species have highly divergent defense profiles, with individual compounds, major compound classes and complete profiles showing little to no phylogenetic signal. 3) We show that the evolution of a species’ chemical profile shows a signature of divergent adaptation, implying that it is advantageous for a species to have distinct chemistry from close relatives to avoid shared natural enemies. 4) Finally, we hypothesize a model where deep homology of biosynthetic pathways and rapid changes in regulatory mechanisms may better explain the observed large shifts in defense chemicals between closely related taxa.
Percolation transition determines protein size limit for passive transport through the nuclear pore complex
Authors: Winogradoff David , Chou Han-Yi , Maffeo Christopher , Aksimentiev Aleksei 
Published: December 2021

AbstractNuclear pore complexes (NPCs) control biomolecular transport in and out of the nucleus. Disordered nucleoporins in the complex”s central pore form a permeation barrier, preventing unassisted transport of large biomolecules. Here, we combine coarse-grained simulations of an experimentally-derived NPC structure with a theoretical model to determine the microscopic mechanism of passive transport. Brute-force simulations of protein diffusion through the NPC reveal telegraph-like behavior, where prolonged diffusion on one side of the NPC is interrupted by rapid crossings to the other. We rationalize this behavior using a theoretical model that reproduces the energetics and kinetics of permeation solely from statistical analysis of transient voids within the disordered mesh. As the protein size increases, the mesh transforms from a soft to a hard barrier, enabling orders-of-magnitude reduction in permeation rate for proteins beyond the percolation size threshold. Our model enables exploration of alternative NPC architectures and sets the stage for uncovering molecular mechanisms of facilitated nuclear transport.
Bayesian inference in ring attractor networks
Authors: Kutschireiter Anna , Basnak Melanie A , Drugowitsch Jan 
Published: December 2021

AbstractWorking memories are thought to be held in attractor networks in the brain. These attractors should keep track of the uncertainty associated with each memory, so as to weigh it properly against conflicting new evidence. However, conventional attractors do not represent uncertainty. Here we show how uncertainty could be incorporated into an attractor, specifically a ring attractor that encodes head direction. First, we introduce the first rigorous normative framework (the circular Kalman filter) for benchmarking the performance of a ring attractor under conditions of uncertainty. Next we show that the recurrent connections within a conventional ring attractor can be re-tuned to match this benchmark. This allows the amplitude of network activity to grow in response to confirmatory evidence, while shrinking in response to poor-quality or strongly conflicting evidence. This “Bayesian ring attractor” performs near-optimal angular path integration and evidence accumulation. Indeed, we show that a Bayesian ring attractor is consistently more accurate than a conventional ring attractor. Moreover, near-optimal performance can be achieved without exact tuning of the network connections. Finally, we use large-scale connectome data to show that the network can achieve near-optimal performance even after we incorporate biological constraints. Our work demonstrates how attractors can implement a dynamic Bayesian inference algorithm in a biologically plausible manner, and it makes testable predictions with direct relevance to the head direction system, as well as any neural system that tracks direction, orientation, or periodic rhythms.Significance StatementData from human subjects as well as animals shows that working memories are associated with a sense of uncertainty. Indeed, a sense of uncertainty is what allows an observer to properly weigh new evidence against their current memory. However, we do not understand how the brain tracks uncertainty. Here we describe a simple and biologically plausible network model that can track the uncertainty associated with a working memory. The representation of uncertainty in this model improves the accuracy of its working memory, as compared to conventional models, because it assigns the proper weight to new conflicting evidence. Our model provides a new interpretation for observed fluctuations in brain activity, and it makes testable new predictions.
In situcontrol of root–bacteria interactions using optical trapping in transparent soil
Authors: Ge Sisi , Wright Kathryn M , Humphris Sonia N , Dupuy Lionel X , MacDonald Michael P 
Published: December 2021

AbstractBacterial attachment on root surfaces is an important step preceding the colonisation or internalisation and subsequent infection of plants by pathogens. Unfortunately, bacterial attachment is not well understood because the phenomenon is difficult to observe. Here we assessed whether this limitation could be overcome using optical trapping approaches. We have developed a system based on counter-propagating beams and studied its ability to guidePectobacterium atrosepticum(Pba) cells to different root cell types within the interstices of transparent soils. Bacterial cells were successfully trapped and guided to root hair cells, epidermis cells, border cells and tissues damaged by laser ablation. Finally, we used the system to quantify the bacterial cell detachment rate of Pba cells on root surfaces following reversible attachment. Optical trapping techniques could greatly enhance our ability to deterministically characterise mechanisms linked to attachment and formation of biofilms in the rhizosphere.
Dynamics of DNA replication during male gametogenesis in the malaria parasite Plasmodium falciparum
Authors: Matthews Holly , McDonald Jennifer , Totanes Francis Isidore G. , Merrick Catherine J. 
Published: December 2021

ABSTRACTMalaria parasites undergo a single phase of sexual reproduction in their complex lifecycle, during which they cycle between mosquito and vertebrate hosts. Sexual reproduction occurs only at the point when parasites move into the mosquito host. It involves specialised, sexually committed cells called gametocytes, which develop very rapidly into mature gametes and then mate inside the mosquito midgut. The gamete development process is unique, involving unprecedentedly fast replication and cell division to produce male gametes. A single male gametocyte replicates its ∼23Mb genome three times over to produce 8 genomes, segregates these into newly-assembled flagellated gamete cells and releases them to seek out female gametes, all within ∼15 minutes. Here, for the first time, we use fluorescent labelling of de novo DNA synthesis to follow this process at the whole-cell and single-molecule levels, yielding several novel observations. Firstly, we confirm that no DNA replication occurs before gametogenesis is triggered, although the origin recognition complex protein Orc1 is abundant even in immature gametocytes. Secondly, between repeated rounds of DNA replication there is no detectable karyokinesis – in contrast to the repeated replicative rounds that occur in asexual schizonts. Thirdly, cytokinesis is clearly uncoupled from DNA replication, and can occur even if replication fails, implying a lack of cell cycle checkpoints. Finally the single-molecule dynamics of DNA replication are entirely different from those in asexual schizonts.
Reviving ghost alleles: Genetically admixed coyotes along the American Gulf Coast are critical for saving the endangered red wolf
Authors: vonHoldt Bridgett M. , Hinton Joseph W. , Shutt Amy C. , Adams Jennifer R. , Waits Lisette P. , Brzeski Kristin E. 
Published: December 2021

AbstractThe last red wolves were captured along the Gulf Coast in 1980, where they hybridized with coyote, to establish the captive breeding population. However, red wolf ancestry persists in local coyotes and could be leveraged by genomic innovations to support species persistence. We assessed genomic ancestry and morphology of coyotes in southwestern Louisiana, and find they carried 38-62% red wolf ancestry acquired in the last 30 years, which is enriched on land with minimal coyote hunting. These coyotes were also similar in ancestry to canids captured in the 1970s that initiated the red wolf captive breeding program. Further, we reported that coyotes with higher red wolf ancestry are larger in size. Our findings evidence the importance of hybrids as a reservoir of endangered species ancestry for contemporary conservation efforts. Admixed genomes are at the forefront of innovative solutions, with red wolf survival a prime candidate for this new paradigm.TeaserCoyotes along the American Gulf Coast carry genetic variation critical for the survival of the endangered red wolf species.
Household food waste and pathways to responsible consumer behaviour: evidence from Australia
Authors: Haque Amlan , Karunasena Gamithri Gayana , Pearson David 
Published: December 2021

PurposeThis paper aims to stimulate the pursuit of waste-free food consumption and develop guidelines to avoid irresponsible consumer behaviours. In doing so, the paper answers the questions: How much food is thrown away by Australian households? What are the causes of food wasted? And, how motivated are Australian household members to reduce food waste?Design/methodology/approachAn online survey was completed by a demographically representative sample of 5,272 households in Australia to address these questions. Using the state-wise data set and a structural equation modelling technique, this paper analyses behavioural and socio-demographic factors that influence household food waste in Australia.FindingsThe study identified that inedible food waste was the most common waste that people threw away (69%). The second-largest contribution towards waste came from meal leftovers (44%). The study identified household members not finishing their meal and cooking too much food as the leading causes of food waste from meal leftovers. Furthermore, household food members were unable to identify whether the food was safe to eat, uncertain whether they would eat prepared food that was saved for later consumption and remained confused about when to discard food. Finally, 42% indicated a high level of motivation to reduce food waste, while 34% indicated a moderated level.Originality/valueThis study's findings contribute to the practical challenges associated with the measurement of food waste in households. Further, the study provides insights to policymakers and practitioners to develop customised interventions to reduce household food waste.
Commentary: the unintended consequences of digital service technologies
Authors: Rosenbaum Mark S. , Walters Gabby , Edwards Karen L. , Gonzalez-Arcos Claudia Fernanda 
Published: December 2021

Purpose
This commentary puts forth a conceptual framework, referred to as the consumer, organization, government framework of unintended digital technology service failures, that specifies consumer, organizational and governmental shortcomings that result in digital technologies failing in terms of negatively affecting consumer, communal, national and/or global welfare.

Design/methodology/approach
The authors conceptualize an original framework by engaging in a literature review regarding marketplace failures associated with digital service technologies.

Findings
The framework shows that three drivers explain why commercial digital technologies often fail. The first driver highlights misuse or criminal intent from individuals. The second involves organizations failing to prevent or to address technology failures. The third pertains to failures that stem from governmental institutions.

Research limitations/implications
The authors encourage researchers to build on their framework by putting forth research questions. To prevent or lessen opportunities for digital technologies to result in service failures, the authors also offer practitioners a “digital technology service failure audit.” This audit shows how digital technology creators and managers can anticipate and address consumer, organizational and governmental factors that often cause digital service technologies failures.

Social implications
Despite the absence of industry-specific regulations and the existence of some regulatory immunities, digital technology providers have an ethical duty, and may be obligated under applicable tort law principles, to take steps to prevent unintended harm to consumers before launching their service technologies.

Originality/value
This work reveals that digital technologies represent new and different threats to vulnerable consumers, who often rely on, but do not fully understand, these technologies in their everyday living. The framework helps consumers, organizations and government agencies to identify and remedy current and potential instances of harmful digital technologies.