Mammals of Fort A. P. Hill, Caroline County, Virginia and Vicinity

Fort A.P. Hill (APH) is a 30,329 ha military training installation (U.S. Army) located in the upper Coastal Plain of Caroline County, Virginia. It was formed in 1941 and named in honor of Civil War Confederate Lt. General Ambrose Powell Hill. The current landscape includes a mosaic of habitats that range from old fields to hardwood forests. Forty species of mammals are known to exist on or near the installation. These include one marsupial, five insectivores, 9 chiropterans, one lagomorph, 12 rodents, 10 carnivores, and one cervid. We have studied many of the species on APH since 1997. In this paper we describe the physical environment of the area and 7 important habitats used by mammals. We also summarize the ecology and natural history of each species and provide statistical summaries of original measurements from mammals caught on the installation. The results of several recent studies on APH allow us to describe habitat affiliations and relative abundance of most of the mammals native to the mid-Atlantic region. Old fields and clearcuts support a total of 20 species, including several found predominately in this habitat. Pine stands and pine plantations support the fewest number of mammal species (17) of any habitat on the installation. Mixed pine and hardwood forests, hardwood forests, and riparian forests support the largest number of species (29-36). With the possible exception of pine plantations, the habitat mosaic found on APH provides abundant resources for mammal communities. We also include an evaluation of age and health attributes of the deer population and describe the hunting program on the base. Number of deer harvested annually 1985-2000 varied from 460 to 1765. Management activities since 1996 when the deer population exceeded carrying capacity have improved herd health. Because much of Caroline County and eastern Virginia is in extensive agriculture and the remaining hardwood forests are being clearcut, APH is becoming a valuable habitat island for the mammalian fauna of the upper Coastal Plain of Virginia and the mid-Atlantic region

Distribution and Abundance of Larval Burbot and Deepwater Sculpin in Lake Michigan

Samples from seven locations at depths to 21 m, collected over periods of up to 8 years, were used to describe the nearshore distribution and abundance of burbot Lota lota and deepwater sculpin Myoxocephalus thompsoni larvae in Lake Michigan. Based upon power‐plant‐entrainment samples and field collections, burbot larvae (3.0–7.5 mm) occurred from late March to mid‐June, most abundantly in April and May, and most often at water temperatures of 6–12 C. Larvae were collected from the 0.5‐ to 13.5‐m depth strata as far lakeward as the 21‐m bottom contour, the limit of offshore sampling. In eastern Lake Michigan, highest densities (up to 843 larvae/1,000 m3) were at the 1‐m contour; in Green Bay, up to 24,000 larvae/1,000 m3 were detected near the Bark River. High densities of burbot larvae at bottom depths 3 m and less indicated inshore spawning and river spawning at some sites. Deepwater sculpin larvae first occurred in early February and were common in March and April entrainment samples. Larvae (8.0–22.0 mm) were in nearshore waters usually through May at depth strata of 0.5 to 17 m as far lakeward as the 18‐m bottom contour. Most larvae occurred at water temperatures below 6 C. Field densities were low, 5 to 78 larvae/1,000 m3. Deepwater sculpin larvae were pelagic and were dispersed over great distances by currents.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141932/1/tafs0162.pd

Structural investigation of Fe silicide films grown by pulsed laser deposition

Pulsed laser deposition was used to grow epitaxial β‐FeSi2 films on Si(111) (1×1) and Si(111) (7×7) with the following epitaxial orientations: β‐FeSi2(001)//Si(111) with β‐FeSi2[010]//Si〈110〉 and three rotational variants. Silicide growth was influenced by substrate temperature and deposition rate, but not by the structure of the starting surface. Films containing both β‐FeSi2 and FeSi were formed at low substrate temperatures and high deposition rates, while films containing only β‐FeSi2 were formed at higher substrate temperatures and lower deposition rates. FeSi grains had the following epitaxial relationship to the Si substrate, FeSi(111)//Si(111) with FeSi(110)//Si(112). The microstructure of the silicide films varied with film thickness, as did the roughness at the silicide/Si interface. These results suggest that an Fe‐rich environment was created during the growth of the silicide films.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/70762/2/JAPIAU-76-4-2202-1.pd

A randomised phase I study of etrolizumab (rhuMAb β7) in moderate to severe ulcerative colitis.

ObjectiveEtrolizumab (rhuMAb β7, anti-β7, PRO145223) is a humanised monoclonal antibody targeting the β7 subunit of the heterodimeric integrins α4β7 and αEβ7, which are implicated in leucocyte migration and retention in ulcerative colitis (UC). This randomised phase I study evaluated the safety and pharmacology of etrolizumab in patients with moderate to severe UC.DesignIn the single ascending dose (SAD) stage, etrolizumab (0.3, 1.0, 3.0, 10 mg/kg intravenous, 3.0 mg/kg subcutaneous (SC) or placebo) was administered 4:1 (n=25) in each cohort. In the multiple dose (MD) stage, new patients received monthly etrolizumab (0.5 mg/kg SC (n=4), 1.5 mg/kg SC (n=5), 3.0 mg/kg SC (n=4), 4.0 mg/kg intravenous (n=5)) or placebo (n=5). The pharmacokinetics was studied and Mayo Clinic Score evaluated at baseline, day 29 (SAD), and days 43 and 71 (MD).ResultsIn the SAD stage, there were no dose limiting toxicities, infusion or injection site reactions. Two impaired wound healing serious adverse events occurred in two patients receiving etrolizumab. In the MD stage, there were no dose limiting toxicities, and no infusion or injection site reactions. Headache was the most common adverse event, occurring more often in etrolizumab patients. Antietrolizumab antibodies were detected in two subjects. The duration of β7 receptor full occupancy was dose related. A clinical response was observed in 12/18 patients, and clinical remission in 3/18 patients treated with etrolizumab in the MD stage, compared with 4/5 and 1/5 placebo patients, respectively.ConclusionEtrolizumab is well tolerated in moderate to severe UC. Further investigation is warranted

Standing Genetic Variation in Contingency Loci Drives the Rapid Adaptation of Campylobacter jejuni to a Novel Host

The genome of the food-borne pathogen Campylobacter jejuni contains multiple highly mutable sites, or contingency loci. It has been suggested that standing variation at these loci is a mechanism for rapid adaptation to a novel environment, but this phenomenon has not been shown experimentally. In previous work we showed that the virulence of C. jejuni NCTC11168 increased after serial passage through a C57BL/6 IL-10-/- mouse model of campylobacteriosis. Here we sought to determine the genetic basis of this adaptation during passage. Re-sequencing of the 1.64Mb genome to 200-500X coverage allowed us to define variation in 23 contingency loci to an unprecedented depth both before and after in vivo adaptation. Mutations in the mouse-adapted C. jejuni were largely restricted to the homopolymeric tracts of thirteen contingency loci. These changes cause significant alterations in open reading frames of genes in surface structure biosynthesis loci and in genes with only putative functions. Several loci with open reading frame changes also had altered transcript abundance. The increase in specific phases of contingency loci during in vivo passage of C. jejuni, coupled with the observed virulence increase and the lack of other types of genetic changes, is the first experimental evidence that these variable regions play a significant role in C. jejuni adaptation and virulence in a novel host

Genetic dissection of the tissue‐specific roles of type III effectors and phytotoxins in the pathogenicity of Pseudomonas syringae pv. syringae to cherry

When compared with other phylogroups (PGs) of the Pseudomonas syringae species complex, P. syringae pv. syringae (Pss) strains within PG2 have a reduced repertoire of type III effectors (T3Es) but produce several phytotoxins. Effectors within the cherry pathogen Pss 9644 were grouped based on their frequency in strains from Prunus as the conserved effector locus (CEL) common to most P. syringae pathogens; a core of effectors common to PG2; a set of PRUNUS effectors common to cherry pathogens; and a FLEXIBLE set of T3Es. Pss 9644 also contains gene clusters for biosynthesis of toxins syringomycin, syringopeptin and syringolin A. After confirmation of virulence gene expression, mutants with a sequential series of T3E and toxin deletions were pathogenicity tested on wood, leaves and fruits of sweet cherry (Prunus avium) and leaves of ornamental cherry (Prunus incisa). The toxins had a key role in disease development in fruits but were less important in leaves and wood. An effectorless mutant retained some pathogenicity to fruit but not wood or leaves. Striking redundancy was observed amongst effector groups. The CEL effectors have important roles during the early stages of leaf infection and possibly acted synergistically with toxins in all tissues. Deletion of separate groups of T3Es had more effect in P. incisa than in P. avium. Mixed inocula were used to complement the toxin mutations in trans and indicated that strain mixtures may be important in the field. Our results highlight the niche‐specific role of toxins in P. avium tissues and the complexity of effector redundancy in the pathogen Pss 9644

The stealth episome: suppression of gene expression on the excised genomic island PPHGI-1 from Pseudomonas syringae pv. phaseolicola

Pseudomonas syringae pv. phaseolicola is the causative agent of halo blight in the common bean, Phaseolus vulgaris. P. syringae pv. phaseolicola race 4 strain 1302A contains the avirulence gene avrPphB (syn. hopAR1), which resides on PPHGI-1, a 106 kb genomic island. Loss of PPHGI-1 from P. syringae pv. phaseolicola 1302A following exposure to the hypersensitive resistance response (HR) leads to the evolution of strains with altered virulence. Here we have used fluorescent protein reporter systems to gain insight into the mobility of PPHGI-1. Confocal imaging of dual-labelled P. syringae pv. phaseolicola 1302A strain, F532 (dsRFP in chromosome and eGFP in PPHGI-1), revealed loss of PPHGI-1::eGFP encoded fluorescence during plant infection and when grown in vitro on extracted leaf apoplastic fluids. Fluorescence-activated cell sorting (FACS) of fluorescent and non-fluorescent PPHGI-1::eGFP F532 populations showed that cells lost fluorescence not only when the GI was deleted, but also when it had excised and was present as a circular episome. In addition to reduced expression of eGFP, quantitative PCR on sub-populations separated by FACS showed that transcription of other genes on PPHGI-1 (avrPphB and xerC) was also greatly reduced in F532 cells harbouring the excised PPHGI-1::eGFP episome. Our results show how virulence determinants located on mobile pathogenicity islands may be hidden from detection by host surveillance systems through the suppression of gene expression in the episomal state

Persistent enteric murine norovirus infection is associated with functionally suboptimal virus-specific CD8 T cell responses

Norovirus (NV) gastroenteritis is a major contributor to global morbidity and mortality, yet little is known about immune mechanisms leading to NV control. Previous studies using the murine norovirus (MNV) model have established a key role for T cells in MNV clearance. Despite these advances, important questions remain regarding the magnitude, location, and dynamics of the MNV-specific T cell response. To address these questions, we identified MNV-specific major histocompatibility complex (MHC) class I immunodominant epitopes using an overlapping peptide screen. One of these epitopes (amino acids 519 to 527 of open reading frame 2 [ORF2(519-527)]) was highly conserved among all NV genogroups. Using MHC class I peptide tetramers, we tracked MNV-specific CD8 T cells in lymphoid and mucosal sites during infection with two MNV strains with distinct biological behaviors, the acutely cleared strain CW3 and the persistent strain CR6. Here, we show that enteric MNV infection elicited robust T cell responses primarily in the intestinal mucosa and that MNV-specific CD8 T cells dynamically regulated the expression of surface molecules associated with activation, differentiation, and homing. Furthermore, compared to MNV-CW3 infection, chronic infection with MNV-CR6 resulted in fewer and less-functional CD8 T cells, and this difference was evident as early as day 8 postinfection. Finally, MNV-specific CD8 T cells were capable of reducing the viral load in persistently infected Rag1(−/−) mice, suggesting that these cells are a crucial component of NV immunity. Collectively, these data provide fundamental new insights into the adaptive immune response to two closely related NV strains with distinct biological behaviors and bring us closer to understanding the correlates of protective antiviral immunity in the intestine

αEβ7 Integrin Identifies Subsets of Pro-Inflammatory Colonic CD4+ T Lymphocytes in Ulcerative Colitis.

Background and Aims The αEβ7 integrin is crucial for retention of T lymphocytes at mucosal surfaces through its interaction with E-cadherin. Pathogenic or protective functions of these cells during human intestinal inflammation, such as ulcerative colitis [UC], have not previously been defined, with understanding largely derived from animal model data. Defining this phenotype in human samples is important for understanding UC pathogenesis and is of translational importance for therapeutic targeting of αEβ7-E-cadherin interactions. Methods αEβ7+ and αEβ7- colonic T cell localization, inflammatory cytokine production and expression of regulatory T cell-associated markers were evaluated in cohorts of control subjects and patients with active UC by immunohistochemistry, flow cytometry and real-time PCR of FACS-purified cell populations. Results CD4+αEβ7+ T lymphocytes from both healthy controls and UC patients had lower expression of regulatory T cell-associated genes, including FOXP3, IL-10, CTLA-4 and ICOS in comparison with CD4+αEβ7- T lymphocytes. In UC, CD4+αEβ7+ lymphocytes expressed higher levels of IFNγ and TNFα in comparison with CD4+αEβ7- lymphocytes. Additionally the CD4+αEβ7+ subset was enriched for Th17 cells and the recently described Th17/Th1 subset co-expressing both IL-17A and IFNγ, both of which were found at higher frequencies in UC compared to control. Conclusion αEβ7 integrin expression on human colonic CD4+ T cells was associated with increased production of pro-inflammatory Th1, Th17 and Th17/Th1 cytokines, with reduced expression of regulatory T cell-associated markers. These data suggest colonic CD4+αEβ7+ T cells are pro-inflammatory and may play a role in UC pathobiology

Efficacy of Memantine for Agitation in Alzheimer’s Dementia: A Randomised Double-Blind Placebo Controlled Trial

Agitation in Alzheimer's disease (AD) is common and associated with poor patient life-quality and carer distress. The best evidence-based pharmacological treatments are antipsychotics which have limited benefits with increased morbidity and mortality. There are no memantine trials in clinically significant agitation but post-hoc analyses in other populations found reduced agitation. We tested the primary hypothesis, memantine is superior to placebo for clinically significant agitation, in patients with moderate-to-severe AD