bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic selection for survival under naturally occurring Saprolegnia oomycete infection in farmed European whitefish Coregonus lavaretus
Authors: Calboli Federico C F , Iso-Touru Terhi , Bitz Oliver , Fischer Daniel , Nousiainen Antti , Koskinen Heikki , Tapio Miika , Tapio Ilma , Kause Antti 
Published: October 2023

Abstract
Saprolegnia oomycete infection causes serious economic losses and reduces fish health in aquaculture. Genomic selection based on thousands of DNA markers is a powerful tool to improve fish traits in selective breeding programs. Our goal was to develop a single nucleotide polymorphism (SNP) marker panel and to test its use in genomic selection for improved survival against Saprolegnia infection in European whitefish Coregonus lavaretus, the second most important farmed fish species in Finland. We used a double digest restriction site associated DNA (ddRAD) genotyping by sequencing method to produce a SNP panel, and we tested it analyzing data from a cohort of 1,335 fish, which were measured at different times for mortality to Saprolegnia oomycete infection and weight traits. We calculated the genetic relationship matrix (GRM) from the genome-wide genetic data, integrating it in multivariate mixed models used for the estimation of variance components and genomic breeding values (GEBVs), and to carry out Genome-Wide Association Studies for the presence of quantitative trait loci (QTL) affecting the phenotypes in analysis. We identified one major QTL on chromosome 6 affecting mortality to Saprolegnia infection, explaining 7.7% to 51.3% of genetic variance, and a QTL for weight on chromosome 4, explaining 1.8% to 5.4% of genetic variance. Heritability for mortality was 0.20 to 0.43 on the liability scale, and heritability for weight was 0.44 to 0.53. The QTL for mortality showed an additive allelic effect. We tested whether integrating the QTL for mortality as a fixed factor, together with a new GRM calculated excluding the QTL from the genetic data, would improve the accuracy estimation of GEBVs. This test was done through a cross-validation approach, which indicated that the inclusion of the QTL increased the mean accuracy of the GEBVs by 0.28 points, from 0.33 to 0.61, relative to the use of full GRM only. The area under the curve of the receiver–operator curve for mortality increased from 0.58 to 0.67 when the QTL was included in the model. The inclusion of the QTL as a fixed effect in the model increased the correlation between the GEBVs of early mortality with the late mortality, compared to a model that did not include the QTL. These results validate the usability of the produced SNP panel for genomic selection in European whitefish and highlight the opportunity for modeling QTLs in genomic evaluation of mortality due to Saprolegnia infection.
Sgo1 interacts with CENP-A to guide accurate chromosome segregation in mitosis
Authors: Wu Fengge , Akbar Hameed , Wang Chunyue , Yuan Xiao , Dou Zhen , Mullen McKay , Niu Liwen , Zhang Liang , Zang Jianye , Wang Zhikai , Yao Xuebiao , Song Xiaoyu , Liu Xing 
Published: October 2023

Abstract
Shugoshin-1 (Sgo1) is necessary for maintaining sister centromere cohesion and ensuring accurate chromosome segregation during mitosis. It has been reported that the localization of Sgo1 at the centromere is dependent on Bub1-mediated phosphorylation of histone H2A at T120. However, it remains uncertain whether other centromeric proteins play a role in regulating the localization and function of Sgo1 during mitosis. Here, we show that CENP-A interacts with Sgo1 and determines the localization of Sgo1 to the centromere during mitosis. Further biochemical characterization revealed that lysine and arginine residues in the C-terminal domain of Sgo1 are critical for binding CENP-A. Interestingly, the replacement of these basic amino acids with acidic amino acids perturbed the localization of Sgo1 and Aurora B to the centromere, resulting in aberrant chromosome segregation and premature chromatid separation. Taken together, these findings reveal a previously unrecognized but direct link between Sgo1 and CENP-A in centromere plasticity control and illustrate how the Sgo1–CENP-A interaction guides accurate cell division.
Hepatic angiomyolipoma, misdiagnosed as hepatocellular carcinoma
Authors: Marinho Bárbara M , Canha António G , Silva Donzília S , Rodrigues Ana P 
Published: October 2023

Abstract
Perivascular epithelioid cell neoplasm (PEComa) is a rare type of tumor, and hepatic PEComa is even rarer. Its preoperative diagnosis is difficult, given the absence of specific clinical manifestations, often constituting an accidental finding, and the lack of a gold standard for identification using imaging studies. Instead, the diagnosis of hepatic PEComa is based on morphological and immunohistochemical features. We describe a case of an asymptomatic hepatic PEComa, angiomyolipoma type, which appeared in a middle-aged woman with chronic liver disease, during her follow-up and screening. Given the patient's context, human immunodeficiency virus-positive with chronic hepatitis C, and the similarities between the two tumors, the hepatic lesion was interpreted as hepatocellular carcinoma. The patient underwent surgical excision of the tumor, and the positive immunohistochemical staining for human melanoma black 45 and Melan A made the definitive diagnosis. In the absence of aggressiveness tumor markers, surveillance was decided. We also provide a literature review of these tumors.
Biostimulated-sesame sprout extracts as potential agents against Leishmania mexicana
Authors: Garduño-Félix Karime G , Rochín-Medina Jesús J , Murua-López Carolina C , López-Moreno Héctor S , Ramírez Karina 
Published: October 2023

Abstract
Leishmania mexicana is one of the causal agents of cutaneous leishmaniasis. Current antileishmanial chemotherapeutics have demonstrated adverse side effects; thus, alternative treatments are needed. In this study, we performed in silico and in vitro analyses of the leishmanicidal potential of the most abundant phenolic compounds identified in black sesame sprouts biostimulated with Bacillus clausii. The molecular docking analysis showed strong interactions (binding free energies between −6.5 and −9.5 kcal/mol) of sesaminol 2-O-triglucoside, pinoresinol dihexoside, isoverbascoside, and apigenin with the arginase, leishmanolysin, cysteine peptidase B, and pyruvate kinase leishmanial enzymes. Furthermore, almost all phenolic compounds interacted with the active site residues of L. mexicana enzymes. In vitro, the B. clausii-biostimulated sprout phenolic extracts and apigenin inhibited the growth of promastigotes with IC50 values of 0.08 mg gallic acid equivalent/mL and 6.42 μM (0.0017 mg/mL), respectively. Additionally, in the macrophage infection model, cells treated with B. clausii-biostimulated sprout phenolic extracts and infected with L. mexicana exhibited significantly (P &lt; 0.05) reduced nitric oxide production and decreased parasite burden. Altogether, our study provides important data related to high efficacy and less toxic natural antileishmanial candidates against promastigotes of L. mexicana.
Characterization of white rot fungi from wood decayed for lignin degradation
Authors: Nurul-Aliyaa Yakath Ali , Awang Nik Azimatolakma , Mohd Masratul Hawa 
Published: October 2023

Abstract
The present study was conducted to isolate and identify white rot fungi (WRF) from wood decayed and to determine their ability to produce lignin-modifying enzymes (LMEs), specifically laccase (Lac), lignin peroxidase (LiP), and manganese peroxidase (MnP), on solid and liquid media supplemented with synthetic dyes namely 2,2′-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), azure B, and phenol red. A total of 23 isolates of WRF were isolated from decayed wood and identified as eight different species namely Phanerochaete australis, Perenniporia tephropora, Lentinus squarrosulus, Ganoderma australe, Trametes polyzona, Lentinus sajor-caju, Gymnopilus dilepis, and Fomitopsis palustris based on morphological characteristics, DNA sequences of the internal transcribed spacer (ITS) region, and phylogenetic inference. The fungal isolates can be divided into four groups based on the type of LMEs produced, namely A (Lac-LiP-MnP) with 16 isolates, B (Lac-MnP) (three isolates), C (Lac) (three isolates), and D (MnP) (one isolate). This study highlights P. australis (BJ38) as the best producer of Lac and LiP, while L. squarrosulus (IPS72) is the best producer of MnP. The present study is the first reported P. australis as an efficient lignin degrader by demonstrating the highest activity of two important LMEs.
Hypocalcemia and cardiovascular mortality in cinacalcet users
Authors: Goto Shunsuke , Hamano Takayuki , Fujii Hideki , Taniguchi Masatomo , Abe Masanori , Nitta Kosaku , Nishi Shinichi 
Published: October 2023

ABSTRACTBackgroundCalcimimetics are widely used in hemodialysis patients and influence serum calcium levels. Although the Kidney Disease: Improving Global Outcomes guidelines argued that low calcium levels induced by calcimimetics may be harmless, large observational studies investigating the association between hypocalcemia and mortality are scarce. We investigated the association between serum calcium levels and cardiovascular mortality in calcimimetics users using the nationwide Japanese registry for dialysis patients.MethodsIn this 9-year prospective cohort study, the baseline data were collected at the end of 2009. We enrolled patients on maintenance hemodialysis or hemodiafiltration. We employed three models (baseline, time-dependent and time-averaged) to conduct Cox proportional hazard regression analyses.ResultsCinacalcet was prescribed to 12.7% (N = 22 853) at baseline. The median observation period was 98 (interquartile range 40–108) months and 108 (interquartile range 59–108) months in the whole cohort (N = 180 136) and in cinacalcet users, respectively. Three-quarters of survivors at the end of 2019 had continued calcimimetic therapy for 10 years, corresponding to a mean annual dropout rate of 2.9%. Hypocalcemia was not associated with cardiovascular mortality in the baseline or time-averaged model. In the time-dependent model, however, the lowest calcium decile (corrected calcium &lt;8.4 mg/dL) was significantly associated with higher cardiovascular mortality than the reference (corrected calcium 8.7–8.9 mg/dL) in both cinacalcet users and all patients [hazard ratio (95% confidence interval) 1.32 (1.00, 1.75) and 1.15 (1.05, 1.26), respectively]. Hypocalcemia was especially associated with sudden death and death due to hemorrhagic stroke, heart failure and ischemic heart disease. Higher rate of fatal and non-fatal cardiovascular events was observed in hypocalcemic patients regardless of cinacalcet usage.ConclusionsOur findings suggest that transient hypocalcemia was associated with an increased risk of cardiovascular death independent of cinacalcet usage. We should pay attention to hypocalcemia transiently induced by cinacalcet.
Gender balance and suitable positive actions to promote gender equality among healthcare professionals in neuro-oncology: The EANO positive action initiative
Authors: Le Rhun Emilie , Boele Florien , Minniti Giuseppe , Galldiks Norbert , Taphoorn Martin , Piil Karin , Rudà Roberta , Niclou Simone P , Geurts Marjolein , Preusser Matthias , Weller Michael , Short Susan C , Dirven Linda 
Published: October 2023

Abstract

Background
The proportion of women among healthcare and biomedical research professionals in neuro-oncology is growing. With changes in cultural expectations and work-life balance considerations, more men aspire to nonfull-time jobs, yet, leadership positions remain dominated by men.

Methods
The European Association of Neuro-Oncology (EANO) disparity committee carried out a digital survey to explore gender balance and actions suitable to promote gender equality. The survey was distributed among EANO members in 2021, with responses analyzed descriptively.

Results
In total, 262 participants completed the survey (141 women, 53.8%; median age 43). Respondents were neurosurgeons (68, 26.0%); neurologists (67, 25.6%), medical oncologists (43, 16.4%), or other healthcare or research professionals; 208 participants (79.4%) worked full-time. Positive action to enforce the role of women in neuro-oncology was deemed necessary by 180 participants (68.7%), but only 28 participants (10.7%) agreed that women only should be promoted until gender balance is reached. A majority of respondents (162, 61.8%) felt that women with an equivalent CV should be prioritized over men to reach gender balance. If in the future the balance favored women at higher positions, 112 respondents (42.7%) agreed to apply positive action for men. The top indicators considered relevant to measure gender balance were: salary for similar positions (183/228, 80.3%), paid overtime (176/228, 77.2%), number of permanent positions (164/228, 71.9%), protected time for research (161/227, 70.9%), and training opportunities (157/227, 69.2%).

Conclusions
Specific indicators may help to measure and promote gender balance and should be considered for implementation among healthcare professionals in neuro-oncology.
Revisiting the phylogeny of the scolebythid wasps (Hymenoptera: Aculeata) through Bayesian model evaluation and parsimony, with description of a new fossil family of Chrysidoidea
Authors: Lepeco Anderson , Melo Gabriel A R 
Published: October 2023

Abstract
Scolebythidae constitute the smallest family of Aculeata in number of extant species, but with a considerable diversity of extinct lineages. Twenty Cretaceous species are attributed to the family coming from deposits in Canada, Lebanon, Myanmar, New Jersey, and Spain. However, several of these taxa lack characters of the family groundplan. Although phylogenetic investigations have been conducted for the family based on a relatively small set of morphological characters, the substantial diversity of species from Burmese amber have not yet been accounted for in a phylogenetic perspective. In the present work, we reconstruct the phylogenetic relationships of Scolebythidae using a new morphological matrix and explore it through parsimony and Bayesian model evaluation. In Bayesian analyses, homoplasy-based partitioning outperformed anatomy-based partitioning and the unpartitioned models. Our phylogenetic results support the relocation of a few taxa previously attributed to Scolebythidae to the families Bethylidae and Chrysididae. We also describe †Chrysopsenellidae fam. nov., a new family of Chrysidoidea, based on an inclusion in Burmese amber. In all analyses the new family is recovered as closely related to Scolebythidae, with the whole clade being sister-group to Chrysididae + †Chrysobythidae. Finally, we discuss the origin of the Burmese amber biota distinctiveness.
PADI6: What we know about the elusive fifth member of the peptidyl arginine deiminase family
Authors: Williams Jack P. C. , Walport Louise J. 
Published: October 2023

Peptidyl arginine deiminase 6 (PADI6) is a maternal factor that is vital for early embryonic development. Deletion and mutations of its encoding gene in female mice or women lead to early embryonic developmental arrest, female infertility, maternal imprinting defects and hyperproliferation of the trophoblast. PADI6 is the fifth and least well-characterized member of the peptidyl arginine deiminases (PADIs), which catalyse the post-translational conversion of arginine to citrulline. It is less conserved than the other PADIs, and currently has no reported catalytic activity. While there are many suggested functions of PADI6 in the early mouse embryo, including in embryonic genome activation, cytoplasmic lattice formation, maternal mRNA and ribosome regulation, and organelle distribution, the molecular mechanisms of its function remain unknown. In this review, we discuss what is known about the function of PADI6 and highlight key outstanding questions that must be answered if we are to understand the crucial role it plays in early embryo development and female fertility.
This article is part of the Theo Murphy meeting issue ‘The virtues and vices of protein citrullination’.
Small molecule activates citrullination through targeting PAD2
Authors: Zhang Xue , Shen Mengzhen , Zhu Huimin , Zhang Junjie , Yang Min , Su Kaiyan , Zhang Yirong , Fu Wei , Ke Xisong , Qu Yi 
Published: October 2023

Citrullination is a post-translational modification catalysed by peptidyl arginine deiminase (PAD) enzymes, and dysregulation of protein citrullination is involved in various pathological disorders. During the past decade, a panel of citrullination inhibitors has been developed, while small molecules activating citrullination have rarely been reported so far. In this study, we screened citrullination activator using an antibody against citrullinated histone H3 (cit-H3), and a natural compound demethoxycurcumin (DMC) significantly activated citrullination. The requirement of PAD2 for DMC-activated citrullination was confirmed by a loss of function assay. Notably, DMC directly engaged with PAD2, and showed binding selectivity among PAD family enzymes. Point mutation assay indicated that residue E352 is essential for DMC targeting PAD2. Consistently, DMC induced typical phenotypes of cells with dysregulation of PAD2 activity, including citrullination-associated cell apoptosis and DNA damage. Overall, our study not only presents a strategy for rationally screening citrullination activators, but also provides a chemical approach for activating protein citrullination.
This article is part of the Theo Murphy meeting issue ‘The virtues and vices of protein citrullination’.
An unbiased proteomic analysis of PAD4 in human monocytes: novel substrates, binding partners and subcellular localizations
Authors: Thomas Mekha A. , Kim Seok-Young , Curran Ashley M. , Smith Barbara , Antiochos Brendan , Na Chan Hyun , Darrah Erika 
Published: October 2023

Peptidylarginine deiminase IV (PAD4) post-translationally converts arginine residues in proteins to citrullines and is implicated in playing a central role in the pathogenesis of several diseases. Although PAD4 was historically thought to be a nuclear enzyme, recent evidence has revealed a more complex localization of PAD4 with evidence of additional cytosolic and cell surface localization and activity. However, the mechanisms by which PAD4, which lacks conventional secretory signal sequences, traffics to extranuclear localizations are unknown. In this study, we show that PAD4 was enriched in the organelle fraction of monocytes with evidence of citrullination of organelle proteins. We also demonstrated that PAD4 can bind to several cytosolic, nuclear and organelle proteins that may serve as binding partners for PAD4 to traffic intracellularly. Additionally, cell surface expression of PAD4 increased with monocyte differentiation into monocyte-derived dendritic cells and co-localized with several endocytic/autophagic and conventional secretory pathway markers, implicating the use of these pathways by PAD4 to traffic within the cell. Our results suggest that PAD4 is expressed in multiple subcellular localizations and may play previously unappreciated roles in physiological and pathological conditions.
This article is part of the Theo Murphy meeting issue ‘The virtues and vices of protein citrullination’.
Learning patterns of HIV-1 co-resistance to broadly neutralizing antibodies with reduced subtype bias using multi-task learning
Authors: Igiraneza Aime Bienfait , Zacharopoulou Panagiota , Hinch Robert , Wymant Chris , Abeler-Dörner Lucie , Frater John , Fraser Christophe 
Published: October 2023

AbstractThe ability to predict HIV-1 resistance to broadly neutralizing antibodies (bnAbs) will increase bnAb therapeutic benefits. Machine learning is a powerful approach for such prediction. One challenge is that some HIV-1 subtypes in currently available training datasets are underrepresented, which likely affects models’ generalizability across subtypes. A second challenge is that combinations of bnAbs are required to avoid the inevitable resistance to a single bnAb, and computationally determining optimal combinations of bnAbs is an unsolved problem. Recently, machine learning models trained using resistance outcomes for multiple antibodies at once, a strategy called multi-task learning (MTL), have been shown to achieve better performance in several cases than previous approaches. We develop a new model and show that, beyond the boost in performance, MTL also helps address the previous two challenges. Specifically, we demonstrate empirically that MTL can mitigate bias from underrepresented subtypes, and that MTL allows the model to learn patterns of co-resistance between antibodies, thus providing tools to predict antibodies’ epitopes and to potentially select optimal bnAb combinations. Our analyses, publicly available athttps://github.com/iaime/LBUM, can be adapted to other infectious diseases that are treated with antibody therapy.
T cells in testicular germ cell tumors: new evidence of fundamental contributions by rare subsets
Authors: Islam Rashidul , Heyer Jannis , Figura Miriam , Wang Xiaoyan , Nie Xichen , Nathaniel Benedict , Indumathy Sivanjah , Hartmann Katja , Pleuger Christiane , Fijak Monika , Kliesch Sabine , Dittmar Florian , Pilatz Adrian , Wagenlehner Florian , Hedger Mark , Loveland Bruce , Hotaling James H. , Guo Jingtao , Loveland Kate , Schuppe Hans-Christian , Fietz Daniela 
Published: October 2023

ABSTRACTBACKGROUNDImmune cell infiltration is heterogeneous but common in testicular germ cell tumors (TGCT) and pre-invasive germ cell neoplasia in situ (GCNIS). Tumor-infiltrating T cells including regulatory T (Treg) and follicular helper T (Tfh) cells are found in other cancer entities, but their contributions to TGCT are unknown.METHODSHuman testis specimens from independent patient cohorts were analyzed using immunohistochemistry, flow cytometry and single-cell RNA sequencing (scRNA-seq) with special emphasis on delineating T cell subtypes.RESULTSProfound changes in immune cell composition within TGCT, shifting from macrophages in normal testes to T cells plus B and dendritic cells in TGCT, were documented. In most samples (96%), the CD4+ T cell frequency exceeded that of CD8+ cells, with decreasing numbers from central to peripheral tumor areas, and to tumor-free, contralateral testes. T cells including Treg and Tfh were most abundant in seminoma compared to mixed tumors and embryonal carcinoma.CONCLUSIONDespite considerable heterogeneity between patients, T cell subtypes form a key part of the TGCT microenvironment. The novel finding of rare Treg and Tfh cells in human testis suggests their involvement in TGCT pathobiology, with implications for understanding tumor progression, to assess patients’ prognosis, and as putative targets for personalized immunotherapy.