bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure, function and assembly of soybean primary cell wall cellulose synthases
Authors: Ho Ruoya , Purushotham Pallinti , Wilson Louis F. L. , Wan Yueping , Zimmer Jochen
Published: February 2024

Plant cell walls contain a meshwork of cellulose fibers embedded into a matrix of other carbohydrate and non-carbohydrate-based biopolymers. This composite material exhibits extraordinary properties, from stretchable and pliable cell boundaries to solid protective shells. Cellulose, a linear glucose polymer, is synthesized and secreted across the plasma membrane by cellulose synthase (CesA), of which plants express multiple isoforms. Different subsets of CesA isoforms are necessary for primary and secondary cell wall biogenesis. Here, we structurally and functionally characterize theGlycine max(soybean) primary cell wall CesAs CesA1, CesA3, and CesA6. The CesA isoforms exhibit robustin vitrocatalytic activity. Cryo-electron microscopy analyses reveal their assembly into homotrimeric complexesin vitroin which each CesA protomer forms a cellulose-conducting transmembrane channel with a large lateral opening. Biochemical and co-purification analyses demonstrate that different CesA isoforms interactin vitro, leading to synergistic cellulose biosynthesis. Interactions between CesA trimers are only observed between different CesA isoforms and require the class-specific region (CSR). The CSR forms a hook-shaped extension of CesA’s catalytic domain at the cytosolic water-lipid interface. Negative stain and cryo-electron microscopy analyses of mixtures of different CesA isoform trimers reveal their side-by-side arrangement into loose clusters. Our data suggest a model by which CesA homotrimers of different isoforms assemble into cellulose synthase complexes to synthesize and secrete multiple cellulose chains for microfibril formation. Inter-trimer interactions are mediated by fuzzy interactions between their CSR extension.
Development of subunit selective proteasome substrates forSchistosoma species
Authors: Jiang Zhenze , Silva Elany B. , Liu Chenxi , Fajtová Pavla , Liu Lawrence J. , El-Sakkary Nelly , Skinner Danielle E. , Syed Ali , Wang Steven C , Caffrey Conor R. , O’Donoghue Anthony J.
Published: February 2024

Schistosomiasis, or bilharzia, is a neglected tropical disease caused bySchistosomaspp. blood flukes that infects over 200 million people worldwide. Just one partially effective drug is available, and new drugs and drug targets would be welcome. The 20S proteasome is a validated drug target for many parasitic infections, including those caused byPlasmodiumandLeishmania. We previously showed that anticancer proteasome inhibitors that act through theSchistosoma mansoni20S proteasome (Sm20S) kill the parasitein vitro. To advance these initial findings, we employed Multiplex Substrate Profiling by Mass Spectrometry (MSP-MS) to define the substrate cleavage specificities of the three catalytic β subunits of purified Sm20S. The profiles in turn were used to design and synthesize subunit-specific optimized substrates that performed two to eight fold better than the equivalent substrates used to measure the activity of the constitutive human proteasome (c20S). These specific substrates also eliminated the need to purify Sm20S from parasite extracts - a single step enrichment was sufficient to accurately measure substrate hydrolysis and its inhibition with proteasome inhibitors. Finally, we show that the substrate and inhibition profiles for the 20S proteasome from the three medically important schistosome species are similar, suggesting that data arising from an inhibitor development campaign that focuses on Sm20S can be extrapolated to the other two targets with consequent time and cost savings.
Herbarium specimens reveal links betweenCapsella bursa-pastorisleaf shape and climate
Authors: Hightower Asia T , Chitwood Daniel H , Josephs Emily B
Published: February 2024

Studies into the evolution and development of leaf shape have connected variation in plant form, function, and fitness. For species with consistent leaf margin features, patterns in leaf architecture are related to both biotic and abiotic factors. However, for species with inconsistent leaf margin features, quantifying leaf shape variation and the effects of environmental factors on leaf shape has proven challenging.

To investigate leaf shape variation in species with inconsistent shapes, we analyzed approxi-mately 500 digitizedCapsella bursa-pastorisspecimens collected throughout the continental U.S. over a 100-year period with geometric morphometric modeling and deterministic techniques. We generated a morphospace ofC. bursa-pastorisleaf shapes and modeled leaf shape as a function of environment and time.

Our results suggestC. bursa-pastorisleaf shape variation is strongly associated with temperature over theC. bursa-pastorisgrowing season, with lobing decreasing as temperature increases. While we expected to see changes in variation over time, our results show that level of leaf shape variation is consistent over the 100-year period.

Our findings showed that species with inconsistent leaf shape variation can be quantified using geometric morphometric modeling techniques and that temperature is the main environmental factor influencing leaf shape variation.
Fraudulent studies are undermining the reliability of systematic reviews – a study of the prevalence of problematic images in preclinical studies of depression
Authors: Berrío Jenny P. , Kalliokoski Otto
Published: February 2024

Systematic reviews are considered by many to constitute the highest level of scientific evidence. A caveat is that the methods used in a systematic review – combining information from multiple studies – are predicated on all of the reports being truthful. Currently, we do not know how frequent fraudulent studies are in systematic reviews, or how they affect the resulting evidence base. For a systematic review of preclinical studies of depression, we found that potentially fraudulent studies were not only common but also that they biased the findings of the review. In a sample of 1,035 studies, we found that 19 % of peer-reviewed reports displayed data in the form of problematic images. In a majority of the cases, images had been altered or recycled in a way that makes us suspect foul play. Making things worse, these studies reported larger effect sizes, on average, than did studies where we did not identify problems. Counter to commonly held beliefs, reports with problematic images were not cited less or published in lower-impact journals, nor were their authors isolated to any specific geographic area. The sheer prevalence of problematic studies, and the fact that we could not find a simple pattern for identifying them, undermines the validity of systematic reviews within our research field. We suspect that this is symptomatic of a broader problem that needs immediate addressing.
Angiogenin regulates mitochondrial stress and function via tRNA-derived fragments generation and impacting tRNA modifications
Authors: Al-Mesitef Shadi , Tominaga Keita , Mousa Abdulrahman , Begley Thomas J , Dedon Peter C , Rashad Sherif , Niizuma Kuniyasu
Published: February 2024

Mitochondrial stress and dysfunction play an important role in many diseases, such as cancer, diabetes, and neurodegenerative diseases. We previously observed that mitochondrial electron transport chain (ETC) inhibition can induce tRNA cleavage and tsRNAs (tRNA-derived small non-coding RNAs) generation. However, whether this process is mediated via Angiogenin (ANG), the canonical enzyme responsible for tRNA cleavage, and whether it has a role in regulating the mitochondrial stress response remains to be understood. ANG is linked to Amyotrophic Lateral Sclerosis (ALS) and other conditions where mitochondrial stress plays a role in pathophysiology. Here, we aimed to examine the role of ANG in regulating the translational response to mitochondrial stress. We observed that ANG protected the cells from respiratory complex III and V inhibition specifically. Furthermore, we validated that the tsRNAs generated during mitochondrial and oxidative stress are mediated by ANG, given that their production is abrogated after ANG knock-out (KO). In addition, we observed that ANG-KO altered the tRNA modification status. Namely, we observed that ANG-KO led to the downregulation of queuosine tRNA modifications (tRNA-Q). tRNA-Q itself is related to mitochondrial translation and function. Indeed, we observed that ANG-KO led to reduced mitochondrial respiration and function. ANG altered how the cells respond to mitochondrial stress by altering the dynamic tRNA modification changes occurring during the stress response. We further examined the impact of ANG-KO on stress granules (SG) assembly as well as the knockdown of G3BP1 (core protein of SGs) on tsRNAs generation. Our results indicate that ANG regulates mitochondrial function and stress via tsRNAs generation as well as altering tRNA modifications levels. Our data also indicate that there are no direct links between tRNA cleavage and SG assembly, and both could be parallel systems for translation repression during stress.
Inflammatory bowel disease and risk of more than 1500 comorbidities: A disease-wide pre- and post-diagnostic phenomic association study
Authors: Ebert Anthony C , Elmahdi Rahma , Verstockt Bram , Bøgsted Martin , Poulsen Gry , Sazonovs Aleksejs , Lees Charlie W , Jess Tine
Published: February 2024

Introduction

Inflammatory bowel disease (IBD) is associated with various extra-intestinal manifestations. We aim to identify comorbidities in IBD and the timing of their development to provide valuable insight into the mechanisms under-lying IBD.

Methods

We conducted a population– and disease-wide phenomic association study in IBD, using>6 million ICD-10 coded healthcare contacts from 10 years before and up-to 17 years after IBD diagnosis to investigate associations with 1583 comorbidities. To explore diseases with potential aetiological significance, we compared association in the pre-diagnostic and the post-diagnostic periods. We corrected also for multiple-testing. These estimates were validated with publically available data from Finland.

Results

We identified 312 significant associations with 125 appearing before diagnosis. Risk of immune-mediated diseases and extra-intestinal manifestations was increased up to 10 years prior to IBD diagnosis, such as psoriasis (ORCD: 2.58 95% CI: [2.00-3.31]; ORUC: 1.54 [1.26-1.88]) and reactive arthropathies (ORCD: 2.07 [1.42-2.96]; ORUC: 1.42 [1.08-1.84]). Risk of cardiometabolic and neuropsychological disorders was increased both pre– and post-diagnostically. Potential treatment sequelae, such as osteoporosis (HRCD: 2.56 [2.30-2.86]; HRUC: 1.92 [1.79-2.07]) were primarily seen post-diagnostically. In only 15.7% (44/281) and 11.4% (35/301) of comorbidities in CD and UC respectively did we observe heterogeneity between Denmark and Finland.

Conclusion

Findings demonstrate that IBD is a multisystemic disease, particularly manifesting with metabolic, im-mune, and neuropsychological disorders, up-to 10 years prior to diagnosis. We find evidence for the generality of these findings with an international comparison. Diseases of etiological interest warrant further investigation.

STUDY HIGHLIGHTS

WHAT IS KNOWN

IBD is strongly associated with other diseases

IBD has a complex etiology

WHAT IS NEW HERE

IBD appears to be a multiorgan systemic disease not confined to the gut

Associations between IBD and non-digestive disorders are present up to 10 years prior to diagnosis either reflecting a prolonged pre-diagnostic phase or common etiologies

These findings are validated in an international comparison
Anti-inflammatory effects of oral prednisolone at stable state in people treated with mepolizumab: a proteomic and bulk transcriptomics analysis
Authors: Howell I. , Yang F. , Brown V. , Cane J. , Marchi E. , Azim A , Busby J. , McDowell P.J. , Diver S.E. , Borg C. , Heaney L. G. , Pavord I. D. , Brightling C. E. , Chaudhuri R. , Hinks T.S.C.
Published: February 2024

Mepolizumab is an anti-interleukin-5 monoclonal antibody treatment for severe eosinophilic asthma (SEA) that reduces asthma exacerbations. Residual airway inflammation on mepolizumab may lead to persistent exacerbations. Oral corticosteroids have broad anti-inflammatory effects and remain the main treatment for these residual exacerbations. Our study aimed to explore the nature and corticosteroid-responsiveness of airway inflammation after mepolizumab treatment to find potentially treatable inflammatory mechanisms.

The MAPLE trial was a multi-centre, randomized, double-blind, placebo-controlled, crossover study of 2 weeks of high-dose oral prednisolone treatment at stable state in patients treated with mepolizumab for SEA. We analysed sputum and plasma samples from the MAPLE trial using high-throughput Olink® proteomics. We also analysed plasma microRNA, sputum proteins using ELISA, and nasal mucosal bulk RNA sequencing.

In patients receiving mepolizumab, prednisolone significantly downregulated sputum proteins related to type-2 inflammation and chemotaxis including IL-4, IL-5, IL-13, CCL24, CCL26, EDN, CCL17, CCL22, OX40 receptor, FCER2, and the ST2 receptor. Prednisolone also downregulated cell adhesion molecules, prostaglandin synthases, mast cell tryptases, MMP1, MMP12, and neuroimmune mediators. Tissue repair and neutrophilic pathways were upregulated. Type-2 proteins were also downregulated in plasma, combined with IL-12, IFN-γ, and IP-10. IL-10 and amphiregulin were upregulated. In the nasal transcriptome, prednisolone suppressed genes involved in leucocyte chemotaxis, mast cell tryptase, 15-lipoxygenase andMMP12. By contrast, mepolizumab differentially regulated only Galectin-10 in plasma and no sputum proteins, and in nasal tissue affected genes related to cilia, keratinisation, extracellular matrix formation, and IL-4/13 signalling.

At stable state, prednisolone has broad anti-inflammatory effects on top of mepolizumab.

Graphical abstract
Perceptions of Complementary, Alternative, and Integrative Medicine Among Neurology Researchers and Clinicians: A Large-Scale, International Cross-Sectional Survey
Authors: Ng Jeremy Y. , Li Stephanie Y. , Cramer Holger
Published: February 2024

Background

While many patients with neurological disorders and conditions use complementary, alternative, and integrative medicine (CAIM), little is known about the use and perceptions of CAIM among neurology researchers and clinicians. With the increasing popularity of CAIM, our objective was to assess practices, perceptions, and attitudes towards CAIM among neurology researchers and clinicians.

Methods

We conducted an anonymous online survey of authors who had published articles in neurology journals indexed in MEDLINE. We emailed potential participants our cross-sectional electronic survey after extracting their email addresses from one of their publications in our sample of journals. Basic descriptive statistics were drawn from quantitative data, and thematic content analysis was used to analyse qualitative data from any open-ended questions.

Results

The survey was completed by 783 neurology researchers and/or clinicians (1.5% response rate, 83.9% completion rate). Overall, respondents perceived CAIM to be promising in preventing, treating, and/or managing neurological diseases. Mind-body therapies received the most positive responses, indicated by over half of respondents cumulatively agreeing that they are promising (n=368, 59.0%) and safe (n=280, 50.3%). Whole medical systems and biofield therapy were less favourable. Most neurology clinicians reported a lack of formal (n=211, 70.3%) and supplementary training (n=158, 52.5%) on CAIM. Nearly half of clinicians did not feel comfortable counselling patients about CAIM (n = 121, 44.5%), and over half did not feel comfortable recommending it (n=161, 59.3%). A lack of scientific evidence for CAIM’s safety and efficacy was reported as the greatest challenge to CAIM (n=515, 92.5%). The majority of respondents believed there is value to conducting research on this topic (n=461, 82.0%) and supported increasing allocation of research funding towards CAIM (n=241, 58.9%).

Conclusions

Although many participants found CAIM to be promising to the field of neurology, the vast majority did not feel open to integrating CAIM into mainstream medical practices on account of a perceived lack of scientific evidence for its safety and efficacy. Future studies can use our findings to improve educational resources on CAIM within neurology, as well as examine what effects a tailored CAIM education has on the perceptions of neurology researchers and clinicians.
Shifting to biology promotes highly efficient iron removal in groundwater filters
Authors: Müller Simon , Corbera-Rubio Francesc , Schoonenberg-Kegel Frank , Laureni Michele , van Loosdrecht Mark C.M. , van Halem Doris
Published: February 2024

Rapid sand filters are established and widely applied technologies for groundwater treatment. Conventionally, intensive aeration is employed to provide oxygen for the oxidation and removal of the main groundwater contaminants. While effective, intensive aeration promotes flocculent iron removal, which results in iron flocs that rapidly clog the filter. In this study, we operated two parallel full-scale sand filters at different aeration intensities to resolve the relative contribution of homogeneous, heterogeneous and biological iron removal pathways, and identify their operational controls. Our results show that mild aeration in the LOW filter (5 mg/L O2pH 6.9) promoted biological iron removal and enabled iron oxidation at twice the rate compared to the intensively aerated HIGH filter (>10mg/L O2,pH 7.4). ESEM images showed distinctive twisted stalk-like Fe solids, biosignatures ofGallionella ferruginea, both in the LOW filter sand coatings as well as in its backwash solids. In accordance, 10 times higher DNA copy numbers ofG. ferrugineawere found in the LOW filter effluent. Clogging by biogenic FeOx was slower than by chemical FeOx flocs, resulting in lower backwash frequencies and yielding four times more water per run. Ultimately, our results reveal that biological Fe2+oxidation can be actively controlled and favoured over competing physico-chemical routes. The resulting operational benefits are only starting to be appreciated, with the counterintuitive higher oxidation rates and water yields at lower aeration regimes, and the production of more compact and practically valuable FeOx solids being of outmost interest.
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

Progesterone 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.

Significance

The 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

Exploring 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.

Significance

Sex/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

Idiopathic 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

Non-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

Mitochondria-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

The 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

Studying 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

Major 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

A 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

Background

Reliable 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.

Methods

Blood 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.

Results

Responders 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.

Conclusion

The 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

Anthropogenic 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

Tissue 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
The De Bruijn Graph Sequence Mapping Problem with Changes in the Graph
Authors: Rocha Lucas B. , Adi Said Sadique , Araujo Eloi
Published: February 2024

In computational biology, mapping a sequencesonto a sequence graphGposes a significant challenge. One possible approach to tackling this problem is to find a walkpinGthat spells a sequence most similar tos. This challenge is formally known as the Graph Sequence Mapping Problem (GSMP). In this paper, we delve into an alternative problem formulation known as the De Bruijn Graph Sequence Mapping Problem (BSMP). Both problems have three variants: changes only in the sequence, changes in the graph, and changes in both the sequence and the graph. We concentrate on addressing the variant involving changes in the graph. In the literature, when this problem does not allow the De Bruijn graph to induce new arcs after changes, it becomes NP-complete, as proven by Gibneyet. al[4]. However, we reformulate the problem by considering the characteristics of the arcs induced in the De Bruijn graph. This reformulation alters the problem definition, thereby enabling the application of a polynomial-time algorithm for its resolution. Approaching the problem with this arc-inducing characteristic is new, and the algorithm proposed in this work is new in the literature.
Adeno-associated viruses for efficient gene expression in the axolotl nervous system
Authors: Lust Katharina , Tanaka Elly M.
Published: February 2024

Axolotls are models for studying nervous system evolution, development, and regeneration. Tools to visualize and manipulate cells of the axolotl nervous system with high efficiency, spatial and temporal precision are therefore greatly required. Recombinant adeno-associated viruses (AAVs) are frequently used forin vivogene transfer of the nervous system but virus-mediated gene delivery to the axolotl nervous system has not yet been described. Here, we demonstrate the use of AAVs for efficient gene transfer within the axolotl brain and the retina. We show that serotypes AAV8, AAV9, AAVRG and AAVPHP.eB are suitable viral vectors to infect both excitatory and inhibitory neuronal populations of the axolotl brain. We further use AAV9 to trace retrograde and anterograde projections between the retina and the brain and identify a cell population projecting from the brain to the retina. Together, our work establishes AAVs as a powerful tool to interrogate neuronal organization in the axolotl.
Dispersal and gene flow in anadromous salmonids: a systematic review
Authors: Lamarins Amaïa , Carlson Stephanie M. , Buoro Mathieu
Published: February 2024

Dispersal is a ubiquitous ecological process that has been extensively studied in many plants and animals. Anadromous salmonids are an interesting system for examining dispersal, in part because of their well-known philopatric behavior, but also because of the conservation challenges related to the dispersal of hatchery-origin fish. Building on earlier work, we provide an updated systematic review of dispersal and gene flow in anadromous salmonids. In particular, we compared studies on dispersal of anadromous salmonids from wild and hatchery origins, including studies providing estimates of dispersal rates, observations of dispersal, and results from modelling studies. We reviewed 228 studies and found these were unevenly distributed among species, with Atlantic salmon, Chinook salmon, and sea trout being well-represented. Our results showcase considerable variability in estimated dispersal rates within and across studies, which is likely related to the different methodologies, dispersal propensities across species and populations, and spatial extents considered. Overall, our results confirmed a higher tendency of hatchery fish to disperse relative to wild fish, but we also found some variation across species that warrants further study. Moreover, we found that dispersal propensity tended to decline exponentially with distance, and that the drivers of dispersal varied considerably among studies. Additionally, we highlight various facets of dispersal captured across this suite of studies, including variation in terminology, methods and metrics for characterizing dispersal, and the spatio-temporal scales considered. Finally, our review revealed that few studies considered, and even fewer assessed, the implications of dispersal for the conservation and management of anadromous salmonids.
Multibaryon configurations in a simple chromomagnetic model
Authors: Park Aaron
Published: February 2024

In this work, we study the multibaryon configurations in a simple chromomagnetic model. We first construct the wave function of the multibaryon states using the multiquark configuration. We consider all possible quantum numbers assuming the spatial part of the wave function to be totally symmetric. Then, we calculate the color-spin factors for tetrabaryons, pentabaryons, and hexabaryons in the flavor SU(3) breaking case and discuss its physical application.

Published by the American Physical Society
2024
Elastic nucleon-pion scattering amplitudes in the
Δ
channel at physical pion mass from lattice QCD
Authors: Alexandrou Constantia , Bacchio Simone , Koutsou Giannis , Leontiou Theodoros , Paul Srijit , Petschlies Marcus , Pittler Ferenc
Published: February 2024

We present an investigation of pion-nucleon elastic scattering in the I(JP)=32(32+) channel using lattice QCD with degenerate up and down, strange and charm quarks with masses tuned to their physical values. We use an ensemble of twisted mass fermions with box size L=5.1  fm and lattice spacing a=0.08  fm and we consider the πN system in rest and moving frames up to total momentum P→2=3(2π/L)2=0.17  GeV2. We take into account the finite volume symmetries and S- and P-wave mixing, and use the Lüscher formalism to simultaneously constrain the J=1/2,ℓ=0 and J=3/2,ℓ=1 scattering amplitudes. We estimate the Δ resonance pole in the P-wave channel as well as the S-wave isospin-3/2 scattering length.

Published by the American Physical Society
2024
No-
π
schemes for multicoupling theories
Authors: Jack I.
Published: February 2024

We show that even ζ-functions may be removed from the β-functions of general multicoupling theories up to high loop order by means of coupling redefinitions. For theories whose β-function is determined by the anomalous dimensions of the fields, such as supersymmetric theories, this corresponds to a renormalization scheme change to a momentum subtraction scheme.

Published by the American Physical Society
2024