Two (or more) viruses in one bat: a systematic quantitative literature review of viral coinfection in bats

Viral coinfection is an important topic in pathogen dynamics, and can increase viral shedding and change disease outcomes. As bats are carriers of important zoonoses, such as the SARS coronaviruses, rabies, and other deadly viruses, knowing more about their coinfection dynamics is important. This quantitative systematic literature review sought to show how many papers reported bat viral coinfections, and created three databases. The first database, the SQLR database was based on searches for coinfections. The second database, the Astrovirus database was to determine how much of the literature was being missed by examining a single viral family more in depth and determining how many papers were identified in the SQLR database. The third database focused on Dependoparvovirus, a viral genus which has been thought to require coinfection in the past. A total of 725 coinfected bats became a part of the SQLR database. The studies were mostly done in Asia, and a few trends in bat and viral families appeared. Bat field virology has a lot of valuable data, and not all of it is reported in an accessible way

Proinflammatory cytokines are elevated in serum of patients with multiple system atrophy.

Despite several lines of evidence from preclinical and post-mortem studies suggesting that inflammation is involved in Multiple System Atrophy (MSA), no previous studies have measured peripheral indices of inflammation in MSA patients

The Light vs. Dark Triad of Personality: Contrasting Two Very Different Profiles of Human Nature

While there is a growing literature on “dark traits” (i.e., socially aversive traits), there has been a lack of integration with the burgeoning research literature on positive traits and fulfilling and growth-oriented outcomes in life. To help move the field toward greater integration, we contrasted the nomological network of the Dark Triad (a well-studied cluster of socially aversive traits) with the nomological network of the Light Triad, measured by the 12-item Light Triad Scale (LTS). The LTS is a first draft measure of a loving and beneficent orientation toward others (“everyday saints”) that consists of three facets: Kantianism (treating people as ends unto themselves), Humanism (valuing the dignity and worth of each individual), and Faith in Humanity (believing in the fundamental goodness of humans). Across four demographically diverse samples (N = 1,518), the LTS demonstrated excellent reliability and validity, predicting life satisfaction and a wide range of growth-oriented and self-transcendent outcomes above and beyond existing measures of personality. In contrast, the Dark Triad was negatively associated with life satisfaction and growth-oriented outcomes, and showed stronger linkages to selfish, exploitative, aggressive, and socially aversive outcomes. This exploratory study of the contrasting nomological networks of the Light vs. Dark Triad provides several ways forward for more principled and data driven approaches to explore both the malevolent and beneficent sides of human nature

Oncoprotein DEK as a tissue and urinary biomarker for bladder cancer

<p>Abstract</p> <p>Background</p> <p>Bladder cancer is a significant healthcare problem in the United States of America with a high recurrence rate. Early detection of bladder cancer is essential for removing the tumor with preservation of the bladder, avoiding metastasis and hence improving prognosis and long-term survival. The objective of this study was to analyze the presence of DEK protein in voided urine of bladder cancer patients as a urine-based bladder cancer diagnostic test.</p> <p>Methods</p> <p>We examined the expression of DEK protein by western blot in 38 paired transitional cell carcinoma (TCC) bladder tumor tissues and adjacent normal tissue. The presence of DEK protein in voided urine was analyzed by western blot in 42 urine samples collected from patients with active TCC, other malignant urogenital disease and healthy individuals.</p> <p>Results</p> <p>The DEK protein is expressed in 33 of 38 bladder tumor tissues with no expression in adjacent normal tissue. Based on our sample size, DEK protein is expressed in 100% of tumors of low malignant potential, 92% of tumors of low grade and in 71% of tumors of high grade. Next, we analyzed 42 urine samples from patients with active TCC, other malignant urogenital disease, non-malignant urogenital disease and healthy individuals for DEK protein expression by western blot analysis. We are the first to show that the DEK protein is present in the urine of bladder cancer patients. Approximately 84% of TCC patient urine specimens were positive for urine DEK.</p> <p>Conclusion</p> <p>Based on our pilot study of 38 bladder tumor tissue and 42 urine samples from patients with active TCC, other malignant urogenital disease, non-malignant urogenital disease and healthy individuals; DEK protein is expressed in bladder tumor tissue and voided urine of bladder cancer patients. The presence of DEK protein in voided urine is potentially a suitable biomarker for bladder cancer and that the screening for the presence of DEK protein in urine can be explored as a noninvasive diagnostic test for bladder cancer.</p

Newly discovered mutations in the GALNT3 gene causing autosomal recessive hyperostosis-hyperphosphatemia syndrome

Background and purpose Periosteal new bone formation and cortical hyperostosis often suggest an initial diagnosis of bone malignancy or osteomyelitis. In the present study, we investigated the cause of persistent bone hyperostosis in the offspring of two consanguineous parents

Diversification of T Cell Responses to Carboxy-terminal Determinants within the 65-kD Heat-shock Protein Is Involved in Regulation of Autoimmune Arthritis

The T cell response to the 65-kD mycobacterial heat-shock protein (Bhsp65) has been implicated in the pathogenesis of autoimmune arthritis. Adjuvant arthritis (AA) induced in the Lewis rat (RT-1l) by injection of Mycobacterium tuberculosis serves as an experimental model for human rheumatoid arthritis (RA). However, the immunological basis of regulation of acute AA, or of susceptibility/resistance to AA is not known. We have defined the specificity of the proliferative T cell responses to Bhsp65 during the course of AA in the Lewis rat. During the early phase of the disease (6–9 d after onset of AA), Lewis rats raised T cell responses to many determinants within Bhsp65, spread throughout the molecule. Importantly, in the late phase of the disease (8–10 wk after onset of AA), there was evidence for diversification of the T cell responses toward Bhsp65 carboxy-terminal determinants (BCTD) (namely, 417–431, 441–455, 465–479, 513–527, and 521–535). Moreover, arthritic rats in the late phase of AA also raised vigorous T cell responses to those carboxy-terminal determinants within self(rat) hsp65 (Rhsp65) that correspond in position to the above BCTD. These results suggest that the observed diversification is possibly triggered in vivo by induction of self(Rhsp65)-reactive T cells. Interestingly, another strain of rat, the Wistar Kyoto (WKY/NHsd) rat (RT-1l), with the same major histocompatibility complex class II molecules as the Lewis rat, was found to be resistant to AA. In WKY rats, vigorous responses to the BCTD, to which the Lewis rat responded only in the late phase of AA, were observed very early, 10 d after injection of M. tuberculosis. Strikingly, pretreatment with the peptides comprising the set of BCTD, but not its amino-terminal determinants, provided significant protection to naive Lewis rats from subsequent induction of AA. Thus, T cell responses to the BCTD are involved in regulating inflammatory arthritis in the Lewis rat and in conferring resistance to AA in the WKY rat. These results have important implications in understanding the pathogenesis of RA and in devising new immunotherapeutic strategies for this disease

Increased expression of transcription factor TFAP2α correlates with chemosensitivity in advanced bladder cancer

<p>Abstract</p> <p>Background</p> <p>The standard treatment for patients with advanced transitional cell carcinoma of the bladder is platin based chemotherapy. Only approximately 50% of the patients respond to chemotherapy. Therefore, molecular predictive markers for identification of chemotherapy sensitive subgroups of patients are highly needed. We selected the transcription factor <it>TFAP2α </it>from a previously identified gene expression signature for chemotherapy response.</p> <p>Methods</p> <p><it>TFAP2α </it>expression and localization was assessed by immunohistochemistry using a tissue microarray (TMA) containing 282 bladder cancer tumors from patients with locally advanced (pT2-T4_band N_1-3) or metastatic (M₁) disease. All patients had received cisplatin containing chemotherapy. Furthermore, QPCR analysis of three <it>TFAP2α </it>isoforms was performed on tumor specimens of advanced muscle invasive bladder cancers (T2-4). Using the bladder cell lines T24 and SW780 the relation of <it>TFAP2α </it>and cisplatin and gemcitabine sensitivity as well as cell proliferation was examined using siRNA directed <it>TFAP2α </it>knockdown.</p> <p>Results</p> <p>TFAP2α protein expression was analyzed on a TMA with cores from 282 advanced bladder cancer tumors from patients treated with cisplatin based combinational chemotherapy. <it>TFAP2α </it>was identified as a strong independent predictive marker for a good response and survival after cisplatin-containing chemotherapy in patients with advanced bladder cancer. Strong TFAP2α nuclear and cytoplasmic staining predicted good response to chemotherapy in patients with lymph node metastasis, whereas weak TFAP2α nuclear staining predicted good response in patients without lymph node metastasis. In vitro studies showed that siRNA mediated knockdown of TFAP2α increased the proliferation of SW780 cells and rendered the cells less sensitive to cisplatin and gemcitabine. In contrast to that T24 bladder cells with mutated p53 showed to be more drug sensitive upon TFAP2α depletion.</p> <p>Conclusions</p> <p>High levels of nuclear and cytoplasmic TFAP2α protein were a predictor of increased overall survival and progression free survival in patients with advanced bladder cancer treated with cisplatin based chemotherapy. TFAP2α knockdown increased the proliferation of the SW780 bladder cells and reduced cisplatin and gemcitabine induced cell death. The inverse effect was observed in the <it>TP53 </it>mutated T24 cell line where TFAP2α silencing augmented cisplatin and gemcitabine sensitivity and did not stimulate proliferation.</p