bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of processing or concentration of dried distillers grain with solubles on the growth of finishing lambs
Authors: Thompson Brayden , Relling Alejandro E , Ferreira Evandro M , Campbell Braden J 
Published: November 2024

Abstract
Dried distiller grains with solubles (DDGS) are a popular byproduct used in the livestock feed industry as it is a cost-effective feedstuff that is rich in crude protein and minerals. However, a common concern related to the use of DDGS in livestock diets is the negative impact that affects animal dry matter intake (DMI) and growth. To further investigate this challenge, the experiments aimed to evaluate the effect of feeding 1) two different diets, control versus heat processed DDGS or 2) increasing the concentration of DDGS and its effect on body weight (BW), average daily gain (ADG), DMI, and gain to feed ratio (G:F) in finishing lambs. In experiment 1, both diets were the same except for the heat processing of DDGS; the control diet used a commercial DDGS source directly from the supplier and the processed diet contained the same commercial DDGS source that differed through additional heat processing. For DDGS heat processing, 40% moisture was added to the DDGS and heated at 150 °C for 70 min. After the heating process, the DDGS was placed in a second oven at 56 °C for 2 d to allow for humidity evaporation. Lambs (n = 34), blocked by sex and BW, were housed in pens (2 to 3 lambs/pen, 6 pens/treatment) and were fed for 42 d. Lamb DMI was measured daily, and BW was measured every 14 d. In experiment 2, lambs (n = 75) were blocked by BW (5 lambs/ pen, 5 pens/treatment) and fed diets differing in inclusion rates of DDGS (10%, 20%, and 30%). The feeding period lasted for 56 d, and lamb DMI and BW were measured daily or every 28 d, respectively. In both experiments, diets were isonitrogenous, and the feeding procedure utilized slick bunk management. Data were analyzed in SAS using a mixed model considering the treatments as fixed effects and pen and block as random effects. In experiment 1, there were no treatment differences (P ≥ 0.13) in ADG, DMI, and G:F in finishing lambs. In experiment 2, a linear and quadratic contrast were used to separate the mean and demonstrated that increasing the concentration of DDGS decreased lamb DMI (linear P &lt; 0.01; quadratic P = 0.05), but did not affect lamb BW, ADG, or G:F (P ≥ 0.26). Despite that previous research shows differences in animal growth because of an increase in DDGS concentration, our experiments illustrated that heat processing or increased concentrations of DDGS up to 30% in finishing lamb diets are not responsible for a decrease in lamb performance.
Empowering older workers through self-regulation: how job crafting and leisure crafting enhance mindfulness and well-being at work
Authors: Xin Xun , Gao Lili , He Yuting 
Published: November 2024

Abstract
The capacity for self-regulation is crucial for older workers to maintain adaptability and well-being under aging-related challenges. Building on recent research suggesting that practices of self-regulation can enhance self-regulatory capacity, our study employs self-regulation theory to investigate how two distinct self-regulatory practices—job crafting (JC) and leisure crafting (LC)—support older workers in enhancing their work well-being through the lens of self-regulatory capacity, specifically mindfulness. Within this theoretical framework, we further explore the combined effects of JC and LC on adaptation to the aging process. A three-wave time-lagged survey was conducted among 227 older Chinese workers from science and technology enterprises. The results from latent structural equation modeling indicate that mindfulness at work mediates the relationship between crafting practices (both JC and LC) and work well-being. Moreover, JC and LC exhibit a compensatory relationship in facilitating mindfulness at work, which in turn promotes the work well-being of older workers. These findings offer a novel perspective grounded in self-regulation theory, highlighting how JC and LC contribute to successful aging by strengthening mindfulness capacity.
Oxidative stress drives endometrial fibrosis via TGF‐β1/MAPK signaling pathway in breast cancer
Authors: Chen Hui , Wang Minghua , Zhang Zhejun , Lin Fangfang , Guo Bihui , Lu Qinsheng , Lash Gendie E. , Li Ping 
Published: November 2024

AbstractBreast cancer patients have high serum reactive oxygen species (ROS) levels, which exert toxicity on the ovary. However, it is still unclear whether tumor‐derived ROS play a role in endometrial development and function in breast cancer. Breast cancer patients and healthy controls were recruited and endometrial thickness was measured by transvaginal ultrasound (TVUS). Xenograft tumors of the breast cancer cell line MDA–MB–231 in a female BALB/c nude mice model were established, and the therapeutic mechanism of vitamin C (VC) was investigated on uterine pathology in vivo and the contribution of co‐culture of breast cancer cell and endometrial epithelial cell on this process was examined in vitro. Median thickness in endometria was lower in breast cancer patients and tumor‐bearing mice compared to controls. A gene signature of uteri in tumor‐bearing mice demonstrated differential expression of genes (DEGs) regulating extracellular matrix (ECM) and epithelial–mesenchymal transition (EMT), and activation of TGF‐β and MAPK signaling pathways. In addition, ROS, EMT‐ and ECM‐related protein levels were enhanced in uteri in tumor‐bearing mice, as well as in Ishikawa cells which were co‐cultured with MDA‐MB‐231 cells compared to controls. Supplementation with VC reduced endometrial damage, inhibited the EMT process and collagen deposition, and maintained better histologic architecture of uteri in tumor‐bearing mice via inactivation of the TGF‐β1/p38MAPK pathway. In women with breast cancer oxidative stress in the endometrium results in a fibrotic response as a consequence of EMT. VC could alleviate endometrial fibrosis via TGF‐β1/p38MAPK pathway and provide new predictive and therapeutic targets for fertility preservation in younger breast cancer patients.
Mutations in Mig6 reduce inhibition of the epidermal growth factor receptor
Authors: Hayashi Samantha Y. , Pak Steven , Torlentino Antonio , Rizzo Robert C. , Miller W. Todd 
Published: November 2024

AbstractMitogen‐inducible gene 6 (Mig6) is a cellular inhibitor of epidermal growth factor receptor (EGFR) that binds directly to the EGFR kinase domain and interferes with signaling. Reduced Mig6 expression is correlated with increased EGFR activity in multiple cancer models. Here, we investigated whether disease‐associated point mutations could reduce the inhibitory potency of Mig6. We show that several cancer‐associated mutations, and a mutation derived from Alzheimer's Disease patients, diminish the ability of Mig6 to bind and inhibit EGFR in vitro. In mammalian cells, the mutations decreased the Mig6‐induced suppression of basal and EGF‐stimulated autophosphorylation, MAP kinase phosphorylation, and cell migration. To probe the mechanisms by which the mutations could lead to reduced Mig6 inhibition, we constructed atomic‐level computational models of Mig6 complexed with the EGFR catalytic domain, and performed molecular dynamics simulations for wild‐type and mutant complexes.
Reassessing Asymmetry Reduction in Psychosis: Cingulate Folding and Gyrification Covariance in Patients with Auditory Hallucinations
Authors: Wu Shun-Chin Jim , de Vareilles Héloïse , Mitchell Samantha C. , Al-Manea Atheer , Garrison Jane , Mamalakis Michail , Simons Jon S. , Cachia Arnaud , Mangin Jean-François , Nerland Stener , Mørch-Johnsen Lynn , Agartz Ingrid , Suckling John , Murray Graham K. 
Published: November 2024

AbstractBackground and HypothesisPrior research links a shorter paracingulate sulcus (PCS) to hallucinations in schizophrenia, but its symmetry hemispheric specificity and relevance to bipolar disorders remain unclear. We hypothesized that reduced PCS asymmetry and interhemispheric gyrification covariance in salience and auditory networks are associated with lifetime auditory hallucinations (AH) in psychotic spectrum disorders.Study DesignWe compared patients with and without AH, and healthy controls, focusing on PCS asymmetry in five ordinal classes, sulcal length and depth, and interhemispheric gyrification covariance.Study ResultsAmong 351 patients with schizophrenia or bipolar spectrum disorders (SSD/BSD), 194 (55.3%) had AH, compared to 157 without and 278 healthy controls. We found no significant PCS class asymmetry between hemispheres (V = 6648.5,P= .097) and decreased leftward asymmetry in PCS length (F(2,626) = 3.19,P= .013) in patients with AH, compared with those without and healthy controls. Compared to patients without AH, those with AH showed increased gyrification covariance in the auditory network (F(2,625) = 42.5,P< .001). In the salience network, patients with SSD and AH had increased covariance (F(2,625) = 299,P< .001), while patients with BSD and AH displayed decreased covariance (F(2,625) = 102,P< .001).ConclusionsThis study, featuring the largest cohort to date, links the AH trait to replicable reduced leftward PCS asymmetry and altered interhemispheric covariance in psychotic spectrum disorders, supporting theories of reduced asymmetry and altered brain network coordination as part of the mechanistic pathway to psychosis.
The Impact of Spinal Manipulation on Lumbar Proprioception and its Link to Pain Relief: A Randomized Controlled Trial
Authors: Luana Nyirö , Monika Dörig , Magdalena Suter , Lukas Connolly , Noemi Vogel , Stadler Carla , John-Cecere Giovanna , Petra Schweinhardt , Lukas Meier Michael 
Published: November 2024

AbstractManual therapy, such as spinal manipulation (SM), is commonly used to treat non-specific chronic low back pain (CLBP), although its mechanisms remain poorly understood. It has been hypothesized that the mechanical forces applied during spinal manipulation (SM) influence proprioceptive function, which is often impaired in patients with CLBP. This study aimed to investigate the effect of a single SM intervention on lumbar proprioceptive function and its potential relationship with analgesic effects in patients with CLBP. In a single-blind randomized controlled trial, data from 142 adults with or without CLBP were analyzed after random assignment to receive lumbar spinal manipulation (LMANIP), lumbar mobilization (LMOB), or no intervention (NI). The primary outcome was the proprioceptive weighting (PW) ratio, which reflects the central nervous system’s preferred source of proprioceptive input for balance control, specifically from the lumbar and ankle muscles. PW ratios were assessed immediately before and after intervention by analyzing postural sway changes during vibrotactile stimulation (60 Hz). PW changed in both healthy participants and patients after the intervention, with a significantly stronger lumbar-steered PW following LMANIP compared to NI (β = -0.047, t(422) = -2.71, p = 0.007) and LMOB (β = -0.039, t(422) = - 2.17, p = 0.030). Moreover, LMANIP was particularly effective in reducing pain in patients with stronger lumbar-steered PW before intervention (p < 0.017). These findings suggest that a single SM session enhances proprioceptive input from the lumbar muscles and that the strength of the analgesic effect is associated with the baseline PW status.
Primary Central Nervous System Lymphoma Tumor Biopsies Show Heterogeneity in Gene Expression Profiles, Genetic Subtypes, and in vitro Drug Sensitivity to Kinase Inhibitors
Authors: Zhu Yuan Xiao , Wong Jasper CH , Hilal Talal , Maguire Alanna , Ocal Jon , Zellner Katie , Chen Xianfeng , Link Brian K , Habermann Thomas M , Maurer Matthew J , Cerhan James R , Johnston Patrick B , Feldman Andrew L , Scott David W. , Rosenthal Allison , Rimsza Lisa 
Published: November 2024

ABSTRACTPrimary central nervous system lymphoma (PCNSL) is clinically challenging due to its location and small biopsy size, leading to a lack of comprehensive molecular and biologic description. We previously demonstrated that 91% of PCNSL belong to the activated B-cell-like (ABC) molecular subtype of diffuse large B-cell lymphoma (DLBCL). Here we investigated the expression of 739 cancer related genes in HIV (-) patients using NanoString digital gene expression profiling in 25 ABC-PCNSL and 43 ABC-systemic DLBCL, all tumors were EBV (-). We found that two-thirds of ABC-PCNSL samples had a transcriptional landscape distinct from ABC-systemic DLBCL samples. Of the 739 genes measured, 135 were identified as differentially expressed between these ABC-PCNSL and ABC-systemic DLBCL (p<0.05). Compared with ABC-systemic DLBCL, ABC-PCNSL showed higher gene expression in several cancer related gene sets including genes related to Hedgehog, DNA damage repair, Wnt and MAPK signaling. Hierarchical clustering 28 PCNSL samples (25 ABC and 3 GCB subtypes) identified two transcriptional subgroups, P1 (n=9) and P2 (n=19). P2 showed higher activities across most of the cancer related pathways and had a significantly shorter patient survival time (p<0.01). Whole exome sequencing showed that some distinct genetic features of PCNSL compared to DLBCL. The genetic subtypes (“LymphGen”) of PCNSL consisted mainly of “MCD” and “Other” subtypes, which did not correlate with clinical survival. These data provide more information about unique characters of PCNSL, which may help to identify novel drug targets for developing therapeutic strategies.
Open-source 3D Printable Forearm Crutch
Authors: Mottaghi Maryam , Woods Morgan , Danier Laura , So Anita , Reeves Jacob M. , Pearce Joshua M. 
Published: November 2024

AbstractAlthough there has been considerable progress in distributed manufacturing of open-source designs for mobility aids, there is a notable lack of affordable, open-source crutches. Crutches are a vital tool for many individuals with mobility impairments, yet the high costs limit accessibility. Even more, they are in short supply in regions undergoing conflict. The goal of this study is to address this need by leveraging the principles of free and open-source hardware and the capabilities of digital distributed manufacturing to create a low-cost, functional crutch that can be easily produced and customized locally using inexpensive desktop 3D printers. All the design files are open-source, and the design process incorporated load-bearing tests using a hydraulic actuator under static loading conditions to meet the ISO 11334-1:2007 standard for walking aids. The open-source forearm crutch developed in this study not only surpasses the requirements of the ISO method for load capacity (1,516.3 ± 169.9 N, which is 51.6% percent above needs), weighs a fraction of comparable commercial systems (0.612 kg or 27%% of proprietary devices), and is customizable, but also offers a highly cost-effective solution; costing CAD $36 in material, which is less than all equivalent crutches on the open market. If recycled plastic is used, the material cost of the crutch could be further reduced to under CAD $13, making it much more accessible.
Unveiling novel conserved HIV-1 open reading frames encoding T cell antigens using ribosome profiling
Authors: Bertrand Lisa , Nelde Annika , Ramirez Bertha Cecilia , Hatin Isabelle , Arbes Hugo , François Pauline , Demais Stephane , Labaronne Emmanuel , Decimo Didier , Guiguettaz Laura , Grégoire Sylvie , Bet Anne , Beauclair Guillaume , Gross Antoine , Ziegler Maja C. , Pereira Mathias , Jeger-Madiot Raphaël , Verdier Yann , Vinh Joelle , Cardinaud Sylvain , Graff-Dubois Stéphanie , Esclatine Audrey , Gouttefangeas Cécile , Altfeld Marcus , Hocqueloux Laurent , Samri Assia , Autran Brigitte , Lambotte Olivier , Rammensee Hans-Georg , Ricci Emiliano P. , Walz Juliane , Namy Olivier , Moris Arnaud 
Published: November 2024

AbstractThe development of ribosomal profiling (Riboseq) revealed the immense coding capacity of human and viral genomes. Here, we used Riboseq to delineate the first translatome of HIV-1 in infected CD4+T cells. In addition to canonical viral protein coding sequences (CDSs), we identify 98 alternative open reading frames (ARFs), corresponding to small Open Reading Frames (sORFs) that are distributed across the HIV genome including the UTR regions. Using a database of HIV genomes, we observed that most ARF amino-acid sequences are likely conserved among clade B and C of HIV-1, with 8 ARF-encoded amino-acid sequences being more conserved than the overlapping CDSs. Using T cell-based assays and mass spectrometry-based immunopeptidomics, we demonstrate that ARFs encode viral polypeptides. In the blood of HIV-infected individuals, ARF-derived peptides elicit potent poly-functional T cell responses mediated by both CD4+and CD8+T cells. Our discovery expands the list of conserved viral polypeptides that are targets for vaccination strategies and might reveal the existence of viral microproteins or pseudogenes.
Covalent adducts formed by the androgen receptor transactivation domain and small molecule drugs remain disordered
Authors: Zhu Jiaqi , Robustelli Paul J. 
Published: November 2024

AbstractIntrinsically disordered proteins are implicated in many human diseases. Small molecules that target the disordered androgen receptor transactivation domain have entered human trials for the treatment of castration-resistant prostate cancer. These molecules have been shown to react with cysteine residues of the androgen receptor transactivation domain and form covalent adducts under physiological conditions. It is currently unclear how covalent attachment of these molecules alters the conformational ensemble of the androgen receptor. Here, we utilize all-atom molecular dynamics computer simulations to simulate covalent adducts of the small molecule ligands EPI-002 and EPI-7170 bound to the disordered androgen receptor transactivation domain. Our simulations reveal that the conformational ensembles of androgen receptor transactivation domain covalent adducts are heterogeneous and disordered. We find that covalent attachment of EPI-002 and EPI-7170 increases the population of collapsed helical transactivation domain conformations relative to the populations observed in non-covalent binding simulations and we identify networks of protein-ligand interactions that stabilize collapsed conformations in covalent adduct ensembles. We compare the populations of protein-ligand interactions observed in covalent adduct ensembles to those observed in non-covalent ligand-bound ensembles and find substantial differences. Our results provide atomically detailed descriptions of covalent adducts formed by small molecules and an intrinsically disordered protein and suggest strategies for developing more potent covalent inhibitors of intrinsically disordered proteins.
Butyrophilin 2A2 promotes T cell immunoregulation by enhancing CD45 phosphatase activity within the immune synapse
Authors: Ali Shafat , Berg Anders H. , Yamashita Michifumi , Covarrubias Ambart E. , Zhang Ruan , Dupont Vincent , Shin Bong-Ha , Yang Shen , Murali Ramachandran , Katiki Madhusudhanarao , Pisarska Margareta D. , Thadhani Ravi , Heeger Peter S. , Jordan Stanley C. , Karumanchi S. Ananth 
Published: November 2024

ABSTRACTB7 costimulatory family member Butyrophilin 2A2(BTN2A2) is predominantly expressed by antigen presenting cells and regulates T cell immunity, but molecular mechanisms are unclear. Using immunoblots analyzing TCR-initiated signaling intermediaries, co-immunoprecipitation studies, confocal microscopy, structural modeling-guided mutational analyses, and microscale thermophoresis, we demonstrate that BTN2A2 directly interacts with CD45RO, resulting in CD45 retention within the immune synapse during TCR activation. Recombinant BTN2A2 increased murine CD4+Foxp3+ regulatory T cells (Treg) and reduced T helper 17 (Th17) cells in vitro through mechanisms dependent on CD45 phosphatase activity. BTN2A2 treatment reduced clinical expression of two murine autoimmune disease models and increased Treg/Th17 ratios. Analyses of BTN2A2-deficient animals showed exacerbated disease associated with reduced Treg/Th17 ratios. Addition of BTN2A2 to human mixed lymphocyte responses similarly enhanced human Treg and suppressed Th17 cells and was CD45 phosphatase dependent. Together, our studies identify BTN2A2 as a physiological CD45RO ligand that enhances CD45 phosphatase activity in murine and human T cells, providing mechanisms for BTN2A2-mediated amelioration of autoimmunity.SummaryButyrophilin 2A2 ameliorates autoimmunity by binding to CD45RO on activated T cell surfaces leading to dampened TCR signaling which in turn leads to expansion of T regulatory cells and reduction of Th17 differentiation.
Antiviral defense in agedCaenorhabditis elegansdeclines due to loss of DRH-1/RIG-I deSUMOylation via ULP-4/SENP7
Authors: Zhang Yun , Samuelson Andrew V. 
Published: November 2024

AbstractInnate host defense mechanisms require posttranslational modifications (PTM) to protect against viral infection. Age-associated immunosenescence results in increased pathogenesis and mortality in the elderly, but the contribution of altered PTM regulation to immunosenescence is unknown. SUMOylation is a rapid and reversible post-translational modification that has been implicated in age-associated disease and plays conflicting roles in viral replication and antiviral defenses in mammals. We have discovered inCaenorhabditis elegansthat induction of antiviral defense is regulated through SUMOylation of DRH-1, the ortholog of the DEAD/H-box helicase and cytosolic pattern recognition receptor RIG-I, and that this regulation breaks down during aging. We find the SUMO isopeptidase ULP-4 is essential for deSUMOylation of DRH-1 and activation of the intracellular pathogen response (IPR) after exposure to Orsay virus (OV), a natural entericC. eleganspathogen. ULP-4 promotes stabilization of DRH-1, which translocates to the mitochondria to activate the IPR in young animals exposed to virus. Loss of eitherdrh-1orulp-4compromises antiviral defense resulting in a failure to clear the virus and signs of intestinal pathogenesis. During aging, expression ofulp-4decreases, which results in increased proteosomal degradation of DRH-1 and loss of the IPR. Mutating the DRH-1 SUMOylated lysines resulted in the constitutive activation of the IPR in young animals and partially rescued the age-associated lost inducibility of the IPR. Our work establishes that aging results in dysregulated SUMOylation and loss of DRH-1, which compromises antiviral defense and creates a physiological shift to favor chronic pathological infection in older animals.