Parent-offspring transmission of adipocytokine levels and their associations with metabolic traits

Adipose tissue secreted cytokines (adipocytokines) have significant effects on the physiology and pathology of human metabolism relevant to diabetes and cardiovascular disease. We determined the relationship of the pattern of these circulating hormones with obesity-related phenotypes and whether such pattern is transmitted from parent to offspring. A combined total of 403 individuals from 156 consenting Saudi families divided into initial (119 families with 123 adults and 131 children) and replication (37 families with 58 adults and 91 children) cohorts were randomly selected from the RIYADH Cohort study. Anthropometrics were evaluated and metabolic measures such as fasting serum glucose, lipid profiles, insulin, leptin, adiponectin, resistin, tumor necrosis factor alpha (TNFα), activated plasminogen activator inhibitor 1 (aPAI1), high sensitivity C-reactive protein (hsCRP) and angiotensin II were also assessed. Parent-offspring regressions revealed that with the exception of hsCRP, all hormones measured showed evidence for significant inheritance. Principal component (PC) analysis of standardized hormone levels demonstrated surprising heritability of the three most common axes of variation. PC1, which explained 21% of the variation, was most strongly loaded on levels of leptin, TNFα, insulin, and aPAI1, and inversely with adiponectin. It was significantly associated with body mass index (BMI) and phenotypically stronger in children, and showed a heritability of ∼50%, after adjustment for age, gender and generational effects. We conclude that adipocytokines are highly heritable and their pattern of co-variation significantly influences BMI as early as the pre-teen years. Investigation at the genomic scale is required to determine the variants affecting the regulation of the hormones studied.     

Current status and recent trend of the Eurasian Woodcock Scolopax rusticola as a breeding bird in Britain

Capsule The breeding Woodcock population in Britain in 2013 was estimated at 55?241 males (95% CL: 41?806–69?004), suggesting a large-scale decline that is supported by 2 additional sources of data.

Aims To provide an updated estimate of the size of Britain's breeding Woodcock population, measure recent trends and identify spatial patterns of change.

Methods Displaying male Woodcock were surveyed at a stratified sample of 834 randomly selected sites. Population estimates were compared with a baseline survey conducted in 2003 and the trend with data from annual Woodcock counts (2003–13) and Bird Atlas 2007–11.

Results Woodcock were estimated to be present at 22% of 1?×?1?km squares containing ≥10?ha of woodland, compared to 35% in 2003. The British population estimate fell by 29% between 2003 and 2013. The Atlas suggests that presence at the 10?×?10?km scale has declined by 56% between 1970 and 2010. Both data sources suggest regional variation in the rate of decline, with losses greatest in the West and South.

Conclusion The Woodcock's population size and breeding range appear to be declining severely across Britain. Regional variation in the rate of decline might be explained by the distribution of large continuous woodlands.     

Status and distribution of European Nightjars Caprimulgus europaeus in the UK in 2004

Capsule The population of Nightjars in the UK increased by over 36% between 1992 and 2004.

Aims To determine the population size and distribution of Nightjars in the UK and examine associations with forestry and heathland habitat features.

Methods A volunteer survey was supported by professional cover in remote parts of Wales, and areas of Dorset and lowland Scotland. Two visits to allocated 1-km squares were made between late May and mid-July. Each surveyor recorded the locations of calling males onto maps and the occurrence of habitat categories within 50 m of each Nightjar registration.

Results Observers surveyed 3264 1-km squares in 2004 and, on average, 78% of the target habitat (90% in southern England). The total number of males counted was 4131 (range 3850–4414), adjusted to 4606 (95% CL ± 913) to account for unsurveyed habitat. The adjusted total represented a 36% increase in 12 years. Nightjars were recorded in 275 10-km squares in 2004, a 2.6% increase since 1992. However, there was evidence of population decline and range contractions in northwest Britain, including north Wales, northwest England and in Scotland. In 2004, 57% of Nightjars were associated with forest plantations (similar to 1992) and 59% with heathland (slightly higher than in 1992).

Conclusion National objectives for Nightjar conservation (UK Biodiversity Action Plan: UKBAP) were reached in respect of population size and stability, but the target for a 5% range increase by 2003 was not met. The continued increase in the national population is probably attributable to habitat protection, management and restoration of heathlands, and the continued availability of clear-fell/young plantations in conifer forests. Management and/or protection/restoration/re-creation of these key habitats remains critical for the long-term objectives of UKBAP. The issue of providing foraging habitats, perhaps via agri-environment schemes, is also raised.     

Clarification of recombinant proteins from high cell density mammalian cell culture systems using new improved depth filters

Increasingly high cell density, high product titer cell cultures containing mammalian cells are being used for the production of recombinant proteins. These high productivity cultures are placing a larger burden on traditional downstream clarification and purification operations due to higher product and impurity levels. Controlled flocculation and precipitation of mammalian cell culture suspensions by acidification or using polymeric flocculants have been employed to enhance clarification throughput and downstream filtration operations. While flocculation is quite effective in agglomerating cell debris and process related impurities such as (host cell) proteins and DNA, the resulting suspension is generally not easily separable solely using conventional depth filtration techniques. As a result, centrifugation is often used for clarification of cells and cell debris before filtration, which can limit process configurations and flexibility due to the investment and fixed nature of a centrifuge. To address this challenge, novel depth filter designs were designed which results in improved primary and secondary direct depth filtration of flocculated high cell density mammalian cell cultures systems feeds, thereby providing single‐use clarification solution. A framework is presented here for optimizing the particle size distribution of the mammalian cell culture systems with the pore size distribution of the gradient depth filter using various pre‐treatment conditions resulting in increased depth filter media utilization and improved clarification capacity. Feed conditions were optimized either by acidification or by polymer flocculation which resulted in the increased average feed particle‐size and improvements in throughput with improved depth filters for several mammalian systems. Biotechnol. Bioeng. 2013; 110: 1964–1972. © 2013 Wiley Periodicals, Inc.     

Structure,Dynamics, and Specificity of Endoglucanase D from Clostridium cellulovorans

The enzymatic degradation of cellulose is a critical step in the biological conversion of plant biomass into an abundant renewable energy source. An understanding of the structural and dynamic features that cellulases utilize to bind a single strand of crystalline cellulose and hydrolyze the β-1,4-glycosidic bonds of cellulose to produce fermentable sugars would greatly facilitate the engineering of improved cellulases for the large-scale conversion of plant biomass. Endoglucanase D (EngD) from Clostridium cellulovorans is a modular enzyme comprising an N-terminal catalytic domain and a C-terminal carbohydrate-binding module, which is attached via a flexible linker. Here, we present the 2.1-Å-resolution crystal structures of full-length EngD with and without cellotriose bound, solution small-angle X-ray scattering (SAXS) studies of the full-length enzyme, the characterization of the active cleft glucose binding subsites, and substrate specificity of EngD on soluble and insoluble polymeric carbohydrates. SAXS data support a model in which the linker is flexible, allowing EngD to adopt an extended conformation in solution. The cellotriose-bound EngD structure revealed an extended active-site cleft that contains seven glucose-binding subsites, but unlike the majority of structurally determined endocellulases, the active-site cleft of EngD is partially enclosed by Trp162 and Tyr232. EngD variants, which lack Trp162, showed a significant reduction in activity and an alteration in the distribution of cellohexaose degradation products, suggesting that Trp162 plays a direct role in substrate binding.     

Tetherin Restricts Herpes Simplex Virus 1 and Is Antagonized by Glycoprotein M

Tetherin is a broadly active antiviral effector that works by tethering nascent enveloped virions to a host cell membrane, thus preventing their release. In this study, we demonstrate that herpes simplex virus 1 (HSV-1) is targeted by tetherin. We identify the viral envelope glycoprotein M (gM) as having moderate anti-tetherin activity. We show that gM but not gB or gD efficiently removes tetherin from the plasma membrane and can functionally substitute for the human immunodeficiency virus type 1 (HIV-1) Vpu protein, the prototypic viral tetherin antagonist, in rescuing HIV-1 release from tetherin-expressing cells. Our data emphasize that tetherin is a broadly active antiviral effector and contribute to the emerging hypothesis that viruses must suppress or evade an array of host cell countermeasures in order to establish a productive infection.     

Gastric intrinsic factor: The gastric and small intestinal stages of cobalamin absorption. A personal journey

Intrinsic factor (IF) was first identified as a component of the gastric mucosa that reacted with an extrinsic factor, later discovered to be vitamin B12 (VB12). IF has been extensively characterized, and its cloned cDNA used to produce sufficient IF to produce high quality antibodies, and to elucidate its 3-dimensional structure bound to cobalamin (Cbl, VB12). The absorption of the IF–Cbl complex involves internalization by endocytosis, incorporation into multivesicular/lysosomal bodies, release of Cbl by lysosomal proteolysis and pH effects, with subsequent binding to transcobalamin (TC). Hereditary IF deficiency is rare, consistent with the need for IF to absorb Cbl, a vitamin essential for cell replication. When mutations occur, they are most often associated with loss of function, but some mutations occur outside the coding region. The IF-mediated intestinal uptake of Cbl has been harnessed for use as a transporter for peptides, proteins and even nanoparticles. Nanoparticle (NP) technology has produced Cbl-coated NPs that can incorporate peptides (insulin, IgG) that can be absorbed orally to function as hormones and antibodies in rodent models, but these systems are not yet ready for clinical use.     

Food Intake in Healthy Young Adults: Effects of Time Pressure and Social Factors

Some factors influencing food intake and subjective responses to meals were assessed in 2 groups (n=40 and n=36) of healthy university students. Both groups were studied for 6 days and included both “structured” and “unstructured” times. A questionnaire was completed by all subjects at 3 h intervals while awake. The questionnaires asked the subjects to state the factors that led them to choose to eat or not to eat a meal in the previous 3 h. If they ate a meal, they were required to describe the type of meal eaten and their responses to it—their hunger before it, their enjoyment of the meal itself, and their degree of satisfaction afterwards. Subjects were also asked to describe the type of meal that they would like to have eaten (the desired meal) in the absence of any restraints due to time pressure, cost, and so on. In the first group, 3 “structured” (working) and 3 “unstructured” (rest) days were chosen. Consistant with our previous studies, structured days, as compared to unstructured days, were associated with smaller meals and less positive subjective responses to them. Also, the meals that were eaten were often smaller than those that were desired, or were even missed altogether, due to time pressure. Not only were the meals eaten on unstructured days larger and rated, to by the subjects more positively, but also there was an additional positive effect if the meal played a social role. In the second group, 6 days were chosen, during which there were structured and unstructured 3 h periods. Many of the findings (with regard to reasons for eating or not eating a meal, and the effect of meal size upon subjective responses to it, for example) were the same as in the first group. However, the effect of structured vs. unstructured 3 h periods was significantly less marked than the effect of structured vs. unstructured days that had been found in the first group, and effects due to social factors and time pressure were less reliably present. The results indicate that food intake is affected by whether the whole or only part of the day is “structured” or “unstructured.” These findings might be relevant to some problems faced by the workforce, in general, and by night workers, in particular.     

Uterine histotroph and conceptus development: select nutrients and secreted phosphoprotein 1 affect mechanistic target of rapamycin cell signaling in ewes

Interferon tau (IFNT), the pregnancy recognition signal in ruminants, abrogates the uterine luteolytic mechanism to ensure maintenance of function for the corpora lutea to produce progesterone (P4). IFNT also suppresses expression of classical IFN-stimulated genes by uterine lumenal epithelium (LE) and superficial glandular (sGE) epithelium but, acting in concert with progesterone, affects expression of a multitude of genes critical to growth and development of the conceptus. The LE and sGE secrete proteins and transport nutrients into the uterine lumen necessary for conceptus development, pregnancy recognition signaling, and implantation. Secretions include arginine and secreted phosphoprotein 1 (SPP1). Arginine can be metabolized to nitric oxide and to polyamines or act directly to activate the mechanistic target of rapamycin cell signaling pathway to stimulate proliferation, migration, and mRNA translation in trophectoderm cells. SPP1 binds alphavbeta3 and alpha5beta1 integrins to induce focal adhesion assembly, adhesion, and migration of conceptus trophectoderm cells during implantation. Thus, arginine and SPP1 mediate growth, migration, cytoskeletal remodeling, and adhesion of trophectoderm essential for pregnancy recognition signaling and implantation. This minireview focuses on components of histotroph that affect conceptus development in the ewe.