Extended parental provisioning and variation in vertebrate brain sizes

Large brains provide adaptive cognitive benefits but require unusually high, near-constant energy inputs and become fully functional well after their growth is completed. Consequently, young of most larger-brained endotherms should not be able to independently support the growth and development of their own brains. This paradox is solved if the evolution of extended parental provisioning facilitated brain size evolution. Comparative studies indeed show that extended parental provisioning coevolved with brain size and that it may improve immature survival. The major role of extended parental provisioning supports the idea that the ability to sustain the costs of brains limited brain size evolution

Hibernation constrains brain size evolution in mammals

The expensive brain hypothesis predicts that the lowest stable level of steady energy input acts as a strong constraint on a species’ brain size, and thus, that periodic troughs in net energy intake should select for reduced brain size relative to body mass. Here, we test this prediction for the extreme case of hibernation. Hibernators drastically reduce food intake for up to several months and are therefore expected to have smaller relative brain sizes than nonhibernating species. Using a comparative phylogenetic approach on brain size estimates of 1104 mammalian species, and controlling for possible confounding variables, we indeed found that the presence of hibernation in mammals is correlated with decreased relative brain size. This result adds to recent comparative work across mammals and amphibians supporting the idea that environmental seasonality (where in extremis hibernation is necessary for survival) imposes an energetic challenge and thus acts as an evolutionary constraint on relative brain size

Rural and urban exposures shape early life immune development in South African children with atopic dermatitis and nonallergic children

Background Immunological traits and functions have been consistently associated with environmental exposures and are thought to shape allergic disease susceptibility and protection. In particular, specific exposures in early life may have more significant effects on the developing immune system, with potentially long‐term impacts. Methods We performed RNA‐Seq on peripheral blood mononuclear cells (PBMCs) from 150 children with atopic dermatitis and healthy nonallergic children in rural and urban settings from the same ethnolinguistic AmaXhosa background in South Africa. We measured environmental exposures using questionnaires. Results A distinct PBMC gene expression pattern was observed in those children with atopic dermatitis (132 differentially expressed genes [DEGs]). However, the predominant influences on the immune cell transcriptome were related to early life exposures including animals, time outdoors, and types of cooking and heating fuels. Sample clustering revealed two rural groups (Rural_1 and Rural_2) that separated from the urban group (3413 and 2647 DEGs, respectively). The most significantly regulated pathways in Rural_1 children were related to innate activation of the immune system (e.g., TLR and cytokine signaling), changes in lymphocyte polarization (e.g., TH17 cells), and immune cell metabolism (i.e., oxidative phosphorylation). The Rural_2 group displayed evidence for ongoing lymphocyte activation (e.g., T cell receptor signaling), with changes in immune cell survival and proliferation (e.g., mTOR signaling, insulin signaling). Conclusions This study highlights the importance of the exposome on immune development in early life and identifies potentially protective (e.g., animal) exposures and potentially detrimental (e.g., pollutant) exposures that impact key immunological pathways

Manipulation complexity in primates coevolved with brain size and terrestriality

Humans occupy by far the most complex foraging niche of all mammals, built around sophisticated technology, and at the same time exhibit unusually large brains. To examine the evolutionary processes underlying these features, we investigated how manipulation complexity is related to brain size, cognitive test performance, terrestriality, and diet quality in a sample of 36 non-human primate species. We categorized manipulation bouts in food-related contexts into unimanual and bimanual actions, and asynchronous or synchronous hand and finger use, and established levels of manipulative complexity using Guttman scaling. Manipulation categories followed a cumulative ranking. They were particularly high in species that use cognitively challenging food acquisition techniques, such as extractive foraging and tool use. Manipulation complexity was also consistently positively correlated with brain size and cognitive test performance. Terrestriality had a positive effect on this relationship, but diet quality did not affect it. Unlike a previous study on carnivores, we found that, among primates, brain size and complex manipulations to acquire food underwent correlated evolution, which may have been influenced by terrestriality. Accordingly, our results support the idea of an evolutionary feedback loop between manipulation complexity and cognition in the human lineage, which may have been enhanced by increasingly terrestrial habits.Peer reviewe

Sensitivity, specificity, and diagnostic accuracy of WHO 2013 criteria for diagnosis of gestational diabetes mellitus in low risk early pregnancies: international, prospective, multicentre cohort study

Objective: To evaluate the predictability of gestational diabetes mellitus wth a 75 g oral glucose tolerance test (OGTT) in early pregnancy, based on the 2013 criteria of the World Health Organization, and to test newly proposed cut-off values. Design: International, prospective, multicentre cohort study.SettingSix university or cantonal departments in Austria, Germany, and Switzerland, from 1 May 2016 to 31 January 2019.ParticipantsLow risk cohort of 829 participants aged 18-45 years with singleton pregnancies attending first trimester screening and consenting to have an early 75 g OGTT at 12-15 weeks of gestation. Participants and healthcare providers were blinded to the results. Main outcome measures: Fasting, one hour, and two hour plasma glucose concentrations after an early 75 g OGTT (12-15 weeks of gestation) and a late 75 g OGTT (24-28 weeks of gestation). Results: Of 636 participants, 74 (12%) developed gestational diabetes mellitus, according to World Health Organization 2013 criteria, at 24-28 weeks of gestation. Applying WHO 2013 criteria to the early OGTT with at least one abnormal value gave a low sensitivity of 0.35 (95% confidence interval 0.24 to 0.47), high specificity of 0.96 (0.95 to 0.98), positive predictive value of 0.57 (0.41 to 0.71), negative predictive value of 0.92 (0.89 to 0.94), positive likelihood ratio of 10.46 (6.21 to 17.63), negative likelihood ratio of 0.65 (0.55 to 0.78), and diagnostic odds ratio of 15.98 (8.38 to 30.47). Lowering the postload glucose values (75 g OGTT cut-off values of 5.1, 8.9, and 7.8 mmol/L) improved the detection rate (53%, 95% confidence interval 41% to 64%) and negative predictive value (0.94, 0.91 to 0.95), but decreased the specificity (0.91, 0.88 to 0.93) and positive predictive value (0.42, 0.32 to 0.53) at a false positive rate of 9% (positive likelihood ratio 5.59, 4.0 to 7.81; negative likelihood ratio 0.64, 0.52 to 0.77; and diagnostic odds ratio 10.07, 6.26 to 18.31). Conclusions: The results of this prospective low risk cohort study indicated that the 75 g OGTT as a screening tool in early pregnancy is not sensitive enough when applying WHO 2013 criteria. Postload glucose values were higher in early pregnancy complicated by diabetes in pregnancy. Lowering the postload cut-off values identified a high risk group for later development of gestational diabetes mellitus or those who might benefit from earlier treatment. Results from randomised controlled trials showing a beneficial effect of early intervention are unclear. Trial registrationClinicalTrials.govNCT02035059

Reproductive seasonality in primates: patterns, concepts and unsolved questions

Primates, like other mammals, exhibit an annual reproductive pattern that ranges from strictly seasonal breeding to giving birth in all months of the year, but factors mediating this variation are not fully understood. We applied both a categorical description and quantitative measures of the birth peak breadth based on daily observations in zoos to characterise reproductive seasonality in 141 primate species with an average of 941 birth events per species. Absolute day length at the beginning of the mating season in seasonally reproducing species was not correlated between populations from natural habitats and zoos. The mid‐point of latitudinal range was a major factor associated with reproductive seasonality, indicating a correlation with photoperiod. Gestation length, annual mean temperature, natural diet and Malagasy origin were other important factors associated with reproductive seasonality. Birth seasons were shorter with increasing latitude of geographical origin, corresponding to the decreasing length of the favourable season. Species with longer gestation periods were less seasonal than species with shorter ones, possibly because shorter gestation periods more easily facilitate the synchronisation of reproductive activity with annual cycles. Habitat conditions with higher mean annual temperature were also linked to less‐seasonal reproduction, independently of the latitude effect. Species with a high percentage of leaves in their natural diet were generally non‐seasonal, potentially because the availability of mature leaves is comparatively independent of seasons. Malagasy primates were more seasonal in their births than species from other regions. This might be due to the low resting metabolism of Malagasy primates, the comparatively high degree of temporal predictability of Malagasy ecosystems, or historical constraints peculiar to Malagasy primates. Latitudinal range showed a weaker but also significant association with reproductive seasonality. Amongst species with seasonal reproduction in their natural habitats, smaller primate species were more likely than larger species to shift to non‐seasonal breeding in captivity. The percentage of species that changed their breeding pattern in zoos was higher in primates (30%) than in previous studies on Carnivora and Ruminantia (13 and 10%, respectively), reflecting a higher concentration of primate species in the tropics. When comparing only species that showed seasonal reproduction in natural habitats at absolute latitudes ≤11.75°, primates did not differ significantly from these two other taxa in the proportion of species that changed to a less‐seasonal pattern in zoos. However, in this latitude range, natural populations of primates and Carnivora had a significantly higher proportion of seasonally reproducing species than Ruminantia, suggesting that in spite of their generally more flexible diets, both primates and Carnivora are more exposed to resource fluctuation than ruminants

Efficacy of Neoadjuvant Carboplatin plus Docetaxel in Triple-Negative Breast Cancer: Combined Analysis of Two Cohorts

Recent studies demonstrate that addition of neoadjuvant (NA) carboplatin (Cb) to anthracycline/taxane chemotherapy improves pathological complete response (pCR) in triple negative breast cancer (TNBC). Effectiveness of anthracycline-free, platinum combinations in TNBC is not well known. Here we report efficacy of NA carboplatin + docetaxel (CbD) in TNBC

Environmental Seasonality and Mammalian Brain Size Evolution

Ecology has been shown to be among the main drivers of brain size evolution. One important ecological aspect is environmental seasonality. Seasonality is related to brain size evolution in two different ways: On one hand, seasonality acts as energetic constraint on brain size because it forces animals to deal with periodic food shortages (expensive brain hypothesis). On the other hand, seasonality may act as a selective pressure to increase brain size, as cognitive and behavioural flexibility helps to overcome periods of food scarcity (cognitive buffer hypothesis). Current evidence suggests that energetic constraints imposed by environmental seasonality play a crucial role in mammalian brain size evolution, cognitive buffering; on the contrary, seems to be less ubiquitous and is mainly found in large‐brained species such as haplorrhine primates and birds