bluuebunny/crossref_metadata_2025_split huggingface dataset:
Central Role for Glycolysis and Fatty Acids in LH-responsive Progesterone Synthesis
Authors: Przygrodzka Emilia , Binderwala Fatema , Powers Robert , McFee Renee M. , Cupp Andrea S. , Wood Jennifer R. , Davis John S. 
Published: February 2024

AbstractProgesterone production by the corpus luteum is fundamental for establishing and maintaining pregnancy. The pituitary gonadotropin luteinizing hormone (LH) is recognized as the primary stimulus for luteal formation and progesterone synthesis, regardless of species. Previous studies demonstrated an elevation in abundance of genes related to glucose and lipid metabolism during the follicular to luteal transition. However, the metabolic phenotype of these highly steroidogenic cells has not been studied. Herein, we determined acute metabolic changes induced by LH in primary luteal cells and defined pathways required for progesterone synthesis. Untargeted metabolomics analysis revealed that LH induces rapid changes in vital metabolic pathways, including glycolysis, tricarboxylic acid (TCA) cycle, pentose phosphate pathway,de novolipogenesis, and hydrolysis of phospholipids. LH stimulated glucose uptake, enhanced glycolysis, and flux of [U-13C6]-labeled glucose-derived carbons into metabolic branches associated with adenosine 5’-triphosphate (ATP) and NADH/NADPH production, synthesis of nucleotides, proteins, and lipids, glycosylation of proteins or lipids, and redox homeostasis. Selective use of small molecule inhibitors targeting the most significantly changed pathways, such as glycolysis, TCA cycle, and lipogenesis, uncovered cellular metabolic routes required for LH-stimulated steroidogenesis. Furthermore, LH via the protein kinase A (PKA) pathway triggeredpost-translational modification of acetyl-CoA carboxylase alpha (ACACA) and ATP citrate lyase (ACLY), enzymes involved inde novosynthesis of fatty acids. Inhibition of ACLY and fatty acid transport into mitochondria reduced LH-stimulated ATP, cAMP production, PKA activation, and progesterone synthesis. Taken together, these findings reveal novel hormone-sensitive metabolic pathways essential for maintaining LHCGR/PKA signaling and steroidogenesis in ovarian luteal cells.SignificanceThe establishment and maintenance of pregnancy require a well-developed corpus luteum, an endocrine gland within the ovary that produces progesterone. Although there is increased awareness of intracellular signaling events initiating the massive production of progesterone during the reproductive cycle and pregnancy, there are critical gaps in our knowledge of the metabolic and lipidomic pathways required for initiating and maintaining luteal progesterone synthesis. Here, we describe rapid, hormonally triggered metabolic pathways, and define metabolic targets crucial for progesterone synthesis by ovarian steroidogenic cells. Understanding hormonal control of metabolic pathways may help elucidate approaches for improving ovarian function and successful reproduction or identifying metabolic targets for developing nonhormonal contraceptives.
Local variation in brain temperature explains gender-specificity of working memory performance
Authors: Rogala Jacek , Dreszer Joanna , Sińczuk Marcin , Miciuk Łukasz , Piątkowska-Janko Ewa , Bogorodzki Piotr , Wolak Tomasz , Wróbel Andrzej , Konarzewski Marek 
Published: February 2024

AbstractExploring gender differences in cognitive abilities offers vital insights into human brain functioning. Our study utilized advanced techniques like magnetic resonance thermometry, standard working memory n-back tasks, and functional MRI to investigate if gender-based variations in brain temperature correlate with distinct neuronal responses and working memory capabilities. Interestingly, our findings revealed no gender disparity in working memory performance. However, we observed a significant decrease in average brain temperature in males during working memory tasks, a phenomenon not seen in females. Although changes in female brain temperature were not statistically significant, we found an inverse relationship between the absolute temperature change (ATC) and cognitive performance, alongside a correlation with blood oxygen level dependent (BOLD) neuronal responses. This suggests that in females, ATC is a crucial determinant for the link between cognitive performance and BOLD responses, a linkage not evident in males. Our results also suggest that females compensate for their brain’s heightened temperature sensitivity by activating additional neuronal networks to support working memory. This study not only underscores the complexity of gender differences in cognitive processing but also opens new avenues for understanding how temperature fluctuations influence brain functionality.SignificanceSex/gender differences in cognition are of high scientific and social interest. Yet, those differences (if any) remain elusive. Here we used magnetic resonance thermometry and functional MRI to examine, whether gender differences in working memory performance (WMP) are determined by subtle, yet detectable between-sex differences in local brain temperature fluctuations mediated by blood oxygen level-dependent (BOLD) neuronal responses. We found that WMP did not differ between genders. Yet, a female’s WMP was more sensitive to brain temperature variation compared to males. Furthermore, the negative impact of temperature on female cognitive functions was compensated by higher BOLD activity in other task-specific brain areas. This compensation may account for equivocal results of studies on the between-sex differences in cognitive performance.
SOCS domain targets ECM assembly in lung fibroblasts and experimental lung fibrosis
Authors: Magdaleno Carina , Tschumperlin Daniel J. , Rajasekaran Narendiran , Varadaraj Archana 
Published: February 2024

AbstractIdiopathic pulmonary fibrosis (IPF) is a fatal disease defined by a progressive decline in lung function due to scarring and accumulation of extracellular matrix (ECM) proteins. The SOCS (Suppressor Of Cytokine Signaling) domain is a 40 amino acid conserved domain known to form a functional ubiquitin ligase complex targeting the Von Hippel Lindau (VHL) protein for proteasomal degradation. Here we show that the SOCS conserved domain operates as a molecular tool, to disrupt collagen and fibronectin fibrils in the ECM associated with fibrotic lung myofibroblasts. Our results demonstrate that fibroblasts differentiated using TGFß, followed by transduction with the SOCS domain, exhibit significantly reduced levels of the contractile myofibroblast-marker, α-SMA. Furthermore, in support of its role to retard differentiation, we find that lung fibroblasts expressing the SOCS domain present with significantly reduced levels of α-SMA and fibrillar fibronectin after differentiation with TGFß. We show that adenoviral delivery of the SOCS domain in the fibrotic phase of experimental lung fibrosis in mice, significantly reduces collagen accumulation in disease lungs. These data underscore a novel function for the SOCS domain and its potential in ameliorating pathologic matrix deposition in lung fibroblasts and experimental lung fibrosis.
A single amino acid in theSalmonellaeffector SarA/SteE triggers supraphysiological activation of STAT3 for anti-inflammatory target gene expression
Authors: Gaggioli Margaret R. , Jones Angela G. , Panagi Ioanna , Washington Erica J. , Loney Rachel E. , Muench Janina H. , Brennan Richard G. , Thurston Teresa L. M. , Ko Dennis C. 
Published: February 2024

SummaryNon-typhoidalSalmonella entericacause an estimated 1 million cases of gastroenteritis annually in the United States. These serovars use secreted protein effectors to mimic and reprogram host cellular functions. We previously discovered that the secreted effector SarA (Salmonellaanti-inflammatory response activator; also known as SteE) was required for increased intracellular replication ofS.Typhimurium and production of the anti-inflammatory cytokine interleukin-10 (IL-10). SarA facilitates phosphorylation of STAT3 through a region of homology with the host cytokine receptor gp130. Here, we demonstrate that a single amino acid difference between SarA and gp130 is critical for the anti-inflammatory bias of SarA-STAT3 signaling. An isoleucine at the pY+1 position of the YxxQ motif in SarA (which binds the SH2 domain in STAT3) causes increased STAT3 phosphorylation and expression of anti-inflammatory target genes. This isoleucine, completely conserved in ∼4000Salmonellaisolates, renders SarA a better substrate for tyrosine phosphorylation by GSK-3. GSK-3 is canonically a serine/threonine kinase that nonetheless undergoes tyrosine autophosphorylation at a motif that has an invariant isoleucine at the pY+1 position. Our results provide a molecular basis for how aSalmonellasecreted effector achieves supraphysiological levels of STAT3 activation to control host genes during infection.
Development of a signal-integrating reporter to monitor mitochondria-ER contacts
Authors: Yang Zheng , Chan David C. 
Published: February 2024

AbstractMitochondria-ER contact sites (MERCS) serve as hotspots for important cellular processes, including calcium homeostasis, phospholipid homeostasis, mitochondria dynamics, and mitochondrial quality control. MERCS reporters based on complementation of GFP fragments have been designed to visualize MERCS in real-time, but we find that they do not accurately respond to changes in MERCS content. Here, we utilize split LacZ complementing fragments to develop the first MERCS reporter system (termed SpLacZ-MERCS) that continuously integrates the MERCS information within a cell and generates a fluorescent output. Our system exhibits good organelle targeting, no artifactual tethering, and effective, dynamic tracking of the MERCS level in single cells. The SpLacZ-MERCS reporter was validated by drug treatments and genetic perturbations known to affect mitochondria-ER contacts. The signal-integrating nature of SpLacZ-MERCS may enable systematic identification of genes and drugs that regulate mitochondria-ER interactions. Our successful application of the split LacZ complementation strategy to study MERCS may be extended to study other forms of inter-organellar crosstalk.
Protein UFMylation regulates early events of ribosomal DNA double-stranded break response
Authors: Panichnantakul Pudchalaluck , Aguilar Lisbeth C. , Daynard Evan , Guest Mackenzie , Peters Colten , Vogel Jackie , Oeffinger Marlene 
Published: February 2024

ABSTRACTThe highly repetitive and transcriptionally active ribosomal DNA (rDNA) genes are exceedingly susceptible to genotoxic stress. Induction of DNA double-strand breaks (DSBs) in rDNA repeats is associated with ATM-dependent rDNA silencing and nucleolar reorganization where rDNA is segregated into nucleolar caps. However, the regulatory events underlying this response remain elusive. Here, we identify protein UFMylation as essential for rDNA damage response in human cells. We further show the only UFM1-E3-ligase UFL1 and its binding partner DDRGK1 localize to nucleolar caps upon rDNA damage, and that UFL1 loss impairs ATM activation and rDNA transcriptional silencing, leading to reduced rDNA segregation. A first-ever analysis of nuclear and nucleolar UFMylation targets in response to DSBs induction further identified key DNA repair factors including ATM, in addition to chromatin and actin network regulators. Taken together, our data provides the first evidence of an essential role for UFMylation in orchestrating rDNA DSB repair.
Multi-species community platform for comparative neuroscience in teleost fish
Authors: Vohra Sumit , Herrera Kristian , Tavhelidse-Suck Tinatini , Wittbrodt Joachim , Knoblich Simon , Seleit Ali , Aulehla Alexander , Boulanger-Weill Jonathan , Chambule Sydney , Aspiras Ariel , Santoriello Cristina , Fishman Mark , Hege Hans-Christian , Baum Daniel , Engert Florian , Isoe Yasuko 
Published: February 2024

AbstractStudying neural mechanisms in complementary model organisms from different ecological niches in the same animal class can leverage the comparative brain analysis at the cellular level. To advance such a direction, we developed a unified brain atlas platform and specialized tools that allowed us to quantitatively compare neural structures in two teleost larvae, medaka (Oryzias latipes) and zebrafish (Danio rerio). Leveraging this quantitative approach we found that most brain regions are similar but some subpopulations are unique in each species. Specifically, we confirmed the existence of a clear dorsal pallial region in the telencephalon in medaka lacking in zebrafish. Further, our approach allows for extraction of differentially expressed genes in both species, and for quantitative comparison of neural activity at cellular resolution. The web-based and interactive nature of this atlas platform will facilitate the teleost community’s research and its easy extensibility will encourage contributions to its continuous expansion.
Programmed cell death and the origin of wing polyphenism in ants: implications for major evolutionary transitions in individuality
Authors: Hanna Lisa , Boudinot Brendon E. , Liebig Jürgen , Abouheif Ehab 
Published: February 2024

ABSTRACTMajor evolutionary transitions in individuality occur when solitary individuals unite to form a single replicating organism with a division of labor between constituent individuals. Key examples include the evolution of multicellularity, eusociality, and obligate endosymbiosis. Programmed Cell Death (PCD) has been proposed to play an important role during major transitions to multicellularity, yet it remains unclear to what extent PCD plays a role in other major transitions. Here we test if PCD was involved in the major transition to eusociality in ants, where solitary individuals united to form eusocial colonies with a division of labor between a winged queen caste and a wingless worker caste. The development of wings in queens but not in workers in response to environmental cues is called wing polyphenism, which evolved once and is a general feature of ants. Both wing polyphenism and eusociality evolved at the same time during the origin of ants and were likely intimately linked––the suppression of wings in workers may have reduced their ability to participate in mating flights thereby reinforcing the reproductive division of labor within the parental nest. We therefore tested whether PCD plays a role in the degeneration of wings during development of the worker caste across the ant phylogeny encompassing species with both ancestral-like and derived characteristics. We show that PCD, mediated by the apoptosis pathway, is present in the degenerating wing primordia of worker larvae in 15 out of the 16 species tested. Using ancestral state reconstruction, we infer a role for PCD in regulating wing polyphenism in the last common ancestor of all extant ants. Our findings provide evidence that a degenerative mechanism (PCD) plays a role in the origin of wing polyphenism, and therefore, in facilitating the major transition to eusociality in ants. PCD may generally play a key role in the evolution of biological complexity by facilitating major transitions at different scales, such as multicellularity and eusociality.
Long-Term Impact of Molecular Epidemiology Shifts of Methicillin-resistantStaphylococcus aureuson Severity and Mortality of Bloodstream Infection
Authors: Kaku Norihito , Ishige Masaki , Yasutake Go , Sasaki Daisuke , Ota Kenji , Mitsumoto-Kaseida Fujiko , Kosai Kosuke , Hasegawa Hiroo , Izumikawa Koichi , Mukae Hiroshi , Yanagihara Katsunori 
Published: February 2024

AbstractA 2019 nationwide study in Japan revealed the predominant methicillin-resistant Staphylococcus aureus (MRSA) types in bloodstream infections (BSIs) to be sequence type (ST)8-carrying SCCmectype IV (ST8-MRSA-IV) and clonal complex 1-carrying SCCmectype IV (CC1- MRSA-IV). However, detailed patient characteristics and how these MRSA types evolve over time remain largely unknown. In this long-term single-center study, MRSA strains isolated from blood cultures at Nagasaki University Hospital from 2012 to 2019 were sequenced and analyzed. Additionally, we compared the SCCmectypes and patient characteristics identified in this study with previous data from our hospital spanning 2003 to 2007 and 2008 to 2011. Over this 16-year period, SCCmectype II decreased significantly from 79.2% to 15.5%, while type IV increased from 18.2% to 65.5%. This shift in SCCmectypes was associated with notable changes in severity and outcomes; the sequential organ failure assessment (SOFA) score decreased from 5.8 to 3.1; in-hospital mortality declined from 39.8% to 15.5%. In contrast, no significant changes in patient demographics, such as age, sex, or underlying diseases, were observed. Between 2012 and 2019, the major combinations of SCCmectype and sequence type were ST8-MRSA-IV, ST8-MRSA-I, CC1-MRSA-IV, and ST5-MRSA-II. Additionally, ST8-MRSA-IV was divided into CA-MRSA/J, t5071-ST8-MRSA-IV, and USA300-like clone based on the results of molecular analysis. These major combinations showed similar drug resistance patterns, molecular characteristics, and phylogenetic features to those identified in nationwide surveillance. This study highlights the evolving nature of MRSA types in bloodstream infections, correlating with improved patient outcomes over time.
Changes in serum CXCL13 levels are associated with outcomes of Colorectal Cancer Patients Undergoing First-Line Oxaliplatin-Based Treatment
Authors: Cabrero-de las Heras Sara , Hernández-Yagüe Xavier , González Andrea , Losa Ferran , Soler Gemma , Bugés Cristina , Baraibar Iosune , Esteve Anna , Pardo-Cea Miguel Ángel , Ree Anne Hansen , Martínez-Bosch Neus , Nieva Maria , Musulén Eva , Meltzer Sebastian , Lobato Tania , Vendrell-Ayats Carla , Queralt Cristina , Navarro Pilar , Montagut Clara , Grau-Leal Ferran , Camacho David , Legido Raquel , Mulet-Margalef Núria , Martínez-Balibrea Eva 
Published: February 2024

AbstractBackgroundReliable biomarkers for precision medicine in metastatic colorectal cancer (mCRC) are needed. Blood biomarkers like chemokines may offer insights into overall tumor burden, yet, few prospective studies explore chemokine dynamics during treatment. This study investigates the behavior of a chemokine panel in mCRC patients during first-line oxaliplatin-based treatment, aiming to identify predictive and prognostic biomarkers.MethodsBlood from oxaliplatin-treated mCRC patients was collected at three time points: before treatment (PRET), at response evaluation (EVAR), and at disease progression or last follow-up (LFUP). A custom 11-chemokine panel assessed serum chemokine levels by Luminex®, correlating them with treatment response, overall survival (OS), and progression-free survival (PFS) using the Cox proportional hazards models with the inverse probability weighting (IPW) approach. Additionally, immune system-associated gene expression was studied by Nanostring® in 15 primary tumor samples and correlated with CXCL13 expression, OS, and PFS.In silicoanalysis of 119 liver metastases from CRC patients, post neoadjuvant oxaliplatin-based treatment or untreated, evaluated CXCL13 expression’s correlation with immune cell infiltration, tertiary lymphoid structure (TLS) presence, OS, and PFS. Additionally, CXCL13 dynamics was studied by ELISA in 36 mCRC patients from the METIMMOX study control arm.ResultsResponders exhibited increased CXCL13 at EVAR, contrasting with non-responders whose levels decreased at EVAR and LFUP. Increased CXCL13 independently associated with improved PFS (median 14.5 vs. 8.9 months; HR = 0.34, p = 0.003) and OS (median 39.7 vs. 15.3 months; HR = 0.34, p = 0.003). CXCL13 expression correlated positively with an immunogenic tumor microenvironment, increased B cells, T cells (mainly CD8+) and enhanced OS.In silico, higher CXCL13 expression associated significantly with increased immune infiltration and improved OS. High CXCL13 expression was linked to the presence of TLSs, also associated with enhanced OS, especially in neoadjuvant-treated patients. Similar trends were obtained using the METIMMOX cohort.ConclusionThe increase of CXCL13 levels in peripheral blood and its association with the formation of TLSs within the metastatic lesions, emerges as a potential biomarker indicative of the therapeutic efficacy in metastatic CRC patients undergoing oxaliplatin-based treatment.
Anthropogenic noise affects vocalisation properties of the territorial song of Western Australian magpies
Authors: Blackburn Grace , Dutour Mylene , Ashton Benjamin J. , Thornton Alex , Ridley Amanda R. 
Published: February 2024

AbstractAnthropogenic noise is considered one of the most serious forms of pollution globally and has been shown to have negative effects on the distribution, behaviour, cognition and reproductive success of animal species worldwide. One of the most well researched impacts of anthropogenic noise is its effect on acoustic communication. Animals may adjust the rate, amplitude, duration, and/or frequency of their acoustic signals to better maintain communication when anthropogenic noise is present. In this study, we combine behavioural focals, amplitude measurements and audio recordings to investigate how female Western Australian magpies (Gymnorhina tibicen dorsalis) alter the acoustic features of their territorial song (known as a carol) when anthropogenic noise is present. Magpies reduced the rate at which they carolled when loud anthropogenic noise was present, and increased their peak frequency during anthropogenic noise, but, contrary to our hypotheses did not alter the amplitude, duration, or other frequency parameters of their carols. Results from this study add to the growing body of literature documenting changes to the vocal behaviour of wildlife in the presence of anthropogenic noise and highlights the importance of investigating multiple acoustic parameters to understand how species adjust their vocalisations in response to this pollutant.
The transmembrane protein Syndecan regulates stem cell nuclear properties and cell maintenance
Authors: Eldridge-Thomas Buffy L. , Bohere Jerome G. , Roubinet Chantal , Barthelemy Alexandre , Samuels Tamsin J. , Teixeira Felipe Karam , Kolahgar Golnar 
Published: February 2024

AbstractTissue maintenance is underpinned by resident stem cells whose activity is modulated by microenvironmental cues. UsingDrosophilaas a simple model to identify regulators of stem cell behaviour and survivalin vivo, we have identified novel connections between the conserved transmembrane proteoglycan Syndecan, nuclear properties and stem cell function. In theDrosophilamidgut, Syndecan depletion in intestinal stem cells results in their loss from the tissue, impairing tissue renewal. At the cellular level, Syndecan depletion alters cell and nuclear shape, and causes nuclear lamina invaginations and DNA damage. In a second tissue, the developingDrosophilabrain, live imaging revealed that Syndecan depletion in neural stem cells results in nuclear envelope remodelling defects which arise upon cell division. Our findings reveal a new role for Syndecan in the maintenance of nuclear properties in diverse stem cell types.Graphical Abstract