Emerging roles of epigenetic mechanisms in the enduring effects of early-life stress and experience on learning and memory.

Epigenetic mechanisms are involved in programming gene expression throughout development. In addition, they are key contributors to the processes by which early-life experience fine-tunes the expression levels of key neuronal genes, governing learning and memory throughout life. Here we describe the long-lasting, bi-directional effects of early-life experience on learning and memory. We discuss how enriched postnatal experience enduringly augments spatial learning, and how chronic early-life stress results in persistent and progressive deficits in the structure and function of hippocampal neurons. The existing and emerging roles of epigenetic mechanisms in these fundamental neuroplasticity phenomena are illustrated

SpoT Induces Intracellular Salmonella Virulence Programs in the Phagosome.

Guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp), together named (p)ppGpp, regulate diverse aspects of Salmonella pathogenesis, including synthesis of nutrients, resistance to inflammatory mediators, and expression of secretion systems. In Salmonella, these nucleotide alarmones are generated by the synthetase activities of RelA and SpoT proteins. In addition, the (p)ppGpp hydrolase activity of the bifunctional SpoT protein is essential to preserve cell viability. The contribution of SpoT to physiology and pathogenesis has proven elusive in organisms such as Salmonella, because the hydrolytic activity of this RelA and SpoT homologue (RSH) is vital to prevent inhibitory effects of (p)ppGpp produced by a functional RelA. Here, we describe the biochemical and functional characterization of a spoT-Δctd mutant Salmonella strain encoding a SpoT protein that lacks the C-terminal regulatory elements collectively referred to as "ctd." Salmonella expressing the spoT-Δctd variant hydrolyzes (p)ppGpp with similar kinetics to those of wild-type bacteria, but it is defective at synthesizing (p)ppGpp in response to acidic pH. Salmonella spoT-Δctd mutants have virtually normal adaptations to nutritional, nitrosative, and oxidative stresses, but poorly induce metal cation uptake systems and Salmonella pathogenicity island 2 (SPI-2) genes in response to the acidic pH of the phagosome. Importantly, spoT-Δctd mutant Salmonella replicates poorly intracellularly and is attenuated in a murine model of acute salmonellosis. Collectively, these investigations indicate that (p)ppGpp synthesized by SpoT serves a unique function in the adaptation of Salmonella to the intracellular environment of host phagocytes that cannot be compensated by the presence of a functional RelA.IMPORTANCE Pathogenic bacteria experience nutritional challenges during colonization and infection of mammalian hosts. Binding of the alarmone nucleotide guanosine tetraphosphate (ppGpp) to RNA polymerase coordinates metabolic adaptations and virulence gene transcription, increasing the fitness of diverse Gram-positive and Gram-negative bacteria as well as that of actinomycetes. Gammaproteobacteria such as Salmonella synthesize ppGpp by the combined activities of the closely related RelA and SpoT synthetases. Due to its profound inhibitory effects on growth, ppGpp must be removed; in Salmonella, this process is catalyzed by the vital hydrolytic activity of the bifunctional SpoT protein. Because SpoT hydrolase activity is essential in cells expressing a functional RelA, we have a very limited understanding of unique roles these two synthetases may assume during interactions of bacterial pathogens with their hosts. We describe here a SpoT truncation mutant that lacks ppGpp synthetase activity and all C-terminal regulatory domains but retains excellent hydrolase activity. Our studies of this mutant reveal that SpoT uniquely senses the acidification of phagosomes, inducing virulence programs that increase Salmonella fitness in an acute model of infection. Our investigations indicate that the coexistence of RelA/SpoT homologues in a bacterial cell is driven by the need to mount a stringent response to a myriad of physiological and host-specific signatures

Early Sport Specialization: Overuse Injury and Burnout

There are an increasing number of opportunities for today’s youth to participate in year-round sport organizations that promote early sport specialization before the age of fifteen. Early sport specialization is linked to a higher rate of overuse injury of frequently used muscle groups. The physical, mental, and psychological demands of early sport specialization increase likelihood of burnout and cessation of sport participation. Early sport generalization allows physiological and psychological rest and recovery in youth athletes that lead to decreased injury rates and less burnout with more individuals continuing to participate in competitive sports throughout the collegiate years. The purpose of this research was to determine what effect, if any, early sport specialization in youth has on rate of overuse injury and burnout in NCAA Division III athletes at a small, private University. A 12-question, retrospective, written survey classified each participant as an early sport specialist or early sport generalist and gathered information on frequency of overuse injury and development of burnout during the high school and college competitive sport years. Statistical analysis indicated early sport generalists were more likely to participate in competitive collegiate athletics at the NCAA Division III Institution analyzed in this study (71.8%). Early sport specialists were more likely to experience burnout (P = 0.088) and may be more likely to develop overuse injury during the high school years (P = 0.254) but not the college years (P=0.385). It is unknown if early sport specialists are more likely to develop a greater number of overuse injuries throughout their competitive sport career than early sport generalists. Young athletes are encouraged to participate in multiple competitive sports but the results of this research were not statistically significant and further research needs to be done to support these conclusions

Crustal shortening, exhumation, and strain localization in a collisional orogen: the Bajo Pequeño Shear Zone, Sierra de Pie de Palo, Argentina

The Bajo Pequeño Shear Zone (BPSZ) is a lower-crustal shear zone that records shortening and exhumation associated with the establishment of a new plate boundary, and its placement in a regional structural context suggests that local- to regional-scale strain localization occurred with progressive deformation. A kilometer-scale field and analytical cross section through the ~80 m thick BPSZ and its adjacent rocks indicates an early Devonian (405–400 Ma) phase of deformation on the western margin of Gondwanan continental crust. The earliest stages of the BPSZ, recorded by metamorphic and microstructural data, involved thrusting of a hotter orthogneiss over a relatively cool pelitic unit, which resulted in footwall garnet growth and reset footwall white mica 40Ar/39Ar ages in proximity to the shear zone. Later stages of BPSZ activity, as recorded by additional microstructures and quartz c-axis opening angles, were characterized by strain localization to the center of the shear zone coincident with cooling and exhumation. These and other data suggest that significant regional tectonism persisted in the Famatinian orogenic system for 60–70 million years after one microplate collision (the Precordillera) but ceased 5–10 million years prior to another (Chilenia). A survey of other synchronous structures shows that strain was accommodated on progressively narrower structures with time, indicating a regional pattern of strain localization and broad thermal relaxation as the Precordillera collision evolved.Fil: Garber, Joshua M.. University of California at Davis; Estados UnidosFil: Roeske, Sarah M.. University of California at Davis; Estados UnidosFil: Warren, Jessica. University of Stanford; Estados UnidosFil: Mulcahy, Sean R.. University of California at Berkeley; Estados UnidosFil: McClelland, William C.. University of Iowa; Estados UnidosFil: Austin, Lauren J.. University of Oregon; Estados UnidosFil: Renne, Paul R.. University of California at Berkeley; Estados UnidosFil: Vujovich, Graciela Irene. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Geología. Laboratorio de Tectónica Andina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Vascular Health in American Football Players: Cardiovascular Risk Increased in Division III Players

Studies report that football players have high blood pressure (BP) and increased cardiovascular risk. There are over 70,000 NCAA football players and 450 Division III schools sponsor football programs, yet limited research exists on vascular health of athletes. This study aimed to compare vascular and cardiovascular health measures between football players and nonathlete controls. Twenty-three athletes and 19 nonathletes participated. Vascular health measures included flow-mediated dilation (FMD) and carotid artery intima-media thickness (IMT). Cardiovascular measures included clinic and 24 hr BP levels, body composition, VO2 max, and fasting glucose/cholesterol levels. Compared to controls, football players had a worse vascular and cardiovascular profile. Football players had thicker carotid artery IMT (0.49 ± 0.06 mm versus 0.46 ± 0.07 mm) and larger brachial artery diameter during FMD (4.3 ± 0.5 mm versus 3.7 ± 0.6 mm), but no difference in percent FMD. Systolic BP was significantly higher in football players at all measurements: resting (128.2 ± 6.4 mmHg versus 122.4 ± 6.8 mmHg), submaximal exercise (150.4 ± 18.8 mmHg versus 137.3 ± 9.5 mmHg), maximal exercise (211.3 ± 25.9 mmHg versus 191.4 ± 19.2 mmHg), and 24-hour BP (124.9 ± 6.3 mmHg versus 109.8 ± 3.7 mmHg). Football players also had higher fasting glucose (91.6 ± 6.5 mg/dL versus 86.6 ± 5.8 mg/dL), lower HDL (36.5±11.2 mg/dL versus 47.1±14.8 mg/dL), and higher body fat percentage (29.2±7.9% versus 23.2±7.0%). Division III collegiate football players remain an understudied population and may be at increased cardiovascular risk