bluuebunny/crossref_metadata_2025_split huggingface dataset:
Specific pelvic shape in patients with developmental dysplasia of the hip on 3D morphometric homologous model analysis
Authors: Sasaki Yui , Suzuki Daisuke , Tokita Ryo , Takashima Hiroyuki , Matsumura Hirofumi , Nagoya Satoshi 
Published: March 2024

AbstractPurposeTo clarify the morphological factors of the pelvis in patients with developmental dysplasia of the hip (DDH), three-dimensional (3D) pelvic morphology was analyzed using a template-fitting technique.MethodsThree-dimensional pelvic data of 50 patients with DDH (DDH group) and 3D pelvic data of 50 patients without obvious pelvic deformity (Normal group) were used. All patients were female. A template model was created by averaging the normal pelvises into a symmetrical and isotropic mesh. Next, 100 homologous models were generated by fitting the pelvic data of each group of patients to the template model. Principal component analysis was performed on the coordinates of each vertex (15,235 vertices) of the pelvic homologous model. In addition, a receiver-operating characteristic (ROC) curve was calculated from the sensitivity of DDH positivity for each principal component, and principal components for which the area under the curve was significantly large were extracted (p<0.05). Finally, which components of the pelvic morphology frequently seen in DDH patients are related to these extracted principal components was evaluated.ResultsThe first, third, and sixth principal components showed significantly larger areas under the ROC curves. The morphology indicated by the first principal component was associated with a decrease in coxal inclination in both the coronal and horizontal planes. The third principal component was related to the sacral inclination in the sagittal plane. The sixth principal component was associated with narrowing of the superior part of the pelvis.ConclusionThe most important factor in the difference between normal and DDH pelvises was the change in the coxal angle in both the coronal and horizontal planes. That is, in the anterior and superior views, the normal pelvis is a triangle, whereas in DDH, it was more like a quadrilateral.
Transcriptomic profile of normal breast tissue post-mifepristone treatment: secondary outcomes of a randomized controlled trial
Authors: Utjés Deborah , Boggavarapu Nageswara Rao , Rasul Mohammed , Koberg Isabelle , Zulliger Alexander , Ponandai-Srinivasan Sakthivignesh , von Grothusen Carolina , Lalitkumar Parameswaran Grace , Papaikonomou Kiriaki , Alkasalias Twana , Gemzell-Danielsson Kristina 
Published: March 2024

AbstractProgesterone receptor antagonism is gaining attention due to progesterone’s recognized role as a major mitogen in breast tissue. Limited but promising data suggest the potential efficacy of antiprogestins in breast cancer prevention. The present study presents secondary outcomes from a randomized controlled trial and examine changes in breast mRNA expression following mifepristone treatment in healthy women. We analyzed 32 paired breast biopsies from 16 healthy premenopausal women at baseline and after two months of mifepristone treatment. In total, twenty-seven differentially expressed genes were identified, with enriched biological functions related to extracellular matrix remodeling. Notably, the altered gene signature induced by mifepristonein vivowas rather similar to thein vitrosignature. Furthermore, this expression gene signature was associated with breast carcinogenesis and significantly correlated with progesterone receptor expression status in breast cancer, as validated in The Cancer Genome Atlas dataset using the R2 platform. The present study is the first to explore the breast transcriptome following mifepristone treatment in healthy breast tissuein vivo, enhancing the understanding of progesterone receptor antagonism and its potential protective effect against breast cancer by investigating its action in healthy breast tissue.
Cryo-EM confirms a common fibril fold in the heart of four patients with ATTRwt amyloidosis
Authors: Nguyen Binh An , Singh Virender , Afrin Shumaila , Singh Preeti , Pekala Maja , Ahmed Yasmin , Pedretti Rose , Canepa Jacob , Lemoff Andrew , Kluve-Beckerman Barbara , Wydorski Pawel , Chhapra Farzeen , Saelices Lorena 
Published: March 2024

AbstractATTR amyloidosis results from the conversion of transthyretin into amyloid fibrils that deposit in tissues causing organ failure and death. This conversion is facilitated by mutations in ATTRv amyloidosis, or aging in ATTRwt amyloidosis. ATTRv amyloidosis exhibits extreme phenotypic variability, whereas ATTRwt amyloidosis presentation is consistent and predictable. Previously, we found an unprecedented structural variability in cardiac amyloid fibrils from polyneuropathic ATTRv-I84S patients. In contrast, cardiac fibrils from five genotypically-different patients with cardiomyopathy or mixed phenotypes are structurally homogeneous. To understand fibril structure’s impact on phenotype, it is necessary to study the fibrils from multiple patients sharing genotype and phenotype. Here we show the cryo-electron microscopy structures of fibrils extracted from four cardiomyopathic ATTRwt amyloidosis patients. Our study confirms that they share identical conformations with minimal structural variability, consistent with their homogenous clinical presentation. Our study contributes to the understanding of ATTR amyloidosis biopathology and calls for further studies.One-Sentence Summary:Wild-type cardiac ATTR fibrils are structurally homogeneous.
Non-mechanical disruption ofBacillus subtilis sporesallows sensitive and deep characterization of the minimal proteome for resuming a cellular lifestyle
Authors: Huang Yixuan , de Koster Alphonse , Tu Zhiwei , Gao Xiaowei , Roseboom Winfried , Brul Stanley , Setlow Peter , Kramer Gertjan 
Published: March 2024

AbstractIn response to extreme conditions,Bacillus subtilisgenerates highly resilient spores characterized by a unique multilayered structure. This confers resistance against various chemicals and enzymes yet adding complexity to the analysis of the spore proteome. As the first step in bottom-up proteomics, sample preparation poses a significant challenge. We assessed how an optimized protocol for sample preparation by easy extraction and digestion (SPEED) performed compared to previously established methods “One-pot” (OP) and single-pot, solid phase-enhanced sample-preparation (SP3) for the proteomic analysis ofB. subtiliscell and spore samples. We found that SPEED outperformed both OP and SP3 in terms of peptides and proteins identified, moreover SPEED highly reproducibly quantified over 1000 proteins in limited input samples as low as 1 OD600ofB. subtiliscells and spores. SPEED was applied to analyze spore samples of different purity by applying sequential purification following harvesting of spores. Comparison of the differential abundance of proteins revealed clusters likely partially stemming from remaining vegetative cells in less purified spore samples. We show that ranking of absolute protein abundance in cellular and spore samples further enables us to rationally differentiate integral spore proteins from vegetative remnants. This is of importance in applications and organisms where highly homogenous spore samples are difficult to obtain. A deep proteomic analysis of spore and vegetative cell samples with the new approach led to the identification of 2447 proteins, 2273 of which were further quantified and compared betweenB. subtilisspores and cells. Our findings indicate that pathways related to peptidoglycan biosynthesis, glycolysis, carbon metabolism, and biosynthesis of secondary metabolites are shared between cells and spores. This corroborates and extends earlier work stressing that despite marked differences in their physiological states, spores preserve vegetative cell (core) proteins, essential for revival under conditions conducive to growth.Abstract Figure
GATLncLoc+C&S: Prediction of LncRNA subcellular localization based on corrective graph attention network
Authors: Deng Xi , Tang Lin , Liu Lin 
Published: March 2024

AbstractLong non-coding RNAs (LncRNAs) have a wide range of regulatory roles in gene expression, and the subcellular localization identification of LncRNAs is of great value in understanding their biological functions. Graph neural networks can not only utilize sequence characteristics, but also learn hidden features from non-Euclidean data structures to obtain features with powerful characterization capabilities. To learn more fully from the limited LncRNA localization samples and efficiently exploit easily ignored label features, we propose a corrective graph attention network prediction model GATLncLoc+C&S in this paper. Compared with previous methods, the similarity of optimal features is first used to construct the graph. Then, a re-weighted graph attention network R-GAT is constructed and the soft labels obtained from it are used to correct the graph. Finally, the predicted localization label is further obtained by label propagation. Based on the combination of R-GAT and label propagation, GATLncLoc+C&S effectively solves the problems of few samples and data imbalance in LncRNA subcellular localization. The accuracy of GATLncLoc+C&S reached 95.8% and 96.8% in the experiments of 5- and 4-localization benchmark datasets, which reflects the great potential of our proposed method in predicting LncRNA subcellular localization. The source code and data of GATLncLoc+C&S are available athttps://github.com/GATLncLoc-C-S/GATLncLoc-C-S.
Proteolytic activity of surface exposed HtrA determines its expression level and is needed to survive acidic conditions inClostridioides difficile
Authors: Corver Jeroen , Claushuis Bart , Shamorkina Tatiana M. , de Ru Arnoud H. , van Leeuwen Merle M. , Hensbergen Paul J. , Smits Wiep Klaas 
Published: March 2024

AbstractTo survive in the host, pathogenic bacteria need to be able to react to the unfavourable conditions that they encounter, like low pH, elevated temperatures, antimicrobial peptides and many more. These conditions may lead to unfolding of envelope proteins and this may be lethal. One of the mechanisms through which bacteria are able to survive these conditions is through the protease/foldase activity of the high temperature requirement A (HtrA) protein. The gut pathogenClostridioides difficileencodes one HtrA homolog that is predicted to contain a membrane anchor and a single PDZ domain. The function of HtrA inC. difficileis hitherto unknown but previous work has shown that an insertional mutant ofhtrAdisplayed elevated toxin levels, less sporulation and decreased binding to target cells. Here, we show that HtrA is membrane associated and localized on the surface ofC. difficileand characterize the requirements for proteolytic activity of recombinant soluble HtrA. In addition, we show that the level of HtrA in the bacteria heavily depends on its proteolytic activity. Finally, we show that proteolytic activity of HtrA is required for survival under acidic conditions.
Uncovering the translatome impact of transcriptome induced diversity in eukaryotes: framework and innovative insights
Authors: Verma Paras , Thakur Deeksha , Pandit Shashi Bhushan 
Published: March 2024

AbstractIsoform diversity is known to enhance a gene’s functional repertoire. Insights into the extent of such sequence variability generated through alternative splicing (AS), may unveil the layers of gene function/regulation. Despite studies on transcriptome diversifying processes, the impact of AS or related processes on sequence diversity still needs to be explored. Current study presents an innovative framework that centralizes exonic loci while integrating protein sequence per entity with attention to splice site variability assessment. The resulting framework enables exon (features) to be tractable, facilitating a systematic, detailed analysis of isoform diversity. We analyzed isoform diversity in five representative organisms and detailed the role of AS and related processes influencing exon inclusion in imparting sequence variation for human genome. Through analyses of exonic variations in two maximally diverged isoforms of human genes, we unraveled intricate splicing patterns prevalent in coding and non-coding regions. We observed that alternative splice sites, sequence changes, and skipping of exons are prevalent in coding exons, while the alternate first exon events are predominant in non-coding exons. Our findings offer a comprehensive understanding of isoform diversity as a function of exonic entity framework, providing valuable insights into the orchestration of exonic events in shaping the proteogenomic landscape.
Novel Polymycoviruses Are Encapsidated in Filamentous Virions
Authors: Han Zhenhao , Jiang Jingjing , Xu Wenxing 
Published: March 2024

AbstractPolymycoviridaeis a new viral family that was established nearly five years ago, but their viral morphologies (naked or encapsidated) remain controversy since only one member namely, Colletotrichum camelliae filamentous virus 1 (CcFV1), was identified as being encapsidated in filamentous virions. Here, three novel dsRNA viruses belonging to the familyPolymycoviridaewere identified in three phytopathogenic fungal strains and tentatively named Pseudopestalotiopsis camelliae-sinensis polymycovirus 1 (PscPmV1), and Phyllosticta capitalensis polymycovirus 1 (PhcPmV1) and -2 (PhcPmV2), respectively. PscPmV1 and PhcPmVs have five or six genomic dsRNAs, ranging from 1055 to 2405 bp, encoding five or seven putative open reading frames (ORFs), of which ORF1 encodes an RNA-dependent RNA polymerase, ORF5 encodes a P-A-S-rich protein behaving as coat protein (CP); and dsRNAs 4 and 6 encode putative proteins with unknown functions and share no detectable identities with known viral sequences. Upon examination under transmission electron microscopy after purification from fungal mycelia, PscPmV1 and PhcPmVs were found to be encapsidated in filamentous particles, as was a known polymycovirus, Botryosphaeria dothidea RNA virus 1 (BdRV1), which was previously assumed to likely have no conventional virions. The morphology of PscPmV1 was further supported by the observation that its particles could be decorated by polyclonal antibodies against its CP and bound by immuno-gold particles conjugated to the specific CP antibody. Together with CcFV1 and BdRV1, PcsPmV1 PhcPmVs provide strong evidence to support the notion that polymycoviruses are encapsidated in filamentous virions constituted by P-A-S-rich CPs. Moreover, their biological effects on their fungal hosts were assessed.Significance statementPolymycoviridae, a recently established viral family, has raised questions about encapsidation. Here, we identify and characterize three novel polymycoviral dsRNA viruses in phytopathogenic fungal strains, tentatively named Pseudopestalotiopsis camelliae-sinensis polymycovirus 1, and Phyllosticta capitalensis polymycovirus 1 and -2, respectively. These polymycoviruses possess five or six genomic dsRNAs, ranging from 1055 to 2405 bp, with two encoding putative proteins of unknown functions and sharing no detectable identities with known viral sequences. Their morphologies indicate filamentous virions constituted by P-A-S-rich coat proteins, observed using immunosorbent electron microscopy combined with immune-gold labeling techniques. Additionally, Botryosphaeria dothidea RNA virus 1, previously assumed to lack conventional virions, is also shown to be encapsidated in filamentous particles. This study provides new evidence supporting the encapsidation of polymycoviruses into elongated and flexuous virions, significantly contributing to our understanding of the evolutionary particle architecture within the virosphere and expanding our knowledge of viral diversity and evolution.
Cerebral perfusion metrics calculated directly, model-free, from a hypoxia-induced step change in deoxyhemoglobin
Authors: Duffin James , Sayin Ece Su , Sobczyk Olivia , Poublanc Julien , Mikulis David J. , Fisher Joseph A. 
Published: March 2024

ABSTRACTDynamic susceptibility contrast (DSC) perfusion MRI measures blood flow metrics via application of a BOLD pulse sequence during transit of a gadolinium-based contrast agent (GBCA), We have previously shown that can also be performed using endogenous deoxyhemoglobin (dOHb) as a replacement for GBCA since dOHb also has the necessary paramagnetic properties similar to GBCA1. Conventional analysis with these contrast agents includes deconvolution of an arterial input function (AIF) assuming a kinetic model. However, the immediate decrease in dOHb that occurs during reoxygenation from a transient hypoxia constitutes a step reduction in susceptibility that permits direct, model-free, calculation of relative resting perfusion metrics. The metrics from this step analysis for seven healthy volunteers were compared to those from a conventional analysis of GBCA and dOHb. Voxel- wise maps of mean transit time, and relative cerebral blood flow and cerebral blood volume, had a high spatial congruence for all three analyses and were similar in appearance to published maps. The time course of the T2*-weighted signal step response identifies both the arrival time, the distribution of the step increase in arterial oxygen saturation, SaO2, and the voxel filling phase. The analysis of a step change in dOHb during rapid reoxygenation is an alternative way of calculating perfusion metrics directly from measurements of the resulting T2*-weighted signal, avoiding the potential errors from the use of a kinetic model and requirement for selection of an AIF.
Transcriptional plasticity of virulence genes provides malaria parasites with greater adaptive capacity for avoiding host immunity
Authors: Florini Francesca , Visone Joseph E. , Hadjimichael Evi , Malpotra Shivali , Nötzel Christopher , Kafsack Björn F.C. , Deitsch Kirk W. 
Published: March 2024

AbstractChronic, asymptomatic malaria infections contribute substantially to disease transmission and likely represent the most significant impediment preventing malaria elimination and eradication.Plasmodium falciparumparasites evade antibody recognition through transcriptional switching between members of thevargene family, which encodes the major virulence factor and surface antigen on infected red blood cells. This process can extend infections for up to a year; however, infections have been documented to last for over a decade, constituting an unseen reservoir of parasites that undermine eradication and control efforts. How parasites remain immunologically “invisible” for such lengthy periods is entirely unknown. Here we show that in addition to the accepted paradigm of mono-allelicvargene expression, individual parasites can simultaneously express multiplevargenes or enter a state in which little or novargene expression is detectable. This unappreciated flexibility provides parasites with greater adaptive capacity than previously understood and challenges the dogma of mutually exclusivevargene expression. It also provides an explanation for the antigenically “invisible” parasites observed in chronic asymptomatic infections.
Evidence of microglial involvement in the childhood abuse-associated increase in perineuronal nets in the ventromedial prefrontal cortex
Authors: Belliveau Claudia , Rahimian Reza , Fakhfouri Gohar , Hosdey Clémentine , Simard Sophie , Davoli Maria Antonietta , Mirault Dominique , Giros Bruno , Turecki Gustavo , Mechawar Naguib 
Published: March 2024

AbstractMicroglia, known for their diverse roles in the central nervous system, have recently been recognized for their involvement in degrading the extracellular matrix. Perineuronal nets (PNNs), a specialized form of this matrix, are crucial for stabilizing neuronal connections and constraining plasticity. Our group recently reported increased PNN densities in the ventromedial prefrontal cortex (vmPFC) of depressed individuals that died by suicide in adulthood after experiencing childhood abuse (DS-CA) compared to matched controls. To explore potential underlying mechanisms, we employed a comprehensive approach in similar postmortem vmPFC samples, combining a human matrix metalloproteinase and chemokine array, isolation of CD11b-positive microglia and enzyme-linked immunosorbent assays (ELISA). Our findings indicate a significant downregulation of matrix metalloproteinase (MMP)-9 and tissue inhibitors of metalloproteinases (TIMP)-2 in both whole vmPFC grey matter and isolated microglial cells from DS-CA samples. Furthermore, our experiments reveal that a history of child abuse is associated with diminished levels of microglial CX3CR1 and IL33R in both vmPFC whole lysate and CD11b isolated cells. However, levels of the CX3CR1 ligand, CX3CL1 (Fractalkine), did not differ between groups. While these data suggest potential long-lasting alterations in microglial markers in the vmPFC of individuals exposed to severe childhood adversity, direct functional assessments were not conducted. Nonetheless, these findings offer insight into how childhood abuse may contribute to PNN alterations via microglial-related mechanisms.Graphical Abstract
Specific proteolysis mediated by a p97-directed proteolysis-targeting chimera (PROTAC)
Authors: Salinas-Rebolledo Constanza , Blesa Javier , Valenzuela-Nieto Guillermo , Schwefel David , del Rey Natalia López González , Méndez-Ruette Maxs , Burkhalter Janine , Bátiz Luis Federico , Jara Ronald , Obeso José A. , Chana-Cuevas Pedro , Sapkota Gopal P. , Rojas-Fernandez Alejandro 
Published: March 2024

AbstractThe p97 protein is a member of the AAA + family of ATPases. It is a mechanoenzyme that uses energy from ATP hydrolysis to promote protein unfolding and segregation actively. The unfolded products of p97 are presented to the 26S Proteasome for degradation. p97 substrate recognition is mediated by adaptors, which interact with substrates directly or indirectly through ubiquitin modifications, resulting in substrate funnelling into the central pore of the p97 hexamer and unfolding. We have engineered synthetic adaptors to target specific substrates to p97, using the extraordinary intracellular binding capabilities of camelid nanobodies fused to the UBX domain of the p97 Adapter FAF1. In such a way, we created a p97-directed proteolysis-targeting chimera (PROTAC), representing a unique E3 ubiquitin ligase-independent strategy to promote specific proteolysis.