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Bowel urgency, the sudden or immediate need for a bowel movement, is one of the most common and disruptive symptoms experienced by patients with ulcerative colitis. Distinct from the separate symptom of increased stool frequency, bowel urgency has a substantial negative impact on quality of life and psychosocial functioning. Among patients with ulcerative colitis, bowel urgency is one of the top reasons for treatment dissatisfaction and one of the symptoms patients most want improved. Patients may not discuss bowel urgency often due to embarrassment, and healthcare providers may not address the symptom adequately due to lack of awareness of validated tools and/or knowledge of the importance of assessing bowel urgency. The mechanism of bowel urgency in ulcerative colitis is multifactorial and includes inflammatory changes in the rectum that may be linked to hypersensitivity and reduced compliance of the rectum. Responsive and reliable patient-reported outcome measures of bowel urgency are needed to provide evidence of treatment benefits in clinical trials and facilitate communication in clinical practice. This review discusses the pathophysiology and clinical importance of bowel urgency in ulcerative colitis and its impact on quality of life and psychosocial functioning. Patient-reported outcome measures developed to assess the severity of bowel urgency in ulcerative colitis are discussed alongside overviews of treatment options and clinical guidelines. Implications for the future management of ulcerative colitis from the perspective of bowel urgency are also explored.

Background Alternative splicing (AS) may play an important role in gonadal sex determination (GSD) in mammals. The present study was designed to identify differentially expressed isoforms and AS modifications accompanying GSD in mice. Results Using deep RNA-sequencing, we performed a transcriptional analysis of XX and XY gonads during sex determination on embryonic days 11 (E11) and 12 (E12). Analysis of differentially expressed genes (DEG) identified hundreds of genes related to GSD and early sex differentiation that may represent good candidates for sex reversal. Expression at time point E11 in males was significantly enriched in RNA splicing and mRNA processing Gene Ontology terms. Differentially expressed isoform analysis identified hundreds of specific isoforms related to GSD, many of which showed no differences in the DEG analysis. Hundreds of AS events were identified as modified at E11 and E12. Female E11 gonads featured sex-biased upregulation of intron retention (in genes related to regulation of transcription, protein phosphorylation, protein transport and mRNA splicing) and exon skipping (in genes related to chromatin repression) suggesting AS as a post-transcription mechanism that controls sex determination of the bipotential fetal gonad. Conclusion Our data suggests an important role of splicing regulatory mechanisms for sex determination in mice.

Iberian ham is one of the most representative Spanish products and presents an excellent nutritional and sensory quality. Iberian ham trimming fat is considered a by-product and to give a new use to this remaining part could represent a healthy and innovative option for obtaining sustainable foods. The purpose of this work was to obtain a new bioactive ingredient from Iberian ham trimming fat with the highest amount of antioxidants and monounsaturated fatty acids (MUFA), using a new non-invasive solvent-free method. To obtain the essence, two different extraction procedures were carried out. After fatty acid characterization, degree of acidity, peroxide index and a basic sensory analysis were performed. Antioxidant in vitro activity and total phenolic compounds (TPC) were also determined. This new ingredient showed a better sensory profile than raw ham fat, a lower degree of acidity, a higher content of MUFAs, and also showed a higher antioxidant capacity and an increase in phenolic compounds compared to the raw material. This bioactive essence could be used as a food, a cosmetic or a nutraceutical ingredient to prevent certain diseases related to oxidative stress and could also contribute to the maintenance of the circular economy.

Minor splicing plays an important role in vertebrate development. Zrsr1 and Zrsr2 paralog genes have essential roles in alternative splicing, mainly participating in the recognition of minor (U12) introns. To further explore their roles during early embryo development, we produced Zrsr1mu and Zrsr2mu mutant mice, containing truncating mutations within the second zinc finger domain. Both homozygous mutant mice were viable with a normal lifespan. When we crossed a homozygous Zrsr2mu/mu female with Zrsr1mu/mu male, the double heterozygotes were non-viable, giving rise to embryos that stopped developing mainly between the 2- and 4-cell stages, just after zygotic gene activation. RNA-seq analysis of Zrsr1/2mu 2-cell embryos showed altered gene and isoform expression of thousands of genes enriched in gene ontology terms and biological pathways related to ribosome, RNA transport, spliceosome, and essential zygotic gene activation steps. Alternative splicing was analyzed, showing a significant increase in intron retention in both U2 and U12 intron-containing genes related to cell cycle and mitotic nuclear division. Remarkably, both Zrsr1 and Zrsr2 were required for the conversion of mouse-induced pluripotent stem cells into 2C-like cells. According to our results, Zrsr1 or Zrsr2 are necessary for ZGA and both are indispensable for the conversion of induced pluripotent stem cells into 2C-like cells.

We hypothesized that sexually dimorphic differences exist in the expression of miRNAs in amniotic fluid (AF) and maternal blood plasma (MP) in association with the process of sex determination and gonad differentiation in cattle. Amniotic fluid and MP were collected from six pregnant heifers (three carrying a single male and three a single female embryo) following slaughter on Day 39 postinsemination, coinciding with the peak of SRY expression. Samples (six AF and six MP) were profiled using an miRNA Serum/Plasma Focus PCR Panel. Differentially expressed (DE) miRNAs were identified in AF (n = 5) and associated MP (n = 56) of male vs. female embryos (P < 0.05). Functional analysis showed that inflammatory and immune response were among the 13 biological processes enriched by miRNAs DE in MP in the male group (FDR < 0.05), suggesting that these sex-dependent DE miRNAs may be implicated in modulating the receptivity of the dam to a male embryo. Further, we compared the downstream targets of the sex-dependent DE miRNAs detected in MP with genes previously identified as DE in male vs. female genital ridges. The analyses revealed potential targets that might be important during this developmental stage such as SHROOM2, DDX3Y, SOX9, SRY, PPP1CB, JARID2, USP9X, KDM6A, and EIF2S3. Results from this study highlight novel aspects of sex determination and embryo–maternal communication in cattle such as the potential role of miRNAs in gonad development as well as in the modulation of the receptivity of the dam to a male embryo. Summary sentence Sex-dependent differentially expressed miRNAs identified in amniotic fluid and maternal plasma on Day 39 of pregnancy are associated with gonad development as well as the modulation of the receptivity of the dam to a male embryo.

Mutations in splicing factors are recurrent somatic alterations identified in myelodysplastic syndromes (MDS) and they frequently coincide with mutations in epigenetic factors. About 25% of patients present concurrent mutations in such pathways, suggesting a cooperative role in the pathogenesis of MDS. We focused on the splicing factor U2AF1 involved in the recognition of the 3′ splice site during pre-mRNA splicing. Using a CRISPR/Cas9 system, we created heterozygous mice with a carboxy-terminal truncated U2af1 allele (U2af1mut/+), studied the U2af1mut/+ hematopoietic system, and did not observe any gross differences in both young (12–13 weeks) and old (23 months) U2af1mut/+ mice, except for a reduction in size of approximately 20%. However, hematopoietic stem/progenitor cells lacked reconstitution capacity in transplantation assays and displayed an aberrant RNA splicing by RNA sequencing. We also evaluated U2af1mut/+ in conjunction with Tet2-deficiency. Novel double mutant U2af1mut/+Tet2−/− mice showed increased monogranulocytic precursors. Hematopoietic stem/progenitor cells were also enhanced and presented functional and transcriptomic alterations. Nonetheless, U2af1mut/+Tet2−/− mice did not succumb to MDS disease over a 6-month observation period. Collectively, our data suggest that cooperation between mutant U2af1 and Tet2 loss is not sufficient for MDS initiation in mice.

This work was funded by a grant from Cárnicas Joselito SA through research project FUO-222-16 to University of Oviedo and Universidad Complutense de Madrid, and by grant IDI/2018/000120 from Programa de Ayudas a Gru-pos de Investigación del Principado de Asturias.

Most current knowledge of sex determination in mammals has emerged from mouse and human studies. To investigate the molecular regulation of the sex determination process in cattle, we used an RNA sequencing strategy to analyze the transcriptome landscape of male and female bovine fetal gonads collected in vivo at key developmental stages: before, during, and after SRY gene activation on fetal days D35 (bipotential gonad formation), D39 (peak SRY expression), and D43 (early gonad differentiation). Differentially expressed genes (DEGs) were identified in male vs. female germinal ridges and among group genes showing similar expression profiles during the three periods. There were 143, 96, and 658 DEG between males and female fetuses at D35, D39, and D43, respectively. On D35, genes upregulated in females were enriched in translation, nuclear export, RNA localization, and mRNA splicing events, whereas those upregulated in males were enriched in cell proliferation regulation and male sex determination terms. In time-course experiments, 767 DEGs in males and 545 DEGs in females were identified between D35 vs. D39, and 3157 DEGs in males and 2008 in females were identified between D39 vs. D43. Results highlight unique aspects of sex determination in cattle, such as the expression of several Y chromosome genes (absent in mice and humans) before SRY expression and an abrupt increase in the nuclear expression of SOX10 (instead of SOX9 expression in the Sertoli cell cytoplasm as observed in mice) during male determination and early differentiation. Summary sentence Gene expression analysis of male and female bovine fetal gonads collected in vivo before and after SRY expression sheds light on unique aspects of sex determination and early sex differentiation in cattle.

The authors thank funding from Convocatoria 2017 de Ayudas Destinadas a Financiar la Realizacin de Proyectos de Investigacin Industrial y Desarrollo Experimental a las Empresas de la Comunidad Autnoma de Extremadura (FUO-181-18) and [FUO-181-18]; Ayudas para Grupos de Investigacin de Organismos del Principado de Asturias [AYUD/2021/51347, PAPI-20-PF-20, PAPI-21-PF-16]

Postbiotics—defined in 2021 by the International Scientific Association of Probiotics and Prebiotics (ISAPP) as preparations of inactivated microorganisms and/or their components that confer health benefits to the host—are a promising tool in veterinary medicine. This systematic review and meta-analysis evaluated their types, mechanisms of action, and physiological effects in dogs. A literature search was conducted in PubMed, Scopus, and Web of Science up to 10 October 2024. Eligible studies included peer-reviewed trials in dogs or mechanistic studies on postbiotics; studies in other species or without peer review were excluded. Risk of bias was assessed, and random-effects meta-analyses were performed when appropriate. Of 157 records, 69 met the inclusion criteria, including 13 in vivo studies in dogs. Meta-analyses of selected outcomes showed no statistically significant differences between postbiotic and control groups. Evidence is limited by small sample sizes, strain heterogeneity, and varied study designs. Despite nonsignificant results, existing evidence from other species suggests that postbiotics improve the gut microbiota composition, modulate immune and inflammatory responses, reduce oxidative stress, and aid in the treatment of chronic conditions such as atopic dermatitis. Taken together with their potential role as an alternative to antimicrobial use, these findings highlight the need for further research in canine health to support the use of postbiotics in the treatment of common canine diseases, either as a standalone therapy or in combination with existing therapeutic options.