Regulation of alternative polyadenylation in the yeast Saccharomyces cerevisiae by histone H3K4 and H3K36 methyltransferases.

Adjusting DNA structure via epigenetic modifications, and altering polyadenylation (pA) sites at which precursor mRNA is cleaved and polyadenylated, allows cells to quickly respond to environmental stress. Since polyadenylation occurs cotranscriptionally, and specific patterns of nucleosome positioning and chromatin modifications correlate with pA site usage, epigenetic factors potentially affect alternative polyadenylation (APA). We report that the histone H3K4 methyltransferase Set1, and the histone H3K36 methyltransferase Set2, control choice of pA site in Saccharomyces cerevisiae, a powerful model for studying evolutionarily conserved eukaryotic processes. Deletion of SET1 or SET2 causes an increase in serine-2 phosphorylation within the C-terminal domain of RNA polymerase II (RNAP II) and in the recruitment of the cleavage/polyadenylation complex, both of which could cause the observed switch in pA site usage. Chemical inhibition of TOR signaling, which causes nutritional stress, results in Set1- and Set2- dependent APA. In addition, Set1 and Set2 decrease efficiency of using single pA sites, and control nucleosome occupancy around pA sites. Overall, our study suggests that the methyltransferases Set1 and Set2 regulate APA induced by nutritional stress, affect the RNAP II C-terminal domain phosphorylation at Ser2, and control recruitment of the 3 end processing machinery to the vicinity of pA sites.post-print1.432 K

Clinical effectiveness of cell therapies in patients with chronic liver disease and acute-on-chronic liver failure: a systematic review protocol

PRISMA-P (Preferred Reporting Items for Systematic review and Meta-Analysis Protocols) 2015 checklist: recommended items to address in a systematic review protocol*. (DOC 82 kb

Macrophage differentiation is marked by increased abundance of the mRNA 3’ end processing machinery, altered poly(A) site usage, and sensitivity to the level of CstF64

Regulation of mRNA polyadenylation is important for response to external signals and differentiation in several cell types, and results in mRNA isoforms that vary in the amount of coding sequence or 3’ UTR regulatory elements. However, its role in differentiation of monocytes to macrophages has not been investigated. Macrophages are key effectors of the innate immune system that help control infection and promote tissue-repair. However, overactivity of macrophages contributes to pathogenesis of many diseases. In this study, we show that macrophage differentiation is characterized by shortening and lengthening of mRNAs in relevant cellular pathways. The cleavage/polyadenylation (C/P) proteins increase during differentiation, suggesting a possible mechanism for the observed changes in poly(A) site usage. This was surprising since higher C/P protein levels correlate with higher proliferation rates in other systems, but monocytes stop dividing after induction of differentiation. Depletion of CstF64, a C/P protein and known regulator of polyadenylation efficiency, delayed macrophage marker expression, cell cycle exit, attachment, and acquisition of structural complexity, and impeded shortening of mRNAs with functions relevant to macrophage biology. Conversely, CstF64 overexpression increased use of promoter-proximal poly(A) sites and caused the appearance of differentiated phenotypes in the absence of induction. Our findings indicate that regulation of polyadenylation plays an important role in macrophage differentiation

Linking the Green and Brown Worlds: the Prevalence and Effect of Multichannel Feeding in Food Webs

Recent advances in food‐web ecology highlight that most real food webs (1) represent an interplay between producer‐ and detritus‐based webs and (2) are governed by consumers which are rampant omnivores; feeding on varied prey across trophic levels and resource channels. A possible avenue to unify these advances comes from models demonstrating that predators feeding on distinctly different channels may stabilize food webs. Empirical studies suggest many consumers engage in such behavior by feeding on prey items from both living‐autotroph (green) and detritus‐based (brown) webs, what we term “multichannel feeding,” yet we know little about how common such feeding is across systems and trophic levels, or its effect on system stability. Considering 23 empirical webs, we find that multichannel feeding is equally common across terrestrial, freshwater, and marine systems, with \u3e50% of consumers classified as multichannel consumers. Multichannel feeding occurred most often at the first consumer level, indicating that most taxa at the herbivore/detritivore level are more aptly described as multichannel consumers, and that such feeding is not restricted to predators. We next developed a simple four‐compartment nutrient cycling model for consumers eating both autotrophs and detritus with separate parameter sets to represent aquatic vs. terrestrial ecosystems. Modeling results showed that, across terrestrial and aquatic ecosystems, multichannel feeding is stabilizing at low attack rates on autotrophs or when attack rates are asymmetric (moderate on autotrophs while low on detritus), but destabilizing at high attack rates on autotrophs, compared to herbivory‐ or detritivory‐only models. The set of conditions with stable webs with multichannel consumers is narrower, however, for aquatic systems, suggesting that multichannel feeding may generally be more stabilizing in terrestrial systems. Together, our results demonstrate that multichannel feeding is common across ecosystems and may be a stabilizing force in real webs that have consumers with low or asymmetric attack rates

National Leadership Index 2008: A National Study of Confidence in Leadership

The National Study of Confidence in Leadership is a social science research program examining the attitudes of the American public toward the nation’s leadership. The study includes the National Leadership Index 2008, a multidimensional measure of the public’s confidence in leadership within different sectors of society. The study was pioneered in 2005 by the Center’s Research Director, Professor Todd L. Pittinsky.Center for Public Leadershi

Comparison of Regional Body Composition Estimates Obtained from Dual-energy X-ray Absorptiometry and Single-frequency Bioelectrical Impedance Analysis

The anatomical distribution of fat mass (FM) and lean mass (LM) is significant for health and athletic performance. Dual-energy x-ray absorptiometry (DXA) is often used for regional body composition analysis but is not portable, often inaccessible, and costly, while single-frequency bioelectrical impedance analysis (SFBIA) is a more affordable and accessible alternative. PURPOSE: The purpose of this analysis was to compare regional body composition estimates obtained via DXA and SFBIA. METHODS: After an overnight food and fluid fast, 102 adults (64 F, 38 M; age: 29.2 ± 13.4 y; BMI: 24.3 ± 3.9 kg/m2; BF%: 24.6 ± 8.3%) underwent assessments via DXA and SBFIA, each of which provided estimates of FM and LM for the whole body, torso, legs, and arms. DXA scans were performed using custom-made foam blocks to enhance accuracy of regional body composition estimates. SFBIA was performed using an 8-lead device with a 12-channel multiplexer. Both DXA and SFBIA were performed in the supine position. DXA was designated as the criterion method, and body composition estimates were compared using paired-samples t-tests using a Bonferroni-corrected significance level of p ≤ 0.00625. Additional evaluations were conducted using the correlation coefficient (r), constant error (CE), standard error of the estimate (SEE), and total error (TE). RESULTS: Correlations between DXA and SFBIA were high, and the magnitude of errors was generally small: LMTOTAL (r: 0.97; CE: 1.4 kg; SEE: 2.7 kg; TE: 2.9 kg), LMLEGS (r: 0.85; CE: -0.3 kg; SEE: 2.0 kg; TE: 2.1 kg), LMTORSO (r: 0.92; CE: 1.0 kg; SEE: 2.2 kg; TE: 2.5 kg), LMARMS (r: 0.96; CE: 0.6 kg; SEE: 0.6 kg; TE: 0.8 kg), FMTOTAL (r: 0.95; CE: -2.3 kg; SEE: 2.6 kg; TE: 3.5 kg), FMLEGS (r: 0.83; CE: -1.0 kg; SEE: 1.2 kg; TE: 2.0 kg), FMTORSO (r: 0.90; CE: -1.3 kg; SEE: 2.2 kg; TE: 2.6 kg), and FMARMS (r: 0.89; CE: -0.1 kg; SEE: 0.5 kg; TE: 0.5 kg). Despite the relatively small magnitude of differences in FM and LM estimates between DXA and SFBIA, results of paired-samples t-tests indicated that all differences were statistically significant (p \u3c 0.0001), with the exception of LMLEGS (p=0.13) and FMARMS (p=0.11). CONCLUSION: Despite the fact that body composition estimates for most regions exhibited statistically significant differences between DXA and SFBIA, the strong correlations (r: 0.83 to 0.97) and relatively low magnitude of error (CE: -2.3 to 1.4 kg; TE: 0.8 to 3.5 kg) indicate that SFBIA may be an acceptable alternative to DXA when regional body composition is being evaluated and DXA is unavailable. However, additional research is needed to determine the ability of SFBIA to accurately track changes in regional body composition over time. Due to its low cost, portability, and ease of use, the presently examined SFBIA device may represent a useful tool for the evaluation of regional body composition when more advanced methods are unavailable

Regulation of the Ysh1 endonuclease of the mRNA cleavage/polyadenylation complex by ubiquitinmediated degradation.

Mutation of the essential yeast protein Ipa1 has previously been demonstrated to cause defects in premRNA 3ʹ end processing and growth, but the mechanism underlying these defects was not clear. In this study, we show that the ipa1-1 mutation causes a striking depletion of Ysh1, the evolutionarily conserved endonuclease subunit of the 19-subunit mRNA Cleavage/Polyadenylation (C/P) complex, but does not decrease other C/P subunits. YSH1 overexpression rescues both the growth and 3ʹ end processing defects of the ipa1-1 mutant. YSH1 mRNA level is unchanged in ipa1-1 cells, and proteasome inactivation prevents Ysh1 loss and causes accumulation of ubiquitinated Ysh1. Ysh1 ubiquitination is mediated by the Ubc4 ubiquitin-conjugating enzyme and Mpe1, which in addition to its function in C/P, is also a RING ubiquitin ligase. In summary, Ipa1 affects mRNA processing by controlling the availability of the C/P endonuclease and may represent a regulatory mechanism that could be rapidly deployed to facilitate reprogramming of cellular responses.post-print4,60 M

Validity of Four-Compartment Model Body Fat Using Single- or Multi-frequency Bioelectrical Impedance Analysis to Estimate Body Water

Most common body composition assessment techniques make assumptions about the body, including the density and hydration of fat-free mass (FFM). An advantage of the four-compartment (4C) model is the ability to take these FFM characteristics into account when assessing body composition, thus reducing potential error. The total body water (TBW) estimate utilized in 4C models is particularly important due to the large contribution of water to an adult human’s total body mass (~40 - 70%) and FFM (~68 - 81%); however, the impact of utilizing different estimates of TBW within 4C model has not been fully explored. PURPOSE: The purpose of this investigation was to examine the validity of body fat percentage (BF%) estimates produced by 4C models utilizing single- or multi-frequency bioelectrical impedance analysis (BIA) TBW estimates as compared to a criterion 4C with TBW from bioimpedance spectroscopy (BIS). METHODS: After an overnight food and fluid fast, a sample of 101 adults (63 F, 38 M; age: 29.3 ± 13.5 y; BMI: 24.3 ± 4.0 kg/m2; BF%: 24.5 ± 8.3%) completed assessments via dual-energy x-ray absorptiometry (DXA), air displacement plethysmography (ADP), BIS, single-frequency BIA (SFBIA), multi-frequency BIA (MFBIA) and a body mass scale. A criterion 4C model (4CBIS) estimate of BF% was obtained using DXA for bone mineral, ADP for body volume, scale for body mass, and BIS for TBW. BIS was used as the reference TBW method due to its more direct estimation of TBW via mathematical procedures (i.e. Cole modeling and mixture theories) as compared to the prediction equations used by BIA. Alternate 4C estimates of BF% were produced using TBW values from MFBIA (4CMFBIA) and SFBIA (4CSFBIA). BF% estimates were compared using one-way ANOVA, and additional evaluations were conducted using the coefficient of determination (R2), constant error (CE), total error (TE), and 95% limits of agreement (LOA). RESULTS: BF% did not differ between 4CBIS (24.5 ± 8.3%), 4CMFBIA (24.4 ± 8.9%), and 4CSFBIA (25.7 ± 8.3%; p=0.52). 4CMFBIA exhibited negligible CE (-0.1 ± 2.3%), R2 of 0.97, TE of 2.3%, and LOA of 4.4%. 4CSFBIA exhibited a small CE (1.2 ± 1.2%), R2 of 0.98, TE of 1.6%, and LOA of 2.3%. CONCLUSION: At the group level, BF% estimates did not differ between any 4C model, indicating that both SFBIA and MFBIA can serve as viable alternatives to BIS for TBW estimation. Although the magnitude of group error (i.e. CE) was slightly smaller in 4CMFBIA, the individual error (i.e. LOA) and total error were smaller in 4CSFBIA,indicating that SFBIA TBW estimates may be more appropriate when tracking body composition changes within individuals using a 4C model. While the MFBIA and SFBIA technologies employed in the present study exhibited good validity, these results may not be attributable to all BIA analyzers. The quality of assessment device, affordability, portability and ease of use should be considered when utilizing an impedance-based technology for TBW estimation in a 4C model

Validity of Infrared 3-dimensional Scanning for Estimation of Body Composition: A 4-Compartment Model Comparison

Multiple infrared 3-dimensional (3D) scanning technologies exist, including time of flight (ToF) scanners and structured light scanners with static (SL-S) and dynamic (SL-D) configurations. ToF scanners measure depth by using the round-trip time of reflected photons, whereas SL scanners measure deformations in light patterns and allow for creation of a depth image using geometric triangulation. Recently, 3D scanning technologies have been proposed as novel methods of body composition assessment. PURPOSE: The purpose of this analysis was to examine the validity of four different commercially-available 3D scanners for estimation of body fat percentage (BF%) as compared to a 4-compartment (4C) model criterion. METHODS: After an overnight fast, 101 adults (63 F, 38 M; age: 29.3 ± 13.5 y; BMI: 24.3 ± 3.9 kg/m2; BF%: 24.6 ± 8.3%) completed assessments via dual-energy x-ray absorptiometry (DXA), air displacement plethysmography (ADP), bioimpedance spectroscopy (BIS), a standard body mass scale, and four infrared 3D scanners. Two scanners (3DSSL-D1; 3DSSL-D2) utilized structured light scanning with a dynamic configuration, one utilized structured light scanning with a static configuration (3DSSL-S), and one utilized time-of-flight technology (3DSToF). Using the equation of Wang et al. (2002), a criterion 4C estimate of BF% was obtained using DXA for bone mineral, ADP for body volume, scale for body mass, and BIS for total body water. BF% estimates were compared using one-way ANOVA with Bonferroni adjustment for multiple comparisons, and additional evaluations were conducted using the correlation coefficient (r), constant error (CE), standard error of the estimate (SEE), total error (TE), and 95% limits of agreement (LOA). RESULTS: Estimates of BF% did not significantly differ between 4C and any of the 3D scanners. However, metrics of group, individual, and prediction errors varied between scanners: 3DSSL-D1: p=1.0; CE: 0.4%; r: 0.91; SEE: 2.5%; TE: 3.6%; LOA: ±7.0%; 3DSSL-D2: p= 1.0; CE: 0.8%; r: 0.86; SEE: 4.2%; TE: 4.7%; LOA: ±9.2%; 3DSSL-S: p= 1.0; CE: 1.0%; r: 0.81; SEE: 4.0%; TE: 5.0%; LOA: ±9.7%; 3DSToF: p=0.08; CE: -2.9%; r: 0.86, SEE: 2.5%; TE: 5.2%; LOA: ±8.6%. CONCLUSION: All three structured light scanners exhibited low magnitudes of group error (CE ≤ 1%) and may be valid assessment methods when analyzing the body composition of groups. 3DSSL-D1 exhibited the lowest group-level error (i.e. CE), prediction errors (i.e. SEE; TE), and individual error (i.e. LOA) of all scanners. Therefore, this device was deemed the most valid 3D scanner for body composition assessment. 3DSSL-D2, 3DSSL-S, and 3DSToF exhibited comparable TE, although group-level error was lower in 3DSSL-D2 and 3DSSL-S, while the SEE and individual-level error was lower for 3DSToF. However, individual-level errors were relatively high with all scanners (LOA ≥ 7%), which calls into question the utility of these methods for assessing the body composition of individuals. Nonetheless, additional research is needed regarding the ability of 3DS to successfully detect changes in body composition over time

Perturbations highlight importance of social history in parakeet rank dynamics

Dominance hierarchies can provide many benefits to individuals, such as access to resources or mates, depending on their ranks. In some species, rank can emerge as a product of a group’s history of social interactions. However, it can be difficult to determine whether social history is critical to rank in observation-based studies. Here, we investigated rank dynamics in three captive groups of monk parakeets (Myiopsitta monachus). We used experimental social perturbations to test whether social history shapes rank emergence in these groups. Using targeted removals and reintroductions, we tested whether differently ranked individuals could re-take their ranks in hierarchies after reintroduction following their removal period from the group. We performed perturbations that consisted of an 8-day removal and an 8-day reintroduction period of 15 differently ranked focal birds. We found that no focal birds could regain their previous rank immediately following reintroduction and that the top-ranked birds showed greater relative rank loss than middle/low-ranked birds. We also found that morphology, specifically bodyweight, was unassociated with rank. Combined with previous results, this experiment supports the hypothesis that rank in monk parakeet dominance hierarchies is more likely to be an emergent outcome of past interactions and memory rather than based on individual characteristics. Gaining a better understanding of how individuals achieve and maintain rank can give insight into the role of cognition on rank acquisition, as rank position can have significant biological effects on individuals in hierarchically structured groups