bluuebunny/crossref_metadata_2025 huggingface dataset:
Pontixanthobacter rizhaonensis sp. nov., a marine bacterium isolated from surface seawater of the Yellow Sea, and proposal of Pseudopontixanthobacter gen. nov., Pseudopontixanthobacter confluentis comb. nov. and Pseudopontixanthobacter sediminis comb. nov.
Authors: Liu Ang , Xue Qing-Jie , Li Shi-Gen , Zhang Yan-Jiao
Published: April 2021

A bacterial strain designated RZ02T was isolated from surface seawater collected from the Yellow Sea in PR China and characterized by polyphasic taxonomy. Cells of strain RZ02T were Gram-stain-negative, aerobic, non-motile, catalase- and oxidase-positive rods forming ochre-pigmented colonies. Growth occurred at 7–36 °C (optimum, 30 °C), at pH 6.0–9.0 (optimum, pH 7.0) and with 1–5 % (optimum, 2 %) NaCl. The major cellular fatty acids (>10 %) of strain RZ02T were summed feature 8 (C18 : 1
 ω6c and/or C18 : 1
 ω7c), summed feature 3 (C16 : 1
 ω7c and/or C16 : 1
 ω6c) and C16 : 0. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, diphosphatidylglycerol and sphingoglycolipid. The genome size of strain RZ02T was 2.79 Mbp with a G+C content of 55.5 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain RZ02T was mostly related to

Pontixanthobacter luteolus

SW-109T and

Pontixanthobacter aestiaquae

HDW-31T (97.3 and 97.1% sequence similarity, respectively), and formed a phyletic lineage with members of the genus

Pontixanthobacter

. The phylogenetic analysis based on the up-to-date bacterial core gene sequences confirmed that strain RZ02T clustered within the genus

Pontixanthobacter

. The average nucleotide identity and in silico DNA–DNA hybridization values between strain RZ02T and

P. luteolus

SW-109T and

P. aestiaquae

HDW-31T were 72.8 and 72.9 % and 18.7 and 18.5%, respectively. Based on these evidences, strain RZ02T is proposed to represent a novel species of the genus

Pontixanthobacter

under the name Pontixanthobacter rizhaonensis sp. nov. The type strain is RZ02T (=KCTC 62828T=MCCC 1K04521T). In addition, based on the results of whole genome analyses, proposals of

Pseudopontixanthobacter

gen. nov., Pseudopontixanthobacter confluentis comb. nov. and Pseudopontixanthobacter sediminis comb. nov. are also included.
Rapid nanopore-based DNA sequencing protocol of antibiotic-resistant bacteria for use in surveillance and outbreak investigation
Authors: Ferreira Fabienne Antunes , Helmersen Karin , Visnovska Tina , Jørgensen Silje Bakken , Aamot Hege Vangstein
Published: April 2021

Outbreak investigations are essential to control and prevent the dissemination of pathogens. This study developed and validated a complete analysis protocol for faster and more accurate surveillance and outbreak investigations of antibiotic-resistant microbes based on Oxford Nanopore Technologies (ONT) DNA whole-genome sequencing. The protocol was developed using 42 methicillin-resistant

Staphylococcus aureus

(MRSA) isolates identified from former well-characterized outbreaks. The validation of the protocol was performed using Illumina technology (MiSeq, Illumina). Additionally, a real-time outbreak investigation of six clinical

S. aureus

isolates was conducted to test the ONT-based protocol. The suggested protocol includes: (1) a 20 h sequencing run; (2) identification of the sequence type (ST); (3) de novo genome assembly; (4) polishing of the draft genomes; and (5) phylogenetic analysis based on SNPs. After the sequencing run, it was possible to identify the ST in 2 h (20 min per isolate). Assemblies were achieved after 4 h (40 min per isolate) while the polishing was carried out in 7 min per isolate (42 min in total). The phylogenetic analysis took 0.6 h to confirm an outbreak. Overall, the developed protocol was able to at least discard an outbreak in 27 h (mean) after the bacterial identification and less than 33 h to confirm it. All these estimated times were calculated considering the average time for six MRSA isolates per sequencing run. During the real-time

S. aureus

outbreak investigation, the protocol was able to identify two outbreaks in less than 31 h. The suggested protocol enables identification of outbreaks in early stages using a portable and low-cost device along with a streamlined downstream analysis, therefore having the potential to be incorporated in routine surveillance analysis workflows. In addition, further analysis may include identification of virulence and antibiotic resistance genes for improved pathogen characterization.
Complete, closed and curated genome sequences of Photobacterium damselae subsp. piscicida isolates from Australia indicate mobilome-driven localized evolution and novel pathogenicity determinants
Authors: Baseggio Laura , Rudenko Oleksandra , Buller Nicky , Landos Matt , Englestädter Jan , Barnes Andrew C.
Published: April 2021

Despite the recent advances in sequencing technologies, the complete assembly of multi-chromosome genomes of the

Vibrionaceae

, often containing several plasmids, remains challenging. Using a combination of Oxford Nanopore MinION long reads and short Illumina reads, we fully sequenced, closed and curated the genomes of two strains of a primary aquatic pathogen

Photobacterium damselae

subsp.

piscicida

isolated in Australia. These are also the first genome sequences of

P. damselae

subsp.

piscicida

isolated in Oceania and, to our knowledge, in the Southern hemisphere. We also investigated the phylogenetic relationships between Australian and overseas isolates, revealing that Australian

P. damselae

subsp.

piscicida

are more closely related to the Asian and American strains rather than to the European ones. We investigated the mobilome and present new evidence showing that a host specialization process and progressive adaptive evolution to fish are ongoing in

P. damselae

subsp.

piscicida

, and are largely mediated by transposable elements, predominantly in chromosome 2, and by plasmids. Finally, we identified two novel potential virulence determinants in

P. damselae

subsp.

piscicida

– a chorismate mutase gene, which is ubiquitously retained and co-localized with the AIP56 apoptogenic toxin-encoding gene on the pPHDP10 plasmid, and transfer-messenger RNA gene ssrA located on the main chromosome, homologous to a critical-to-virulence determinant in

Yersinia pseudotuberculosis

. Our study describes, to our knowledge, the only fully closed and manually curated genomes of

P. damselae

subsp.

piscicida

available to date, offering new insights into this important fish pathogen and its evolution.
Donor genetic variants in interleukin-6 and interleukin-6 receptor associate with biopsy-proven rejection following kidney transplantation
Authors: Poppelaars Felix , Gaya da Costa Mariana , Eskandari Siawosh K. , Damman Jeffrey , Seelen Marc A.
Published: April 2021

Rejection after kidney transplantation remains an important cause of allograft failure that markedly impacts morbidity. Cytokines are a major player in rejection, and we, therefore, explored the impact of interleukin-6 (IL6) and IL-6 receptor (IL6R) gene polymorphisms on the occurrence of rejection after renal transplantation. We performed an observational cohort study analyzing both donor and recipient DNA in 1,271 renal transplant-pairs from the University Medical Center Groningen in The Netherlands and associated single nucleotide polymorphisms (SNPs) with biopsy-proven rejection after kidney transplantation. The C-allele of the IL6R SNP (Asp358Ala; rs2228145 A>C, formerly rs8192284) in donor kidneys conferred a reduced risk of rejection following renal transplantation (HR 0.78 per C-allele; 95%-CI 0.67–0.90; P=0.001). On the other hand, the C-allele of the IL6 SNP (at position-174 in the promoter; rs1800795 G>C) in donor kidneys was associated with an increased risk of rejection for male organ donors (HR per C-allele 1.31; 95%-CI 1.08–1.58; P=0.0006), but not female organ donors (P=0.33). In contrast, neither the IL6 nor IL6R SNP in the recipient showed an association with renal transplant rejection. In conclusion, donor IL6 and IL6R genotypes but not recipient genotypes represent an independent prognostic marker for biopsy-proven renal allograft rejection.
Tracing the Indian Population Ancestry bycis-linked Mutations inHBBGene
Authors: Panja Amrita , Chowdhury Prosanto , basu Anupam
Published: April 2021

Background

Human left their genetic footprints during the time of migration throughout the different countries all over the world. Human evolution was studied through various markers. India is a country of rich heritage and cultural diversity. The modern Indian population is derived from two ancestral groups, viz.-Ancestral North Indians (ANI) and Ancestral South Indians (ASI).

Aim

Finding out the migratory route of the modern Indian population by studying ‘cis’ acting mutations of human beta-globin (HBB) genes.

Subjects and methods

A total of 120 thalassemia subjects were enrolled. DNA sequencing was done for mutation detection in theHBBgene. Some previous literature reviews were gone through for tracing mutations, all over the world and in the Indian subcontinent.

Results

Nine thalassemia patients were found whereHBB:c.92G>C andHBB:c.-92C>G mutations co-exist together in ‘cis’ condition. Only one patient hadHBB:c.51delC andHBB:c.33C>A. The pedigree analysis confirmed the presence of these mutations in ‘cis’ condition and vertical transmission from one generation to the next. Literature reviews also reassure the co-existence of these mutations from different countries.

Conclusion

The co-existence of these ‘cis’ acting mutations helps to point out the possible migratory route of ANI population after venturing out of Africa.
B and T cell immune responses elicited by the BNT162b2 (Pfizer–BioNTech) COVID-19 vaccine in nursing home residents
Authors: Torres Ignacio , Albert Eliseo , Giménez Estela , Alcaraz María Jesús , Botija Pilar , Amat Paula , Remigia María José , Beltrán María José , Rodado Celia , Huntley Dixie , Olea Beatriz , Navarro David
Published: April 2021

Objectives

The immunogenicity of the BNT162b2 COVID-19 vaccine is understudied in elderly people with comorbidities. We assessed SARS-CoV-2-S-targeted antibody and T cell responses following full vaccination in nursing home residents (NHR).

Methods

We recruited 60 NHR (44 female; median age, 87.5 years), of whom 10 had previously had COVID-19, and 18 healthy controls (15 female; median age, 48.5 years). Pre- and post-vaccination blood specimens were available for quantitation of total antibodies binding RBD and enumeration of SARS-CoV-2-S-reactive IFN-γ CD4+ and CD8+ T cells by flow cytometry.

Results

The seroconversion rate in presumably SARS-CoV-2 naïve NHR (95.3%), either with or without comorbidities, was similar to controls (94.4%). A robust booster effect was documented in NHR with prior COVID-19. Plasma antibody levels were higher in convalescent NHR than in individuals across the other two groups. A large percentage of NHR had SARS-CoV-2 S-reactive IFN-γ CD8+ and/or CD4+ T cells at baseline, in contrast to healthy controls. Either CD8+ and/or CD4+ T-cell responses were documented in all control subjects after vaccination. Contrariwise, the percentage of NHR exhibiting detectable SARS-CoV-2 IFN-γ CD8+ or CD4+ T-cell responses (or both), irrespective of their baseline SARS-CoV-2 infection status, dropped consistently after vaccination. Overall, SARS-CoV-2 IFN-γ CD8+ and CD4+ T-cell responses in NHR decreased in post-vaccination specimens.

Conclusion

The BNT162b2 COVID-19 vaccine elicits robust SARS-CoV-2-S antibody responses in NHR. Nevertheless, the frequency and magnitude of detectable SARS-CoV-2 IFN-γ T-cell responses after vaccination was lower in NHR compared to controls.
SCALP HIGH FREQUENCY OSCILLATION RATE DEPENDS ON SLEEP STAGE AND DECREASES WITH TIME SPENT IN SLEEP
Authors: Cserpan Dorottya , Rosch Richard , Lo Biundo Santo Pietro , Sarnthein Johannes , Ramantani Georgia
Published: April 2021

High frequency oscillations (HFO) in scalp EEG are a new and promising epilepsy biomarker. HFO analysis is typically restricted to random and relatively brief sleep segments. However, considerable fluctuations of HFO rates have been observed over the recording nights, particularly in relation to sleep stages and cycles. Here, we identify the timing within the sleep period and the minimal data interval length that allow for sensitive and reproducible detection of scalp HFO. We selected 16 seizure-free whole-night scalp EEG recordings of children and adolescents with focal lesional epilepsy (median age 7.6 y, range 2.2-17.4 y). We used an automated and clinically validated HFO detector to determine HFO rates (80-250 Hz) in bipolar channels. To identify significant variability over different NREM sleep stages and over time spent in sleep, we modelled HFO rate as a Poisson process. We analysed the test-retest reliability to evaluate the reproducibility of HFO detection across recording intervals. Scalp HFO rates were higher in N3 than in N2 sleep and highest in the first sleep cycle, decreasing with time spent in sleep. In N3 sleep, the median reliability of HFO detection increased from 67% to 79% to 100% for 5-, 10-, and 15-min data intervals, improving significantly (p=0.004) from 5 to 10 min but not from 10 to 15 min. In this analysis of whole-night scalp EEG, we identified the first N3 sleep stage as the most sensitive time window for HFO rate detection. N3 data intervals of 10 min duration are required and sufficient for reliable measurements of HFO rates. Our study provides a robust and reliable framework for implementing scalp HFO as an EEG biomarker in pediatric epilepsy.
ReCOVer study: A Cross-sectional Observational Study to Identify the Rehabilitation Need in Post-discharge COVID-19 Survivors
Authors: Swarnakar Raktim , Yadav S. L. , Srikumar V , Soni Kapil Dev , Aggrawal Richa , Trikha Anjan
Published: April 2021

Introduction

With the increasing number of Coronavirus disease-2019 (COVID-19) cases there is simultaneous increase in recovered cases too. There are many post-covid complications where need for rehabilitation intervention is very conspicuous especially pulmonary, neurological complications. Hence data are of utmost importance to find out those rehabilitation needs among post-covid survivors.

Methods and analysis

ReCOVer (Rehabilitation Need in Post-discharge COVID-19 Survivors), a cross-sectional observational study protocol has been planned to find out rehab-need by assessing International Classification of Functioning, Disability and Health (ICF) core data set, COVID-19 Yorkshire Rehab Screen (C19-YRS) tool, The Post-COVID-19 Functional Status (PCFS) scale, barriers to functional independence and rehab services (affordability & availability). Post-discharge (minimum 1 weeks) Covid patients (required hospitalisation) will be included in the study. Study will be conducted through Telerehabilitation facility. Study will conform to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.

Ethics and dissemination

Study received ethical approval from Institute Ethics Committee, All India Institute of Medical Sciences (AIIMS), New Delhi, India. Findings will be disseminated at scientific conferences/meetings, peer-reviewed journals, and to relevant stakeholders including the ministry of health (if required).
Accounting for age-of-onset and family history improves power in genome-wide association studies
Authors: Pedersen Emil M , Agerbo Esben , Plana-Ripoll Oleguer , Grove Jakob , Dreier Julie W. , Musliner Katherine L. , Bækvad-Hansen Marie , Athanasiadis Georgios , Schork Andrew , Bybjerg-Grauholm Jonas , Hougaard David M. , Werge Thomas , Nordentoft Merete , Mors Ole , Dalsgaard Søren , Christensen Jakob , Børglum Anders D. , Mortensen Preben B. , McGrath John J. , Privé Florian , Vilhjálmsson Bjarni J.
Published: April 2021

Genome-wide association studies (GWAS) have revolutionized human genetics, allowing researchers to identify thousands of disease-related genes and possible drug targets. However, case-control status does not account for the fact that not all controls may have lived through their period of risk for the disorder of interest. This can be quantified by examining the age-of-onset distribution and the age of the controls or the age-of-onset for cases. The age-of-onset distribution may also depend on information such as sex and birth year. In addition, family history is not routinely included in the assessment of control status. Here we present LT-FH++, an extension of the liability threshold model conditioned on family history (LT-FH), that jointly accounts for age-of-onset and sex, as well as family history. Using simulations, we show that, when family history and the age-of-onset distribution are available, the proposed approach yields large power gains over both LT-FH and genome-wide association study by proxy (GWAX). We applied our method to four psychiatric disorders available in the iPSYCH data, and to mortality in the UK Biobank, finding 20 genome-wide significant associations with LT-FH++, compared to 10 for LT-FH and 8 for a standard case-control GWAS. As more genetic data with linked electronic health records become available to researchers, we expect methods that account for additional health information, such as LT-FH++, to become even more beneficial.
Strengthened mutualistic adaptation between teosinte and its rhizosphere biota in cold climates
Authors: O’Brien Anna M. , Sawers Ruairidh J.H. , Gasca-Pineda Jaime , Baxter Ivan , Eguiarte Luis E. , Ross-Ibarra Jeffrey , Strauss Sharon Y.
Published: April 2021

While abiotic environments consistently shape local adaptation, the strength of local adaptation to biotic interactions may vary more. One theory, COCO (CO-evolutionary Outcomes across Conditionality), predicts it may be strongest where species experience greater stress, because stress increases fitness impacts of species interactions. For example, in plant interactions with rhizosphere biota, positive outcomes increase with stress from low soil fertility, drought and cold.

To investigate the influence of abiotic stress gradients on adaptation between plants and rhizosphere biota, we used a greenhouse common garden experiment recombining teosinte,Zea maysssp.mexicana(wild relative of maize), and rhizosphere biota, collected across a stress gradient (elevational variation in temperature, precipitation, and nutrients).

We found stronger local adaptation between teosinte and rhizosphere biota from colder, more stressful sites, as expected by COCO. However, biota from less stressful, warmer sites provided greater average benefits across teosinte populations. Links between plant traits and 20-element profiles of plant leaves explained fitness variation, persisted in the field, were influenced by both plants and biota, and largely reflected patterns of local adaptation.

In sum, we uncovered greater local adaptation to biotic interactions in colder sites, and that both plants and rhizosphere biota affect the expression of plant phenotypes.
TheMagnaporthe oryzaeMAP kinase Pmk1 regulates polycomb repressive complex 2 to reprogram genes expression for biotrophic growth
Authors: Cai Xuan , Tang Bozeng , Hendy Ahmed , Ren Zhiyong , Liu Caiyun , Kamran Muhammad , Xing Junjie , Zheng Lu , Liu Hao , Huang Junbing , Chen Xiao-Lin
Published: April 2021

Biotrophic and hemibiotrophic fungi have evolved the ability to colonize living plant cells, but how they establish biotrophic growth by remodeling gene expression is poorly understood. By usingin plantainvasive hyphae (IH) ofMagnaporthe oryzaeto perform an integrated Chromatin immunoprecipitation sequencing (ChIPseq) and RNA-seq analysis, combining with biological and cellular analyses, we found Polycomb repressive complex 2 (PRC2)-mediated epigenetic repression plays a key role in regulating biotrophic growth. ChIPseq for biotrophic IH samples identified 1701 PRC2 target genes. RNA-seq analysis showed that expression of 462 PRC2 target genes were up-regulated in the Δsuz12mutant, while 82 were down-regulated, indicating a major role of PRC2 in gene repression of IH. During biotrophic growth, PRC2 repressed fungal cell wall synthesis genes and extracellular enzyme genes required for penetration, and secondary metabolites biosynthesis genes required for necrotrophic growth. A great number of effector-encoding genes were repressed by PRC2, which were highly expressed during penetration stage, suggesting PRC2 coordinates biotrophic growth by regulating effector suppression for immune evasion. This regulation was finely coordinated by Pmk1, through regulating phosphorylation, nuclear localization and protein abundance of Suz12. Our results indicate that the Pmk1-PRC2 regulatory module is required for gene remodeling to facilitate biotrophic growth inM. oryzae.

IMPORTANCE

Biotrophic and hemibiotrophic fungi establish a biotrophic stage for infection in host cells. For example,M. oryzaeforms appressoria to penetrate host cell and establish a biotrophic growth stage for infection. How gene expression patterns are elaborately controlled for fungal biotrophic growth is largely unknown. In this study, we found that, the PRC2-mediated H3K27me3 repressed fungal penetration-required cell wall synthesis genes and extracellular enzyme genes, and necrotrophic growth-required secondary metabolites biosynthesis genes for biotrophic growth. Interestingly, a great number of effector-encoding genes were also repressed by PRC2 at biotrophic stage, which were highly expressed at penetration stage, suggesting PRC2 coordinates biotrophic growth by regulating effector suppression for immune evasion. The PRC2-mediated epigenetic repression is therefore required for the gene expression remodeling during fungal infection. This regulation was finely coordinated by Pmk1, through regulating nuclear localization and protein abundance of the PRC2 component Suz12.
Inference of Morphogen Gradient Precision from Molecular Noise Data
Authors: Vetter Roman , Iber Dagmar
Published: April 2021

During development, morphogen gradients provide spatial information for tissue patterning. Gradients and readout mechanisms are inevitably variable, yet the resulting patterns are strikingly precise. Measurement limitations currently preclude precise detection of morphogen gradients over long distances. Here, we develop a new formalism to estimate gradient precision along the entire patterning axis from measurements close to the source. Using numerical simulations, we infer gradient variability from measured molecular noise levels in morphogen production, decay, and diffusion. The predicted precision is much higher than previously measured—precise enough to allow even single gradients to define the central progenitor boundaries during neural tube development. Finally, we show that the patterning mechanism is optimized for precise progenitor cell numbers, rather than precise boundary positions, as the progenitor domain size is particularly robust to gradient alterations. We conclude that single gradients can yield the observed developmental precision, which provides new prospects for tissue engineering.
HIV-1 provirus transcription and translation in macrophages differs from pre-integrated cDNA complexes and requires E2F transcriptional programs
Authors: Lim Albebson L. , Moos Philip , Pond Christopher D. , Larson Erica C. , Martins Laura J. , Szaniawski Matthew A , Planelles Vicente , Barrows Louis R.
Published: April 2021

HIV-1 cDNA pre-integration complexes have been shown to persist for weeks in macrophages and to be transcriptionally active. Early and late gene transcripts are produced, along with some viral proteins, yet whole virus is not. While previous work has focused on the transcription and translation of HIV-1 genes; our understanding of cellular milieu that accompanies viral production is incomplete. We have used anin vitrosystem to model HIV-1 infection of macrophages, and single cell RNA sequencing (scRNA-seq) to compare the transcriptomes of uninfected cells, cells harboring pre-integration HIV-1 complexes (PIC) and those containing integrated provirus and actively making late HIV proteins. These are also compared to control cells, not exposed to virus.

Several observations provide new perspective on the effects of HIV-1 transcription from pre-integrated cDNA versus from integrated provirus. First, HIV-1 transcript levels do not necessarily correlate with virus production, cells harboring PIC cDNA have transcript loads comparable to cells transcribing from provirus and making p24, mCherry, and vpu proteins. Second, all HIV-1 transcripts are easily detectable in abundance from PIC cDNA transcription, as is the case with cells transcribing from provirus, although the frequency of PIC cells with detectable gag-pol, tat, env, and nef transcripts is higher than the corresponding frequencies observed for “Provirus cells”. Third, the background transcriptomes of cells harboring pre- integrated HIV-1 cDNA are not otherwise detectably altered from cells not containing any HIV- 1 transcript. Fourth, integration and production of p24, mCherry, and Vpu proteins is accompanied by a switch from transcriptomes characterized by NFkB and AP-1 promoted transcription to a transcriptome characterized by E2F family transcription products. While some of these observations may seem heretical, single cell analysis provides a more nuanced understanding of PIC cDNA transcription and the transcriptomic changes that support HIV-1 protein production from integrated provirus.

Author Summary

Single cell analysis is able to distinguish between HIV-1 infected macrophage cells that are transcribing pre-integrated HIV-1 cDNA and those transcribing HIV-1 provirus. Only cells transcribing HIV-1 provirus are making p24, marker mCherry and Vpu proteins, which corresponds with a change in the host cell’s background transcriptome from one expressing viral restriction and immunological response genes to one that is expressing genes associated with cell replication and oxidative phosphorylation.
Viromes in Marine Ecosystems Reveal Remarkable Invertebrate RNA Virus Diversity
Authors: Zhang Yu-Yi , Chen Yicong , Wei Xiaoman , Cui Jie
Published: April 2021

Ocean viromes remain poorly understood and little is known about the ecological factors driving aquatic RNA virus evolution. In this study, we used a meta-transcriptomic approach to characterize the viromes of 58 marine invertebrate species across three seas. This revealed the presence of 315 newly identified RNA viruses in nine viral families or orders (Durnavirales, Totiviridae, Bunyavirales, Hantaviridae, Picornavirales, Flaviviridae, Hepelivirales, SolemoviridaeandTombusviridae), with most of them are sufficiently divergent to the documented viruses. With special notice that we first time revealed an ocean virus rooting to mammalian hantaviruses. We also found evidence for possible host sharing and switch events during virus evolution. In sum, we demonstrated the hidden diversity of marine invertebrate RNA viruses.
Three bacterium-plasmid golden combinations facilitate the spread of ST11/CG258 carbapenemase-producingKlebsiella pneumoniaein China
Authors: Li Cuidan , Jiang Xiaoyuan , Yang Tingting , Ju Yingjiao , Yin Zhe , Yue Liya , Ma Guanan , Wang Xuebing , Jing Ying , Luo Xinhua , Li Shuangshuang , Yang Xue , Chen Fei , Zhou Dongsheng
Published: April 2021

Carbapenemase-producingKlebsiella pneumoniae(cpKP) poses serious threats to public health. Previous studies showed that only ST11/CG258-cpKP successfully disseminated in China, however, the underlying genetic bases are still unknown. We conducted a comprehensive genomic-epidemiology analysis on 420 cpKP isolates from 70 hospitals in 24 Chinese provinces during 2009-2017 based on short-/long-reads sequencing. Three ‘golden’ combinations of host––blaKPC-carrying plasmids (Clade 3.1+3.2—IncFIIpHN7A8, Clade 3.1+3.2—IncFIIpHN7A8:IncR, Clade 3.3—IncFIIpHN7A8:IncpA1763-KPC) endowed cpKP with advantages both in genotypes (strong-correlation/co-evolution) and phenotypes (resistance/growth/competition), thereby facilitating nationwide spread of ST11/CG258-cpKP. Intriguingly, Bayesian skyline illustrated that the three ‘golden’ combinations might directly lead to the strong population expansion during 2007-2008 and subsequent maintenance of the dissemination of ST11/CG258-cpKP after 2008. We tested drug-resistance profiles and proposed combination treatment regimens for CG258/non-CG258 cpKP. Our findings systematically revealed the molecular-epidemiology and genetic-basis for dissemination of Chinese ST11/CG258 cpKP and reminded us to monitor the ‘golden’ combinations of cpKP- plasmid closely.
Mapping the biogenesis of forward programmed megakaryocytes from induced pluripotent stem cells
Authors: Lawrence Moyra , Shahsavari Arash , Bornelöv Susanne , Moreau Thomas , Kania Katarzyna , Paramor Maike , McDonald Rebecca , Baye James , Perrin Marion , Steindel Maike , Jimenez-Gomez Paula , Penfold Christopher , Mohorianu Irina , Ghevaert Cedric
Published: April 2021

Platelet deficiency, known as thrombocytopenia, can cause haemorrhage and is treated with platelet transfusions. We developed a system for the production of platelet precursor cells, megakaryocytes, from pluripotent stem cells. These cultures can be maintained for >100 days, implying culture renewal by megakaryocyte progenitors (MKPs). However, it is unclear whether the MKP statein vitromirrors the statein vivo, and MKPs cannot be purified using conventional surface markers. We performed single cell RNA sequencing throughoutin vitrodifferentiation and mapped each state to its equivalentin vivo. This enabled the identification of 5 surface markers which reproducibly purify MKPs, allowing us an insight into their transcriptional and epigenetic profiles. Finally, we performed culture optimisation, increasing MKP production. Altogether, this study has mapped parallels between the MKP statesin vivoandin vitroand allowed the purification of MKPs, accelerating the progress ofin vitro-derived transfusion products towards the clinic.
Evolutionary rates of testes-expressed genes differ in monogamous and promiscuousPeromyscusspecies
Authors: Gozashti Landen , Corbett-Detig Russell , Roy Scott W.
Published: April 2021

Reproductive proteins, including those expressed in the testes, are among the fastest evolving proteins across the tree of life. Sexual selection on traits involved in sperm competition is thought to be a primary driver of testes gene evolution and is expected to differ between promiscuous and monogamous species due to intense competition between males to fertilize females in promiscuous lineages and lack thereof in monogamous ones. Here, we employ the rodent genusPeromyscusas a model to explore differences in evolutionary rates between testes-expressed genes in monogamous and promiscuous species. We find candidate genes that may be associated with increased sperm production in promiscuous species and gene ontology categories that show patterns of molecular convergence associated with phenotypic convergence in independently evolved monogamous species. Overall, our results highlight the possible molecular consequences of differences in mating system, likely due to differences in selective pressures.
No evidence that HLA genotype influences the driver mutations that occur in cancer patients
Authors: Kherreh Noor , Cleary Siobhán , Seoighe Cathal
Published: April 2021

The major histocompatibility (MHC) molecules are capable of presenting neoantigens resulting from somatic mutations on cell surfaces, potentially directing immune responses against cancer. This led to the hypothesis that cancer driver mutations may occur in gaps in the capacity to present neoantigens that are dependent on MHC genotype. If this is correct, it has important implications for understanding oncogenesis and may help to predict driver mutations based on genotype data. In support of this hypothesis, it has been reported that driver mutations that occur frequently tend to be poorly presented by common MHC alleles and that the capacity of a patient’s MHC alleles to present the resulting neoantigens is predictive of the driver mutations that are observed in their tumour. Here we show that these reports of a strong relationship between driver mutation occurrence and patient MHC alleles are a consequence of unjustified statistical assumptions. Our reanalysis of the data provides no evidence of an effect of MHC genotype on the oncogenic mutation landscape.
Invasive alien mammals of European Union concern
Authors: Tedeschi Lisa , Biancolini Dino , Capinha César , Rondinini Carlo , Essl Franz
Published: April 2021

Biological invasions have emerged as one of the main drivers of biodiversity change and decline, and numbers of alien species are rapidly rising. The European Union established a dedicated regulation to limit the impacts of invasive alien species (IAS), which is focused on a Union List of IAS of particular concern. However, no previous study has specifically addressed the ecology of invasive alien mammals included in the Union List.

We performed a systematic review of published literature on these species. We retrieved 262 studies dealing with 16 species, and we complemented these with the most up-to-date information extracted from global databases on IAS.

We show that most of the study species reached Europe as pets that escaped from captivity or were intentionally released. On average, 1.2 species’ new first records/year were documented in European countries in the period 1981-2020, and most species are still expanding their alien ranges colonising neighbouring territories. France, Germany, Italy, and The Netherlands are the most invaded nations, and the muskrat (Ondatra zibethicus), the raccoon dog (Nyctereutes procyonoides), and the American mink (Neovison vison) are the most widespread species, having invaded at least 27 countries each. Invasive mammals of European Union concern are threatening native biodiversity and human well-being: worryingly, 81.3% of the study species are implicated in the epidemiological cycle of zoonotic pathogens.

Containing the secondary spread to further countries is of paramount importance to avoid the establishment of new populations of invasive mammals and the related impacts on native communities, ecosystem services, and human health.

Our results offer the most updated compendium on the ecology of invasive mammals of European Union concern, that can be used to assist environmental policies, identify and subsequently fill knowledge gaps, and inform stakeholders.

GRAPHICAL ABSTRACT

Graphical abstract: Invasive alien mammals of European Union concern.

The figure illustrates how the introduction of a species in few new areas, followed by a lag phase of adaptation and sometimes enriched by further subsequent releases, can rapidly lead to the colonisation of large parts of a continent. On the top left, a heat map with species’ richness in countries of Europe. On the top right, a word cloud with the main keywords of our literature search and some of the study species’ names. On the bottom left, four out of 16 study species: in clockwise order, the raccoon dog (Nyctereutes procyonoides), the muskrat (Ondatra zibethicus), the American mink (Neovison vison), and the raccoon (Procyon lotor). On the bottom right, the temporal distribution of the first records of the study species in the countries of Europe.
Genomic time-series data show that gene flow maintains high genetic diversity despite substantial genetic drift in a butterfly species
Authors: Gompert Zachariah , Springer Amy , Brady Megan , Chaturvedi Samridhi , Lucas Lauren K.
Published: April 2021

Effective population size affects the efficacy of selection, rate of evolution by drift, and neutral diversity levels. When species are subdivided into multiple populations connected by gene flow, evolutionary processes can depend on global or local effective population sizes. Theory predicts that high levels of diversity might be maintained by gene flow, even very low levels of gene flow, consistent with species long-term effective population size, but tests of this idea are mostly lacking. Here, we show thatLycaeidesbutterfly populations maintain low contemporary (variance) effective population sizes (e.g., ∼200 individuals) and thus evolve rapidly by genetic drift. Contemporary effective sizes were consistent with local census populations sizes. In contrast, populations harbored high levels of genetic diversity consistent with an effective population size several orders of magnitude larger. We hypothesized that the differences in the magnitude and variability of contemporary versus long-term effective population sizes were caused by gene flow of sufficient magnitude to maintain diversity but only subtly affect evolution on generational time scales. Consistent with this hypothesis, we detected low but non-trivial gene flow among populations. Furthermore, using population-genomic time-series data, we documented patterns consistent with predictions from this hypothesis, including a weak but detectable excess of evolutionary change in the direction of the mean (migrant gene pool) allele frequencies across populations, and consistency in the direction of allele frequency change over time. The documented decoupling of diversity levels and short-term change by drift inLycaeideshas implications for our understanding of contemporary evolution and the maintenance of genetic variation in the wild.
Tracheal motile cilia in mice require CAMSAP3 for formation of central microtubule pair and coordinated beating
Authors: Saito Hiroko , Matsukawa-Usami Fumiko , Fujimori Toshihiko , Kimura Toshiya , Ide Takahiro , Yamamoto Takaki , Shibata Tatsuo , Onoue Kenta , Okayama Satoko , Yonemura Shigenobu , Misaki Kazuyo , Soba Yurina , Kakui Yasutaka , Sato Masamitsu , Toya Mika , Takeichi Masatoshi
Published: April 2021

Motile cilia of multiciliated epithelial cells undergo synchronized beating to produce fluid flow along the luminal surface of various organs. Each motile cilium consists of an axoneme and a basal body, which are linked by a ‘transition zone’. The axoneme exhibits a characteristic 9+2 microtubule arrangement important for ciliary motion, but how this microtubule system is generated is not yet fully understood. Here we show that CAMSAP3, a protein that can stabilize the minus end of a microtubule, concentrates at multiple sites of the cilium–basal body complex, including the upper region of the transition zone or the axonemal basal plate where the central pair of microtubules (CP) initiates. CAMSAP3 dysfunction resulted in loss of the CP and partial distortion of the basal plate, as well as the failure of multicilia to undergo synchronized beating. These findings suggest that CAMSAP3 plays pivotal roles in the formation or stabilization of the CP by localizing at the basal region of the axoneme, and thereby supports the coordinated motion of multicilia in airway epithelial cells.
Two isoleucyl tRNAs that decode ‘synonymous’ codons divergently regulate breast cancer progression
Authors: Earnest-Noble Lisa B. , Hsu Dennis , Asgharian Hosseinali , Nandan Mandayam , Passarelli Maria C. , Goodarzi Hani , Tavazoie Sohail F.
Published: April 2021

The human genome contains 61 codons that encode for the 20 amino acids. The synonymous codons of a given amino acid are decoded by a set of transfer RNAs (tRNAs) called isoacceptors. We report the surprising observation that two isoacceptor tRNAs that decode synonymous codons are modulated in opposing directions during breast cancer progression. Specifically, tRNAIleUAUis upregulated, whereas tRNAIleGAUis repressed as breast cancer cells attained enhanced metastatic capacity. Functional studies revealed that tRNAIleUAUpromoted and tRNAIleGAUsuppressed metastatic colonization. The expression of these tRNAs mediated opposing effects on codon-dependent translation of growth promoting genes. Consistent with this, multiple mitotic gene sets in the human genome are significantly enriched in the codon cognate to the growth-promoting tRNAIleUAUand significantly depleted of the codon cognate to the growth-suppressive tRNAIleGAU. Our findings uncover a specific isoacceptor tRNA pair that act in opposition—divergently regulating genes that contribute to growth and a disease phenotype. The degeneracy of the genetic code can thus be biologically exploited by human cancer cells via tRNA isoacceptor shifts that facilitate the transition towards a growth-promoting state.
Meikin synergizes with shugoshin to protect cohesin Rec8 during meiosis I
Authors: Ma Wei , Zhou Jingwen , Chen Jian , Carr Antony M. , Watanabe Yoshinori
Published: April 2021

The conserved meiosis-specific kinetochore regulator, meikin (Moa1 in fission yeast) plays a central role in establishing meiosis-specific kinetochore function. However, the underlying molecular mechanisms remain elusive. Here, we show how Moa1 regulates centromeric cohesion protection, a function that has been previously attributed to shugoshin (Sgo1). Moa1 is known to associate with Plo1 kinase. We explore Plo1-dependent Rec8 phosphorylation and identify a key phosphorylation site required for cohesion protection. The phosphorylation of Rec8 by Moa1-Plo1 potentiates the activity of PP2A associated with Sgo1. This leads to dephosphorylation of Rec8 at another site, which thereby prevents cleavage of Rec8 by separase.
Protein phosphatases in the RNAPII transcription cycle: erasers, sculptors, gatekeepers, and potential drug targets
Authors: Cossa Giacomo , Parua Pabitra K. , Eilers Martin , Fisher Robert P.
Published: April 2021

The transcription cycle of RNA polymerase II (RNAPII) is governed at multiple points by opposing actions of cyclin-dependent kinases (CDKs) and protein phosphatases, in a process with similarities to the cell division cycle. While important roles of the kinases have been established, phosphatases have emerged more slowly as key players in transcription, and large gaps remain in understanding of their precise functions and targets. Much of the earlier work focused on the roles and regulation of sui generis and often atypical phosphatases—FCP1, Rtr1/RPAP2, and SSU72—with seemingly dedicated functions in RNAPII transcription. Decisive roles in the transcription cycle have now been uncovered for members of the major phosphoprotein phosphatase (PPP) family, including PP1, PP2A, and PP4—abundant enzymes with pleiotropic roles in cellular signaling pathways. These phosphatases appear to act principally at the transitions between transcription cycle phases, ensuring fine control of elongation and termination. Much is still unknown, however, about the division of labor among the PPP family members, and their possible regulation by or of the transcriptional kinases. CDKs active in transcription have recently drawn attention as potential therapeutic targets in cancer and other diseases, raising the prospect that the phosphatases might also present opportunities for new drug development. Here we review the current knowledge and outstanding questions about phosphatases in the context of the RNAPII transcription cycle.
Structural and enhanced hydrogen storage properties of the Li12Mg3Si3Al phase
Authors: Pavlyuk Volodymyr , Ciesielski Wojciech , Kulawik Damian , Pavlyuk Nazar , Dmytriv Grygoriy
Published: April 2021

The multicomponent alumosilicide Li12Mg3Si3Al (cubic, space group I-43d, cI76) belongs to the structural family based on the Cu15Si4 type. The Li atoms are ordered and occupy the site with symmetry 1 and the Mg atoms occupy the site with -4.. symmetry. The Si/Al statistical mixture occupies the site with .3. symmetry. The coordination polyhedra around the Li atoms are 13-vertex distorted pseudo-Frank–Kasper polyhedra. The environments of the Mg and Si/Al atoms are icosahedral. The hydrogen storage characteristics of Li12Mg3Si3Al were investigated. The reversible hydrogen storage capacity of the title compound is excellent and the gravimetric storage capacity of this new material, corresponding to 9.1 wt% H2, is higher compared to Li12Mg3Si4 (8.8 wt%). The enthalpy of hydrogen desorption is 86 kJ mol−1 and is lower compared to known lithium-based hydrides.
Vitamins in wine: Which, what for, and how much?
Authors: Evers Marie Sarah , Roullier‐Gall Chloé , Morge Christophe , Sparrow Celine , Gobert Antoine , Alexandre Hervé
Published: April 2021

Vitamins are essential compounds to yeasts, and notably in winemaking contexts. Vitamins are involved in numerous yeast metabolic pathways, including those of amino acids, fatty acids, and alcohols, which suggests their notable implication in fermentation courses, as well as in the development of aromatic compounds in wines. Although they are major components in the course of those microbial processes, their significance and impact have not been extensively studied in the context of winemaking and wine products, as most of the studies focusing on the subject in the past decades have relied on relatively insensitive and imprecise analytical methods. Therefore, this review provides an extensive overview of the current knowledge regarding the impacts of vitamins on grape must fermentations, wine‐related yeast metabolisms, and requirements, as well as on the profile of wine sensory characteristics. We also highlight the methodologies and techniques developed over time to perform vitamin analysis in wines, and assess the importance of precisely defining the role played by vitamins in winemaking processes, to ensure finer control of the fermentation courses and product characteristics in a highly complex matrix.
Understanding the oral processing of solid foods: Insights from food structure
Authors: Guo Qing
Published: April 2021

Understanding the relationship between the structure of solid foods and their oral processing is paramount for enhancing features such as texture and taste and for improving health‐related factors such as management of body weight or dysphagia. This paper discusses the main aspects of the oral processing of solid foods across different categories: (1) oral physiology related to chewing, (2) in‐mouth food transformation, (3) texture perception, and (4) taste perception, and emphasis is placed on unveiling the underlying mechanisms of how food structure influences the oral processing of solid foods; this is exemplified by comparing the chewing behaviors for a number of representative solid foods. It highlights that modification of the texture/taste of food based on food structure design opens up the possibility for the development of food products that can be applied in the management of health.
Structural breakdown of starch‐based foods during gastric digestion and its link to glycemic response: In vivo and in vitro considerations
Authors: Nadia Joanna , Bronlund John , Singh Rajinder Paul , Singh Harjinder , Bornhorst Gail M.
Published: April 2021

The digestion of starch‐based foods in the small intestine as well as factors affecting their digestibility have been previously investigated and reviewed in detail. Starch digestibility has been studied both in vivo and in vitro, with increasing interest in the use of in vitro models. Although previous in vivo studies have indicated the effect of mastication and gastric digestion on the digestibility of solid starch‐based foods, the physical breakdown of starch‐based foods prior to small intestinal digestion is often less considered. Moreover, gastric digestion has received little attention in the attempt to understand the digestion of solid starch‐based foods in the digestive tract. In this review, the physical breakdown of starch‐based foods in the mouth and stomach, the quantification of these breakdown processes, and their links to physiological outcomes, such as gastric emptying and glycemic response, are discussed. In addition, the physical breakdown aspects related to gastric digestion that need to be considered when developing in vitro–in vivo correlation in starch digestion studies are discussed. The discussion demonstrates that physical breakdown prior to small intestinal digestion, especially during gastric digestion, should not be neglected in understanding the digestion of solid starch‐based foods.