Haploinsufficiency of myostatin protects against aging‐related declines in muscle function and enhances the longevity of mice

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/112228/1/acel12339-sup-0003-TableS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/112228/2/acel12339.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/112228/3/acel12339-sup-0004-TableS2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/112228/4/acel12339-sup-0002-FigureS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/112228/5/acel12339-sup-0001-DataS1.pd

Changes in skeletal muscle and tendon structure and function following genetic inactivation of myostatin in rats

Myostatin is a negative regulator of skeletal muscle and tendon mass. Myostatin deficiency has been well studied in mice, but limited data are available on how myostatin regulates the structure and function of muscles and tendons of larger animals. We hypothesized that, in comparison to wild‐type (MSTN+/+) rats, rats in which zinc finger nucleases were used to genetically inactivate myostatin (MSTNΔ/Δ) would exhibit an increase in muscle mass and total force production, a reduction in specific force, an accumulation of type II fibres and a decrease and stiffening of connective tissue. Overall, the muscle and tendon phenotype of myostatin‐deficient rats was markedly different from that of myostatin‐deficient mice, which have impaired contractility and pathological changes to fibres and their extracellular matrix. Extensor digitorum longus and soleus muscles of MSTNΔ/Δ rats demonstrated 20–33% increases in mass, 35–45% increases in fibre number, 20–57% increases in isometric force and no differences in specific force. The insulin‐like growth factor‐1 pathway was activated to a greater extent in MSTNΔ/Δ muscles, but no substantial differences in atrophy‐related genes were observed. Tendons of MSTNΔ/Δ rats had a 20% reduction in peak strain, with no differences in mass, peak stress or stiffness. The general morphology and gene expression patterns were similar between tendons of both genotypes. This large rodent model of myostatin deficiency did not have the negative consequences to muscle fibres and extracellular matrix observed in mouse models, and suggests that the greatest impact of myostatin in the regulation of muscle mass may not be to induce atrophy directly, but rather to block hypertrophy signalling.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111244/1/tjp6572.pd

Enhancing climate services design and implementation through gender-responsive evaluation

Assessing and responding to gender inequalities, and promoting women’s empowerment, can be critical to achieving the goals of climate services, such as improved climate resilience, productivity, food security and livelihoods. To this end, our paper seeks to provide guidance to rural climate service researchers, implementing organizations, and funders on gender-responsive evaluation of climate services, including key questions to be asked and appropriate methodology. We draw on case studies of rural climate services in Mali, Rwanda and Southeast Asia to illustrate how gender-responsive evaluations have framed and attempted to answer questions about climate information needs, access to information and support through group processes, and contribution of climate services to empowerment. Evaluation of how group participatory processes can enable women’s and men’s demand for weather and climate information can help close knowledge gaps on gender equity in access to climate services. Quantitative methods can rigorously identify changes in demand associated with varying interventions, but qualitative approaches may be necessary to help assess the nuances of participatory communication processes. Furthermore, evaluation of how women’s and men’s information needs differ according to their roles and responsibilities in distinct climate-sensitive decisions can help assess gender inequities in climate services use. Evaluation that critically considers the local normative and institutional environment influencing empowerment can help identify pathways for climate services to contribute to women’s empowerment. Qualitative and mixed method methodologies can be helpful for assessing the normative and institutional changes upon which empowerment depends. Although evaluations are often conducted too late to inform the design of time-bound projects, they can contribute to improvements to climate services if results are shared widely, if implementers and funders consistently factor evidence and insights from prior evaluations into the design of new initiatives, and if ongoing climate service initiatives conduct preliminary evaluations regularly to support mid-course adjustments

Different hepatocytes express the cholesterol 7Α-hydroxylase gene during its circadian modulation in vivo

Cholesterol 7Α-hydroxylase, the rate-limiting enzyme in bile salt synthesis from cholesterol is a P450 enzyme (CYP7A). Its expression and activity are regulated by bile salts, cholesterol, hormones and a circadian modulator. Here we define the hepatocytes contributing to the expression of the rat CYP7A gene during its in vivo circadian variation. The diurnal expression of the CYP7A messenger RNA (mRNA) was studied by in situ hybridization and correlated with the diurnal rate of CYP7A gene transcription and mRNA expression. At 10 AM, the time of lowest mRNA expression and gene transcription rate, only four to five hepatocytes, located close to the hepatic venules (“perivenular”), contained the CYP7A mRNA. At 10 PM, the time of highest mRNA expression and fastest in vitro transcription rate, approximately one half of the hepatocytes (still in a “perivenular” location) contained the cholesterol 7Α-hydroxylase mRNA. In addition, the measured half-life of the CYP7A mRNA was shorter at 10 AM than at 10 PM suggesting that posttranscriptional mechanisms also contributed to the observed circadian differences. Therefore, the basal transcription rate of the CYP7A gene is maintained by four to five “perivenular” hepatocytes. During the circadian variation, the rate of gene transcription increases in these “perivenular” hepatocytes, but in addition, there is recruitment of other more proximal hepatocytes to transcribe the gene. It is proposed here that the response of specific hepatocytes to the various modulators of CYP7A gene expression is dependent on the relative position of these hepatocytes within the liver cell plate.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38410/1/1840210626_ftp.pd

Assessing phylogenetic motif models for predicting transcription factor binding sites

Motivation: A variety of algorithms have been developed to predict transcription factor binding sites (TFBSs) within the genome by exploiting the evolutionary information implicit in multiple alignments of the genomes of related species. One such approach uses an extension of the standard position-specific motif model that incorporates phylogenetic information via a phylogenetic tree and a model of evolution. However, these phylogenetic motif models (PMMs) have never been rigorously benchmarked in order to determine whether they lead to better prediction of TFBSs than obtained using simple position weight matrix scanning

Four challenges in the field of alternative, radical and citizens’ media research

In January 1994 the Zapatista movement in southern Mexico inaugurated a new era of media use for dissent. Since that time, an array of dissenting collectives and individuals have appropriated media technologies in order to make their voices heard or to articulate alternative identities. From Zapatista media to the Arab Spring, social movements throughout the world are taking over, hybridizing, recycling, and adapting media technologies. This new era poses a new set of challenges for academics and researchers in the field of Communication for Social Change (CfSC). Based on examples from Mexico, Lebanon, and Colombia, this article highlights and discusses four such research challenges: accounting for historical context; acknowledging the complexity of communication processes; anchoring analysis in a political economy of information and communication technologies; and positioning new research in relation to existing knowledge and literature within the field of communication and social change.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Chromosomal localization of the transcription factor YY1 in the mouse and human

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47010/1/335_2004_Article_BF00360552.pd

A study of the distribution of phylogenetically conserved blocks within clusters of mammalian homeobox genes

Genome sequencing efforts of the last decade have produced a large amount of data, which has enabled whole-genome comparative analyses in order to locate potentially functional elements and study the overall patterns of phylogenetic conservation. In this paper we present a statistically based method for the characterization of these patterns in mammalian DNA sequences. We have applied this approach to the study of exceptionally well conserved homeobox gene clusters (Hox), based on an alignment of six species, and we have constructed a map of Hox cataloguing the conserved fragments, along with their locations in relation to the genes and other landmarks, sometimes showing unexpected layouts