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We conducted a preregistered multilaboratory project ( k = 36; N = 3,531) to assess the size and robustness of ego-depletion effects using a novel replication method, termed the paradigmatic replication approach. Each laboratory implemented one of two procedures that was intended to manipulate self-control and tested performance on a subsequent measure of self-control. Confirmatory tests found a nonsignificant result ( d = 0.06). Confirmatory Bayesian meta-analyses using an informed-prior hypothesis (δ = 0.30, SD = 0.15) found that the data were 4 times more likely under the null than the alternative hypothesis. Hence, preregistered analyses did not find evidence for a depletion effect. Exploratory analyses on the full sample (i.e., ignoring exclusion criteria) found a statistically significant effect ( d = 0.08); Bayesian analyses showed that the data were about equally likely under the null and informed-prior hypotheses. Exploratory moderator tests suggested that the depletion effect was larger for participants who reported more fatigue but was not moderated by trait self-control, willpower beliefs, or action orientation.

peer-reviewed Bovine mastitis is an inflammation-driven disease of the bovine mammary gland that costs the global dairy industry several billion dollars per annum. Because disease susceptibility is a multi-factorial complex phenotype, an integrative biology approach is required to dissect the molecular networks involved. Here, we report such an approach, using next generation sequencing combined with advanced network and pathway biology methods to simultaneously profile mRNA and miRNA expression at multiple time-points (0, 12, 24, 36 and 48h) in both milk and blood FACS-isolated CD14+ monocytes from animals infected in vivo with Streptococcus uberis. More than 3,700 differentially expressed (DE) genes were identified in milk-isolated monocytes (MIMs), a key immune cell recruited to the site of infection during mastitis. Up-regulated genes were significantly enriched for inflammatory pathways, while down-regulated genes were enriched for non-glycolytic metabolic pathways. Monocyte transcriptional changes in the blood, however, were more subtle but highlighted the impact of this infection systemically. Genes up-regulated in blood-isolated-monocytes (BIMs) showed a significant association with interferon and chemokine signalling. Furthermore, twenty-six miRNAs were differentially expressed in MIMs and three in BIMs. Pathway analysis revealed that predicted targets of down-regulated miRNAs were highly enriched for roles in innate immunity (FDR < 3.4E-8) in particular TLR signalling, while up-regulated miRNAs preferentially targeted genes involved in metabolism. We conclude that during S. uberis infection miRNAs are key amplifiers of monocyte inflammatory response networks and repressors of several metabolic pathways. This study was funded in part by Teagasc RMIS 6018 and United States Department of Agriculture ARS funding 3625-32000-102-00. NL is supported by a Teagasc Walsh Fellowship.

The process of germ cell development is under the tight control of various signaling pathways, among which the PI3K-Akt-mTOR pathway is of critical importance. Previous studies have demonstrated sex-specific roles for several components of this pathway. In the current study, we aimed to evaluate the role of Rheb, a member of the small GTPase superfamily and a critical component for mTORC1 activation, in male and female gametogenesis. The function of Rheb in development and the nervous system has been extensively studied, but little is known about its role in the germ line. We have exploited genetic approaches in the mouse to study the role of Rheb in the germ line and have identified an essential role in spermatogenesis. Conditional knockout (cKO) of Rheb in the male germ line resulted in severe oligoasthenoteratozoospermia and male sterility. More detailed phenotypic analyses uncovered an age-dependent meiotic progression defect combined with subsequent abnormalities in spermiogenesis as evidenced by abnormal sperm morphology. In the female, however, germ-cell specific inactivation of Rheb was not associated with any discernible abnormality; these cKO mice were fertile with morphologically unremarkable ovaries, normal primordial follicle formation, and subsequent follicle maturation. The absence of an abnormal ovarian phenotype is striking given previous studies demonstrating a critical role for the mTORC1 pathway in the maintenance of primordial follicle pool. In conclusion, our findings demonstrate an essential role of Rheb in diverse aspects of spermatogenesis but suggest the existence of functionally redundant factors that can compensate for Rheb deficiency within oocytes.

Snags are used as roosting sites by many bats living in coniferous forests of western North America. Thus, providing sufficient numbers of snags both spatially and temporally in forested landscapes is critical to sustaining populations of these species. One aspect that remains poorly understood is length of time that roost snags persist on the landscape in a form suitable for use by bats. This information is critical for forest-planning efforts in ensuring long-term availability of snag resources on forested landscapes. We monitored condition of 339 snags used as roosting sites by long-legged myotis (Myotis volans) 1–5 years post-discovery from 2001 to 2006 across 6 watersheds in Washington, Oregon, and Idaho, USA. Persistence rates (i.e., probability a snag remains standing from year x to x + 1) of roost snags declined with year post-discovery in all study areas. Fir snags (Abies spp.) exhibited lower persistence rates than other conifer species. Data for the Washington area indicated only 4.3% of roost snags likely remain standing 10 years post-discovery, with half-lives of all snag species

Two pilot and six studies indicated that poor self-control causes people to violate social norms and rules that are effortful to follow. Lower trait self-control was associated with a greater willingness to take ethical risks and use curse words. Participants who completed an initial self-control task that reduced the capacity for self-control used more curse words and were more willing to take ethical risks than participants who completed a neutral task. Poor self-control was also associated with violating explicit rules given by the experimenter. Depleting self-control resources in a self-control exercise caused participants subsequently to talk when they had been instructed to remain silent. Low trait self-control and poor performance on a behavioral measure of self-control (the Stroop task) predicted poor compliance following experimental instructions over a 2-week span. Poor self-control thus undermines adherence to some social rules and regulations, therefore possibly contributing to a broad variety of social ills.

Several species of bats in the Pacific Northwest of the United States, including long-legged myotis (Myotis volans), are dependent on snags in coniferous forests during summer for roosting and rearing young. Thus, data on roosting preferences of this species are needed to integrate their habitat requirements into shifting plans for management of forests in this region. Therefore, from 2001 to 2006, we radiotracked adult female long-legged myotis (n = 153) to day roosts (n = 395) across 6 watersheds in Washington, Oregon, and Idaho, USA, and compared characteristics associated with roosting sites to those of random snags (n = 260) sampled in the same watersheds using use–availability logistic regression and an information-theoretic approach. Model rankings varied among geographic locations, with quantity of stem surface for roosting the best model for explaining roost-site selection of long-legged myotis in both Washington and Oregon. Model rankings for populations of bats in Idaho found sta...

The beetle suborder Adephaga is traditionally divided into two sections on the basis of habitat, terrestrial Geadephaga and aquatic Hydradephaga. Monophyly of both groups is uncertain, and the relationship of the two groups has implications for inferring habitat transitions within Adephaga. Here we examine phylogenetic relationships of these groups using evidence provided by DNA sequences from all four suborders of beetles, including 60 species of Adephaga, four Archostemata, three Myxophaga, and ten Polyphaga. We studied 18S ribosomal DNA and 28S ribosomal DNA, aligned with consideration of secondary structure, as well as the nuclear protein-coding gene wingless. Independent and combined Bayesian, likelihood, and parsimony analyses of all three genes supported placement of Trachypachidae in a monophyletic Geadephaga, although for analyses of 28S rDNA and some parsimony analyses only if Coleoptera is constrained to be monophyletic. Most analyses showed limited support for the monophyly of Hydradephaga. Outside of Adephaga, there is support from the ribosomal genes for a sister group relationship between Adephaga and Polyphaga. Within the small number of sampled Polyphaga, analyses of 18S rDNA, wingless, and the combined matrix supports monophyly of Polyphaga exclusive of Scirtoidea. Unconstrained analyses of the evolution of habitat suggest that Adephaga was ancestrally aquatic with one transition to terrestrial. However, in analyses constrained to disallow changes from aquatic to terrestrial habitat, the phylogenies imply two origins of aquatic habit within Adephaga.

Limited information exists on the foraging ecology of the long-legged myotis (Myotis volans), especially with regard to use of available foraging habitats in large, relatively contiguous forested landscapes. During the summers of 2004 and 2005, we radiotagged adult long-legged myotis (n = 70) in north-central Idaho to estimate the size of home ranges and to evaluate use of available foraging habitats. Size of home range and core areas was measured for individuals with ≥31 locations (n = 30) using the adaptive kernel method, and selection among available foraging habitats was evaluated using Euclidean distance analysis. Home-range estimates did not differ among males, pregnant females, and lactating females (P = 0.52). Core-area estimates also did not differ among males, pregnant females, and lactating females (P = 0.62). Second-order habitat analysis, based on vegetation, showed that home ranges of males (P = 0.01), pregnant females (P = 0.001), and lactating females (P = 0.001) all were closest ...

We radiotracked 25 adult female fringed myotis (Myotis thysanodes) to day roosts in xeric ponderosa pine (Pinus ponderosa) forests on the east side of the Cascade range in Washington and Oregon from 2001 to 2003. Bats were tracked for an average of 9.6 days/bat ± 0.1 SE for a total of 240 roost-days. Bats used 118 roosts, 93% of which were in the crevices of rocks. Pregnant females chose horizontal crevices 58.8% of the time, whereas lactating (60.9%) and postlactating (75%) females selected vertical crevices more often. There was no difference in crevice length or crevice width among roosts in rocks used by pregnant, lactating, and postlactating females. Snags were used as roosts on only 6 occasions, and all were in ponderosa pines situated within a single watershed. The largest emergence count of fringed myotis that we recorded was 118 bats from a ponderosa pine snag. Snags used as roosts were larger in diameter, taller in height, and extended farther above the local canopy than random snags. B...

Foxo3 protein is required in the oocyte nucleus for the maintenance of primordial follicles in a dormant state. PI3K/AKT-dependent phosphorylation of Foxo3 leads to its relocalization to the cytoplasm and subsequent follicular activation. However, the nature of the upstream signals controlling Foxo3 activity and subcellular localization remains unknown. We aimed to study the in vitro effects of Kit ligand (stem cell factor) on the subcellular localization of Foxo3 in primordial follicles within the postnatal mouse ovary. This was an in vitro study using explants of intact neonatal mouse ovaries. The study was performed in laboratory animal facility and basic science research laboratory at a University Hospital. The animals used for this study were FVB mice. Neonatal FVB mice ovaries at postnatal day 7 (PD7) were harvested and incubated in culture medium (DMEM) at 37 °C and 5 % CO2 for 60–90 min with (n = 3) or without (n = 3) Kit ligand at 150 ng/mL (8 nM). Similar experimental conditions were used to establish a dose–response curve for the effects of Kit ligand and assess the effects of imatinib (small molecule inhibitor of the Kit receptor). Immunofluorescence was used to identify the subcellular location of Foxo3 in oocytes. Proportions of cytoplasmic versus nuclear Foxo3 in primordial follicles were determined. Kit ligand treatment increased the cytoplasmic localization of Foxo3 from 40 % in the untreated ovaries to 74 % in the treated group (p = 0.007 in paired samples and p = 0.03 in unpaired samples). Furthermore, this effect was reversible with imatinib (p = 0.005). A dose–response curve for Kit ligand treatment showed that maximum effect was seen at 150 ng/mL. Kit ligand treatment in vitro increases the proportion of cytoplasmic Foxo3 in primordial follicles at PD7, lending support to the idea that Kit receptor/ligand controls Foxo3 activity in the context of primordial follicle activation

We studied use of day roosts by adult, female long-legged myotis (Myotis volans) in 4 watersheds dominated by ponderosa pine (Pinus ponderosa) forest east of the Cascade Crest in Washington and Oregon, USA, 2001–2003. To investigate maternity habitat in managed, xeric forests we radiotracked 87 bats to 195 snag roosts and 34 rock crevices totaling 842 roost-days. Bats changed roosts every 2.7 ± 0.1 (SE) days and averaged 3.6 ± 0.3 roosts per bat. Roosts were 2.0 ± 0.1 km from capture sites, and bats moved 1.4 ± 0.1 km between successive roosts. Six bats (6.9%) day-roosted in rock crevices exclusively, 9 bats (10.3%) used snags and rock crevices, and the remaining bats (82.8%) day-roosted in snags exclusively. Most snag roosts were thick-bark ponderosa pine (n = 103; 52.8%) or thin-bark grand fir (Abies grandis) and white fir (Abies concolor) (n = 74; 37.9%). Over half of all snag roosts (n = 101; 52%) were used by solitary bats; 28 snag roosts (14%) housed >50 bats (large-flyout roosts). Ninety-three percent of large-flyout roosts were in ponderosa pine snags. Large-flyout roosts were larger, taller, and retained more exfoliating bark and total bark than small-flyout roosts (P 25 cm diameter, and were lower in elevation than random snags (P < 0.05). Pregnant bats divided roost-days almost evenly between thick and thin-bark snags (52.7 vs. 47.3%), whereas lactating bats roosted in thick-bark snags more often than they did in thin-bark snags (80.3 vs. 19.7%, P < 0.0001). Pregnant bats roosted in both upslope and riparian zones (57.5 vs. 42.5%), but lactating bats spent more days roosting upslope than in riparian zones (73.1 vs. 26.9%, P < 0.0001). These findings suggest that reproductive female long-legged bats choose roosts relative to their changing physiological needs. We recommend that management of forests for sustaining habitat of female long-legged myotis in the east Cascades ensure the continued availability of both thick- and thin-bark snags in early stages of decay, in both riparian and upslope positions.

Spermatogenesis is a complex, multistep process that maintains male fertility and is sustained by rare germline stem cells. Spermatogenic progression begins with spermatogonia, populations of which express distinct markers. The identity of the spermatogonial stem cell population in the undisturbed testis is controversial due to a lack of reliable and specific markers. Here we identified the transcription factor PAX7 as a specific marker of a rare subpopulation of A(single) spermatogonia in mice. PAX7+ cells were present in the testis at birth. Compared with the adult testis, PAX7+ cells constituted a much higher percentage of neonatal germ cells. Lineage tracing in healthy adult mice revealed that PAX7+ spermatogonia self-maintained and produced expanding clones that gave rise to mature spermatozoa. Interestingly, in mice subjected to chemotherapy and radiotherapy, both of which damage the vast majority of germ cells and can result in sterility, PAX7+ spermatogonia selectively survived, and their subsequent expansion contributed to the recovery of spermatogenesis. Finally, PAX7+ spermatogonia were present in the testes of a diverse set of mammals. Our data indicate that the PAX7+ subset of A(single) spermatogonia functions as robust testis stem cells that maintain fertility in normal spermatogenesis in healthy mice and mediate recovery after severe germline injury, such as occurs after cancer therapy.

Current hypotheses regarding family relationships in the suborder Adephaga (Coleoptera) are conflicting. Here we report full-length 18S ribosomal RNA sequences of 39 adephagans and 13 outgroup taxa. Data analysis focused on the impact of sequence alignment on tree topology, using two principally different approaches. Tree alignments, which seek to minimize indels and substitutions on the tree in a single step, as implemented in an approximate procedure by the computer program POY, were contrasted with a more traditional procedure based on alignments followed by phylogenetic inference based on parsimony, likelihood, and distance analyses. Despite substantial differences between the procedures, phylogenetic conclusions regarding basal relationships within Adephaga and relationships between the four suborders of Coleoptera were broadly similar. The analysis weakly supports monophyly of Adephaga, with Polyphaga usually as its sister, and the two small suborders Myxophaga and Archostemata basal to them. In some analyses, however, Polyphaga was reconstructed as having arisen from within Hydradephaga. Adephaga generally split into two monophyletic groups, corresponding to the terrestrial Geadephaga and the aquatic Hydradephaga, as initially proposed by Crowson in 1955, consistent with a single colonization of the aquatic environment by adephagan ancestors and contradicting the recent proposition of three independent invasions. A monophyletic Hydradephaga is consistently, though not strongly, supported under most analyses, and a parametric bootstrapping test significantly rejects an hypothesis of nonmonophyly. The enigmatic Trachypachidae, which exhibit many similarities to aquatic forms but whose species are entirely terrestrial, were usually recovered as a basal lineage within Geadephaga. Strong evidence opposes the view that terrestrial trachypachids are related to the dytiscoid water beetles.

Treatment goals for atopic dermatitis consist of attempting to eliminate inflammation and infection, hydrating the skin, controlling pruritus, and avoiding exacerbative factors. The aim of this study was to evaluate the effects of adding a moisturizing regimen to a low-potency topical corticosteroid lotion regimen in the treatment of atopic dermatitis. This controlled, randomized, investigator-masked 3-week study was undertaken to compare twice-daily applications of desonide lotion 0.05% alone with twice-daily applications of desonide lotion 0.05% plus three-times-daily applications of a moisturizing cream. The efficacy variables assessed included erythema, dryness or scaling, pruritus, excoriations, lichenification, oozing or crusting, and induration or papules. Administration of desonide lotion alone created statistically significant improvement in total sign and symptom scores. The addition of a moisturizer to the treatment regimen produced additional statistically significant improvement in total sign and symptom scores, physicians' global assessments of improvement, and most of the individual efficacy variables. Results of this study suggest that the addition of a moisturizer to a low-potency corticosteroid lotion in separate regimens was effective in treating the signs and symptoms of mild-to-moderate atopic dermatitis.

Hippocampal sclerosis of aging (HS-Aging) is a causative factor in a large proportion of elderly dementia cases. The current definition of HS-Aging rests on pathologic criteria: neuronal loss and gliosis in the hippocampal formation that is out of proportion to AD-type pathology. HS-Aging is also strongly associated with TDP-43 pathology. HS-Aging pathology appears to be most prevalent in the oldest-old: autopsy series indicate that 5–30 % of nonagenarians have HS-Aging pathology. Among prior studies, differences in study design have contributed to the study-to-study variability in reported disease prevalence. The presence of HS-Aging pathology correlates with significant cognitive impairment which is often misdiagnosed as AD clinically. The antemortem diagnosis is further confounded by other diseases linked to hippocampal atrophy including frontotemporal lobar degeneration and cerebrovascular pathologies. Recent advances characterizing the neurocognitive profile of HS-Aging patients have begun to provide clues that may help identify living individuals with HS-Aging pathology. Structural brain imaging studies of research subjects followed to autopsy reveal hippocampal atrophy that is substantially greater in people with eventual HS-Aging pathology, compared to those with AD pathology alone. Data are presented from individuals who were followed with neurocognitive and neuroradiologic measurements, followed by neuropathologic evaluation at the University of Kentucky. Finally, we discuss factors that are hypothesized to cause or modify the disease. We conclude that the published literature on HS-Aging provides strong evidence of an important and under-appreciated brain disease of aging. Unfortunately, there is no therapy or preventive strategy currently available.

The Foxos are key effectors of the PI3K/Akt signaling pathway and regulate diverse physiologic processes. Two of these factors, Foxo1 and Foxo3, serve specific roles in reproduction in the mouse. Foxo3 is required for suppression of primordial follicle activation in females, while Foxo1 regulates spermatogonial stem cell maintenance in males. In the mouse ovary, Foxo1 is highly expressed in somatic cells (but not in oocytes), suggesting an important functional role for Foxo1 in these cells. Given that invertebrate model species such as Caenorhabditis elegans and Drosophila melanogaster harbor a single ancestral Foxo homolog, these observations suggest that gene duplication conferred a selective advantage by permitting the Foxos to adopt distinct roles in oogenesis and spermatogenesis. Our objective was to determine if the remarkably specific expression patterns of Foxo1 and Foxo3 in mouse gonads (and, by inference, Foxo function) are conserved in diverse mammalian species. Western blotting was used to validate isoform-specific antibodies in rodents, companion animals, farm animals, nonhuman primates, and humans. Following validation of each antibody, immunohistochemistry was performed to ascertain Foxo1 and Foxo3 gonadal expression patterns. While Foxo1 expression in spermatogonia and granulosa cells was conserved in each species evaluated, Foxo3 expression in oocytes was not. Our findings suggest that Foxo3 is not uniquely required for primordial follicle maintenance in nonrodent species and that other Foxos, particularly Foxo1, may contribute to oocyte maintenance in a functionally redundant manner.

A substantial body of work exists describing timing of migration and hibernation among bats in eastern North America, but less is known about these events among bats inhabiting the Rocky Mountain region. Yellowstone National Park is a geothermally influenced landscape comprised of diverse habitats, creating the opportunity for unique behaviors to develop among local bat populations. We identified the timing of migration for the local bat community and determined if bats overwinter in Yellowstone. To accomplish this, we radiotracked 7 little brown myotis ( Myotis lucifugus ), 5 western long-eared myotis ( M. evotis ), 4 big brown bats ( Eptesicus fuscus ), 4 silver-haired bats ( Lasionycteris noctivagans ), and 1 western small-footed myotis ( M. ciliolabrum ) from August to September 2010 and September to October 2011. We also used acoustic detectors to record bat activity from November through April 2011–2014 and sampled abundance of nocturnal insects using black-light traps from 2011 to 2012. Although availability of insects declined rapidly during August and afterward, several bat species remained active throughout autumn and winter. Bat activity was recorded during all months, even during periods of extreme cold. Radiotagged big brown bats, little brown myotis, and western small-footed myotis remained active in the study area throughout October, after the 1st snowfall of the season. While data for activity patterns in late autumn and winter prevented an estimation of the onset of hibernation, spring emergence occurred in April despite persistence of winter conditions. These data provide insights into the migration and hibernation strategies of bat populations in the Rocky Mountains and highlight gaps in our understanding of seasonal changes in these species.

NSCLC (non-small cell lung cancer) often exhibits resistance to paclitaxel treatment. Identifying the elements regulating paclitaxel response will advance efforts to overcome such resistance in NSCLC therapy. Using in vitro approaches, we demonstrated that over-expression of the microRNA miR-337-3p sensitizes NCI-H1155 cells to paclitaxel, and that miR-337-3p mimic has a general effect on paclitaxel response in NSCLC cell lines, which may provide a novel adjuvant strategy to paclitaxel in the treatment of lung cancer. By combining in vitro and in silico approaches, we identified STAT3 and RAP1A as direct targets that mediate the effect of miR-337-3p on paclitaxel sensitivity. Further investigation showed that miR-337-3p mimic also sensitizes cells to docetaxel, another member of the taxane family, and that STAT3 levels are significantly correlated with taxane resistance in lung cancer cell lines, suggesting that endogenous STAT3 expression is a determinant of intrinsic taxane resistance in lung cancer. The identification of a miR-337-3p as a modulator of cellular response to taxanes, and STAT3 and RAP1A as regulatory targets which mediate that response, defines a novel regulatory pathway modulating paclitaxel sensitivity in lung cancer cells, which may provide novel adjuvant strategies along with paclitaxel in the treatment of lung cancer and may also provide biomarkers for predicting paclitaxel response in NSCLC.

A new lotion formulation of 0.05% desonide was compared with 0.05% desonide cream in a single (investigator)-blind, randomized, paired bilateral comparison study in the treatment of eczematous dermatitis. Eighteen patients with bilateral dermatitis, who would normally be treated with a low- to mid-potency topical corticosteroid, were eligible for entry into the study. A 7-day washout period was required for any potentially interfering therapy. Both treatments were given three times daily for up to 3 weeks. Patients were seen at study entry (baseline), and at 1, 2, and 3 weeks of treatment. Fifteen (83%) of the 18 patients completed the study. Of those, 12 patients completed all 3 weeks of treatment and 3 patients cleared bilaterally before week 3. Two patients were lost to follow-up and 1 patient whose condition worsened was dropped from the study early in order to receive alternative treatment. The overall mean severity score was significantly decreased ( P = 0.0002) for both the lotion and the cream from moderate at baseline to mild, with no statistically significant differences between the two treatments. Few patients experienced stinging or burning (4 of 18) or general irritation (2 of 18). Based on the results of this study, we conclude that desonide lotion is a safe and effective medication for treating the signs and symptoms of eczematous dermatitis and is equal in efficacy to desonide in a cream formulation.

A new lotion formulation of 0.05% desonide was compared with its vehicle and with 0.05% desonide cream in a double-blind, randomized, parallel study in the treatment of psoriasis. Eighty patients with mild to moderate psoriasis, normally treatable with a low-potency topical corticosteroid, were enrolled in the study. All treatments were applied three times daily for up to 3 weeks, with weekly examinations. In both the lotion and cream treatment groups, 93% of patients completed the study. Only 75% of patients in the vehicle group completed the study. There was no statistically significant difference between the lotion and the cream at any of the three visits. Both treatments were well tolerated by the patients. Only 3 of 80 patients reported mild irritation, consisting of two cases of transient stinging and one of erythema without symptoms. Both active treatment groups showed significant improvement from baseline and over the vehicle group, reached a global improvement of 50% to 75% by weeks 2 and 3 compared with

Thirty patients with seborrheic dermatitis of the scalp were evaluated in this double-blind, randomized, bilateral study comparing 0.05% desonide cream with 1.0% hydrocortisone cream. Postauricular areas were treated twice daily for 8 weeks. Clinical evaluations at 1, 2, 4, 6, and 8 weeks included a quantitative assessment of telangiectasia; gradings of epidermal thinning, striae, and shiny surface appearance; and notation of presence or absence of hair loss, muscle waste, fat waste, loss of elasticity or skin markings, and purpura or bruising. No statistical differences were detected between the two products at the end of the 8-week treatment period. There were no signs of atrophy caused by either corticosteroid. The total number of telangiectasia, while few in number, was greater on the hydrocortisone-treated sites than on the desonide-treated sites.

We describe a new microsporidian species, Encephalitozoon romaleae n. sp., isolated from an invertebrate host, the grasshopper Romalea microptera, collected near Weeks Island, Louisiana, and Jacksonville, Florida. This microsporidian is characterized by specificity to the gastric caecae and midgut tissues of the host and a life cycle that is nearly identical to that of Encephalitozoon hellem and Encephalitozoon cuniculi. Mature spores are larger (3.97 × 1.95 µm) than those of other Encephalitozoon species. Polar filament coils number 7 to 8 in a single row. Analysis of the small subunit (SSU) rDNA shows that E. romaleae fits well into the Encephalitozoon group and is a sister taxon to E. hellem. This is the first Encephalitozoon species that has been shown to complete its life cycle in an invertebrate host.

Lung cancer is the leading cause of cancer-related deaths, with the majority of deaths due to failed therapy from tumor drug resistance. Third-generation chemotherapeutic agents represent the standard first-line treatment for advanced small cell (SCLC) and non-small cell (NSCLC) lung cancer patients. Response rates are poor (20-40%) with a median survival of 8-10 months. In an unbiased and comprehensive approach, we have combined a high-throughput screening platform with a library of chemically synthesized microRNA mimics and inhibitors. We have used this platform to identify mimics and inhibitors that reduce cell viability in general, and those that specifically sensitize cells to taxanes. We have identified several miRNAs for which over-expression or inhibition has a dramatic and selective effect on cell viability or drug response. We have demonstrated that miR-337-3p mimic sensitizes NSCLC cells to taxanes. By combining in vitro and in silico approaches, we identified STAT3 and RAP1A as direct targets that mediate the effect of miR-337-3p by enhancing taxane-induced arrest in the G2 phase of the cell cycle. We have identified an inhibitor of miR-139-5p as a potent and selective regulator of SCLC cell viability. Inhibiting miR-139-5p decreases SCLC cell viability by over 80%, but has a minimal cytotoxic effect on that of NSCLCs or immortalized human bronchial epithelial cells. We are currently investigating the targets of miR-139-5p that mediate its effect on SCLC cell viability. We also identified miR-10a inhibitor as increasing cell viability, with the converse observed for miR-10a mimic, suggesting that miR-10a acts as a tumor suppressor gene by directly decreasing expression of gene(s) that promote cell survival and growth. Manipulation of miR-10a levels also resulted in significant changes in both mRNA and protein levels of its predicted target, the catalytic subunit of phosphatidylinositol 3-kinase (PI3K), which has been shown to play a major role in proliferation and survival in a number of human cancers and is a significant therapeutic target. We have identified miR-337-3p as a regulator of taxane sensitivity, and miR-10a and miR-139-5p as modulators of cell viability. Increasing levels of miR-337-3p and inhibiting miR-10a and miR-139-5p may therefore provide novel therapeutic tools for the treatment of NSCLC and SCLC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 140. doi:1538-7445.AM2012-140

We are addressing the questions of whether microRNAs (miRNAs) play a functional role in modulating drug sensitivity of lung cancer cells, and whether miRNA expression levels can be manipulated to increase drug sensitivity in lung cancer treatment. Using a combination of in silico and in vitro approaches, we identified miR-337-3p as a modulator of paclitaxel sensitivity in NSCLC cell lines where over-expression of miR-337-3p sensitizes NSCLC NCI-H1155 cells to paclitaxel (>2 fold) and docetaxel (>10 fold) by enhancing taxane-induced mitotic arrest. Of several possible targets of miR-337-3p we found that Stat3 and Rap1A are the direct targets responsible for mediating miR-337-3p sensitization to paclitaxel. In studies of multiple NSCLC lines we found that miR-337-3p can, in general, sensitize NSCLC lines to paclitaxel, and that Stat3 expression is significantly correlated with paclitaxel resistance in NSCLC lines, suggesting that tumor Stat3 expression is an intrinsic determinant and biomarker for paclitaxel response. We conclude we have discovered a novel pathway modulating NSCLC paclitaxel sensitivity, which involves the down-regulation of Stat3 and Rap1A expression by miR-337-3p. These findings have prompted: our ongoing studies of patient samples annotated for miR-337-3p, Stat3, and Rap1A expression and response to taxane therapy; preclinical testing of a miR-337-3p mimic as an adjuvant to taxanes for NSCLC therapy; and further tests of this pathway to provide both new therapeutic targets and biomarkers predictive of response for NSCLC taxane based therapy. This research was supported by NIH R01 CA129632 from the National Cancer Institute and by P50 CA70907 from the UT Southwestern/MD Anderson Cancer Center Lung Specialized Program of Research Excellence. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4709. doi:10.1158/1538-7445.AM2011-4709

We identified 25 studies published between 1988 and 2001 that measured characteristics of roosting sites of tree-roosting bats, and where measures were compared to characteristics of random or available locations. The most frequently measured habitat characteristics were roost-tree diameter (n = 23), roost-tree height (21), roost-tree canopy cover (16), roost height (14), and slope (10). Habitat characteristics of the roost tree itself were measured more frequently than stand or landscape characteristics; a total of 31 different habitat characteristics was used to describe stand or landscape conditions as opposed to 23 different habitat characteristics used to describe features of the roost tree. The overall mean (± SE) number of habitat characteristics examined per study was 8.0 ± 1.1, with an average of 4.2 ± 0.7 characteristics reported to be significant (P < 0.05). Mean estimated effect size, or the absolute value of the difference between means divided by the population standard deviation, of habitat characteristics ranged from 0.83 to 1.52. A sample size of 11 radio-tagged bats was sufficient to achieve acceptable power, i.e., 0.80, for all habitat characteristics examined when only using the upper limit of the 95% confidence intervals for estimated effect sizes. In contrast, a sample size of 39 radio-tagged bats was sufficient in achieving the same level of power for only 50% of the habitat characteristics evaluated at the lower end of the 95% confidence intervals. We encourage researchers to conduct pilot studies, and estimate effect sizes and variances to assess the level of sampling effort required to evaluate habitat characteristics in studies of tree-roosting bats.