bluuebunny/crossref_metadata_2025 huggingface dataset:
Transfer of weight information depends differently on used hand and handedness for perception and action
Authors: van Polanen Vonne
Published: May 2022

When lifting an object sequentially with the two hands, information about object weight can be transferred from one hand to the other. This information can be used to predictively scale fingertip forces and to form a perceptual estimation about the object’s weight. This study investigated how weight information can be transferred between the two hands and how this depends on the used hand and handedness of the participant. Right- and left-handed participants lifted light and heavy objects with the right or left hand in a pseudorandomized order and estimated the object’s weight. Results showed that predictive force scaling depended on the previously lifted object, with higher forces rates if a previous object was heavy. This known effect of sensorimotor memory was mostly independent of the used hand and handedness, indicating that weight information could be transferred for fingertip force scaling. Furthermore, a perceptual bias depending on the previous lifted object was found, with lower weight estimations when the previous object was heavy compared to light. In contrast to the results on force scaling, a transfer of this perceptual bias was only found in left-handed participants. In addition, right-handers only showed a bias when they used their dominant hand. These findings indicate that the transfer of weight information depends differently on the used hand and handedness for perceptual estimations and predictive force scaling.
SeATAC: a tool for exploring the chromatin landscape and the role of pioneer factors
Authors: Dsouza Nikita , Gong Wuming , Garry Daniel J.
Published: May 2022

The position of the nucleosome and chromatin packaging in eukaryotic genomes govern gene regulation and cellular functions. Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) is an efficient and precise method for revealing chromatin accessibility across the genome. However, there is no method that is specifically designed for detecting differential chromatin accessibility using ATAC-seq datasets. In this study, we developed a bioinformatics tool called SeATAC, that used a conditional variational autoencoder (CVAE) model to learn the latent representation of ATAC-seq V-plots, and to estimate the statistically differential chromatin accessibility. We demonstrated that SeATAC outperformed MACS2 and NucleoATAC on four separate tasks including: (1) detection of differential V-plots; (2) definition of nucleosome positions; (3) detection of nucleosome changes and (4) designation of transcriptional factor binding sites (TFBS) with differential chromatin accessibility. By applying SeATAC to several pioneer factor induced differentiation or reprogramming ATAC-seq datasets, we found that induction of these pioneer factors not only relaxed the closed chromatin but also decreased the chromatin accessibility of 20% - 30% of their target sites. These two groups of TF binding sites were characterized by different genomic distribution and histone marks. Here, we present SeATAC as a novel tool to accurately reveal the genomic regions with differential chromatin accessibility from ATAC-seq data.
Whole genome sequencing of three mesorhizobia isolated from northern Canada to identify genomic adaptations promoting nodulation in cold climates
Authors: Duan Yi Fan , Grogan Paul , Walker Virginia K , diCenzo George C
Published: May 2022

The N2-fixing symbiosis between rhizobia and legumes is negatively impacted by numerous stresses, including low temperatures. To identify genomic features and biochemical pathways of rhizobia that could foster improved symbiotic function under low temperatures, we isolated and characterized three Mesorhizobium strains from legume nodules collected at two distant northern Canadian sites. Whereas the classical determinants of nodulation and nitrogen fixation are located on the chromosome of most mesorhizobia, whole genome sequencing revealed that these genes are on a large symbiotic megaplasmid in all three of the newly isolated strains. A pangenome-wide association study identified 25 genes putatively associated with mesorhizobia isolated from arctic or subarctic environments, with the genomic location of many of these genes implying a relationship with legume symbiosis. Phylogenetic and sequence analyses of the common nodulation genes revealed alleles that are highly conserved amongst mesorhizobia isolated from northern climates but uncommon in mesorhizobia isolated from similar plant hosts in other climatic regions, suggesting potential functional adaptive differences and the horizontal transfer of these alleles between northern rhizobia. We speculate that nod sequence divergence was driven by climatic factors, and that the encoded proteins may be particularly stable and/or active at low temperatures.
Pericytes and Astrocytes Instruct Glioblastoma Invasion, Proliferation, and Therapeutic Response within an Engineered Brain Perivascular Niche Model
Authors: Ngo Mai T. , Sarkaria Jann N. , Harley Brendan A.C.
Published: May 2022

Glioblastoma (GBM) tumor cells are found in the perivascular niche microenvironment and are believed to associate closely with the brain microvasculature. However, it is largely unknown how the resident cells of the perivascular niche, such as endothelial cells, pericytes, and astrocytes, influence GBM tumor cell behavior and disease progression. We describe a three-dimensional in vitro model of the brain perivascular niche developed by encapsulating brain-derived endothelial cells, pericytes, and astrocytes in a gelatin hydrogel. We show that pericytes and astrocytes explicitly contribute to vascular architecture and maturation. We use co-cultures of patient-derived GBM tumor cells with brain microvascular cells to identify a role for pericytes and astrocytes in establishing a perivascular niche environment that modulates GBM cell invasion, proliferation, and therapeutic response. Engineered models provides unique insight regarding the spatial patterning of GBM cell phenotypes in response to a multicellular model of the perivascular niche. Critically, we show that engineered perivascular models provide an important resource to evaluate mechanisms by which inter- cellular interactions modulate GBM tumor cell behavior, drug response, and provide a framework to consider patient-specific disease phenotypes.
A role for the circadian transcription factor NPAS2 in the progressive loss of non-rapid eye movement sleep and increased arousal during fentanyl withdrawal in male mice
Authors: Gamble Mackenzie C. , Chuan Byron , Gallego-Martin Teresa , Shelton Micah A. , Puig Stephanie , O’Donnell Christopher P. , Logan Ryan W.
Published: May 2022

Abstract

Rationale

Synthetic opioids like fentanyl are contributing to the rise in rates of opioid use disorder and drug overdose deaths. Sleep dysfunction and circadian rhythm disruption may worsen during opioid withdrawal and persist during abstinence. Severe and persistent sleep and circadian alterations are putative factors in opioid craving and relapse. However, very little is known about the impact of fentanyl on sleep architecture and sleep-wake cycles, particularly opioid withdrawal. Further, circadian rhythms regulate sleep-wake cycles, and the circadian transcription factor, neuronal PAS domain 2 (NPAS2) is involved in the modulation of sleep architecture and drug reward. Here, we investigate the role of NPAS2 in fentanyl-induced sleep alterations.

Objectives

To determine the effect of fentanyl administration and withdrawal on sleep architecture, and the role of NPAS2 as a factor in fentanyl-induced sleep changes.

Methods

Electroencephalography (EEG) and electromyography (EMG) was used to measure non-rapid eye movement sleep (NREMS) and rapid eye movement sleep (REMS) at baseline and following acute and chronic fentanyl administration in wild-type and NPAS2-deficient male mice.

Results

Acute and chronic administration of fentanyl led to increased wake and arousal in both wild-type and NPAS2-deficient mice, an effect that was more pronounced in NPAS2-deficient mice. Chronic fentanyl administration led to decreased NREMS, which persisted during withdrawal, progressively decreasing from day 1 to 4 of withdrawal. The impact of fentanyl on NREMS and arousal was more pronounced in NPAS2-deficient mice.

Conclusions

Chronic fentanyl disrupts NREMS, leading to a progressive loss of NREMS during subsequent days of withdrawal. Loss of NPAS2 exacerbates the impact of fentanyl on sleep and wake, revealing a potential role for the circadian transcription factor in opioid-induced sleep changes.
RT-RPA-Cas12a-based discrimination of SARS-CoV-2 variants of concern
Authors: Tang Guiyue , Zhang Zilong , Tan Wei , Long Fei , Sun Jingxian , Li Yingying , Zou Siwei , Yang Yujiao , Cai Kezhu , Li Shenwei , Wang Zhiyi , Liu Jiakun , Mao Guobing , Ma Yingxin , Zhao Guo-Ping , Tian Zhen-Gan , Zhao Wei
Published: May 2022

Timely and accurate detection of SARS-CoV-2 variants of concern (VOCs) is urgently needed for pandemic surveillance and control. However, current methods are limited by the low sensitivity, long turn-around time or high cost. Here, we report a nucleic acid testing-based method aiming to detect and discriminate SARS-CoV-2 VOCs by combining RT-RPA and CRISPR-Cas12a detecting assays (RRCd). With a detection limit of 10 copies RNA/reaction, RRCd was validated in 204 clinical samples, showing 99% positive predictive agreement and 100% negative predictive agreement, respectively. Critically, using specific crRNAs, representatives of single nucleotide polymorphisms and small deletions in SARS-CoV-2 VOCs including N501Y, T478K and ΔH69-V70 were discriminated by RRCd, demonstrating 100% accuracy in clinical samples with Ct < 33. The method completes within 65 min and could offer visible results without using any electrical devices, which may facilitate point-of-care testing of SARS-CoV-2 and its variants.
Application of aptamer technology in enterobacteria and non-fermenters: literature review
Authors: Bes Taniela Marli , Cortês Farrel Marina , Santos Carlos , Sabino Ester Cerdeira , Costa Silvia Figueiredo
Published: May 2022

Antimicrobial resistance has grown exponentially in the last decade and become a global health threat. The antibiotic resistance crisis has guided the scientific community to explore non-conventional interventions to target resistant bacteria. Development of new technologies, such as aptamers-based treatment and diagnosis, has shown to be promising with remarkable advantages over the past five years. This narrative review aims on what is already known regarding application of aptamer technology in enterobacteria and non-fermenters, and the prospects for future achievements. A systematic search of the English literature was performed on the 7th of December 2021 to identify papers on aptamer discovery, with a focus on gram negative isolates, published from January 01, 1993, to December 07, 2021, under the topics: (aptamer OR aptamers OR SELEX) AND (bacteria OR sepsis OR non-fermenter OR Enterobacteriaceae OR infection)). The reference lists of included articles were also searched, in addition to hand-searching of various relevant high-impact journals. Out of 2,474 articles, 30 experimental studies were recruited for review, and are chronologically described. Although the number of publications regarding development of aptamers to target these pathogenic agents has increased over the years, the recent publications are mostly around diagnostic devices manufactured using previously described aptamers. There have been less than one-third of the studies describing new and specific aptamers. From the 30 selected papers, 18 are regarding non-fermenters, seven approaching multi-species of bacteria and only five regarding a single enterobacteria. Even for the newly described aptamers, most of the published papers pertain to diagnostic aptamers and only seven focus on aptamers for therapeutics. The number of aptamers with strong and specific binding capacity are still limited. Improving the current SELEX and developing more APT remains the major hurdle for aptamer related studies.
Clinical Validation and Diagnostic Utility of Optical Genome Mapping in Prenatal Diagnostic Testing
Authors: Sahajpal Nikhil Shri , Mondal Ashis K , Fee Timothy , Hilton Benjamin , Layman Lawrence , Hastie Alex R , Chaubey Alka , DuPont Barbara R. , Kolhe Ravindra
Published: May 2022

The standard-of-care (SOC) diagnostic prenatal testing includes a combination of cytogenetic methods such as karyotyping, fluorescence in situ hybridization (FISH), and chromosomal microarray (CMA) using either direct or cultured amniocytes or chorionic villi sampling (CVS). However, each technology has its limitations: karyotyping has a low resolution (>5Mb), FISH is targeted, and CMA does not detect balanced structural variants (SVs) or decipher complex rearrangements in the genome. These limitations necessitate the use of multiple tests, either simultaneously or sequentially to reach a genetic diagnosis. This long-standing prenatal testing workflow demonstrates the need for an alternative technology that can provide high-resolution results in a cost and time-effective manner. Optical genome mapping (OGM) is an emerging technology that has demonstrated its ability to detect all classes of SVs, including copy number variations (CNVs) and balanced abnormalities in a single assay, but has not been evaluated in the prenatal setting. This retrospective validation study analyzed 114 samples (including replicates), representing 94 unique and well-characterized samples that were received in our laboratory for traditional cytogenetic analysis with karyotyping, FISH, and/or CMA. Samples comprised 84 cultured amniocytes, and 10 phenotypically normal and cytogenetically negative controls. Six samples were run in triplicate to evaluate intra-run, inter-run, and inter-instrument reproducibility. Clinically relevant SVs and CNVs were reported using the Bionano Access software with standardized and built-in filtration criteria and phenotype-specific analysis. OGM was 100% concordant in identifying the 101 aberrations that included 29 interstitial/terminal deletions, 28 duplications, 26 aneuploidies, 6 absence of heterozygosity (AOH), 3 triploid genomes, 4 Isochromosomes, 1 translocation, and revealed the identity of 3 marker chromosomes, and 1 chromosome with additional material not determined by karyotyping. Additionally, OGM detected 64 additional clinically reportable SVs in 43 samples. OGM demonstrated high technical and analytical robustness and a limit of detection of 5% allele fraction for interstitial deletions and duplications, and 10% allele fraction for translocation and aneuploidy. This study demonstrates that OGM has the potential to identify unique genomic abnormalities such as CNVs, AOHs, and several classes of SVs including complex structural rearrangements. OGM has a standardized laboratory workflow and reporting solution that can be adopted in routine clinical laboratories and demonstrates the potential to replace the current SOC methods for prenatal diagnostic testing. We recommend its use as a first-tier genetic diagnostic test in a prenatal setting.
JBrowse Jupyter: A Python interface to JBrowse 2
Authors: Martinez Teresa De Jesus , Hershberg Elliot A. , Guo Emma , Stevens Garrett J , Diesh Colin , Xie Peter , Bridge Caroline , Cain Scott , Haw Robin , Buels Robert M. , Stein Lincoln D. , Holmes Ian H.
Published: May 2022

Abstract

Motivation

JBrowse Jupyter is a package that aims to close the gap between Python programming and genomic visualization. Web-based genome browsers are routinely used for publishing and inspecting genome annotations. Historically they have been deployed at the end of bioinformatics pipelines, typically decoupled from the analysis itself. However, emerging technologies such as Jupyter notebooks enable a more rapid iterative cycle of development, analysis and visualization.

Results

We have developed a package that provides a python interface to JBrowse 2’s suite of embeddable components, including the primary Linear Genome View. The package enables users to quickly set up, launch and customize JBrowse views from Jupyter notebooks. In addition, users can share their data via Google’s Colab notebooks, providing reproducible interactive views.

Availability

JBrowse Jupyter is released under the Apache License and is available for download on PyPI. Source code and demos are available on GitHub at https://github.com/GMOD/jbrowse-jupyter.

Contact

ihh@berkeley.edu
Analysis of the All of Us Research Program Researcher Workbench Workspaces
Authors: Kerawala Rhea P. , King Paula F. , Mayo Kelsey Ross , Vogel Julia Moore ,   the All of Us Research Program
Published: May 2022

The All of Us Research Program, through the All of Us Research Hub platform’s Researcher Workbench, provides researchers and citizen scientists with access to a broad dataset of surveys, electronic health records, physical measurements, genetic data, and Fitbit device wearable data. All of Us has a goal of recruiting a minimum of one million participants and aims to capture the diversity of individuals in the United States. The All of Us Research Hub platform includes a Research Projects Directory on its website, displaying researcher-provided descriptions of each active workspace on the Researcher Workbench. Inspired by the initial work completed by All of Us investigators in 2019, these workspace descriptions were analyzed with a new methodology. Genetic, methods and validation studies, and educational research purposes were associated with disease-focused research, as compared to non-disease focused research. Of all the population categories of interest, only race and ethnicity were associated with disease-focused research. Further categorization of the disease-focused workspaces revealed the top five disease categories: cardiovascular disease, brain and mental health disorders, cancer and benign tumors, diabetes, and immunology-related conditions. Athena OHDSI catalog terms were sorted and helped classify the workspaces by each disease category. Subcategory distribution for the cancer, genetic, and cardiovascular disease-related conditions was examined as well. This framework has the potential to be used for continued longitudinal analysis of the workspaces and continued learnings regarding the importance of disease-focused research in public health. Additionally, as workspace descriptions are created at project initiation, this can provide us with a leading-edge indication of researcher interest in the All of Us Research Program data.
“Puberty age gap”: New method of assessing pubertal timing and its association with mental health problems
Authors: Dehestani Niousha , Vijayakumar Nandita , Ball Gareth , Sina Mansour L. , Whittle Sarah , Silk Timothy J.
Published: May 2022

Puberty is linked to mental health problems during adolescence, and in particular, the timing of puberty is thought to be an important risk factor. This study developed a new measure of pubertal timing using multiple pubertal features and nonlinear associations with age and investigated its association with mental health problems. Using the Adolescent Brain Cognitive Development (ABCD) cohort, we implemented three models of pubertal timing by predicting chronological age from i) observed physical development, ii) hormones (testosterone and dehydroepiandrosterone [DHEA]), and iii) a combination of the two, using a supervised machine learning method (n ∼9,900). Accuracy of the new models, and their associations with mental health problems were evaluated. The new pubertal timing measure performed better in capturing age variance compared to a commonly used method, and the physical measure accounted for more variance in mental health, such that earlier pubertal timing was associated with higher symptoms. This study demonstrates the utility for a new model of pubertal timing and suggests that physical maturation may play a predominant role in predicting mental health problems in early adolescence.
AI-based search for convergently expanding, advantageous mutations in SARS-CoV-2 by focusing on oligonucleotide frequencies
Authors: Ikemura Toshimichi , Iwasaki Yuki , Wada Kennosuke , Wada Yoshiko , Abe Takashi
Published: May 2022

Among mutations that occur in SARS-CoV-2, efficient identification of mutations advantageous for viral replication and transmission is important to characterize and defeat this rampant virus. Mutations rapidly expanding frequency in a viral population are candidates for advantageous mutations, but neutral mutations hitchhiking with advantageous mutations are also likely to be included. To distinguish these, we focus on mutations that appear to occur independently in different lineages and expand in frequency in a convergent evolutionary manner. Batch-learning SOM (BLSOM) can separate SARS-CoV-2 genome sequences according by lineage from only providing the oligonucleotide composition. Focusing on remarkably expanding 20-mers, each of which is only represented by one copy in the viral genome, allows us to correlate the expanding 20-mers to mutations. Using visualization functions in BLSOM, we can efficiently identify mutations that have expanded remarkably both in the Omicron lineage, which is phylogenetically distinct from other lineages, and in other lineages. Most of these mutations involved changes in amino acids, but there were a few that did not, such as an intergenic mutation.
Identifying the modification factors of exercise therapy on biomechanical load in patients with knee osteoarthritis: A systematic review and meta-analysis
Authors: Yokoyama Moeka , Iijima Hirotaka , Kubota Keisuke , Kanemura Naohiko
Published: May 2022

Objective

As the progression of knee osteoarthritis (OA) is associated with large biomechanical loads, an optimally designed intervention is needed to prevent disease progression and symptoms. We aimed to investigate the effect of exercise therapy—the gold standard intervention—on biomechanical loads in patients with knee OA and identify its modification factors.

Design

Systematic review and meta-analysis

Data sources

PubMed, PEDro, and CINAHL; from study inception to May 2021

Eligibility criteria

Studies evaluating the first peak knee adduction moment (KAM), peak knee flexion moment (KFM), maximal knee joint compression force (KCF), or co-contraction during walking before and after exercise therapy in patients with knee OA

Risk of Bias

PEDro scale and NIH scale.

Results

Among 11 RCTs and nine non-RCTs, 1100 patients with knee OA were included. First peak KAM (SMD 0.11; 95% CI: -0.03–0.24), peak KFM (SMD 0.13; 95% CI: -0.03–0.29), and maximal KCF (SMD 0.09; 95% CI -0.05–0.22) tended to increase. An increased first peak KAM was significantly associated with a larger improvement in knee muscle strength and WOMAC pain. The quality of evidence regarding the biomechanical loads was low-to-moderate according to the GRADE approach.

Conclusions

Exercise therapy tends to increase biomechanical loads. The improvement in pain and knee muscle strength may mediate the increase in first peak KAM, suggesting difficulty in balancing symptom relief and biomechanical load reduction. Therefore, exercise therapy may satisfy both aspects simultaneously when combined with biomechanical interventions, such as a valgus knee brace or insoles.

Funding

Grant-in-Aid for JSPS Research Fellows, 19J23020.

Registration

PROSPERO (CRD42021230966)
Questioning the axiom: Is hyperflexed scaphoid a common occurrence in South Indian population? - An observational study
Authors: Ashik Mohamed Nazir , Sethu Maithreyi , Rajappa Srinivasan
Published: May 2022

Background

Scapholunate angle SLA greater than 80° is one of the indicators of surgery for carpal instability. The normal SLA is between 30-60°. This is based on studies which were conducted several decades ago in the western part of the world. The SLA of Indian population has never been measured before. The knowledge of normal SLA in each population becomes imperative because it lays down the guidelines for surgical and non-surgical management of wrist fractures and instability in that population. In this study, we aim to measure the SLAs in asymptomatic volunteers of South Indian origin and compare the results with existing data.

Methods

An observational study was done in a tertiary care hospital in South India. Lateral radiographs of the wrist of asymptomatic volunteers were taken. The SLA was measured using a software in the PACS system. The relation of SLA to gender, age, left and right sides and handedness was compared. These were compared to pre-existing global data available on SLAs.

Results

The SLA of the 202 radiographs with 47 males and 54 females were studied.

The average SLA was 51.33° and the range was between 29° and 74°.

The average SLA of males was 51.8° and females 50.8°. There was no significant difference between the two.

Similarly, there was no significant difference between the SLA of right and left sides in right handed and left handed subgroups.

However, there was an increasing trend in SLA among females with age. But no similar pattern was seen among males.

Interestingly, 39 out of the 202 radiographs (19.3%) had a SLA above 60°.

Conclusion

This study suggests the normal SLA in South Indians may be higher than the previously established reference values and serves as a pilot project and a reference for further studies on SLA.
Genetic aetiologies for childhood speech disorder: novel pathways co-expressed during brain development
Authors: Kaspi Antony , Hildebrand Michael S. , Jackson Victoria E. , Braden Ruth , van Reyk Olivia , Howell Tegan , Debono Simone , Lauretta Mariana , Morison Lottie , Coleman Matthew , Webster Richard , Coman David , Goel Himanshu , Wallis Mathew , Dabscheck Gabriel , Downie Lilian , Baker Emma K. , Parry-Fielder Bronwyn , Ballard Kirrie , Harrold Eva , Ziegenfusz Shaun , Bennett Mark F. , Robertson Erandee , Wang Longfei , Boys Amber , Fisher Simon E. , Amor David J. , Scheffer Ingrid E. , Bahlo Melanie , Morgan Angela T.
Published: May 2022

Childhood apraxia of speech (CAS), the prototypic severe childhood speech disorder, is characterized by motor programming and planning deficits. Genetic factors make substantive contributions to CAS aetiology, with a monogenic pathogenic variant identified in a third of cases, implicating around 20 single genes to date. Here we ascertained 70 unrelated probands with a clinical diagnosis of CAS and performed trio genome sequencing. Our bioinformatic analysis examined single nucleotide, indel, copy number, structural and short tandem repeat variants. We prioritised appropriate variants arising de novo or inherited that were expected to be damaging based on in silico predictions. We identified high confidence variants in 18/70 (26%) probands, almost doubling the current number of candidate genes for CAS. Three of the 18 variants affected SETBP1, SETD1A and DDX3X, thus confirming their roles in CAS, while the remaining 15 occurred in genes not previously associated with this disorder. Fifteen variants arose de novo and three were inherited. We provide further novel insights into the biology of child speech disorder, highlighting the roles of chromatin organization and gene regulation in CAS, and confirm that genes involved in CAS are co-expressed during brain development. Our findings confirm a diagnostic yield comparable to, or even higher, than other neurodevelopmental disorders with substantial de novo variant burden. Data also support the increasingly recognised overlaps between genes conferring risk for a range of neurodevelopmental disorders. Understanding the aetiological basis of CAS is critical to end the diagnostic odyssey and ensure affected individuals are poised for precision medicine trials.
NEAT (NicotinE As Treatment) Trial: Protocol of a randomised controlled trial of vaporised nicotine products compared with nicotine replacement therapy following discharge from residential withdrawal services
Authors: Bonevski B , Rich JL , Skelton E , Garfield J , Baker AL , Segan C , Gartner C , Walker N , Borland R , Daglish M , Dunlop A , Oldmeadow C , Bauld L , Bullen C , Ezard N , McCrohan R , Jacka D , White S , Lubman DI , Manning V
Published: May 2022

Background

Tobacco smoking rates in alcohol and other drug (AOD) treatment settings is much higher than in the general Australian population. As a result, people seeking treatment for AOD use experience a greater tobacco-related burden of illness. Attempts to reduce smoking rates in AOD treatment consumers have failed to identify smoking cessation strategies with long term effectiveness. The primary aim of this study is to examine the effectiveness of nicotine vaporised products (NVPs) or nicotine replacement therapy (NRT)on self-reported 6 months continuous abstinence at the 9-month follow-up (6 months following end-of 12 weeks of nicotine treatment) for people leaving smoke-free residential withdrawal treatment. Both groups will also receive Quitline telephone counselling. Secondary outcomes and process measures will also be collected.

Methods

A two-arm, single-blinded, parallel-group randomised trial with a 6-month post-intervention follow-up (9 months following baseline) will be conducted. The setting is five residential and inpatient government-funded AOD withdrawal units across three cities in three states of Australia (New South Wales, Queensland, Victoria). Participants will be service users aged 18 years or over who smoked at least 10 cigarettes per day, interested in quitting in the next 30 days and have capacity to give informed consent. Research assistants will recruit participants during intake, who then complete a baseline survey, will be randomised to a condition, and receive their first Quitline call during AOD treatment. At discharge, all participants receive a discharge pack containing either NVPs or NRT, depending on condition allocation.

Discussion

This is the first study we know of that will be testing intervening with a tobacco smoking cessation approach during the transition phase from AOD treatment to community. From a public health perspective, this approach has the potential to have tremendous reach into a priority population for smoking cessation.

Trial registration

Australian and New Zealand Clinical Trials Registry (ACTRN12619001787178)
CITE-Viz: Replicating the Interactive Flow Cytometry Workflow in CITE-Seq
Authors: Kong Garth L. , Nguyen Thai T. , Rosales Wesley K. , Panikar Anjali D. , Cheney John H. W. , Curtiss Brittany M. , Carratt Sarah A. , Braun Theodore P. , Maxson Julia E.
Published: May 2022

The rapid advancement of new genomic sequencing technology has enabled the development of multi-omic single-cell sequencing assays. These assays profile multiple modalities in the same cell and can often yield new insights not revealed with a single modality. For example, CITE-Seq (Cellular Indexing of Transcriptomes and Epitopes by Sequencing) simultaneously profiles the single-cell RNA transcriptome and the surface protein expression. The extra dimension of surface protein markers can be used to further identify cell clusters – an essential step for downstream analyses and interpretation. Additionally, multi-dimensional datasets like CITE-Seq require nuanced visualization methods to accurately assess the data. To facilitate cell cluster classification and visualization in CITE-Seq, we developed CITE-Viz. CITE-Viz is a single-cell visualization platform with a custom module that replicates the interactive flow-cytometry gating workflow. With CITE-Viz, users can investigate CITE-Seq specific quality control (QC) metrics, view multi-omic co-expression feature plots, and classify cell clusters by iteratively gating on the abundance of cell surface markers. CITE-Viz was developed to make multi-modal single-cell analysis accessible to a wide variety of biologists, with the aim to discover new insights into their data and to facilitate novel hypothesis generation.

Availability and Implementation

CITE-Viz installation and usage instructions can be found in the GitHub repository https://github.com/maxsonBraunLab/CITE-Viz

Contact

maxsonj@ohsu.edu

Supplementary Information

Down-sampled peripheral blood mononuclear dataset (Hao et al. 2021): https://bit.ly/3vxbhfW
Shelf-Life Specific Moisture Variation in Chitosan of Genus Fenneropenaeus Distributed Along Arabian Sea, India
Authors: R S Sreelekshmi , Alex Lincy , Jose Jean J
Published: May 2022

Chitosan is a characteristic polysaccharide, naturally extracted from the crustacean’s shells. The stability and shelf-life of chitosan are affected by a few parameters, basically the moisture content. In this study, three species of shrimps such as Indian white shrimp (Fenneropenaeus indicus), banana shrimp (F. merguensis), and tiger prawn (F. monodon) were utilized for the extraction of chitosan. The extraction strategy included the method of demineralization, deproteinization, and deacetylation. Later the yield and moisture of chitosan were examined from three diverse species. The yield of shell waste ranged between 46% to 50% (on moist weight premise) and the chitosan was between 18.0 to 20.2%. Moisture content always plays a critical part in chitosan shelf life and stability and was between 5.2% to 6.8 %.
Adaptive Immune Landscape of T-Cell Mediated Rejection of Human Kidney Allografts
Authors: Mueller Franco B. , Yang Hua , Li Carol , Snopkowski Catherine , Dadhania Darshana M. , Xiang Jenny Z. , Salvatore Steven , Seshan Surya V. , Sharma Vijay K. , Suthanthiran Manikkam , Muthukumar Thangamani
Published: May 2022

The frequently occurring T cell mediated rejection (TCMR) is a risk factor for allograft failure. Immunosuppressive therapy fails to reverse almost 40% of TCMRs occurring in human kidney allografts. A better understanding of the molecular mechanisms of TCMR and precision therapeutics may improve allograft longevity. We investigated adaptive immune landscape of TCMR by genome wide RNA sequencing of 34 prototypic kidney allograft biopsies from 34 adult recipients of human kidney allografts. Sixteen of the 34 biopsies were categorized as Banff TCMR and the remaining 18 as Banff Normal biopsies. Computational analysis identified higher intragraft abundance of the gene sets for key players of adaptive immune system in TCMR. TCMR allografts were characterized by, i) increased antigen processing and presentation and T cell receptor signaling, ii) increased memory T cells, Tregs, Th1, Th2 and Th17 subsets, iii) increased aerobic glycolysis of lymphocytes and reduced metabolic activity of graft parenchymal cells, iv) increased T cell inhibitory receptors and exhaustion markers, v) increased apoptosis and necroptosis, and vi) increased extracellular matrix remodeling, all in comparison to Normal biopsies. Our genome-wide transcriptomics provides an atlas of adaptive immune landscape of TCMR in human kidney allografts, help deduce molecular mechanisms and prioritization of therapeutic targets.
Adult Hox gene expression promotes periosteal stem cell maintenance and mediates reprogramming in a regionally restricted manner
Authors: Leclerc Kevin , Remark Lindsey H. , Ramsukh Malissa , Josephson Anne Marie , Morgani Sophie M. , Palma Laura , Parente Paulo EL , Lee Sooyeon , Lopez Emma Muiños , Leucht Philipp
Published: May 2022

Periosteal stem and progenitor cells are pivotal to the growth and lifelong turnover of bone and underpin its capacity to regenerate. Adjusting the potency of this cell population will therefore be critical to the successful generation and application of new bone repair therapies. Following their role in patterning the embryonic skeleton, Hox genes remain regionally expressed in mesenchymal stromal cell populations of the adult skeleton. Here we show that Hoxa10 is most expressed in the most uncommitted periosteal stem cell and that Hox maintains these skeletal stem cells in a multipotential, uncommitted state, thereby preventing their differentiation into bone. We demonstrate that Hoxa10 mediates the reprogramming of periosteal progenitors towards a stem cell state with greater self-renewal capacity and also establish that region-specific Hox genes mediate cell reprogramming in distinct anatomical regions, demonstrating the continued functional relevance of the embryonic Hox profile in adult stem cells. Together, our data describe a master regulator role of Hox in skeletal stem and progenitor cells and help provide insight into the development of cell-based therapies for treatment of at-risk bone fractures and other bone-related ailments.
The origin and evolution of mitochondrial tropism inMidichloriabacteria
Authors: Floriano Anna Maria , Batisti Biffignandi Gherard , Castelli Michele , Olivieri Emanuela , Clementi Emanuela , Comandatore Francesco , Rinaldi Laura , Opara Maxwell , Plantard Olivier , Palomar Ana M. , Noël Valérie , Vijay Amrita , Lo Nathan , Makepeace Benjamin L. , Duron Olivier , Jex Aaron , Guy Lionel , Sassera Davide
Published: May 2022

Midichloriaare intracellular bacterial symbionts of ticks. Some representatives of this genus have the unique capability to colonize mitochondria in the cells of their hosts. Hypotheses on the nature of this interaction have proven difficult to test, partly due to a lack of data. Indeed, until now, mitochondrial tropism information and genomes were available only for symbionts of three and two tick host species, respectively. Here we analyzed the mitochondrial tropism of three additionalMidichloriaand sequenced nine novel genomes, showing that the tropism is pnon-monophyletic, either due to losses of the trait or multiple parallel acquisitions. Comparative genome analyses support the first hypothesis, as the genomes of non-mitochondrial symbionts appear to be reduced subsets of those capable of colonizing the organelles. We detect genomic signatures of mitochondrial tropism, showing a set of candidate genes characteristic of the strains capable of mitochondrial colonization. These include the type IV secretion system and the flagellum, which could allow the secretion of unique effectors, direct interaction with, or invasion of the mitochondria. Other genes, including putative adhesion molecules, proteins possibly involved in actin polymerization, cell wall and outer membrane proteins, are only present in mitochondrial symbionts. The bacteria could use these to manipulate host structures, including mitochondrial membranes, in order to fuse with the organelles or manipulate the mitochondrial network.
A Unified Catalog of 19,251 Non-human Reference Species Genomes Provides New Insights into the Mammalian Gut Microbiomes
Authors: Li Xiaoping , Tian Chen , Zhuang Daohua , Tian Liu , Shi Xingwei , Bai Yanli , Gao Han , Zhou Hong , Zhao Fangfang , Dai Min , Zhu Lei , Wu Qunfu , Liu Xiaotong , Zhang Tao , Sang Jianan , Sahu Sunil Kumar , Xu Xun , Jia Huijue , Liu Huan , Xiao Liang , Kristiansen Karsten , Zhang Zhigang
Published: May 2022

The gut microbiota is essential for host health and survival. Here, using samples from animals living in the Qinghai-Tibetan Plateau, we recovered 119,568 metagenome-assembled genomes (MAGs) that were clustered into 19,251 species-level genome bins (SGBs) of which most represent novel species. We present a novel mechanism shaping mammalian gut microbiomes using ancestral founder bacteria (AFB) as a core skeleton and recurring lineage-specific gains of microbial species that are transferred frequently among multiple hosts, not strictly limited by host phylogeny. Such lineage specific gains are responsible for increasing gut microbial diversity, maintaining functional stability, and endowing specific functions for host adaptions. Our analyses did not support the existence of co-phylogeny or co-speciation events between mammal hosts and their individual gut symbionts. The results presented in this study not only reveal novel unique gut microbial species and offer insight of value for understanding the diversity, stability, functionality of the mammalian gut microbiomes, and the co-evolution with their hosts, but also emphasize that animals living in extreme environments are a promising resource for the discovery of novel biological functions.
Insertions and deletions mediated functional divergence of Rossmann fold enzymes
Authors: Toledo-Patiño Saacnicteh , Pascarelli Stefano , Uechi Gen-ichiro , Laurino Paola
Published: May 2022

Nucleobase-containing coenzymes are considered the relics of an early RNA-based world that preceded the emergence of protein domains. Despite the importance of coenzyme-protein synergisms, their emergence and evolution remain poorly understood. An excellent target to address this issue is the Rossman fold, the most catalytically diverse and abundant protein architecture in Nature. Here, we investigatedted the two largest Rossman lineages, namely the nicotinamide adenine dinucleotide phosphate (NAD(P))-binding and the S-adenosyl methionine (SAM)-dependent superfamilies. With the aim to identify the evolutionary changes that lead to a switch in coenzyme specificity on these superfamilies, we performed structural and sequence-based Hidden Markov Models to systematically search for key motifs in their coenzyme-binding pockets. Our analyses revealed how insertions and deletions (InDels) reshaped the ancient β1−loop−α1 coenzyme-binding structure of NAD(P) into the well-defined SAM-binding β1−loop−α1 structure. To prove this observation experimentally, we removed an InDel of three amino acids from the NAD(P) coenzyme pocket and solved the structure of the resulting mutant, revealing the characteristic features of the SAM-binding pocket. To confirm the binding to SAM, we performed isothermal titration calorimetry measurements, validating the successful coenzyme switch. Molecular dynamics simulations also corroborated the role of InDels in abolishing NAD-binding and acquiring SAM binding. Our results uncovered how Nature utilized insertions and deletions to switch coenzyme specificity, and in turn, functionalities between these superfamilies. This work also establishes how protein structures could have been recycled through the course of evolution to adopt different coenzymes and confer different chemistries.

Significance Statement

Cofactors are ubiquitous molecules necessary to drive about half of the enzymatic reactions in Nature. Among them, organic cofactors (coenzymes) that contain nucleotide moieties are believed to be relics of a hypothetical RNA world. Understanding coenzyme-binding transitions sheds light onto the emergence of the first enzymes and their chemical diversity. Rossmann enzymes bind to 7 out of 10 nucleotide coenzymes, representing an ideal target to study how different coenzyme specificities emerged and evolved. Here we demonstrated how insertions and deletions reshape coenzyme-specificity in Rossmann enzymes by retracing the emergence of the SAM-binding function from an NAD-binding ancestor. This work constitutes the first example of an evolutionary bridge between redox and methylation reactions, providing a new strategy to engineer coenzyme specificity.
The Limits of Molecular Signatures for Pancreatic Ductal Adenocarcinoma Subtyping
Authors: Lautizi Manuela , Baumbach Jan , Weichert Wilko , Steiger Katja , List Markus , Pfarr Nicole , Kacprowski Tim
Published: May 2022

Molecular signatures have been suggested as biomarkers to classify pancreatic ductal adenocarcinoma (PDAC) into two, three or four subtypes. Since the robustness of existing signatures is controversial, we performed a systematic evaluation of three established signatures for PDAC stratification across eight publicly available datasets. Clustering revealed inconsistency of subtypes across independent datasets and in some cases a different number of PDAC subgroups than in the original study, casting doubt on the actual number of existing subtypes. Next, we built nine classification models to investigate the ability of the signatures for tumor subtype prediction. The overall classification performance ranged from ∼35% to ∼90% accuracy, suggesting instability of the signatures. Notably, permuted subtypes and random gene sets achieved very similar performance. Cellular decomposition and functional pathway enrichment analysis revealed strong tissue-specificity of the predicted classes. Our study highlights severe limitations and inconsistencies that can be attributed to technical biases in sample preparation and tumor purity, suggesting that PDAC molecular signatures do not generalize across datasets. How stromal heterogeneity and immune compartment interplay in the diverging development of PDAC is still unclear. Therefore, a more mechanistic or at least multi-omic approach seems necessary to extract more robust and clinically exploitable insights.
Coexistence of Cue-specific and Cue-independent Spatial Representations for Landmarks and Self-motion Cues in Human Retrosplenial Cortex
Authors: Chen Xiaoli , Wei Ziwei , Wolbers Thomas
Published: May 2022

Landmark-based and self-motion-based navigation are two fundamental forms of spatial navigation, which involve distinct cognitive mechanisms. A critical question is whether these two navigation modes invoke common or distinct spatial representations for a given environment in the brain. While a number of electrophysiological studies in non-human animals have investigated this question but yielded inconsistent results, it still awaits rigorous investigation in humans. In the current study, we combined ultra-high field fMRI at 7T and desktop virtual reality with state-of-the-art fMRI data analysis techniques. Using a novel linear track navigation task, we dissociated the use of landmarks and self-motion cues, so that participants used different spatial cues to encode and retrieve the same set of spatial locations. Focusing on the retrosplenial cortex (RSC) and the hippocampus, we observed that RSC contained both cue-specific and cue-independent spatial representations, which were driven by objective location (where the participant was actually located) and subjective location (the participant’s self-reported location), respectively. The hippocampus showed strong functional coupling with RSC and exhibited a similar spatial coding scheme, but with reduced effect sizes. Taken together, the current study demonstrated for the first time concurrent cue-specific and cue-independent spatial representations in RSC in the same spatial context, suggesting that this area might transform cue-specific spatial inputs into coherent cue-independent spatial representations to guide navigation behavior.
Multiplexed chromatin imaging reveals predominantly pairwise long-range coordination betweenDrosophilaPolycomb genes
Authors: Gurgo Julian , Walter Jean-Charles , Fiche Jean-Bernard , Houbron Christophe , Schaeffer Marie , Cavalli Giacomo , Bantignies Frédéric , Nollmann Marcelo
Published: May 2022

Polycomb (Pc) group proteins are transcriptional regulators with key roles in development, cell identity and differentiation. Pc-bound chromatin regions form repressive domains that interact in 3D to assemble repressive nuclear compartments. Here, we used multiplexed chromatin imaging to investigate whether Pc compartments involve the clustering of multiple Pc domains during Drosophila development. Notably, 3D proximity between Pc targets is rare and involves predominantly pairwise interactions. These 3D proximities are particularly enhanced in segments where Pc genes are co-repressed. In addition, segment-specific expression ofHoxPc targets leads to their spatial segregation from Pc repressed genes. Finally, non-Hox Pc targets are proximal in regions where they are co-expressed. These results indicate that long-range Pc interactions are temporally and spatially regulated during differentiation and development but do not involve clustering of multiple distant Pc genes.