bluuebunny/crossref_metadata_2025 huggingface dataset:
Cachexia and bladder cancer: clinical impact and management
Authors: Lokeshwar Soum D. , Press Benjamin H. , Nie James , Klaassen Zachary , Kenney Patrick A. , Leapman Michael S.
Published: October 2021

Purpose of review

The purpose of this review is to describe the causes, management, and clinical outcomes associated with cachexia and related components including sarcopenia, among patients with bladder cancer (BCa).

Recent findings

Cachexia in patients with BCa is associated with poorer outcomes after radical cystectomy (RC), radiation, and chemotherapy. Nutritional supplements and novel pharmaceutical agents including magnolol, flucoidan and Anamorelin are currently undergoing investigation for their potential use in BCa patients with cachexia.

Cachexia is a hypercatabolic state thought to be caused by an immune-regulated release of cytokines and disruptions of molecular pathways within the tumor microenvironment and systemically. Nutritional deficiencies in patients with BCa also contribute to cachexia and sarcopenia. Patients with BCa -related cachexia and sarcopenia experience worse survival and therapeutic outcomes after RC, chemotherapy, and radiation therapy. Patients with cachexia also experience more postoperative complications after RC. The management of cachexia in patients with BCa remains challenging and requires timely identification, and multidisciplinary management including nutritional supplementation, physical therapy, palliative care, and pharmacological agents. Clinical trials and human studies are still required to determine which pharmacological agents are optimal for BCa cachexia.
Point-of-Care Lung Ultrasonography
Authors: Gonzalez Juan M. , Crenshaw Nichole , Larrieu-Jimenez Patricia , Groom Jeffrey , Hauglum Shayne , Ortega Johis
Published: October 2021

Since the introduction of ultrasonography, clinicians have discovered different uses for embedding this technology in the clinical setting. The use of point-of-care ultrasonography has gained a lot of interest in the emergency department. It is a procedure that a clinician can rapidly utilize to triage, risk stratify, evaluate, and monitor the patient's condition. The COVID-19 pandemic has highlighted the significance and application of ultrasonography in identifying and managing patients presenting with lung pathology in the emergency setting.
Haemodynamic dependence of mechano-genetic evolution of the cardiovascular system in Japanese medaka
Authors: Chakraborty Sreyashi , Allmon Elizabeth , Sepúlveda Maria S. , Vlachos Pavlos P.
Published: October 2021

The progression of cardiac gene expression–wall shear stress (WSS) interplay is critical to identifying developmental defects during cardiovascular morphogenesis. However, mechano-genetics from the embryonic to larval stages are poorly understood in vertebrates. We quantified peak WSS in the heart and tail vessels of Japanese medaka from 3 days post fertilization (dpf) to 14 dpf using
in vivo
micro-particle image velocimetry flow measurements, and in parallel analysed the expression of five cardiac genes (
fgf8
,
hoxb6b
,
bmp4
,
nkx2.5
,
smyd1
). Here, we report that WSS in the atrioventricular canal (AVC), ventricular outflow tract (OFT), and the caudal vessels in medaka peak with inflection points at 6 dpf and 10–11 dpf instead of a monotonic trend. Retrograde flows are captured at the AVC and OFT of the medaka heart for the first time. In addition, all genes were upregulated at 3 dpf and 7 dpf, indicating a possible correlation between the two, with the cardiac gene upregulation preceding WSS increase in order to facilitate cardiac wall remodelling.
Staphylococcus singaporensis sp. nov., a new member of the Staphylococcus aureus complex, isolated from human clinical specimens
Authors: Chew Ka Lip , Octavia Sophie , Lai Deborah , Lin Raymond T. P. , Teo Jeanette W. P.
Published: October 2021

Staphylococcus argenteus

and

Staphylococcus schweitzeri

are the newest members of the

Staphylococcus aureus

complex. The number of clinical reports attributed to these new

S. aureus

complex members is limited. In a retrospective clinical laboratory study conducted over a 4-month period investigating the prevalence of

S. argenteus

and

S. schweitzeri

, a total of 43 isolates were selected. Phylogeny based on core-gene multilocus sequence typing (MLST) analysis confirmed that 37 were

S. argenteus

but a genetically distinct clade of six isolates was identified. Digital DNA–DNA hybridization (dDDH) and average nucleotide identity (ANI) analyses further supported the classification of these six isolates as a separate species. When compared to

S. aureus

complex reference genomes, the ANI values were ≤94 % and the dDDH values were <53 %. Based on the seven-gene

S. aureus

MLST scheme, the six isolates belong to five novel allelic profiles (ST6105, ST6106, ST6107, ST6108 and ST109). Their clinical infection features were similar to

S. aureus

. Skin and soft tissue infections presented in four out of the six cases. Routine clinical diagnostic identification using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and biochemical profiling does not differentiate these new members from the rest of the complex. Genotypic analysis suggests that the six isolates belong to a novel species, Staphylococcus singaporensis sp. nov. with isolate SS21T (=DSM 111408T=NCTC14419T) designated as the type strain.
In vitro activity of bedaquiline against Mycobacterium avium complex
Authors: Litvinov Vitaly , Makarova Marina , Kudlay Dmitry , Nikolenko Nikolai , Mikhailova Julia
Published: October 2021

Introduction. Nontuberculous mycobacteria (NTM) are widespread in the environment and can cause various diseases in humans, especially immunocompromised patients.

Hypothesis. Treatment of diseases caused by NTM is a complicated issue, mainly due to the resistance of the pathogen to most antimicrobial agents. Bedaquiline (Bdq) is now widely used for the treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB).

Aim. The main goal of our study was to evaluate the activity of Bdq against

Mycobacterium avium

complex (MAC), the most common species among NTM.

Methodology. A total of 166 MAC cultures (124

Mycobacterium avium

and 42

Mycobacterium intracellulare

) were studied. The minimum inhibitory concentrations (MICs) of Bdq for

M. avium

and

M. intracellulare

were obtained by twofold serial dilutions in the Middlebrook 7H9 medium. MIC ranges were determined and the MIC50, MIC90 and ECOFF values were obtained.

Results. The MICs in respect of

M. avium

ranged from 0.003 to 1.0 µg ml−1; those for

M. intracellulare

ranged from 0.003 to 0.5 µg ml−1. The Bdq MIC50 and MIC90 values were found to be 0.015 and 0.12 µg ml−1
, respectively, for

M. avium

and 0.007 and 0.06 µg ml−1, respectively, for

M. intracellulare

. The tentative ECOFF values for

M. avium

and

M. intracellulare

were 0.12 and 0.06 µg ml−1, respectively.

Conclusion. The main bedaquiline susceptibility parameters for MAC strains isolated in the Moscow region were determined.
Integrated Genomic Surveillance reveals extensive onward transmission of travel-imported SARS-CoV-2 infections in the community
Authors: Houwaart Torsten , Belhaj Samir , Tawalbeh Emran , Nagels Dirk , Finzer Patrick , Fröhlich Yara , Benmoumene Assia , Asskali Dounia , Haidar Hussein , von Dahlen Janina , Nicolai Jessica , Stiller Lisa , Blum Jacqueline , Lange Christian , Adelmann Carla , Schroer Britta , Osmers Ute , Grice Christiane , Kirfel Phillipp P. , Jomaa Hassan , Strelow Daniel , Hülse Lisanna , Pigulla Moritz , Kreuzer Pascal , Tyshaieva Alona , Weber Jonas , Wienemann Tobias , Vasconcelos Malte Kohns , Hoffmann Katrin , Lübke Nadine , Hauka Sandra , Andree Marcel , Jürgen Scholz Claus , Jazmati Nathalie , Göbels Klaus , Zotz Rainer , Pfeffer Klaus , Timm Jörg , Ehlkes Lutz , Walker Andreas , Dilthey Alexander T. ,   German COVID-19 OMICS Initiative (DeCOI)
Published: October 2021

Integration of genomic surveillance with contact tracing provides a powerful tool for the reconstruction of person-to-person pathogen transmission chains. We report two large clusters of SARS-CoV-2 cases (“Delta” clade, 110 cases combined) detected in July 2021 by Integrated Genomic Surveillance in Düsseldorf. Structured interviews and deep contact tracing demonstrated an association to a single SARS-CoV-2 infected return traveller (Cluster 1) and to return travel from Catalonia and other European countries (Cluster 2), highlighting the importance of containing travel-imported SARS-CoV-2 infections.
Genome-wide rare variant score associates with morphological subtypes of autism spectrum disorder
Authors: Chan Ada J.S. , Engchuan Worrawat , Reuter Miriam S. , Wang Zhuozhi , Thiruvahindrapuram Bhooma , Trost Brett , Nalpathamkalam Thomas , Negrijn Carol , Lamoureux Sylvia , Pellecchia Giovanna , Patel Rohan , Sung Wilson W.L. , MacDonald Jeffrey R. , Howe Jennifer L. , Vorstman Jacob , Sondheimer Neal , Takahashi Nicole , Miles Judith H. , Anagnostou Evdokia , Tammimies Kristiina , Zarrei Mehdi , Merico Daniele , Stavropoulos Dimitri J. , Yuen Ryan K.C. , Fernandez Bridget A. , Scherer Stephen W.
Published: October 2021

Defining different genetic subtypes of autism spectrum disorder (ASD) can enable the prediction of developmental outcomes. Based on minor physical and major congenital anomalies, we categorized 325 Canadian children with ASD into dysmorphic and nondysmorphic subgroups. We developed a method for calculating a patient-level, genome-wide rare variant score (GRVS) from whole-genome sequencing (WGS) data. GRVS is a sum of the number of variants in morphology-associated coding and non-coding regions, weighted by their effect sizes. Probands with dysmorphic ASD had a significantly higher GRVS compared to those with nondysmorphic ASD (P= 0.027). Using the polygenic transmission disequilibrium test, we observed an over-transmission of ASD-associated common variants in nondysmorphic ASD probands (P= 2.9×10−3). These findings replicated using WGS data from 442 ASD probands with accompanying morphology data from the Simons Simplex Collection. Our results provide support for an alternative genomic classification of ASD subgroups using morphology data, which may inform intervention protocols.
Cerebrospinal fluid purinomics as a biomarker approach to predict outcome after severe traumatic brain injury
Authors: Strogulski Nathan Ryzewski , Stefani Marco Antonio , Böhmer Ana Elisa , Hansel Gisele , Rodolphi Marcelo S. , Kopczynski Afonso , de Oliveira Vitória Girelli , Stefani Eduarda Tanus , Portela Juliana Vinadé , Schmidt André P. , Oses Jean Pierre , Smith Douglas H. , Portela Luis V.
Published: October 2021

Severe traumatic brain injury (TBI) is associated with high rates of mortality and long-term disability linked to neurochemical abnormalities. Although purine-derivatives play important roles in TBI pathogenesis in preclinical models, little is known about potential changes in purine levels and their implications in human TBI. We assessed cerebrospinal fluid (CSF) levels of purines in severe TBI patients as potential biomarkers that predict mortality and long-term dysfunction. This was a cross-sectional study performed in 17 severe TBI patients (Glasgow Coma Scale < 8) and 51 controls. Two to four hours after admission to ICU, patients were submitted to ventricular drainage, and CSF collection for quantification of adenine and guanine purine-derivatives by HPLC. TBI patients survival was followed up to 3 days from admission. A neurofunctional assessment was performed through modified Rankin Scale (mRS) two years after ICU admission. Purine levels were compared between control and TBI patients, and between surviving and non-surviving patients. Relative to controls, TBI patients presented increased CSF levels of GDP, guanosine, adenosine, inosine, hypoxanthine, and xanthine. Further, GTP, GDP, IMP, and xanthine levels were different between surviving and non-surviving patients. Among the purines, guanosine was associated with improved mRS (p=0.042; r= −0.506). Remarkably, GTP displayed predictive value (AUC=0.841, p=0.024) for discriminating survival vs. non-survival patients up to three days from admission. These results support TBI-specific purine signatures, suggesting GTP as a promising biomarker of mortality, and guanosine as an indicator of long-term functional disability.

Highlights

CSF levels of guanosine, GDP, adenosine, inosine, hypoxanthine, and xanthine are increased in severe TBI patients.

GTP, GDP, IMP and xanthine levels were different between surviving and non-surviving patients.

Guanosine was associated to improved neurological outcomes two years after TBI.

CSF GTP levels at admission predicted patient death.
Seroprevalence, prevalence, and genomic surveillance: monitoring the initial phases of the SARS-CoV-2 pandemic in Betim, Brazil
Authors: Gilson Silva Ana Valesca Fernandes , Menezes Diego , Moreira Filipe Romero Rebello , Torres Octavio Alcântara , Fonseca Paula Luize Camargos , Moreira Rennan Garcias , Alves Hugo José , Alves Vivian Ribeiro , de Resende Amaral Tania Maria , Coelho Adriano Neves , Saraiva Duarte Júlia Maria , da Rocha Augusto Viana , de Almeida Luiz Gonzaga Paula , de Araújo João Locke Ferreira , de Oliveira Hilton Soares , de Oliveira Nova Jersey Claudio , de Sá Camila Zolini , de Sousa Jôsy Hubner , de Souza Elizângela Gonçalves , de Souza Rafael Marques , de Lima Ferreira Luciana , Gerber Alexandra Lehmkuhl , de Campos Guimarães Ana Paula , Maia Paulo Henrique Silva , Marim Fernanda Martins , Miguita Lucyene , Monteiro Cristiane Campos , Neto Tuffi Saliba , Pugêdo Fabricia Soares Freire , Queiroz Daniel Costa , Cuzzuol Queiroz Damares Nigia Alborguetti , Resende-Moreira Luciana Cunha , Santos Franciele Martins , Souza Erika Fernanda Carlos , Voloch Carolina Moreira , Vasconcelos Ana Tereza , de Aguiar Renato Santana , de Souza Renan Pedra
Published: October 2021

The Covid-19 pandemic has created an unprecedented need for epidemiological monitoring using diverse strategies. We conducted a project combining prevalence, seroprevalence, and genomic surveillance approaches to describe the initial pandemic stages in Betim City, Brazil. We collected 3239 subjects in a population-based age-, sex- and neighbourhood-stratified, household, prospective; cross-sectional study divided into three surveys 21 days apart sampling the same geographical area. In the first survey, overall prevalence (participants positive in serological or molecular tests) reached 0.46% (90% CI 0.12% – 0.80%), followed by 2.69% (90% CI 1.88% – 3.49%) in the second survey and 6.67% (90% CI 5.42% - 7.92%) in the third. The underreporting reached 11, 19.6, and 20.4 times in each survey, respectively. We observed increased odds to test positive in females compared to males (OR 1.88 95% CI 1.25 – 2.82), while the single best predictor for positivity was ageusia/ anosmia (OR 8.12, 95% CI 4.72 – 13.98). Thirty-five SARS-CoV-2 genomes were sequenced, of which 18 were classified as lineage B.1.1.28, while 17 were B.1.1.33. Multiple independent viral introductions were observed. Integration of multiple epidemiological strategies was able to describe Covid-19 dispersion in the city adequately. Presented results have helped local government authorities to guide pandemic management.
Reproducible neuroimaging features for diagnosis of Autism spectrum disorder with machine learning
Authors: Mellema Cooper J. , Nguyen Kevin P. , Treacher Alex , Montillo Albert
Published: October 2021

Autism spectrum disorder (ASD) is the fourth most common neurodevelopmental disorder, with a prevalence of 1 in 160 children. Accurate diagnosis relies on experts, but such individuals are scarce. This has led to increasing interest in the development of machine learning (ML) models that can integrate neuroimaging features from functional and structural MRI (fMRI and sMRI) to measure alterations manifest in ASD. We optimized and compared the performance of 12 of the most popular and powerful ML models. Each was separately trained using 15 different combinations of fMRI and sMRI features and optimized with an unbiased model search. Deep learning models predicted ASD with the highest diagnostic accuracy and generalized well to other MRI datasets. Our model achieves state-of-the-art 80% area under the ROC curve (AUROC) in diagnosis on test data from the IMPAC dataset; and 86% and 79% AUROC on the external ABIDE I and ABIDE II datasets. The highest performing models identified reproducible putative biomarkers for accurate ASD diagnosis in accord with known ASD markers as well as novel cerebellum biomarkers. Such reproducibility lends credence to their tremendous potential for defining and using a set of truly generalizable ASD biomarkers that will advance scientific understanding of neuronal changes in ASD.
Occupational versus community risk of SARS-CoV-2 infection among employees of a long-term care facility: an observational study
Authors: Lenggenhager L. , Martischang R. , Sauser J. , Perez M. , Vieux L. , Graf C. , Cordey S. , Laubscher F. , Nunes T. Robalo , Zingg Walter , Cori A. , Harbarth S. , Abbas M.
Published: October 2021

Objectives

We investigated the relative contribution of occupational (vs. community) exposure for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among employees of a university-affiliated long-term care facility (LTCF), during the 1stpandemic wave in Switzerland (March to June 2020).

Methods

We performed a nested analysis of a seroprevalence study among all volunteering LTCF staff to determine community and nosocomial risk factors for SARS-CoV-2 seropositivity using modified Poison regression. We also combined epidemiological and genetic sequencing data from a coronavirus disease 2019 (COVID-19) outbreak investigation in a LTCF ward to infer transmission dynamics and acquisition routes of SARS-CoV-2, and evaluated strain relatedness using a maximum likelihood phylogenetic tree.

Results

Among 285 LTCF employees, 176 participated in the seroprevalence study, of whom 30 (17%) were seropositive for SARS-CoV-2. Most (141/176, 80%) were healthcare workers (HCWs). Risk factors for seropositivity included exposure to a COVID-19 inpatient (adjusted prevalence ratio [aPR] 2.6; 95%CI 0.9-8.1) and community contact with a COVID-19 case (aPR 1.7; 95%CI 0.8-3.5). Among 18 employees included in the outbreak investigation, the outbreak reconstruction suggests 4 likely importation events by HCWs with secondary transmissions to other HCWs and patients.

Conclusions

These two complementary epidemiologic and molecular approaches suggest a substantial contribution of both occupational and community exposures to COVID-19 risk among HCWs in LTCFs. These data may help to better assess the importance of occupational health hazards and related legal implications during the COVID-19 pandemic.
Leptospira infection in rural areas of Urabá region, Colombia: a prospective study
Authors: Quintero-Vélez Juan C. , Rodas G Juan D. , Rojas A Carlos , Ko Albert I. , Wunder Elsio A.
Published: October 2021

The objective of this study was to analyze the eco-epidemiological aspects of Leptospira seroprevalence and seroincidence, and its associated factors in two municipalities of northwest Colombia. A prospective study was performed in rural areas of Urabá, Antioquia, Colombia. The study enrolled 597 people between November-2015 and January-2016, of which 274 people were followed up one year later. Serologic testing was performed by a microscopic agglutination. The outcomes were seroprevalent and seroincident cases, and the main exposure was an outdoor occupation. A binary and mixed-effect multinomial logistic regression model was used to estimate factors associated with seroprevalent or seroincident cases of Leptospira infection. The overall Leptospira seroprevalence was 27.81% (95%CI:23.62-32.49) and the overall cumulative seroincidence for Leptospira was 14.60% (95%CI:10.33–20.23). Multivariable analysis showed that factors associated with L. interrogans serogroups seropositivity were outdoor occupation, male gender, older age, the presence of dirt soil in the household, and the presence of piglets and opossums. It also showed that factors associated with other Leptospira species serogroups were the presence of pit latrines and of turkeys. In addition, the multivariable model of seroincident cases of L. interrogans serogroups evidenced outdoor occupations, the presence of rats, and corn cultivation as risk factors. Likewise, the multivariable model for seroincident cases of other Leptospira species showed that the presence of hunting canines and cassava cultivation were risk factors. We found specific factors associated with the transmission of Leptospira serogroups contribute to the understanding of the epidemiology of Leptospira infection in rural areas of Urabá, Colombia.

AUTHOR SUMMARY

More than one million cases of leptospirosis occur each year, and about 60,000 people die of the disease worldwide. Leptospirosis is a zoonotic bacterial disease imparting its heaviest burden on resource-poor populations. It is also a major cause of economic loss in farm animals causing fetal infections, abortion, stillbirths, infertility, and increased culling rate. Leptospires also contaminate surface waters and survive in mud and moist soils, facilitating transmission among hosts. This complex cycle of transmission makes the disease a suitable model for a one-health approach. This is a prospective study conducted in rural areas of Colombia aimed at identifying the factors associated with seroprevalent and seroincident Leptospira cases. In addition, the results showed that the presence of synanthropic and domestic animals, the characteristics of household materials, and individual variables were factors associated with Leptospira seropositivity. This study clarifies the epidemiology of Leptospira infection and could improve the surveillance program in Colombia, especially in rural areas.
Main COVID-19 information sources in a culturally and linguistically diverse community in Sydney, Australia: A cross-sectional survey
Authors: Ayre J , Muscat DM , Mac O , Batcup C , Cvejic E , Pickles K , Dolan H , Bonner C , Mouwad D , Zachariah D , Turalic U , Santalucia Y , Chen T , Vasic G , McCaffery KJ
Published: October 2021

Background

Little is known about COVID-19 information-seeking experiences for culturally and linguistically diverse groups in Australia.

Methods

Participants were recruited using a cross-sectional survey from March 21 to July 9, 2021, translated into 11 languages, and with supporting bilingual staff. Linear regression models identified factors associated with difficulty finding easy-to-understand COVID-19 information.

Results

Across 708 participants (88% born overseas, 31% poor English proficiency), difficulty finding easy-to-understand COVID-19 information was rated 4.13 for English materials (95%CI: 3.85 to 4.41) and 4.36 for translated materials (95%CI: 4.07 to 4.66) (1 easy to 10 hard). Participants who were older (p<0.001), had inadequate health literacy (Mean Difference (MD)=-1.43, 95%CI -2.03 to - 0.82, p<0.001), or poor English proficiency (MD=-1.9, 95%CI-2.51 to -1.29, p<0.001) found it harder to find easy-to-understand English-language COVID-19 information. Those who had greater difficulty finding easy-to-understand translated COVID-19 information were younger (p=0.004), had poor English proficiency (MD=-1.61, 95%CI -2.29 to -0.9, p<0.001), university education (MD=0.77, 95%CI 0.00 to 1.53, p=0.05), and had spent longer living in Australia (p=0.001). They were more likely to rely on friends and family for COVID-19 information (p=0.02). There was significant variation in information-seeking experiences across language groups (p’s<0.001).

Conclusions

Easy-to-understand and accessible COVID-19 information is needed to meet the needs of people in culturally and linguistically diverse communities. This approach should involve working alongside these communities to tailor messages and leverage existing communication channels.
The novel conserved NAD+-binding micropeptide SGHRT regulates mitochondrial function and metabolism in human cardiomyocytes
Authors: Do Vinh Dang , Tulsian Nikhil Kumar , Tan Warren KY , Li Zhe , Cheng Liyi , Autio Matias I. , Tan Wilson LW , Tiang Zenia , Perrin Arnaud , Ching Jianhong , Lee Mayin , Bonne Isabelle , Ramachandra Chrishan , Lim Choon Kiat , Hausenloy Derek J , Drum Chester Lee , Richards A. Mark , Anand Ganesh S. , Foo Roger SY
Published: October 2021

Abstracts

Nicotinamide adenine dinucleotide (NAD) is a critical metabolite and coenzyme for multiple metabolic pathways and cellular processes (1-4). In this study, we identified Singheart, SGHRT as a nuclear genome-encoded NAD+-binding mitochondrial micropeptide. SGHRT, present in both monomeric and dimeric forms, binds directly to NAD, but not NADH or flavin adenine dinucleotide (FAD). Localized to the inner mitochondrial membrane and mitochondrial matrix, SGHRT interacts with the mitochondrial enzymes Succinate-CoA Ligase and Succinate Dehydrogenase.SGHRTdeletion in human embryonic stem cell derived cardiomyocytes disrupted mitochondria morphology, decreased total NAD and ATP abundance, and resulted in defective TCA cycle metabolism, the electron transport chain and in Ox-Phos processes. These results comprise the first report of an NAD+-binding micropeptide, SGHRT, required for mitochondrial function and metabolism.
The establishment of multiple knockout mutants of Colletotrichum orbiculare by CRISPR/Cas9 and Cre/loxP systems
Authors: Yamada Kohji , Yamamoto Toya , Uwasa Kanon , Osakabe Keishi , Takano Yoshitaka
Published: October 2021

Phytopathogenic fungi belonging to the Colletotrichum genus cause devastating damage for many plant species. Among them, Colletotrichum orbiculare is employed as a model fungus to analyze molecular aspects of plant-fungus interactions. Although gene disruption via homologous recombination (HR) was established for C. orbiculare, this approach is laborious due to its low efficiency. Here we developed methods to efficiently generate multiple knockout mutants of C. orbiculare. We first found that CRISPR/Cas9 system massively promoted gene-targeting efficiency. By transiently introducing a CRISPR/Cas9 vector, more than 90 % of obtained transformants were knockout mutants. Furthermore, we optimized a self-excision Cre/loxP marker recycling system for C. orbiculare because limited availability of desired selective markers hampers sequential gene disruption. In this system, integrated selective marker is removable from the genome via Cre recombinase driven by a xylose-inducible promoter, enabling reuse of the same selective marker for the next transformation. Using our CRISPR/Cas9 and Cre/loxP systems, we attempted to identify functional sugar transporters in C. orbiculare. Multiple disruptions of putative quinate transporter genes restrict fungal growth on media containing quinate as a sole carbon source, confirming their functionality as quinate transporters. Our analyses revealed that quinate acquisition is dispensable during fungal infection because this mutant displayed normal virulence to host plants. In addition, we successfully built mutations of 17 cellobiose transporter genes in a strain. From the data of knockout mutants established in this study, we inferred that repetitive rounds of gene disruption using CRISPR/Cas9 and Cre/loxP systems do not cause negative effects for fungal virulence and growth. Therefore, these systems will be powerful tools to perform systematic gene targeting approach for C. orbiculare.
Sperm and northern bottlenose whale interactions with deep-water trawlers in the western North Atlantic
Authors: Oyarbide Usua , Feyrer Laura , Gordon Jonathan
Published: October 2021

Commercial fisheries have increased in all the world’s oceans with diverse unintended impacts on marine ecosystems. As a result of resource overlap, interactions between cetaceans and fisheries are a common occurrence and, in many cases, these give rise to significant conservation issues. Research on the distribution and types of such interactions is important for efficient management. In this study, we describe the behaviors of two whale species: sperm whales (Physeter macrocephalus) and northern bottlenose whales (Hyperoodon ampullatus), interacting with benthic trawlers fishing off the eastern Grand Banks of the western North Atlantic in 2007. Whale interactions were only observed when vessels were targeting Greenland halibut (Reinnhardtius hippoglossoides) in deep-water fishing areas and were most common during net hauling. Sperm whales and northern bottlenose whales appeared to engage in feeding behavior close to the surface during hauling, especially during the latter stages, suggesting they targeted fish escapees rather than discards. Using photo-identification methods, seven individual sperm whales were identified with multiple resights of six individuals being recorded over an almost two month period. The maximum distance between two resights was 234 km, suggesting individual sperm whales were repeatedly targeting and even following fishing vessels over multiple days and between fishing areas. By contrast, there were no photographic resights of individual northern bottlenose whales within this study, or with substantial photo-identification catalogues from other adjacent high density areas, suggesting that individuals of this species may be less likely to follow vessels or move between areas. This study documents the earliest confirmed records of northern bottlenose whales in this remote region. These interactions and high encounter rates may indicate that adjacent populations are recovering from the previous century of commercial whaling. Our study provides new insights and details on whale-fisheries interactions, which can inform future research and help managers understand the real and perceived impacts on fisheries and whales.
Limited adaptive evolution ofStaphylococcus aureusduring transition from colonization to invasive infection
Authors: Räz Anna K. , Andreoni Federica , Boumasmoud Mathilde , Bergada-Pijuan Judith , Schweizer Tiziano A. , Shambat Srikanth Mairpady , Hasse Barbara , Zinkernagel Annelies S. , Brugger Silvio D.
Published: October 2021

Staphylococcus aureuscarriage is a risk factor for invasive infections. Unique genetic elements favoring the transition from colonizing to invasive phenotype have not yet been identified and phenotypic traits are understudied. We therefore assessed pheno- and genotypic profiles of elevenS. aureusisolate pairs sampled from colonized patients simultaneously suffering from invasiveS. aureusinfections. Ten out of 11 isolate pairs presented the samespaand MLST suggesting colonization as origin for the invasive infection. Systematic analysis of colonizing and invasive isolate pairs showed similar adherence, hemolysis and reproductive fitness properties, minimal genetic differences, identical antibiotic tolerance and bacterial virulence inGalleria mellonella. Our results provide insights into the similar phenotype associated with limited adaptive genetic evolution between the colonizing and invasive isolates. Disruption of the physical barriers mucosa or skin were identified in the majority of patients further emphasizing colonization as a major risk factor for invasive disease.

Importance

S. aureusis a major pathogen of humans causing a wide range of disease. The failure to develop a vaccine and antibiotic warrant the exploration of novel treatment strategies. Asymptomatic colonization of the human nasal passages is a major risk factor for invasive disease and decolonization procedures have shown efficacy in preventing invasive infections. However, the transition ofS. aureusfrom a benign colonizer of the nasal passages to a major pathogen is not well understood and host as well as bacterial properties have been discussed as being relevant for this behavioral change. We conducted a thorough investigation of patient-derived strain pairs reflecting colonizing and invasive isolates in a given patient. Although we identified limited genetic adaptation in certain strains as well as slight differences in adherence capacity of colonizing and invasive isolates, our work suggests that barrier breaches are a key event in the disease continuum ofS. aureus.
Behavioral and slice electrophysiological assessment of DREADD ligand, deschloroclozapine (DCZ) in rats
Authors: Nentwig Todd B. , Obray J. Daniel , Vaughan Dylan T. , Chandler L. Judson
Published: October 2021

Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) have become a premier neuroscience research tool in the past decade for their utility in providing reversible manipulations of cellular activity following experimenter-controlled delivery of a DREADD-specific ligand. However, the commonly used DREADD ligand, clozapine-N-oxide (CNO), has metabolic and off-target effects that may confound experimental results and interpretations. Moreover, CNO has relatively poor affinity for DREADD receptors, which necessitates high doses for systemic administration applications. New DREADD ligands aim to reduce metabolic and potential off-target effects while maintaining strong efficacy for the designer receptors. Recently a novel DREADD ligand, deschloroclozapine (DCZ), was shown to induce chemogenetic-mediated cellular and behavioral effects in mice and monkeys without detectable side effects. While promising, further testing of DCZ across species and experimental paradigms is warranted. The goal of the present study was to examine the effectiveness of systemic DCZ for DREADD-based chemogenetic manipulations in behavioral and slice electrophysiological applications in rats. We demonstrate that a relatively low dose of DCZ (0.1 mg/kg) supports excitatory DREADD-mediated cFos induction, DREADD-mediated inhibition of a central amygdala-dependent behavior, and DREADD-mediated inhibition of neuronal activity in a slice electrophysiology preparation. In addition, we show that this dose of DCZ does not alter gross locomotor activity or induce a place preference/aversion in control rats without DREADD expression. Together, our findings support the use of systemic DCZ for DREADD-based manipulations in rats, and provide evidence that DCZ is a superior alternative to CNO.
Optimized Multicolour Immunofluorescence Panel for Cattle B Cell Phenotyping by an 8-Colour, 10-Parameter Panel
Authors: Roos Eduard O. , Placido Marie Bonnet-Di , Mwangi William N , Moffat Katy , Fry Lindsay , Waters Ryan , Hammond John A.
Published: October 2021

This 8-colour, 10-parameter panel has been optimised to distinguish between functionally distinct subsets of cattle B cells in both fresh and cryopreserved peripheral blood mononuclear cells (PBMCs). Existing characterised antibodies against cell surface molecules (immunoglobulin light chain (S-Ig(L)), CD20, CD21, CD40, CD71 and CD138) enabled the discrimination of 24 unique populations within the B cell population. This allows the identification of five putative functionally distinct B cell subsets critical to infection and vaccination responses; 1) naïve B cells (BNaïve), 2) regulatory B cells (BReg), 3) memory B cells (BMem), 4) plasmablasts (PB) and 5) plasma cells (PC). Although CD3 and CD8α can be included as an additional dump channel, it does not significantly improve the panel’s ability to separate “Classical” B cells. This panel will promote better characterisation and tracking of B cell responses in cattle as well as other bovid species as the reagents are likely to cross react.
Multi-omic analysis of the Arabidopsis clock activator mutantrve 4 6 8reveals connections to carbohydrate metabolism and proteasome regulation
Authors: Scandola S , Mehta D , Li Q , Rodriguez M , Castillo B , Uhrig RG
Published: October 2021

Plants are able to sense changes in their light environments, such as the onset of day and night, as well as anticipate these changes in order to adapt and survive. Central to this ability is the plant circadian clock, a molecular circuit that precisely orchestrates plant cell processes over the course of a day. REVEILLE proteins (RVEs) are recently discovered members of the plant circadian circuitry that activate the evening complex and PRR genes to maintain regular circadian oscillation. The RVE 8 protein and its two homologs, RVE 4 and 6, have been shown to limit the length of the circadian period, withrve 4 6 8triple-knockout plants possessing an elongated period along with increased leaf surface area, biomass, cell size and delayed flowering relative to wild-type Col-0 plants. Here, using a multi-omics approach consisting of phenomics, transcriptomics, proteomics, and metabolomics we draw novel connections between RVE8-like proteins and a number of core plant cell processes. In particular, we reveal that loss of RVE8-like proteins results in altered carbohydrate, organic acid and lipid metabolism, including a starch excess phenotype at dawn. We further demonstrate thatrve 4 6 8plants have lower levels of 20S proteasome subunits and possess significantly reduced proteasome activity, potentially explaining the increase in cell-size observed in RVE8-like mutants. Overall, this robust, multi-omic dataset, provides substantial new insights into the far reaching impact RVE8-like proteins have on the diel plant cell environment.
Multi-omics analysis reveals cross-organism interactions in coral holobiont
Authors: Maruyama Toru , Ito Michihiro , Wakaoji Satoshi , Okubo Yusuke , Ide Keigo , Nishikawa Yohei , Fujimura Hiroyuki , Suda Shoichiro , Nakano Yoshikatsu , Satoh Noriyuki , Shinzato Chuya , Yura Kei , Takeyama Haruko
Published: October 2021

Corals create an ecosystem, called a holobiont, with intracellular algae (zooxanthellae) and resident bacteria. Zooxanthellae and some bacteria play major roles in the physiological properties of the coral host. However, because of the difficulties in experimental verification of cross-organism interactions, the mechanisms underpinning these interactions are largely unknown. To address this, we here generated and then analyzed multi-omics datasets for corals, zooxanthellae, and bacteria collected at Okinawa, Japan, from November 2014 to September 2016. Using cross-organism co-expression analysis, we successfully characterized the host–alga relationship in the coral holobiont. Specifically, we observed that the coral host dominates the zooxanthellae. The multi-omics analysis also suggested that infection with coral-associated bacteria Endozoicomonas likely involves coral-like ephrin ligands, triggering an immune response of the coral host. This study highlights the potential of the multi-omics approach to elucidate coral–microbe interactions.
A method for identifying environmental stimuli and genes responsible for genotype-by-environment interactions from a large-scale multi-environment data set
Authors: Onogi Akio , Sekine Daisuke , Kaga Akito , Nakano Satoshi , Yamada Tetsuya , Yu Jianming , Ninomiya Seishi
Published: October 2021

It has not been fully understood in real fields what environment stimuli cause the genotype-by-environment (G × E) interactions, when they occur, and what genes react to them. Large-scale multi-environment data sets are attractive data sources for these purposes because they potentially experienced various environmental conditions. Here we developed a data-driven approach termed Environmental Covariate Search Affecting Genetic Correlations (ECGC) to identify environmental stimuli and genes responsible for the G × E interactions from large-scale multi-environment data sets. ECGC was applied to a soybean (Glycine max) data set that consisted of 25,158 records collected at 52 environments. ECGC illustrated what meteorological factors shaped the G × E interactions in six traits including yield, flowering time, and protein content and when they were involved. For example, it illustrated the relevance of precipitation around sowing dates and hours of sunshine just before maturity to the interactions observed for yield. Moreover, genome-wide association mapping on the sensitivities to the identified stimuli discovered candidate and known genes responsible for the G × E interactions. Our results demonstrate the capability of data-driven approaches to bring novel insights on the G × E interactions observed in fields.

Key message

The proposed method is able to identify environmental stimuli and genes responsible for the G × E interactions observed in multi-environmental trials. The method is based on similarity search between genetic correlation and environmental stimuli among environments.
Italian universities do not recruit according to proficiency in scientific production
Authors: Gallina Pasquale , Porfirio Berardino
Published: October 2021

We analyzed the files regarding recruitment competitions won by 186 professors of selected bibliometric disciplines in Florence between January 2014 and 30 June 2021. An equal number of professors recruited at other Italian universities and of researchers who never attained professorship in Italy were randomly chosen in the same disciplines as each Florentine professor among individuals possessing National Scientific Qualification, a prerequisite for professorship. The H-indexes at the time of qualification (T1), of the Florence call (T2), and the current (T3) time were obtained from Scopus.

Non-recruited researchers were more likely (Chi-square test) to show a higher H-index than both Florentine (T1 p=0.0005, T2 p=0.0015, T3 p=0.0095) and non-Florentine professors (T1 p=0.0078, T2 p=0.0245, T3 p=0.0500). Fifty-four non-recruited scientists serve in foreign universities, 100 at national/international research centers. The remaining 32 scientists (25 who keep producing despite precarious employment, and seven who have stopped publishing) were, at any rate, as likely as Florentine (T3 p=0.69) and non-Florentine professors (T3 p=0.14) to show a higher H-index.

This study suggests that Italian academia does not recruit professors according to their qualitative/quantitative ability to publish, a detriment to knowledge for the nationwide system and on a global scale.
Regulation of skeletal muscle metabolism and contraction performance via teneurin-latrophilin action
Authors: Reid Andrea L. , Hogg David W. , Dodsworth Thomas L. , Chen Yani , Reid Ross M. , Xu Mei , Husic Mia , Biga Peggy R. , Slee Andrew , Buck Leslie T. , Barsyte-Lovejoy Dalia , Locke Marius , Lovejoy David A.
Published: October 2021

Skeletal muscle regulation is responsible for voluntary muscular movement in vertebrates. The genes of two essential proteins, teneurins and latrophilins (LPHN), evolving in ancestors of multicellular animals, form a ligand-receptor pair, and are now shown to be required for skeletal muscle function. Teneurins possess a bioactive peptide, termed the teneurin C-terminal associated peptide (TCAP) that interacts with the LPHNs to regulate skeletal muscle contractility strength and fatigue by an insulin-independent glucose importation mechanism. CRISPR-based knockouts and siRNA-associated knockdowns of LPHN-1 and-3 shows that TCAP stimulates an LPHN-mediated cytosolic Ca2+ signal transduction cascade to increase energy metabolism and enhance skeletal muscle function via increases in type-1 oxidative fiber formation and reduce the fatigue response. Thus, the teneurin/TCAP-LPHN system is presented as a novel mechanism likely to regulate the energy requirements and performance of skeletal muscle.
Female choice can explain the fertilization pattern in oaks
Authors: Schneider Katharina , Staňková Kateřina , Brown Joel S.
Published: October 2021

We extend a two-step lottery model of Craft et al. to test the hypothesis that oak trees pursue a form of within-flower female choice to increase the diversity of fathers. Oak trees produce six ovules per flower while maturing just one acorn. When assuming a random ovule selection - which is a natural assumption in the absence of other hypotheses - observed fertilization patterns in oaks cannot be explained: long-distance fertilization is unusually common, even as nearby oak trees may be absent as pollen donors. Our model demonstrates how producing multiple ovules per flower permits selection for rare, distant fathers. The number of ovules per flower that maximizes paternal diversity increases with the number of trees. We introduce a cost function for ovule production for which six ovules per flower balance these costs with the benefits of diversifying fathers. Using data from two published field studies, 7 of 8 investigated maternal oaks had actual paternal diversity indices (average diversity index of 15.42) that fit the female choice hypothesis (estimated diversity of 14.66) significantly better than assuming a random selection from the six available ovules (estimated diversity of 7.649). A third field study permitted us to compare paternity by distance classes for two maternal trees. Both fit the female choice model better than random ovule selection.
Ultrahigh-Throughput Ambient MS: Direct Analysis at 22 Samples per Second by Infrared Matrix-Assisted Laser Desorption Electrospray Ionization Mass Spectrometry
Authors: Radosevich Andrew J. , Pu Fan , Chang-Yen David , Sawicki James W. , Talaty Nari N. , Elsen Nathaniel L. , Williams Jon D. , Pan Jeffrey Y
Published: October 2021

Infrared Matrix-Assisted Laser Desorption Electrospray Ionization (IR-MALDESI) mass spectrometry is an ambient-direct sampling method being developed for high-throughput, label-free, biochemical screening of large-scale compound libraries. Here, we report the development of an ultrahigh-throughput continuous motion IR-MALDESI sampling approach capable of acquiring data at rates up to 22.7 samples per second in a 384-well microtiter plate. At top speed, less than 1% analyte carryover is observed from well-to-well and signal intensity relative standard deviations (RSD) of 11.5% and 20.9% for 3 μM 1-hydroxymidazolam and 12 μM dextrorphan, respectively, are achieved. The ability to perform parallel kinetics studies on 384 samples with ~30s time resolution using an isocitrate dehydrogenase 1 (IDH1) enzyme assay is shown. Finally, we demonstrate the repeatability and throughput of our approach by measuring 115,200 samples from 300 microtiter plate reads consecutively over 5.54 hours with RSDs under 8.14% for each freshly introduced plate. Taken together, these results demonstrate the use of IR-MALDESI at sample acquisition rates that surpass other currently reported direct sampling mass spectrometry approaches used for high throughput compound screening.

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