Allometric escape and acoustic signal features facilitate high-frequency communication in an endemic Chinese primate.

The principle of acoustic allometry-the larger the animal, the lower its calls' fundamental frequency-is generally observed across terrestrial mammals. Moreover, according to the Acoustic Adaptation Hypothesis, open habitats favor the propagation of high-frequency calls compared to habitats with complex vegetational structures. We carried out playback experiments in which the calls of the Guizhou snub-nosed monkey (Rhinopithecus brelichi) were used as stimuli in sound attenuation and degradation experiments to test the hypothesis that propagation of Guizhou snub-nosed monkey calls is favored above vs through the forest floor vegetation. We found that low-pitched Guizhou snub-nosed monkey vocalizations suffered less attenuation than its high-pitched calls. Guizhou snub-nosed monkeys were observed emitting high-pitched calls from 1.5 to 5.0 m above the ground. The use of high-pitched calls from these heights coupled with the concomitant behavior of moving about above the understory may provide a signal for receivers which maximizes potential transmission and efficacy. Our results support the Acoustic Adaptation Hypothesis and suggest that by uncoupling its vocal output from its size, this monkey can produce a high-pitched call with a broad spectral bandwidth, thereby increasing both its saliency and the frequency range over which the animal may more effectively communicate in its natural habitat.

Cross-feeding between Bifidobacterium infantis and Anaerostipes caccae on lactose and human milk oligosaccharides.

The establishment of the gut microbiota immediately after birth is a dynamic process that may impact lifelong health. At this important developmental stage in early life, human milk oligosaccharides (HMOs) serve as specific substrates to shape the gut microbiota of the nursling. The well-orchestrated transition is important as an aberrant microbial composition and bacterial-derived metabolites are associated with colicky symptoms and atopic diseases in infants. Here, we study the trophic interactions between an HMO-degrader, Bifidobacterium infantis and the butyrogenic Anaerostipes caccae using carbohydrate substrates that are relevant in the early life period including lactose and total human milk carbohydrates. Mono- and co-cultures of these bacterial species were grown at pH 6.5 in anaerobic bioreactors supplemented with lactose or total human milk carbohydrates. A. caccae was not able to grow on these substrates except when grown in co-culture with B. infantis, leading to growth and concomitant butyrate production. Two levels of cross-feeding were observed, in which A. caccae utilised the liberated monosaccharides as well as lactate and acetate produced by B. infantis. This microbial cross-feeding points towards the key ecological role of bifidobacteria in providing substrates for other important species that will colonise the infant gut. The progressive shift of the gut microbiota composition that contributes to the gradual production of butyrate could be important for host-microbial crosstalk and gut maturation.

Factors Related to Cervical Cancer Screening Experience among Women Aged 15 and above in Eswatini: The World Health Organisation STEP's Data 2014:A Household Cross Sectional Survey.

PURPOSE: To understand factors related to cervical cancer screening behaviors and factors that influence these behaviors among women living in Eswatini. METHODS: Data from the World Health Organization STEP's data - A household cross sectional survey in Eswatini in 2014 for 1217 eligible women aged 15 and above. The dependent variable was binary categorized, into two levels: With or without cervical cancer screening experience and independent variables were factors related to cervical cancer screening. The binary logistic regression models were used to analyze the factors related to cervical cancer screening. RESULTS: Women with cervical cancer screening experience were 15.2%. The multiple logistic regression analysis revealed that women's age, education, employment status, history of cardiovascular disease and community environment were significantly correlated with the cervical cancer screening behavior. CONCLUSION: Screening for cervical cancer is still low among women living in Eswatini. Our findings provide a greater understanding of African women's factors related to cervical cancer screening among African countries which are age, education, employment status and environmental issues. This can particularly be attributed to the limited availability and accessibility of cervical cancer screening services among socio-economically disadvantaged populations.

Gut microbiota in wild and captive Guizhou snub-nosed monkeys, Rhinopithecus brelichi.

Many colobine species-including the endangered Guizhou snub-nosed monkey (Rhinopithecus brelichi) are difficult to maintain in captivity and frequently exhibit gastrointestinal (GI) problems. GI problems are commonly linked to alterations in the gut microbiota, which lead us to examine the gut microbial communities of wild and captive R. brelichi. We used high-throughput sequencing of the 16S rRNA gene to compare the gut microbiota of wild (N = 7) and captive (N = 8) R. brelichi. Wild monkeys exhibited increased gut microbial diversity based on the Chao1 but not Shannon diversity metric and greater relative abundances of bacteria in the Lachnospiraceae and Ruminococcaceae families. Microbes in these families digest complex plant materials and produce butyrate, a short chain fatty acid critical to colonocyte health. Captive monkeys had greater relative abundances of Prevotella and Bacteroides species, which degrade simple sugars and carbohydrates, like those present in fruits and cornmeal, two staples of the captive R. brelichi diet. Captive monkeys also had a greater abundance of Akkermansia species, a microbe that can thrive in the face of host malnutrition. Taken together, these findings suggest that poor health in captive R. brelichi may be linked to diet and an altered gut microbiota.

Current Practice of Therapeutic Hypothermia for Mild Hypoxic Ischemic Encephalopathy.

CONTEXT: Therapeutic hypothermia is the recommended treatment for neonates with moderate or severe hypoxic ischemic encephalopathy (HIE). There is an increasing trend to use therapeutic hypothermia even in infants with mild hypoxic ischemic encephalopathy, even though there is little evidence to support/refute this. OBJECTIVE: To estimate the incidences of mild hypoxic ischemic encephalopathy among infants who received therapeutic hypothermia, and its short- and long-term outcomes. DATA SOURCES AND STUDY SELECTION: PubMed, Embase, CINAHL, and Cochrane library were searched to identify observational studies reporting on therapeutic hypothermia in term and near-term infants with mild hypoxic ischemic encephalopathy. The JBI (Joanna Briggs Institute) tools were used to assess the risk of bias in the included studies. Random effects meta-analysis was conducted to find out the percentage of cooled infants who had only mild hypoxic ischemic encephalopathy. RESULTS: A total of 3590 citations were screened, of which 13 were included. Of the 2783 infants who received therapeutic hypothermia, 573 had mild hypoxic ischemic encephalopathy. Meta-analysis found that 22% of the infants who underwent therapeutic hypothermia had only mild hypoxic ischemic encephalopathy (95% confidence interval: 16%-27%; I2 statistic = 90.5%). Five studies provided information on adverse effects of therapeutic hypothermia in mild hypoxic ischemic encephalopathy. The reported adverse effects were extreme hypothermia, bradycardia, hypoglycemia, sepsis, skin necrosis, pulmonary hypertension, and systemic hypotension. Limitation: The limitations included relatively small sample size and the lack of data for short- and long-term neurodevelopmental outcome. CONCLUSIONS: A significant proportion of infants who received therapeutic hypothermia had mild hypoxic ischemic encephalopathy. Randomized trials are urgently needed to evaluate the efficacy and safety of therapeutic hypothermia in infants with mild hypoxic ischemic encephalopathy.

Diet Versus Phylogeny: a Comparison of Gut Microbiota in Captive Colobine Monkey Species.

Both diet and host phylogeny shape the gut microbial community, and separating out the effects of these variables can be challenging. In this study, high-throughput sequencing was used to evaluate the impact of diet and phylogeny on the gut microbiota of nine colobine monkey species (N = 64 individuals). Colobines are leaf-eating monkeys that fare poorly in captivity-often exhibiting gastrointestinal (GI) problems. This study included eight Asian colobines (Rhinopithecus brelichi, Rhinopithecus roxellana, Rhinopithecus bieti, Pygathrix nemaeus, Nasalis larvatus, Trachypithecus francoisi, Trachypithecus auratus, and Trachypithecus vetulus) and one African colobine (Colobus guereza). Monkeys were housed at five different captive institutes: Panxi Wildlife Rescue Center (Guizhou, China), Beijing Zoo, Beijing Zoo Breeding Center, Singapore Zoo, and Singapore Zoo Primate Conservation Breeding Center. Captive diets varied widely between institutions, but within an institution, all colobine monkey species were fed nearly identical or identical diets. In addition, four monkey species were present at multiple captive institutes. This allowed us to parse the effects of diet and phylogeny in these captive colobines. Gut microbial communities clustered weakly by host species and strongly by diet, and overall, colobine phylogenetic relationships were not reflected in gut microbiota analyses. Core microbiota analyses also identified several key taxa-including microbes within the Ruminococcaceae and Lachnospiraceae families-that were shared by over 90% of the monkeys in this study. Microbial species within these families include many butyrate producers that are important for GI health. These results highlight the importance of diet in captive colobines.

Effects of field conditions on fecal microbiota.

Gut microbiota can provide great insight into host health, and studies of the gut microbiota in wildlife are becoming more common. However, the effects of field conditions on gut microbial samples are unknown. This study addresses the following questions: 1) How do environmental factors such as sunlight and insect infestations affect fecal microbial DNA? 2) How does fecal microbial DNA change over time after defecation? 3) How does storage method affect microbial DNA? Fresh fecal samples were collected, pooled, and homogenized from a family group of 6 spider monkeys, Ateles geoffroyi. Samples were then aliquoted and subjected to varying light conditions (shade, sun), insect infestations (limited or not limited by netting over the sample), and sample preservation methods (FTA - Fast Technology for Analysis of nucleic acid - cards, or freezing in liquid nitrogen then storing at -20°C). Changes in the microbial communities under these conditions were assessed over 24h. Time and preservation method both effected fecal microbial community diversity and composition. The effect size of these variables was then assessed in relation to fecal microbial samples from 2 other primate species (Rhinopithecus bieti and R. brelichi) housed at different captive institutions. While the microbial community of each primate species was significantly different, the effects of time and preservation method still remained significant indicating that these effects are important considerations for fieldwork.

The High Mobility Group A1 (HMGA1) Transcriptome in Cancer and Development.

BACKGROUND & OBJECTIVES: Chromatin structure is the single most important feature that distinguishes a cancer cell from a normal cell histologically. Chromatin remodeling proteins regulate chromatin structure and high mobility group A (HMGA1) proteins are among the most abundant, nonhistone chromatin remodeling proteins found in cancer cells. These proteins include HMGA1a/HMGA1b isoforms, which result from alternatively spliced mRNA. The HMGA1 gene is overexpressed in cancer and high levels portend a poor prognosis in diverse tumors. HMGA1 is also highly expressed during embryogenesis and postnatally in adult stem cells. Overexpression of HMGA1 drives neoplastic transformation in cultured cells, while inhibiting HMGA1 blocks oncogenic and cancer stem cell properties. Hmga1 transgenic mice succumb to aggressive tumors, demonstrating that dysregulated expression of HMGA1 causes cancer in vivo. HMGA1 is also required for reprogramming somatic cells into induced pluripotent stem cells. HMGA1 proteins function as ancillary transcription factors that bend chromatin and recruit other transcription factors to DNA. They induce oncogenic transformation by activating or repressing specific genes involved in this process and an HMGA1 "transcriptome" is emerging. Although prior studies reveal potent oncogenic properties of HMGA1, we are only beginning to understand the molecular mechanisms through which HMGA1 functions. In this review, we summarize the list of putative downstream transcriptional targets regulated by HMGA1. We also briefly discuss studies linking HMGA1 to Alzheimer's disease and type-2 diabetes. CONCLUSION: Further elucidation of HMGA1 function should lead to novel therapeutic strategies for cancer and possibly for other diseases associated with aberrant HMGA1 expression.

Effect of preservation method on spider monkey (Ateles geoffroyi) fecal microbiota over 8 weeks.

Studies of the gut microbiome have become increasingly common with recent technological advances. Gut microbes play an important role in human and animal health, and gut microbiome analysis holds great potential for evaluating health in wildlife, as microbiota can be assessed from non-invasively collected fecal samples. However, many common fecal preservation protocols (e.g. freezing at -80 °C) are not suitable for field conditions, or have not been tested for long-term (greater than 2 weeks) storage. In this study, we collected fresh fecal samples from captive spider monkeys (Ateles geoffroyi) at the Columbian Park Zoo (Lafayette, IN, USA). The samples were pooled, homogenized, and preserved for up to 8 weeks prior to DNA extraction and sequencing. Preservation methods included: freezing at -20 °C, freezing at -80 °C, immersion in 100% ethanol, application to FTA cards, and immersion in RNAlater. At 0 (fresh), 1, 2, 4, and 8 weeks from fecal collection, DNA was extracted and microbial DNA was amplified and sequenced. DNA concentration, purity, microbial diversity, and microbial composition were compared across all methods and time points. DNA concentration and purity did not correlate with microbial diversity or composition. Microbial composition of frozen and ethanol samples were most similar to fresh samples. FTA card and RNAlater-preserved samples had the least similar microbial composition and abundance compared to fresh samples. Microbial composition and diversity were relatively stable over time within each preservation method. Based on these results, if freezers are not available, we recommend preserving fecal samples in ethanol (for up to 8weeks) prior to microbial extraction and analysis.

Investigation of treadmill and overground running: implications for the measurement of oxygen cost in children with developmental coordination disorder.

Differences in the kinematics and kinetics of overground running have been reported between boys with and without developmental coordination disorder (DCD). This study compared the kinematics of overground and treadmill running in children with and without DCD to determine whether any differences in technique are maintained, as this may influence the outcome of laboratory treadmill studies of running economy in this population. Nine boys with DCD (10.3 ± 1.1 year) and 10 typically developing (TD) controls (9.7 ± 1 year) ran on a treadmill and overground at a matched velocity (8.8 ± 0.9 km/h). Kinematic data of the trunk and lower limb were obtained for both conditions using a 12-camera Vicon MX system. Both groups displayed an increase in stance time (p < 0.001), shorter stride length (p < 0.001), higher cadence (p < 0.001) and reduced ankle plantar flexion immediately after toe-off (p < 0.05) when running on the treadmill compared with overground. The DCD group had longer stance time (p < 0.009) and decreased knee flexion at mid-swing (p = 0.04) while running overground compared to their peers, but these differences were maintained when running on the treadmill. Treadmill running improved ankle joint symmetry in the DCD group compared with running overground (p = 0.019). Overall, these findings suggest that there are limited differences in joint kinematics and lower limb symmetry between overground and treadmill running in this population. Accordingly, laboratory studies of treadmill running in children with DCD are likely representative of the energy demands of running.

A comparison of the oxygen cost and physiological responses to running in children with and without Developmental Coordination Disorder.

The aim of this study was to compare the oxygen cost of running in boys with and without Developmental Coordination Disorder (DCD). Fourteen boys with DCD (9.1 ± 1.4 yr) and 16 typically developing (TD) controls (9.4 ± 1.3 yr) were tested on two separate occasions at least a week apart. On the first visit, motor proficiency, body composition and maximal aerobic capacity were established. On the second visit, oxygen consumption was determined via indirect calorimetry while participants ran at three submaximal speeds (7.2 km/h, 8.0 km/h and 8.8 km/h) on a motorised treadmill for 4 min each. Additional physiological responses such as blood lactate, respiratory exchange ratio (RER), heart rate, salivary alpha amylase and pain threshold were monitored at baseline and after each submaximal effort. Although there were no differences in the oxygen cost of running at all three speeds, the boys with DCD had higher blood lactate concentration (7.2 km/h, p=0.05; 8.0 km/h p=0.019), heart rate (p ≤ 0.001), RER (8.0 km/h, p=0.019; 8.8 km/h, p=0.001), salivary alpha amylase (8.0 km/h, p=0.023; 8.8 km/h, p=0.020) and a lower pain threshold (p<0.01). The higher overall metabolic cost of running in boys with DCD as indicated by the higher RER, heart rate and blood lactate concentrations, together with the higher levels of sympathoadrenal medullary activity and sensitivity to pain, may be deterring factors for participation in physical activity in this population.

A comparison of running kinematics and kinetics in children with and without developmental coordination disorder.

The aim of this study was to compare running gait in children with and without developmental coordination disorder (DCD). Fourteen boys with DCD (9.5 ± 1 yr) and 14 typically developing (TD) controls (9.6 ± 1 yr) ran at a velocity of 2.44 ± 0.25 m/s along a 15m track, with kinematic and kinetic data of the trunk and lower limb obtained for three cycles of each limb using a 12-camera Vicon MX system and AMTI force plate. Although features of the kinematic and kinetic trajectories were similar between groups, the DCD group displayed decreased peak knee extension compared with the TD group prior to initial foot contact (p = 0.016). Furthermore, the DCD group displayed increased variability in sagittal plane kinematics at the hip and ankle during toe off compared with the TD group. Kinetic analysis revealed that children with DCD displayed significantly reduced knee extensor moments during the stance phase of the running cycle (p = 0.033). Consequently, peak knee power absorption and ankle power generation was significantly lower in the DCD group (p = 0.041; p = 0.017). Furthermore, there was a trend for children with DCD to have shorter strides (p = 0.052, ES = 0.499) and a longer stance period than the TD controls (p=0.06, ES = 0.729). These differences may have implications for the economy of running and subsequently the planning of targeted intervention programs to improve running gait in children with DCD.

Into the night: camera traps reveal nocturnal activity in a presumptive diurnal primate, Rhinopithecus brelichi.

Most living primates exhibit a daytime or nighttime activity pattern. Strict diurnality is thought to be the rule among anthropoids except for owl monkeys. Here we report the diel activity pattern of an Asian colobine, the Guizhou snub-nosed monkey Rhinopithecus brelichi, based on a methodology that relied on using 24-h continuously operating camera traps. We conducted the study in Fanjingshan National Nature Reserve in Guizhou, China from March 22 to May 19 and from June 17 to October 14, 2011. After standardizing all time elements to a meridian-based time according to the geographic coordinates of the study site, we showed unequivocally that the monkeys, though predominantly diurnal, exhibited activity beyond daylight hours throughout the study. Specifically, their activity at night and during twilight periods suggests a complex interplay of behavioral adaptations, among others, to living in a temperate environment where day length and food resources fluctuate substantially across seasons. We contend that, under prevailing ecological conditions, so-called strictly diurnal primates may adjust their activity schedule opportunistically in order to increase energy intake. We also discuss the advantages of using camera traps in primate studies, and how the standardized use of meridian-based time by researchers would benefit comparisons of diel activity patterns among primates.

Measurement of macrophage marker in hyperhaemolytic transfusion reaction: a case report.

BACKGROUND: Hyperhaemolytic transfusion reaction (HHTR) has been well described in patients with sickle cell disease (SCD). It is characterised by a decrease in haemoglobin concentration to levels below those before transfusion and a fall in the absolute reticulocyte count. As red blood cells (RBC) alloantibodies are typically not detected in post-transfusion samples in acute forms of HHTR, we have previously proposed that both the transfused and autologous RBCs cells (HbSS/reticulocytes) are destroyed by activated macrophages. CASE REPORTS: We report a patient with SCD who presented with vaso-occlusive sickle cell crisis and developed a severe HHTR attributable to anti-Fy3. In addition to the usual supportive measures, the patient was treated with intravenous immunoglobulin (IVIG) and steroids. Serum ferritin levels were measured as an aspecific marker of macrophage activation. RESULTS: Steroids and IVIG were effective in managing HHTR. Ferritin levels were high at the time of haemolysis, (>10000 µg L(-1)) whereas recovery and cessation of haemolysis correlated with a decrease in ferritin levels. CONCLUSION: Serum ferritin values >10,000 µg L(-1) are considered pathognomic for conditions characterised by abnormal macrophage activation. In our case, serum ferritin levels correlate well with the disease activity and clinical response. This further supports our previous proposal that the activated macrophages play an important role in HHTR. Serum ferritin is a nonspecific marker of inflammation. A rapid specific bio-marker to measure the activity of macrophages in SCD in HHTR is desirable, and this area warrants further investigation.

Inter-unit contests within a provisioned troop of Sichuan snub-nosed monkeys (Rhinopithecus roxellana) in the Qinling Mountains, China.

Numerical superiority does not always ensure victory in intergroup contests. Although group size is likely to determine the maximum resource holding potential (RHP) of a group, the realized RHP is the collective outcome of individual group members' choices about participation in any given contest. For any group member, the choice about participation should be based on the assessment of costs and benefits that are affected by both ecological and social factors. In this study, we studied inter-unit contests in a provisioned troop of Sichuan snub-nosed monkeys (Rhinopithecus roxellana). We spent 368 hr in contact with 9 one-male units sharing the same home range, during which we recorded 148 inter-unit contests at a provisioning site. Inter-unit contests always started as inter-individual contests. Contests escalated only when the two individuals were of different age-sex classes and one was an adult male. When a contest escalated, additional individuals were likely to get involved, and the outcome of the contest depended on unit members' choices about participation. The superiority in the number of participants rather than the superiority in unit size led to victory in inter-unit contests, given that the difference in unit size did not predict a difference in the number of participants. Unit members were more likely to support others in inter-unit contests in winter when food was sparse than in spring when food was abundant. In addition, unit members were more likely to support others in escalated contests than in those resulting in displacement, indicating that they tended to alter the outcome of a contest to gain immediate benefit. Although males initiated most inter-unit contests, a clear win-loss was most likely when females joined the fight. This sex difference may reflect the benefits to males vs. females of living in a multi-level society.

Altitudinal movements of Guizhou snub-nosed monkeys (Rhinopithecus brelichi) in Fanjingshan National Nature Reserve, China: implications for conservation management of a flagship species.

Primate movements can include a substantial altitudinal component, depending on the complexity of the landscape and the distribution of the inherent vegetation zones. We investigated altitudinal movements of Guizhou snub-nosed monkeys (Rhinopithecus brelichi) at Fanjingshan National Nature Reserve, China. The monkeys ranged at elevations between 1,350 and 1,870 m with an overall mean of 1,660 m. We did not find a significant difference in the mean elevations among seasons or evidence of winter migration to lower elevations. The monkeys exhibited a distinct daily altitudinal movement pattern that coincided with their activities. During the day, the monkeys consistently traveled from lower to higher elevations in the morning (98% of records) and then descended to lower elevations in the afternoon (96%). Hence, the mean elevation of night roosts was significantly lower (1,561 m) than those of feeding sites and day roosts (1,735 and 1,737 m, respectively). We suggest that this daily pattern of R. brelichi may reflect a trade-off between finding food and avoiding predation within the mixed evergreen and deciduous broadleaf vegetation zone at the study site, which may constitute the most important habitat for R. brelichi in the reserve.

Calcitonin impairs the anabolic effect of PTH in young rats and stimulates expression of sclerostin by osteocytes.

The therapeutic goal of increasing bone mass by co-treatment of parathyroid hormone (PTH) and an osteoclast inhibitor has been complicated by the undefined contribution of osteoclasts to the anabolic activity of PTH. To determine whether active osteoclasts are required at the time of PTH administration, we administered a low dose of the transient osteoclast inhibitor salmon calcitonin (sCT) to young rats receiving an anabolic PTH regimen. Co-administration of sCT significantly blunted the anabolic effect of PTH as measured by peripheral quantitative computer tomography (pQCT) and histomorphometry in the femur and tibia, respectively. To determine gene targets of sCT, we carried out quantitative real time PCR and microarray analysis of metaphyseal samples 1.5, 4 and 6.5h after administration of a single injection of PTH, sCT or PTH+sCT. Known targets of PTH action, IL-6, ephrinB2 and RANKL, were not modified by co-administration with sCT. Surprisingly, at all time points, we noted a significant upregulation of sclerostin mRNA by sCT treatment, as well as down-regulation of two other osteocyte gene products, MEPE and DMP1. Immunohistochemistry confirmed that sCT administration increased the percentage of osteocytes expressing sclerostin, suggesting a mechanism by which sCT reduced the anabolic effect of PTH. Neither mRNA for CT receptor (Calcr) nor labeled CT binding could be detected in sclerostin-enriched cells differentiated from primary calvarial osteoblasts. In contrast, osteocytes freshly isolated from calvariae expressed a high level of Calcr mRNA. Furthermore immunohistochemistry revealed co-localization of CT receptor (CTR) and sclerostin in some osteocytes in calvarial sections. Taken together these data indicate that co-treatment with sCT can blunt the anabolic effect of PTH and this may involve direct stimulation of sclerostin production by osteocytes. These data directly implicate calcitonin as a negative regulator of bone formation through a previously unsuspected mechanism.

Semi-quantitative tests of cyanide in foods and excreta of Three Hapalemur species in Madagascar.

Three sympatric Hapalemur species (H. g. griseus, H. aureus, and H. (Prolemur) simus) in Ranomafana National Park, Madagascar are known to eat bamboo food parts that contain cyanide. How these lemurs avoid cyanide poisoning remains unknown. In this study, we tested for the presence/absence of cyanide in bamboo lemur foods and excreta to (1) document patterns of cyanide consumption among species with respect to diet, (2) identify routes of elimination of cyanide from the gastrointestinal tract, and (3) determine whether cyanide is absorbed from the diet. We tested 102 food, urine, and fecal samples for hydrogen cyanide (HCN) during two "pre-dry" seasons (April 2006, May 2007) using commercially available Cyantesmo test strips. The test strips changed color in the presence of HCN, and we recorded color change on a scale of 0 (no change) to 5 (cobalt) at preset intervals with a final score taken at 24 hr. We detected cyanide in bamboo food parts and urine of all three Hapalemur species. Time to color change of the test strips ranged from almost instantaneous to >12 hr incubation. Of the foods tested, only bamboo contained cyanide, but results differed among bamboo species and plant parts of the same species. Specifically, branch shoot and culm pith of the giant bamboo produced strong, immediate reactions to the test paper, whereas parts of liana bamboos produced either weak or no color change. Cyanide was present in almost all urine samples but rarely in fecal samples. This suggests that dietary cyanide is absorbed in the gastrointestinal tract of the Hapalemur species and excreted, at least in part, by the kidneys. Samples from H. griseus exhibited lower, though still detectable, cyanide levels compared with H. simus and H. aureus. Differences among lemur species appear to be related to the specific bamboo parts consumed.

Intermedin/adrenomedullin-2 is a hypoxia-induced endothelial peptide that stabilizes pulmonary microvascular permeability.

Accumulating evidence suggests a pivotal role of the calcitonin receptor-like receptor (CRLR) signaling pathway in preventing damage of the lung by stabilizing pulmonary barrier function. Intermedin (IMD), also termed adrenomedullin-2, is the most recently identified peptide targeting this receptor. Here we investigated the effect of hypoxia on the expression of IMD in the murine lung and cultured murine pulmonary microvascular endothelial cells (PMEC) as well as the role of IMD in regulating vascular permeability. Monoclonal IMD antibodies were generated, and transcript levels were assayed by quantitative RT-PCR. The promoter region of IMD gene was analyzed, and the effect of hypoxia-inducible factor (HIF)-1alpha on IMD expression was investigated in HEK293T cells. Isolated murine lungs and a human lung microvascular endothelial cell monolayer model were used to study the effect of IMD on vascular permeability. IMD was identified as a pulmonary endothelial peptide by immunohistochemistry and RT-PCR. Hypoxia caused an upregulation of IMD mRNA in the murine lung and PMEC. As shown by these results, HIF-1alpha enhances IMD promoter activity. Our functional studies showed that IMD abolished the increase in pressure-induced endothelial permeability. Moreover, IMD decreased basal and thrombin-induced hyperpermeability of an endothelial cell monolayer in a receptor-dependent manner and activated PKA in these cells. In conclusion, IMD is a novel hypoxia-induced gene and a potential interventional agent for the improvement of endothelial barrier function in systemic inflammatory responses and hypoxia-induced vascular leakage.