Wolbachia infection can bias estimates of intralocus sexual conflict

Males and females share most of their genome and develop many of the same traits. However, each sex frequently has different optimal values for these shared traits, creating intralocus sexual conflict. This conflict has been observed in wild and laboratory populations of insects and affects important evolutionary processes such as sexual selection, the maintenance of genetic variation, and possibly even speciation. Given the broad impacts of intralocus conflict, accurately detecting and measuring it is important. A common way to detect intralocus sexual conflict is to calculate the intersexual genetic correlation for fitness, with negative values suggesting conflict. Here, we highlight a potential confounder of this measure—cytoplasmic incompatibility caused by the intracellular parasite Wolbachia. Infection with Wolbachia can generate negative intersexual genetic correlations for fitness in insects, suggestive of intralocus sexual conflict. This is because cytoplasmic incompatibility reduces the fitness of uninfected females mated to infected males, while uninfected males will not suffer reductions in fitness if they mate with infected females and may even be fitter than infected males. This can lead to strong negative intersexual genetic correlations for fitness, mimicking intralocus conflict. We illustrate this issue using simulations and then present Drosophila simulans data that show how reproductive incompatibilities caused by Wolbachia infection can generate signals of intralocus sexual conflict. Given that Wolbachia infection in insect populations is pervasive, but populations usually contain both infected and uninfected individuals providing scope for cytoplasmic incompatibility, this is an important consideration for sexual conflict research but one which, to date, has been largely underappreciated.     

Does inbreeding affect personality traits?

The question of why variation is maintained in personality traits is an evolutionary puzzle. According to the condition‐dependence hypothesis, such traits depend on condition, which limits the behavioral choices available to individuals. Because condition is affected by many genes, it can effectively be manipulated by inbreeding, which exposes the effects of deleterious recessive mutations. Here, I compared two personality traits, boldness and tendency to explore, of male guppies (Poecilia reticulata) from first‐generation inbred and outbred treatments. Boldness in guppies is associated with increased sexual attractiveness and is thus expected to affect fitness. Therefore, I hypothesized that the personality traits would be negatively affected by inbreeding. However, the results indicated that inbred guppies did not differ in either personality trait from their outbred counterparts. This finding suggests that mechanisms other than condition dependence are maintaining personality variation in the guppy.     

microRNAs: Key players in virus-associated hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is known as one of the major health problems worldwide. Pathological analysis indicated that a variety of risk factors including genetical (i.e., alteration of tumor suppressors and oncogenes) and environmental factors (i.e., viruses) are involved in beginning and development of HCC. The understanding of these risk factors could guide scientists and clinicians to design effective therapeutic options in HCC treatment. Various viruses such as hepatitis B virus (HBV) and hepatitis C virus (HCV) via targeting several cellular and molecular pathways involved in HCC pathogenesis. Among various cellular and molecular targets, microRNAs (miRNAs) have appeared as key players in HCC progression. miRNAs are short noncoding RNAs which could play important roles as oncogenes or tumor suppressors in several malignancies such as HCC. Deregulation of many miRNAs (i.e., miR-222, miR-25, miR-92a, miR-1, let-7f, and miR-21) could be associated with different stages of HCC. Besides miRNAs, exosomes are other particles which are involved in HCC pathogenesis via targeting different cargos, such as DNAs, RNAs, miRNAs, and proteins. In this review, we summarize the current knowledge of the role of miRNAs and exosomes as important players in HCC pathogenesis. Moreover, we highlighted HCV- and HBV-related miRNAs which led to HCC progression.     

Early calcium handling imbalance in pressure overload-induced heart failure with nearly normal left ventricular ejection fraction

Heart failure with preserved ejection fraction (HFpEF) is a common clinical syndrome associated with high morbidity and mortality. Therapeutic options are limited due to a lack of knowledge of the pathology and its evolution. We investigated the cellular phenotype and Ca²⁺ handling in hearts recapitulating HFpEF criteria. HFpEF was induced in a portion of male Wistar rats four weeks after abdominal aortic banding. These animals had nearly normal ejection fraction and presented elevated blood pressure, lung congestion, concentric hypertrophy, increased LV mass, wall stiffness, impaired active relaxation and passive filling of the left ventricle, enlarged left atrium, and cardiomyocyte hypertrophy. Left ventricular cell contraction was stronger and the Ca²⁺ transient larger. Ca²⁺ cycling was modified with a RyR2 mediated Ca²⁺ leak from the sarcoplasmic reticulum and impaired Ca²⁺ extrusion through the Sodium/Calcium exchanger (NCX), which promoted an increase in diastolic Ca²⁺. The Sarcoplasmic/endoplasmic reticulum Ca²⁺ ATPase (SERCA2a) and NCX protein levels were unchanged. The phospholamban (PLN) to SERCA2a ratio was augmented in favor of an inhibitory effect on the SERCA2a activity. Conversely, PLN phosphorylation at the calmodulin-dependent kinase II (CaMKII)-specific site (PLN-Thr17), which promotes SERCA2A activity, was increased as well, suggesting an adaptive compensation of Ca²⁺ cycling. Altogether our findings show that cardiac remodeling in hearts with a HFpEF status differs from that known for heart failure with reduced ejection fraction. These data also underscore the interdependence between systolic and diastolic “adaptations” of Ca²⁺ cycling with complex compensative interactions between Ca²⁺ handling partner and regulatory proteins.     

Comparative expression of endogenous retrotransposons in adult mouse mammary gland during normal development and differentiation

Amplified expression of the endogenous retrotransposons, intracisternal A particles (IAPs) and murine leukemia virus-related elements (MLVEs), along with decreased expression of VL30 elements frequently occurs during mouse mammary tumorigenesis. We have now analyzed the expression of these retroelements during the normal developmental and differentiation cycle of the mammary gland as found in virgin, pregnant, lactating, and post-lactation adult female BALB/c mice. Retrotransposon expression was either unchanged or decreased during the progressive stages of the cycle compared to virgin tissue. Likewise, growth of mammary epithelial cells in primary culture had little or no effect on expression of IAPs, MLVEs and VL30 sequences. Thus, the dramatic changes involving these retrotransposons in many mouse mammary tumors appear unrelated to any normal state.     

Genotyping‐by‐sequencing analysis of Orobanche crenata populations in Algeria reveals genetic differentiation

Crenate broomrape (Orobanche crenata Forsk.) is a serious long‐standing parasitic weed problem in Algeria, mainly affecting legumes but also vegetable crops. Unresolved questions for parasitic weeds revolve around the extent to which these plants undergo local adaptation, especially with respect to host specialization, which would be expected to be a strong selective factor for obligate parasitic plants. In the present study, the genotyping‐by‐sequencing (GBS) approach was used to analyze genetic diversity and population structure of 10 Northern Algerian O. crenata populations with different geographical origins and host species (faba bean, pea, chickpea, carrot, and tomato). In total, 8004 high‐quality single‐nucleotide polymorphisms (5% missingness) were obtained and used across the study. Genetic diversity and relationships of 95 individuals from 10 populations were studied using model‐based ancestry analysis, principal components analysis, discriminant analysis of principal components, and phylogeny approaches. The genetic differentiation (F _ST) between pairs of populations was lower between adjacent populations and higher between geographically separated ones, but no support was found for isolation by distance. Further analyses identified four genetic clusters and revealed evidence of structuring among populations and, although confounded with location, among hosts. In the clearest example, O. crenata growing on pea had a SNP profile that was distinct from other host/location combinations. These results illustrate the importance and potential of GBS to reveal the dynamics of parasitic weed dispersal and population structure.     

Innate versus adaptive immunity in Candida albicans infection

Candida albicans is a common opportunistic pathogen, causing both superficial and systemic infection. Clinical observations indicate that mucocutaneous infections are commonly associated with defective cell-mediated immune responses, whereas systemic infection is more frequently seen in patients with deficiencies in neutrophil number or function. Analysis of mechanisms of host resistance against gastrointestinal and oral infection in mouse models has demonstrated an absolute dependence on CD4(+) T cells, although clearance also involves phagocytic cells. Both IL-12 and TNF-alpha appear to be important mediators, but mouse strain-dependent variations in susceptibility to infection may be related to T-cell enhancement of production of phagocytic cells by the bone marrow. In murine systemic infection, the role of innate and adaptive responses is less well defined. Studies in immunodeficient and T-cell-depleted mice suggest that clearance of the yeast may be predominantly a function of the innate response, whereas the adaptive response may either limit tissue damage or have the potential to cause immunopathology, depending on the host genetic context in which the infection takes place.     

Testing the status-dependent ESS model: population variation in fighter expression in the mite Sancassania berlesei

The conditional evolutionarily stable strategy (ESS) with status-dependent tactics is the most commonly invoked ESS for alternative reproductive tactics within the sexes. Support for this model has recently been criticized as apparent rather than real. We address key predictions of the status-dependent ESS in three populations of the male dimorphic mite Sancassania berlesei. In S. berlesei'fighter' males are characterized by a thickened pair of legs used for killing rivals; 'scramblers' are benign. Most males in each population could be manipulated to become fighters by decreasing density, fulfilling the prediction that males make a 'decision'. There was evidence of genetic covariance between sire status and offspring morph, but also a strong effect of sire morph on offspring morph ratio. This was consistent with considerable genetic variation for the status-dependent switch point as a breeding experiment found no support for single-locus inheritance. We also found evidence that switch points evolve independently of distributions of status. This study supports the current status-dependent ESS model.     

Cytokine gene polymorphisms in endemic pemphigus foliaceus: a possible role for IL6 variants

Endemic pemphigus foliaceus (EPF) is a complex autoimmune disease characterized by the presence of antibodies against desmoglein 1, which lead to the loss of adhesion among keratinocytes (acantholysis). Variants of HLA class II genes have been the only genetic factors found to modulate susceptibility to EPF. This study aims at investigating the influence of cytokine genetic variants in the pathogenesis of EPF, since they may affect the expression levels of these immunomodulatory molecules. The sample included 168 patients and 189 controls and was comprised of mostly Caucasoids and Mulattos. The approach consisted of a case-control association study and the alleles were identified by mismatched PCR-RFLP. No associations were found with variants of IL1A, IL1B, IL1RN, IL4R and IL10. There was a weak negative association with the haplotype -1082G -592C (OR=0.49) of the IL10 gene in Mulattos. In regard to polymorphism -590 of the IL4 gene, a positive association with the T/T genotype (OR=2.71) and a negative association with the C variant (OR=0.37) were found. Associations with IL6 -174 variants suggest that the C/C genotype has a protective effect (OR=0.13) while carriers of the G allele are more susceptible (OR=7.66) to EPF.     

Lipoplex size determines lipofection efficiency with or without serum

In order to identify factors affecting cationic liposome-mediated gene transfer, the relationships were examined among cationic liposome/DNA complex (lipoplex)-cell interactions, lipoplex size and lipoplex-mediated transfection (lipofection) efficiency. It was found that lipofection efficiency was determined mainly by lipoplex size, but not by the extent of lipoplex-cell interactions including binding, uptake or fusion. In addition, it was found that serum affected mainly lipoplex size, but not lipoplex-cell interactions, which effect was the major reason behind the inhibitory effect of serum on lipofection efficiency. It was concluded that, in the presence or absence of serum, lipoplex size is a major factor determining lipofection efficiency. Moreover, in the presence or absence of serum, lipoplex size was found to affect lipofection efficiency by controlling the size of the intracellular vesicles containing lipoplexes after internalization, but not by affecting lipoplex-cell interactions. In addition, large lipoplex particles showed, in general, higher lipofection efficiency than small particles. These results imply that, by controlling lipoplex size, an efficient lipid delivery system may be achieved for in vitro and in vivo gene therapy.