bluuebunny/crossref_metadata_2025 huggingface dataset:
A cap 0-dependent mRNA capture method to analyze the yeast transcriptome
Authors: Nowacka Martyna , Latoch Przemysław , Izert Matylda A , Karolak Natalia K , Tomecki Rafal , Koper Michał , Tudek Agnieszka , Starosta Agata L , Górna Maria W
Published: October 2022

Analysis of the protein coding transcriptome by the RNA sequencing requires either enrichment of the desired fraction of coding transcripts or depletion of the abundant non-coding fraction consisting mainly of rRNA. We propose an alternative mRNA enrichment strategy based on the RNA-binding properties of the human IFIT1, an antiviral protein recognizing cap 0 RNA. Here, we compare for Saccharomyces cerevisiae an IFIT1-based mRNA pull-down with yeast targeted rRNA depletion by the RiboMinus method. IFIT1-based RNA capture depletes rRNA more effectively, producing high quality RNA-seq data with an excellent coverage of the protein coding transcriptome, while depleting cap-less transcripts such as mitochondrial or some non-coding RNAs. We propose IFIT1 as a cost effective and versatile tool to prepare mRNA libraries for a variety of organisms with cap 0 mRNA ends, including diverse plants, fungi and eukaryotic microbes.
PGG.SV: a whole-genome-sequencing-based structural variant resource and data analysis platform
Authors: Wang Yimin , Ling Yunchao , Gong Jiao , Zhao Xiaohan , Zhou Hanwen , Xie Bo , Lou Haiyi , Zhuang Xinhao , Jin Li ,   The Han100K Initiative, Fan Shaohua , Zhang Guoqing , Xu Shuhua
Published: October 2022

Structural variations (SVs) play important roles in human evolution and diseases, but there is a lack of data resources concerning representative samples, especially for East Asians. Taking advantage of both next-generation sequencing and third-generation sequencing data at the whole-genome level, we developed the database PGG.SV to provide a practical platform for both regionally and globally representative structural variants. In its current version, PGG.SV archives 584 277 SVs obtained from whole-genome sequencing data of 6048 samples, including 1030 long-read sequencing genomes representing 177 global populations. PGG.SV provides (i) high-quality SVs with fine-scale and precise genomic locations in both GRCh37 and GRCh38, covering underrepresented SVs in existing sequencing and microarray data; (ii) hierarchical estimation of SV prevalence in geographical populations; (iii) informative annotations of SV-related genes, potential functions and clinical effects; (iv) an analysis platform to facilitate SV-based case-control association studies and (v) various visualization tools for understanding the SV structures in the human genome. Taken together, PGG.SV provides a user-friendly online interface, easy-to-use analysis tools and a detailed presentation of results. PGG.SV is freely accessible via https://www.biosino.org/pggsv.
Catalytically inactive DNA ligase IV promotes DNA repair in living cells
Authors: Goff Noah J , Brenière Manon , Buehl Christopher J , de Melo Abinadabe J , Huskova Hana , Ochi Takashi , Blundell Tom L , Mao Weifeng , Yu Kefei , Modesti Mauro , Meek Katheryn
Published: October 2022

DNA double strand breaks (DSBs) are induced by external genotoxic agents (ionizing radiation or genotoxins) or by internal processes (recombination intermediates in lymphocytes or by replication errors). The DNA ends induced by these genotoxic processes are often not ligatable, requiring potentially mutagenic end-processing to render ends compatible for ligation by non-homologous end-joining (NHEJ). Using single molecule approaches, Loparo et al. propose that NHEJ fidelity can be maintained by restricting end-processing to a ligation competent short-range NHEJ complex that ‘maximizes the fidelity of DNA repair’. These in vitro studies show that although this short-range NHEJ complex requires DNA ligase IV (Lig4), its catalytic activity is dispensable. Here using cellular models, we show that inactive Lig4 robustly promotes DNA repair in living cells. Compared to repair products from wild-type cells, those isolated from cells with inactive Lig4 show a somewhat increased fraction that utilize micro-homology (MH) at the joining site consistent with alternative end-joining (a-EJ). But unlike a-EJ in the absence of NHEJ, a large percentage of joints isolated from cells with inactive Lig4 occur with no MH – thus, clearly distinct from a-EJ. Finally, biochemical assays demonstrate that the inactive Lig4 complex promotes the activity of DNA ligase III (Lig3).
Analysis of nested alternate open reading frames and their encoded proteins
Authors: Vasu Kommireddy , Khan Debjit , Ramachandiran Iyappan , Blankenberg Daniel , Fox Paul L
Published: October 2022

Transcriptional and post-transcriptional mechanisms diversify the proteome beyond gene number, while maintaining a sequence relationship between original and altered proteins. A new mechanism breaks this paradigm, generating novel proteins by translating alternative open reading frames (Alt-ORFs) within canonical host mRNAs. Uniquely, ‘alt-proteins’ lack sequence homology with host ORF-derived proteins. We show global amino acid frequencies, and consequent biochemical characteristics of Alt-ORFs nested within host ORFs (nAlt-ORFs), are genetically-driven, and predicted by summation of frequencies of hundreds of encompassing host codon-pairs. Analysis of 101 human nAlt-ORFs of length ≥150 codons confirms the theoretical predictions, revealing an extraordinarily high median isoelectric point (pI) of 11.68, due to anomalous charged amino acid levels. Also, nAlt-ORF proteins exhibit a >2-fold preference for reading frame 2 versus 3, predicted mitochondrial and nuclear localization, and elevated codon adaptation index indicative of natural selection. Our results provide a theoretical and conceptual framework for exploration of these largely unannotated, but potentially significant, alternative ORFs and their encoded proteins.
Prevalence and Factors Associated With Antigen Test Positivity Following SARS-CoV-2 Infection Among Health Care Workers in Los Angeles
Authors: Adamson Paul C , Currier Judith S , Uslan Daniel Z , Garner Omai B
Published: October 2022

Surges of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections among health care workers (HCWs) have led to critical staffing shortages. From January 4 to February 4, 2022, we implemented a return-to-work antigen testing program for HCWs, and 870 HCWs participated. Antigen test positivity was 60.5% for those ≤5 days from symptom onset or positive polymerase chain reaction (PCR), and 47.4% were positive at day 7. Antigen positivity was associated with receiving a booster vaccination and being ≤6 days from symptom onset or PCR test, but not age or a symptomatic infection. Rapid antigen testing can be a useful tool to guide return-to-work and isolation precautions for HCWs following infection.
Steady jet ejections from the innermost region of advection-dominated accretion flow around a black hole
Authors: Inoue Hajime
Published: October 2022

We study ejection mechanisms for two kinds of steady jets: one observed from black hole binaries in the low/hard state and the other from SS 433. The specific energy of the ejected gas is required to be positive for the jets to get to infinity, while that of the accreted gas is naively considered to be negative at the outermost boundary of the accretion flow. To reconcile the opposite sign of the specific energies, we propose a situation where two layers exist in the accretion flow and one layer receives energy from the other sufficiently for the specific energy to be positive. For the steady jets in the low/hard state, the accretion ring at the outermost end of the accretion flow is considered to yield two-layer flow in which a geometrically thick advection-dominated accretion flow (ADAF) sandwiches a geometrically thin accretion disk and the thin disk is supposed to change to another ADAF on the inner side. The energy transfer is expected to occur through turbulent mixing between the two layers and the upper layer is discussed as having a positive specific energy large enough for the terminal velocity to be ∼0.1 c. For the steady jets from SS 433, it is argued that a slim disk separates into two stratified layers due to the photon diffusion in the direction perpendicular to the equatorial plane under the advection-dominated situation. In this case, the specific energy of the upper layer is expected to be positive such that the terminal velocity exceeds 0.2c. The jet ejection process near the black hole is investigated commonly to both the two-layer cases and predicts that the jet opening angle becomes as small as 2°.
The Language of Incarceration and of Persons Subject to Incarceration
Authors: Reid Lynette
Published: October 2022

Reflecting on Smith (2021) in this issue, this commentary extends our consideration of issues in carceral health and questions the dehumanizing language we sometimes use—including in public health and public health ethics—to talk about persons held in incarceration. Even the language we use for the carceral system itself (such as ‘criminal justice system’) is fraught: it casts a laudatory light on the system and papers over its role in compounding racial health inequities and in sustaining colonialism. A host of issues call out for ethical analysis, using lenses that can encompass the tensions and contradictions experienced by people within the system who deliver healthcare and those within the system trying to access that care. Beyond access to health care (promotion, prevention, treatment and palliation), the societal commitment to dealing with social issues by depriving people of many key social determinants of health is at the heart of many of these tensions and contradictions.
Hurdles in responsive community engagement for the development of environmental biotechnologies
Authors: Normandin Avery M , Fitzgerald Lily M , Yip Julianne , Evans Sam Weiss
Published: October 2022

Recent calls for engaging communities in biotechnology development do not draw enough attention to the hurdles that must be overcome for engagement strategies to effectively feed back into research design and conduct. These hurdles call into question many standard ways of operating and assessing in traditional scientific disciplines. The first steps in addressing these hurdles can be the most difficult. In reflecting on our own experiences in the early-stage development of environmental biotechnologies, we provide a set of techniques to help scientists and their collaborators learn to become more responsive to the needs and attitudes of communities with which they are engaging.

Graphical Abstract
Spiking burstiness and working memory in the human medial temporal lobe
Authors: Cocina Francesco , Vitalis Andreas , Caflisch Amedeo
Published: October 2022

Persistent activity has commonly been considered to be a hallmark of working memory (WM). Recent evidence indicates that neuronal discharges in the medial temporal lobe (MTL) are compatible with WM neural patterns observed in cortical areas. However, the characterization of this activity rarely consists of measurements other than firing rates of single neurons. Moreover, a varied repertoire of firing dynamics has been reported in the MTL regions, which motivate the more detailed examination of the relationships between WM processes and discharge patterns undertaken here. Specifically, we investigate‚ at different resolution levels, firing irregularities in electrode recordings from the hippocampus, amygdala, and the entorhinal cortex of epileptic patients during a WM task. We show that some types of (ir)regularities predict response times of the patients depending on the trial periods under consideration. Prominent burst activity at the population level is observed in the amygdala and entorhinal cortex during memory retrieval. In general, regular and bursty neurons contribute to the decoding of the memory load, yet they display important differences across the three anatomical areas. Our results suggest that nonrandom (non-Poisson) patterns are relevant for WM, which calls for the development and use of statistics complementary to mere spike counts.
Value of whole-body MRI for the assessment of response to albendazole in disseminated neurocysticercosis: a prospective follow-up study
Authors: Wangda Kinzang , Kumar Neeraj , Garg Ravindra Kumar , Malhotra Hardeep Singh , Rizvi Imran , Uniyal Ravi , Pandey Shweta , Malhotra Kiran Preet , Verma Rajesh , Sharma Praveen Kumar , Parihar Anit , Jain Amita
Published: October 2022

Background

Disseminated neurocysticercosis is defined as simultaneous involvement of the brain (≥3 cysts) and at least one additional body site/organ. We aimed to identify disseminated cystic lesions in other body parts and investigate the effect of albendazole.

Methods

We enrolled patients with multiple (≥3) neurocysticercosis brain lesions. Whole-body MRI (short tau inversion recovery coronal sequences) was performed to assess the number of lesions in the brain and other body parts at baseline and 3 months after albendazole therapy.

Results

We screened 35 patients with multiple brain neurocysticercosis. In 13 patients, whole-body MRI demonstrated disseminated neurocysticercosis lesions. Ten patients were treated with albendazole. We excluded three patients. Brain MRI showed a mean lesion count of 163.6±193.8. Whole-body MRI (excluding the brain) showed a mean lesion count of 629.9±486.1. After albendazole therapy, the lesion load of the brain reduced significantly (163.6±193.8 to 99±178.3; p=0.008). Similarly, whole-body MRI showed a significant reduction in extracerebral neurocysticercosis lesion load (629.9±486.1 to 183.4±301.9; p=0.005). Three patients had complete resolution, five patients showed ≥50% reduction and two patients had <50% reduction in extracerebral lesion load.

Conclusion

Whole-body MRI should routinely be performed in multiple neurocysticercosis lesions of the brain. Albendazole treatment leads to a remarkable reduction in neurocysticercosis lesions throughout the body.
Outpatient management of adults with COVID-19
Authors: Pullen Richard L.
Published: October 2022

This article discusses the outpatient management of adults with COVID-19 that reflects current evidence and best practices. Variants of concern, clinical presentation, assessment of the patient's clinical status, vaccination, medication management, and patient teaching are presented.
Current Management of Late Posttraumatic Enophthalmos
Authors: DeSerres Joshua J. , Budning Andrew , Antonyshyn Oleh M.
Published: October 2022

Learning Objectives:

After studying this article, the participant should be able to: 1. Describe the orbital anatomy and completely understand the important components relevant to surgical correction of enophthalmos, including oculo-orbito relations. 2. Understand the pathophysiology and predictive factors for posttraumatic enophthalmos and identify the challenges associated with correction of enophthalmos in the late setting. 3. Develop a surgical plan for late enophthalmos repair and understand the value and utility of osteotomies, intraoperative navigation, and patient-specific implants. 4. Discuss the expected outcomes, possible complications, and adjunctive surgery as related to late enophthalmos repair.

This article addresses the current management of late posttraumatic enophthalmos. In this article, the authors describe surgically relevant orbital anatomy and oculo-orbital relations, the pathophysiology of enophthalmos, clinical and radiologic findings, decision-making in management, and surgical treatment. The authors attempt to cover some of the main challenges and recent advances in the management of late posttraumatic enophthalmos, including intraoperative navigation and patient-specific implants.
Class II transactivator induces expression of MHC-I and MHC-II in transmissible Tasmanian devil facial tumours
Authors: Ong Chrissie E. B. , Cheng Yuanyuan , Siddle Hannah V. , Lyons A. Bruce , Woods Gregory M. , Flies Andrew S.
Published: October 2022

MHC-I and MHC-II molecules are critical components of antigen presentation and T cell immunity to pathogens and cancer. The two monoclonal transmissible devil facial tumours (DFT1, DFT2) exploit MHC-I pathways to overcome immunological anti-tumour and allogeneic barriers. This exploitation underpins the ongoing transmission of DFT cells across the wild Tasmanian devil population. We have previously shown that the overexpression of NLRC5 in DFT1 and DFT2 cells can regulate components of the MHC-I pathway but not MHC-II, establishing the stable upregulation of MHC-I on the cell surface. As MHC-II molecules are crucial for CD4
+
T cell activation, MHC-II expression in tumour cells is beginning to gain traction in the field of immunotherapy and cancer vaccines. The overexpression of Class II transactivator in transfected DFT1 and DFT2 cells induced the transcription of several genes of the MHC-I and MHC-II pathways. This was further supported by the upregulation of MHC-I protein on DFT1 and DFT2 cells, but interestingly MHC-II protein was upregulated only in DFT1 cells. This new insight into the regulation of MHC-I and MHC-II pathways in cells that naturally overcome allogeneic barriers can inform vaccine, immunotherapy and tissue transplant strategies for human and veterinary medicine.
A low-rank ensemble Kalman filter for elliptic observations
Authors: Le Provost Mathieu , Baptista Ricardo , Marzouk Youssef , Eldredge Jeff D.
Published: October 2022

We propose a regularization method for ensemble Kalman filtering (EnKF) with elliptic observation operators. Commonly used EnKF regularization methods suppress state correlations at long distances. For observations described by elliptic partial differential equations, such as the pressure Poisson equation (PPE) in incompressible fluid flows, distance localization should be used cautiously, as we cannot disentangle slowly decaying physical interactions from spurious long-range correlations. This is particularly true for the PPE, in which distant vortex elements couple nonlinearly to induce pressure. Instead, these inverse problems have a low effective dimension: low-dimensional projections of the observations strongly inform a low-dimensional subspace of the state space. We derive a low-rank factorization of the Kalman gain based on the spectrum of the Jacobian of the observation operator. The identified eigenvectors generalize the source and target modes of the multipole expansion, independently of the underlying spatial distribution of the problem. Given rapid spectral decay, inference can be performed in the low-dimensional subspace spanned by the dominant eigenvectors. This low-rank EnKF is assessed on dynamical systems with Poisson observation operators, where we seek to estimate the positions and strengths of point singularities over time from potential or pressure observations. We also comment on the broader applicability of this approach to elliptic inverse problems outside the context of filtering.
Two-dimensional signature of images and texture classification
Authors: Zhang Sheng , Lin Guang , Tindel Samy
Published: October 2022

We introduce a proper notion of two-dimensional signature for images. This object is inspired by the so-called rough paths theory, and it captures many essential features of a two-dimensional object such as an image. It thus serves as a low-dimensional feature for pattern classification. Here, we implement a simple procedure for texture classification. In this context, we show that a low-dimensional set of features based on signatures produces an excellent accuracy.
Temperature-driven heterochrony as a main evolutionary response to climate changes in conodonts
Authors: Souquet Louise , Guenser Pauline , Girard Catherine , Mazza Michele , Rigo Manuel , Goudemand Nicolas
Published: October 2022

Can we predict the evolutionary response of organisms to climate changes? The direction of greatest intraspecific phenotypic variance is thought to correspond to an ‘
evolutionary line of least resistance
’, i.e. a taxon's phenotype is expected to evolve along that general direction, if not constrained otherwise. In particular, heterochrony, whereby the timing or rate of developmental processes are modified, has often been invoked to describe evolutionary trajectories and it may be advantageous to organisms when rapid adaptation is critical. Yet, to date, little is known empirically as to which covariation patterns, whether static allometry, as measured in adult forms only, or ontogenetic allometry, the basis for heterochrony, may be prevalent in what circumstances. Here, we quantify the morphology of segminiplanate conodont elements during two distinct time intervals separated by more than 130 Myr: the Devonian-Carboniferous boundary and the Carnian-Norian boundary (Late Triassic). We evidence that the corresponding species share similar patterns of intraspecific static allometry. Yet, during both crises, conodont evolution was decoupled from this common evolutionary line of least resistance. Instead, it followed heterochrony-like trajectories that furthermore appear as driven by ocean temperature. This may have implications for our interpretation of conodonts' and past marine ecosystems’ response to environmental perturbations.
Agricultural policies against invasive species generate contrasting outcomes for climate change mitigation and biodiversity conservation
Authors: Pérez-Méndez N. , Alcaraz C. , Bertolero A. , Català-Forner M. , Garibaldi L. A. , González-Varo J. P. , Rivaes S. , Martínez-Eixarch M.
Published: October 2022

Direct consequences of biological invasions on biodiversity and the environment have been largely documented. Yet collateral indirect effects mediated by changes in agri-environmental policies aimed at combating invasions remain little explored. Here we assessed the effects of recent changes in water management in rice farming, which are aimed at buffering the impact of the invasive apple snail (
Pomacea maculata,
Lamarck) on greenhouse gas emissions and diversity of waterbird communities. We used observational data from a 2-year field monitoring (2015–2016) performed at the Ebro Delta regional scale. We found that drying rice fields reduced methane emission rates by 82% (2015) and 51% (2016), thereby reducing the contribution of rice farming to climate change. However, there was a marked reduction (75% in 2015 and 57% in 2016) in waterbird diversity in dry fields compared with flooded fields, thus suggesting that post-invasion policies might hinder biodiversity conservation. Our results highlight the need for accounting for potential collateral effects during the policy decision-making process to design efficient agricultural management plans that lessen undesirable agri-environmental outcomes.
Social interaction can select for reduced ability
Authors: McNamara John M. , Wolf Max
Published: October 2022

Animals, including humans, differ in a wide range of physical and cognitive abilities ranging from measures of running speed and physical strength to learning ability and intelligence. We consider the evolution of ability when individuals interact pairwise over their contribution to a common good. In this interaction, the contribution of each is assumed to be the best given their own ability and the contribution of their partner. Since there is a tendency for individuals to partially compensate for a low contribution by their partner, low-ability individuals can do well. As a consequence, for benefit and cost structures for which individuals have a strong response to partner’s contribution, there can be selection for reduced ability. Furthermore, there can be disruptive selection on ability, leading to a bimodal distribution of ability under some modes of inheritance.
Methanobacterium alkalithermotolerans sp. nov., a novel alkaliphilic and hydrogen-utilizing methanogen isolated from an alkaline geothermal spring (La Crouen, New Caledonia)
Authors: Mei Nan , Postec Anne , Bartoli Manon , Vandecasteele Céline , Wils Laura , Gil Lisa , Monnin Christophe , Pelletier Bernard , Erauso Gael , Quéméneur Marianne
Published: October 2022

An anaerobic, hydrogenotrophic methane-producing archaeon was isolated from an alkaline thermal spring (42 °C, pH 9.0) in New Caledonia. This methanogen, designated strain CANT, is alkaliphilic, thermotolerant, with Gram-positive staining non-motile cells. Strain CANT grows autotrophically using hydrogen exclusively as an energy source and carbon dioxide as the sole carbon source (without the requirement of yeast extract or other organic compounds). It grows at 20–45 °C (optimum, 45 °C) and pH 7.3–9.7 (optimum, pH 9.0). NaCl is not required for growth (optimum 0 %) but is tolerated up to 1.5 %. It resists novobiocin, streptomycin and vancomycin but is inhibited by ampicillin and penicillin, among other antibiotics. The genome consists of a circular chromosome (2.2 Mb) containing 2126 predicted protein-encoding genes with a G+C content of 36.4 mol%. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that strain CANT is a member of the genus

Methanobacterium

, most closely related to the alkaliphilic

Methanobacterium alcaliphilum

WeN4T with 98.5 % 16S rRNA gene sequence identity. The genomes of strain CANT and

M. alcaliphilum

DSM 3459, sequenced in this study, share 71.6 % average nucleotide identity and 14.0 % digital DNA–DNA hybridization. Therefore, phylogenetic and physiological results indicate that strain CANT represents a novel species, for which the name Methanobacterium alkalithermotolerans sp. nov. is proposed, and strain CANT (=DSM 102889T= JCM 31304T) is assigned as the type strain.
KmerAperture: Retainingk-mer synteny for alignment-free extraction of core and accessory differences between bacterial genomes
Authors: Moore Matthew P. , Laager Mirjam , Ribeca Paolo , Didelot Xavier
Published: October 2022

By decomposing genome sequences intok-mers, it is possible to estimate genome differences without alignment. Techniques such ask-mer minimisers (MinHash), have been developed and are often accurate approximations of distances based on fullk-mer sets. These and other alignment-free methods avoid the large temporal and computational expense of alignment or mapping. However, thesek-mer set comparisons are not entirely accurate within-species and can be completely inaccurate within-lineage. This is due, in part, to their inability to distinguish core polymorphism from accessory differences. Here we present a new approach,KmerAperture, which uses information on thek-mer relative genomic positions to determine the type of polymorphism causing differences ink-mer presence and absence between pairs of genomes. Single SNPs are expected to result in contiguous series of relative uniquek-mers of lengthL=k. On the other hand, series of lengthL>kmay be caused by accessory differences of lengthL-k+1; when the start and end of the sequence are contiguous with homologous sequence. Alternatively, they may be caused by multiple SNPs withinkbp from each other andKmerAperturecan determine whether that is the case. To demonstrate use casesKmerAperturewas benchmarked using datasets including a very low diversity simulated population with accessory content independent from the number of SNPs, a simulated population were SNPs are spatially dense, a moderately diverse real cluster of genomes (Escherichia coliST1193) with a large accessory genome and a low diversity real genome cluster (SalmonellaTyphimurium ST34). We show thatKmerAperturecan accurately distinguish both core and accessory sequence diversity without alignment, outperforming otherk-mer based tools.
A spatio-temporal framework for modelling wastewater concentration during the COVID-19 pandemic
Authors: Li Guangquan , Denise Hubert , Diggle Peter , Grimsley Jasmine , Holmes Chris , James Daniel , Jersakova Radka , Mole Callum , Nicholson George , Smith Camila Rangel , Richardson Sylvia , Rowe William , Rowlingson Barry , Torabi Fatemeh , Wade Matthew J. , Blangiardo Marta
Published: October 2022

The potential utility of wastewater-based epidemiology as an early warning tool has been explored widely across the globe during the current COVID-19 pandemic. Methods to detect the presence of SARS-CoV-2 RNA in wastewater were developed early in the pandemic, and extensive work has been conducted to evaluate the relationship between viral concentration and COVID-19 case numbers at the catchment areas of sewage treatment works (STWs) over time. However, no attempt has been made to develop a model that predicts wastewater concentration at fine spatio-temporal resolutions covering an entire country, a necessary step towards using wastewater monitoring for the early detection of local outbreaks.

We consider weekly averages of flow-normalised viral concentration, reported as the number of SARS-CoV-2 N1 gene copies per litre (gc/L) of wastewater available at 303 STWs over the period between 1 June 2021 and 30 March 2022. We specify a spatially continuous statistical model that quantifies the relationship between weekly viral concentration and a collection of covariates covering socio-demographics, land cover and virus-associated genomic characteristics at STW catchment areas while accounting for spatial and temporal correlation.

We evaluate the model’s predictive performance at the catchment level through 10-fold cross-validation. We predict the weekly viral concentration at the population-weighted centroid of the 32,844 lower super output areas (LSOAs) in England, then aggregate these LSOA predictions to the Lower Tier Local Authority level (LTLA), a geography that is more relevant to public health policy-making. We also use the model outputs to quantify the probability of local changes of direction (increases or decreases) in viral concentration over short periods (e.g. two consecutive weeks).

The proposed statistical framework is able to predict SARS-CoV-2 viral concentration in wastewater at high spatio-temporal resolution across England. Additionally, the probabilistic quantification of local changes can be used as an early warning tool for public health surveillance.
Long-read genome sequencing accelerated the cloning ofPm69by resolving the complexity of a rapidly evolving resistance gene cluster in wheat
Authors: Li Yinghui , Wei Zhen-Zhen , Sela Hanan , Govta Liubov , Klymiuk Valentyna , Roychowdhury Rajib , Chawla Harmeet Singh , Ens Jennifer , Wiebe Krystalee , Bocharova Valeria , Ben-David Roi , Pawar Prerna B. , Jaiwar Samidha , Molnár István , Doležel Jaroslav , Pozniak Curtis J. , Fahima Tzion
Published: October 2022

Gene cloning in repeat-rich polyploid genomes remains challenging. Here we describe a strategy for overcoming major bottlenecks in the cloning of the powdery mildew (Pm) resistance gene (R-gene)Pm69derived from tetraploid wild emmer wheat (WEW). A conventional positional cloning approach encountered suppressed recombination due to structural variations, while chromosome sorting yielded an insufficient purity level. APm69physical map, constructed by assembling ONT long-read genome sequences, revealed a rapidly evolving nucleotide-binding leucine-rich repeat (NLR) R-gene cluster. A single candidate NLR was identified within this cluster by anchoring RNASeq reads of susceptible mutants to ONT contigs and was validated by the virus-induced gene silencing (VIGS) approach.Pm69, comprising Rx_N with RanGAP interaction sites, NB-ARC, and LRR domains, is probably a newly evolved NLR discovered only in one location across the WEW distribution range in the Fertile Crescent.Pm69was successfully introgressed into durum and bread wheat, and a diagnostic molecular marker could be used to accelerate its deployment and pyramiding with other resistance genes.
Mitotic chromosomes are self-entangled and disentangle through a Topoisomerase II-dependent two stage exit from mitosis
Authors: Hildebrand Erica M. , Polovnikov Kirill , Dekker Bastiaan , Liu Yu , Lafontaine Denis L. , Fox A. Nicole , Li Ying , Venev Sergey V. , Mirny Leonid , Dekker Job
Published: October 2022

The topological state of chromosomes determines their mechanical properties, dynamics, and function. Recent work indicated that interphase chromosomes are largely free of entanglements. Here, we use Hi-C, polymer simulations and multi-contact 3C, and propose that, in contrast, mitotic chromosomes are self-entangled. We explore how a mitotic self-entangled state is converted into an unentangled interphase state during mitotic exit. Most mitotic entanglements are removed during anaphase/telophase, with remaining ones removed during early G1, in a Topoisomerase II-dependent process. Polymer models suggest a two-stage disentanglement pathway: first, decondensation of mitotic chromosomes with remaining condensin loops produces entropic forces that bias Topoisomerase II activity towards decatenation. At the second stage, the loops are released, and formation of new entanglements is prevented by lower Topoisomerase II activity, allowing the establishment of unentangled and territorial G1 chromosomes. When mitotic entanglements are not removed, in experiment and models, a normal interphase state cannot be acquired.
The Symmetry and Asymmetry Behind Histone Folding Across Eukarya and Archaea
Authors: Zhao Haiqing , Wu Hao , Guseman Alex , Abeykoon Dulith , Camara Christina M. , Dalal Yamini , Fushman David , Papoian Garegin A.
Published: October 2022

Histones are the dominant proteins to compact and store DNA in both Eukarya and Archaea. For a long time, histones are observed to exist in the unit of dimers but diverge into different formats such as heterodimers in Eukarya or homodimers in Archaea. Here, by studying 11 types of histone proteins, both monomers and their dimeric complexes, using multiscale molecular dynamics (MD) simulations combined with NMR and circular dichroism experiments, we confirm the widely applied “folding upon binding” mechanism of histone structures. A histone dimer appears to form the longestα2 helices followed by other shorter helices and inter-molecular tertiary structures. We report an alternative conformation, namely, the inverted non-native dimer, which has a minimum free energy state. Protein sequence analysis indicates that the inverted conformation can be attributed to a hidden head-tail sequence symmetry underlying all histone proteins. This finding strongly support previously proposed histone evolution hypotheses. Finally, we separately used the MD-based AWSEM and AI-based AlphaFold-Multimer model to predict eukaryotic histone homodimer structures and performed extensive allatom MD simulations to examine their structural stabilities. Our results suggest that eukaryotic histones can also form stable homodimers, whereas their disordered tails— the structurally asymmetrical region—may tip the balance towards the formation of heterotypic dimers.
Viral DNA SIP: the isotopic composition of virions is correlated with that of the substrate used for host growth
Authors: Ngo Vuong Quoc Hoang , Sotomski Maximilien , Guenne Angeline , Mariadassou Mahendra , Krupovic Mart , Enault François , Bize Ariane
Published: October 2022

DNA Stable Isotope Probing is emerging as a powerful tool to study host-virus interactions. Indeed, since all viruses depend on a host for virion production, a link between the isotopic compositions of hosts and the virions they produce is expected. However, stable isotope probing applied to viral DNA has never been evaluated on simple biological models. Here, this method was tested on the bacteriophage T4 and its hostEscherichia coli. To validate that E. coli cells cultivated using a substrate enriched in13C isotope were resulting on the production of 13C-labeled T4 DNA.

T4 DNA buoyant density in CsCl gradient was overall higher than the values predicted by a previously established empirical model, highlighting the need to adapt this type of models when analysing modified viral DNA. Moreover, our results show a strong correlation between the proportion of13C6-D-glucose in the substrate used for host growth and the buoyant density of T4 DNA, validating the use of DNA SIP in viral ecology, to identify viruses infecting hosts with a specific metabolism.
CogGame: Gamified Cognitive Assessments in Young Adults with Suicidal Thoughts
Authors: Shin Christina Chae Yon , LaMonica Haley M , Mowszowski Loren , Cheng Vanessa Wan Sze , Kampel Laura , Han Jin
Published: October 2022

Introduction

The susceptibility to suicidal behaviour has been linked to cognitive functioning deficits. Gamified assessments have emerged as a practical and engaging approach to assess these deficits, though their acceptability amongst young adults with suicidal thoughts is currently understudied.

Methods

Thirteen young Australian adults aged 18 to 25 years who experienced suicidal thoughts in the past year were recruited to evaluate the smartphone based CogGame app. Inductive thematic analysis was utilised to identify the themes obtained from the interviews. The relationships between cognitive functioning deficits and the severity of suicidal thoughts were explored by correlational analyses.

Results

All participants found the GogGame app easy to learn to use and navigate. Positive experiences and high user satisfaction were reported with the use of CogGame app. Major areas for improvement include having clearer instructions and app information, adjusting the difficulty of the exercises, and addressing a few technical issues such as decreasing loading time. Higher levels of suicidal thoughts were found to be significantly associated with poorer visual learning performance on the CogGame app (p= .01).

Conclusion

Positive participant experiences with CogGame revealed the promising potential of gamified assessments to measure cognitive functioning in young adults with suicidal thoughts.
Evaluation of statistical methods used to meta-analyse results from interrupted time series studies: a simulation study
Authors: Korevaar Elizabeth , Turner Simon L , Forbes Andrew B , Karahalios Amalia , Taljaard Monica , McKenzie Joanne E
Published: October 2022

Background

Interrupted time series (ITS) are often meta-analysed to inform public health and policy decisions but examination of the statistical methods for ITS analysis and meta-analysis in this context is limited.

Methods

We simulated meta-analyses of ITS studies with continuous outcome data, analysed the studies using segmented linear regression with two estimation methods [ordinary least squares (OLS) and restricted maximum likelihood (REML)], and meta-analysed the immediate level- and slope-change effect estimates using fixed-effect and (multiple) random-effects meta-analysis methods. Simulation design parameters included varying series length; magnitude of lag-1 autocorrelation; magnitude of level- and slope-changes; number of included studies; and, effect size heterogeneity.

Results

All meta-analysis methods yielded unbiased estimates of the interruption effects. All random effects meta-analysis methods yielded coverage close to the nominal level, irrespective of the ITS analysis method used and other design parameters. However, heterogeneity was frequently overestimated in scenarios where the ITS study standard errors were underestimated, which occurred for short series or when the ITS analysis method did not appropriately account for autocorrelation.

Conclusions

The performance of meta-analysis methods depends on the design and analysis of the included ITS studies. Although all random effects methods performed well in terms of coverage, irrespective of the ITS analysis method, we recommend the use of effect estimates calculated from ITS methods that adjust for autocorrelation when possible. Doing so will likely to lead to more accurate estimates of the heterogeneity variance.
Cortico-Cerebellar Neurodynamics during Social Interaction in Autism Spectrum Disorder
Authors: Gaudfernau Fleur , Lefebvre Aline , Engemann Denis-Alexander , Pedoux Amandine , Bánki Anna , Baillin Florence , Landman Benjamin , Amsellem Frederique , Bourgeron Thomas , Delorme Richard , Dumas Guillaume
Published: October 2022

Background

Exploring neural network dynamics during social interaction could help to identify biomarkers of Autism Spectrum Disorders (ASD). Recently, the cerebellum, a brain structure that plays a key role in social cognition, has attracted growing interest. Here, we investigated the electrophysiological activity of the cortico-cerebrum network during real-time social interaction in ASD. We focused our analysis on theta oscillations (3-8 Hz), which have been associated with large-scale coordination of distant brain areas and might contribute to interoception, motor control, and social event anticipation, all skills known to be altered in ASD.

Methods

We combined the Human Dynamic Clamp, a paradigm for studying realistic social interactions using a virtual avatar, with high-density electroencephalography (HD-EEG). Using source reconstruction, we investigated power in the cortex and the cerebellum, along with coherence between the cerebellum and three cortical areas, and compared our findings in a sample of participants with ASD and with typical development (TD) (n = 140). We developed an open-source pipeline to analyse neural dynamics at the source level from HD-EEG data.

Results

Individuals with ASD showed a significant increase in theta band power during social interaction compared to resting state, unlike individuals with TD. In particular, we observed a higher theta power over the cerebellum and the frontal and temporal cortices in the ASD group compared to the TD group, alongside bilateral connectivity alterations between the cerebellum and the sensorimotor and parietal cortices.

Conclusions

This study uncovered ASD-specific alterations in the theta dynamics, especially in a network between the cerebellum and social-associated cortical networks.
N6-Adenosine Methylation of SARS-CoV-2 5’-UTR Regulates Translation
Authors: Aly Ammar , Scott Gary , Calderon Mario , Haghighi A. Pejmun
Published: October 2022

The coronavirus disease 2019 (COVID19) continues to spread despite global vaccination efforts (1). This, alongside the rapid emergence of vaccine resistant variants, creates a need for orthogonal therapeutic strategies targeting more conserved facets of severe acute respiratory syndrome coronavirus (SARS-CoV-2) (2–4). One conserved feature of all coronaviruses is their ability to undergo discontinuous transcription wherein individual open reading frames fuse with the 5’-UTR leader sequence during negative-strand RNA synthesis (5). As such all viral protein coding genes use the same 5’-UTR for translation (6). Usingin vitroreporter assays, we demonstrate that the SARS-CoV-2 5’-UTR efficiently initiates protein translation despite its predicted structural complexity. Through a combination of bioinformatic and biochemical assays, we demonstrate that a single METTL3-dependent m6A methylation event in SARS-CoV-2 5’-UTR regulates the rate of translation initiation. We show that m6A likely exerts this effect by destabilizing secondary structure in the 5’-UTR, thereby facilitating access to the ribosomal pre-initiation complex. This discovery opens new avenues for novel therapeutic strategies aimed at controlling the ability of SARS-CoV-2 to replicate in host cells.
On the Ca2+elevation in vascular endothelial cells due to inositol trisphosphate-sensitive store receptor activation: a data-driven modeling approach
Authors: Coccarelli Alberto , Pant Sanjay
Published: October 2022

Agonist-induced Ca2+signalling is essential for the regulation of many vital functions in endothelial cells (ECs). A broad range of stimuli elevate the cytosolic Ca2+concentration by promoting a pathway mediated by inositol 1,4,5 trisphosphate (IP3) which causes Ca2+release from intracellular stores. Despite its importance, there are very few studies focusing on the quantification of such dynamics. Here, by using data from isolated ECs, we constructed and tested a minimalistic model that can be used for capturing the main features (averaged over a cell population) of the Ca2+response to different IP3stimulation levels. A suitable description of Ca2+-regulatory function of inositol 1,4,5 trisphosphate receptors (IP3Rs) is identified by comparing the different model variants against experimental mean population data. The same approach is used to numerically assess the relevance of cytosolic Ca2+buffering, as well as Ca2+store IP3-sensitivity in the overall cell dynamics. The variability in the dynamics’ features observed across the population can be explained (at least in part) through variation of certain model parameters (such as buffering capacity or Ca2+store sensitivity to IP3). The results, in terms of experimental fitting and validation, support the proposed minimalistic model as a reference framework for the quantification of the EC Ca2+dynamics induced by IP3Rs activation.
SituSeq: An offline protocol for rapid and remote Nanopore amplicon sequence analysis
Authors: Zorz Jackie , Li Carmen , Chakraborty Anirban , Gittins Daniel , Surcon Taylor , Morrison Natasha , Bennett Robbie , MacDonald Adam , Hubert Casey R.J.
Published: October 2022

Microbiome analysis through 16S rRNA gene sequencing is a crucial tool for understanding the microbial ecology of any habitat or ecosystem. However, workflows require large equipment, stable internet, and extensive computing power such that most of the work is performed far away from sample collection in both space and time. Performing amplicon sequencing and analysis at sample collection would have positive implications in many instances including remote fieldwork and point-of-care medical diagnoses. Here we presentSituSeq, an offline and portable workflow for the sequencing and analysis of 16S rRNA gene amplicons using the Nanopore MinION and a standard laptop computer.SituSeqwas validated using the same environmental DNA to sequence Nanopore 16S rRNA gene amplicons, Illumina 16S rRNA gene amplicons, and Illumina metagenomes. Comparisons revealed consistent community composition, ecological trends, and sequence identity across platforms. Correlation between the abundance of phyla in Illumina and Nanopore data sets was high (Pearson’s r = 0.9), and over 70% of Illumina 16S rRNA gene sequences matched a Nanopore sequence with greater than 97% sequence identity. On board a research vessel on the open ocean,SituSeqwas used to analyze amplicon sequences from deep sea sediments less than two hours after sequencing, and eight hours after sample collection. The rapidly available results informed decisions about subsequent sampling in near real-time while the offshore expedition was still underway.SituSeqis a portable and robust workflow that helps to bring the power of microbial genomics and diagnostics to many more researchers and situations.