Adaptation to milking agropastoralism in Chilean goat herders and nutritional benefit of lactase persistence

The genetic trait of lactase persistence (LP) evolved as an adaptation to milking pastoralism in the Old World and is a well-known example of positive natural selection in humans. However, the specific mechanisms conferring this selective advantage are unknown. To understand the relationship between milk drinking, LP, growth, reproduction, and survival, communities of the Coquimbo Region in Chile, with recent adoption of milking agropastoralism, were used as a model population. DNA samples and data on stature, reproduction, and diet were collected from 451 participants. Lactose tolerance tests were done on 41 of them. The European -13,910*T (rs4988235) was the only LP causative variant found, showing strong association (99.6%) with LP phenotype. Models of associations of inferred LP status and milk consumption, with fertility, mortality, height, and weight were adjusted with measures of ancestry and relatedness to control for population structure. Although we found no statistically significant effect of LP on fertility, a significant effect (P = 0.002) was observed of LP on body mass index (BMI) in males and of BMI on fertility (P = 0.003). These results fail to support a causal relationship between LP and fertility yet suggest the idea of a nutritional advantage of LP. Furthermore, the proportion of European ancestry around the genetic region of -13,910*T is significantly higher (P = 0.008) than the proportion of European ancestry genome-wide, providing evidence of recent positive selection since European-Amerindian admixture. This signature was absent in nonpastoralist Latin American populations, supporting the hypothesis of specific adaptation to milking agropastoralism in the Coquimbo communities

Compromised Hippocampal Neuroplasticity in the Interferon-α and Toll-like Receptor-3 Activation-Induced Mouse Depression Model.

Disrupted neuronal plasticity due to subtle inflammation is considered to play a fundamental role in the pathogenesis of major depressive disorder. Interferon-α (IFN-α) potentiates immune responses against viral pathogens that induce toll-like receptor-3 (TLR3) activation but evokes severe major depressive disorder in humans by mechanisms that remain insufficiently described. By using a previously established mouse model of depression induced by combined delivery of IFN-α and polyinosinic:polycytidylic acid (poly(I:C)), a TLR3 agonist, we provide evidence that IFN-α and poly(I:C) reduce apical dendritic spine density in the hippocampal CA1 area ex vivo via mechanisms involving decreased TrkB signaling. In vitro, IFN-α and poly(I:C) treatments required neuronal activity to reduce dendritic spine density and TrkB signaling. The levels of presynaptic protein vesicular glutamate transporter (VGLUT)-1 and postsynaptic protein postsynaptic density-95 (PSD95) were specifically decreased, whereas the expression of both synaptic and extrasynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor 1 (AMPAR1) was increased by IFN-α and poly(I:C) delivery. Patch clamp recordings in primary hippocampal neurons revealed that morphological changes at the synapse induced by IFN-α and poly(I:C) costimulation were accompanied by an increased action potential threshold and action potential frequency, indicative of impaired neuronal excitability. Taken together, IFN-α and poly(I:C) delivery leads to structural and functional alterations at the synapse indicating that compromised neuroplasticity may play an integral role in the pathogenesis of immune response-induced depression

Early Predictors of Objectively Measured Physical Activity and Sedentary Behaviour in 8–10 Year Old Children: The Gateshead Millennium Study

With a number of studies suggesting associations between early life influences and later chronic disease risk, it is suggested that associations between early growth and later physical activity (PA) may be a mediator. However, conflicting evidence exists for association between birth weight and childhood PA. In addition, it is important to know what other, potentially modifiable, factors may influence PA in children given its' association with childhood and later adiposity. We used the Gateshead Millennium Study (GMS) to identify predictors of childhood PA levels. The GMS is a cohort of 1029 infants born in 1999–2000 in Gateshead in northern England. Throughout infancy and early childhood, detailed information was collected. Assessments at age 9 years included body composition, objective measures of habitual PA and a range of lifestyle factors. Mean total volumes of PA (accelerometer count per minute, cpm) and moderate-vigorous intensity PA (MVPA), and the percentage of time spent in sedentary behaviour (%SB) were quantified and related to potential predictors using linear regression and path analysis. Children aged 8–10 years were included. Significant differences were seen in all three outcome variables between sexes and season of measurement (p<0.001). Restricting children’s access to television was associated with decreased MVPA. Increased paternal age was associated with significant increases in %SB (p = 0.02), but not MVPA or total PA. Increased time spent in out of school sports clubs was significantly associated with decreased %SB (p = 0.02). No significant associations were seen with birth weight. A range of factors, directly or indirectly, influenced PA and sedentary behaviour. However, associations differed between the different constructs of PA and %SB. Exploring further the sex differences in PA would appear to be useful, as would encouraging children to join out of school sports clubs

The beta-Oslo method: experimentally constrained (n,γn,\gamma) reaction rates relevant to the rr-process

Unknown neutron-capture reaction rates remain a significant source of uncertainty in state-of-the-art $r$-process nucleosynthesis reaction network calculations. As the $r$-process involves highly neutron-rich nuclei for which direct ($n,\gamma$) cross-section measurements are virtually impossible, indirect methods are called for to constrain ($n,\gamma$) cross sections used as input for the $r$-process nuclear network. Here we discuss the newly developed beta-Oslo method, which is capable of providing experimental input for calculating ($n,\gamma$) rates of neutron-rich nuclei. The beta-Oslo method represents a first step towards constraining neutron-capture rates of importance to the $r$-process.Comment: 4 pages, 1 figure, conference proceedings Nuclei in the Cosmos XV 2018, Italy

Assessment of fatigue in chronic disease: a bibliographic study of fatigue measurement scales

A large number of fatigue scales exist and there is no consensus on which fatigue measuring scales that are most appropriate for use in assessment of fatigue in different diseases. We aimed to describe the use of fatigue scales in studies of disease-related fatigue during the last three decades. We searched databases from 1975 to 2004 for original studies reporting on disease-related fatigue and extracted information on method used to assess fatigue, diseases under study and year of publication. A total of 2285 papers reported measures of fatigue in chronic non-acute diseases of which 80% were published during the last decade. We identified 252 different ways to measure fatigue, of which 150 were use only once. Multi-symptom scales (n = 156) were used in 670 studies, while 71 scales specifically designed to measure fatigue were applied in 416 studies. The majority of these studies used scales with a multidimensional approach to fatigue, and most studies used scales that were disease-specific or only applied to few different diseases. Research in disease-related fatigue has increased exponentially during the last three decades, even if we adjust for the general increase in publishing activity. The number of scales has also increased and the majority of scales were developed for specific diseases. There is need for measure instruments with different sizes and dimensionality, and due to ceiling and floor effects, the same scale may not be useful for patients with different severity of fatigue. However, since fatigue is an unspecific symptom there should not be need for adopting disease specific fatigue scales for each individual disease. There may be differences in characteristics of fatigue between diseases and generic measurement instruments may facilitate documentation of such differences, which may be of clinical importance

Building Babies - Chapter 16

In contrast to birds, male mammals rarely help to raise the offspring. Of all mammals, only among rodents, carnivores, and primates, males are sometimes intensively engaged in providing infant care (Kleiman and Malcolm 1981). Male caretaking of infants has long been recognized in nonhuman primates (Itani 1959). Given that infant care behavior can have a positive effect on the infant’s development, growth, well-being, or survival, why are male mammals not more frequently involved in “building babies”? We begin the chapter defining a few relevant terms and introducing the theory and hypotheses that have historically addressed the evolution of paternal care. We then review empirical findings on male care among primate taxa, before focusing, in the final section, on our own work on paternal care in South American owl monkeys (Aotus spp.). We conclude the chapter with some suggestions for future studies.Deutsche Forschungsgemeinschaft (HU 1746/2-1) Wenner-Gren Foundation, the L.S.B. Leakey Foundation, the National Geographic Society, the National Science Foundation (BCS-0621020), the University of Pennsylvania Research Foundation, the Zoological Society of San Dieg

Predictive factors of virological success to salvage regimens containing protease inhibitors in HIV-1 infected children

<p>Abstract</p> <p>Background</p> <p>The impact of HIV drug resistance mutations in salvage therapy has been widely investigated in adults. By contrast, data available of predictive value of resistance mutations in pediatric population is scarce.</p> <p>Methods</p> <p>A multicenter, retrospective, observational study was conducted in children who received rescue salvage antiretroviral therapy after virologic failure. CD4 counts and viral load were determined at baseline and 6 months after rescue intervention. Genotypic HIV-1 resistance test and virtual phenotype were assessed at baseline.</p> <p>Results</p> <p>A total of 33 children met the inclusion criteria and were included in the analysis. The median viral load (VL) and median percentage of CD4+ at baseline was 4.0 HIV-RNA log copies/ml and 23.0% respectively. The median duration that children were taking the new rescue regimen was 24.3 weeks (23.8–30.6). Overall, 47% of the 33 children achieved virological response at 24 weeks. When we compared the group of children who achieved virological response with those who did not, we found out that mean number of PI related mutations among the group of responders was 3.8 <it>vs</it>. 5.4 (p = 0.115). Moreover, the mean number of susceptible drugs according to virtual phenotype clinical cut-off for maximal virologic response was 1.7 <it>vs</it>. 0.8 and mean number of susceptible drugs according to virtual phenotype cut-off for minimal virlologic response was 2.7 <it>vs</it>. 1.3 (p < 0.01 in all cases). Eighteen children were rescued with a regimen containing a boosted-PI and virological response was significantly higher in those subjects compared with the others (61.1% <it>vs</it>. 28.6%, p < 0.01).</p> <p>Conclusion</p> <p>Salvage treatment containing ritonavir boosted-PIs in children with virological failure was very efficient. The use of new tools as virtual phenotype could help to improve virologic success in pediatric population.</p