Biological network design strategies: discovery through dynamic optimization

An important challenge in systems biology is the inherent complexity of biological network models, which complicates the task of relating network structure to function and of understanding the conceptual design principles by which a given network operates. Here we investigate an approach to analyze the relationship between a network structure and its function using the framework of optimization. A common feature found in a variety of biochemical networks involves the opposition of a pair of enzymatic chemical modification reactions such as phosphorylation-dephosphorylation or methylation-demethylation. The modification pair frequently adjusts biochemical properties of its target, such as activating and deactivating function. We applied optimization methodology to study a reversible modification network unit commonly found in signal transduction systems, and we explored the use of this methodology to discover design principles. The results demonstrate that different sets of rate constants used to parameterize the same network topology represent different compromises made in the resulting network operating characteristics. Moreover, the same topology can be used to encode different strategies for achieving performance goals. The ability to adopt multiple strategies may lead to significantly improved performance across a range of conditions through rate modulation or evolutionary processes. The optimization framework explored here is a practical approach to support the discovery of design principles in biological networks.     

Seasonal changes in the dietary compositions of rusa deer in Pangandaran Nature Reserve,West Java,Indonesia

Information regarding the food habits of tropical cervids is limited. We studied the food habits of rusa deer (Rusa timorensis), a tropical cervid in the Pangandaran Nature Reserve, West Java, Indonesia. The faecal composition of the rusa deer collected over a year was analysed using microscopy of plant fragments. The results showed marked seasonal changes: in the rainy season, the rusa deer mainly fed on Cynodon dactylon, a lawn-like grass, which accounted for approximately 50% of the faecal composition. During the dry season, C. dactylon in the faeces decreased to approximately 20%, while the composition of fruits increased, suggesting that food conditions for the deer were better in this season. This pattern differs from that of temperate cervids which can feed on abundant plant leaves during summer but are forced to consume low-quality foods such as bark and dead leaves during winter.     

Advantage of dichromats over trichromats in discrimination of color-camouflaged stimuli in nonhuman primates

Due to a middle- to long-wavelength-sensitive (M/LWS) cone opsin polymorphism, there is considerable phenotypic variation in the color vision of New World monkeys. Many females have trichromatic vision, whereas some females and all males have dichromatic vision. The selective pressures that maintain this polymorphism are unclear. In the present study we compared the performance of dichromats and trichromats in a discrimination task. We examined tri- and dichromatic individuals of two species: brown capuchin monkeys (Cebus apella) and long-tailed macaques (Macaca fascicularis). We also examined one protanomalous chimpanzee (Pan troglodytes). The subjects' task was to discriminate a circular pattern from other patterns in which textural elements differed in orientation and thickness from the background. After they were trained with stimuli of a single color, the subjects were presented with color-camouflaged stimuli with a green/red mosaic overlaid onto the pattern. The dichromatic monkeys and the protanomalous chimpanzee selected the correct stimulus under camouflaged conditions at rates significantly above chance levels, while the trichromats did not. These findings demonstrate that dichromatic nonhuman primates possess a superior visual ability to discriminate color-camouflaged stimuli, and that such an ability may confer selective advantages with respect to the detection of cryptic foods and/or predators.     

Heart Failure Care in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis

Background

Heart failure places a significant burden on patients and health systems in high-income countries. However, information about its burden in low- and middle-income countries (LMICs) is scant. We thus set out to review both published and unpublished information on the presentation, causes, management, and outcomes of heart failure in LMICs.

Methods and Findings

Medline, Embase, Global Health Database, and World Health Organization regional databases were searched for studies from LMICs published between 1 January 1995 and 30 March 2014. Additional unpublished data were requested from investigators and international heart failure experts. We identified 42 studies that provided relevant information on acute hospital care (25 LMICs; 232,550 patients) and 11 studies on the management of chronic heart failure in primary care or outpatient settings (14 LMICs; 5,358 patients). The mean age of patients studied ranged from 42 y in Cameroon and Ghana to 75 y in Argentina, and mean age in studies largely correlated with the human development index of the country in which they were conducted (r = 0.71, p<0.001). Overall, ischaemic heart disease was the main reported cause of heart failure in all regions except Africa and the Americas, where hypertension was predominant. Taking both those managed acutely in hospital and those in non-acute outpatient or community settings together, 57% (95% confidence interval [CI]: 49%–64%) of patients were treated with angiotensin-converting enzyme inhibitors, 34% (95% CI: 28%–41%) with beta-blockers, and 32% (95% CI: 25%–39%) with mineralocorticoid receptor antagonists. Mean inpatient stay was 10 d, ranging from 3 d in India to 23 d in China. Acute heart failure accounted for 2.2% (range: 0.3%–7.7%) of total hospital admissions, and mean in-hospital mortality was 8% (95% CI: 6%–10%). There was substantial variation between studies (p<0.001 across all variables), and most data were from urban tertiary referral centres. Only one population-based study assessing incidence and/or prevalence of heart failure was identified.

Conclusions

The presentation, underlying causes, management, and outcomes of heart failure vary substantially across LMICs. On average, the use of evidence-based medications tends to be suboptimal. Better strategies for heart failure surveillance and management in LMICs are needed. Please see later in the article for the Editors'' Summary     

Female long-tailed macaques with scrotum-like structure

Female long-tailed macaques (Macaca fascicularis) living in multimale and multifemale societies show a swelling and reddening of the sexual skin around the anogenital region when they approach ovulation. These swellings are limited to the base of the tail in many local populations. We recently observed another type of sexual swelling in long-tailed macaques inhabiting localities north of the Isthmus of Kra, Thailand. This swelling was located in the inguinal region in pubertal females. These swellings develop bilaterally into a globular structure, which so strongly resembles the male scrotum that it is difficult to reliably identify an individual's sex at a distance using only the standard phenotypic features of differential presence of clitoris or scrotum. The sex of the monkeys possessing the scrotum-like swelling was examined at the chromosomal and gonadal levels by determining the presence of two sex-related genes (the SRY and the AMEL), and sex-steroid hormone levels, respectively. For chromosomal sex, polymerase chain reaction (PCR)-based assays suggested the absence of the Y-linked SRY and AMEL loci but the presence of the X-linked AMEL locus in the scrotum-like monkeys, consistent with them being XX and not XY. Plasma testosterone levels of the monkeys possessing the inguinal sex skin swelling did not differ from those of ordinary females and was significantly lower than that of subadult and adult males. However, plasma estradiol levels were higher than those of both ordinary adult males and ordinary adult females. Together, the data strongly support the suggestion that these are XX females. Indeed, most of the tissue components of the scrotum-like swelling were in fact adipose cells. Upon our latest survey in Thailand, the scrotum-like swellings were observed only in long-tailed macaques inhabiting the Indochinese region, above the Isthmus of Kra. To understand whether the scrotum-like swelling is related to geographical distribution, further study is necessary.     

Hematological values and parasite fauna in free-rangingMacaca hecki and theM. hecki/M. tonkeana hybrid group of Sulawesi Island, Indonesia

Hematological values and parasitological fauna of free-rangingMacaca hecki and the hybrid group betweenM. hecki/M. tonkeana of Sulawesi Island, Indonesia, were investigated. The hematological values, especially the red cell number (RBC), were lower than those of other macaque species, indicating that Sulawesi macaques are slightly anemic. Several parasites including Plasmodium sp., trombiculid mites, andTrichuris trichiura were identified. Although infection by Plasmodium was observed with considerable frequency, no clear relationship between its infection and the occurrence of anemia was found. Trombiculid mites and eggs ofAnatrichosoma sp. were detected in foci of the ears of most monkeys. The infection with a trombiculid mite is the first recorded occurrence in free-ranging wild Sulawesi macaques. Gastrointestinal parasites were identified from their eggs in fecal samples, where five species of nematoda and one trematoda species were found.     

Are right- and left-handedness relevant as general categories in a non-industrialized country?

Whether right- and left-handedness are defined as a function of individual tasks or represent general categories across tasks has been long debated. However, the literature on handedness primarily concerns industrialized societies in which manual work has been extensively automated, and the majority of individuals in those countries do not use their arms and hands intensively for highly specialized tasks on an everyday basis. Thus, the question remains whether results from those countries regarding handedness are transferable to countries where the majority of individuals are still exploiting their lateralized skills. Here, we sampled 506 individuals from 143 locations on the islands of Flores and Adonara, Indonesia, to assess their hand preference for and hand performance on several tasks in order to evaluate, in a non-industrialized country, the level of manual specialization and the relevance of right- or left-handedness as general categories. Generalized-declared handedness was consistent with task-declared handedness across 10 specific tasks and with a measure of strength and a measure of skilfulness, suggesting that general handedness is a valid concept. This hand specialization for tasks is discussed in the context of intense and daily tool use in this agricultural society.