Demography of the Giant Otter (Pteronura brasiliensis) in Manu National Park,South-Eastern Peru: Implications for Conservation

The giant otter (Pteronura brasiliensis) is an endangered semi-aquatic carnivore of South America. We present findings on the demography of a population inhabiting the floodplain of Manu National Park, south-eastern Peru, arising from 14 annual dry season censuses over a 16 year period. The breeding system of territorial groups, including only a single breeding female with non-reproductive adult ‘helpers’, resulted in a low intrinsic rate of increase (0.03) and a slow recovery from decades of hunting for the pelt trade. This is explained by a combination of factors: (1) physiological traits such as late age at first reproduction and long generation time, (2) a high degree of reproductive skew, (3) small litters produced only once a year, and (4) a 50% mortality between den emergence and age of dispersal, as well as high mortality amongst dispersers (especially males). Female and male giant otters show similar traits with respect to average reproductive life-spans (female 5.4 yrs., male 5.2 yrs.) and average cub productivity (female 6.9, male 6.7 cubs per lifetime); the longest reproductive life spans were 11 and 13 years respectively. Individual reproductive success varied substantially and depended mainly on the duration of dominance tenure in the territory. When breeding females died, the reproductive position in the group was usually occupied by sisters or daughters (n = 11), with immigrant male partners. Male philopatry was not observed. The vulnerability of the Manu giant otter population to anthropogenic disturbance emphasises the importance of effective protection of core lake habitats in particular. Riverine forests are the most endangered ecosystem in the Department of Madre de Dios due to the concentration of gold mining, logging and agricultural activities in floodplains, highlighting the need for a giant otter habitat conservation corridor along the Madre de Dios River.     

Isolation and characterization of <Emphasis Type="Italic">Clostridium difficile</Emphasis> from shellfish and marine environments

This pilot study was carried out to evaluate the occurrence of Clostridium difficile in marine environments and in edible shellfish. Samples of seawater, sediment, and zooplankton were collected at five sampling stations in the Gulf of Naples. Six samples of edible shellfish, furthermore, were obtained: two from mussel farms and four from wholesalers. The isolation and the characterization of C. difficile strains were carried out using selective media and molecular techniques, respectively. C. difficile was isolated from nine of the 21 samples investigated. Shellfish and zooplankton showed the highest prevalence of positive samples. No C. difficile was detected in marine sediment. Majority of the C. difficile isolates were toxin A/B positive. Six known different PCR ribotypes (003, 005, 009, 010, 056, and 066) were identified, whereas one strain may represent a new PCR ribotype. C. difficile may be present in the marine environment in Southern Italy, including shellfish and zooplankton. This study is reporting the isolation of C. difficile from zooplankton, clams, and mussels and pointing out a new possible route to exposure to C. difficile of healthy individuals in the community.     

Tumor-Endothelial Cell Three-dimensional Spheroids: New Aspects to Enhance Radiation and Drug Therapeutics

Classic cancer research for several decades has focused on understanding the biology of tumor cells in vitro. However, extending these findings to in vivo settings has been impeded owing to limited insights on the impact of microenvironment on tumor cells. We hypothesized that tumor cell biology and treatment response would be more informative when done in the presence of stromal components, like endothelial cells, which exist in the tumor microenvironment. To that end, we have developed a system to grow three-dimensional cultures of GFP-4T1 mouse mammary tumor and 2H11 murine endothelial cells in hanging drops of medium in vitro. The presence of 2H11 endothelial cells in these three-dimensional cocultures was found to sensitize 4T1-GFP tumor cells to chemotherapy (Taxol) and, at the same time, protect cells from ionizing radiation. These spheroidal cultures can also be implanted into the dorsal skinfold window chamber of mice for fluorescence imaging of vascularization and disease progression/treatment response. We observed rapid neovascularization of the tumor-endothelial spheroids in comparison to tumor spheroids grown in nude mice. Molecular analysis revealed pronounced up-regulation of several proangiogenic factors in the tumor tissue derived from the tumor-endothelial spheroids compared with tumor-only spheroids. Furthermore, the rate of tumor growth from tumor-endothelial spheroids in mice was faster than the tumor cell-only spheroids, resulting in greater metastasis to the lung. This three-dimensional coculture model presents an improved way to investigate more pertinent aspects of the therapeutic potential for radiation and/or chemotherapy alone and in combination with antiangiogenic agents.     

Plasma proteomics and the paediatric patient

Introduction: Plasma proteomics has been extensively utilized for studies that investigate various disease settings (e.g. cardiovascular disease), as well as to monitor the effect of pharmaceuticals on the plasma proteome (e.g. chemotherapy). However, plasma proteomic studies focusing on children represent a very small proportion of the plasma proteomic studies completed to date. Early disease detection and prevention is critical in pediatrics, as children must live with the disease outcomes for many years and often carry negative outcomes into adulthood. Pediatrics represents an area of plasma proteomics that is about to undergo a significant expansion.

Areas covered: This review is based on a PubMed search focusing on five keywords that are plasma, biomarkers, pediatric, proteomics, and children. It is a comprehensive summary of plasma proteomic studies specific to the pediatric patient and discusses aspects such as the clinical setting, sample size, methodological approaches and outlines the significance of the findings.

Expert commentary: Plasma proteomics is expanding significantly as a result of major advancements in proteomic technology. This is in synergy with the growing focus on true early disease detection and prevention in early life. We are about to see a new era of advanced medical science built from pediatric proteomics.     

Enhancing the ligand efficiency of anti-HIV compounds targeting frameshift-stimulating RNA

Ribosomal frameshifting, a process whereby a translating ribosome is diverted from one reading frame to another on a contiguous mRNA, is an important regulatory mechanism in biology and an opportunity for therapeutic intervention in several human diseases. In HIV, ribosomal frameshifting controls the ratio of Gag and Gag-Pol, two polyproteins critical to the HIV life cycle. We have previously reported compounds able to selectively bind an RNA stemloop within the Gag-Pol mRNA; these compounds alter the production of Gag-Pol in a manner consistent with increased frameshifting. Importantly, they also display antiretroviral activity in human T-cells. Here, we describe new compounds with significantly reduced molecular weight, but with substantially maintained affinity and anti-HIV activity. These results suggest that development of more “ligand efficient” enhancers of ribosomal frameshifting is an achievable goal.     

Fibroblast growth factor receptor 1-IIIb is dispensable for skin morphogenesis and wound healing

Alternative splicing in the extracellular domain is a characteristic feature of members of the fibroblast growth factor receptor (FGFR) family. This splicing event generates receptor variants, which differ in their ligand binding specificities. A poorly characterized splice variant is FGFR1-IIIb, recently found to be a functional FGF receptor predominantly expressed in the skin. Here we show that FGFR1-IIIb is expressed in normal and wounded mouse skin. Reduced expression of this type of receptor was found in wounds of healing-impaired genetically diabetic mice, suggesting that downregulation of FGFR1-IIIb is associated with wound healing defects. To address this possibility, we deleted the IIIb exon of FGFR1 in mice. The lack of FGFR-IIIb did not alter the expression of either FGFR1-IIIc, other FGF receptor genes or of FGFR1-IIIb ligands in normal and wounded skin. Histological analysis of the skin of FGFR1-IIIb knockout animals did not reveal any obvious abnormalities. Furthermore, full-thickness excisional skin wounds in these mice healed normally and no defects could be observed at the macroscopic or histological level. Finally, several genes that encode key players in wound repair were normally expressed in these animals. These data demonstrate that FGFR1-IIIb is dispensable for skin development and wound repair.     

Seven days of aerobic exercise training improves conduit artery blood flow following glucose ingestion in patients with type 2 diabetes

The vasodilatory effects of insulin account for up to 40% of insulin-mediated glucose disposal; however, insulin-stimulated vasodilation is impaired in individuals with type 2 diabetes, limiting perfusion and delivery of glucose and insulin to target tissues. To determine whether exercise training improves conduit artery blood flow following glucose ingestion, a stimulus for increasing circulating insulin, we assessed femoral blood flow (FBF; Doppler ultrasound) during an oral glucose tolerance test (OGTT; 75 g glucose) in 11 overweight or obese (body mass index, 34 ± 1 kg/m2), sedentary (peak oxygen consumption, 23 ± 1 ml·kg?1·min?1) individuals (53 ± 2 yr) with non-insulin-dependent type 2 diabetes (HbA1c, 6.63 ± 0.18%) before and after 7 days of supervised treadmill and cycling exercise (60 min/day, 60-75% heart rate reserve). Fasting glucose, insulin, and FBF were not significantly different after 7 days of exercise, nor were glucose or insulin responses to the OGTT. However, estimates of whole body insulin sensitivity (Matsuda insulin sensitivity index) increased (P < 0.05). Before exercise training, FBF did not change significantly during the OGTT (1 ± 7, -7 ± 5, 0 ± 6, and 0 ± 5% of fasting FBF at 75, 90, 105, and 120 min, respectively). In contrast, after exercise training, FBF increased by 33 ± 9, 39 ± 14, 34 ± 7, and 48 ± 18% above fasting levels at 75, 90, 105, and 120 min, respectively (P < 0.05 vs. corresponding preexercise time points). Additionally, postprandial glucose responses to a standardized breakfast meal consumed under "free-living" conditions decreased during the final 3 days of exercise (P < 0.05). In conclusion, 7 days of aerobic exercise training improves conduit artery blood flow during an OGTT in individuals with type 2 diabetes.     

POM121 and Sun1 play a role in early steps of interphase NPC assembly

Nuclear pore complexes (NPCs) assemble at the end of mitosis during nuclear envelope (NE) reformation and into an intact NE as cells progress through interphase. Although recent studies have shown that NPC formation occurs by two different molecular mechanisms at two distinct cell cycle stages, little is known about the molecular players that mediate the fusion of the outer and inner nuclear membranes to form pores. In this paper, we provide evidence that the transmembrane nucleoporin (Nup), POM121, but not the Nup107-160 complex, is present at new pore assembly sites at a time that coincides with inner nuclear membrane (INM) and outer nuclear membrane (ONM) fusion. Overexpression of POM121 resulted in juxtaposition of the INM and ONM. Additionally, Sun1, an INM protein that is known to interact with the cytoskeleton, was specifically required for interphase assembly and localized with POM121 at forming pores. We propose a model in which POM121 and Sun1 interact transiently to promote early steps of interphase NPC assembly.     

A tyrosine-sulfated CCR5-mimetic peptide promotes conformational transitions in the HIV-1 envelope glycoprotein

The HIV-1 envelope glycoprotein is a trimeric complex of heterodimers composed of a surface glycoprotein, gp120, and a transmembrane component, gp41. The association of this complex with CD4 stabilizes the coreceptor-binding site of gp120 and promotes the exposure of the gp41 helical region 1 (HR1). Here, we show that a 15-amino-acid peptide mimetic of the HIV-1 coreceptor CCR5 fused to a dimeric antibody Fc domain (CCR5mim-Ig) bound two gp120 molecules per envelope glycoprotein complex and by itself promoted HR1 exposure. CCR5mim-Ig also stabilized the association of a CD4-mimetic peptide with the envelope glycoprotein. A fusion of the CD4- and CCR5-mimetic peptides, DM1, bound gp120 and neutralized R5, R5X4, and X4 HIV-1 isolates comparably to CD4, and they did so markedly more efficiently than either peptide alone. Our data indicate that the potency of DM1-Ig derives from its avidity for the HIV-1 envelope glycoprotein trimer and from the bidirectional induction of its receptor-mimetic components. DM1 has significant advantages over other inhibitors that target both coreceptor and CD4-binding sites, and it may serve as a lead for a new class of HIV-1 inhibitor peptides.     

Fairness expectations and altruistic sharing in 15-month-old human infants

Human cooperation is a key driving force behind the evolutionary success of our hominin lineage. At the proximate level, biologists and social scientists have identified other-regarding preferences--such as fairness based on egalitarian motives, and altruism--as likely candidates for fostering large-scale cooperation. A critical question concerns the ontogenetic origins of these constituents of cooperative behavior, as well as whether they emerge independently or in an interrelated fashion. The answer to this question will shed light on the interdisciplinary debate regarding the significance of such preferences for explaining how humans become such cooperative beings. We investigated 15-month-old infants' sensitivity to fairness, and their altruistic behavior, assessed via infants' reactions to a third-party resource distribution task, and via a sharing task. Our results challenge current models of the development of fairness and altruism in two ways. First, in contrast to past work suggesting that fairness and altruism may not emerge until early to mid-childhood, 15-month-old infants are sensitive to fairness and can engage in altruistic sharing. Second, infants' degree of sensitivity to fairness as a third-party observer was related to whether they shared toys altruistically or selfishly, indicating that moral evaluations and prosocial behavior are heavily interconnected from early in development. Our results present the first evidence that the roots of a basic sense of fairness and altruism can be found in infancy, and that these other-regarding preferences develop in a parallel and interwoven fashion. These findings support arguments for an evolutionary basis--most likely in dialectical manner including both biological and cultural mechanisms--of human egalitarianism given the rapidly developing nature of other-regarding preferences and their role in the evolution of human-specific forms of cooperation. Future work of this kind will help determine to what extent uniquely human sociality and morality depend on other-regarding preferences emerging early in life.