The tumor necrosis factor receptor stalk regions define responsiveness to soluble versus membrane-bound ligand

The family of tumor necrosis factor receptors (TNFRs) and their ligands form a regulatory signaling network that controls immune responses. Various members of this receptor family respond differently to the soluble and membrane-bound forms of their respective ligands. However, the determining factors and underlying molecular mechanisms of this diversity are not yet understood. Using an established system of chimeric TNFRs and novel ligand variants mimicking the bioactivity of membrane-bound TNF (mTNF), we demonstrate that the membrane-proximal extracellular stalk regions of TNFR1 and TNFR2 are crucial in controlling responsiveness to soluble TNF (sTNF). We show that the stalk region of TNFR2, in contrast to the corresponding part of TNFR1, efficiently inhibits both the receptor's enrichment/clustering in particular cell membrane regions and ligand-independent homotypic receptor preassembly, thereby preventing sTNF-induced, but not mTNF-induced, signaling. Thus, the stalk regions of the two TNFRs not only have implications for additional TNFR family members, but also provide potential targets for therapeutic intervention.     

Protozoan parasites in group-living primates: testing the biological island hypothesis

A series of articles by W.J. Freeland published in the 1970s proposed that social organization and behavioral processes were heavily influenced by parasitic infections, which led to a number of intriguing hypotheses concerning how natural selection might act on social factors because of the benefits of avoiding parasite infections. For example, Freeland [1979] showed that all individuals within a given group harbored identical gastrointestinal protozoan faunas, which led him to postulate that social groups were akin to "biological islands" and suggest how this isolation could select specific types of ranging and dispersal patterns. Here, we reexamine the biological island hypothesis by quantifying the protozoan faunas of the same primate species examined by Freeland in the same location; our results do not support this hypothesis. In contrast, we quantified two general changes in protozoan parasite community of primates in the study area of Kibale National Park, Uganda, over the nearly 35 years between sample collections: (1) the colobines found free of parasites in the early 1970s are now infected with numerous intestinal protozoan parasites and (2) groups are no longer biological islands in terms of their protozoan parasites. Whatever the ultimate explanation for these changes, our findings have implications for studies proposing selective forces shaping primate behavior and social organization.     

How different are robust and gracile capuchin monkeys? An argument for the use of sapajus and cebus

Capuchin monkey behavior has been the focus of increasing numbers of captive and field studies in recent years, clarifying behavioral and ecological differences between the two morphological types: the gracile and the robust capuchins (also referred to as untufted and tufted). Studies have tended to focus on the gracile species Cebus capucinus (fewer data are available for C. albifrons, C. olivaceus, and C. kaapori) and on Cebus apella, a name that has encompassed all of the robust capuchins since the 1960s. As a result, it is difficult to ascertain the variation within either gracile or robust types. The phylogenetic relationships between gracile and robust capuchins have also, until now, remained obscure. Recent studies have suggested two independent Pliocene radiations of capuchins stemming from a common ancestor in the Late Miocene, about 6.2 millions of years ago (Ma). The present-day gracile capuchins most likely originated in the Amazon, and the robust capuchins in the Atlantic Forest to the southeast. Sympatry between the two types is explained by a recent expansion of robust capuchins into the Amazon (ca. 400,000 years ago). Morphological data also support a division of capuchins into the same two distinct groups, and we propose the division of capuchin monkeys into two genera, Sapajus Kerr, 1792, for robust capuchins and Cebus Erxleben, 1777, for gracile capuchins, based on a review of extensive morphological, genetic, behavioral, ecological, and biogeographic evidence.     

Movements,reproductive seasonality,and fisheries interactions in the whitetip reef shark (<Emphasis Type="Italic">Triaenodon obesus</Emphasis>) from community-contributed photographs

Despite being a common apex-level predator on coral reefs throughout the tropical Indo-Pacific, surprisingly little is known about whitetip reef shark (Triaenodon obesus) movements and biology. This study used photo-identification from community-contributed photographs to reveal patterns in movements, reproductive biology, and fisheries interactions in this species that have not been previously revealed through more traditional methods. At least 178 individual sharks were identified, and 26 movements were observed. These included movement distances of up to 26.4 km, movement rates of up to 3.27 km/day (9.8 km in 3 days), and movements that required the transit of a 140 m deep channel. Other animals showed high philopatry, being re-sighted at the same locality on multiple occasions (up to 13 sightings for one individual) over periods of up to 7 years. Females showed higher philopatry than males and were more likely than males to be found at shallow (<10 m depth) localities throughout the year. The proportion of male sightings at shallow localities was significantly higher in April and May than other months of the year, possibly due to males coming into the shallows to mate with females. A peak in sightings of late-term females followed by an abrupt decline suggests that pupping season is May into early June, and two females were observed pregnant in consecutive years despite evidence that the gestation period is approximately 1 year for this species. Nine percent of animals carried fishing tackle or exhibited jaw injuries associated with fishery interactions, with multiple individuals found dead after being hooked by fishers.     

Coxiella burnetii infection of marine mammals in the Pacific Northwest, 1997-2010

Q fever is a zoonotic disease caused by the bacterium Coxiella burnetii. Humans are commonly exposed via inhalation of aerosolized bacteria derived from the waste products of domesticated sheep and goats, and particularly from products generated during parturition. However, many other species can be infected with C. burnetii, and the host range and full zoonotic potential of C. burnetii is unknown. Two cases of C. burnetii infection in marine mammal placenta have been reported, but it is not known if this infection is common in marine mammals. To address this issue, placenta samples were collected from Pacific harbor seals (Phoca vitulina richardsi), harbor porpoises (Phocoena phocoena), and Steller sea lions (Eumetopias jubatus). Coxiella burnetii was detected by polymerase chain reaction (PCR) in the placentas of Pacific harbor seals (17/27), harbor porpoises (2/6), and Steller sea lions (1/2) collected in the Pacific Northwest. A serosurvey of 215 Pacific harbor seals sampled in inland and outer coastal areas of the Pacific Northwest showed that 34.0% (73/215) had antibodies against either Phase 1 or Phase 2 C. burnetii. These results suggest that C. burnetii infection is common among marine mammals in this region.     

Role of rpoS in Escherichia coli O157:H7 Strain H32 Biofilm Development and Survival

The protein RpoS is responsible for mediating cell survival during the stationary phase by conferring cell resistance to various stressors and has been linked to biofilm formation. In this study, the role of the rpoS gene in Escherichia coli O157:H7 biofilm formation and survival in water was investigated. Confocal scanning laser microscopy of biofilms established on coverslips revealed a nutrient-dependent role of rpoS in biofilm formation, where the biofilm biomass volume of the rpoS mutant was 2.4- to 7.5-fold the size of its rpoS⁺ wild-type counterpart in minimal growth medium. The enhanced biofilm formation of the rpoS mutant did not, however, translate to increased survival in sterile double-distilled water (ddH₂O), filter-sterilized lake water, or unfiltered lake water. The rpoS mutant had an overall reduction of 3.10 and 5.30 log₁₀ in sterile ddH₂O and filter-sterilized lake water, respectively, while only minor reductions of 0.53 and 0.61 log₁₀ in viable counts were observed for the wild-type form in the two media over a 13-day period, respectively. However, the survival rates of the detached biofilm-derived rpoS⁺ and rpoS mutant cells were comparable. Under the competitive stress conditions of unfiltered lake water, the advantage conferred by the presence of rpoS was lost, and both the wild-type and knockout forms displayed similar declines in viable counts. These results suggest that rpoS does have an influence on both biofilm formation and survival of E. coli O157:H7 and that the advantage conferred by rpoS is contingent on the environmental conditions.     

Impact of oncogenic driver mutations on feedback between the PI3K and MEK pathways in cancer cells

Inhibition of the PI3K (phosphoinositide 3-kinase)/Akt/mTORC1 (mammalian target of rapamycin complex 1) and Ras/MEK [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase]/ERK pathways for cancer therapy has been pursued for over a decade with limited success. Emerging data have indicated that only discrete subsets of cancer patients have favourable responses to these inhibitors. This is due to genetic mutations that confer drug insensitivity and compensatory mechanisms. Therefore understanding of the feedback mechanisms that occur with respect to specific genetic mutations may aid identification of novel biomarkers that predict patient response. In the present paper, we show that feedback between the PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways is cell-line-specific and highly dependent on the activating mutation of K-Ras or overexpression c-Met. We found that cell lines exhibited differential signalling and apoptotic responses to PD184352, a specific MEK inhibitor, and PI103, a second-generation class I PI3K inhibitor. We reveal that feedback from the PI3K/Akt/mTORC1 to the Ras/MEK/ERK pathway is present in cancer cells harbouring either K-Ras activating mutations or amplification of c-Met but not the wild-type counterparts. Moreover, we demonstrate that inhibition of protein phosphatase activity by OA (okadaic acid) restored PI103-mediated feedback in wild-type cells. Together, our results demonstrate a novel mechanism for feedback between the PI3K/Akt/mTORC1 and the Ras/MEK/ERK pathways that only occurs in K-Ras mutant and c-Met amplified cells but not the isogenic wild-type cells through a mechanism that may involve inhibition of a specific endogenous phosphatase(s) activity. We conclude that monitoring K-Ras and c-Met status are important biomarkers for determining the efficacy of PI103 and other PI3K/Akt inhibitors in cancer therapy.