Population level dynamics of grasshopper sparrow populations breeding on reclaimed mountaintop mines in West Virginia

During 2001 and 2002, I surveyed three mountaintop mining/valley fill (MTMVF) complexes in southern West Virginia to determine vegetation characteristics important to nest site selection and to estimate nest success for Grasshopper Sparrow populations inhabiting these complexes. I also performed genetic analyses to assess overall population structure, mating system, parentage, kinship, and gender of individuals comprising these populations. A total of 415 grasshopper sparrows were captured and systematic searches of study plots produced 75 active nests. Nest survival for 2001--2002 breeding season (33%) is comparable to survival rates previously reported in the literature. Nest survival rates decreased with increased reclamation age suggesting that vegetation changes and the reduction of bare ground on available grasslands may negatively impact reproductive success. Habitat variables measured at nests and at fixed habitat plots suggest differences in several of the ground cover estimates. Percent green and grass height at 1 m were significantly lower at the nest plots while percent bare ground, percent litter at 1 and 5 m from the nest, grass height at 3 m, shrub stem density, and Robel pole indices at the nest were significantly higher at nest plots. Large reclaimed grassland habitats available on the MTMVF complexes appear sufficient to support breeding populations of grasshopper sparrows; however, habitat will become unsuitable as succession occurs. Genetic analyses suggest low but significant differentiation among mine complexes while the genetic structure of breeding assemblages within mine complexes appears to be homogeneous. The five microsatellite loci screened in this study are robust and appear to be effective in allocating parentage when neither parent is known. Using maximum likelihood methods, I was successful at assigning at least one parent to 80% of the offspring surveyed. The lack of extra-pair paternity within the grasshopper sparrow broods implies a socially and genetically monogamous mating system in this species. Gender assignment data obtained for adult Grasshopper Sparrows by application of the 2550F/2718R primers was in 100% agreement with morphological data collected in the field

Thermographic imaging in sports and exercise medicine: A Delphi study and consensus statement on the measurement of human skin temperature

This is an accepted manuscript of an article published by Elsevier in Journal of Thermal Biology on 18/07/2017, available online: https://doi.org/10.1016/j.jtherbio.2017.07.006 The accepted version of the publication may differ from the final published version.© 2017 Elsevier Ltd The importance of using infrared thermography (IRT) to assess skin temperature (tsk) is increasing in clinical settings. Recently, its use has been increasing in sports and exercise medicine; however, no consensus guideline exists to address the methods for collecting data in such situations. The aim of this study was to develop a checklist for the collection of tsk using IRT in sports and exercise medicine. We carried out a Delphi study to set a checklist based on consensus agreement from leading experts in the field. Panelists (n  =  24) representing the areas of sport science (n = 8; 33%), physiology (n = 7; 29%), physiotherapy (n = 3; 13%) and medicine (n = 6; 25%), from 13 different countries completed the Delphi process. An initial list of 16 points was proposed which was rated and commented on by panelists in three rounds of anonymous surveys following a standard Delphi procedure. The panel reached consensus on 15 items which encompassed the participants’ demographic information, camera/room or environment setup and recording/analysis of tsk using IRT. The results of the Delphi produced the checklist entitled “Thermographic Imaging in Sports and Exercise Medicine (TISEM)” which is a proposal to standardize the collection and analysis of tsk data using IRT. It is intended that the TISEM can also be applied to evaluate bias in thermographic studies and to guide practitioners in the use of this technique.Published versio

Ischemic Stroke Alters Immune Cell Niche and Chemokine Profile in Mice Independent of Spontaneous Bacterial Infection

Background The aim of this study is to report the long-term efficacy and safety of thoracoscopic epicardial left atrial ablation (TELA) in patients with paroxysmal atrial fibrillation (AF). Methods This was a retrospective review of medical records. We included all patients diagnosed with paroxysmal AF who underwent TELA at our institution between 04/2011 and 06/2017. TELA included pulmonary vein isolation, LA dome lesions and LA appendage exclusion. All (n = 55) patients received an implantable loop recorder (ILR), 30 days post-operatively. Antiarrhythmic and anticoagulation therapy were discontinued at 90 and 180 days postoperatively, respectively, if patients were free of AF recurrence. Failure was defined as ≥two minutes of continuous AF, or atrial tachycardia. Results Fifty-five patients (78% males, mean age = 61.6 years) qualified for the study. The average duration in AF was 3.64 +/− 3.4 years, mean CHA2DS2-VASc Score was 2.0 +/− 1.6. The procedure was attempted in 57 patients and completed successfully in 55 (96.5%). Two patients experienced a minor pulmonary vein bleed that was managed conservatively. Post procedure, one patient experienced pulmonary edema, another experienced a pneumothorax requiring a chest tube and another experienced acute respiratory distress syndrome resulting in longer hospitalization. Otherwise, there were no major procedural complications. Success rates were 89.1% (n = 49/55), 85.5% (n = 47/55) and 76.9% (n = 40/52) at 6, 12 and 24 months, respectively. In the multivariate cox-proportional hazard model, survival at the mean of covariates was 86 and 74% at 12 and 24 months, respectively. Conclusion In this single center experience, TELA was a safe and efficacious procedure for patients with paroxysmal AF

Src Binds Cortactin Through An Sh2 Domain Cystine-Mediated Linkage

Tyrosine-kinase-based signal transduction mediated by modular protein domains is critical for cellular function. The Src homology (SH)2 domain is an important conductor of intracellular signaling that binds to phosphorylated tyrosines on acceptor proteins, producing molecular complexes responsible for signal relay. Cortactin is a cytoskeletal protein and tyrosine kinase substrate that regulates actin-based motility through interactions with SH2-domain-containing proteins. The Src kinase SH2 domain mediates cortactin binding and tyrosine phosphorylation, but how Src interacts with cortactin is unknown. Here we demonstrate that Src binds cortactin through cystine bonding between Src C185 in the SH2 domain within the phosphotyrosine binding pocket and cortactin C112/246 in the cortactin repeats domain, independent of tyrosine phosphorylation. Interaction studies show that the presence of reducing agents ablates Src-cortactin binding, eliminates cortactin phosphorylation by Src, and prevents Src SH2 domain binding to cortactin. Tandem MS/MS sequencing demonstrates cystine bond formation between Src C185 and cortactin C112/246. Mutational studies indicate that an intact cystine binding interface is required for Src-mediated cortactin phosphorylation, cell migration, and pre-invadopodia formation. Our results identify a novel phosphotyrosine-independent binding mode between the Src SH2 domain and cortactin. Besides Src, one quarter of all SH2 domains contain cysteines at or near the analogous Src C185 position. This provides a potential alternative mechanism to tyrosine phosphorylation for cysteine-containing SH2 domains to bind cognate ligands that may be widespread in propagating signals regulating diverse cellular functions

Depletion of Macrophages Improves Therapeutic Response to Gemcitabine in Murine Pancreas Cancer.

BACKGROUND: The tumor microenvironment (TME) is composed of fibro-inflammatory cells and extracellular matrix (ECM) components. However, the exact contribution of the various TME compartments towards therapeutic response is unknown. Here, we aim to dissect the specific contribution of tumor-associated macrophages (TAMs) towards drug delivery and response in pancreatic ductal adenocarcinoma (PDAC). METHODS: The effect of gemcitabine was assessed in human and murine macrophages, human pancreatic stellate cells (hPSCs), and tumor cells (L3.6pl, BxPC3 and KPC) in vitro. The drug metabolism of gemcitabine was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Preclinical studies were conducted using KrasG12D;p48-Cre and KrasG12D;p53172H;Pdx-Cre mice to investigate gemcitabine delivery at different stages of tumor progression and upon pharmacological TAM depletion. RESULTS: Gemcitabine accumulation was significantly increased in murine PDAC tissue compared to pancreatic intraepithelial neoplasia (PanIN) lesions and healthy control pancreas tissue. In vitro, macrophages accumulated and rapidly metabolized gemcitabine resulting in a significant drug scavenging effect for gemcitabine. Finally, pharmacological TAM depletion enhanced therapeutic response to gemcitabine in tumor-bearing KPC mice. CONCLUSION: Macrophages rapidly metabolize gemcitabine in vitro, and pharmacological depletion improves the therapeutic response to gemcitabine in vivo. Our study supports the notion that TAMs might be a promising therapeutic target in PDAC

Constraints From b→sγb \to s\gamma on the Left-Right Symmetric Model

Recent results from the CLEO Collaboration on both inclusive and exclusive radiative $B$ decays are used to constrain the parameter space of two versions of the Left-Right Symmetric Model. In the first scenario, when the left- and right-handed Cabibbo-Kobayashi-Maskawa mixing matrices are equal, $V_L=V_R$, the radiative $B$ decay data is shown to lead to strong bounds on the $W_L-W_R$ mixing angle that are quite insensitive to either the top quark or $W_R$ mass. The second scenario examined is that of Gronau and Wakaizumi wherein $b$-quark decays proceed only via right-handed currents and $V_L$ and $V_R$ are quite distinct. For this model, the combined constraints from Tevatron $W_R$ searches, the $B$ lifetime, and radiative $B$ decays lead to a very highly restricted allowed range for the $W_L-W_R$ mixing angle.Comment: 16 pages, 9 figures(not included), LaTex, SLAC-PUB-642

Regulation of anti-apoptotic signaling by Kruppel-like factors 4 and 5 mediates lapatinib resistance in breast cancer

The Kruppel-like transcription factors (KLFs) 4 and 5 (KLF4/5) are coexpressed in mouse embryonic stem cells, where they function redundantly to maintain pluripotency. In mammary carcinoma, KLF4/5 can each impact the malignant phenotype, but potential linkages to drug resistance remain unclear. In primary human breast cancers, we observed a positive correlation between KLF4/5 transcript abundance, particularly in the human epidermal growth factor receptor 2 (HER2)-enriched subtype. Furthermore, KLF4/5 protein was rapidly upregulated in human breast cancer cells following treatment with the HER2/epidermal growth factor receptor inhibitor, lapatinib. In addition, we observed a positive correlation between these factors in the primary tumors of genetically engineered mouse models (GEMMs). In particular, the levels of both factors were enriched in the basal-like tumors of the C3(1) TAg (SV40 large T antigen transgenic mice under control of the C3(1)/prostatein promoter) GEMM. Using tumor cells derived from this model as well as human breast cancer cells, suppression of KLF4 and/or KLF5 sensitized HER2-overexpressing cells to lapatinib. Indicating cooperativity, greater effects were observed when both genes were depleted. KLF4/5-deficient cells had reduced basal mRNA and protein levels of the anti-apoptotic factors myeloid cell leukemia 1 (MCL1) and B-cell lymphoma-extra large (BCL-XL). Moreover, MCL1 was upregulated by lapatinib in a KLF4/5-dependent manner, and enforced expression of MCL1 in KLF4/5-deficient cells restored drug resistance. In addition, combined suppression of KLF4/5 in cultured tumor cells additively inhibited anchorage-independent growth, resistance to anoikis and tumor formation in immunocompromised mice. Consistent with their cooperative role in drug resistance and other malignant properties, KLF4/5 levels selectively stratified human HER2-enriched breast cancer by distant metastasis-free survival. These results identify KLF4 and KLF5 as cooperating protumorigenic factors and critical participants in resistance to lapatinib, furthering the rationale for combining anti-MCL1/BCL-XL inhibitors with conventional HER2-targeted therapies

An observational study of temperature and thermal images of surgical wounds for detecting delayed wound healing within four days after surgery

Aim: This study aimed to elucidate the infrared thermal patterns and temperature readings of the surfaces of surgical wounds for detecting delayed wound healing within four days after surgery. Background: The nursing assessment of surgical wounds within the first four days after surgery is commonly based on visual and physical examination. Surgical wounds with delayed healing may be not detected if they do not exhibit signs such as redness or exudate within four days after surgery. Design: This study was conducted using prospective observational design with reference to the STROBE Statement to examine the temperatures of surgical wounds in their natural settings. Methods: Based on convenience sampling, 60 participants admitted to the colorectal surgical ward for enterostoma closure from January to November 2013 were recruited. Results: Although both infected and non-infected surgical wounds exhibited a significant increase in wound temperature from Days 1 to 4, the infected wounds revealed a statistically significantly lower temperature than the non-infected ones. Within the infrared thermal images, the infected wounds presented with partial warming of the skin surrounding and along the incision, suggesting that delayed healing could be identified. Conclusion: This study demonstrates that delayed wound healing can be detected within the first four days after surgery for early intervention of prevention and treatment before discharge

Insights from regional and short-term biodiversity monitoring datasets are valuable: a reply to Daskalova et al. 2021

Reports of major losses in insect biodiversity have stimulated an increasing interest in temporal population changes. Existing datasets are often limited to a small number of study sites, few points in time, a narrow range of land-use intensities and only some taxonomic groups, or they lack standardised sampling. While new monitoring programs have been initiated, they still cover rather short time periods. Daskalova et al. 2021 (Insect Conservation and Diversity, 14, 1-18) argue that temporal trends of insect populations derived from short time series are biased towards extreme trends, while their own analysis of an assembly of shorter- and longer-term time series does not support an overall insect decline. With respect to the results of Seibold et al. 2019 (Nature, 574, 671–674) based on a 10-year multi-site time series, they claim that the analysis suffers from not accounting for temporal pseudoreplication. Here, we explain why the criticism of missing statistical rigour in the analysis of Seibold et al. (2019) is not warranted. Models that include ‘year’ as random effect, as suggested by Daskalova et al. (2021), fail to detect non-linear trends and assume that consecutive years are independent samples which is questionable for insect time-series data. We agree with Daskalova et al. (2021) that the assembly and analysis of larger datasets is urgently needed, but it will take time until such datasets are available. Thus, short-term datasets are highly valuable, should be extended and analysed continually to provide a more detailed understanding of insect population changes under the influence of global change, and to trigger immediate conservation actions