A case of bronchogenic adenocarcinoma in a guinea pig (Cavia porcellus)

A spontaneous case of bronchogenic adenocarcinoma in an adult female albino guinea pig characterized by presence of proliferative neoplastic bronchial epithelial cells forming nests, and vacuolation in the liver parenchyma, is reported

Global optimization in systems biology: stochastic methods and their applications

Mathematical optimization is at the core of many problems in systems biology: (1) as the underlying hypothesis for model development, (2) in model identification, or (3) in the computation of optimal stimulation procedures to synthetically achieve a desired biological behavior. These problems are usually formulated as nonlinear programing problems (NLPs) with dynamic and algebraic constraints. However the nonlinear and highly constrained nature of systems biology models, together with the usually large number of decision variables, can make their solution a daunting task, therefore calling for efficient and robust optimization techniques. Here, we present novel global optimization methods and software tools such as cooperative enhanced scatter search (eSS), AMIGO, or DOTcvpSB, and illustrate their possibilities in the context of modeling including model identification and stimulation design in systems biology.This work was supported by the Spanish MICINN project ”MultiSysBio” (ref. DPI2008-06880-C03-02), and by CSIC intramural project ”BioREDES” (ref. PIE-201170E018).Peer reviewe

Joint genetic analysis for dairy cattle performance across countries in sub-Saharan Africa

This study assessed the feasibility of across-country genetic evaluation of dairy cattle in sub-Saharan Africa where data on livestock production are scarce. Genetic parameters were estimated for the 305-day milk yield in the first lactation and across five lactations, for age at first calving and for interval between first and second calving. Estimated breeding values of individual animals for these traits were calculated. There were records from 2 333, 25 208, and 5 929 Holstein cows in Kenya, South Africa, and Zimbabwe, and 898 and 65134 Jersey cows from Kenya and South Africa. Genetic gain from sire selection within and across countries. was predicted Genetic links between countries were determined from sires with daughters that had records in two or more countries, and from common ancestral sires across seven generations on both the maternal and paternal sides of the pedigree. Each country was treated as a trait in the across-country evaluation. The results showed that genetic variance and heritability were not always estimable within country, but were significantly different from zero in the across-country evaluation. In all three countries, there was greater genetic gain in all traits from an across-country genetic evaluation owing to greater accuracy of selection compared with within country. Kenya stood to benefit most from an across-country evaluation, followed by Zimbabwe, then South Africa. An across-country breeding programme using joint genetic evaluation would be feasible, provided that there were genetic links across countries, and would provide a platform for accelerated genetic progress through selection and germplasm exchange between sub-Saharan African countries.Keywords: across-country genetic evaluation, genetic connectedness, genetic progres

CD32⁺ and PD-1⁺ Lymph Node CD4 T Cells Support Persistent HIV-1 Transcription in Treated Aviremic Individuals.

A recent study conducted in blood has proposed CD32 as the marker identifying the "elusive" HIV reservoir. We have investigated the distribution of CD32 <sup>+</sup> CD4 T cells in blood and lymph nodes (LNs) of HIV-1-uninfected subjects and viremic untreated and long-term-treated HIV-1-infected individuals and their relationship with PD-1 <sup>+</sup> CD4 T cells. The frequency of CD32 <sup>+</sup> CD4 T cells was increased in viremic compared to treated individuals in LNs, and a large proportion (up to 50%) of CD32 <sup>+</sup> cells coexpressed PD-1 and were enriched within T follicular helper (Tfh) cells. We next investigated the role of LN CD32 <sup>+</sup> CD4 T cells in the HIV reservoir. Total HIV DNA was enriched in CD32 <sup>+</sup> and PD-1 <sup>+</sup> CD4 T cells compared to CD32 <sup>-</sup> and PD-1 <sup>-</sup> cells in both viremic and treated individuals, but there was no difference between CD32 <sup>+</sup> and PD-1 <sup>+</sup> cells. There was no enrichment of latently infected cells with inducible HIV-1 in CD32 <sup>+</sup> versus PD-1 <sup>+</sup> cells in antiretroviral therapy (ART)-treated individuals. HIV-1 transcription was then analyzed in LN memory CD4 T cell populations sorted on the basis of CD32 and PD-1 expression. CD32 <sup>+</sup> PD-1 <sup>+</sup> CD4 T cells were significantly enriched in cell-associated HIV RNA compared to CD32 <sup>-</sup> PD-1 <sup>-</sup> (averages of 5.2-fold in treated individuals and 86.6-fold in viremics), CD32 <sup>+</sup> PD-1 <sup>-</sup> (2.2-fold in treated individuals and 4.3-fold in viremics), and CD32 <sup>-</sup> PD-1 <sup>+</sup> (2.2-fold in ART-treated individuals and 4.6-fold in viremics) cell populations. Similar levels of HIV-1 transcription were found in CD32 <sup>+</sup> PD-1 <sup>-</sup> and CD32 <sup>-</sup> PD-1 <sup>+</sup> CD4 T cells. Interestingly, the proportion of CD32 <sup>+</sup> and PD-1 <sup>+</sup> CD4 T cells negatively correlated with CD4 T cell counts and length of therapy. Therefore, the expression of CD32 identifies, independently of PD-1, a CD4 T cell population with persistent HIV-1 transcription and coexpression of CD32 and PD-1, the CD4 T cell population with the highest levels of HIV-1 transcription in both viremic and treated individuals.IMPORTANCE The existence of long-lived latently infected resting memory CD4 T cells represents a major obstacle to the eradication of HIV infection. Identifying cell markers defining latently infected cells containing replication-competent virus is important in order to determine the mechanisms of HIV persistence and to develop novel therapeutic strategies to cure HIV infection. We provide evidence that PD-1 and CD32 may have a complementary role in better defining CD4 T cell populations infected with HIV-1. Furthermore, CD4 T cells coexpressing CD32 and PD-1 identify a CD4 T cell population with high levels of persistent HIV-1 transcription

Current situations of animal data recording, dairy improvement infrastructure, human capacity and strategic issues affecting dairy production in sub-Saharan Africa

An online survey on the state of existing dairy data, dairy improvement infrastructure and human capacity in sub-Saharan Africa (SSA) was undertaken with the aim of assessing whether the state of existing animal recording, dairy improvement methods and key issues facing dairy production together with means of addressing the issues differ among countries and regions of SSA. Respondents comprised experts and practitioners in livestock production and genetic resources from research institutes, animal breeding companies, universities, non-governmental organisations and government agricultural ministries. The main dairy farming system in which the respondents were involved was mixed crop-livestock system (30.2%), and this was mainly practised in the private land tenure system (46.3%). Data were analysed using linear model and paired Student t test in R software package. Respondents identified key issues affecting dairy production as poor genetic assessment of imported exotic breeds and crosses in Africa (62.3%), fluctuations in milk prices within both the formal and informal markets (50.9%), no comprehensive sire ranking systems (39.6%), housing and health management regimes which adversely affect milk yield (32.1%), poor market networks for dairy products (25.5%), poor feeding (13.3%), inadequate genetic technologies (9.4%) and poor animal performance recording systems (9.4%). Respondents emphasised the need for updated breeding policies, sire ranking systems, adequate farm management systems, capacity building, across-country collaborations and joint genetic assessments of dairy breeds found in sub-Saharan Africa. The current situation of dairy production though similar for the different countries, differed in order of emphasis and magnitude across the countries and regions in sub-Saharan Africa.</p

Association between Antibodies to the MR 67,000 Isoform of Glutamate Decarboxylase (GAD) and Type 1 (Insulin-Dependent) Diabetes Mellitus with Coexisting Autoimmune Polyendocrine Syndrome Type II

By using an immunoprecipitation assay, we analysed reactivity of autoantibodies to human recombinant GAD65 and GAD67 in sera from patients with autoimmune polyendocrine syndrome Type II (APS II) with and without Type 1 (insulin-dependent) diabetes mellitus (IDDM) compared to patients with organ-specific autoimmunity. Overall antibodies to GAD65 were correlated with IDDM in all study groups, whereas GAD67 antibodies were associated with IDDM when APS II coexists. Antibodies to GAD65 and GAD67 were detected in 13 (44.8%) and 7 (24.1%) out of 29 APS II patients with IDDM, but in only 4 (13.8%) and 2 (6.9%) out of 29 APS II patients without IDDM, respectively (p < 0.05). In short-standing IDDM (< 1 year), antibodies to GAD67 were significantly more frequent in patients with APS II (5 of 9 [55.6%] subjects) compared to matched diabetic patients without coexisting polyendocrinopathy (1 of 18 [5.6%] subjects) (p < 0.02). The levels of GAD65 (142 ± 90 AU) and GAD67 antibodies (178 ± 95 AU) were significantly higher in patients with polyglandular disease than in patients with isolated IDDM (91 ± 85 AU and 93 ± 57 AU) (p < 0.02). Interestingly, all 11 GAD67 antibody positive subjects also had GAD65 antibodies (p < 0.0001), and in 10 of 11 anti-GAD67 positive sera the GAD67 antibodies could be blocked by either GAD67 or GAD65, suggesting the presence of cross-reactive autoantibodies. No correlation was observed between GAD antibodies and age, sex or any particular associated autoimmune disease, besides IDDM. GAD antibodies were present in only 1 of 6 (16.7%) patients with APS Type I, in 1 of 26 (3.9%) patients with autoimmune thyroid disease but in none of the patients with Addison's disease (n = 16), pernicious anaemia (n = 7) or normal controls (n = 50). Our data suggest distinct antibody specificities reactive to GAD isoforms in APS II and IDDM, which might reflect different mechanisms of autoimmune response in IDDM with coexisting autoimmune polyendocrine autoimmunity

Locality-Aware Request Distribution in Cluster-Based Network Servers

We consider cluster-based network servers in which a front-end directs incoming requests to one of a number of back-ends. Specifically, we consider content-based request distribution: the front-end uses the content requested, in addition to information about the load on the back-end nodes, to choose which back-end will handle this request. Content-based request distribution can improve locality in the back-ends’ main memory caches, increase secondary storage scalability by partitioning the server’s database, and provide the ability to employ back-end nodes that are specialized for certain types of requests. As a specific policy for content-based request distribution, we introduce a simple, practical strategy for locality-aware request distribution (LARD). With LARD, the front-end distributes incoming requests in a manner that achieves high locality in the back-ends’ main memory caches as well as load balancing. Locality is increased by dynamically subdividing the server’s working set over the back-ends. Trace-based simulation results and measurements on a prototype implementation demonstrate substantial performance improvements over state-of-the-art approaches that use only load information to distribute requests. On workloads with working sets that do not fit in a single server node’s main memory cache, the achieved throughput exceeds that of the state-of-the-art approach by a factor of two to four. With content-based distribution, incoming requests must be handed off to a back-end in a manner transparent to the client, after the front-end has inspected the content of the request. To this end, we introduce an efficient TCP handoflprotocol that can hand off an established TCP connection in a client-transparent manner