Balancing Thymocyte Adhesion and Motility: A Functional Linkage Between β1 Lntegrins and The Motility Receptor RHAMM

Thymocyte differentiation involves several processes that occur in different anatomic sites within the thymus. Therefore, thymocytes must have the ability to respond to signals received from stromal cells and adopt either adhesive or motile behavior. We will discuss our data indicating human thymocytes use α4β1 integrin, α5β1 integrin and RHAMM to mediate these activities. Immature multinegative (MN; CD3–4–8–19-) thymocytes use α4β1 and α5β1 integrins to mediate weak and strong adhesion. This subset also uses α4β1 integrin to mediate motility. As thymocytes differentiate, they begin to express and use RHAMM to mediate motility in conjunction with α4β1 and α5β1 integrins. Motile thymocytes use β1 integrins to maintain weakly adhesive contacts with substrate to provide traction for locomoting cells, thus weak adhesion is a requirement of motile behavior. Hyaluronan (HA) is also required by thymocytes to mediate motility. HA binding to cell surface RHAMM redistributes intracellular RHAMM to the cell surface where it functions to mediate motility. We propose that the decision to maintain adhesive or motile behavior is based on the balance between low and high avidity binding conformations of β1 integrins on thymocytes and that RHAMM:HA interactions decrease high avidity binding conformations of integrins pushing the balance toward motile behavior

Temporal-Difference Learning to Assist Human Decision Making during the Control of an Artificial Limb

In this work we explore the use of reinforcement learning (RL) to help with human decision making, combining state-of-the-art RL algorithms with an application to prosthetics. Managing human-machine interaction is a problem of considerable scope, and the simplification of human-robot interfaces is especially important in the domains of biomedical technology and rehabilitation medicine. For example, amputees who control artificial limbs are often required to quickly switch between a number of control actions or modes of operation in order to operate their devices. We suggest that by learning to anticipate (predict) a user's behaviour, artificial limbs could take on an active role in a human's control decisions so as to reduce the burden on their users. Recently, we showed that RL in the form of general value functions (GVFs) could be used to accurately detect a user's control intent prior to their explicit control choices. In the present work, we explore the use of temporal-difference learning and GVFs to predict when users will switch their control influence between the different motor functions of a robot arm. Experiments were performed using a multi-function robot arm that was controlled by muscle signals from a user's body (similar to conventional artificial limb control). Our approach was able to acquire and maintain forecasts about a user's switching decisions in real time. It also provides an intuitive and reward-free way for users to correct or reinforce the decisions made by the machine learning system. We expect that when a system is certain enough about its predictions, it can begin to take over switching decisions from the user to streamline control and potentially decrease the time and effort needed to complete tasks. This preliminary study therefore suggests a way to naturally integrate human- and machine-based decision making systems.Comment: 5 pages, 4 figures, This version to appear at The 1st Multidisciplinary Conference on Reinforcement Learning and Decision Making, Princeton, NJ, USA, Oct. 25-27, 201

A Single Nucleotide Polymorphism in the RASGRF2 Gene Is Associated with Alcoholic Liver Cirrhosis in Men

Background Genetic polymorphisms in the RAS gene family are associated with different diseases, which may include alcohol-related disorders. Previous studies showed an association of the allelic variant rs26907 in RASGRF2 gene with higher alcohol intake. Additionally, the rs61764370 polymorphism in the KRAS gene is located in a binding site for the let-7 micro-RNA family, which is potentially involved in alcohol-induced inflammation. Therefore, this study was designed to explore the association between these two polymorphisms and susceptibility to alcoholism or alcoholic liver disease (ALD). Methods We enrolled 301 male alcoholic patients and 156 healthy male volunteers in this study. Polymorphisms were genotyped by using TaqMan® PCR assays for allelic discrimination. Allelic and genotypic frequencies were compared between the two groups. Logistic regression analysis was performed to analyze the inheritance model. Results The A allele of the RASGRF2 polymorphism (rs26907) was significantly more prevalent among alcoholic patients with cirrhosis (23.2%) compared to alcoholic patients without ALD (14.2%). This difference remained significant in the group of patients with alcohol dependence (28.8% vs. 14.3%) but not in those with alcohol abuse (15.1% vs. 14.4%). Multivariable logistic regression analysis showed that the A allele of this polymorphism (AA or GA genotype) was associated with alcoholic cirrhosis both in the total group of alcoholics (odds ratio [OR]: 2.33, 95% confidence interval [CI]: 1.32–4.11; P = 0.002) and in the group of patients with alcohol dependence (OR: 3.1, 95% CI: 1.50–6.20; P = 0.001). Allelic distributions of the KRAS polymorphism (rs61764370) did not differ between the groups. Conclusions To our knowledge, this genetic association study represents the first to show an association of the RASGRF2 G>A (rs26907) polymorphism with ALD in men, particularly in the subgroup of patients with AD. The findings suggest the potential relevance of the RAS gene family in alcoholism and ALD

Sanidade.

Introdução. Comportamento e sinais clínicos. Doenças virais. Varíola da carpa. Herpevírus da necrose hematopoiética do kinguio. Herpevírus da carpa. Viremia-primaveril da carpa. Linfocistose. Doenças bacterianas. Infecções por Aeromonas spp. Infecções por Flavobacterium columnare. Infecções por Edwardsiella spp. Infecções por Vibrio spp. Infecções por Streptococcus spp. Infecções por Mycobacterium spp. Infecções por Francisella spp. Doenças parasitárias causadas por protozoários: Doença do buraco na cabeça. Tricodiníase. Tetrahymenose ou doença dos guppies. Ictioftiríase ou doença dos pontos brancos. Piscinoodiníase ou doença do veludo. Doenças parasitárias causadas por helmintos: Monogenea. Digenea. Cestoda. Nematoda. Acantocephala. Doenças parasitárias causadas por crustáceos: Copépodes. Branquiúros. Isópodes. Doenças causadas por fungos: Saprolegniose. Doenças causadas por microsporídeos: Microsporídeos. Profilaxia. Aclimatação. Quarentena. Tratamento com quimioterápicos. Cuidados na aplicação de produtos e medicamentos. Seleção do método de aplicação. Considerações finais.bitstream/item/225453/1/pl-cap4.pd

An enclosed in-gel PCR amplification cassette with multi-target, multi-sample detection for platform molecular diagnostics

This work describes a self-contained, simple, disposable, and inexpensive gel capillary cassette for DNA amplification in near point of care settings. The cassette avoids the need for pumps or valves during raw sample delivery or polymerase chain reaction (PCR) amplification steps. The cassette contains capillary reaction units that can be stored at room temperature for up to 3 months. The current cassette configuration format can simultaneously tests up to 16 patients for two or more targets, accommodates different sample types on the same cassette, has integrated positive and negative controls and allows flexibility for multiple geometries. PCR reagents in the cassette are desiccated to allow storage at room temperature with rehydration by raw sample at the time of testing. The sample is introduced to the cassette via a transfer pipette simply by capillary force. DNA amplification was carried out in a portable prototype instrument for PCR thermal cycling with fluorescence detection of amplified products by melt curve analysis. To demonstrate performance, raw genital swabs and urine were introduced to the same cassette to simultaneously detect four sexually transmitted infections. Herpes Simplex Viruses (HSV-1 and HSV-2) were detected from raw genital swabs. Ureaplasma Urealyticum (UU) and Mycoplasma Homonis (MH) were detected from raw urine. Results for multiple patients were obtained in as little as 50'. This platform allows multiparameter clinical testing with a pre-assembled cassette that requires only the introduction of raw sample. Modification of the prototype device to accommodate larger cassettes will ultimately provide high throughput simultaneous testing of even larger numbers of samples for many different targets, as is required for most clinical applications. Combinations of wax and/or polymer cassettes holding capillary reaction units are feasible. The components of the cassette are suited to mass production and robotic assembly to produce a readily manufactured disposable reaction cassette that can be configured for disease-specific testing panels. Rapid testing with a disposable reaction cassette on an inexpensive instrument will permit on the spot evaluation of patients in the clinic for faster medical decision-making and more informed therapeutic choices

Ocimum gratissimum essential oil improved the health, innate immunity and resistance to Aeromonas hydrophila infection in Pseudoplatystoma reticulatum.

This study evaluated the effects of diets containing alfavaca essential oil on the zootechnical performance, plasma glucose, leukocyte respiratory activity, haematology, and intestinal histomorphometry in "cachara" (Pseudoplatystoma reticulatum) challenged with Aeromonas hydrophila. Este estudo avaliou os efeitos de dietas contendo óleo essencial de alfavaca sobre o desempenho zootécnico, glicose plasmática, atividade respiratória leucocitária, hematologia e histomorfometria intestinal em cachara (Pseudoplatystoma reticulatum) desafiado com Aeromonas hydrophila.Título em português: Óleo essencial de Ocimum gratissinum melhorou a saúde, imunidade inata e resistência à infecção por Aeromonas hydrophila em Pseudoplatystoma reticulatum

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Beta catenin and cytokine pathway dysregulation in patients with manifestations of the "PTEN hamartoma tumor syndrome"

Background. The "PTEN hamartoma tumor syndrome" (PHTS) includes a group of syndromes caused by germline mutations within the tumor suppressor gene "phosphatase and tensin homolog deleted on chromosome ten" (PTEN), characterized by multiple polyps in the gastrointestinal tract and by a highly increased risk of developing malignant tumours in many tissues. The current work clarifies the molecular basis of PHTS in three unrelated Italian patients, and sheds light on molecular pathway disregulation constitutively associated to PTEN alteration. Methods. We performed a combination of RT-PCR, PCR, sequencing of the amplified fragments, Real Time PCR and western blot techniques. Results. Our data provide the first evidence of β-catenin accumulation in blood cells of patients with hereditary cancer syndrome caused by germ-line PTEN alteration. In addition, for the first time we show, in all PHTS patients analysed, alterations in the expression of TNFα, its receptors and IL-10. Importantly, the isoform of TNFRI that lacks the DEATH domain (TNFRSF1β) was found to be overexpressed. Conclusion. In light of our findings, we suggest that the PTEN pathway disregulation could determine, in non-neoplastic cells of PHTS patients, cell survival and pro-inflammatory stimulation, mediated by the expression of molecules such as β-catenin, TNFα and TNFα receptors, which could predispose these patients to the development of multiple cancers