bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oral mucosal changes in tight junction proteins in patients with oral lichen planus
Authors: Ren Xiaomeng , Li Kaiyi , Fang Xin , Zhu Zhengda , Chen Qianming , Li Chunlei , Hua Hong 
Published: March 2024

AbstractObjectiveThis study aimed to investigate the expression of tight junction, its distribution pattern in oral lichen planus samples and its potential association with the severity of oral lichen planus.Materials and MethodsCross‐sectional study designs were conducted. Transcriptome sequencing was conducted using oral mucosal tissues from 22 patients with oral lichen planus and 11 healthy controls. Immunohistochemistry and quantitative reverse transcription PCR were performed to verify the expression of claudin‐1, claudin‐4, occludin and zonula occludens‐1 in oral mucosal tissues from another 30 patients with oral lichen planus and 26 healthy controls. The relationship between tight junction protein expression and oral lichen planus severity was explored using correlation analysis.Results5603 and 2475 differentially expressed genes were upregulated and downregulated respectively, in oral lichen planus tissues. KEGG analysis showed that tight junctions including CLDN1, CLDN4, OCLN and TJP1 were downregulated in oral lichen planus. Claudin‐1, claudin‐4, occludin and zonula occludens‐1 expression was verified to be significantly lower in oral lichen planus. Furthermore, correlation analyses showed that decreased occludin expression was positively related to oral lichen planus severity.ConclusionDecreased expression of TJ barrier proteins may be associated with the development of oral lichen planus.
Genetic insights into Tietz albinism‐deafness syndrome: A new dominant‐negative mutation in MITF
Authors: Yamamoto Kohei , Okamura Ken , Wakamatsu Kazumasa , Ito Shosuke , Akabane Kozue , Arai Yosuke , Kawaguchi Junnosuke , Hozumi Yutaka , Suzuki Tamio 
Published: March 2024

AbstractTietz albinism‐deafness syndrome (TADS) is a rare and severe manifestation of Waardenburg syndrome that is primarily linked to mutations in MITF. In this report, we present a case of TADS resulting from a novel c.637G>C mutation in MITF (p.Glu213Gln; GenBank Accession number: NM_000248). A 3‐year‐old girl presented with congenital generalized hypopigmentation of the hair, skin, and irides along with complete sensorineural hearing loss. Histopathological and electron microscopy investigations indicated that this variant did not alter the number of melanocytes in the skin but significantly impaired melanosome maturation within melanocytes. Comprehensive melanin analysis revealed marked reductions in both eumelanin (EM) and pheomelanin (PM) rather than changes in the EM‐to‐PM ratio observed in oculocutaneous albinism. We conducted an electrophoretic mobility shift assay to investigate the binding capability of the identified variant to DNA sequences containing the E‐box motif along with other known variants (p.Arg217del and p.Glu213Asp). Remarkably, all three variants exhibited dominant‐negative effects, thus providing novel insights into the pathogenesis of TADS. This study sheds light on the genetic mechanisms underlying TADS and offers a deeper understanding of this rare condition and its associated mutations in MITF.
The Two Faces of Binding Precedents: A Hohfeldian Look
Authors: Arriagada María Beatriz 
Published: March 2024

AbstractTaking into account one of the meanings of the expression binding precedent and stipulating a definition for that meaning, this article aims to contribute to the concept's structural characterization. By this I mean the effort to identify the legal norms on which the existence and functioning of binding precedents depend and to show that these norms constitute a group of Hohfeldian legal relations between the courts whose precedents must be followed, the courts that must follow them, and the individuals whose legal situations are as a result modified by the observance and the breach of those precedents.
Effects of Leonurine on oocyte maturation and parthenogenetic embryo development in sheep
Authors: Wei Panpan , Wang Jing , Yu Hengbin , Chen Yan , Liu Chang , Zhang Yue , Zeng Weibin , Hu Guangdong 
Published: March 2024

AbstractLeonurine (LEO), an alkaloid isolated from Leonurus spp., has anti‐oxidant, anti‐inflammatory and anti‐apoptotic effects and can prevent damage caused by reactive oxygen species (ROS). These properties suggest that it can improve the maturation rate of oocytes and developmental ability of embryos, which are key parameters in animal breeding. In this study, the effects of LEO on in vitro maturation and early embryonic development in sheep oocytes were evaluated. Among various doses examined (0, 10, 20 and 40 μM), a dose of 20 μM was optimal with respect to the oocyte maturation rate. Compared with estimates in the control group, GSH levels and mitochondrial membrane potential of sheep oocytes treated with 20 μM LEO were significantly higher, and 40 μM LEO would affect oocyte maturation. Additionally, ROS levels were significantly lower, expression levels of the antioxidant genes CAT and SOD1 were significantly higher, and there was no significant difference in GPX3 expression. The Bax/Bcl‐2 ratio and Caspase‐3 expression were significantly reduced in the 20 μM LEO group. During early embryonic development in vitro, the cleavage rate and blastocyst rate were significantly higher in the 20 μM LEO treatment group compared to other groups. GSH levels and mitochondrial membrane potential were significantly higher, while ROS levels were significantly lower, and expression levels of the antioxidant genes CAT, GPX3 and SOD1 were significantly higher in eight‐cell embryos treated with 20 μM LEO than in the control group. The Bax/Bcl‐2 ratio and Caspase‐3 levels were significantly decreased. In summary, LEO can reduce the effect of oxidative stress, improve the oocyte maturation rate and enhance embryonic development.
Blood defense system – Proposal for a new concept of an immune system against blood borne pathogens comprising the liver, spleen and bone marrow
Authors: Kashimura Makoto 
Published: March 2024

AbstractBlood‐borne pathogen (BBP) infections can rapidly progress to life‐threatening sepsis and must therefore be promptly eliminated by the host's immune system. Intravascular macrophages of the liver sinusoid, splenic marginal zone and red pulp and perisinusoidal macrophage protrusions in the bone marrow (BM) directly phagocytose BBPs in the blood as an innate immune response. The liver, spleen and BM thereby work together as the blood defence system (BDS) in response to BBPs by exerting their different immunological roles. The liver removes the vast majority of these invading organisms via innate immunity, but their complete elimination is not possible without the actions of antibodies. Splenic marginal zone B cells promptly produce IgM and IgG antibodies against BBPs. The splenic marginal zone transports antigenic information from the innate to the adaptive immune systems. The white pulp of the spleen functions as adaptive immune tissue and produces specific and high‐affinity antibodies with an immune memory against BBPs. The BM works to maintain immune memory by supporting the survival of memory B cells, memory T cells and long‐lived plasma cells (LLPCs), all of which have dedicated niches. Furthermore, BM perisinusoidal naïve follicular B cells promptly produce IgM antibodies against BBPs in the BM sinusoid and the IgG memory B cells residing in the BM rapidly transform to plasma cells which produce high‐affinity IgG antibodies upon reinfection. This review describes the complete immune defence characteristics of the BDS against BBPs through the collaboration of the liver, spleen and BM with combined different immunological roles.
Postsynaptic β1 spectrin maintains Na+ channels at the neuromuscular junction
Authors: Sert Ozlem , Ding Xiaoyun , Zhang Chuansheng , Mi Ruifa , Hoke Ahmet , Rasband Matthew N. 
Published: March 2024

AbstractSpectrins function together with actin as obligatory subunits of the submembranous cytoskeleton. Spectrins maintain cell shape, resist mechanical forces, and stabilize ion channel and transporter protein complexes through binding to scaffolding proteins. Recently, pathogenic variants of SPTBN4 (β4 spectrin) were reported to cause both neuropathy and myopathy. Although the role of β4 spectrin in neurons is mostly understood, its function in skeletal muscle, another excitable tissue subject to large forces, is unknown. Here, using a muscle specific β4 spectrin conditional knockout mouse, we show that β4 spectrin does not contribute to muscle function. In addition, we show β4 spectrin is not present in muscle, indicating the previously reported myopathy associated with pathogenic SPTBN4 variants is neurogenic in origin. More broadly, we show that α2, β1 and β2 spectrins are found in skeletal muscle, with α2 and β1 spectrins being enriched at the postsynaptic neuromuscular junction (NMJ). Surprisingly, using muscle specific conditional knockout mice, we show that loss of α2 and β2 spectrins had no effect on muscle health, function or the enrichment of β1 spectrin at the NMJ. Muscle specific deletion of β1 spectrin also had no effect on muscle health, but, with increasing age, resulted in the loss of clustered NMJ Na+ channels. Together, our results suggest that muscle β1 spectrin functions independently of an associated α spectrin to maintain Na+ channel clustering at the postsynaptic NMJ. Furthermore, despite repeated exposure to strong forces and in contrast to neurons, muscles do not require spectrin cytoskeletons to maintain cell shape or integrity.
imageKey points
The myopathy found in pathogenic human SPTBN4 variants (where SPTBN4 is the gene encoding β4 spectrin) is neurogenic in origin.
β1 spectrin plays essential roles in maintaining the density of neuromuscular junction Nav1.4 Na+ channels.
By contrast to the canonical view of spectrin organization and function, we show that β1 spectrin can function independently of an associated α spectrin.
Despite the large mechanical forces experienced by muscle, we show that spectrins are not required for muscle cell integrity. This is in stark contrast to red blood cells and the axons of neurons.
Estradiol mediates greater germinal center responses to influenza vaccination in female than male mice
Authors: Dhakal Santosh , Park Han-Sol , Seddu Kumba , Lee John S. , Creisher Patrick S. , Seibert Brittany , Davis Kimberly M. , Hernandez Isabella R. , Maul Robert W. , Klein Sabra L. 
Published: March 2024

ABSTRACT

Adult females of reproductive age develop greater antibody responses to inactivated influenza vaccines (IIV) than males. How sex, age, and sex steroid concentrations impact B cells and durability of IIV-induced immunity and protection over 4 months post-vaccination (mpv) was analyzed. Vaccinated adult females had greater germinal center B cell and plasmablast frequencies in lymphoid tissues, higher neutralizing antibody responses 1–4 mpv, and better protection against live H1N1 challenge than adult males. Aged mice, regardless of sex, had reduced B cell frequencies, less durable antibody responses, and inferior protection after challenge than adult mice, which correlated with diminished estradiol among aged females. To confirm that greater IIV-induced immunity was caused by sex hormones, four core genotype (FCG) mice were used, in which the testes-determining gene,
Sry
, was deleted from chromosome Y (ChrY) and transferred to Chr3 to separate gonadal sex (i.e., ovaries or testes) from sex chromosome complement (i.e., XX or XY complement). Vaccinated, gonadal female FCG mice (XXF and XYF) had greater numbers of B cells, higher antiviral antibody titers, and reduced pulmonary virus titers following live H1N1 challenge than gonadal FCG males (XYM and XXM). To establish that lower estradiol concentrations cause diminished immunity, adult and aged females received either a placebo or estradiol replacement therapy prior to IIV. Estradiol replacement significantly increased IIV-induced antibody responses and reduced morbidity after the H1N1 challenge among aged females. These data highlight that estradiol is a targetable mechanism mediating greater humoral immunity following vaccination among adult females.

IMPORTANCE
Females of reproductive ages develop greater antibody responses to influenza vaccines than males. We hypothesized that female-biased immunity and protection against influenza were mediated by estradiol signaling in B cells. Using diverse mouse models ranging from advanced-age mice to transgenic mice that separate sex steroids from sex chromosome complement, those mice with greater concentrations of estradiol consistently had greater numbers of antibody-producing B cells in lymphoid tissue, higher antiviral antibody titers, and greater protection against live influenza virus challenge. Treatment of aged female mice with estradiol enhanced vaccine-induced immunity and protection against disease, suggesting that estradiol signaling in B cells is critical for improved vaccine outcomes in females.
Complete genome sequence of an ovine ancestral strain of
Mycobacterium avium
subspecies
paratuberculosis
6756
Authors: Biet Franck , Conde Cyril , Cochard Thierry , Mcintoch Fiona A. , Behr Marcel A. , Bannantine John P. 
Published: March 2024

ABSTRACT

The complete genome sequence of the most ancestral type SI strain of
Mycobacterium avium
subspecies
paratuberculosis
6756, isolated from a sheep, was determined. The genome was sequenced using PacBio technology, yielding a genome size of 4,830,294 nucleotides with no identified plasmids.
Upregulation of outer membrane porin gene
ompC
contributed to enhancement of azithromycin susceptibility in multidrug-resistant
Escherichia coli
Authors: Luo Xing-Wei , Li Peng-Liang , Zhai Ya-Jun , Pan Yu-Shan , Hu Gong-Zheng , He Dan-Dan 
Published: March 2024

ABSTRACT

The outer membrane (OM) in gram-negative bacteria contains proteins that regulate the passive or active uptake of small molecules for growth and cell function, as well as mediate the emergence of antibiotic resistance. This study aims to explore the potential mechanisms for restoring bacteria to azithromycin susceptibility based on transcriptome analysis of bacterial membrane-related genes. Transcriptome sequencing was performed by treating multidrug-resistant
Escherichia coli
T28R with azithromycin or in combination with colistin and confirmed by reverse transcription-quantitative PCR (RT-qPCR). Azithromycin enzyme-linked immunosorbent assay (ELISA) test,
ompC
gene overexpression, and molecular docking were utilized to conduct the confirmatory research of the potential mechanisms. We found that colistin combined with azithromycin led to 48 differentially expressed genes, compared to azithromycin alone, such as downregulation of
tolA
,
eptB
,
lpxP
, and
opgE
and upregulation of
ompC
gene. Interestingly, the addition of colistin to azithromycin differentially downregulated the
mph
(A) gene mediating azithromycin resistance, facilitating the intracellular accumulation of azithromycin. Also, overexpression of the
ompC
elevated azithromycin susceptibility, and colistin contributed to further suppression of the Mph(A) activity in the presence of azithromycin. These findings suggested that colistin firstly enhanced the permeability of bacterial OM, causing intracellular drug accumulation, and then had a repressive effect on the Mph(A) activity along with azithromycin. Our study provides a novel perspective that the improvement of azithromycin susceptibility is related not only to the downregulation of the
mph
(A) gene and conformational remodeling of the Mph(A) protein but also the upregulation of the membrane porin gene
ompC
.

IMPORTANCE

Usually, active efflux via efflux pumps is an important mechanism of antimicrobial resistance, such as the AcrAB-TolC complex and MdtEF. Also, bacterial porins exhibited a substantial fraction of the total number of outer membrane proteins in Enterobacteriaceae, which are involved in mediating the development of the resistance. We found that the upregulation or overexpression of the
ompC
gene contributed to the enhancement of resistant bacteria to azithromycin susceptibility, probably due to the augment of drug uptakes caused and the opportunity of Mph(A) function suppressed by azithromycin with colistin. Under the combination of colistin and azithromycin treatment, OmpC exhibited an increased selectivity for cationic molecules and played a key role in the restoral of the antibiotic susceptibility. Investigations on the regulation of porin expression that mediated drug resistance would be important in clinical isolates treated with antibiotics.
Development and utilization of new O
2
-independent bioreporters
Authors: Agranier Eva , Crétin Pauline , Joublin-Delavat Aurélie , Veillard Léa , Touahri Katia , Delavat François 
Published: March 2024

ABSTRACT

Fluorescent proteins have revolutionized science since their discovery in 1962. They have enabled imaging experiments to decipher the function of proteins, cells, and organisms, as well as gene regulation. Green fluorescent protein and all its derivatives are now standard tools in cell biology, immunology, molecular biology, and microbiology laboratories around the world. A common feature of these proteins is their dioxygen (O
2
)-dependent maturation allowing fluorescence, which precludes their use in anoxic contexts. In this work, we report the development and
in cellulo
characterization of genetic circuits encoding the O
2
-independent KOFP-7 protein, a flavin-binding fluorescent protein. We have optimized the genetic circuit for high bacterial fluorescence at population and single-cell level, implemented this circuit in various plasmids differing in host range, and quantified their fluorescence under both aerobic and anaerobic conditions. Finally, we showed that KOFP-7-based constructions can be used to produce fluorescing cells of
Vibrio diazotrophicus
, a facultative anaerobe, demonstrating the usefulness of the genetic circuits for various anaerobic bacteria. These genetic circuits can thus be modified at will, both to solve basic and applied research questions, opening a highway to shed light on the obscure anaerobic world.

IMPORTANCE

Fluorescent proteins are used for decades, and have allowed major discoveries in biology in a wide variety of fields, and are used in environmental as well as clinical contexts. Green fluorescent protein (GFP) and all its derivatives share a common feature: they rely on the presence of dioxygen (O
2
) for protein maturation and fluorescence. This dependency precludes their use in anoxic environments. Here, we constructed a series of genetic circuits allowing production of KOFP-7, an O
2
-independant flavin-binding fluorescent protein. We demonstrated that
Escherichia coli
cells producing KOFP-7 are fluorescent, both at the population and single-cell levels. Importantly, we showed that, unlike cells producing GFP, cells producing KOFP-7 are fluorescent in anoxia. Finally, we demonstrated that
Vibrio diazotrophicus
NS1, a facultative anaerobe, is fluorescent in the absence of O
2
when KOFP-7 is produced. Altogether, the development of new genetic circuits allowing O
2
-independent fluorescence will open new perspective to study anaerobic processes.
A scoping review to map the research on the mental health of students and graduates during their university-to-work transitions
Authors: Edmonds David Matthew , Zayts-Spence Olga , Fortune Zoë , Chan Angus , Chou Jason Shang Guan 
Published: March 2024

ObjectivesThis scoping review maps the extant literature on students’ and graduates’ mental health experiences throughout their university-to-work transitions. The current review investigates the methodological features of the studies, the main findings, and the theories that the studies draw on to conceptualise mental health and transitions.DesignThis project used a scoping review methodology created and developed by Peters and colleagues and the Joanna Briggs Institute. The review searched academic databases and screened existing studies that met predetermined inclusion criteria.Data sourcesSeven academic databases and Google Scholar were searched with sets of search terms.EligibilityThe included studies examined participants who were final-year university students or those who had graduated from university within a 3-year period. Studies published in English since 2000 and from any country were included. The review included studies examining the negative dimensions of mental health. The review excluded studies focusing on medical students and graduates.Data extractionBasic information about the studies and their findings on mental health and university-to-work transitions was retrieved. The findings are presented in tables and in a qualitative thematic summary.ResultsThe scoping review included 12 studies. Mental health was often not explicitly defined and it’s theoretical foundations were not clearly articulated. The review identified factors, including a lack of social support and economic precarity, as sources of adverse mental health. Otherprotectivefactors in these studies—variables that guard against mental health problems—were identified, such as career preparedness and having a good job.ConclusionsDespite the methodological focus on the negative aspects of mental health, people’s mental health experiences during university-to-work transitions are not uniformly negative. Clear conceptualisations of mental health in future studies will aid in developing resources to improve well-being.Trial registration numberThis scoping review adhered to a protocol previously published in this journal and that is registered on the Open Science Framework website (https://osf.io/gw86x).
Importance of kidney function, number of chronic conditions and medications for hospitalisation in elderly in Blekinge County, Sweden: a case–control study
Authors: Norstedt Isabell , Thorell Kristine , Halling Anders 
Published: March 2024

ObjectivesTo study the association between risk for hospitalisation in an elderly population related to renal function, number of chronic diseases and number of prescribed drugs.DesignA case–control study. Persons hospitalised were included and their controls were obtained from electronic hospital medical records. If data were lacking on creatinine levels, multiple imputation was used.SettingBlekinge County in southwestern Sweden.ParticipantsStudy of individuals aged 75 years or older in 2013. We identified a total of 2,941 patients with a first hospitalisation. Of these, 81 were excluded, 78 due to incomplete data and 3 because of lack of control persons. Controls were matched to the same sex and birth year, which resulted in 5720 persons.Primary and secondary outcome measuresTo analyse the OR for hospitalisation conditional logistic regression was used.ResultsA total of 695 persons lacked creatinine value. Using imputation values comparing persons with estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2with ≥30 univariate analyses showed an increased OR 2.35 (95% CI 1.83 to 3.03). Adjusted analyses demonstrated an OR of 1.90 (95% CI 1.46 to 2.47). Comparing eGFR<45 mL/min/1.73 m2against ≥45 univariate analyses showed OR 1.38 (95% CI 1.22 to 1.57). Adjusted analyses OR for the same group were 1.17 (95% CI 1.03 to 1.33). In both models, the OR for five or more chronic conditions and five or more medications showed a statistically increased risk for hospitalisation.ConclusionsThere is a need for systems using data collected in routine care to follow elderly patients to minimise avoidable hospitalisations that can cause adverse effects. Renal function, number of chronic conditions and medications are factors that are of significant importance. This study demonstrates the complexity of this patient group.