The role of innate immune-stimulated epithelial apoptosis during gastrointestinal inflammatory diseases

The maintenance of mucosal barrier equilibrium in the intestine requires a delicate and dynamic balance between enterocyte loss by apoptosis and the generation of new cells by proliferation from stem cell precursors at the base of the intestinal crypts. When the balance shifts towards either excessive or insufficient apoptosis, a broad range of gastrointestinal diseases can manifest. Recent work from a variety of laboratories has provided evidence in support of a role for receptors of the innate immune system, including Toll-like receptors 2, 4, and 9 as well as the intracellular pathogen recognition receptor NOD2/CARD15, in the initiation of enterocyte apoptosis. The subsequent induction of enterocyte apoptosis in response to the activation of these innate immune receptors plays a key role in the development of various intestinal diseases, including necrotizing enterocolitis, Crohn’s disease, ulcerative colitis, and intestinal cancer. This review will detail the regulatory pathways that govern enterocyte apoptosis, and will explore the role of the innate immune system in the induction of enterocyte apoptosis in gastrointestinal disease.     

SecA,a remarkable nanomachine

Biological cells harbor a variety of molecular machines that carry out mechanical work at the nanoscale. One of these nanomachines is the bacterial motor protein SecA which translocates secretory proteins through the protein-conducting membrane channel SecYEG. SecA converts chemically stored energy in the form of ATP into a mechanical force to drive polypeptide transport through SecYEG and across the cytoplasmic membrane. In order to accommodate a translocating polypeptide chain and to release transmembrane segments of membrane proteins into the lipid bilayer, SecYEG needs to open its central channel and the lateral gate. Recent crystal structures provide a detailed insight into the rearrangements required for channel opening. Here, we review our current understanding of the mode of operation of the SecA motor protein in concert with the dynamic SecYEG channel. We conclude with a new model for SecA-mediated protein translocation that unifies previous conflicting data.     

Beta-carotene affects gene expression in lungs of male and female <Emphasis Type="Italic">Bcmo1</Emphasis><Superscript>−/−</Superscript> mice in opposite directions

Molecular mechanisms triggered by high dietary beta-carotene (BC) intake in lung are largely unknown. We performed microarray gene expression analysis on lung tissue of BC supplemented beta-carotene 15,15′-monooxygenase 1 knockout (Bcmo1 ^−/−) mice, which are—like humans—able to accumulate BC. Our main observation was that the genes were regulated in an opposite direction in male and female Bcmo1 ^−/− mice by BC. The steroid biosynthetic pathway was overrepresented in BC-supplemented male Bcmo1 ^−/− mice. Testosterone levels were higher after BC supplementation only in Bcmo1 ^−/− mice, which had, unlike wild-type (Bcmo1 ^+/+) mice, large variations. We hypothesize that BC possibly affects hormone synthesis or metabolism. Since sex hormones influence lung cancer risk, these data might contribute to an explanation for the previously found increased lung cancer risk after BC supplementation (ATBC and CARET studies). Moreover, effects of BC may depend on the presence of frequent human BCMO1 polymorphisms, since these effects were not found in wild-type mice.     

Protecting the boundary: the sentinel role of host defense peptides in the skin

The skin is our primary shield against microbial pathogens and has evolved innate and adaptive strategies to enhance immunity in response to injury or microbial insult. The study of antimicrobial peptide (AMP) production in mammalian skin has revealed several of the elegant strategies that AMPs use to prevent infection. AMPs are inducible by both infection and injury and protect the host by directly killing pathogens and/or acting as multifunctional effector molecules that trigger cellular responses to aid in the anti-infective and repair response. Depending on the specific AMP, these molecules can influence cytokine production, cell migration, cell proliferation, differentiation, angiogenesis and wound healing. Abnormal production of AMPs has been associated with the pathogenesis of several cutaneous diseases and plays a role in determining a patient’s susceptibility to pathogens. This review will discuss current research on the regulation and function of AMPs in the skin and in skin disorders.     

Effects of grazing exclusions on rangeland vegetation and soils, east central Idaho

Nineteen exclosures on sagebrush steppe and shadscale rangelands, varying in age from 18 to 38 years, were sampled for plant species richness, plant composition, indicators of soil erosion, ground cover, vegetative cover, and herb-low shrub layer screening cover. Features within the exclosures were compared with adjacent sites of the same size that were open to grazing by livestock and wildlife. Species richness typically was slightly greater inside exclosures than in adjacent grazed sites (median = 2 more species inside exclosures), but the difference was not significant ( P = 0.16). Similarity of plant community composition between exclosures and adjacent grazed sites ranged from 45% to 82%. Evidences of soil movement, soil pedestals, and soil flow patterns were all more pronounced outside exclosures than inside ( P ≤ 0.02), even though many sites were on flat to mild slopes (median slope = 12%). Meta-analysis of the 19 exclosure sites indicated that grazing exclusion resulted in less bare ground cover compared with adjacent grazed sites ( P ≤ 0.05). The effect of grazing exclusion on visible soil surface cryptogams was significant ( P ≤ 0.05), with generally greater cover inside exclosures. Cryptogam cover differences between grazed sites and exclosures tended to increase with the number of years of grazing exclusion ( r = 0.64, P = 0.046). Pseudoroegneria spicata , a principal livestock forage, averaged greater basal cover inside exclosures than outside on 4 of 10 sites where it occurred, although no exclosure sites had greater P. spicata cover on grazed sites. Meta-analysis of the 10 sites indicated that grazing exclusion resulted in greater P. spicata cover compared with adjacent grazed areas ( P ≤ 0.05). Poa secunda , a short-growing grass that initiates growth early in the spring and is not important livestock forage, averaged greater basal cover outside exclosures on 5 of 15 sites where it occurred. Meta-analysis of the 15 sites indicated a significant treatment effect ( P ≤ 0.05), with greater Poa secunda basal cover outside exclosures. Grazing exclusion resulted in greater screening cover in the herb-low shrub layer (0-0.5 m height; P ≤ 0.05). These results indicate that despite improved livestock grazing management over the past half century, livestock grazing still can limit the potential of native plant communities in sagebrush steppe ecosystems, and that the health of semiarid ecosystems can improve with livestock exclusion in the absence of other disturbances. A few exclosure sites were similar for the measured parameters, suggesting that these sites were ecologically stable and that exclusion of livestock grazing was not sufficient to move succession toward more pristine conditions, at least within the time periods studied. Managed disturbance such as fire or mechanical brush treatments may be necessary to restore herb productivity on these ecologically stable sites.     

Temperature and high salinity effects in germinating dimorphic seeds of Atriplex rosea

Atriplex rosea L. (Chenopodiaceae; tumbling orach), an annual herb, is a widely established weedy species of disturbed sites in all counties of Utah. Seeds of Atriplex rosea were collected from a salt marsh in Faust, Utah, and are dimorphic, light brown, and 2-2.5 mm wide, or black and 1-2 mm wide. Seed germination responses of the black and brown seeds were studied over a range of salinity and temperature. Both brown and black seeds germinated at 1000 mM NaCl, and the optimal temperature for germination of both types was 20°-30°C. Variation in temperature, however, affected germination of black seeds more than brown seeds. At lower thermoperiod only 40%-50% black seeds germinated in nonsaline control, and germination was almost completely inhibited with the inclusion of salinity. However, all brown seeds germinated in control at temperatures above 5°-15°C, and inhibition caused by salinity was comparatively lower. Brown seeds had a higher germination rate than black seeds at all temperature and salinity treatments. The highest rate of germination of both seeds occurred at the temperature regime of 5°-15°C. Recovery of germination for black seeds when transferred to distilled water after being in various salinity treatments for 20 days was quite variable. Recovery decreased with increase in salinity at lower temperature regimes, increased with salinity at optimal thermoperiod, and had no effect at 20°-30°C. Brown seeds recovered poorly from salinity at all thermoperiods except 5°-15°C, where recovery decreased with an increase in salinity. Brown seeds are adapted to germination in the early part of the growing season, whereas black seeds are capable of surviving harsher conditions and can germinate in later time periods. Characteristics of the dimorphic seeds increase chances for survival in the harsh saline desert environment.     

Optimal temperatures for growth and upper thermal tolerance of juvenile northern leatherside chub

We examined optimal temperatures for growth and the upper thermal tolerance of juvenile northern leatherside chub ( Lepidomeda copei ). We conducted 2 experiments using the acclimated chronic-exposure method to estimate optimal temperature for growth of age-0 northern leatherside chub (range 12.8–28.3 °C). Upper thermal tolerance was estimated using the critical thermal maximum (CTM) and upper incipient lethal temperature (UILT) methods for fish acclimated at 15, 18, 23, and 28 °C. We also measured stream temperatures in Yellow Creek, Summit County, Utah, during July–August 2006 to compare our results to actual summer stream temperatures. Survival in growth tests was not significantly different between treatment temperatures in either experiment (P > 0.098). The optimal temperature for growth in the 1st trial estimated from the 2nd-order polynomial regression was 23.0 °C, falling outside the range of experimental temperatures (12.8–22.2 °C). The estimated optimal temperature for growth in the 2nd trial was 23.2 °C. In the upper thermal tolerance tests, juvenile northern leatherside chub had CTM values between 29.6 and 35.0 °C; CTM values increased as acclimation temperature increased. Upper incipient lethal temperatures (LT50) ranged from 26.5 to 30.2 °C, increasing with acclimation temperature. Summer stream temperatures in Yellow Creek had a lower mean (14.0–18.1 °C) than did the optimal temperature for growth determined in these studies, but these temperatures exhibited diel fluctuations as large as 15.7 °C.     

Pygmy rabbits in the Colorado River drainage

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Winter habitats and foods of Blue Grouse in the Sheeprock Mountains, Utah

Winter habitat use and food habits of Blue Grouse ( Dendragapus obscurus ) were studied in an isolated Utah desert mountain range that contained little typical Douglas-fir ( Pseudotsuga menziesii ) winter habitat. Habitat use was concentrated in the Douglas-fir and pinyon ( Pinus edulis )-juniper ( Juniperus spp. ) habitat. Douglas-fir and pinyon pine were the most consumed foods. Other foods that represented >15% of the composition of an individual fecal sample were limber pine ( Pinus flexilis ), mahogany ( Cercocarpus ledifoliu ), juniper, and an Anteunaria-Cirsium type. The breadth in winter diet indicates that Blue Grouse may successfully occupy other habitats when typical winter habitat is scarce.