Significant sex difference in the association between C‐reactive protein concentration and anthropometry among 13‐ to 19‐year olds,but not 6‐ to 12‐year olds in Nepal

Life history theory predicts a trade‐off between immunostimulation and growth. Using a cross‐sectional study design, this study aims to test the hypothesis that C‐reactive protein (CRP) is negatively associated with height‐for‐age z‐scores (HAZ scores) and BMI‐for‐age z‐scores (BAZ scores) among 6‐ to 19‐year olds (N = 426) residing in five Nepalese communities. Dried blood spot (DBS) samples were collected and assayed for CRP using an in‐house enzyme immunoassay (EIA). Sex‐ and age‐group‐specific CRP quartiles were used to examine its association with growth in linear mixed‐effects (LME) models. A significant difference was found in the proportion of elevated CRP (>2 mg/L, equivalent to ～3.2 mg/L serum CRP) between 13‐ and 19‐year‐old boys (12%) and girls (4%). Concentrations of CRP were positively associated with HAZ score among adolescent (13–19 years) boys, which may indicate that individuals with greater energy resources have better growth and a better response to infections, thus eliminating the expected trade‐off between body maintenance (immunostimulation) and growth. Adolescent boys with low BAZ and HAZ scores had low CRP values, suggesting that those who do not have enough energy for growth cannot increase their CRP level even when infected with pathogens. Among adolescent girls a positive association was observed between CRP and BAZ scores suggesting the possible effects of chronic low‐grade inflammation due to body fat rather than infection. The association between CRP and growth was less evident among children (6–12 years) compared with adolescents, indicating that the elevated energy requirement needed for the adolescent growth spurt and puberty may play some role. Am J Phys Anthropol 154:42–51, 2014. © 2014 Wiley Periodicals, Inc.     

Low levels of methyl β‐cyclodextrin disrupt GluA1‐dependent synaptic potentiation but not synaptic depression

Methyl‐β‐cyclodextrin (MβCD) is a reagent that depletes cholesterol and disrupts lipid rafts, a type of cholesterol‐enriched cell membrane microdomain. Lipid rafts are essential for neuronal functions such as synaptic transmission and plasticity, which are sensitive to even low doses of MβCD. However, how MβCD changes synaptic function, such as N‐methyl‐d ‐aspartate receptor (NMDA‐R) activity, remains unclear. We monitored changes in synaptic transmission and plasticity after disrupting lipid rafts with MβCD. At low concentrations (0.5 mg/mL), MβCD decreased basal synaptic transmission and miniature excitatory post‐synaptic current without changing NMDA‐R‐mediated synaptic transmission and the paired‐pulse facilitation ratio. Interestingly, low doses of MβCD failed to deplete cholesterol or affect α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor (AMPA‐R) and NMDA‐R levels, while clearly reducing GluA1 levels selectively in the synaptosomal fraction. Low doses of MβCD decreased the inhibitory effects of NASPM, an inhibitor for GluA2‐lacking AMPA‐R. MβCD successfully decreased NMDA‐R‐mediated long‐term potentiation but did not affect the formation of either NMDA‐R‐mediated or group I metabotropic glutamate receptor‐dependent long‐term depression. MβCD inhibited de‐depression without affecting de‐potentiation. These results suggest that MβCD regulates GluA1‐dependent synaptic potentiation but not synaptic depression in a cholesterol‐independent manner.

     

α8‐Integrins are required for hippocampal long‐term potentiation but not for hippocampal‐dependent learning

Integrins are heterodimeric transmembrane cell adhesion receptors that are essential for a wide range of biological functions via cell–matrix and cell–cell interactions. Recent studies have provided evidence that some of the subunits in the integrin family are involved in synaptic and behavioral plasticity. To further understand the role of integrins in the mammalian central nervous system, we generated a postnatal forebrain and excitatory neuron‐specific knockout of α8‐integrin in the mouse. Behavioral studies showed that the mutant mice are normal in multiple hippocampal‐dependent learning tasks, including a T‐maze, non‐match‐to‐place working memory task for which other integrin subunits like α3‐ and β1‐integrin are required. In contrast, mice mutant for α8‐integrin exhibited a specific impairment of long‐term potentiation (LTP) at Schaffer collateral–CA1 synapses, whereas basal synaptic transmission, paired‐pulse facilitation and long‐term depression (LTD) remained unaffected. Because LTP is also impaired in the absence of α3‐integrin, our results indicate that multiple integrin molecules are required for the normal expression of LTP, and different integrins display distinct roles in behavioral and neurophysiological processes like synaptic plasticity.     

Herbivore‐induced plants do not affect oviposition but do affect fitness of subsequent herbivores on canola

The diamondback moth (DBM), Plutella xylostella (L.) (Lepidoptera: Plutellidae), is oligophagous on plants in the Brassicaceae, and is considered one of the most significant insect pests of canola (Brassica napus L.), a major oilseed crop grown in the Prairie Provinces of Canada. The bertha armyworm (BAW), Mamestra configurata Walker (Lepidoptera: Noctuidae), is a generalist herbivore that preferentially feeds on canola plants. In the canola growing season in the Prairie Provinces of Canada, DBM feeding occurs prior to BAW herbivory. In this study, we test the effect of DBM herbivory on subsequent host use by BAW. Oviposition by female BAW was not influenced by previous DBM‐herbivory or mechanical damage of canola plants. Bertha armyworm larvae were deterred from feeding on canola previously damaged by DBM and larvae developed into lighter pupae when reared on DBM‐damaged plants. Bertha armyworm pupae that developed from larvae fed on mechanically damaged plants had similar pupal weights to those fed undamaged plants. Adult BAW reared on canola with previous DBM feeding damage had marginally smaller wings than moths reared on canola treated differently. The combination of these results suggests that herbivory by the brassicaceous specialist, DBM, negatively influences host use and larval performance by the generalist, BAW, on canola.     

Beta‐amyloid 1‐42 monomers,but not oligomers,produce PHF‐like conformation of Tau protein

The mechanistic relationship between amyloid β1‐42 (Aβ1‐42) and the alteration of Tau protein are debated. We investigated the effect of Aβ1‐42 monomers and oligomers on Tau, using mice expressing wild‐type human Tau that do not spontaneously develop Tau pathology. After intraventricular injection of Aβ1‐42, mice were sacrificed after 3 h or 4 days. The short‐lasting treatment with Aβ monomers, but not oligomers, showed a conformational PHF‐like change of Tau, together with hyperphosphorylation. The same treatment induced increase in concentration of GSK3 and MAP kinases. The inhibition of the kinases rescued the Tau changes. Aβ monomers increased the levels of total Tau, through the inhibition of proteasomal degradation. Aβ oligomers reproduced all the aforementioned alterations only after 4 days of treatment. It is known that Aβ1‐42 monomers foster synaptic activity. Our results suggest that Aβ monomers physiologically favor Tau activity and dendritic sprouting, whereas their excess causes Tau pathology. Moreover, our study indicates that anti‐Aβ therapies should be targeted to Aβ1‐42 monomers too.     

SUMO1‐conjugation is altered during normal aging but not by increased amyloid burden

A proper equilibrium of post‐translational protein modifications is essential for normal cell physiology, and alteration in these processes is key in neurodegenerative disorders such as Alzheimer's disease. Recently, for instance, alteration in protein SUMOylation has been linked to amyloid pathology. In this work, we aimed to elucidate the role of protein SUMOylation during aging and increased amyloid burden in vivo using a His₆‐HA‐SUMO1 knock‐in mouse in the 5XFAD model of Alzheimer's disease. Interestingly, we did not observe any alteration in the levels of SUMO1‐conjugation related to Alzheimer's disease. SUMO1 conjugates remained localized to neuronal nuclei upon increased amyloid burden and during aging and were not detected in amyloid plaques. Surprisingly however, we observed age‐related alterations in global levels of SUMO1 conjugation and at the level of individual substrates using quantitative proteomic analysis. The identified SUMO1 candidate substrates are dominantly nuclear proteins, mainly involved in RNA processing. Our findings open novel directions of research for studying a functional link between SUMOylation and its role in guarding nuclear functions during aging.     

A 120‐year record of resilience to environmental change in brachiopods

The inability of organisms to cope in changing environments poses a major threat to their survival. Rising carbon dioxide concentrations, recently exceeding 400 μatm, are rapidly warming and acidifying our oceans. Current understanding of organism responses to this environmental phenomenon is based mainly on relatively short‐ to medium‐term laboratory and field experiments, which cannot evaluate the potential for long‐term acclimation and adaptation, the processes identified as most important to confer resistance. Here, we present data from a novel approach that assesses responses over a centennial timescale showing remarkable resilience to change in a species predicted to be vulnerable. Utilising museum collections allows the assessment of how organisms have coped with past environmental change. It also provides a historical reference for future climate change responses. We evaluated a unique specimen collection of a single species of brachiopod (Calloria inconspicua) collected every decade from 1900 to 2014 from one sampling site. The majority of brachiopod shell characteristics remained unchanged over the past century. One response, however, appears to reinforce their shell by constructing narrower punctae (shell perforations) and laying down more shell. This study indicates one of the most calcium‐carbonate‐dependent species globally to be highly resilient to environmental change over the last 120 years and provides a new insight for how similar species might react and possibly adapt to future change.     

Treadmill desks: A 1‐year prospective trial

Objective: Sedentariness is associated with weight gain and obesity. A treadmill desk is the combination of a standing desk and a treadmill that allow employees to work while walking at low speed. Design and Methods: The hypothesis was that a 1‐year intervention with treadmill desks is associated with an increase in employee daily physical activity (summation of all activity per minute) and a decrease in daily sedentary time (zero activity). Employees (n = 36; 25 women, 11 men) with sedentary jobs (87 ± 27 kg, BMI 29 ± 7 kg/m², n = 10 Lean BMI < 25 kg/m², n = 15 Overweight 25 < BMI < 30 kg/m², n = 11 Obese BMI > 30 kg/m²) volunteered to have their traditional desk replaced with a treadmill desk to promote physical activity for 1 year. Results: Daily physical activity (using accelerometers), work performance, body composition, and blood variables were measured at Baseline and 6 and 12 months after the treadmill desk intervention. Subjects who used the treadmill desk increased daily physical activity from baseline 3,353 ± 1,802 activity units (AU)/day to, at 6 months, 4,460 ± 2,376 AU/day (P < 0.001), and at 12 months, 4,205 ± 2,238 AU/day (P < 0.001). Access to the treadmill desks was associated with significant decreases in daily sedentary time (zero activity) from at baseline 1,020 ± 75 min/day to, at 6 months, 929 ± 84 min/day (P < 0.001), and at 12 months, 978 ± 95 min/day (P < 0.001). For the whole group, weight loss averaged 1.4 ± 3.3 kg (P < 0.05). Weight loss for obese subjects was 2.3 ± 3.5 kg (P < 0.03). Access to the treadmill desks was associated with increased daily physical activity compared to traditional chair‐based desks; their deployment was not associated with altered performance. For the 36 participants, fat mass did not change significantly, however, those who lost weight (n = 22) lost 3.4 ± 5.4 kg (P < 0.001) of fat mass. Weight loss was greatest in people with obesity. Conclusions: Access to treadmill desks may improve the health of office workers without affecting work performance.     

Activated human langerhans cells express mRNA for IL-1α and IL-1β and produce these cytokines but do not secrete them

Human Langerhans cells (LC) were isolated from epidermal cell preparations by panning with mouse anti-CD1 monoclonal antibody. RNA was prepared and probed for the presence of mRNAs for various cytokines using radiolabeled cDNAs. After stimulation with phorbol myristate acetate LC express RNA for interleukin 1α (IL-1α) and interleukin 1β (IL-1β) and produce proteins but do not secrete them at detectable levels. LC-associated IL-1, particularly IL-1α, may play a role in antigen presentation. PMA did not induce IL-6 expression in LC. The addition of lipopolysaccharide, a muramyl dipeptide analog, ionomycin, IL-1α, tumor necrosis factor-α, insulin-like growth factor-1 or IL-6 did not induce IL-1 mRNA in LC. UVB augmented IL-1β mRNA expression. Glucocorticoids did not detectably affect IL-1α or IL-1β mRNA levels following PMA induction, however, staurosporin inhibited IL-1β mRNA synthesis. Thus the inducers and regulators of IL-1 formation in human LC and monocytes are not identical.     

Salmonella enterica synthesizes 5,6‐dimethylbenzimidazolyl‐(DMB)‐α‐riboside. Why some Firmicutes do not require the canonical DMB activation system to synthesize adenosylcobalamin

5,6‐Dimethylbenzimidazolyl‐(DMB)‐ α ‐ribotide [ α ‐ribazole‐5′‐phosphate ( α ‐RP)] is an intermediate in the biosynthesis of adenosylcobalamin (AdoCbl) in many prokaryotes. In such microbes, α ‐RP is synthesized by nicotinate mononucleotide (NaMN):DMB phosphoribosyltransferases (CobT in Salmonella enterica), in a reaction that is considered to be the canonical step for the activation of the base of the nucleotide present in adenosylcobamides. Some Firmicutes lack CobT‐type enzymes but have a two‐protein system comprised of a transporter (i.e., CblT) and a kinase (i.e., CblS) that can salvage exogenous α ‐ribazole ( α ‐R) from the environment using CblT to take up α ‐R, followed by α ‐R phosphorylation by CblS. We report that Geobacillus kaustophilus CblT and CblS proteins restore α ‐RP synthesis in S. enterica lacking the CobT enzyme. We also show that a S. enterica cobT strain that synthesizes GkCblS ectopically makes only AdoCbl, even under growth conditions where the synthesis of pseudoCbl is favored. Our results indicate that S. enterica synthesizes α ‐R, a metabolite that had not been detected in this bacterium and that GkCblS has a strong preference for DMB‐ribose over adenine‐ribose as substrate. We propose that in some Firmicutes DMB is activated to α ‐RP via α ‐R using an as‐yet‐unknown route to convert DMB to α ‐R and CblS to convert α ‐R to α ‐RP.     

Maternal weight change between 1 and 2 years postpartum: the importance of 1 year weight retention

Pregnancy weight gain may lead to long-term increases in maternal BMI for some women. The objective of this study was to examine maternal body weight change 1y-2y postpartum, and to compare classifications of 2y weight retention with and without accounting for 1y-2y weight gain. Early pregnancy body weight (EPW, first trimester) was measured or imputed, and follow-up measures obtained before delivery, 1 year postpartum (1y) and 2 years postpartum (2y) in an observational cohort study of women seeking prenatal care in several counties in upstate New York (n = 413). Baseline height was measured; demographic and behavioral data were obtained from questionnaires and medical records. Associations of 1y-2y weight change (kg) and 1y-2y weight gain (≥2.25 kg) with anthropometric, socioeconomic, and behavioral variables were evaluated using linear and logistic regressions. While mean ± SE 1y-2y weight change was 0.009 ± 4.6 kg, 1y-2y weight gain (≥2.25 kg) was common (n = 108, 26%). Odds of weight gain 1y-2y were higher for overweight (OR(adj) = 2.63, CI(95%) = 1.43-4.82) and obese (OR(adj) = 2.93, CI(95%) = 1.62-5.27) women than for women with BMI <25. Two year weight retention (2y-EPW ≥2.25 kg) was misclassified in 38% (n = 37) of women when 1y-2y weight gain was ignored. One year weight retention (1YWR) (1y-EPW) was negatively related to 1y-2y weight change (β(adj) ± SE = -0.28 ± 0.04, P < 0.001) and weight gain (≥2.25 kg) (OR(adj) = 0.91, CI(95%) = 0.87-0.95). Relations between 1y weight retention and 1y-2y weight change were attenuated for women with higher early pregnancy BMI. Weight change 1y-2y was predicted primarily by an inverse relation with 1y weight retention. The high frequency of weight gain has important implications for classification of postpartum weight retention.     

Coping with multiple enemies: pairwise interactions do not predict evolutionary change in complex multitrophic communities

Predicting the ecological and evolutionary trajectories of populations in multispecies communities is one of the fundamental challenges in ecology. Many of these predictions are made by scaling patterns observed from pairwise interactions. Here, we show that the coupling of ecological and evolutionary outcomes is likely to be weaker in increasingly complex communities due to greater chance of life‐history trait correlations. Using model microbial communities comprising a focal bacterial species, Bacillus subtilis, a bacterial competitor, protist predator and phage parasite, we found that increasing the number of enemies in a community had an overall negative effect on B. subtilis population growth. However, only the competitor imposed direct selection for B. subtilis trait evolution in pairwise cultures and this effect was weakened in the presence of other antagonists that had a negative effect on the competitor. In contrast, adaptation to parasites was driven indirectly by correlated selection where competitors had a positive and predators a negative effect. For all measured traits, selection in pairwise communities was a poor predictor of B. subtilis evolution in more complex communities. Together, our results suggest that coupling of ecological and evolutionary outcomes is interaction‐specific and generally less evident in more complex communities where the increasing number of trait correlations could mask weak ecological signals.