Developmental changes in the embryo, pronymph, and first molt of the scorpion Centruroides vittatus (scorpiones: buthidae)

For the first time the scanning electron microscope was used to compare developmental changes in scorpion embryos and the first and second stadia. In the buthid species of this study, Centruroides vittatus, and all other scorpions, the newborn climb up on their mother's back and remain there without feeding for several days. At this location, they undergo their first molt and in a few days they disperse, fully capable of foraging in the terrestrial environment. The results here support earlier suggestions that the first stadium (pronymph) is a continuation and extension of embryological development. The first molt results in a nymph with exoskeletal features much like those in the adult. In the first molt the metasoma becomes relatively longer, and the sting (aculeus) becomes sharp and functional. The metasomal segments are modified for dorsal flexion and sting use. The embryos and the pronymphs have spiracles that open into an invagination near the posterior margin of flap-like abdominal plates in segments 4-7 of the ventral mesosoma. The second instars have spiracles that lead to book lungs farther anterior in sternites. Tubular legs with cylindrical segments in embryos and pronymphs become more sculptured and oval in the transverse plane. Each leg in the pronymph has a blunt, cup-shaped tip while distal claws (ungues, dactyl) are present in the second instar and subsequent stages. There are some sharp bristles and primordial sensilla in the pronymphs, but the second stadium has adult-like surface features: rows of knobs or granulations (carinae), serrations on the inner surfaces of cheliceral and pedipalpal claws, filtering hairs at the mouthparts, peg sensilla on the pectines, and mechano- and chemoreceptor sensilla on the body and appendages. Scorpion embryos and pronymphs have some structures like fossil scorpions thought to have been aquatic. There is a gradual development of features that appear to be terrestrial adaptations. Evidence is provided for the formation of the sternum from third and fourth leg coxal primordia and possibly from the first abdominal segment. This study is the first to provide evidence for a forward shift of the gonopore along with other structures in the anterior abdomen.     

Bos taurus and Bos indicus (Sahiwal) calves respond differently to infection with Theileria annulata and produce markedly different levels of acute phase proteins

Disease-resistant livestock could provide a potentially sustainable and environmentally sound method of controlling tick and tick-borne diseases of livestock in the developing world. Advances in the knowledge and science of genomics open up opportunities to identify selectable genes controlling disease resistance but first, breeds and individuals with distinguishable phenotypes need to be identified. The Bos indicus breed, Sahiwal, has been exploited in dairy breeding programmes, because it is resistant to ticks and has relatively good performance characteristics compared to other indigenous cattle breeds of tropical regions. The analyses reported here show that Sahiwal calves were also more resistant than European Bos taurus (Holstein) dairy breed calves to tick-borne tropical theileriosis (Theileria annulata infection). Following experimental infection with T. annulata sporozoites, a group of Sahiwal calves all survived without treatment, with significantly lower maximum temperatures (P<0.01) and lower rates of parasite multiplication (P<0.05) than a group of Holstein calves, which all had severe responses. Although the Sahiwals became as anaemic as the Holsteins, other measures of pathology, including enlargement of the draining lymph node and the acute phase proteins, alpha1 acid glycoprotein and haptoglobin, were significantly less in the Sahiwals than in the Holsteins (P<0.05). Additionally, the Sahiwals had significantly lower resting levels of alpha1 acid glycoprotein than the Holsteins (P<0.05). Production of a third acute phase proteins, serum amyloid A, had very similar kinetics in both breeds. Acute phase proteins are produced in response to systemic release of the kinds of pro-inflammatory cytokines that are thought to be responsible for the pyrexic, cachectic and anorexic responses characteristic of tropical theileriosis. The prolonged production of alpha1 acid glycoprotein in the Holsteins is indicative of chronic production of circulating pro-inflammatory cytokines. In contrast, Sahiwals appear able to overcome infection with T. annulata as well as limit pathology by preventing the over-stimulation of pathways involving these cytokines.     

A Francisella tularensis pathogenicity island required for intramacrophage growth

Francisella tularensis is a gram-negative, facultative intracellular pathogen that causes the highly infectious zoonotic disease tularemia. We have discovered a ca. 30-kb pathogenicity island of F. tularensis (FPI) that includes four large open reading frames (ORFs) of 2.5 to 3.9 kb and 13 ORFs of 1.5 kb or smaller. Previously, two small genes located near the center of the FPI were shown to be needed for intramacrophage growth. In this work we show that two of the large ORFs, located toward the ends of the FPI, are needed for virulence. Although most genes in the FPI encode proteins with amino acid sequences that are highly conserved between high- and low-virulence strains, one of the FPI genes is present in highly virulent type A F. tularensis, absent in moderately virulent type B F. tularensis, and altered in F. tularensis subsp. novicida, which is highly virulent for mice but avirulent for humans. The G+C content of a 17.7-kb stretch of the FPI is 26.6%, which is 6.6% below the average G+C content of the F. tularensis genome. This extremely low G+C content suggests that the DNA was imported from a microbe with a very low G+C-containing chromosome.     

Fyn promotes phosphorylation of collapsin response mediator protein 1 at tyrosine 504, a novel,isoform‐specific regulatory site

In vertebrates the collapsin response mediator proteins (CRMPs) are encoded by five highly related genes. CRMPs are cytosolic phosphoproteins abundantly expressed in developing and mature mammalian brains. CRMPs are best understood as effectors of Semaphorin 3A signaling regulating growth cone collapse in migratory neurons. Phosphorylation in the carboxyl‐terminal regulatory domain of CRMPs by several serine/threonine kinases has been described. These phoshorylation events appear to function, at least in part, to disrupt the interaction of CRMPs with tubulin heterodimers. In a large‐scale phosphoproteomic analysis of murine brain, we recently identified a number of in vivo tyrosine phosphorylation sites on CRMP isoforms. Using biochemical approaches and quantitative mass spectrometry we demonstrate that one of these sites, CRMP1 tyrosine 504 (Y504), is a primary target of the Src family of tyrosine kinases (SFKs), specifically Fyn. Y504 is adjacent to CDK5 and GSK‐3β sites that regulate the interaction of CRMPs with tubulin. Although Y504 is highly conserved among vertebrate CRMP1 orthologs, a residue corresponding to Y504 is absent in CRMP isoforms 2–5. This suggests an isoform‐specific regulatory role for CRMP1 Y504 phosphorylation and may help explain the observation that CRMP1‐deficient mice exhibit neuronal migration defects not compensated for by CRMPs 2–5. J. Cell. Biochem. 111: 20–28, 2010. © 2010 Wiley‐Liss, Inc.     

In vivo two-photon imaging reveals a role of arc in enhancing orientation specificity in visual cortex

Cortical representations of visual information are modified by an animal's visual experience. To investigate the mechanisms in mice, we replaced the coding part of the neural activity-regulated immediate early gene Arc with a GFP gene and repeatedly monitored visual experience-induced GFP expression in adult primary visual cortex by in vivo two-photon microscopy. In Arc-positive GFP heterozygous mice, the pattern of GFP-positive cells exhibited orientation specificity. Daily presentations of the same stimulus led to the reactivation of a progressively smaller population with greater reactivation reliability. This adaptation process was not affected by the lack of Arc in GFP homozygous mice. However, the number of GFP-positive cells with low orientation specificity was greater, and the average spike tuning curve was broader in the adult homozygous compared to heterozygous or wild-type mice. These results suggest a physiological function of Arc in enhancing the overall orientation specificity of visual cortical neurons during the post-eye-opening life of an animal.     

Snowy plover nest survival in Kansas and effective management to counter negative effects of precipitation

Snowy plovers (Charadrius nivosus) are a species of conservation concern throughout North America and listed as a threatened species in Kansas. Management to minimize the effects of flooding and predation were implemented at Kansas breeding sites in the 1980s to encourage reproductive success. However, the effectiveness of those strategies and the effect of other variables that may influence nest survival have not been formally assessed. We used Program MARK to model the daily survival rate (DSR) of 317 snowy plover nests with 14 habitat- and management-related covariates to identify factors that influence nest survival and examine the efficacy of current management practices. In 2005 and 2006, we monitored nests and collected habitat data at the 2 known breeding sites in Kansas, Quivira National Wildlife Refuge (NWR) and Cheyenne Bottoms Wildlife Area (WA). Overall DSR was greater at Quivira NWR in 2006 (0.954) than at Cheyenne Bottoms WA (0.917) and Quivira NWR (0.942) in 2005. We developed 88 candidate models of which 4 competing models (ΔAIC_c < 2) were identified. We selected the most parsimonious model (K = 14, w_i = 0.23) as the remaining 3 included covariates deemed biologically uninformative. This model included the effect of study site and year on a quadratic time trend, and included covariates quantifying nest age; precipitation; the proportion of gravel, rock, and vegetation at nests; occurrence within an electric fence and within 20 m of a road; occurrence on a human-constructed nest mound; and adult capture during incubation. We found a strong positive relationship between the use of nest mounds and DSR, and a strong negative relationship between precipitation and DSR. We also found a strong positive relationship between DSR and the proportion of vegetation at nest sites, the occurrence of a nest within an electric fence, and adult capture at a nest. We noted a strong negative relationship between DSR and occurrence within 20 m of a road. However, we found that DSR was not sensitive to the proportion of vegetation at a nest, occurrence within an electric fence or within 20 m of a road, and to adult capture at a nest in light of covariates quantifying precipitation and the use of nest mounds. We found weak support for a positive relationship between DSR, nest age, and the proportion of gravel and rock at nests. Our results indicate that large rainfall events are a major source of snowy plover nest loss in Kansas that can be mitigated by the construction of nest mounds. Limited influence of environmental variables found to influence nest survival at other breeding sites suggests that threats to snowy plover nest survival are site specific and managers should assess local sources of nest loss prior to implementing management strategies to improve reproductive success. © 2012 The Wildlife Society.     

G-protein-coupled receptors in intestinal chemosensation

Food intake is detected by the chemical senses of taste and smell and subsequently by chemosensory cells?in the gastrointestinal tract that link the composition of ingested foods to feedback circuits controlling gut motility/secretion, appetite, and peripheral nutrient disposal. G-protein-coupled receptors responsive to?a range of nutrients and other food components have been identified, and many are localized to intestinal chemosensory cells, eliciting hormonal and neuronal signaling to the brain and periphery. This review examines the role of G-protein-coupled receptors as signaling molecules in the gut, with a particular focus on pathways relevant to appetite and glucose homeostasis.     

SUMMER DIVING BEHAVIOR OF MALE WALRUSES IN BRISTOL BAY, ALASKA

Pacific walruses ( Odobenus rosmarus divergens ) make trips from ice or land haul-out sites to forage for benthic prey. We describe dive and trip characteristics from time-depth-recorder data collected over a one-month period during summer from four male Pacific walruses in Bristol Bay, Alaska. Dives were classified into four types. Shallow (4 m), short (2.7 min), square-shaped dives accounted for 11% of trip time, and many were probably associated with traveling. Shallow (2 m) and very short (0.5 min) dives composed only 1% of trip time. Deep (41 m), long (7.2 min), square-shaped dives accounted for 46% of trip time and were undoubtedly associated with benthic foraging. V-shaped dives ranged widely in depth, were of moderate duration (4.7 min), and composed 3% of trip time. These dives may have been associated with navigation or exploration of the seafloor for potential prey habitat. Surface intervals between dives were similar among dive types, and generally lasted 1–2 min. Total foraging time was strongly correlated with trip duration and there was no apparent diel pattern of diving in any dive type among animals. We found no correlation between dive duration and postdive surface interval within dive types, suggesting that diving occurred within aerobic dive limits. Trip duration varied considerably within and among walruses (0.3–9.4 d), and there was evidence that some of the very short trips were unrelated to foraging. Overall, walruses were in the water for 76.6% of the time, of which 60.3% was spent diving.     

Design, synthesis, and SAR of heterocycle-containing antagonists of the human CCR5 receptor for the treatment of HIV-1 infection

Replacement of the large hydantoin-indole moiety from our previous work with a variety of smaller heterocyclic analogues gave rise to potent CCR5 antagonists having binding affinity comparable to the hydantoin analogues. The synthesis, SAR, and biological profiles of this class of antagonists are described.