Marooned on an Extinct Volcano: the Conservation Status of Four Endemic Land Snails (Gastropoda: Pulmonata) at Mount Kaputar, New South Wales

Volcanic activity in northern inland New South Wales between 40 and 15 million years ago was followed by general continental-scale drying and coastward contraction of mesic ecosystems between 15 and 2 million years ago. Together, these processes resulted in the creation of high-elevation climatic refuges such as Coolah Tops, Mount Kaputar and the Warrumbungle Range as western outposts of the mesic eastern highlands on the dry western slopes. These areas are important hotspots of land snail species diversity and endemism. A high-elevation and dry rainforest land snail community at Mount Kaputar, recognised as being of outstanding conservation significance, was listed as an endangered ecological community under NSW legislation in 2013. Two species from this community, the Kaputar Pink Slug Triboniophorus sp. nov. “Kaputar” and Bronze Rippled Pinwheel Snail Cralopa kaputarensis , are currently listed on the IUCN Red List , as endangered and data deficient respectively. This paper provides an updated assessment of the conservation status of the Kaputar Pink Slug, a reassessment of the Bronze Rippled Pinwheel Snail and original assessment of another two endemic Mount Kaputar species (Kaputar Carnivorous Snail Vitellidelos kaputarensis and Kaputar Keeled Snail Thersites sp. nov. “Kaputar”), concluding that all four species meet the criteria for listing as endangered on the IUCN Red List

A Community-Based Social Networking Intervention to Increase Walking in Dog Owners

Roughly 40% of U.S. households own a dog and while dog ownership is associated with greater engagement in physical activity, up to 60% of dog owners do not achieve the recommended 150 minutes of weekly physical activity. The present study aims to develop and test a dog walking intervention addressing individual, interpersonal, and community factors. The study represents collaboration between UMass Medical School, UMass Lowell and their community partners, Common Pathways and the Greater Lowell Health Alliance. The developmental phase uses a community-based participatory research approach by creating community advisory boards and conducting focus groups with residents to ensure community perspectives are represented throughout intervention development. Information gathered from the developmental phase will inform the intervention. The intervention phase will determine the feasibility and efficacy of a multi-component dog walking intervention using a group randomized controlled trial. The intervention uses a social networking website, newsletters, pedometers, neighborhood walks, and community events to educate owners on the benefits of walking, create a supportive environment, and increase the “dog friendliness” of a community. Communities in Worcester and Lowell will be randomized to the intervention or control condition. Outcome measures include pedometer steps, time spent walking the dog, social support for exercise, and sense of community. This study is one of the first studies to test whether increasing dog walking in dog owners can increase owner physical activity via a social networking website. If successful, we will assess the extent to which the community can sustain the intervention

Utility of point‐of‐care lung ultrasound for monitoring cardiogenic pulmonary edema in dogs

Background Point‐of‐care lung ultrasound (LUS) is an effective tool to diagnose left‐sided congestive heart failure (L‐CHF) in dogs via detection of ultrasound artifacts (B‐lines) caused by increased lung water. Hypothesis/Objectives To determine whether LUS can be used to monitor resolution of cardiogenic pulmonary edema in dogs, and to compare LUS to other indicators of L‐CHF control. Animals Twenty‐five client‐owned dogs hospitalized for treatment of first‐onset L‐CHF. Methods Protocolized LUS, thoracic radiographs (TXR), and plasma N‐terminal pro‐B‐type natriuretic peptide were performed at hospital admission, hospital discharge, and recheck examinations. Lung ultrasound findings were compared between timepoints and to other clinical measures of L‐CHF. Results From time of hospital admission to discharge (mean 19.6 hours), median number of LUS sites strongly positive for B‐lines (\u3e3 B‐lines per site) decreased from 5 (range, 1‐8) to 1 (range, 0‐5; P \u3c .001), and median total B‐line score decreased from 37 (range, 6‐74) to 5 (range, 0‐32; P = .002). Lung ultrasound indices remained improved at first recheck (P \u3c .001). Number of strong positive sites correlated positively with respiratory rate (r = 0.52, P = .008) and TXR edema score (r = 0.51, P = .009) at hospital admission. Patterns of edema resolution differed between LUS and TXR, with cranial quadrants showing more significant reduction in B‐lines compared to TXR edema score (80% vs 29% reduction, respectively; P = .003). Conclusions and Clinical Importance Lung ultrasound could be a useful tool for monitoring resolution of pulmonary edema in dogs with L‐CHF

Simple inhibitors of histone deacetylase activity that combine features of short-chain fatty acid and hydroxamic acid inhibitors

Butyric acid and trichostatin A (TSA) are anti-cancer compounds that cause the upregulation of genes involved in differentiation and cell cycle regulation by inhibiting histone deacetylase (HDAC) activity. In this study we have synthesized and evaluated compounds that combine the bioavailability of short-chain fatty acids, like butyric acid, with the bidentate binding ability of TSA. A series of analogs were made to examine the effects of chain length, simple aromatic cap groups, and substituted hydroxamates on the compounds\u27 ability to inhibit rat-liver HDAC using a fluorometric assay. In keeping with previous structure-activity relationships, the most effective inhibitors consisted of longer chains and hydroxamic acid groups. It was found that 5-phenylvaleric hydroxamic acid and 4-benzoylbutyric hydroxamic acid were the most potent inhibitors with IC50\u27s of 5 microM and 133 microM respectively

Polymorphisms in IL12A and cockroach allergy in children with asthma

<p>Abstract</p> <p>Background</p> <p>IL12A has been implicated in T-cell development and may thus influence the development of atopy and allergic diseases.</p> <p>Methods</p> <p>We tested for association between four linkage disequilibrium (LD)-tagging SNPs (rs2243123, rs2243151, rs668998, and rs17826053) in <it>IL12A </it>and asthma and allergy-related (serum total and allergen-specific IgE, and skin test reactivity [STR] to two common allergens) phenotypes in two samples: 417 Costa Rican children with asthma and their parents, and 470 families of 503 white children in the Childhood Asthma Management Program (CAMP). The analysis was conducted using the family-based association test (FBAT) statistic implemented in the PBAT program.</p> <p>Results</p> <p>Among Costa Rican children with asthma, homozygosity for the minor allele of each of two SNPs in <it>IL12A </it>(rs2243123 and rs2243151) was associated with increased risks of STR to American cockroach (P ≤ 0.03 for both SNPs), STR to German cockroach (P ≤ 0.01 for both SNPs), and having a positive IgE to German cockroach (P < 0.05 for both SNPs). Among children in CAMP, homozygosity for the minor allele of SNP rs2243151 in <it>IL12A </it>was inversely associated with STR to German cockroach (P = 0.03) and homozygosity for the minor allele of SNP rs17826053 in <it>IL12A </it>was associated with increased risks of STR to American cockroach (P = 0.01) and STR to German cockroach (P = 0.007). There was no significant association between any SNP in <it>IL12A </it>and asthma, STR to dust mite, or total IgE in Costa Rica or CAMP.</p> <p>Conclusion</p> <p>Our findings suggest that variants in <it>IL12A </it>influence cockroach allergy among children with asthma.</p

A Bitter Taste Receptor as a Novel Molecular Target on Cancer-Associated Fibroblasts in Pancreatic Ductal Adenocarcinoma

Cancer-associated fibroblasts (CAFs) execute diverse and complex functions in cancer progression. While reprogramming the crosstalk between CAFs and cancer epithelial cells is a promising avenue to evade the adverse effects of stromal depletion, drugs are limited by their suboptimal pharmacokinetics and off-target effects. Thus, there is a need to elucidate CAF-selective cell surface markers that can improve drug delivery and efficacy. Here, functional proteomic pulldown with mass spectrometry was used to identify taste receptor type 2 member 9 (TAS2R9) as a CAF target. TAS2R9 target characterization included binding assays, immunofluorescence, flow cytometry, and database mining. Liposomes conjugated to a TAS2R9-specific peptide were generated, characterized, and compared to naked liposomes in a murine pancreatic xenograft model. Proof-of-concept drug delivery experiments demonstrate that TAS2R9-targeted liposomes bind with high specificity to TAS2R9 recombinant protein and exhibit stromal colocalization in a pancreatic cancer xenograft model. Furthermore, the delivery of a CXCR2 inhibitor by TAS2R9-targeted liposomes significantly reduced cancer cell proliferation and constrained tumor growth through the inhibition of the CXCL-CXCR2 axis. Taken together, TAS2R9 is a novel cell-surface CAF-selective target that can be leveraged to facilitate small-molecule drug delivery to CAFs, paving the way for new stromal therapies

A Correlation Between Galaxy Morphology and MgII Halo Absorption Strength

(Abridged) We compared the quantified morphological properties of 37 intermediate redshift MgII absorption selected galaxies to the properties of the absorbing halo gas, observed in the spectra of background quasars. The galaxy morphologies were measured using GIM2D modeling of Hubble Space Telescope WFPC-2 images and the absorbing gas properties were obtained from HIRES/Keck and UVES/VLT quasar spectra. We found a 3.1 sigma correlation between galaxy morphological asymmetries normalized by the quasar-galaxy projected separations, A/D, and the MgII rest-frame equivalent widths. Saturation effects cause increased scatter in the relationship with increasing W_r(2796). We defined a subsample for which the fraction of saturated pixels in the absorption profiles is f_sat<0.5. The correlation strengthened to 3.3 sigma. We also find a paucity of small morphological asymmetries for galaxies selected by MgII absorption as compared to those of the general population of field galaxies, as measured in the Medium Deep Survey. The K-S probability that the two samples are drawn from the same galaxy population is ruled out at a 99.8% confidence level. The A/D-W_r(2796) correlation suggests a connection between the processes that perturb galaxies and the quantity of gas in their halos, normalized by the impact parameter. Since the perturbations are minor, it is clear that dramatic processes or events are not required for a galaxy to have an extended halo; the galaxies appear "normal". We suggest that common, more mild processes that populate halos with gas, such as satellite galaxy merging, accretion of the local cosmic web, and longer-range galaxy-galaxy interactions, consequently also induce the observed minor perturbations in the galaxies.Comment: Accepted for publication in the Astrophysical Journa

The genome of Aeromonas salmonicida subsp. salmonicida A449: insights into the evolution of a fish pathogen

Background Aeromonas salmonicida subsp. salmonicida is a Gram-negative bacterium that is the causative agent of furunculosis, a bacterial septicaemia of salmonid fish. While other species of Aeromonas are opportunistic pathogens or are found in commensal or symbiotic relationships with animal hosts, A. salmonicida subsp. salmonicida causes disease in healthy fish. The genome sequence of A. salmonicida was determined to provide a better understanding of the virulence factors used by this pathogen to infect fish. Results The nucleotide sequences of the A. salmonicida subsp. salmonicida A449 chromosome and two large plasmids are characterized. The chromosome is 4,702,402 bp and encodes 4388 genes, while the two large plasmids are 166,749 and 155,098 bp with 178 and 164 genes, respectively. Notable features are a large inversion in the chromosome and, in one of the large plasmids, the presence of a Tn21 composite transposon containing mercury resistance genes and an In2 integron encoding genes for resistance to streptomycin/spectinomycin, quaternary ammonia compounds, sulphonamides and chloramphenicol. A large number of genes encoding potential virulence factors were identified; however, many appear to be pseudogenes since they contain insertion sequences, frameshifts or in-frame stop codons. A total of 170 pseudogenes and 88 insertion sequences (of ten different types) are found in the A. salmonicida genome. Comparison with the A. hydrophila ATCC 7966T genome reveals multiple large inversions in the chromosome as well as an approximately 9% difference in gene content indicating instances of single gene or operon loss or gain. A limited number of the pseudogenes found in A. salmonicida A449 were investigated in other Aeromonas strains and species. While nearly all the pseudogenes tested are present in A. salmonicida subsp. salmonicida strains, only about 25% were found in other A. salmonicida subspecies and none were detected in other Aeromonas species. Conclusion Relative to the A. hydrophila ATCC 7966T genome, the A. salmonicida subsp. salmonicida genome has acquired multiple mobile genetic elements, undergone substantial rearrangement and developed a significant number of pseudogenes. These changes appear to be a consequence of adaptation to a specific host, salmonid fish, and provide insights into the mechanisms used by the bacterium for infection and avoidance of host defence systems.Peer reviewed: YesNRC publication: Ye

Appetite and gut hormone responses to moderate-intensity continuous exercise versus high-intensity interval exercise, in normoxic and hypoxic conditions.

This study investigated the effects of continuous moderate-intensity exercise (MIE) and high-intensity interval exercise (HIIE) in combination with short exposure to hypoxia on appetite and plasma concentrations of acylated ghrelin, peptide YY (PYY), and glucagon-like peptide-1 (GLP-1). Twelve healthy males completed four, 2.6 h trials in a random order: 1) MIE-normoxia, 2) MIE-hypoxia, 3) HIIE-normoxia, and 4) HIIE-hypoxia. Exercise took place in an environmental chamber. During MIE, participants ran for 50 min at 70% of altitude-specific maximal oxygen uptake ( 2max) and during HIIE performed 6 x 3 min running at 90% 2max interspersed with 6 x 3 min active recovery at 50% 2max with a 7 min warm-up and cool-down at 70% 2max (50 min total). In hypoxic trials, exercise was performed at a simulated altitude of 2,980 m (14.5% O2). Exercise was completed after a standardised breakfast. A second meal standardised to 30% of participants’ daily energy requirements was provided 45 min after exercise. Appetite was suppressed more in hypoxia than normoxia during exercise, post-exercise, and for the full 2.6 h trial period (linear mixed modelling, p 0.05). These findings demonstrate that short exposure to hypoxia causes suppressions in appetite and plasma acylated ghrelin concentrations. Furthermore, appetite responses to exercise do not appear to be influenced by exercise modality