Histone Variant Macroh2a In The Gut And Beyond: A Study Of Intestinal Fortitude

Epigenetic factors guide chromatin remodeling during cell state transitions and confer resistance to genotoxic stressors that could induce deleterious transformations. A particularly peculiar component of the epigenome with emerging roles in fine-tuning cell identity and upholding genomic stability is the structural histone variant macroH2A. Relatively little is currently known about macroH2A’s influence on overall cell developmental potency and less still is known about macroH2A’s contributions to adult stem cell identity and function in vivo. In this work, we use induced pluripotent stem cell (iPSC) reprogramming and the murine intestinal stem cell (ISC) system to model macroH2A’s overall impact on cell epigenetic identity from embryo to adult. We manipulated macroH2A content during iPSC reprogramming and concluded that macroH2A removal from somatic chromatin constitutes a mild, but present epigenetic bottleneck to pluripotency acquisition. Using epitope-tagged-macroH2A-expressing cells, we demonstrated that embryonic stem cells (ESCs) display significantly more dynamic macroH2A incorporation and turnover than fibroblasts, particularly proximal to the promoters of highly transcribed genes, concluding that macroH2A is less stably associated with ESC chromatin. In a separate study, we bred macroH2A double germline knockout (DKO) and strain-matched wildtype (WT) mice into reporter strains for ISC subpopulations, enabling us to functionally test active and reserve ISCs during homeostasis and following γ-irradiation injury. We showed that macroH2A DKO intestine is host to elevated numbers of putative reserve ISCs, suggesting that macroH2A may normally limit the size of the reserve ISC pool. We further determined that although macroH2A is unnecessary for intestinal homeostasis, macroH2A strongly bolsters the intestinal regeneration response following irradiative injury by promoting reserve ISC radioresistance. We thus conclude overall that macroH2A imposes a minor resistance to induced pluripotency, limits the size of the reserve ISC pool in adult mice and finally upholds genomic stability by providing resistance to genotoxic stress in vivo

A Comparison of Constrained and Unconstrained Upper Quarter Y-Balance Tests Performance in the Adult Active Population

Common screening tools for upper extremity functionality tend to focus only on power, speed, and/or stability of the shoulder. Previous research studies validated the reliability of the Upper Quarter Y-Balance Test (UQYBT) as a clinical tool to measure unilateral upper extremity function, dynamics, as well as indirectly thoracic mobility. The distinctiveness of this test is the combination of shoulder girdle mobility and stability, core stability, thoracic rotation, and overall muscles strength to reach as far as possible without losing balance in the single arm stance position. Thus, measuring upper body strength and thoracic rotation may predict performance. PURPOSE: The aim of this study is to compare the performance of physically active individuals in two variations of the UQYBT, constrained and unconstrained, and to measure the relation of upper body strength and trunk mobility with the UQYBT reach scores. METHODS: Five male (31.2±9.0 years, 1.73±.02 m, 78.8±7.0 kg) and five female (24.4±.8 years, 1.67±.06 m, 71.4±2.7 kg) college students participated in two testing sessions. Participants completed a maximal push-up test and a maximal seated trunk rotation mobility test. During the second session, participants performed the Constrained UQYBT (participant keeps the push-up position) and the Unconstrained variation in which it was allowed to flex elbow of supporting arm and flex the hip when reaching in any direction. For each test, subjects completed three reaches in medial, inferolateral, and superolateral directions. Maximal reach scores in each direction were identified and composite scores were calculated for the two UQYBTs. MANOVA was used to identify differences in reach scores between the Constrained and Unconstrained UQYBTs, significance level was set to .05. Pearson correlation was used to identify relations between maximal push-up score and maximal trunk rotation range of motion (ROM) with the UQYBT reach scores. RESULTS: Significant differences were observed for all reach scores between the Constrained and Unconstrained UQYBTs. Unconstrained UQYBT had higher reach score scores than the Constrained UQYBT in the medial (119±9% vs 100±7%, p-value\u3c.001), inferolateral (110±14% vs 80±10%, p-value\u3c.001), and superolateral (82±13% vs 73±13%, p-value=.042) directions, and in the composite score (103±10% vs 84±8%, p-value\u3c.001). Moderate to strong positive correlations were observed between maximal trunk rotation ROM and most reach scores in Constrained and Unconstrained UQYBTs. The correlation coefficients were between .331 to .605. Moderate positive coefficient (r=.365) was identified between max push-ups and Constrained Inferolateral reach. In contrast, strong negative correlation (r=-584) was identified between Unconstrained superolateral reach and max push-ups. CONCLUSION: The main finding of this study identified the big difference in reach scores between Constrained and Unconstrained UQYBTs. Practitioners need to be cautious when performing the UQYBT and when comparing reach scores from different resources. Moreover, it seems that large trunk mobility is associated with higher UQYBT reach scores

Differences in Reach Scores Between Three Upper Quarter Y-Balance Test Versions in Older Adults

The Upper Quarter Y-Balance Test (UQYBT) is often used to measure shoulder mobility and stability and screen for upper extremities musculoskeletal disorders in the physically active and athletic population. Shoulder injuries are typical among older adults, often decreasing the quality of life. There are no studies investigating the functionality of the UQYBT in older adults. PURPOSE: To examine the functionality of the UQYBT and two variations on the older population, 50 years old and older. METHODS: Eight individuals (2 males and 6 females) participated in this study (56.8±3.9 years, 166.0±10.0 cm, 69.6±13.5 kg). Each participant completed a five-minute warm-up on an arm ergometer followed by an arm length measurement. Participants completed the three UQYBT variations in a randomized order; Standard push-up position (SUQYBT), Modified push-up position (MUQYBT), and Wall push-up position (WUQYBT). In each variation, participants completed three reaches in the medial, inferolateral, and superolateral directions for the right and left hands. Highest score for each reach from the different UQYBT variations and supporting hand were saved to further analysis. Relative reach scores were calculated using the right arm length as reference. Composite scores were calculated by averaging the reach scores of the three directions. Repeated measured ANOVAs were used to compare reach score between the UQYBT variations in the older population. This was followed by post-hoc analysis; alpha level was set to 0.05. RESULTS: Significant main effects were identified in the medial reach (p-value CONCLUSION: Several differences were observed between the three UQYBT variations. When the reach was outside of the participant’s base of support (medial and superolateral reaches) WUQYBT had the highest score followed by MUQYBT and last SUQYBT. During the inferolateral reach, participants were able to get similar reach scores between the different UQYBT variations. Further studies should study the option to use the two UQYBT variations in the older population

Gender Performance Differences in Standard Upper Quarter Y-Balance Test and Two Modified Versions

Preparticipation screening evaluating musculoskeletal functioning is gaining popularity in young adults. The Upper Quarter Y-Balance Test (UQYBT) is often used to measure shoulder mobility and stability, and screening for upper extremities musculoskeletal injuries. The UQYBT is renowned for its unique approach to testing shoulder and core stability in the athletic and active population. Its feasibility in less active individuals is questionable due to its strength and balance requirements. Moreover, there is minimal data comparing UQYBT scores between genders of different fitness levels. PURPOSE: To examine performance differences between women and men executing the standard UQYBT and two modifications. METHODS: Eleven women (22.5±3.2 years, 1.64±0.04 m, 66.1±10.5 kg) and nine men (27.0±8.8 years, 1.74±0.03 m, 74.2±12.8 kg) college students took part in this study. Prior to testing, participants completed five minutes warm-up on an arm ergometer. Participants completed the three UQYBT variations in a randomized order; Standard (traditional push-up position), Modified (modified push-up position), and Wall (standing erect). In each variation, participants completed three reaches in the medial, inferolateral, and superolateral direction. Maximal relative scores were collected, and composite scores were calculated. MANOVA was conducted comparing the differences between women and men reach scores in each direction and for each UQYBT variation. Significance level was set to .05. RESULTS: Significant differences were observed in the Modified UQYBT for the inferolateral reach, women had higher max relative scores than men, p-value\u3c.01. Women average maximal relative score was 89±10%, whereas men average score was 80±8%. Similar significance trend was identified in the Wall UQYBT during the inferolateral reach. Women reach score (82±8%) was higher than the men reach score (72±11%), p-values\u3c.01. No significant differences were observed in any of the other reaches measured during the three UQYBT variations. CONCLUSION: In this study we measured gender differences during three UQYBT variations. The most body weight the upper extremity needs to balance is during the Standard position, followed by the Modified and Wall UQYBT. We have found gender differences in the Modified and Wall UQYBTs during the inferolateral reach. The difference may be related to fact that during the Modified and Wall UQYBTs there is less body weight on the upper extremity which may increase women ability to have better shoulder mobility and stability than the men. Further research is required in this area

A system for genome-wide histone variant dynamics in ES cells reveals dynamic MacroH2A2 replacement at promoters

Dynamic exchange of a subset of nucleosomes in vivo plays important roles in epigenetic inheritance of chromatin states, chromatin insulator function, chromosome folding, and the maintenance of the pluripotent state of embryonic stem cells. Here, we extend a pulse-chase strategy for carrying out genome-wide measurements of histone dynamics to several histone variants in murine embryonic stem cells and somatic tissues, recapitulating expected characteristics of the well characterized H3.3 histone variant. We extended this system to the less-studied MacroH2A2 variant, commonly described as a repressive histone variant whose accumulation in chromatin is thought to fix the epigenetic state of differentiated cells. Unexpectedly, we found that while large intergenic blocks of MacroH2A2 were stably associated with the genome, promoter-associated peaks of MacroH2A2 exhibited relatively rapid exchange dynamics in ES cells, particularly at highly-transcribed genes. Upon differentiation to embryonic fibroblasts, MacroH2A2 was gained primarily in additional long, stably associated blocks across gene-poor regions, while overall turnover at promoters was greatly dampened. Our results reveal unanticipated dynamic behavior of the MacroH2A2 variant in pluripotent cells, and provide a resource for future studies of tissue-specific histone dynamics in vivo

Consensus on Aquatic Primary Productivity Field Protocols for Satellite Validation and Model Synthesis

The NASA PACE project, in conjunction with the IOCCG, EUMETSAT, and JAXA, have initiated an Aquatic Primary Productivity working group, with the aim to develop community consensus on multiple methods for measuring aquatic primary productivity used for satellite validation and model synthesis. A workshop to commence the working group efforts was held December 05-07, 2018 at the University Space Research Association headquarters in Columbia, MD U.S.A., bringing together 26 active researchers from 16 institutions. The group discussed the primary differences, nuances, scales, uncertainties, definitions, and best practices for measurements of primary productivity derived from in situ/on-deck/laboratory radio/stable isotope incubations, dissolved oxygen concentrations (from incubations or autonomous platforms such as floats or gliders), oxygen-argon ratios, triple oxygen isotope, natural fluorescence, and FRRF/ETR/kinetic analysis. These discussions highlighted the necessity to move the community forward towards the establishment of climate-quality primary productivity measurements that follow uniform protocols, which is imperative to ensure that existing and future measurements can be compared, assimilated, and their uncertainties determined for model development and validation. The specific deliverable resulting from of this activity will be a protocol document, published in coordination with the IOCCG. This presentation will discuss the findings of the meeting, and address future activities of the working group

The Msi Family of RNA-Binding Proteins Function Redundantly as Intestinal Oncoproteins

Members of the Msi family of RNA-binding proteins have recently emerged as potent oncoproteins in a range of malignancies. MSI2 is highly expressed in hematopoietic cancers, where it is required for disease maintenance. In contrast to the hematopoietic system, colorectal cancers can express both Msi family members, MSI1 and MSI2. Here, we demonstrate that, in the intestinal epithelium, Msi1 and Msi2 have analogous oncogenic effects. Further, comparison of Msi1/2-induced gene expression programs and transcriptome-wide analyses of Msi1/2-RNA-binding targets reveal significant functional overlap, including induction of the PDK-Akt-mTORC1 axis. Ultimately, we demonstrate that concomitant loss of function of both MSI family members is sufficient to abrogate the growth of human colorectal cancer cells, and Msi gene deletion inhibits tumorigenesis in several mouse models of intestinal cancer. Our findings demonstrate that MSI1 and MSI2 act as functionally redundant oncoproteins required for the ontogeny of intestinal cancers

Glycobiology of immune responses

Unlike their protein roommates and their nucleic acid cousins, carbohydrates remain an enigmatic arm of biology. The central reason for the difficulty in fully understanding how carbohydrate structure and biological function are tied is the non-template nature of their synthesis and the resulting heterogeneity. While this Annals of the NYAS issue does not claim to hold all of the answers, the goal is to highlight what is known about how carbohydrates and their binding partners, on the microbial (non-self), tumor (altered-self) and host (self) sides, cooperate within the immune system while identifying areas of great opportunity to those willing to take up the challenge. In the end, these reviews will serve as specific examples of how carbohydrates are as integral to biology as proteins, nucleic acids, and lipids. In this introductory article we attempt to summarize general concepts on glycans and glycan-binding proteins (mainly C-type lectins, siglecs and galectins) and their contribution to the biology of the immune responses in physiologic and pathologic settings.Fil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Van Kooyk, Yvette. VU University Amsterdam. VU University Medical Center; Países BajosFil: Cobb, Brian A.. Case Western Reserve University; Estados Unido

The Relation Between Measured Subject’s Body Fat Percentage and Three Upper Quarter Y-Balance Test Variations in College Students.

College students tend to gain weight and increase body fat percentage (BF%) during their four academic years. Cross-sectional studies and longitudinal studies are starting to highlight the importance of body composition and its correlation to a decrease in joint health. While the Upper Quarter Y-Balance Test (UQYBT) has been proven to be a reliable tool to measure upper extremity joint mobility and stability in young healthy individuals. Past research has failed to account for physiological differences in body composition and body size of college students. The UQYBT in its current format might not be ideal for overweight individuals since it requires isometric strength to support body weight. PURPOSE: To investigate the relation between BF% of college students with their performance in three UQYBT variations. METHODS: Twenty college students (24.5±6.7 years, 1.69±0.06 m, 69.8±12.1 kg) 11 females and nine males participated in this study. Body fat percentage was collected using handheld BIA prior to testing, followed by five minutes upper extremity warm-up on an arm ergometer. All participants successfully performed the Standard (traditional push-up position), Modified (modified push-up position), and Wall (standing erect) UQYBT variations. Participants max scores of the three reaches (medial, inferolateral, and superolateral) were collected and composite scores were calculated. A Pearson correlation analysis was performed between the reaches scores in each of the UQYBT variations and BF%. Significance level was set to .05. RESULTS: Body fat percentage was found to be 20.8±7.5%. Moderate negative correlation were found between BF% and the max absolute scores in Standard UQYBT medial reach (r=-.33), inferolateral reach (r=-.34), superolateral reach (r=-.40), and in Modified UQYBT superolateral reach (r=-.39). In contrast, moderate to strong positive correlation were found between BF% and the max relative scores in Wall UQYBT inferolateral reach (r=.54), superolateral (r=.48), and composite score (r=.52). In addition, moderate positive correlation was found between BF% and the max absolute scores in Wall UQYBT inferolateral reach (r=.32). CONCLUSION: Our findings identify differences between the three UQYBT variations and BF%. When the participant carries his body weight in the traditional or modify push-up position the correlation is negative, which means that the heavier you are the lower your reach score will be. On the contrary, when performing UQYBT in a standing position the correlation between the BF% and the reach scores were positive. This could be related to gender differences or differences in upper body range of motion. Future studies need to examine gender differences and range of motion of upper body with respect to UQYBT