Morphological characteristics of the uterus and uterine cervix of the plains viscacha (Lagostomus maximus)

The plains viscacha is a hystricognathi rodent with special reproductive characteristics. Despite poly-ovulation of 800 oocytes, it generates a high embryonic mortality since from 10 to 12 implantations only one or two offspring are born. The present work analyses the morphological, morphometrical, histochemical and lectinhistochemical characteristics of the uterus and uterine cervix of pregnant and non-pregnant viscacha. Anatomically, the uterus has two horns each one continued with a short cervix devoid of glands. The structure of the uterus is like that of other species; however, the proportion and size of its glands varies according to the physiological state. In viscacha, there is no uterine body and cervices cannot be differentiated externally. The formation of two sack bottoms is determined by the presence of a middle raphe in the cranial portion of the vagina. The so-described anatomy is different from that described in other hystricognathi such as guinea pig and coypu. The cervix presents two microscopically differentiable regions: the endocervix and the ectocervix lined by epithelia with different characteristics. The general characteristics of the uterus of L. maximus do not show specific differences with those of other mammals that might explain its peculiar gestation.     

Structure of plant–Hymenoptera networks in two coastal shrub sites in Mexico

The study of interaction networks between plants and pollinators allows us to explore interaction patterns at the community level, detect changes in visit frequency and evaluate the nestedness of the networks. The latter allows rare plant species to be visited by more abundant species of pollinators, potentially allowing community diversity to be maintained, and this approach makes it possible to discern the rewiring (changes in connections) of species when their preferred resource is not available. In this study, the topology, species identity and rewiring were compared between two contrasting sites, one within a conservation area and the other subjected to continuous disturbance. The networks of both sites were significantly nested and shared a high number of common species of both plants and pollinators. However, the sites differed notably in the number of exclusive interactions, suggesting a high percentage of interaction rewiring. The introduced bee species, Apis mellifera, was the most frequent species at both sites and also the most connected in terms of the number of its interactions. This is explained by its generalist foraging characteristics that allow it to form part of the networks’ core group. In general, our results underscore the importance of knowing the identity of the participating species when studying networks, and how connections change between them, as well as the potential effect of habitat destruction and the role of invasive species in the rearrangement of the interactions; all factors that can exert an influence on the functioning of plant–pollinator networks.     

BH3-Mimetics- and Cisplatin-Induced Cell Death Proceeds through Different Pathways Depending on the Availability of Death-Related Cellular Components

Background

Owing to their important function in regulating cell death, pharmacological inhibition of Bcl-2 proteins by dubbed BH3-mimetics is a promising strategy for apoptosis induction or sensitization to chemotherapy. However, the role of Apaf-1, the main protein constituent of the apoptosome, in the process has yet not been analyzed. Furthermore as new chemotherapeutics develop, the possible chemotherapy-induced toxicity to rapidly dividing normal cells, especially sensitive differentiated cells, has to be considered. Such undesirable effects would probably be ameliorated by selectively and locally inhibiting apoptosis in defined sensitive cells.

Methodology and Principal Findings

Mouse embryonic fibroblasts (MEFS) from Apaf-1 knock out mouse (MEFS KO Apaf-1) and Bax/Bak double KO (MEFS KO Bax/Bak), MEFS from wild-type mouse (MEFS wt) and human cervix adenocarcinoma (HeLa) cells were used to comparatively investigate the signaling cell death-induced pathways of BH3-mimetics, like ABT737 and GX15-070, with DNA damage-inducing agent cisplatin (cis-diammineplatinum(II) dichloride, CDDP). The study was performed in the absence or presence of apoptosis inhibitors namely, caspase inhibitors or apoptosome inhibitors. BH3-mimetic ABT737 required of Apaf-1 to exert its apoptosis-inducing effect. In contrast, BH3-mimetic GX15-070 and DNA damage-inducing CDDP induced cell death in the absence of both Bax/Bak and Apaf-1. GX15-070 induced autophagy-based cell death in all the cell lines analyzed. MEFS wt cells were protected from the cytotoxic effects of ABT737 and CDDP by chemical inhibition of the apoptosome through QM31, but not by using general caspase inhibitors.

Conclusions

BH3-mimetic ABT737 not only requires Bax/Bak to exert its apoptosis-inducing effect, but also Apaf-1, while GX15-070 and CDDP induce different modalities of cell death in the absence of Bax/Bak or Apaf-1. Inclusion of specific Apaf-1 inhibitors in topical and well-localized administrations, but not in systemic ones, to avoid interferences with chemotherapeutics would be of interest to prevent chemotherapeutic-induced unwanted cell death which could improve cancer patient care.     

Lifestyles and Risk Factors Associated with Adherence to the Mediterranean Diet: A Baseline Assessment of the PREDIMED Trial

Background

The traditional Mediterranean dietary pattern (MedDiet) is associated with longevity and low rates of cardiovascular disease (CVD). However, there is little information on who is more likely to follow this food pattern.

Aim

To evaluate how different factors are associated with lower MedDiet adherence in older Spanish subjects.

Methods

We included 7305 participants (men aged 55–80 y, women 60–80 y) at high-risk of CVD recruited into the PREDIMED trial (ISRCTN35739639). Socioeconomic, anthropometric, lifestyle characteristics and CVD risk factors were recorded. A validated 14-item questionnaire was used to evaluate MedDiet adherence at baseline. Multivariate models were used to estimate odds ratios (OR) and 95% confidence intervals for lower adherence to the MedDiet (<9 points out of 14) and ascertain factors independently associated with it.

Results

Former smoking (OR = 0.87; 95% CI, 0.78–0.98), physical activity (OR for the 3^rd vs. the 1^sttertile: 0.69; 0.62–0.78), and higher educational level (OR for university vs. less than primary school: 0.54; 0.38–0.77) were associated with higher MedDiet adherence. Conversely, having a larger waist-to-height ratio (OR for 0.1 units, 1.35; 1.22–1.49), being diabetic (OR = 1.13; 1.03–1.24), being single (OR = 1.27; 1.01–1.61) or divorced or separated (OR = 1.44; 1.09–1.89), and current smoking (OR = 1.28; 1.11–1.47) were associated with lower adherence.

Conclusions

Participants with little education, a larger waist-to-height ratio, or diabetes and those who were less physically active, single, divorced or separated, or smokers were less likely to adhere to the MedDiet, an ideal model for food choices. Stronger efforts of health promotion are needed in these groups to foster adoption of the MedDiet.     

Metarhizium anisopliae Pathogenesis of Mosquito Larvae: A Verdict of Accidental Death

Metarhizium anisopliae, a fungal pathogen of terrestrial arthropods, kills the aquatic larvae of Aedes aegypti, the vector of dengue and yellow fever. The fungus kills without adhering to the host cuticle. Ingested conidia also fail to germinate and are expelled in fecal pellets. This study investigates the mechanism by which this fungus adapted to terrestrial hosts kills aquatic mosquito larvae. Genes associated with the M. anisopliae early pathogenic response (proteinases Pr1 and Pr2, and adhesins, Mad1 and Mad2) are upregulated in the presence of larvae, but the established infection process observed in terrestrial hosts does not progress and insecticidal destruxins were not detected. Protease inhibitors reduce larval mortality indicating the importance of proteases in the host interaction. The Ae. aegypti immune response to M. anisopliae appears limited, whilst the oxidative stress response gene encoding for thiol peroxidase is upregulated. Cecropin and Hsp70 genes are downregulated as larval death occurs, and insect mortality appears to be linked to autolysis through caspase activity regulated by Hsp70 and inhibited, in infected larvae, by protease inhibitors. Evidence is presented that a traditional host-pathogen response does not occur as the species have not evolved to interact. M. anisopliae retains pre-formed pathogenic determinants which mediate host mortality, but unlike true aquatic fungal pathogens, does not recognise and colonise the larval host.     

Two Functional Variants of IRF5 Influence the Development of Macular Edema in Patients with Non-Anterior Uveitis

Objective

Interferon (IFN) signaling plays a crucial role in autoimmunity. Genetic variation in interferon regulatory factor 5 (IRF5), a major regulator of the type I interferon induction, has been associated with risk of developing several autoimmune diseases. In the current study we aimed to evaluate whether three sets of correlated IRF5 genetic variants, independently associated with SLE and with different functional roles, are involved in uveitis susceptibility and its clinical subphenotypes.

Methods

Three IRF5 polymorphisms, rs2004640, rs2070197 and rs10954213, representative of each group, were genotyped using TaqMan® allelic discrimination assays in a total of 263 non-anterior uveitis patients and 724 healthy controls of Spanish origin.

Results

A clear association between two of the three analyzed genetic variants, rs2004640 and rs10954213, and the absence of macular edema was observed in the case/control analysis (P _FDR=5.07E-03, OR=1.48, CI 95%=1.14-1.92 and P _FDR=3.37E-03, OR=1.54, CI 95%=1.19-2.01, respectively). Consistently, the subphenotype analysis accordingly with the presence/absence of this clinical condition also reached statistical significance (rs2004640: P=0.037, OR=0.69, CI 95%=0.48-0.98; rs10954213: P=0.030, OR=0.67, CI 95%=0.47-0.96), thus suggesting that both IRF5 genetic variants are specifically associated with the lack of macular edema in uveitis patients.

Conclusion

Our results clearly showed for the first time that two functional genetic variants of IRF5 may play a role in the development of macular edema in non-anterior uveitis patients. Identifying genetic markers for macular edema could lead to the possibility of developing novel treatments or preventive therapies.     

A BK (Slo1) channel journey from molecule to physiology

Calcium and voltage-activated potassium (BK) channels are key actors in cell physiology, both in neuronal and non-neuronal cells and tissues. Through negative feedback between intracellular Ca²⁺ and membrane voltage, BK channels provide a damping mechanism for excitatory signals. Molecular modulation of these channels by alternative splicing, auxiliary subunits and post-translational modifications showed that these channels are subjected to many mechanisms that add diversity to the BK channel α subunit gene. This complexity of interactions modulates BK channel gating, modifying the energetic barrier of voltage sensor domain activation and channel opening. Regions for voltage as well as Ca²⁺ sensitivity have been identified, and the crystal structure generated by the 2 RCK domains contained in the C-terminal of the channel has been described. The linkage of these channels to many intracellular metabolites and pathways, as well as their modulation by extracellular natural agents, has been found to be relevant in many physiological processes. This review includes the hallmarks of BK channel biophysics and its physiological impact on specific cells and tissues, highlighting its relationship with auxiliary subunit expression.