Maximizing Lucerne (Medicago sativa) Pasture Intake of Dairy Cows: 1-the Effect of Pre-Grazing Pasture Height and Mixed Ration Level

The effect of lucerne (Medicago sativa L.) pre-grazing pasture height on pasture intake and milk production was investigated in a sub-tropical partial mixed ration (PMR) dairy system in south-east Queensland, Australia. The experiment involved a 26-day adaptation period followed by an eight-day measurement period during April and May 2018. Twenty-four multiparous Holstein-Friesian dairy cows were offered a mixed ration at either 7 (low) or 14 (high) kg dry matter (DM)/cow/day and allocated pastures at pre-grazing heights ranging from 23 to 39 cm. The targeted pasture intake was 14 and 7 kg DM/cow/day for cows offered the low and high mixed ration allowances respectively, with a total intake target of 21 kg DM/cow/day. Pasture structure did not limit pasture intake as the all groups left at least 12% of the allocated area ungrazed, and therefore could selectively graze pasture. There was no significant difference in intake between mixed ration levels, however intake had a positive linear relationship with pre-grazing pasture height. For every one cm increase in pasture height, intake increased by 0.3 kg DM/cow/day. Using a grazing strategy that ensures the some pasture remains ungrazed and the pre-grazing height of lucerne is approximately 39 cm above ground level will maximise pasture intake in sub-tropical PMR dairy systems

Single cell-transcriptomic analysis informs the lncRNA landscape in metastatic castration resistant prostate cancer

Metastatic castration-resistant prostate cancer (mCRPC) is a lethal form of prostate cancer. Although long-noncoding RNAs (lncRNAs) have been implicated in mCRPC, past studies have relied on bulk sequencing methods with low depth and lack of single-cell resolution. Hence, we performed a lncRNA-focused analysis of single-cell RNA-sequencing data (n = 14) from mCRPC biopsies followed by integration with bulk multi-omic datasets. This yielded 389 cell-enriched lncRNAs in prostate cancer cells and the tumor microenvironment (TME). These lncRNAs demonstrated enrichment with regulatory elements and exhibited alterations during prostate cancer progression. Prostate-lncRNAs were correlated with AR mutational status and response to treatment with enzalutamide, while TME-lncRNAs were associated with RB1 deletions and poor prognosis. Finally, lncRNAs identified between prostate adenocarcinomas and neuroendocrine tumors exhibited distinct expression and methylation profiles. Our findings demonstrate the ability of single-cell analysis to refine our understanding of lncRNAs in mCRPC and serve as a resource for future mechanistic studies

Nutrient availability and metabolism Affect the stability of coral–Symbiodiniaceae symbioses

Coral reefs rely upon the highly optimized coral–Symbiodiniaceae symbiosis, making them sensitive to environmental change and susceptible to anthropogenic stress. Coral bleaching is predominantly attributed to photo-oxidative stress, yet nutrient availability and metabolism underpin the stability of symbioses. Recent studies link symbiont proliferation under nutrient enrichment to bleaching; however, the interactions between nutrients and symbiotic stability are nuanced. Here, we demonstrate how bleaching is regulated by the forms and ratios of available nutrients and their impacts on autotrophic carbon metabolism, rather than algal symbiont growth. By extension, historical nutrient conditions mediate host–symbiont compatibility and bleaching tolerance over proximate and evolutionary timescales. Renewed investigations into the coral nutrient metabolism will be required to truly elucidate the cellular mechanisms leading to coral bleaching

Cognitive change in cognitive-behavioural therapy

BACKGROUND: Although cognitive-behavioural therapy (CBT) is a well-established treatment for adult depression, its efficacy and efficiency may be enhanced by better understanding its mechanism(s) of action. According to the theoretical model of CBT, symptom improvement occurs via reductions in maladaptive cognition. However, previous research has not established clear evidence for this cognitive mediation model. METHODS: The present study investigated the cognitive mediation model of CBT in the context of a randomized controlled trial of CBT v. antidepressant medication (ADM) for adult depression. Participants with major depressive disorder were randomized to receive 16 weeks of CBT (n = 54) or ADM (n = 50). Depression symptoms and three candidate cognitive mediators (dysfunctional attitudes, cognitive distortions and negative automatic thoughts) were assessed at week 0 (pre-treatment), week 4, week 8 and week 16 (post-treatment). Longitudinal associations between cognition and depression symptoms, and mediation of treatment outcome, were evaluated in structural equation models. RESULTS: Both CBT and ADM produced significant reductions in maladaptive cognition and depression symptoms. Cognitive content and depression symptoms were moderately correlated within measurement waves, but cross-lagged associations between the variables and indirect (i.e. mediated) treatment effects were non-significant. CONCLUSIONS: The results provide support for concurrent relationships between cognitive and symptom change, but not the longitudinal relationships hypothesized by the cognitive mediation model. Results may be indicative of an incongruence between the timing of measurement and the dynamics of cognitive and symptom change

A single H/ACA small nucleolar RNA mediates tumor suppression downstream of oncogenic RAS.

Small nucleolar RNAs (snoRNAs) are a diverse group of non-coding RNAs that direct chemical modifications at specific residues on other RNA molecules, primarily on ribosomal RNA (rRNA). SnoRNAs are altered in several cancers; however, their role in cell homeostasis as well as in cellular transformation remains poorly explored. Here, we show that specific subsets of snoRNAs are differentially regulated during the earliest cellular response to oncogenic RASG12V expression. We describe a novel function for one H/ACA snoRNA, SNORA24, which guides two pseudouridine modifications within the small ribosomal subunit, in RAS-induced senescence in vivo. We find that in mouse models, loss of Snora24 cooperates with RASG12V to promote the development of liver cancer that closely resembles human steatohepatitic hepatocellular carcinoma (HCC). From a clinical perspective, we further show that human HCCs with low SNORA24 expression display increased lipid content and are associated with poor patient survival. We next asked whether ribosomes lacking SNORA24-guided pseudouridine modifications on 18S rRNA have alterations in their biophysical properties. Single-molecule Fluorescence Resonance Energy Transfer (FRET) analyses revealed that these ribosomes exhibit perturbations in aminoacyl-transfer RNA (aa-tRNA) selection and altered pre-translocation ribosome complex dynamics. Furthermore, we find that HCC cells lacking SNORA24-guided pseudouridine modifications have increased translational miscoding and stop codon readthrough frequencies. These findings highlight a role for specific snoRNAs in safeguarding against oncogenic insult and demonstrate a functional link between H/ACA snoRNAs regulated by RAS and the biophysical properties of ribosomes in cancer

Schistosoma mansoni, nematode infections, and progression to active tuberculosis among HIV-1-infected Ugandans.

Rates of tuberculosis (TB) in Africa are highest among people infected with HIV. Searching for additional risk factors in a cohort of HIV-infected Ugandan adults, we previously found that a type 2 cytokine bias and eosinophilia were associated with progression to active TB. A possible role for helminth infection was assessed in this study. We analyzed TB incidence in 462 members of this cohort who were screened for filarial infections, gastrointestinal nematodes, and schistosomiasis. Progression to TB was not associated with gastrointestinal nematodes (rate ratio [RR], 1.18; confidence intervals [CIs], 0.66-2.10) or Mansonella perstans (RR, 0.42; CI, 0.13-1.34). A weak association between Schistosoma mansoni infection and TB was found (RR, 1.42; CI, 0.86-2.34); after adjusting for potential explanatory variables and using more stringent diagnostic criteria, the association was strengthened (RR, 2.31; 1.00-5.33). This analysis suggests an effect of S. mansoni infection on progression to active TB among HIV-1-infected Ugandans

Network analysis of skin tumor progression identifies a rewired genetic architecture affecting inflammation and tumor susceptibility

11 páginas, 5 figuras, 1 tabla.-- et al.[Background]: Germline polymorphisms can influence gene expression networks in normal mammalian tissues and can affect disease susceptibility. We and others have shown that analysis of this genetic architecture can identify single genes and whole pathways that influence complex traits, including inflammation and cancer susceptibility. Whether germline variants affect gene expression in tumors that have undergone somatic alterations, and the extent to which these variants influence tumor progression, is unknown. [Results]: Using an integrated linkage and genomic analysis of a mouse model of skin cancer that produces both benign tumors and malignant carcinomas, we document major changes in germline control of gene expression during skin tumor development resulting from cell selection, somatic genetic events, and changes in the tumor microenvironment. The number of significant expression quantitative trait loci (eQTL) is progressively reduced in benign and malignant skin tumors when compared to normal skin. However, novel tumor-specific eQTL are detected for several genes associated with tumor susceptibility, including IL18 (Il18), Granzyme E (Gzme), Sprouty homolog 2 (Spry2), and Mitogen-activated protein kinase kinase 4 (Map2k4). [Conclusions]: We conclude that the genetic architecture is substantially altered in tumors, and that eQTL analysis of tumors can identify host factors that influence the tumor microenvironment, mitogen-activated protein (MAP) kinase signaling, and cancer susceptibility.This work was supported by the National Cancer Institute. AB acknowledges support from the Barbara Bass Bakar Chair of Cancer Genetics. MDT was supported in part by a Sandler Foundation postdoctoral research fellowship. JS was supported by the Swedish Research Council and the Tegger Foundation. KKL was supported by an NIH Kirschstein-NRSA postdoctoral research fellowship. JPL is partially supported by Carlos III (FIS)/FEDER, MICIIN/plan-E 2009, JCyL (’Biomedicina y Educación’) and CSIC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe

A gp41 MPER-specific llama VHH requires a hydrophobic CDR3 for neutralization but not for antigen recognition

The membrane proximal external region (MPER) of the HIV-1 glycoprotein gp41 is targeted by the broadly neutralizing antibodies 2F5 and 4E10. To date, no immunization regimen in animals or humans has produced HIV-1 neutralizing MPER-specific antibodies. We immunized llamas with gp41-MPER proteoliposomes and selected a MPER-specific single chain antibody (VHH), 2H10, whose epitope overlaps with that of mAb 2F5. Bi-2H10, a bivalent form of 2H10, which displayed an approximately 20-fold increased affinity compared to the monovalent 2H10, neutralized various sensitive and resistant HIV-1 strains, as well as SHIV strains in TZM-bl cells. X-ray and NMR analyses combined with mutagenesis and modeling revealed that 2H10 recognizes its gp41 epitope in a helical conformation. Notably, tryptophan 100 at the tip of the long CDR3 is not required for gp41 interaction but essential for neutralization. Thus bi-2H10 is an anti-MPER antibody generated by immunization that requires hydrophobic CDR3 determinants in addition to epitope recognition for neutralization similar to the mode of neutralization employed by mAbs 2F5 and 4E10