A Multiscale Investigation of Habitat Use and Within-river Distribution of Sympatric Sand Darter Species

The western sand darter Ammocrypta clara, and eastern sand darter Ammocrypta pellucida are sand-dwelling fishes of conservation concern. Past research has emphasized the importance of studying individual populations of conservation concern, while recent research has revealed the importance of incorporating landscape scale processes that structure habitat mosaics and local populations. We examined habitat use and distributions of western and eastern sand darters in the lower Elk River of West Virginia. At the sandbar habitat use scale, western sand darters were detected in sandbars with greater area, higher proportions of coarse grain sand and faster bottom current velocity, while the eastern sand darter used a wider range of sandbar habitats. The landscape scale analysis revealed that contributing drainage area was an important predictor for both species, while sinuosity, which presumably represents valley type also contributed to the western sand darter’s habitat suitability. Sandbar quality (area, grain size, and velocity) and fluvial geomorphic variables (drainage area and valley type) are likely key driving factors structuring sand darter distributions in the Elk River. This multiscale study of within-river species distribution and habitat use is unique, given that only a few sympatric populations are known of western and eastern sand darters

p120-Catenin Down-Regulation and Epidermal Growth Factor Receptor Overexpression Results in a Transformed Epithelium That Mimics Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy with a poor prognosis due to its highly invasive and metastatic potential. The molecular pathogenesis underlying the invasive mechanism of ESCC is not well known because of the lack of existing models to study this disease. p120-Catenin (p120ctn) and the epidermal growth factor receptor (EGFR) have each been implicated in several cancers, including ESCC. p120ctn is down-regulated in 60% of ESCC tumors, whereas EGFR is the most commonly overexpressed oncogene in ESCC. For these reasons, we investigated the cooperation between p120ctn and EGFR and its effect on ESCC invasion. We show that p120ctn down-regulation is commonly associated with EGFR overexpression. By using a three-dimensional culture system, we demonstrate that the inverse relationship between p120ctn and EGFR has biological implications. Specifically, p120ctn down-regulation coupled with EGFR overexpression in human esophageal keratinocytes (EPC1-PE) was required to promote invasion. Morphological comparison of EPC1-PE cells grown in three-dimensional culture and human ESCC revealed identical features, including significantly increased cellularity, nuclear grade, and proliferation. Molecular characteristics were measured by keratin expression patterns, which were nearly identical between EPC1-PE cells in three-dimensional culture and ESCC samples. Altogether, our analyses have demonstrated that p120ctn down-regulation and EGFR overexpression are able to mimic human ESCC in a relevant three-dimensional culture model

The Neuromodulator Adenosine Regulates Oligodendrocyte Migration at Motor Exit Point Transition Zones

During development, oligodendrocyte progenitor cells (OPCs) migrate extensively throughout the spinal cord. However, their migration is restricted at transition zones (TZs). At these specialized locations, unique glial cells in both zebrafish and mice play a role in preventing peripheral OPC migration, but the mechanisms of this regulation are not understood. To elucidate the mechanisms that mediate OPC segregation at motor exit point (MEP) TZs, we performed an unbiased small-molecule screen. Using chemical screening and in vivo imaging, we discovered that inhibition of A2a adenosine receptors (ARs) causes ectopic OPC migration out of the spinal cord. We provide in vivo evidence that neuromodulation, partially mediated by adenosine, influences OPC migration specifically at the MEP TZ. This work opens exciting possibilities for understanding how OPCs reach their final destinations during development and identifies mechanisms that could promote their migration in disease

Energy density and weight change in a long-term weight-loss trial

<p>Abstract</p> <p>Background</p> <p>Health risks linked to obesity and the difficulty most have in achieving weight loss underscore the importance of identifying dietary factors that contribute to successful weight loss.</p> <p>Methods</p> <p>This study examined the association between change in dietary energy density and weight loss over time. Subjects were 213 men and women with BMI of 30–39 kg/m²and without chronic illness enrolled in 2004 in a randomized trial evaluating behavioral treatments for long-term weight loss. Subjects completed a 62-item food frequency questionnaire at baseline and at 6, 12, and 18 months.</p> <p>Results</p> <p>Pearson correlations between BMI and energy density (kcals/g of solid food) at baseline were not significantly different from zero (r = -0.02, p = 0.84). In a longitudinal analysis, change in energy density was strongly related to change in BMI. The estimated β for change in BMI (kg/m²) of those in the quartile representing greatest decrease in energy density at 18 months compared to those in the quartile with the least was -1.95 (p = 0.006). The association was especially strong in the first six months (estimated β = -1.43), the period with greatest weight loss (mean change in BMI = -2.50 kg/m²from 0–6 months <it>vs. </it>0.23 kg/m²from 12–18 months) and the greatest contrast with respect to change in energy density.</p> <p>Conclusion</p> <p>Decreased energy density predicted weight loss in this 18 month weight loss study. These findings may have important implications for individual dietary advice and public health policies targeting weight control in the general population</p

Ovine Fetal Immune Response to Cache Valley Virus Infection

Cache Valley virus (CVV)-induced malformations have been previously reproduced in ovine fetuses. To evaluate the development of the antiviral response by the early, infected fetus, before the development of immunocompetency, ovine fetuses at 35 days of gestation were inoculated in utero with CVV and euthanized at 7, 10, 14, 21, and 28 days postinfection. The antiviral immune response in immature fetuses infected with CVV was evaluated. Gene expression associated with an innate, immune response was quantified by real-time quantitative PCR. The upregulated genes in infected fetuses included ISG15, Mx1, Mx2, IL-1, IL-6, TNF-α, TLR-7, and TLR-8. The amount of Mx1 protein, an interferon-stimulated GTPase capable of restricting growth of bunyaviruses, was elevated in the allantoic and amniotic fluid in infected fetuses. ISG15 protein expression was significantly increased in target tissues of infected animals. B lymphocytes and immunoglobulin-positive cells were detected in lymphoid tissues and in the meninges of infected animals. These results demonstrated that the infected ovine fetus is able to initiate an innate and adaptive immune response much earlier than previously known, which presumably contributes to viral clearance in infected animals

Human Alcohol-Microbiota Mice have Increased Susceptibility to Bacterial Pneumonia

Preclinical studies have shown that chronic alcohol abuse leads to alterations in the gastrointestinal microbiota that are associated with behavior changes, physiological alterations, and immunological effects. However, such studies have been limited in their ability to evaluate the direct effects of alcohol-associated dysbiosis. To address this, we developed a humanized alcoholmicrobiota mouse model to systematically evaluate the immunological effects of chronic alcohol abuse mediated by intestinal dysbiosis. Germ-free mice were colonized with human fecal microbiota from individuals with high and low Alcohol Use Disorders Identification Test (AUDIT) scores and bred to produce human alcohol-associated microbiota or human control-microbiota F1 progenies. F1 offspring colonized with fecal microbiota from individuals with high AUDIT scores had increased susceptibility to Klebsiella pneumoniae and Streptococcus pneumoniae pneumonia, as determined by increased mortality rates, pulmonary bacterial burden, and post-infection lung damage. These findings highlight the importance of considering both the direct effects of alcohol and alcohol-induced dysbiosis when investigating the mechanisms behind alcohol-related disorders and treatment strategies

The Neuromodulator Adenosine Regulates Oligodendrocyte Migration at Motor Exit Point Transition Zones

During development, oligodendrocyte progenitor cells (OPCs) migrate extensively throughout the spinal cord. However, their migration is restricted at transition zones (TZs). At these specialized locations, unique glial cells in both zebrafish and mice play a role in preventing peripheral OPC migration, but the mechanisms of this regulation are not understood. To elucidate the mechanisms that mediate OPC segregation at motor exit point (MEP) TZs, we performed an unbiased small-molecule screen. Using chemical screening and in vivo imaging, we discovered that inhibition of A2a adenosine receptors (ARs) causes ectopic OPC migration out of the spinal cord. We provide in vivo evidence that neuromodulation, partially mediated by adenosine, influences OPC migration specifically at the MEP TZ. This work opens exciting possibilities for understanding how OPCs reach their final destinations during development and identifies mechanisms that could promote their migration in disease

Novel downstream process and analytical tools developed for Influenza VLP vaccine

Vaccination remains the most effective way to prevent the infection with Influenza viruses. However, their constant antigenic drift implies that current human Influenza vaccines need to be annually updated with high inherent costs. Virus-like particles (VLPs) have become widely used as vaccine candidates because of their versatility, immunogenicity, and safety profile. In this iBET project we are attempting to produce a candidate for a universal vaccine for which 35 different VLPs (mono, trivalent and pentavalent) were purified. Here we describe three recent advances on Influenza VLPs bioprocessing: two new analytical tools and the development of an integrated all filtration purification process, inserted in the “anything but chromatography” concept. The first method is a label-free tool that uses Biolayer interferometry technology applied on an Octet platform to quantify Influenza VLPs at all stages of DSP. Human and avian sialic acid receptors were used, in order to quantify hemagglutinin (HA) content in several mono- and multivalent Influenza VLP strains. The applied method was able to detect and quantify HA from crude sample up to final VLP product with high throughput, real-time results and improved detection limits, when compared to traditional approaches, crucial for in-line monitoring of DSP. Using a click-chemistry approach that involves Azidohomoalanine incorporation and functionalization, Influenza VLPs were selectively and fluorescently tagged. Taking into account that this chemical tag does not affect particle size, charge and biological activity we report here a valuable tool to online/at-line product monitoring during DSP optimization of virus related biopharmaceuticals. Moreover, using this tool coupled with FACS we were able to discriminate between VLPs and baculovirus, the major impurity of the system. The proposed all-filtration process will be described, with special focus on the clarification stage, followed by multiple ultrafiltration and diafiltration steps to achieve the needed concentration and purity specifications. Using this all-filtration platform, we are able to speed up the time process, to improve the scale-up and to reduce costs due to the removal of chromatographic steps

Technical challenges of working with extracellular vesicles

Extracellular Vesicles (EVs) are gaining interest as central players in liquid biopsies, with potential applications in diagnosis, prognosis and therapeutic guidance in most pathological conditions. These nanosized particles transmit signals determined by their protein, lipid, nucleic acid and sugar content, and the unique molecular pattern of EVs dictates the type of signal to be transmitted to recipient cells. However, their small sizes and the limited quantities that can usually be obtained from patient-derived samples pose a number of challenges to their isolation, study and characterization. These challenges and some possible options to overcome them are discussed in this review

Analysis of health related quality of life (HRQoL) of patients with clinically localized prostate cancer, one year after treatment with external beam radiotherapy (EBRT) alone versus EBRT and high dose rate brachytherapy (HDRBT)

<p>Abstract</p> <p>Purpose</p> <p>Prostate cancer is the leading form of cancer diagnosed among North American men. Most patients present with localized disease, which can be effectively treated with a variety of different modalities. These are associated with widely different acute and late effects, which can be both physical and psychological in nature. HRQoL concerns are therefore important for these patients for selecting between the different treatment options.</p> <p>Materials and methods</p> <p>One year after receiving radiotherapy for localised prostate cancer 117 patients with localized prostate cancer were invited to participate in a quality of life (QoL) self reported survey. 111 patients consented and participated in the survey, one year after completion of their treatment. 88 patients received EBRT and 23 received EBRT and HDRBT. QoL was compared in the two groups by using a modified version of Functional Assessment of Cancer Therapy-Prostate (FACT-P) survey instrument.</p> <p>Results</p> <p>One year after completion of treatment, there was no significant difference in overall QoL scores between the two groups of patients. For each component of the modified FACT-P survey, i.e. physical, social/family, emotional, and functional well-being; there were no statistically significant differences in the mean scores between the two groups.</p> <p>Conclusion</p> <p>In prostate cancer patients treated with EBRT alone versus combined EBRT and HDRBT, there was no significant difference in the QoL scores at one year post-treatment.</p