Effect of Augmented Eccentric Training in Older Adults

The purpose of this study was to investigate the effect of a six-week augmented eccentric load program on rate of force development (RFD), center of pressure (COP) excursion and performance in the five-time-sit-to-stand (STS-5) in older adults. Eighteen moderately active older adults, (≥ 60 years) participated in this study. Subjects were separated into two groups; one group added augmented eccentric training in addition to resistance training (AEL) and a resistance training only group (RT). The AEL group participated in a six-week AEL training program that consisted of six lower extremity body exercises. Eccentric phases of each exercise movement were augmented beginning with no weight and increasing by five percent weekly up to 20 percent body weight. AEL group improved the time to complete the clinical STS-5 fall risk assessment test by -2.21 ± 1.50 s, p = 0.03. AEL demonstrated a significant increase in the RFD moving from 785 ± 176 N·s-1 to 1041 ± 187 N·s-1 (p = 0.02) during chair rising. AEL showed significant improvements in M-L and (A-P) excursion from right foot during quiet standing, 0.075 ± 0.07 m to 0.003 ± 0.01 m and 0.157 ± 0.11 to 0.005 ± 0.01. AEL improved M-L excursion in right foot and A-P excursion of left foot compared to baseline, 0.457 ± 0.20 m to 0.012 ± 0.00 m, p =0.002 and 0.465 ± 0.15 m to 0.013 ± 0.01 m, p = 0.0001. Therefore, AEL training may be a beneficial exercise prescription for older adults

Antagonistic and cooperative AGO2-PUM interactions in regulating mRNAs.

Approximately 1500 RNA-binding proteins (RBPs) profoundly impact mammalian cellular function by controlling distinct sets of transcripts, often using sequence-specific binding to 3' untranslated regions (UTRs) to regulate mRNA stability and translation. Aside from their individual effects, higher-order combinatorial interactions between RBPs on specific mRNAs have been proposed to underpin the regulatory network. To assess the extent of such co-regulatory control, we took a global experimental approach followed by targeted validation to examine interactions between two well-characterized and highly conserved RBPs, Argonaute2 (AGO2) and Pumilio (PUM1 and PUM2). Transcriptome-wide changes in AGO2-mRNA binding upon PUM knockdown were quantified by CLIP-seq, and the presence of PUM binding on the same 3'UTR corresponded with cooperative and antagonistic effects on AGO2 occupancy. In addition, PUM binding sites that overlap with AGO2 showed differential, weakened binding profiles upon abrogation of AGO2 association, indicative of cooperative interactions. In luciferase reporter validation of candidate 3'UTR sites where AGO2 and PUM colocalized, three sites were identified to host antagonistic interactions, where PUM counteracts miRNA-guided repression. Interestingly, the binding sites for the two proteins are too far for potential antagonism due to steric hindrance, suggesting an alternate mechanism. Our data experimentally confirms the combinatorial regulatory model and indicates that the mostly repressive PUM proteins can change their behavior in a context-dependent manner. Overall, the approach underscores the importance of further elucidation of complex interactions between RBPs and their transcriptome-wide extent

Space Communications and the Law: Adequate International Control After 1963?

During the current year, a space event of legal and technological significance will occur. The American Telephone and Telegraph Company (A.T. & T.), using the launching facilities of the National Aeronautics and Space Administration (NASA), will launch its first satellite for research in the area of commercial communications.† The A.T. & T. sphere will be the first tested by a private, commercial organization specifically for business purposes- to implement a plan eventually to provide increased and improved telecommunications on a grand scale at a lower cost. The satellite will relay television signals from the United States to England, Germany, and France. Before a communication network can be commercially feasible, however, certain legal problems of space communications must be solved

First North American case of Hemoglobin Shepherds Bush (β 74[E18] Gly → Asp) in a central Pennsylvania family

BACKGROUND: Hemoglobin Shepherds Bush (Human Genome Variation Society name: HBB:c.224G > A) is an unstable hemoglobin variant resulting from a β 74 GGC to GAC mutation (Gly to Asp) that manifests clinically as hemolytic anemia or gall bladder disease due to chronic subclinical hemolysis. CASE PRESENTATION: We report a Pennsylvania family of English descent with this condition, first noticed in a 6-year-old female. The proband presented with splenomegaly, fatigue, dark urine and an elevated indirect bilirubin. Hemoglobin identification studies and subsequent genetic testing performed according to a systematic algorithm elucidated the diagnosis of Hb Shepherds Bush. CONCLUSIONS: This is the first case of this rare hemoglobin variant identified in North America to our knowledge. It was identified using a systematic algorithm of diagnostic tests that should be followed whenever considering a rare hemoglobinopathy as part of the differential diagnosis

Cas Adaptor Proteins Coordinate Sensory Axon Fasciculation.

Development of complex neural circuits like the peripheral somatosensory system requires intricate mechanisms to ensure axons make proper connections. While much is known about ligand-receptor pairs required for dorsal root ganglion (DRG) axon guidance, very little is known about the cytoplasmic effectors that mediate cellular responses triggered by these guidance cues. Here we show that members of the Cas family of cytoplasmic signaling adaptors are highly phosphorylated in central projections of the DRG as they enter the spinal cord. Furthermore, we provide genetic evidence that Cas proteins regulate fasciculation of DRG sensory projections. These data establish an evolutionarily conserved requirement for Cas adaptor proteins during peripheral nervous system axon pathfinding. They also provide insight into the interplay between axonal fasciculation and adhesion to the substrate

Localization of complement factor H gene expression and protein distribution in the mouse outer retina.

To determine the localization of complement factor H (Cfh) mRNA and its protein in the mouse outer retina.Quantitative real-time PCR (qPCR) was used to determine the expression of Cfh and Cfh-related (Cfhr) transcripts in the RPE/choroid. In situ hybridization (ISH) was performed using the novel RNAscope 2.0 FFPE assay to localize the expression of Cfh mRNA in the mouse outer retina. Immunohistochemistry (IHC) was used to localize Cfh protein expression, and western blots were used to characterize CFH antibodies used for IHC.Cfh and Cfhr2 transcripts were detected in the mouse RPE/choroid using qPCR, while Cfhr1, Cfhr3, and Cfhrc (Gm4788) were not detected. ISH showed abundant Cfh mRNA in the RPE of all mouse strains (C57BL/6, BALB/c, 129/Sv) tested, with the exception of the Cfh(-/-) eye. Surprisingly, the Cfh protein was detected by immunohistochemistry in photoreceptors rather than in RPE cells. The specificity of the CFH antibodies was tested by western blotting. Our CFH antibodies recognized purified mouse Cfh protein, serum Cfh protein in wild-type C57BL/6, BALB/c, and 129/Sv, and showed an absence of the Cfh protein in the serum of Cfh(-/-) mice. Greatly reduced Cfh protein immunohistological signals in the Cfh(-/-) eyes also supported the specificity of the Cfh protein distribution results.Only Cfh and Cfhr2 genes are expressed in the mouse outer retina. Only Cfh mRNA was detected in the RPE, but no protein. We hypothesize that the steady-state concentration of Cfh protein is low in the cells due to secretion, and therefore is below the detection level for IHC

PRICE CONTROL - PROBLEMS OF THE OVER-ALL CEILING - RENT CONTROL - RATIONING

Three months after the passage of the Emergency Price Control Act a partial and selective approach to the problem of price control has been abandoned and a comprehensive over-all ceiling has been put into effect. The economic forces generated by total war have quickly proved too powerful for the limited controls originally planned. As a result, a sweeping program of governmental control over the economic life of the nation has been instituted, with consequences too complex and far-reaching to be foreseen in any detail

Short-Term Calorie Restriction in Male Mice Feminizes Gene Expression and Alters Key Regulators of Conserved Aging Regulatory Pathways

Background: Calorie restriction (CR) is the only intervention known to extend lifespan in a wide range of organisms, including mammals. However, the mechanisms by which it regulates mammalian aging remain largely unknown, and the involvement of the TOR and sirtuin pathways (which regulate aging in simpler organisms) remain controversial. Additionally, females of most mammals appear to live longer than males within species; and, although it remains unclear whether this holds true for mice, the relationship between sex-biased and CR-induced gene expression remains largely unexplored. Methodology/Principal Findings: We generated microarray gene expression data from livers of male mice fed high calorie or CR diets, and we find that CR significantly changes the expression of over 3,000 genes, many between 10- and 50-fold. We compare our data to the GenAge database of known aging-related genes and to prior microarray expression data of genes expressed differently between male and female mice. CR generally feminizes gene expression and many of the most significantly changed individual genes are involved in aging, hormone signaling, and p53-associated regulation of the cell cycle and apoptosis. Among the genes showing the largest and most statistically significant CR-induced expression differences are Ddit4, a key regulator of the TOR pathway, and Nnmt, a regulator of lifespan linked to the sirtuin pathway. Using western analysis we confirmed post-translational inhibition of the TOR pathway. Conclusions: Our data show that CR induces widespread gene expression changes and acts through highly evolutionarily conserved pathways, from microorganisms to mammals, and that its life-extension effects might arise partly from a shift toward a gene expression profile more typical of females

Characterization of the fecal microbiome in cats with inflammatory bowel disease or alimentary small cell lymphoma.

Feline chronic enteropathy (CE) is a common gastrointestinal disorder in cats and mainly comprises inflammatory bowel disease (IBD) and small cell lymphoma (SCL). Both IBD and SCL in cats share features with chronic enteropathies such as IBD and monomorphic epitheliotropic intestinal T-cell lymphoma in humans. The aim of this study was to characterize the fecal microbiome of 38 healthy cats and 27 cats with CE (13 cats with IBD and 14 cats with SCL). Alpha diversity indices were significantly decreased in cats with CE (OTU p = 0.003, Shannon Index p = 0.008, Phylogenetic Diversity p = 0.019). ANOSIM showed a significant difference in bacterial communities, albeit with a small effect size (P = 0.023, R = 0.073). Univariate analysis and LEfSE showed a lower abundance of facultative anaerobic taxa of the phyla Firmicutes (families Ruminococcaceae and Turicibacteraceae), Actinobacteria (genus Bifidobacterium) and Bacteroidetes (i.a. Bacteroides plebeius) in cats with CE. The facultative anaerobic taxa Enterobacteriaceae and Streptococcaceae were increased in cats with CE. No significant difference between the microbiome of cats with IBD and those with SCL was found. Cats with CE showed patterns of dysbiosis similar to those in found people with IBD

Narratives of therapeutic art-making in the context of marital breakdown: Older women reflect on a significant mid-life experience

This paper explores the narratives of three women aged 65-72 years. They reflected on an episode of therapeutic art-making in midlife, which addressed depression associated with marital crisis and breakdown. The narrative analysis focused upon on the ways in which participants narrated the events leading up to their participation in therapeutic art-making; the aspects of therapeutic art-making that continued to be given significance; the characters given primacy in the stories they told about their journey through therapy and marital breakdown; meanings, symbolic and otherwise, that participants ascribed to their artwork made during this turning point in their lives; and aspects of the narratives that conveyed present-day identities and artistic endeavors. The narratives revealed the complexity of the journey through marital breakdown and depression into health, and showed that therapeutic art-making could best be understood, not as a stand-alone experience, but as given meaning within the context of wider personal and social resources. Participants looked back on therapeutic art-making that occurred two decades earlier and still described this as a significant turning point in their personal development. Art as an adjunct to counselling/therapy was not only symbolically self-expressive but provided opportunity for decision-making, agency and a reformulated self-image