Nutritional geometry of female chimpanzees (Pan troglodytes).

Primate foraging is influenced by the spatial and temporal distribution of foods, which may facilitate or constrain optimal nutrient intakes. Chimpanzees are frugivorous primates that mainly subsist on ripe fruit that is typically low in available protein (AP) and high in easily digestible carbohydrates. Because chimpanzees prefer ripe fruit and often eat it in large quantities compared with other foods, we hypothesized that protein intake would be tightly regulated while non-protein energy (NPE) would vary with fruit intake. To test this hypothesis, we conducted all-day follows on female chimpanzees, recorded all types of food consumed (i.e., drupes, figs, and non-fruit foods), estimated the nutritional contributions of these foods to daily NPE and AP intake and investigated how the ratio of NPE to AP varied due to changes in the types of foods consumed. Although the proportions of drupes, figs, and non-fruit foods varied in their diets, female chimpanzees maintained a relatively stable intake of AP while intake of NPE varied depending on the daily diet, demonstrating that like other frugivorous primates studied to date, chimpanzees prioritize protein. The mean daily ratio of NPE to AP was 7:1, which is similar to that of other frugivorous primates studied. Our results support the hypothesis that frugivorous animals may generally prioritize AP, while maximizing NPE intake within that constraint, and could shed light on aspects of human dietary evolution.

Effects of a dietary supplement enriched in palmitoleic acid on fatty acid composition of follicular fluid, granulosa cell metabolism, and oocyte developmental capacity in early lactation dairy cows.

In high-yielding dairy cows, some fertility traits can be influenced by the fatty acid (FA) composition of the follicular fluid during early lactation. The first objective of the current study was to evaluate the potential of dietary supplements enriched in specific FA to influence the FA composition of follicular fluid lipid classes in early lactation dairy cows. The second objective was to determine the influence of the resulting follicular fluid FA composition on the folliculogenesis, lipid and energy metabolism of granulosa cells, as well as oocyte quality and embryo development. Twenty Holstein multiparous cows in late gestation were randomly assigned to 200 g/d of FA supplements enriched in (1) palmitic acid (control treatment; 82% 16:0; PA) in the rumen or (2) palmitoleic acid (sea buckthorn oil; 27% cis-9 16:1, 28% 16:0, 22% cis-9 18:1, and 11% cis-9,cis-12 18:2; SBT) in the abomasum. The treatment period ranged from 20 ± 5 d precalving to 67 ± 2 d postcalving. Cumulus-oocyte complexes, granulosa cells, and follicular fluid were recovered from 2 sequential sessions of ovum pick-up (OPU-1 and OPU-2) at 46 and 67 ± 2 d postcalving (mean ± standard deviation). On the same days, blood samples were collected. Milk performance was recorded, and feed and milk samples were collected from d 8 to 10 ± 3 (onset of lactation), d 35 to 37 ± 2 (before OPU-1), and d 63 to 65 ± 2 (before OPU-2). Treatments did not affect milk yield or fat concentration throughout the experimental trial. Compared with PA, SBT increased the cis-9 16:1 concentration in milk fat, in plasma esterified lipid classes (phospholipids, cholesterol esters, and triacylglycerols), and in follicular fluid phospholipids and cholesterol esters at OPU-1. Abundance of mRNA for stearoyl-CoA desaturase 1 and 5, and perilipin 2 in granulosa cells was not different between treatments, but an increase in the level of stearoyl-CoA desaturase 5 was observed between the 2 OPU periods. Treatments did not affect oocyte quality and developmental capacity or embryo lipid metabolism when cultivated in vitro. These results suggest that limited modifications in the FA composition of the oocyte microenvironment via dietary lipid supplements enriched in specific FA had no major effects on granulosa cell metabolism and oocyte developmental capacity in early lactation cows.

Marijuana: the effects on pregnancy, the fetus, and the newborn.

There is growing evidence that there is an increased use of Marijuana (cannabis) during the perinatal period. This review summarizes pertinent legislation (past and present) and the physiology and pathophysiology of cannabis use during pregnancy. The literature which involves issues concerning cannabis and pregnancy is expanding but at present has many gaps and unanswered questions. The effects on the newborn are significant and treatment recommendations including breastfeeding are presented. Also included is a description of developmental delay during the first 2 years of life in infants exposed to prenatal marijuana. In addition, this commentary discusses the increase use of the newer "synthetic" cannabinoids which have greater psychotropic activity and can cause significant harm.

INFLUENCE OF FRUIT AVAILABILITY ON MACRONUTRIENT AND ENERGY INTAKE BY FEMALE CHIMPANZEES.

Daily energy intake of adult female mammals is influenced by environmental conditions and physiological requirements, including reproduction. We examined the effects of fruit availability on macronutrient and metabolisable energy intake by adult female chimpanzees (Pan troglodytes schweinfurthii) of the Kanyawara community in Kibale National Park, Uganda from January 2014 through June 2015. Drupe fruits were abundant for four months, whereas the other fourteen months were dominated by fig fruits. The mean daily intake of food (dry matter) and metabolisable energy, did not differ between drupe-months and fig-months. However, foraging costs were higher during fig-months, as indicated by a 20% increase in feeding time. Furthermore, during drupe-months female chimpanzees ingested more water-soluble carbohydrates and lipids, and less available protein and neutral detergent fibre. Although metabolisable energy intake did not differ consistently between drupe-months and fig-months, they consumed more on days when ripe fruit dominated the diet than when leaves and pithy stems dominated the diet. Our data suggest that differences in diet quality between drupes and figs can have important effects on frugivore foraging, and that they influence net energy gain more by their effects on macronutrient composition or foraging cost than by their direct impact on energy intake.

Quantitative profiling of the UGT transcriptome in human drug-metabolizing tissues.

Alternative splicing as a mean to control gene expression and diversify function is suspected to considerably influence drug response and clearance. We report the quantitative expression profiles of the human UGT genes including alternatively spliced variants not previously annotated established by deep RNA-sequencing in tissues of pharmacological importance. We reveal a comprehensive quantification of the alternative UGT transcriptome that differ across tissues and among individuals. Alternative transcripts that comprise novel in-frame sequences associated or not with truncations of the 5'- and/or 3'- termini, significantly contribute to the total expression levels of each UGT1 and UGT2 gene averaging 21% in normal tissues, with expression of UGT2 variants surpassing those of UGT1. Quantitative data expose preferential tissue expression patterns and remodeling in favor of alternative variants upon tumorigenesis. These complex alternative splicing programs have the strong potential to contribute to interindividual variability in drug metabolism in addition to diversify the UGT proteome.

Broadband spectroscopy of thermodynamic magnetization fluctuations through a ferromagnetic spin-reorientation transition.

We use scanning optical magnetometry to study the broadband frequency spectra of spontaneous magnetization fluctuations, or "magnetization noise", in an archetypal ferromagnetic film that can be smoothly tuned through a spin reorientation transition (SRT). The SRT is achieved by laterally varying the magnetic anisotropy across an ultrathin Pt/Co/Pt trilayer, from the perpendicular to in-plane direction, via graded Ar+ irradiation. In regions exhibiting perpendicular anisotropy, the power spectrum of the magnetization noise, S(ν), exhibits a remarkably robust ν -3/2 power law over frequencies ν from 1 kHz to 1 MHz. As the SRT region is traversed, however, S(ν) spectra develop a steadily-increasing critical frequency, ν 0, below which the noise power is spectrally flat, indicating an evolving low-frequency cutoff for magnetization fluctuations. The magnetization noise depends strongly on applied in- and out-of-plane magnetic fields, revealing local anisotropies and also a field-induced emergence of fluctuations in otherwise stable ferromagnetic films. Finally, we demonstrate that higher-order correlators can be computed from the noise. These results highlight broadband spectroscopy of thermodynamic fluctuations as a powerful tool to characterize the interplay between thermal and magnetic energy scales, and as a means of characterizing phase transitions in ferromagnets.

Improving the magnetoelectric performance of Metglas/PZT laminates by annealing in a magnetic field.

A comprehensive investigation of magnetostriction optimization in Metglas 2605SA1 ribbons is performed to enhance magnetoelectric performance. We explore a range of annealing conditions to relieve remnant stress and align the magnetic domains in the Metglas, while minimizing unwanted crystallization. The magnetostriction coefficient, magnetoelectric coefficient, and magnetic domain alignment are correlated to optimize magnetoelectric performance. We report on direct magnetostriction observed by in-plane Doppler vibrometer and domain imagining using scanning electron microscopy with polarization analysis for a range of annealing conditions. We find that annealing in an oxygen-free environment at 400 °C for 30 min yields an optimal magnetoelectric coefficient, magnetostriction and magnetostriction coefficient. The optimized ribbons had a magnetostriction of 50.6 ± 0.2 µm m-1 and magnetoelectric coefficient of 79.3 ± 1.5 µm m-1 mT-1. The optimized Metglas 2605SA1 ribbons and PZT-5A (d31 mode) sensor achieves a magnetic noise floor of approximately 600 pT Hz-1/2 at 100 Hz and a magnetoelectric coefficient of 6.1 ± 0.03 MV m-1 T-1.

Unravelling the transcriptomic landscape of the major phase II UDP-glucuronosyltransferase drug metabolizing pathway using targeted RNA sequencing.

A comprehensive view of the human UDP-glucuronosyltransferase (UGT) transcriptome is a prerequisite to the establishment of an individual's UGT metabolic glucuronidation signature. Here, we uncover the transcriptome landscape of the 10 human UGT gene loci in normal and tumoral metabolic tissues by targeted RNA next-generation sequencing. Alignment on the human hg19 reference genome identifies 234 novel exon-exon junctions. We recover all previously known UGT1 and UGT2 enzyme-coding transcripts and identify over 130 structurally and functionally diverse novel UGT variants. We further expose a revised genomic structure of UGT loci and provide a comprehensive repertoire of transcripts for each UGT gene. Data also uncover a remodelling of the UGT transcriptome occurring in a tissue- and tumor-specific manner. The complex alternative splicing program regulating UGT expression and protein functions is likely critical in determining detoxification capacity of an organ and stress-related responses, with significant impact on drug responses and diseases.

Application of criteria developed by the Task Force on Neonatal Encephalopathy and Cerebral Palsy to acutely asphyxiated neonates.

OBJECTIVE: To estimate whether term neonates with acute intrapartum hypoxic ischemic encephalopathy and permanent brain injury satisfied the criteria for causation of cerebral palsy developed by the Task Force on Neonatal Encephalopathy and Cerebral Palsy. METHODS: In this descriptive study, patients in the case group were obtained from a registry of singleton, liveborn, term, neurologically impaired neonates. Entry criteria included a reactive intrapartum fetal heart rate pattern followed by a sudden, rapid, and sustained deterioration of the fetal heart rate that lasted until delivery and an umbilical artery cord pH. All patients in the case group were then assessed to determine if they met the criteria developed by the Task Force on Neonatal Encephalopathy and Cerebral Palsy. RESULTS: Thirty-nine neonates met the entry criteria, and the proportion meeting each essential criterion was as follows: 38 of 39 (97.4%) had umbilical artery pH of less than 7.00 and 30 of 30 (100%) had a base deficit of 12 mmol/L or higher; 33 of 34 (97%) had either moderate or severe encephalopathy; 34 of 36 (94%) had spastic quadriplegia or dyskinetic cerebral palsy or death attributable to brain injury; and 39 of 39 (100%) had no identifiable reason for exclusion. CONCLUSION: Fetuses that underwent a sudden and sustained deterioration of the fetal heart rate and that subsequently were found to have cerebral palsy demonstrated characteristics consistent with criteria developed by the Task Force on Neonatal Encephalopathy and Cerebral Palsy for intrapartum asphyxial injury. LEVEL OF EVIDENCE: III.

Causation--fetal brain injury and uterine rupture.

The purpose of this article is to familiarize the reader with the concept of causation and the role of the concept of foreseeability of harm in obstetric malpractice lawsuits. These concepts are incorporated into several hypothetical fetal brain injury and uterine rupture cases. The discussion involves an overview of available scientific evidence used to substantiate or refute whether a child's brain damage or a maternal uterine rupture was in fact related to the obstetric care in question. In the event of the delivery of a depressed newborn, a checklist of scientific evidence to be gathered at the time of delivery is also provided.

Nucleated red blood cell and platelet counts in asphyxiated neonates sufficient to result in permanent neurologic impairment.

OBJECTIVE: Recent research has suggested that a nucleated red blood cell (NRBC) count >or=26 per 100 white blood cells (%) or the development of a platelet count or=26% was: group 1, 10/21 (47.6%); group 2, 0/14 (0%); group 3, 0/12 (0%). Those with a platelet count or=26% than group 3 (p = 0.0135). A platelet count or=26% and/or a platelet count

Competencia clínica de los médicos de familia en 14 Comunidades Autónomas españolas / Clinical competence of the general practitioners in 14 Spanish Different Communities

Fundamento y Objetivo: El Desarrollo Profesional Continuo (DPC) es un proceso de adquisición, mantenimiento y mejora de conocimientos, habilidades, actitudes y competencia profesional. En España, mantener la competencia es responsabilidad del profesional, para ello debe detectar objetivamente sus déficts formativos. Este estudio, pretende detectar diferencias en niveles de competencia clínica y déficits formativos, entre médicos de familia de distintas CC.AA. españolas, en el año 2005. Sujetos y método: Estudio descriptivo transversal. Se evaluaron 1158 médicos de 14 CCAA. Se utilizó como herramienta la Evaluación de Competencia Objetiva Estructurada (ECOE) de 15 estaciones. Se compararon las puntuaciones globales obtenidas, por competencias y área de conocimiento mediante ANOVA, y se estudió la fiabilidad de la prueba, mediante el alfa de Cronbach. Resultados: La puntuación global media fue 59,08 (DE 6,12), (IC 95%: 58,52-59,31). Se detectaron diferencias significativas entre Cataluña (63,65±5,2) y Castilla-León (55,37±5,78), Valencia (57,20±7,18), Andalucía (57,67±6,04), y Murcia (57,19±5,50). Por componente competencial, el mejor resultado correspondió al área de comunicación (80,11% del ideal) y el peor a atención familiar (45,54%). Por áreas de conocimiento, el mayor se obtuvo en dolor abdominal (75,94±14,70) y el menor en diabetes (43,36±15.97). El coeficiente de fiabilidad global de la prueba, alfa de Cronbach, fue 0,79. Conclusiones: Este estudio muestra el mapa competencial de los médicos de familia españoles y las diferencias existentes entre CCAA. La competencia es globalmente buena. Este tipo de estudio aporta una visión integral al médico de familia sobre su DPC, que le servirá de guía en su formación, para conseguir la excelencia profesional y mantenerla (AU)

Objective: The Continuous Professional Development (CPD) is a process of acquisition, maintenance and improvement of knowledge, abilities, attitudes and professional competence. In Spain, the manteinance of the clinical competence is responsibility of the professional. The professional for it must detect his déficts of formation objectively. This study detects differences in levels of clinical competence and deficits of formation in general practitioners of different Spanish Communities, in 2005. Method: Cross sectional study. 1158 doctors of 14 Communities were evaluated. The Objective Structured Clinical Examination (OSCE) was used as a tool with 15 different clinical situations. The global scores were compared. By competitions and area of knowledge by means of ANOVA. The reliability of the test was assessed of alpha Cronbach. Results: The global score average was 59.08 (SD 6,12)(IC 95 58,52-59,31). Significant differences were detected between Cataluña (63,65 SD 5,2) and Castilla Leon (55,37 SD 5,78), Valencia (57,20 SD 7,18), Andalucia (57,67 SD 6,04) and Murcia(57,19 SD 5,50). By competential component, the best result corresponded to the area of communication (80.11% of ideal) and the worse one to family attention (45,54%). By areas of knowledge was detected, the greater in abdominal pain (75,94 SD 14,70) and the minor in diabetes (43,36 SD 15.97). The global coefficient of reliability of the test was 0,79. Conclusions: This study shows to the competential map of the Spanish general practitioner and the existing differences between Communities. The clinical competence is globally good. This type of study contributes to an integral vision of the general practitioner on its CPD, it will serve to him as a guide in their formation, to obtain the professional excellence and to maintain it (AU)

Birth asphyxia and cerebral palsy.

There has been a societal presumption that most, if not all, cases of hypoxic ischemic encephalopathy-induced cerebral palsy occur during the 3 hours that are related to the events of labor and delivery; society has tended to overlook the remaining 7000 hours of the pregnancy. As a result of this societal perspective, often times the obstetrician has been targeted unfairly as the person who is responsible for a given child's neurologic injuries. Rather, the entire pregnancy, labor, delivery, and well beyond birth require examination to understand fully the pathophysiologic mechanisms that are responsible for an infant's brain injuries, and their long-term impact on the child.

A force-based protein biochip.

A parallel assay for the quantification of single-molecule binding forces was developed based on differential unbinding force measurements where ligand-receptor interactions are compared with the unzipping forces of DNA hybrids. Using the DNA zippers as molecular force sensors, the efficient discrimination between specific and nonspecific interactions was demonstrated for small molecules binding to specific receptors, as well as for protein-protein interactions on protein arrays. Finally, an antibody sandwich assay with different capture antibodies on one chip surface and with the detection antibodies linked to a congruent surface via the DNA zippers was used to capture and quantify a recombinant hepatitis C antigen from solution. In this case, the DNA zippers enable not only discrimination between specific and nonspecific binding, but also allow for the local application of detection antibodies, thereby eliminating false-positive results caused by cross-reactive antibodies and nonspecific binding.

Solid-phase synthesis of diamine and polyamine amino acid derivatives as HIV-1 tat-TAR binding inhibitors.

A series of diamine and polyamine derivatives, either free amines or salts (HCl or TFA), of aspartic and glutamic acid were prepared in excellent yields using Rink Amide solid-phase synthesis. The asparagine and glutamine derivatives were all evaluated for their ability to inhibit Tat-TAR binding using a FIGS cellular assay, with the polyamine derivatives exhibiting the most promising binding activity.

Synthesis and biological evaluation of s-triazine substituted polyamines as potential new anti-trypanosomal drugs.

The P2 transporter is a nucleoside transporter which is unique to the protozoan parasite Trypanosoma brucei, the causative organism of Human African Trypanosomasis. The transporter has been shown to bind some structural motifs not recognized by other transporters. In this paper we describe the use of the melamine motif, a substrate of the P2 transporter, as a potential tool to selectively deliver polyamine analogues to the parasites. The synthesis of a number of polyamine analogues attached to a variety of melamine analogues is described. Many of the compounds were shown to competitively inhibit uptake of adenosine, indicating that they are recognized by the transporter. Some of the compounds showed good in vitro activity against the parasites.

Rapid and sensitive quantitation of antibiotics in fermentations by electrospray mass spectrometry.

Electrospray ionisation mass spectrometry (ESI-MS) has been used for the determination and quantitation of a broad range of 24 antibiotics, from groups including aminoglycosides, beta-lactams, tetracyclines, antifungals and glycopeptides. Spectra have been acquired for all 24 antibiotics derived from pure samples dissolved in acetonitrile/water, along with samples extracted from complex fermentation liquor. Quantitation was carried out by the detection of the protonated molecules, using time-scheduled single-ion monitoring (SIM). ESI-MS was used to detect and quantify to 5-microM levels. A one-step extraction of antibiotics with an organic solvent (methanol) was used for this rapid and simple procedure. Specificity is not matched by other methods and antibiotic analogues (e.g. the five forms of erythromycin) can be determined within minutes.

Proximity signal and shade avoidance differences between early and late successional trees.

Competitive interactions between plants determine the success of individuals and species. In developing forests, competition for light is the predominant factor. Shade tolerators acclimate photosynthetically to low light and are capable of long-term survival under the shade cast by others, whereas shade avoiders rapidly dominate gaps but are overtaken in due course by shade-tolerant, later successional species. Shade avoidance results from the phytochrome-mediated perception of far-red radiation (700-800 nm) scattered from the leaves of neighbours, provides early warning of shading, and induces developmental responses that, when successful, result in the overgrowth of those neighbours. Shade tolerators cast a deep shade, whereas less-tolerant species cast light shade, and saplings tend to have high survivorship in shade cast by conspecific adults, but high rates of mortality when shaded by more-tolerant species. Here we report a parallel relationship in which the shade-avoidance responses of three tree species are inversely proportional to proximity signals generated by those species. On this basis, early successional species generate small proximity signals but react strongly to them, whereas late successional species react weakly but generate strong signals.

Novel inhibitors of Trypanosoma cruzi dihydrofolate reductase.

There is an urgent need for the development of new drugs to treat Chagas' disease, which is caused by the protozoan parasite Trypanosoma cruzi. The enzyme dihydrofolate reductase (DHFR) has been a very successful drug target in a number of diseases and we decided to investigate it as a potential drug target for Chagas' disease. A homology model of the enzyme was used to search the Cambridge Structural Database using the program DOCK 3.5. Compounds were then tested against the enzyme and the whole parasite. Compounds were also screened against the related parasite, Trypanosoma brucei.