Going Coastal: Shared Evolutionary History between Coastal British Columbia and Southeast Alaska Wolves (Canis lupus)

Many coastal species occupying the temperate rainforests of the Pacific Northwest in North America comprise endemic populations genetically and ecologically distinct from interior continental conspecifics. Morphological variation previously identified among wolf populations resulted in recognition of multiple subspecies of wolves in the Pacific Northwest. Recently, separate genetic studies have identified diverged populations of wolves in coastal British Columbia and coastal Southeast Alaska, providing support for hypotheses of distinct coastal subspecies. These two regions are geographically and ecologically contiguous, however, there is no comprehensive analysis across all wolf populations in this coastal rainforest.By combining mitochondrial DNA datasets from throughout the Pacific Northwest, we examined the genetic relationship between coastal British Columbia and Southeast Alaska wolf populations and compared them with adjacent continental populations. Phylogenetic analysis indicates complete overlap in the genetic diversity of coastal British Columbia and Southeast Alaska wolves, but these populations are distinct from interior continental wolves. Analyses of molecular variation support the separation of all coastal wolves in a group divergent from continental populations, as predicted based on hypothesized subspecies designations. Two novel haplotypes also were uncovered in a newly assayed continental population of interior Alaska wolves.We found evidence that coastal wolves endemic to these temperate rainforests are diverged from neighbouring, interior continental wolves; a finding that necessitates new international strategies associated with the management of this species

Association of Early Repolarization Pattern on ECG with Risk of Cardiac and All-Cause Mortality: A Population-Based Prospective Cohort Study (MONICA/KORA)

In a population-based cohort study of middle-aged people in Central Europe, Stefan Kääb and colleagues find an association between electrocardiographic early repolarization pattern and mortality risk

Soluble ST2 Levels Are Associated with Bleeding in Patients with Severe Leptospirosis

Leptospirosis is a bacterial disease that is mainly spread by rodents and other small mammals. Transmission frequently occurs in (sub-) tropical countries, where environmental circumstances are most favourable. Severe leptospirosis can cause bleeding and vital organ dysfunction. An exaggerated immune response is thought to play an important role in the pathophysiology of leptospirosis. Soluble ST2 (sST2) is thought to inhibit negative regulatory pathways of this response. Soluble ST2 is produced by cells that surround, for example, blood vessels, and several of these blood cells play an important part in the host immune response. In an observational study, we measured the extent of sST2 release in patients suffering from severe leptospirosis. We found that patients that died from leptospirosis displayed higher levels of sST2. Moreover, from this study we have seen that sST2 levels were associated with bleeding, whereas other markers of infection were not. In an experiment, we showed that (white) blood cells did not seem to be the source of sST2 production. Damage to blood vessels is likely to cause bleeding in leptospirosis patients, exposing sST2 producing cells like fibroblasts to the blood stream. Hence, we believe that sST2 may be used as a marker for tissue damage in patients suffering from severe leptospirosis

Do Children and Adolescents with Anorexia Nervosa Display an Inefficient Cognitive Processing Style?

Objective: This study aimed to examine neuropsychological processing in children and adolescents with Anorexia Nervosa (AN). The relationship of clinical and demographic variables to neuropsychological functioning within the AN group was also explored.  Method: The performance of 41 children and adolescents with a diagnosis of AN were compared to 43 healthy control (HC) participants on a number of neuropsychological measures.  Results: There were no differences in IQ between AN and HC groups. However, children and adolescents with AN displayed significantly more perseverative errors on the Wisconsin Card Sorting Test, and lower Style and Central Coherence scores on the Rey Osterrieth Complex Figure Test relative to HCs.  Conclusion: Inefficient cognitive processing in the AN group was independent of clinical and demographic variables, suggesting it might represent an underlying trait for AN. The implications of these findings are discussed

Toxoplasma Effector MAF1 Mediates Recruitment of Host Mitochondria and Impacts the Host Response

Recent information has revealed the functional diversity and importance of mitochondria in many cellular processes including orchestrating the innate immune response. Intriguingly, several infectious agents, such as Toxoplasma, Legionella, and Chlamydia, have been reported to grow within vacuoles surrounded by host mitochondria. Although many hypotheses have been proposed for the existence of host mitochondrial association (HMA), the causes and biological consequences of HMA have remained unanswered. Here we show that HMA is present in type I and III strains of Toxoplasma but missing in type II strains, both in vitro and in vivo. Analysis of F1 progeny from a type II×III cross revealed that HMA is a Mendelian trait that we could map. We use bioinformatics to select potential candidates and experimentally identify the polymorphic parasite protein involved, mitochondrial association factor 1 (MAF1). We show that introducing the type I (HMA+) MAF1 allele into type II (HMA-) parasites results in conversion to HMA+ and deletion of MAF1 in type I parasites results in a loss of HMA. We observe that the loss and gain of HMA are associated with alterations in the transcription of host cell immune genes and the in vivo cytokine response during murine infection. Lastly, we use exogenous expression of MAF1 to show that it binds host mitochondria and thus MAF1 is the parasite protein directly responsible for HMA. Our findings suggest that association with host mitochondria may represent a novel means by which Toxoplasma tachyzoites manipulate the host. The existence of naturally occurring HMA+ and HMA- strains of Toxoplasma, Legionella, and Chlamydia indicates the existence of evolutionary niches where HMA is either advantageous or disadvantageous, likely reflecting tradeoffs in metabolism, immune regulation, and other functions of mitochondria. © 2014 Pernas et al

Lack of PPARγ in Myeloid Cells Confers Resistance to Listeria monocytogenes Infection

The peroxisomal proliferator-activated receptor γ (PPARγ) is a nuclear receptor that controls inflammation and immunity. Innate immune defense against bacterial infection appears to be compromised by PPARγ. The relevance of PPARγ in myeloid cells, that organize anti-bacterial immunity, for the outcome of immune responses against intracellular bacteria such as Listeria monocytogenes in vivo is unknown. We found that Listeria monocytogenes infection of macrophages rapidly led to increased expression of PPARγ. This prompted us to investigate whether PPARγ in myeloid cells influences innate immunity against Listeria monocytogenes infection by using transgenic mice with myeloid-cell specific ablation of PPARγ (LysMCre×PPARγflox/flox). Loss of PPARγ in myeloid cells results in enhanced innate immune defense against Listeria monocytogenes infection both, in vitro and in vivo. This increased resistance against infection was characterized by augmented levels of bactericidal factors and inflammatory cytokines: ROS, NO, IFNγ TNF IL-6 and IL-12. Moreover, myeloid cell-specific loss of PPARγ enhanced chemokine and adhesion molecule expression leading to improved recruitment of inflammatory Ly6Chi monocytes to sites of infection. Importantly, increased resistance against Listeria infection in the absence of PPARγ was not accompanied by enhanced immunopathology. Our results elucidate a yet unknown regulatory network in myeloid cells that is governed by PPARγ and restrains both listeriocidal activity and recruitment of inflammatory monocytes during Listeria infection, which may contribute to bacterial immune escape. Pharmacological interference with PPARγ activity in myeloid cells might represent a novel strategy to overcome intracellular bacterial infection

The Complete Mitochondrial Genomes of Six Heterodont Bivalves (Tellinoidea and Solenoidea): Variable Gene Arrangements and Phylogenetic Implications

BACKGROUND: Taxonomy and phylogeny of subclass Heterodonta including Tellinoidea are long-debated issues and a complete agreement has not been reached yet. Mitochondrial (mt) genomes have been proved to be a powerful tool in resolving phylogenetic relationship. However, to date, only ten complete mitochondrial genomes of Heterodonta, which is by far the most diverse major group of Bivalvia, have been determined. In this paper, we newly sequenced the complete mt genomes of six species belonging to Heterodonta in order to resolve some problematical relationships among this subclass. PRINCIPAL FINDINGS: The complete mt genomes of six species vary in size from 16,352 bp to 18,182. Hairpin-like secondary structures are found in the largest non-coding regions of six freshly sequenced mt genomes, five of which contain tandem repeats. It is noteworthy that two species belonging to the same genus show different gene arrangements with three translocations. The phylogenetic analysis of Heterodonta indicates that Sinonovacula constricta, distant from the Solecurtidae belonging to Tellinoidea, is as a sister group with Solen grandis of family Solenidae. Besides, all five species of Tellinoidea cluster together, while Sanguinolaria diphos has closer relationship with Solecurtus divaricatus, Moerella iridescens and Semele scaba rather than with Sanguinolaria olivacea. CONCLUSIONS/SIGNIFICANCE: By comparative study of gene order rearrangements and phylogenetic relationships of the five species belonging to Tellinoidea, our results support that comparisons of mt gene order rearrangements, to some extent, are a useful tool for phylogenetic studies. Based on phylogenetic analyses of multiple protein-coding genes, we prefer classifying the genus Sinonovacula within the superfamily Solenoidea and not the superfamily Tellinoidea. Besides, both gene order and sequence data agree that Sanguinolaria (Psammobiidae) is not monophyletic. Nevertheless, more studies based on more mt genomes via combination of gene order and phylogenetic analysis are needed to further understand the phylogenetic relationships in subclass Heterodonta

The mammalian centrosome and its functional significance

Primarily known for its role as major microtubule organizing center, the centrosome is increasingly being recognized for its functional significance in key cell cycle regulating events. We are now at the beginning of understanding the centrosome’s functional complexities and its major impact on directing complex interactions and signal transduction cascades important for cell cycle regulation. The centrosome orchestrates entry into mitosis, anaphase onset, cytokinesis, G1/S transition, and monitors DNA damage. Recently, the centrosome has also been recognized as major docking station where regulatory complexes accumulate including kinases and phosphatases as well as numerous other cell cycle regulators that utilize the centrosome as platform to coordinate multiple cell cycle-specific functions. Vesicles that are translocated along microtubules to and away from centrosomes may also carry enzymes or substrates that use centrosomes as main docking station. The centrosome’s role in various diseases has been recognized and a wealth of data has been accumulated linking dysfunctional centrosomes to cancer, Alstrom syndrome, various neurological disorders, and others. Centrosome abnormalities and dysfunctions have been associated with several types of infertility. The present review highlights the centrosome’s significant roles in cell cycle events in somatic and reproductive cells and discusses centrosome abnormalities and implications in disease