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

Heterosis as Investigated in Terms of Polyploidy and Genetic Diversity Using Designed Brassica juncea Amphiploid and Its Progenitor Diploid Species

Fixed heterosis resulting from favorable interactions between the genes on their homoeologous genomes in an allopolyploid is considered analogous to classical heterosis accruing from interactions between homologous chromosomes in heterozygous plants of a diploid species. It has been hypothesized that fixed heterosis may be one of the causes of low classical heterosis in allopolyploids. We used Indian mustard (Brassica juncea, 2n = 36; AABB) as a model system to analyze this hypothesis due to ease of its resynthesis from its diploid progenitors, B. rapa (2n = 20; AA) and B. nigra (2n = 16; BB). Both forms of heterosis were investigated in terms of ploidy level, gene action and genetic diversity. To facilitate this, eleven B. juncea genotypes were resynthesized by hybridizing ten near inbred lines of B. rapa and nine of B. nigra. Three half diallel combinations involving resynthesized B. juncea (11×11) and the corresponding progenitor genotypes of B. rapa (10×10) and B. nigra (9×9) were evaluated. Genetic diversity was estimated based on DNA polymorphism generated by SSR primers. Heterosis and genetic diversity in parental diploid species appeared not to predict heterosis and genetic diversity at alloploid level. There was also no association between combining ability, genetic diversity and heterosis across ploidy. Though a large proportion (0.47) of combinations showed positive values, the average fixed heterosis was low for seed yield but high for biomass yield. The genetic diversity was a significant contributor to fixed heterosis for biomass yield, due possibly to adaptive advantage it may confer on de novo alloploids during evolution. Good general/specific combiners at diploid level did not necessarily produce good general/specific combiners at amphiploid level. It was also concluded that polyploidy impacts classical heterosis indirectly due to the negative association between fixed heterosis and classical heterosis

Differential evolution for the offline and online optimization of fed-batch fermentation processes

The optimization of input variables (typically feeding trajectories over time) in fed-batch fermentations has gained special attention, given the economic impact and the complexity of the problem. Evolutionary Computation (EC) has been a source of algorithms that have shown good performance in this task. In this chapter, Differential Evolution (DE) is proposed to tackle this problem and quite promising results are shown. DE is tested in several real world case studies and compared with other EC algorihtms, such as Evolutionary Algorithms and Particle Swarms. Furthermore, DE is also proposed as an alternative to perform online optimization, where the input variables are adjusted while the real fermentation process is ongoing. In this case, a changing landscape is optimized, therefore making the task of the algorithms more difficult. However, that fact does not impair the performance of the DE and confirms its good behaviour.(undefined

A cloud-based enhanced differential evolution algorithm for parameter estimation problems in computational systems biology

This is a post-peer-review, pre-copyedit version of an article published in Cluster Computing. The final authenticated version is available online at: https://doi.org/10.1007/s10586-017-0860-1[Abstract] Metaheuristics are gaining increasing recognition in many research areas, computational systems biology among them. Recent advances in metaheuristics can be helpful in locating the vicinity of the global solution in reasonable computation times, with Differential Evolution (DE) being one of the most popular methods. However, for most realistic applications, DE still requires excessive computation times. With the advent of Cloud Computing effortless access to large number of distributed resources has become more feasible, and new distributed frameworks, like Spark, have been developed to deal with large scale computations on commodity clusters and cloud resources. In this paper we propose a parallel implementation of an enhanced DE using Spark. The proposal drastically reduces the execution time, by means of including a selected local search and exploiting the available distributed resources. The performance of the proposal has been thoroughly assessed using challenging parameter estimation problems from the domain of computational systems biology. Two different platforms have been used for the evaluation, a local cluster and the Microsoft Azure public cloud. Additionally, it has been also compared with other parallel approaches, another cloud-based solution (a MapReduce implementation) and a traditional HPC solution (a MPI implementation)Ministerio de Economía y Competitividad; DPI2014-55276-C5-2-RMinisterio de Economía y Competitividad; TIN2013-42148-PMinisterio de Economía y Competitividad; TIN2016-75845-PXunta de Galicia ; R2016/045Xunta de Galicia; GRC2013/05

Inhibition of Host Vacuolar H+-ATPase Activity by a Legionella pneumophila Effector

Legionella pneumophila is an intracellular pathogen responsible for Legionnaires' disease. This bacterium uses the Dot/Icm type IV secretion system to inject a large number of bacterial proteins into host cells to facilitate the biogenesis of a phagosome permissive for its intracellular growth. Like many highly adapted intravacuolar pathogens, L. pneumophila is able to maintain a neutral pH in the lumen of its phagosome, particularly in the early phase of infection. However, in all cases, the molecular mechanisms underlying this observation remain unknown. In this report, we describe the identification and characterization of a Legionella protein termed SidK that specifically targets host v-ATPase, the multi-subunit machinery primarily responsible for organelle acidification in eukaryotic cells. Our results indicate that after being injected into infected cells by the Dot/Icm secretion system, SidK interacts with VatA, a key component of the proton pump. Such binding leads to the inhibition of ATP hydrolysis and proton translocation. When delivered into macrophages, SidK inhibits vacuole acidification and impairs the ability of the cells to digest non-pathogenic E. coli. We also show that a domain located in the N-terminal portion of SidK is responsible for its interactions with VatA. Furthermore, expression of sidK is highly induced when bacteria begin to enter new growth cycle, correlating well with the potential temporal requirement of its activity during infection. Our results indicate that direct targeting of v-ATPase by secreted proteins constitutes a virulence strategy for L. pneumophila, a vacuolar pathogen of macrophages and amoebae

Comprehensive Identification of Protein Substrates of the Dot/Icm Type IV Transporter of Legionella pneumophila

A large number of proteins transferred by the Legionella pneumophila Dot/Icm system have been identified by various strategies. With no exceptions, these strategies are based on one or more characteristics associated with the tested proteins. Given the high level of diversity exhibited by the identified proteins, it is possible that some substrates have been missed in these screenings. In this study, we took a systematic method to survey the L. pneumophila genome by testing hypothetical orfs larger than 300 base pairs for Dot/Icm-dependent translocation. 798 of the 832 analyzed orfs were successfully fused to the carboxyl end of β-lactamase. The transfer of the fusions into mammalian cells was determined using the β-lactamase reporter substrate CCF4-AM. These efforts led to the identification of 164 proteins positive in translocation. Among these, 70 proteins are novel substrates of the Dot/Icm system. These results brought the total number of experimentally confirmed Dot/Icm substrates to 275. Sequence analysis of the C-termini of these identified proteins revealed that Lpg2844, which contains few features known to be important for Dot/Icm-dependent protein transfer can be translocated at a high efficiency. Thus, our efforts have identified a large number of novel substrates of the Dot/Icm system and have revealed the diverse features recognizable by this protein transporter