bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of the kisspeptin/KISS1 receptor system in the testicular development of mice
Authors: Chiang Chi-Ming , Chiu Hsin-Yi , Jong De-Shien , Wu Leang-Shin , Lee Yue-Jia , Chiu Chih-Hsien 
Published: February 2021

Background:
Kisspeptin and its receptor KISS1R have been found to be essential regulators of reproductive function. Previous data have revealed the presence of Kiss1 and Kiss1r mRNAs in the hypothalamus and the testis of humans and rodents. However, the precise location and possible physiological role of the kisspeptin/KISS1R system in the testis remain ambiguous.

Methods:
We first produced an anti-KISS1R immunoglobulin Y antibody for KISS1R identification. To detect the exact sites of KISS1R and kisspeptin expression in the testis, we conducted immunohistochemistry assays on sections of testes. We used real-time polymerase chain reactions to identify Kiss1r in mice and to determine the expression levels of testicular genes. Finally, to verify the upstream regulation on the Kisspeptin/KISS1 receptor system, we treated primary mouse Leydig cells and MA-10 cells with luteinizing hormone (LH) and Br-cAMP, respectively, and examined Kiss1 and Kiss1r mRNA expression.

Results:
Immunohistochemistry assays revealed that kisspeptin was expressed in Leydig cells and KISS1R was localized in the seminiferous tubules. With real-time polymerase chain reactions, we found Kiss1r mRNA was constitutively expressed in the mouse testis from birth until the postnatal fourth week. Furthermore, mRNA expression of Kiss1 was synchronized with that of Insl3 and Cyp19a. However, the expression of the LH receptor-encoding gene increased 1 week earlier than did Kiss1 expression. This indicated that the kisspeptin/KISS1R system in the testis may be controlled by LH and cAMP signaling pathways. Finally, we confirmed that Kiss1 mRNA expression was increased in both LH-treated primary Leydig cells and Br-cAMP-treated MA-10 cells (p < 0.05). On the other hand, cotreatment of both cell lines with Br-cAMP and a protein kinase A inhibitor RP-cAMP significantly suppressed 50% of Br-cAMP-induced Kiss1 expression (p < 0.05).

Conclusion:
We discovered that Kiss1 expression in mouse Leydig cells was induced by LH through the cAMP/PKA pathway. Based on the presence of kisspeptin receptors on spermatids, we inferred that kisspeptin- and development-related factors have synergistic effects on spermatogenesis. Nevertheless, more studies are required to elaborate the role of the kisspeptin/KISS1R system in testicular development.
Paying for Sex Among Males and Females: A Cross-Sectional Survey in Melbourne, Australia
Authors: Chow Eric P.F. , Hocking Jane S. , Bradshaw Catriona S. , Phillips Tiffany R. , Tabesh Marjan , Donovan Basil , Maddaford Kate , Chen Marcus Y. , Fairley Christopher K. 
Published: February 2021

Background
Most research focuses on individual selling sex but very few on paying for sex. This study aimed to determine the proportion of males and females who paid for sex and associated factors.

Methods
We conducted a short survey at the Melbourne Sexual Health Centre between March and April 2019, which included a question on whether they had paid for sex in the past 3 months. The proportion of individuals who had paid for sex was calculated by sex and sexual orientation. Univariable and multivariable logistic regression models were conducted to identify individual's factors (e.g., demographics, sexual orientation, and HIV/sexually transmitted infection [STI] positivity) associated with paying for sex in the past 3 months.

Results
The proportion who reported paying for sex in the past 3 months was 12.2% (42/345) among heterosexual males, followed by 6.4% (23/357) among men who have sex with men (MSM) and 0.2% (1/430) among females. HIV status, preexposure prophylaxis use, and sexual orientation were not associated with paying for sex among MSM. No MSM living with HIV reported paying for sex in the past 3 months. There was a significant association between paying for sex and gonorrhea (odds ratio, 2.84; 95% confidence interval, 1.05–7.71; P = 0.041) but not HIV, syphilis, and chlamydia among MSM. HIV/STI was not associated with paying for sex among heterosexual males.

Conclusions
Paying for sex was more commonly reported among heterosexual males, followed by MSM. Females were very unlikely to pay for sex. There was a limited association between HIV/STI diagnosis and paying for sex among males.
Comparison of Associations Between Glucocorticoids Treatment and Mortality in COVID-19 Patients and SARS Patients: A Systematic Review and Meta-Analysis
Authors: Li Jianbo , Liao Xuelian , Zhou Yue , Wang Luping , Yang Hang , Zhang Wei , Zhang Zhongwei , Kang Yan 
Published: February 2021

ABSTRACT

Background:
The response to glucocorticoids treatment may be different between coronavirus disease 2019 (Covid-19) and severe acute respiratory syndrome (SARS).

Methods:
In this systematic review and meta-analysis, we searched studies on Medline, Embase, EBSCO, ScienceDirect, Web of Science, Cochrane Library, ClinicalTrials.gov, International Clinical Trials Registry Platform from 2002 to October 7, 2020. We used fixed-effects and random-effects models to compute the risk ratio of death in the group receiving glucocorticoids treatment and the control group for COVID-19 and SARS, respectively.

Results:
Ten trials and 71 observational studies, with a total of 45,935 patients, were identified. Glucocorticoids treatment was associated with decreased all-cause mortality both in COVID-19 (risk ratio, 0.88; 95% confidence interval, 0.82–0.94; I2 = 26%) and SARS (0.48; 0.29–0.79; 10%), based on high-quality evidence, as well as decreased all-cause mortality-including composite outcome of COVID-19 (0.89; 0.82–0.98; 0%). In subgroup analyses, all-cause mortality was significantly lower among COVID-19 patients being accompanied by severe ARDS but not mild ARDS, taking low-dose or pulse glucocorticoids, being critically severe but not only severe, being of critical severity and old but not young, being of critical severity and men but not women, non-early taking glucocorticoids, taking dexamethasone or methylprednisolone, and with the increased inflammatory state; but for SARS, lower mortality was observed among those who were taking medium-high dose glucocorticoids, being severe or critically severe, early taking glucocorticoids, and taking methylprednisolone or prednisolone.

Conclusions:
Glucocorticoids treatment reduced mortality in COVID-19 and SARS patients of critical severity; however, different curative effects existed between the two diseases among subpopulations, mainly regarding sex- and age-specific effects, optimal doses, and use timing of glucocorticoids.
Extracellular riboflavin induces anaerobic biofilm formation inShewanella oneidensis
Authors: Edel Miriam , Sturm Gunnar , Sturm-Richter Katrin , Wagner Michael , Ducassou Julia Novion , Couté Yohann , Horn Harald , Gescher Johannes 
Published: February 2021

AbstractSome microorganisms can respire with extracellular electron acceptors using an extended electron transport chain to the cell surface. These organisms apply flavin molecules as cofactors to facilitate one-electron transfer catalysed by the terminal reductases and as endogenous electron shuttles. In the model organismShewanella oneidensis, riboflavin production and excretion triggers a specific biofilm formation response that is initiated at a specific threshold concentration, similar to canonical quorum sensing molecules. Riboflavin-mediated messaging is based on the overexpression of the gene encoding the putrescin decarboxylasespeCwhich leads to posttranscriptional overproduction of proteins involved in biofilm formation. Using a model of growth-dependent riboflavin production under batch and biofilm growth conditions, the number of cells necessary to produce the threshold concentration per time was deduced. Furthermore, our results indicate that specific retention of riboflavin in the biofilm matrix leads to localized concentrations which by far exceed the necessary threshold value.ImportanceFerric iron is the fourth most abundant element of the earth crust. It occurs at neutral pH in the form insoluble iron minerals. The dissimilatory reduction of these minerals is an import part of global geological cycles and is catalyzed by microorganisms through extended respiratory chains to the cell surface.Shewanella oneidensisis one of the best understood model organisms for this kind of extracellular respiration. Flavins are important for the reduction of extracellular electron acceptors byS. oneidensis. since they have a function as (I) cofactors of the terminal reductases and (II) electron shuttles. In this study we reveal that flavin molecules are further employed as quorum sensing molecules. They are excreted by the organisms in a growth dependent manner and lead to anaerobic biofilm formation as a specific response at a certain threshold concentration. Although we know multiple examples of quorum sensing mechanisms, the use of riboflavin was so far not described and at least inS. oneidensisproceeds via a new regulatory routine that proceeds on the trancriptomic and posttranscriptomic level.
Messages From the Small Intestine Carried by Extracellular Vesicles in Prediabetes: a Proteomic Portrait
Authors: Ferreira Inês , de Oliveira Rita Machado , Carvalho Ana Sofia , Teshima Akiko , Beck Hans Christian , Matthiesen Rune , Costa-Silva Bruno , Macedo Maria Paula 
Published: February 2021

AbstractExtracellular vesicles (EVs) mediate communication in physiological and pathological conditions. In the pathogenesis of type 2 diabetes, inter-organ communication plays an important role in its progress and metabolic surgery leads to its remission. Moreover, gut dysbiosis is emerging as a diabetogenic factor. However, it remains unclear how gut senses metabolic alterations and whether this is transmitted to other tissues via EVs. Using a diet induced-prediabetic mouse model, we observed that protein packaging in gut derived EVs (GDE), specifically small intestine, is increased in prediabetes. Proteins related to lipid metabolism and to oxidative stress management were more abundant in prediabetic GDE compared to healthy controls. On the other hand, proteins related to glycolytic activity, as well as those responsible for the degradation of polyubiquitinated composites, were depleted in prediabetic GDE. Together, our findings show that protein packaging in GDE is markedly modified during prediabetes pathogenesis. Thus, suggesting that prediabetic alterations in small intestine are translated into modified GDE proteome, which are dispersed into the circulation where they can interact with and influence the metabolic status of other tissues. This study highlights the importance of the small intestine as a tissue that propagates prediabetic metabolic dysfunction throughout the body and the importance of GDE as the messenger.
Parallel Characterization ofcis-Regulatory Elements for Multiple Genes Using CRISPRpath
Authors: Ren Xingjie , Wang Mengchi , Li Bingkun , Jamieson Kirsty , Zheng Lina , Jones Ian R. , Li Bin , Takagi Maya Asami , Lee Jerry , Maliskova Lenka , Tam Tsz Wai , Yu Miao , Hu Rong , Lee Lindsay , Abnousi Armen , Li Gang , Li Yun , Hu Ming , Ren Bing , Wang Wei , Shen Yin 
Published: February 2021

AbstractCurrent pooled CRISPR screens forcis-regulatory elements (CREs) can only accommodate one gene based on its expression level. Here, we describe CRISPRpath, a scalable screening strategy for parallelly characterizing CREs of genes linked to the same biological pathway and converging phenotypes. We demonstrate the ability of CRISPRpath for simultaneously identifying functional enhancers of six genes in the 6-thioguanine-induced DNA mismatch repair pathway using both CRISPR interference (CRISPRi) and CRISPR nuclease (CRISPRn) approaches. 60% of the identified enhancers are known promoters with distinct epigenomic features compared to other active promoters, including increased chromatin accessibility and interactivity. Furthermore, by imposing different levels of selection pressure, CRISPRpath can distinguish enhancers exerting strong impact on gene expression from those exerting weak impact. Our results offer a nuanced view ofcis-regulation and demonstrate that CRISPRpath can be leveraged for understanding the complex gene regulatory program beyond transcriptional output at scale.
MVPA does not reveal neural representations of hierarchical linguistic structure in MEG
Authors: Arana Sophie , Schoffelen Jan-Mathijs , Mitchell Tom , Hagoort Peter 
Published: February 2021

AbstractDuring comprehension, the meaning extracted from serial language input can be described by hierarchical phrase structure. Whether our brains explicitly encode hierarchical structure during processing is, however, debated. In this study we recorded Magnetoencephalography (MEG) during reading of structurally ambiguous sentences to probe neural activity for representations of underlying phrase structure. 10 human subjects were presented with simple sentences, each containing a prepositional phrase that was ambiguous with respect to its attachment site. Disambiguation was possible based on semantic information. We applied multivariate pattern analyses (MVPA) to the MEG data using linear classifiers as well as representational similarity analysis to probe various effects of phrase structure building on the neural signal. Using MVPA techniques we successfully decoded both syntactic (part-of-speech) as well as semantic information from the brain signal. Importantly, however, we did not find any patterns in the neural signal that differentiate between different hierarchical structures. Nor did we find neural traces of syntactic or semantic reactivation following disambiguating sentence material. These null findings suggest that subjects may not have processed the sentences with respect to their underlying phrase structure. We discuss methodological limits of our analysis as well as cognitive theories of “shallow processing”, i.e. in how far rich semantic information can prevent thorough syntactic analysis during processing.
Comparative Analysis of Genetically-Modified Crops: Conditional Equivalence Criteria
Authors: Jiang Changjian , Meng Chen , Schapaugh Adam W. , Jin Huizhe 
Published: February 2021

AbstractThe comparative assessment of genetically-modified (GM) crops relies on the principle of substantial equivalence, which states that such products should be compared to conventional counterparts that have an established history of safe use. In an effort to operationalize this principle, the GMO Panel of the European Food Safety Authority proposed an equivalence test that directly compares a GM test variety with a set of unrelated, conventionally-bred reference varieties with part of the difference as the known background of the test (the same as the given control). The criterion of the EFSA test, however, is defined solely by genotypic differences between the non-traited control and reference varieties (i.e. the background effect) while assuming the so-called GM trait effect as zero. As the outcome of an EFSA equivalence test is determined primarily by the similarity, or lack thereof, of the control and references, a conditional equivalence criterion is proposed in this investigation that focuses on “unintended” effects of a GM trait which is irrespective of the (random) genotypic value of a given control. The new criterion also includes a mean-scaled standard similar to the 80-125% rule for bioequivalence assessment practiced in the pharmaceutical industry as an alternative when the reference variation is zero or close to zero. In addition, optional criteria are proposed with a step-wise procedure to control the rate of false negatives (non-equivalence by chance) providing a comprehensive assessment under multiple comparisons. An application to maize grain composition data demonstrates that the conditional equivalence criterion provides effect-specific and more robust assessment of equivalence than the EFSA criterion did, especially for GM traits showing negligible or no unintended effects which are likely true for most traits in the current market.
Mosquito saliva sialokinin-dependent enhancement of arbovirus infection through endothelial barrier leakage
Authors: Lefteri Daniella A , Bryden Steven R , Pingen Marieke , Terry Sandra , Beswick Emily F , Georgiev Georgi , Van der Laan Marleen , Mastrullo Valeria , Campagnolo Paola , Waterhouse Robert , Varjak Margus , Merits Andres , Fragkoudis Rennos , Griffin Stephen , Shams Kave , Pondeville Emilie , McKimmie Clive S 
Published: February 2021

SummaryViruses transmitted byAedesmosquitoes constitute an increasingly important global health burden. Defining common determinants of host susceptibility to this large group of heterogenous pathogens are key for informing the rational design of new pan-viral medicines. Infection of the vertebrate host with these viruses is enhanced by the presence of mosquito saliva, a complex mixture of salivary gland-derived factors and microbiota. We show that enhancement of infection by saliva was dependent on vascular function and was independent of most anti-saliva immune responses, including to salivary microbiota. Instead, theAedesgene product sialokinin mediated enhancement of virus infection through a rapid reduction in endothelial barrier integrity. Sialokinin is unique within the insect world as having vertebrate-like tachykinin sequence and is absent from non-vector competentAnophelesmosquitoes, whose saliva was not pro-viral and did not induce similar vascular permeability. Therapeutic strategies targeting sialokinin have potential to limit disease severity following infection withAedesmosquito-borne viruses.
Recoding enhances the metabolic capabilities of two novel methylotrophic Asgardarchaeota lineages
Authors: Sun Jiarui , Evans Paul N. , Gagen Emma J. , Woodcroft Ben J. , Hedlund Brian P. , Woyke Tanja , Hugenholtz Philip , Rinke Christian 
Published: February 2021

AbstractAsgardarchaeota have been proposed as the closest living relatives to eukaryotes, and a total of 72 metagenome-assembled genomes (MAGs) representing six primary lineages in this archaeal phylum have thus far been described. These organisms are predicted to be fermentative organoheterotrophs contributing to carbon cycling in sediment ecosystems. Here, we double the genomic catalogue of Asgardarchaeota by obtaining 71 MAGs from a range of habitats around the globe, including deep subsurface, shallow lake, and geothermal spring sediments. Phylogenomic inferences followed by taxonomic rank normalisation confirmed previously established Asgardarchaeota classes and revealed four novel lineages, two of which were consistently recovered as monophyletic classes. We therefore propose the namesCandidatusHodarchaeia class nov. andCand.Jordarchaeia class nov., derived from the gods Hod and Jord in Norse mythology. Metabolic inference suggests that both novel classes represent methylotrophic acetogens, encoding the transfer of methyl groups, such as methylated amines, to coenzyme M with acetate as the end product in remnants of a methanogen-derived core metabolism. This inferred mode of energy conservation is predicted to be enhanced by genetic code expansions, i.e. recoding, allowing the incorporation of the rare 21st and 22nd amino acids selenocysteine (Sec) and pyrrolysine (Pyl). We found Sec recoding in Jordarchaeia and all other Asgardarchaeota classes, which likely benefit from increased catalytic activities of Sec-containing enzymes. Pyl recoding on the other hand is restricted to Hodarchaeia in the Asgardarchaeota, making it the first reported non-methanogenic lineage with an inferred complete Pyl machinery, likely providing this class with an efficient mechanism for methylamine utilisation. Furthermore, we identified enzymes for the biosynthesis of ester-type lipids, characteristic of Bacteria and Eukaryotes, in both novel classes, supporting the hypothesis that mixed ether-ester lipids are a shared feature among Asgardarchaeota.
Characterization of SdGA, a cold-adapted glucoamylase fromSaccharophagus degradans
Authors: Wayllace Natael M. , Hedín Nicolas , Busi María V. , Gomez-Casati Diego F. 
Published: February 2021

ABSTRACTWe investigated the structural and functional properties of SdGA, a glucoamylase (GA) fromSaccharophagus degradans, a marine bacterium which degrades different complex polysaccharides at high rate. SdGA is composed mainly by a N-terminal GH15_N domain linked to a C-terminal catalytic domain (CD) found in the GH15 family of glycosylhydrolases with an overall structure similar to other bacterial GAs. The protein was expressed inEscherichia colicells, purified and its biochemical properties were investigated. Although SdGA has a maximum activity at 39°C and pH 6.0, it also shows high activity in a wide range, from low to mild temperatures, like cold-adapted enzymes. Furthermore, SdGA has a higher content of flexible residues and a larger CD due to various amino acid insertions compared to other thermostable GAs. We propose that this novel SdGA, is a cold-adapted enzyme that might be suitable for use in different industrial processes that require enzymes which act at low or medium temperatures.
Antiviral activity of influenza A virus defective interfering particles against SARS-CoV-2 replicationin vitrothrough stimulation of innate immunity
Authors: Rand U. , Kupke S.Y. , Shkarlet H. , Hein M.D. , Hirsch T. , Marichal-Gallardo P. , Cicin-Sain L. , Reichl U. , Bruder D. 
Published: February 2021

AbstractSARS-CoV-2 causing COVID-19 emerged in late 2019 and resulted in a devastating pandemic. Although the first approved vaccines were already administered by the end of 2020, worldwide vaccine availability is still limited. Moreover, immune escape variants of the virus are emerging against which the current vaccines may confer only limited protection. Further, existing antivirals and treatment options against COVID-19 only show limited efficacy. Influenza A virus (IAV) defective interfering particles (DIPs) were previously proposed not only for antiviral treatment of the influenza disease but also for pan-specific treatment of interferon (IFN)-sensitive respiratory virus infections. To investigate the applicability of IAV DIPs as an antiviral for the treatment of COVID-19, we conductedin vitroco-infection experiments with cell culture-derived DIPs and the IFN-sensitive SARS-CoV-2 in human lung cells. We show that treatment with IAV DIPs leads to complete abrogation of SARS-CoV-2 replication. Moreover, this inhibitory effect was dependent on janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling. Further, our results suggest boosting of IFN-induced antiviral activity by IAV DIPs as a major contributor in suppressing SARS-CoV-2 replication. Thus, we propose IAV DIPs as an effective antiviral agent for treatment of COVID-19, and potentially also for suppressing the replication of new variants of SARS-CoV-2.