Face–to–face interactions between mothers and female infants in wild bearded capuchin monkeys (Sapajus libidinosus)

Once considered uniquely human, mother–infant face–to–face interactions (FF) were observed in a few captive primates. In these studies, FF were correlated to physical contact suggesting a mechanism mediating proximity between mother and infant, as is the case for humans. We investigated this hypothesis in wild capuchin monkeys (Sapajus libidinosus) during the first year of life of eight female infants. Data were weekly focal-day videos of infants from which we recorded FF with mothers. We expected FF would increase with infants’ age (as time in contact with mothers decreased) and would more likely occur in the absence of physical contact between the dyad. There was no effect of age in the proportion of interaction time spent in FF, nor in types of FF. A quarter of FF episodes occurred in the absence of physical contact between the dyad, and in most of them physical contact was resumed following the FF. Contrary to predictions, the stability in the first year, mainly when mothers–female infants were in contact, indicates that FF act primarily promoting opportunities for affective communication and intuitive care. However, we found some supportive evidence for the hypothesis that FF regulate proximity between mother and infant, mainly in resume physical contact.     

Effects of high fat diet,ovariectomy, and physical activity on leptin receptor expression in rat brain and white fat tissue

Aim

To evaluate in a rat animal model whether ovariectomy, high fat diet (HFD), and physical activity in the form of running affect leptin receptor (Ob-R) distribution in the brain and white fat tissue compared to sham (Sh) surgery, standard diet (StD), and sedentary conditions.

Methods

The study included 48 female laboratory Wistar rats (4 weeks old). Following eight weeks of feeding with standard or HFD, rats were subjected to either OVX or Sh surgery. After surgery, all animals continued StD or HFD for the next 10 weeks. During these 10 weeks, ovariectomy and Sh groups were subjected to physical activity or sedentary conditions. Free-floating immunohistochemistry and Western blot methods were carried out to detect Ob-R in the brain and adipose tissue.

Results

StD-ovariectomy-sedentary group had a greater number of Ob-R positive neurons in lateral hypothalamic nuclei than StD-Sh-sedentary group. There was no difference in Ob-R positive neurons in arcuatus nuclei between all groups. Ob-R distribution in the barrel cortex was higher in HFD group than in StD group. Ob-R presence in perirenal and subcutaneous fat was decreased in StD-ovariectomy group.

Conclusion

HFD and ovariectomy increased Ob-R distribution in lateral hypothalamic nuclei, but there was no effect on arcuatus nuclei. Our results are first to suggest that HFD, ovariectomy, and physical activity affect Ob-R distribution in the barrel cortex, which might be correlated with the role of Ob-R in election of food in rats.Obesity is one of the leading health issues worldwide, associated with an increased risk of morbidity and mortality (1). In 1997, the World Health Organization (WHO) formally recognized obesity as a global epidemic (2). Increase in body fat stores and obesity is caused by an imbalance between energy intake and energy expenditure (3,4). Since childhood obesity is a predictor of an increased death rate, the “obesity epidemic” may reverse the current declining rate of death from cardiovascular diseases (5). Factors that contribute to obesity can be environmental (6), social (7), behavioral (8), psychological (9), and genetic (10,11).Women generally have more body fat than men (12). Nevertheless similar odds ratios were recorded in women and men for the association of abdominal obesity with acute myocardial infarction (13). Weight gain is common after menopause, indicating an association between hormones and fat stores (14). A large scale observational study found that both the body mass index and the level of physical activity were independent predictors of mortality and that a higher level of physical activity did not eliminate the risk associated with adiposity. At the same time, women who were both lean and physically active had the lowest mortality (15). In animal studies menopause can be induced by ovariectomy (OVX) (16).Obesity can also be called a disorder of appetite and it is controlled by complex homeostatic mechanisms involving the hypothalamus and brainstem (17). Many gut peptides like cholecystokinin, ghrelin, glucagon-like peptide-1 (GLP-1), and -2 and peptide YY (PYY) act on the brain to control eating behavior (18). There are two different system for controlling feeding behavior: short-term and long-term (19). Short-term regulation involves neural signals from the GI tract and its hormones, like insulin, glucagon, and ghrelin (20). A hormone that functions mainly within long-term regulation is leptin (16 kD), a hormonal product of the obesity (ob) gen, primarily secreted by adipocytes (21) and released in the brain. It generates a feeling of satisfaction and acts like an appetite-suppressing agent. Circulating leptin levels are lower in ovariectomized rats (22).Food intake is regulated via neural circuits located in the hypothalamus (23). Leptin acts via its leptin or Ob receptors (Ob-R) and is primarily expressed in hypothalamic neurons (19) especially in arcuate, ventromedial, and dorsomedial nuclei (24). Leptin is transported across the blood-brain barrier (BBB) by a saturable transporter (25). Ob-R is also detected in nonhypothalamic areas in the mice and in human brain neocortex, cerebellum, entorinal cortex, amygdale, and rostral medulla (26). Adipocytes, endothelial cells, and macrophages also have leptin receptor at its surface, which suggests autocrine and paracrine action for leptin in human adipose tissue (27). Association between the expression of Ob-R in target tissues and physiological and hormonal controlled processes is still unclear. Leptin receptors mRNA is found in each of the major components of the CNS “feeding” circuitry – the brainstem, hypothalamus, and is distributed reward centers (Allan brain) (28). Therefore, the aim of the current study was to evaluate whether HFD affects Ob-R distribution compared with StD specifically in the barrel field and piriform cortex compared to standard feeding centers in the hypothalamus. We supposed that the combination of OVX and HFD is interesting for further research on selected brain regions, which might be alleviated by physical activity. We also supposed that changes in Ob-R level in white fat tissue would correlate with the changes in brain regions.     

An Alternative Pathway Through the Fenton Reaction for the Formation of Advanced Oxidation Protein Products,a New Class of Inflammatory Mediators

The accumulation of advanced oxidation protein products (AOPPs) has been linked to several pathological conditions, and their levels are formed during oxidative stress as a result of reactions between plasma proteins and chlorinated oxidants produced by myeloperoxidase (MPO). However, it was suggested that the generation of this mediator of inflammation may also occur via an MPO-independent pathway. The aim of this study was to induce the formation of AOPPs in vitro through Fenton reaction and to investigate whether this generation could be counteracted by N-acetylcysteine (NAC) and fructose-1,6-bisphosphate (FBP). The complete Fenton system increased the AOPPs levels and both NAC and FBP were capable of inhibiting the formation of Fenton reaction-induced AOPPs. These data provide a new hypothesis about another pathway of AOPPs formation, as well as report that NAC and FBP may be good candidates to neutralize pro-inflammatory and pro-oxidant effects of AOPPs in several diseases.     

Herpes simplex virus 2 vasculitis as cause of ischemic stroke in a young immunocompromised patient

Journal of NeuroVirology - Herpes simplex virus 2 (HSV-2) is a very rare cause of central nervous system (CNS) infections. We report a case of a young woman with a left middle cerebral artery (MCA)...     

Association of rs1285933 single nucleotide polymorphism in CLEC5A gene with dengue severity and its functional effects

Outbreaks of the Zika, dengue, and chikungunya viruses, especially in the Americas, pose a global threat due to their rapid spread and difficulty controlling the vector. Extreme phenotypes are often observed, from asymptomatic to severe clinical manifestations, which are well-studied in dengue. Host variations are also important contributors to disease outcomes, and many case-control studies have associated single nucleotide polymorphisms (SNPs) with severe dengue. Here, we found that the TC genotype and T-carriers for SNP rs1285933 in the C-type lectin superfamily member 5 (CLEC5A) gene was associated with severe dengue in a Northern Brazilian population (OR = 2.75 and p-value = 0.01, OR = 2.11 and p-value = 0.04, respectively). We also tested the functional effect of the CLEC5A protein and found that it is upregulated on the surface of human monocytes after in vitro dengue infection. CLEC5A was correlated with viral load inside the monocytes (Spearman r = 0.55, p = 0.008) and TNF production in culture supernatants (Spearman r = 0.72, p = 0.03). Analysis of mRNA in blood samples from DENV4-infected patients exhibiting mild symptoms showed that CLEC5A mRNA expression is correlated with TNF (r = 0.67, p = 0.0001) and other immune mediators. Monocytes from rs1285933 TT/TC individuals showed lower CLEC5A expression compared to CC genotypes. However, in these cells, CLEC5A was not correlated with TNF production. In summary, we confirmed that CLEC5A is genetically associated with dengue severity outcome, playing a central role during the immune response triggered by a dengue viral infection, and rs1285933 is a relevant SNP that is able to regulate signaling pathways after interactions between the dengue virus and CLEC5A receptors.     

Malaria: looking for selection signatures in the human PKLR gene region

The genetic component of susceptibility to malaria is both complex and multigenic and the better‐known protective polymorphisms are those involving erythrocyte‐specific structural proteins and enzymes. In vivo and in vitro data have suggested that pyruvate kinase deficiency, which causes a nonspherocytic haemolytic anaemia, could be protective against malaria severity in humans, but this hypothesis remains to be tested. In the present study, we conducted a combined analysis of Short Tandem Repeats (STRs) and Single Nucleotide Polymorphisms (SNPs) in the pyruvate kinase‐encoding gene (PKLR) and adjacent regions (chromosome 1q21) to look for malaria selective signatures in two sub‐Saharan African populations from Angola and Mozambique, in several groups with different malaria infection outcome. A European population from Portugal, including a control and a pyruvate kinase‐deficient group, was used for comparison. Data from STR and SNP loci spread along the PKLR gene region showed a considerably higher differentiation between African and Portuguese populations than that usually found for neutral markers. In addition, a wider region showing strong linkage disequilibrium was found in an uncomplicated malaria group, and a haplotype was found to be associated with this clinical group. Altogether, this data suggests that malaria selective pressure is acting in this genomic region.     

Miocardiopatia hipocalcémica

The association between hypocalcemia and heart failure is rare. There are few reported cases in the literature of this association, which is termed hypocalcemic cardiomyopathy.We report the case of a 61-year-old woman with no relevant medical history, admitted for progressively worsening exertional dyspnea, orthopnea and edema of the lower limbs for a previous month. Physical examination showed diffuse muscle spasms, with no signs of latent tetany.Further investigation revealed ionized calcium 0.54 mmol/l (normal 1.12-1.30), phosphorus 9.8 mg/dl, parathyroid hormone <2.5 pg/ml and CK >3000 U/l, with normal thyroid function. The electrocardiogram showed long QT interval and a pattern of left ventricular overload, and myocardial biomarkers were negative. The echocardiogram revealed regional wall motion abnormalities, coronary angiography was normal and a cranial CT scan detected calcification of basal ganglia and white matter.She started diuretic and calcium replacement therapy which resulted in complete clinical recovery, with no need for heart failure therapy after normalization of serum calcium.     

Preeclampsia: the role of tissue factor and tissue factor pathway inhibitor

Preeclampsia (PE) is a multi-system disorder of human pregnancy, whose etiology remains poorly understood. Preeclamptic women are known to have an increased hypercoagulable state that result in excess fibrin deposition in several organs, which compromises their function. Tissue factor (TF) is the main physiological initiator of blood coagulation and its activity is regulated by a specific inhibitor known as Tissue factor pathway inhibitor (TFPI). Based on the important role of TF and TFPI in hemostasis, we hypothesize that their levels may change in the severe PE contributing to exacerbate hypercoagulable state. Some studies have assessed the balance between TF and TFPI in preeclamptic women, but results are inconsistent. Therefore, the aim of this study was to examine these inconsistencies and to assess TF and TFPI plasma levels in three groups of age matched women; pregnant with severe PE (n = 60), normotensive pregnant (n = 50) and normotensive non-pregnant women (n = 50). There was not significantly different among the three groups for TF plasma levels; severe PE women: 338.4 pg/mL (248.1-457.6), normotensive pregnant women: 301.5 pg/mL (216.4-442.9) and normotensive non-pregnant women 393 pg/mL (310.3-522.9). TFPI plasma levels were higher in severe PE comparing to normotensive pregnant women and normotensive non-pregnant women, 115.8 ng/mL (75-149.8); 80.3 ng/mL (59.6-99.7) and 74.5 ng/mL (47.1-98.0), respectively No difference was found between normotensive pregnant women and normotensive non-pregnant women. As for gestational age, a significant difference in TFPI levels was found between severe PE and normotensive pregnant women up to the 33rd week of pregnancy (p = 0.001), and severe PE and non-pregnant women up to the 34th (p = 0.01). In summary, our results indicated that TF plasma levels did not vary in the studied groups, while TFPI plasma levels were significantly increased in severe PE compared to normotensive pregnant and normotensive non-pregnant women. So, our data do not explain the exacerbated hypercoagulability state observed in severe PE. Further studies evaluating genes expression, TF activity and antigen, total and free TFPI and TFPI-2, both in plasma and obstetric tissues, throughout the pregnancy in PE (mild and severe forms) are required.