Erythropoietin receptor expression is a potential prognostic factor in human lung adenocarcinoma

Recombinant human erythropoietins (rHuEPOs) are used to treat cancer-related anemia. Recent preclinical studies and clinical trials, however, have raised concerns about the potential tumor-promoting effects of these drugs. Because the clinical significance of erythropoietin receptor (EPOR) signaling in human non-small cell lung cancer (NSCLC) also remains controversial, our aim was to study whether EPO treatment modifies tumor growth and if EPOR expression has an impact on the clinical behavior of this malignancy. A total of 43 patients with stage III-IV adenocarcinoma (ADC) and complete clinicopathological data were included. EPOR expression in human ADC samples and cell lines was measured by quantitative real-time polymerase chain reaction. Effects of exogenous rHuEPOalpha were studied on human lung ADC cell lines in vitro. In vivo growth of human ADC xenografts treated with rHuEPOalpha with or without chemotherapy was also assessed. In vivo tumor and endothelial cell (EC) proliferation was determined by 5-bromo-2'-deoxy-uridine (BrdU) incorporation and immunofluorescent labeling. Although EPOR mRNA was expressed in all of the three investigated ADC cell lines, rHuEPOalpha treatment (either alone or in combination with gemcitabine) did not alter ADC cell proliferation in vitro. However, rHuEPOalpha significantly decreased tumor cell proliferation and growth of human H1975 lung ADC xenografts. At the same time, rHuEPOalpha treatment of H1975 tumors resulted in accelerated tumor endothelial cell proliferation. Moreover, in patients with advanced stage lung ADC, high intratumoral EPOR mRNA levels were associated with significantly increased overall survival. This study reveals high EPOR level as a potential novel positive prognostic marker in human lung ADC

Acute mucosal pathogenesis of feline immunodeficiency virus is independent of viral dose in vaginally infected cats

<p>Abstract</p> <p>Background</p> <p>The mucosal pathogenesis of HIV has been shown to be an important feature of infection and disease progression. HIV-1 infection causes depletion of intestinal lamina propria CD4+ T cells (LPL), therefore, intestinal CD4+ T cell preservation may be a useful correlate of protection in evaluating vaccine candidates. Vaccine studies employing the cat/FIV and macaque/SIV models frequently use high doses of parenterally administered challenge virus to ensure high plasma viremia in control animals. However, it is unclear if loss of mucosal T cells would occur regardless of initial viral inoculum dose. The objective of this study was to determine the acute effect of viral dose on mucosal leukocytes and associated innate and adaptive immune responses.</p> <p>Results</p> <p>Cats were vaginally inoculated with a high, middle or low dose of cell-associated and cell-free FIV. PBMC, serum and plasma were assessed every two weeks with tissues assessed eight weeks following infection. We found that irrespective of mucosally administered viral dose, FIV infection was induced in all cats. However, viremia was present in only half of the cats, and viral dose was unrelated to the development of viremia. Importantly, regardless of viral dose, all cats experienced significant losses of intestinal CD4+ LPL and CD8+ intraepithelial lymphocytes (IEL). Innate immune responses by CD56+CD3- NK cells correlated with aviremia and apparent occult infection but did not protect mucosal T cells. CD4+ and CD8+ T cells in viremic cats were more likely to produce cytokines in response to Gag stimulation, whereas aviremic cats T cells tended to produce cytokines in response to Env stimulation. However, while cell-mediated immune responses in aviremic cats may have helped reduce viral replication, they could not be correlated to the levels of viremia. Robust production of anti-FIV antibodies was positively correlated with the magnitude of viremia.</p> <p>Conclusions</p> <p>Our results indicate that mucosal immune pathogenesis could be used as a rapid indicator of vaccine success or failure when combined with a physiologically relevant low dose mucosal challenge. We also show that innate immune responses may play an important role in controlling viral replication following acute mucosal infection, which has not been previously identified.</p

Identification and structural analysis of the tripartite α-pore forming toxin of Aeromonas hydrophila

The alpha helical CytolysinA family of pore forming toxins (α-PFT) contains single, two, and three component members. Structures of the single component Eschericia coli ClyA and the two component Yersinia enterolytica YaxAB show both undergo conformational changes from soluble to pore forms, and oligomerization to produce the active pore. Here we identify tripartite α-PFTs in pathogenic Gram negative bacteria, including Aeromonas hydrophila (AhlABC). We show that the AhlABC toxin requires all three components for maximal cell lysis. We present structures of pore components which describe a bi-fold hinge mechanism for soluble to pore transition in AhlB and a contrasting tetrameric assembly employed by soluble AhlC to hide their hydrophobic membrane associated residues. We propose a model of pore assembly where the AhlC tetramer dissociates, binds a single membrane leaflet, recruits AhlB promoting soluble to pore transition, prior to AhlA binding to form the active hydrophilic lined pore

Apoptosis by feline leukemia virus infection

No abstract available

New trends in machine design within industry 4.0 framework

The basic framework of the Industry 4.0 as an approach and philosophy implies the introduction of new procedures and principles, as well as the development and improvement of machine systems towards the introduction of a high level of manufacturing digitalization. In order to meet the achievements of Industry 4.0, very significant changes are also required in the design, monitoring and maintenance phases of machinery. Therefore, all the research and advancements in the field of calculation and design of machine elements and assemblies have to be observed within the paradigm of Industry 4.0. This paper outlines the main research tasks and aims within the determination of basic principles and methods for suiting and improving machine elements and systems in the context of the requirements of the Industry 4.0. Also, the part of the paper gives the description of the new improved methodology and systems for monitoring the parameters of rolling bearings during their operation, which would significantly contribute to the prediction of the possible failure of the rolling bearings and lead to important savings. The developed methodology is a sample for new trends in the context of the vision of Industry 4.0 machinery and respects the requirements for safety, energy efficiency and reliability

Estimating Statistics of Milk Consumption in Relation to Trends in Fluid Milk Marketing

Excerpt from the Introduction: Many decisions in dairy marketing depend on information about rates of milk consumption, and the U. S. Department of Agriculture has been providing such information for nearly 40 years. During that time, the kinds of information that it has been practicable to gather and the demands of the users have both changed. This report is intended to familiarize users with the information on milk consumption currently being published by the Department

Hand Gesture Recognition for Collaborative Workstations: A Smart Command System Prototype

Human-machine collaboration is a key aspect in modern industries, which must be compliant to the Industry 4.0 paradigm. Although the collaboration can be achieved using a Collaborative Robot in a purposely designed workstation, this solution is not always neither feasible nor affordable for the specific task to be carried out in the workstation. On the other hand, using a smart HMI to make an industrial robot a “smart” robot can be a better and affordable solution depending on the task. In this work we present the preliminary development and characteristics of an experimental HMI for smart manufacturing developed in MATLAB and ROS Industrial. The collaboration between humans and robots is achieved by leveraging the Faster R-CNN Object Detector to robustly detect and recognize the hand gestures performed in real-time. The system is based on a state machine to carry out simple tasks such as the repeated movement of the robot following a given trajectory and a pick and place task where the robot interactively reaches a given point and a jog modality

Defective endogenous proviruses are expressed in feline lymphoid cells: evidence for a role in natural resistance to subgroup B feline leukemia viruses.

Endogenous feline leukemia virus (FeLV)-related sequences (enFeLV) are a family of proviral elements found in domestic cats and their close relatives. These elements can recombine with exogenous, infectious FeLVs of subgroup A (FeLV-A), giving rise to host range variants of FeLV-B. We found that a subset of defective enFeLV proviruses is highly expressed in lymphoma cell lines and in a variety of primary tissues, including lymphoid tissues from healthy specific-pathogen-free cats. At least two RNA species were detected, a 4.5-kb RNA containing gag, env, and long terminal repeat sequences and a 2-kb RNA containing env and long terminal repeat sequences. Cloning of enFeLV cDNA from two FeLV-free lymphoma cell lines (3201 and MCC) revealed a long open reading frame (ORF) encoding a truncated env gene product corresponding to the N-terminal portion of gp70env. Interestingly, all of three natural FeLV-B isolates include 3' env sequences which are missing from the highly transcribed subset and hence must be derived from other enFeLV elements. The enFeLV env ORF cDNA clones were closely similar to a previously characterized enFeLV provirus, CFE-16, but were polymorphic at a site corresponding to an exogenous FeLV neutralization epitope. Site-specific antiserum raised to a C-terminal 30-amino-acid peptide of the enFeLV env ORF detected an intracellular product of 35 kDa which was also shed from cells in stable form. Expression of the 35-kDa protein correlated with enFeLV RNA levels and was negatively correlated with susceptibility to infection with FeLV-B. Cell culture supernatant containing the 35-kDa protein specifically blocked infection of permissive fibroblast cells with FeLV-B isolates. We suggest that the truncated env protein mediates resistance by receptor blockade and that this form of enFeLV expression mediates the natural resistance of cats to infection with FeLV-B in the absence of FeLV-A