Microporous water with high gas solubilities.

Liquids with permanent microporosity can absorb larger quantities of gas molecules than conventional solvents1, providing new opportunities for liquid-phase gas storage, transport and reactivity. Current approaches to designing porous liquids rely on sterically bulky solvent molecules or surface ligands and, thus, are not amenable to many important solvents, including water2-4. Here we report a generalizable thermodynamic strategy to preserve permanent microporosity and impart high gas solubilities to liquid water. Specifically, we show how the external and internal surface chemistry of microporous zeolite and metal-organic framework (MOF) nanocrystals can be tailored to promote the formation of stable dispersions in water while maintaining dry networks of micropores that are accessible to gas molecules. As a result of their permanent microporosity, these aqueous fluids can concentrate gases, including oxygen (O2) and carbon dioxide (CO2), to much higher densities than are found in typical aqueous environments. When these fluids are oxygenated, record-high capacities of O2 can be delivered to hypoxic red blood cells, highlighting one potential application of this new class of microporous liquids for physiological gas transport.

Anatomic position determines oncogenic specificity in melanoma.

Oncogenic alterations to DNA are not transforming in all cellular contexts1,2. This may be due to pre-existing transcriptional programmes in the cell of origin. Here we define anatomic position as a major determinant of why cells respond to specific oncogenes. Cutaneous melanoma arises throughout the body, whereas the acral subtype arises on the palms of the hands, soles of the feet or under the nails3. We sequenced the DNA of cutaneous and acral melanomas from a large cohort of human patients and found a specific enrichment for BRAF mutations in cutaneous melanoma and enrichment for CRKL amplifications in acral melanoma. We modelled these changes in transgenic zebrafish models and found that CRKL-driven tumours formed predominantly in the fins of the fish. The fins are the evolutionary precursors to tetrapod limbs, indicating that melanocytes in these acral locations may be uniquely susceptible to CRKL. RNA profiling of these fin and limb melanocytes, when compared with body melanocytes, revealed a positional identity gene programme typified by posterior HOX13 genes. This positional gene programme synergized with CRKL to amplify insulin-like growth factor (IGF) signalling and drive tumours at acral sites. Abrogation of this CRKL-driven programme eliminated the anatomic specificity of acral melanoma. These data suggest that the anatomic position of the cell of origin endows it with a unique transcriptional state that makes it susceptible to only certain oncogenic insults.

Exploring Nurse Practitioner Students' Perceptions of a Sleep e-Learning Program.

AIM: The aim of this study was to explore nurse practitioner (NP) students' perceptions of a sleep e-learning program. BACKGROUND: Sleep assessment is uncommon as nursing curricula lack sleep education. By preparing NPs to conduct sleep assessment and screening and understand basic sleep diagnostics, sleep health is more likely to be part of the differential diagnosis. METHOD: The study is a qualitative descriptive study utilizing two focus groups. A directed content analysis, guided by the Kirkpatrick model, was used for analysis. RESULTS: Twenty-four students participated in focus groups. Two overarching themes emerged: perceptions of course design and content. Asynchronous, case-based scenarios and quizzes were favorable. Students spoke of content relevance to themselves and patients and intentions to adopt sleep assessment practices. CONCLUSION: NP students embraced sleep education and declared intention to apply learned skills in practice. This study highlights the feasibility of increasing curricular exposure to sleep education and ensuring NPs have skills to recognize implications of poor and disordered sleep in patients.

Better caregiver mastery is associated with less anxiety in individuals with cognitive impairment.

BACKGROUND: When caregivers have a high level of caregiver mastery, their care recipients with cognitive impairment have less behavioral health problems. However, the relationship between caregiver mastery and anxiety among care recipients over time is unknown. Therefore, this study was conducted to examine that better caregiver mastery is associated with less anxiety in individuals with cognitive impairment over time. METHODS: A secondary data analysis was conducted using the Healthy Patterns Clinical Trial (NCT03682185) dataset and guided by Factors Associated with Behavioral and Psychological Symptoms of Dementia conceptual framework. This study included 154 dyads of individuals with cognitive impairment and their caregivers. Multiple linear regression analyses were performed on changes in anxiety. Model 1 included variables at the level of neurodegeneration (i.e., cognitive impairment and age). Model 2 added patient factors (i.e., sleep problems and depression) with the Model 1. Finally, Model 3 included caregiver factor (i.e., caregiver mastery) with the Model 2 to examine how changes in caregiver mastery influence changes in anxiety of care recipients. RESULTS: Model 3 was statistically significant; after controlling for variables at the level of neurodegeneration associated with cognitive impairment and patient factors, improvement of caregiver mastery over time (ß =-0.230, p = 0.015) was related to decreased anxiety over time (R2 = 0.1099). CONCLUSIONS: Caregivers with high caregiver mastery may have better knowledge on how to care for their loved ones and how to manage their neuropsychiatric symptoms. Therefore, improving the level of caregiver mastery by providing psychoeducational programs and resources that family caregivers need will help reduce the frequency of anxiety in individuals with cognitive impairment.

Assisted Relaxation Therapy for Insomnia in Older Adults With Mild Cognitive Impairment: A Pilot Study.

Insomnia symptoms are prevalent in older adults with mild cognitive impairment (MCI) and can pose treatment challenges. We tested the feasibility, acceptability, and preliminary efficacy of assisted relaxation therapy (ART) to improve insomnia symptoms in community-dwelling older adults with MCI. In this pilot RCT, 25 participants were assigned to intervention or control groups for 2 weeks. The final sample (n = 20) consisted of all Black, primarily female (70%) older adults (mean age 69.10; SD = 7.45) with mean Montreal Cognitive Assessment scores of 21.10 (SD = 2.49). Recruitment was timely; attrition was low (80%). Participants were able to use ART (average use 7.00; SD = 5.07 days). Participants in the ART group improved on Insomnia Severity Index (ISI) (- 7.10; 95% CI [-11.63, -2.55]; p = .004) compared to baseline. There were clinically meaningful mean change scores on ISI for the intervention group compared to the control (- 7.10 vs. - 4.33). Results provide justification for testing ART in a fully powered clinical trial.

[«Management of nurses specialized in the aero-evacuation of highly infectious critical patients, during the COVID-19 pandemic. Systematic review¼]. / «Gestión de enfermeras/os especializados en la aeroevacuación de pacientes críticos altamente infecciosos, durante la pandemia por COVID-19. Revisión Sistemática¼.

Introduction: Aeromedical evacuation missions to transport highly infectious critical COVID-19 patients involve multiple factors, therefore planning is essential in their preparation. The management of specialist nurses is cross-cutting, as they participate in the planning, organisation and implementation of aero-evacuation protocols, delivery of care and operational safety procedures throughout the operation, with an integrated aeromedical crew working as a team alongside the air crew. Objective: To study the management of nurses specialised in the aero-evacuation of highly infectious critical patients during the COVID-19 pandemic. Design: Through a systematic search of the biomedical literature, this study was conducted according to the standards of the Cochrane Handbook for Systematic Reviews of Interventions and PRISMA. The literature search included articles published from 2019 to August 2020 and meta-search engines, yielding a total of 142 articles, and a triangulation of information was performed. A total of 11 articles were eventually included in the review, and the validity of each article was determined according to the guidelines of the Joanna Briggs Institute level of evidence. Results and discussion: The systematic review identified 11 studies that use different methodological considerations for conducting an aeromedical evacuation and covering key aspects for a successful operation. Conclusion: The management of specialist nurses has a direct impact on the aeromedical evacuation of the critical patient. It covers planning, organisation, and operational safety, applied in the instruction, training, execution and strict monitoring of the work of the aeromedical crew as a solid team. This contributes to the success of the aero-evacuation mission and the infectious patient's high likelihood of survival during the COVID-19 pandemic.

A critical review of textile industry wastewater: green technologies for the removal of indigo dyes.

The denim textile industry represents an important productive sector. It generates wastewater with low biodegradability due to the presence of persistent pollutants, which can produce toxic and carcinogenic compounds; therefore, wastewater treatment reduces risks to aquatic life and public health. This paper presents a review of 172 papers regarding textile industry wastewater treatment for the removal of contaminants, especially indigo dyes used in the denim industry, in the context of green technologies. The physicochemical characteristics of textile wastewater, its environmental and health impacts, and the permissible limit regulations in different countries were reviewed. Biological, physicochemical and advanced oxidation processes for the removal of indigo dyes were reviewed. The goal of this study was to analyze the characteristics of green technologies; however, the research does not clearly demonstrate an effect on energy consumption savings, carbon footprint decreases, and/or waste generation. Advanced oxidation processes showed the highest color removal efficiency (95 and 97% in synthetic or real wastewater, respectively). Photocatalysis and Fenton reactions were the most efficient processes. None of the revised works presented results regarding upscaling for industrial application, and the results should be discussed in terms of the guidelines and maximum permissible limits established by international legislation. New technologies need to be developed and evaluated in a sustainable context with real wastewater.

"It was terrible, I didn't sleep for two years": A mixed methods exploration of sleep and its effects among family caregivers of in-home hospice patients at end-of-life.

BACKGROUND: Due to overnight caregiving demands; exacerbation of high rates of anxiety, depression, and distress; and inadequate support, millions of family caregivers of patients receiving in-home hospice are at risk of poor sleep and negative health effects. AIM: To describe sleep experiences of family caregivers of in-home hospice patients and perceptions of these experiences on caregivers' wellbeing in the context of caregiver health and live-in status. DESIGN: Developed using the Symptom Management Model, this mixed methods study featured a concurrent nested design prioritizing qualitative reflexive thematic analysis. SETTING/PARTICIPANTS: About 47 family caregivers of in-home hospice patients from two randomized clinical trials (NCT03712410, NCT02929108) were interviewed (United States, 2021). Anxiety (GAD-7), depression (PHQ-9), quality-of-life (QOL) (CQLI-R), and self-rated health and energy were reported prior to interviews. RESULTS: Qualitative analysis revealed three themes: compromised sleep quality, factors influencing sleep, effects of sleep. 72.5% of hospice family caregivers described "fair" or "poor" sleep quality, with "interrupted" sleep and frequent night-waking due to "on-call" "vigilance" and anxiety. Negative effects included exhaustion, mental and physical health decline, and reduced caregiver function. Live-in caregivers reported higher mean depression scores (8.4 vs 4.3, p = 0.08), higher mean anxiety scores (7.7 vs 3.3, p = 0.06), and lower mean QOL scores (24.8 vs 33.6, p < 0.001) than live-out caregivers. Anxiety, depression, and QOL worsened as self-reported caregiver sleep quality decreased. Few caregivers had adequate support. CONCLUSION: End-of-life family caregivers experience disrupted sleep with negative effects and inadequate support. Clinicians must assess sleep, offer sleep interventions, and provide more supports to hospice family caregivers.

An mHealth-Facilitated Personalized Intervention for Physical Activity and Sleep in Community-Dwelling Older Adults.

This randomized controlled pilot trial tested the preliminary effect of a 24-week mHealth-facilitated, personalized intervention on physical activity (PA) and sleep in 21 community-dwelling older adults. The intervention included a personalized exercise prescription, training, goal setting, and financial incentives. mHealth strategies, including self-monitoring, motivational messages, activity reminders, and phone coaching, were used to facilitate PA participation. PA and sleep were measured using actigraphy and questionnaires at baseline and 8-, 16-, and 24-week visits. Participants in the intervention group had lower objective PA levels at 24 weeks than at 8 and 16 weeks, although levels of PA remained higher than at baseline. Compared with the control group, the intervention increased PA at 8, 16, and 24 weeks; improved subjective sleep quality at 16 and 24 weeks; and increased actigraphy-measured sleep duration and sleep efficiency at 24 weeks. mHealth PA interventions may benefit PA and sleep in older adults. Strategies for maintaining long-term PA behavioral changes are needed.

[Academic residents fellowship program at the University of Chile Clinical Hospital]. / Becas para la formación de médicos especialistas académicos del Hospital Clínico de la Universidad de Chile.

The mission of the University of Chile Clinical Hospital is to be the main University Hospital in the country. Along with training of health professionals in clinical practice and research, the Hospital provides comprehensive health solutions to the community. Since its foundation, it played an important role in the training of health professionals and specialists. To fulfill this mission, it is important to have outstanding academics and a system that allows their renewal and replacement. From January 25, 2001, the University of Chile approved the regulations that rule the Residents Program Fellowship, aimed to train the new generations of clinical academics. These regulations allow the financing of training programs in basic or primary specialties (such as internal medicine, surgery, obstetrics and gynecology, among others) or in specialties derived from them (such as cardiology, gastroenterology and reproductive medicine, among others.) The different clinical departments and the Hospital Direction define each year how many places will be offered and in which specialties. The Faculty of Medicine Graduate School carries out the formal selection of the applicants. This article reviews the results of this program between 2013 and 2021, analyzing in detail the traceability of each graduate over the years.

Correlates of Sleep Disturbance Experienced by Informal Caregivers of Persons Living with Dementia: A Systematic Review.

OBJECTIVES: This study aims to comprehensively review and update the literature concerning the correlates of sleep disturbance among caregivers of persons living with Alzheimer's disease and related dementias to identify gaps in the literature and antecedent targets for interventions. METHODS: We searched PubMed, CINAHL, PsycINFO, and Embase using terms related to "sleep," "caregiver," and "dementia." RESULTS: Thirty-six articles were included in this review. Based on the antecedents within the 3P model of insomnia, predisposing factors associated with caregiver sleep included caregiver demographics, and physiological factors like genotype and biomarkers. Precipitating factors related to caregiver sleep included caregiving status and responsibilities, and person living with dementia factors. CONCLUSIONS: Sleep disturbance is a significant issue for caregivers of persons living with dementia. However, this review has identified multiple precipitating factors that are modifiable targets for interventions to improve or enhance caregiver sleep. CLINICAL IMPLICATIONS: Numerous predisposing and precipitating factors contribute to caregivers of persons living with dementia being susceptible to sleep disturbance. Healthcare providers should ask patients about their caregiving status during annual visits. Healthcare providers should also evaluate caregivers' sleep patterns, and the predisposing and precipitating factors of sleep disturbance, with a focus on the modifiable factors, to enable timely intervention.

Delineation of the pH-Responsive Regulon Controlled by the Helicobacter pylori ArsRS Two-Component System.

Helicobacter pylori encounters a wide range of pH within the human stomach. In a comparison of H. pylori cultured in vitro under neutral or acidic conditions, about 15% of genes are differentially expressed, and corresponding changes are detectable for many of the encoded proteins. The ArsRS two-component system (TCS), comprised of the sensor kinase ArsS and its cognate response regulator ArsR, has an important role in mediating pH-responsive changes in H. pylori gene expression. In this study, we sought to delineate the pH-responsive ArsRS regulon and further define the role of ArsR in pH-responsive gene expression. We compared H. pylori strains containing an intact ArsRS system with an arsS null mutant or strains containing site-specific mutations of a conserved aspartate residue (D52) in ArsR, which is phosphorylated in response to signals relayed by the cognate sensor kinase ArsS. We identified 178 genes that were pH-responsive in strains containing an intact ArsRS system but not in ΔarsS or arsR mutants. These constituents of the pH-responsive ArsRS regulon include genes involved in acid acclimatization (ureAB, amidases), oxidative stress responses (katA, sodB), transcriptional regulation related to iron or nickel homeostasis (fur, nikR), and genes encoding outer membrane proteins (including sabA, alpA, alpB, hopD [labA], and horA). When comparing H. pylori strains containing an intact ArsRS TCS with arsRS mutants, each cultured at neutral pH, relatively few genes are differentially expressed. Collectively, these data suggest that ArsRS-mediated gene regulation has an important role in H. pylori adaptation to changing pH conditions.

Dark Energy Survey Year 1 Results: Cosmological Constraints from Cluster Abundances, Weak Lensing, and Galaxy Correlations.

We present the first joint analysis of cluster abundances and auto or cross-correlations of three cosmic tracer fields: galaxy density, weak gravitational lensing shear, and cluster density split by optical richness. From a joint analysis (4×2pt+N) of cluster abundances, three cluster cross-correlations, and the auto correlations of the galaxy density measured from the first year data of the Dark Energy Survey, we obtain Ω_{m}=0.305_{-0.038}^{+0.055} and σ_{8}=0.783_{-0.054}^{+0.064}. This result is consistent with constraints from the DES-Y1 galaxy clustering and weak lensing two-point correlation functions for the flat νΛCDM model. Consequently, we combine cluster abundances and all two-point correlations from across all three cosmic tracer fields (6×2pt+N) and find improved constraints on cosmological parameters as well as on the cluster observable-mass scaling relation. This analysis is an important advance in both optical cluster cosmology and multiprobe analyses of upcoming wide imaging surveys.

Effects of dietary fibre intake in chemotherapy-induced mucositis in murine model.

Mucositis is an inflammation of the gastrointestinal mucosa resulting from high doses of radio/chemotherapy treatment and may lead to interruption of antineoplasic therapy. Soluble fibres, like pectin, increase SCFA production, which play a role in gut homoeostasis and inflammation suppression. Due to the properties of pectin, the aim of the present study was to evaluate the effect of a high-fibre (HF) diet on chemotherapy-induced mucositis in a murine model. C57/BL6 mice received control (AIN93M), HF, low/zero fibre (LF) diets for 10 d prior to mucositis challenging with irinotecan (75 mg/kg), or they were treated with acetate added to drinking water 5 d prior to and during the mucositis induction. Mice that received the HF diet showed decreased immune cells influx and improved histopathological parameters in the intestine, compared with mice that received the normal diet. Furthermore, the HF diet decreased intestinal permeability induced in the mucositis model when compared with the control group. This effect was not observed for acetate alone, which did not improve gut permeability. For instance, mice that received the LF diet had worsened gut permeability, compared with mice that received the normal diet and mucositis. The effects of the HF and LF diets were shown to modulate the intestinal microbiota, in which the LF diet increased the levels of Enterobacteriaceae, a group associated with gut inflammation, whereas the HF diet decreased this group and increased Lactobacillus and Bifidobacterium (SCFA producers) levels. In conclusion, the results demonstrated the importance of dietary fibre intake in the modulation of gut microbiota composition and homoeostasis maintenance during mucositis in this model.

Validation of an in vitro system to trigger changes in the gene expression of effectors of Sclerotinia sclerotiorum.

AIMS: Sclerotinia sclerotiorum, the causal agent of white mold, can infect several host species, including economically important crops. In this study, we propose and validate a new in vitro system able to mimic the conditions of interaction with the host and promote the induction of S. sclerotiorum effectors. METHODS AND RESULTS: For culture media production, we selected three plant species, common bean (Phaseolus vulgaris L, cv. Requinte.), maize (Zea mays, cv. BRS1030) and beggarticks (Bidens pilosa). To validate this system as an in vitro inducer of effectors, the qRT-PCR technique was used to investigate the expression profile of some S. sclerotiorum effector genes in each growth medium at different times after inoculation. CONCLUSION: The results obtained in this study provide a validation of a new method to study S. sclerotiorum during mimetic interaction with different hosts. Although leaf extract does not fully represent the plant environment, the presence of plant components in the culture medium seems to induce effector genes, mimicking in planta conditions. The use of MEVM is simpler than in planta growth, bypasses problems such as the amount of mycelium produced, as well as contamination of host cells during transcriptomic and proteomic analyses. SIGNIFICANCE AND IMPACT OF THE STUDY: We have devised MEVM media as a model mimicking the interaction of S. sclerotiorum and its hosts and used it to evaluate in vitro expression of effectors normally expressed only in planta.

Automated cell tracking identifies mechanically oriented cell divisions during Drosophila axis elongation.

Embryos extend their anterior-posterior (AP) axis in a conserved process known as axis elongation. Drosophila axis elongation occurs in an epithelial monolayer, the germband, and is driven by cell intercalation, cell shape changes, and oriented cell divisions at the posterior germband. Anterior germband cells also divide during axis elongation. We developed image analysis and pattern-recognition methods to track dividing cells from confocal microscopy movies in a generally applicable approach. Mesectoderm cells, forming the ventral midline, divided parallel to the AP axis, while lateral cells displayed a uniform distribution of division orientations. Mesectoderm cells did not intercalate and sustained increased AP strain before cell division. After division, mesectoderm cell density increased along the AP axis, thus relieving strain. We used laser ablation to isolate mesectoderm cells from the influence of other tissues. Uncoupling the mesectoderm from intercalating cells did not affect cell division orientation. Conversely, separating the mesectoderm from the anterior and posterior poles of the embryo resulted in uniformly oriented divisions. Our data suggest that mesectoderm cells align their division angle to reduce strain caused by mechanical forces along the AP axis of the embryo.

Association of health related quality of life domains with daytime sleepiness among elderly recipients of long-term services and supports.

Excessive daytime sleepiness (EDS) is prevalent in older adults; however, data are lacking that examine EDS across living environments. The aims of this secondary data analysis were to identify the prevalence and predictors of EDS among older adults receiving long-term services and supports (LTSS) in assisted living communities (ALCs), nursing homes (NHs), and the community. Participants (n = 470) completed multiple measures including daytime sleepiness. Logistic regression modeling was used to identify EDS predictors. Participants were primarily female and white with a mean age of 81 ± 9 years. The overall prevalence of EDS was 19.4%; the prevalence differed across living environment. Older adults in ALCs and NHs had higher odds of EDS than those living in the community. Also, depressive symptoms and number of bothersome symptoms predicted EDS. Upon admission for LTSS, evaluating older adults, especially those in ALCs and NHs, for depression and bothersome symptoms may reveal modifiable factors of EDS.

Experimental and Computational Characterization of the Interaction between Gold Nanoparticles and Polyamidoamine Dendrimers.

Dendrimers provide a means to control the synthesis of gold nanoparticles and stabilize their suspensions. However, design of improved dendrimers for this application is hindered by a lack of understanding how the dendrimers and synthesis conditions determine nanoparticle morphology and suspension stability. In the present work, we evaluate the effect of polyamidoamine (PAMAM) dendrimers terminated with different functional groups (-OH or -NH3+) and different synthesis conditions on the morphology of the resulting gold nanoparticles and their stability in solution. We leverage molecular dynamics (MD) simulations to identify the atomic interactions that underlie adsorption of PAMAM dendrimers to gold surface and how the thermodynamics of this adsorption depends on the terminal functional groups of the dendrimers. We find that gold nanoparticles formed with hydroxyl-terminated PAMAM (PAMAM-OH) rapidly aggregate, whereas those formed with PAMAM-NH3+ are stable in solution for months of storage. Synthesis under ultrasound sonication is shown to be more rapid than that under agitation, with sonication producing smaller nanoparticles. Free-energy calculations in MD simulations show that all dendrimers have a high affinity for the gold surface, although PAMAM-OH and its oxidized aldehyde form (PAMAM-CHO) have a greater affinity for the nanoparticle surface than PAMAM-NH3+. Although adsorption of PAMAM-OH and PAMAM-CHO has both favorable entropy and enthalpy, adsorption of PAMAM-NH3+ is driven by a strong enthalpic component subject to an unfavorable entropic component.

Effects of supplemental calcium salts of palm oil and chromium-propionate on insulin sensitivity and productive and reproductive traits of mid- to late-lactating Holstein × Gir dairy cows consuming excessive energy.

This experiment compared insulin sensitivity, milk production, and reproductive outcomes in dairy cows consuming excessive energy during mid to late lactation and receiving in a 2 × 2 factorial design (1) concentrate based on ground corn (CRN; n = 20) or including 8% (DM basis) of Ca salts of palm oil (CSPO; n = 20), and (2) supplemented (n = 20) or not (n = 20) with 2.5 g/d of Cr-propionate. During the experiment (d 0-203), 40 multiparous, nonpregnant, lactating 3/4 Holstein × 1/4 Gir cows (initial days in milk = 81 ± 2; mean ± SE) were offered corn silage for ad libitum consumption, and individually received concentrate formulated to allow diets to provide 160% of their daily net energy for lactation requirements. From d -15 to 203, milk production was recorded daily, blood samples collected weekly, and cow body weight (BW) and body condition score (BCS) recorded on d 0 and 203. For dry matter intake evaluation, cows from both treatments were randomly divided in 5 groups of 8 cows each, and allocated to 8 individual feeding stations for 3 d. Intake was evaluated 6 times/group. Glucose tolerance tests (GTT; 0.5 g of glucose/kg of BW) were performed on d -3, 100, and 200. Follicle aspiration for in vitro embryo production was performed via transvaginal ovum pick-up on d -1, 98, and 198. Mean DMI, net energy for lactation intake, as well as BW and BCS change were similar across treatments. On average, cows gained 40 kg of BW and 0.49 BCS during the experiment. Within weekly blood samples, CRN cows had lower serum concentrations of glucose, insulin, fatty acids, and insulin-to-glucose ratio compared with CSPO cows, suggesting increased insulin sensitivity in CRN cows. During the GTT, insulin-sensitivity traits were also greater in CRN versus CSPO cows. Supplemental Cr-propionate resulted in lower serum insulin concentrations and insulin-to-glucose ratio within CRN cows only, indicating that Cr-propionate improved basal insulin sensitivity in CRN but not in CSPO cows. During the GTT, however, Cr-propionate supplementation reduced hyperinsulinemia and insulin-to-glucose ratio across CSPO and CRN cows. Milk production, as well as number of viable oocytes collected and embryos produced within each aspiration, were not affected by treatments. Hence, replacing corn by Ca salts of palm oil in the concentrate did not improve insulin sensitivity in Holstein × Gir dairy cows consuming excessive energy during mid to late lactation, whereas Cr-supplementation was effective in improving basal insulin sensitivity in cows not receiving Ca salts of palm oil.

Cohesin modulates transcription of estrogen-responsive genes.

The cohesin complex has essential roles in cell division, DNA damage repair and gene transcription. The transcriptional function of cohesin is thought to derive from its ability to connect distant regulatory elements with gene promoters. Genome-wide binding of cohesin in breast cancer cells frequently coincides with estrogen receptor alpha (ER), leading to the hypothesis that cohesin facilitates estrogen-dependent gene transcription. We found that cohesin modulates the expression of only a subset of genes in the ER transcription program, either activating or repressing transcription depending on the gene target. Estrogen-responsive genes most significantly influenced by cohesin were enriched in pathways associated with breast cancer progression such as PI3K and ErbB1. In MCF7 breast cancer cells, cohesin depletion enhanced transcription of TFF1 and TFF2, and was associated with increased ER binding and increased interaction between TFF1 and its distal enhancer situated within TMPRSS3. In contrast, cohesin depletion reduced c-MYC mRNA and was accompanied by reduced interaction between a distal enhancer of c-MYC and its promoters. Our data indicates that cohesin is not a universal facilitator of ER-induced transcription and can even restrict enhancer-promoter communication. We propose that cohesin modulates transcription of estrogen-dependent genes to achieve appropriate directionality and amplitude of expression.