Therapeutic Helminth Infection of Macaques with Idiopathic Chronic Diarrhea Alters the Inflammatory Signature and Mucosal Microbiota of the Colon

Idiopathic chronic diarrhea (ICD) is a leading cause of morbidity amongst rhesus monkeys kept in captivity. Here, we show that exposure of affected animals to the whipworm Trichuris trichiura led to clinical improvement in fecal consistency, accompanied by weight gain, in four out of the five treated monkeys. By flow cytometry analysis of pinch biopsies collected during colonoscopies before and after treatment, we found an induction of a mucosal T_H2 response following helminth treatment that was associated with a decrease in activated CD4⁺ Ki67+ cells. In parallel, expression profiling with oligonucleotide microarrays and real-time PCR analysis revealed reductions in T_H1-type inflammatory gene expression and increased expression of genes associated with IgE signaling, mast cell activation, eosinophil recruitment, alternative activation of macrophages, and worm expulsion. By quantifying bacterial 16S rRNA in pinch biopsies using real-time PCR analysis, we found reduced bacterial attachment to the intestinal mucosa post-treatment. Finally, deep sequencing of bacterial 16S rRNA revealed changes to the composition of microbial communities attached to the intestinal mucosa following helminth treatment. Thus, the genus Streptophyta of the phylum Cyanobacteria was vastly increased in abundance in three out of five ICD monkeys relative to healthy controls, but was reduced to control levels post-treatment; by contrast, the phylum Tenericutes was expanded post-treatment. These findings suggest that helminth treatment in primates can ameliorate colitis by restoring mucosal barrier functions and reducing overall bacterial attachment, and also by altering the communities of attached bacteria. These results also define ICD in monkeys as a tractable preclinical model for ulcerative colitis in which these effects can be further investigated.     

Measuring the Toughness of Primate Foods and its Ecological Value

The mechanical properties of plant foods play an important role in the feeding process, being one of many criteria for food acceptance or rejection by primates. One of the simplest justifications for this statement is the general finding that primates tend to avoid foods with high fiber. Although fiber is largely tasteless, odorless, and colorless, it imparts texture, a sensation in the mouth related to the physical properties of foods. All primates encounter such mechanical resistance when they bite into plant food, and studies on humans show that an incisal bite facilitates quick oral assessment of a property called toughness. Thus, it is feasible that primates make similar assessments of quality in this manner. Here, we review methods of measuring the toughness of primate foods, which can be used either for making general surveys of the properties of foods available to primates or for establishing the mechanisms that protect these foods from the evolved form of the dentition.     

Fission–Fusion Dynamics in Southern Muriquis (Brachyteles arachnoides) in Continuous Brazilian Atlantic Forest

Fission–fusion social dynamics, the spatiotemporal variance in subunit size, composition, and cohesion, are the subject of considerable interest owing to their complex nature and widespread appearance in the primate order. We here aim to describe the nature of fission–fusion dynamics in a population of egalitarian southern muriquis inhabiting a relatively undisturbed extension of mildly seasonal Brazilian Atlantic forest to provide insights into the functions of fission–fusion dynamics and to examine the constraints on and opportunities for associations among individuals. We collected instantaneous scan samples and ad libitum data over a total of 13 mo in 2 yr (1599 observation hours) on subunit size at 2 spatiotemporal scales (party and nomadic party), party composition, spatial cohesion, and the behavioral context of fission–fusion events. These southern muriquis exhibited high levels of fission–fusion with significant variation in party size, cohesion, and composition. The group was weakly cohesive with a small mean party size (3.74 adults, 5.32 all individuals) and nomadic party size (13.73 adults, 19.38 all individuals). Mixed parties were the most frequently observed party type, although the high frequency of all-male parties suggests strong relationships based on philopatry and a mating strategy under scramble competition. We compare fission–fusion dynamics across populations of Brachyteles and highlight the striking continuum of these dynamics in the genus. We make interspecific comparisons with Ateles and Pan, with well documented high levels of fission–fusion, and demonstrate interspecific variation and convergence in grouping patterns.     

Receptor-transporter interactions of canonical ATP-binding cassette import systems in prokaryotes

ATP-binding cassette (ABC) transport systems mediate the translocation of solutes across biological membranes at the expense of ATP. They share a common modular architecture comprising two pore-forming transmembrane domains and two nucleotide binding domains. In prokaryotes, ABC transporters are involved in the uptake of a large variety of chemicals, including nutrients, osmoprotectants and signal molecules. In pathogenic bacteria, some ABC importers are virulence factors. Canonical ABC import systems require an additional component, a substrate-specific receptor or binding protein for function. Interaction of the liganded receptor with extracytoplasmic loop regions of the transmembrane domains initiate the transport cycle. In this review we summarize the current knowledge on receptor-transporter interplay provided by crystal structures as well as by biochemical and biophysical means. In particular, we focus on the maltose/maltodextrin transporter of enterobacteria and the transporters for positively charged amino acids from the thermophile Geobacillus stearothermophilus and Salmonella enterica serovar Typhimurium.     

Synergistic Effects of Arsenic Trioxide and Silibinin on Apoptosis and Invasion in Human Glioblastoma U87MG Cell Line

Patients with glioblastoma multiforme (GBM) have poor therapeutic outcomes despite their current therapy. In an attempt to increase the efficacy of therapy for GBM, we studied the efficacy of arsenic trioxide (ATO), a newly introduced treatment for glioma, combined with silibinin, a natural polyphenolic flavonoid, in the GBM cell line, U87MG. The combination therapy synergically inhibited metabolic activity, cell proliferation, and gelatinase A and B activities; it also increased apoptosis. Additionally, it decreased the mRNA level of cathepsin B, uPA, matrix metalloproteinase-2 and 9, membrane type 1-MMP, survivin, BCL2, CA9; it increased mRNA level of caspase-3. Altogether, these results showed that ATO and silibinin in some cases improved and/or complemented the anticancer effects. This study may supply insight into the design of new combination cancer therapies to cells intrinsically less sensitive to routine therapies and suggested a new combination therapy for the highly invasive human glioma treatment.     

An improved heuristic for haplotype inference

Haplotypes include essential SNP information used for a variety of purposes such as investigating potential links between certain diseases and genetic variations. Given a set of genotypes, the haplotype inference problem based on pure parsimony is the problem of finding a minimum set of haplotypes that explains all the given genotypes. The problem is especially important because, while it is fairly inexpensive to obtain genotypes, other approaches to obtaining haplotypes are significantly expensive. There are two types of methods proposed for the problem, namely exact and inexact methods. Existing exact methods guarantee obtaining purely parsimonious solutions but have exponential time-complexities and are not practical for large number or length of genotypes. However, inexact methods are relatively fast but do not always obtain optimum solutions. In this paper, an improved heuristic is proposed, based on which new inexact and exact methods are provided. Experimental results indicate that the proposed methods replace the state-of-the-art inexact and exact methods for the problem.     

The role of tooth enamel mechanical properties in primate dietary adaptation

Primate teeth adapt to the physical properties of foods in a variety of ways including changes in occlusal morphology, enamel thickness, and overall size. We conducted a comparative study of extant primates to examine whether their teeth also adapt to foods through variation in the mechanical properties of the enamel. Nanoindentation techniques were used to map profiles of elastic modulus and hardness across tooth sections from the enamel-dentin junction to the outer enamel surface in a broad sample of primates including apes, Old World monkeys, New World monkeys, and lemurs. The measured data profiles feature considerable overlap among species, indicating a high degree of commonality in mechanical properties. These results suggest that differences in the load-bearing capacity of primate molar teeth are more a function of morphology-particularly tooth size and enamel thickness-than of underlying mechanical properties.     

Possible Fruit Protein Effects on Primate Communities in Madagascar and the Neotropics

Background

The ecological factors contributing to the evolution of tropical vertebrate communities are still poorly understood. Primate communities of the tropical Americas have fewer folivorous but more frugivorous genera than tropical regions of the Old World and especially many more frugivorous genera than Madagascar. Reasons for this phenomenon are largely unexplored. We developed the hypothesis that Neotropical fruits have higher protein concentrations than fruits from Madagascar and that the higher representation of frugivorous genera in the Neotropics is linked to high protein concentrations in fruits. Low fruit protein concentrations in Madagascar would restrict the evolution of frugivores in Malagasy communities.

Methodology/Principal Findings

We reviewed the literature for nitrogen concentrations in fruits from the Neotropics and from Madagascar, and analyzed fruits from an additional six sites in the Neotropics and six sites in Madagascar. Fruits from the Neotropical sites contain significantly more nitrogen than fruits from the Madagascar sites. Nitrogen concentrations in New World fruits are above the concentrations to satisfy nitrogen requirements of primates, while they are at the lower end or below the concentrations to cover primate protein needs in Madagascar.

Conclusions/Significance

Fruits at most sites in the Neotropics contain enough protein to satisfy the protein needs of primates. Thus, selection pressure to develop new adaptations for foods that are difficult to digest (such as leaves) may have been lower in the Neotropics than in Madagascar. The low nitrogen concentrations in fruits from Madagascar may contribute to the almost complete absence of frugivorous primate species on this island.     

Toxicity of fenitrothion, an organophosphorus pesticide, against summer population of sunn pest, Eurygaster integriceps Put. (Hemiptera: Scutelleridae)

The sunn pest are a group of insect representing several genera of the shield bug (Scutelleridae) and stink bug (Pentatomidae) families, with the species Eurygaster integriceps being the most economically important. The sunn pest is a major pest of wheat and barley in central and western Asia and it accounts for annual losses of 20-30% for barley and up to 100% for wheat. In the recent decades problems have intensified largely due to change in farming practices. Thus this pest threatens food security and reduces the stability of traditionally wheat-based agricultural systems. In order to control pest, the major organophosphorus insecticide used is fenitrothion. So, the aim of the current study was to determine toxicity of fenitrothion against summer population of adult sunn pest. Insecticide toxicity was measured using a topical bioassay. To do so, the toxin was dissolved in acetone and six concentrations of toxin including 25, 50, 100, 150, 175 and 200 ppm were prepared. Insects were treated on the pronotum with one micro litre aliquots of insecticide in acetone (for treatments) or acetone alone (for control). The dose-mortality relationship was assessed from above mentioned doses with 30 insects treated per dose. After treatment, insects were maintained at laboratory conditions and mortality was recorded after 48 hours. Results were corrected for control mortality with Abbott's formula and then analyzed and toxicity determined. The obtained results showed that LD10, LD50, and LD90 were 34.7, 90.43, and 235.5, respectively.