Regulation of pro-inflammatory and pro-fibrotic factors by CCN2/CTGF in H9c2 cardiomyocytes

Connective tissue growth factor (CTGF), also known as CCN2, is implicated in fibrosis through both extracellular matrix (ECM) induction and inhibition of ECM degradation. The role of CTGF in inflammation in cardiomyocytes is unknown. In some mesenchymal cell systems, CTGF mediates effects through TGF-β or tyrosine kinase cell surface receptor, TrkA, signalling. In this study, cellular mechanisms by which CTGF regulates pathways involved in fibrosis and inflammation were explored. Murine H9c2 cardiomyocytes were treated with recombinant human (rh)CTGF and ECM formation gene expression: fibronectin, collagen type -I and -III and ECM degradation genes: TIMP-1, TIMP-2 and PAI-1 were found to be induced. CTGF treatment also increased pro-inflammatory cytokines TNF-α, IL-6, MCP-1 and IL-8. CTGF upregulated TGF-β1 mRNA and rapidly induced phosphorylation of TrkA. The CTGF-induced pro-fibrotic and pro-inflammatory effects were blocked by anti-TGF-β neutralizing antibody and Alk 5 inhibitor (SB431542). A specific blocker of TrkA activation, k252a, also abrogated CTGF-induced effects on fibrosis and gene expresison of MCP-1 and IL-8, but not TNF-α or IL-6. Collectively, this data implicates CTGF in effects on pro-fibrotic genes and pro-inflammatory genes via TGF-β pathway signalling and partly through TrkA.     

Surviving at the extreme: Chimpanzee ranging is not restricted in a deforested human‐dominated landscape in Uganda

Endangered wildlife increasingly inhabits human‐dominated landscapes outside protected areas. Large‐bodied mammals require large spaces, and their ranging may be especially impacted by landscape modifications including farming, road development and urbanisation. We studied the Wagaisa community of chimpanzees (Pan troglodytes) in Uganda, which inhabit a landscape characterised by high human population density, widespread deforestation, and rapid agricultural and infrastructural development. We aimed to assess whether this dynamic, fragmented environment constrains the chimpanzees’ ranging, and to identify critical habitat patches to aid their conservation. During March–May 2018, we assessed range use from locations of direct observations and indirect signs, corroborated by longer‐term behavioural monitoring of the chimpanzees (June 2018–December 2019). No evidence of limited ranging was found. The Wagaisa chimpanzees used an area measuring ≥ 43 km² (100% MCP) and ranged extensively in the anthropogenic matrix. Most frequently used parts of the range (‘core habitat areas’) centred around small (5–20 acres), widely dispersed remnant forest patches and exotic eucalyptus plantations. Forty per cent of chimpanzee nests were constructed in eucalyptus trees, suggesting a behavioural adjustment to landscape changes. Actions to facilitate conservation of these ‘village chimpanzees’ and others surviving in transformed human‐dominated habitat need not conflict with the sustainable development of the region.     

Disentangling Woodland Caribou Movements in Response to Clearcuts and Roads across Temporal Scales

Although prey species typically respond to the most limiting factors at coarse spatiotemporal scales while addressing biological requirements at finer scales, such behaviour may become challenging for species inhabiting human altered landscapes. We investigated how woodland caribou, a threatened species inhabiting North-American boreal forests, modified their fine-scale movements when confronted with forest management features (i.e. clearcuts and roads). We used GPS telemetry data collected between 2004 and 2010 on 49 female caribou in a managed area in Québec, Canada. Movements were studied using a use – availability design contrasting observed steps (i.e. line connecting two consecutive locations) with random steps (i.e. proxy of immediate habitat availability). Although caribou mostly avoided disturbances, individuals nonetheless modulated their fine-scale response to disturbances on a daily and annual basis, potentially compromising between risk avoidance in periods of higher vulnerability (i.e. calving, early and late winter) during the day and foraging activities in periods of higher energy requirements (i.e. spring, summer and rut) during dusk/dawn and at night. The local context in which females moved was shown to influence their decision to cross clearcut edges and roads. Indeed, although females typically avoided crossing clearcut edges and roads at low densities, crossing rates were found to rapidly increase in greater disturbance densities. In some instance, however, females were less likely to cross edges and roads as densities increased. Females may then be trapped and forced to use disturbed habitats, known to be associated with higher predation risk. We believe that further increases in anthropogenic disturbances could exacerbate such behavioural responses and ultimately lead to population level consequences.     

Trends in Severity of Illness on ICU Admission and Mortality among the Elderly

Background

There is an increase in admission rate for elderly patients to the ICU. Mortality rates are lower when more liberal ICU admission threshold are compared to more restrictive threshold. We sought to describe the temporal trends in elderly admissions and outcomes in a tertiary hospital before and after the addition of an 8-bed medical ICU.

Methods

We conducted a retrospective analysis of a comprehensive longitudinal ICU database, from a large tertiary medical center, examining trends in patients’ characteristics, severity of illness, intensity of care and mortality rates over the years 2001–2008. The study population consisted of elderly patients and the primary endpoints were 28 day and one year mortality from ICU admission.

Results

Between the years 2001 and 2008, 7,265 elderly patients had 8,916 admissions to ICU. The rate of admission to the ICU increased by 5.6% per year. After an eight bed MICU was added, the severity of disease on ICU admission dropped significantly and crude mortality rates decreased thereafter. Adjusting for severity of disease on presentation, there was a decreased mortality at 28- days but no improvement in one- year survival rates for elderly patient admitted to the ICU over the years of observation. Hospital mortality rates have been unchanged from 2001 through 2008.

Conclusion

In a high capacity ICU bed hospital, there was a temporal decrease in severity of disease on ICU admission, more so after the addition of additional medical ICU beds. While crude mortality rates decreased over the study period, adjusted one-year survival in ICU survivors did not change with the addition of ICU beds. These findings suggest that outcome in critically ill elderly patients may not be influenced by ICU admission. Adding additional ICU beds to deal with the increasing age of the population may therefore not be effective.     

Reliable identification at the species level of Brucella isolates with MALDI-TOF-MS

Background

Brucella abortus is the etiological agent of a worldwide zoonosis called brucellosis. This alpha-proteobacterium is dividing asymmetrically, and PdhS, an essential histidine kinase, was reported to be an old pole marker.

Results

We were interested to identify functions that could be recruited to bacterial poles. The Brucella ORFeome, a collection of cloned predicted coding sequences, was placed in fusion with yellow fluorescent protein (YFP) coding sequence and screened for polar localizations in B. abortus. We report that AidB-YFP was systematically localized to the new poles and at constrictions sites in B. abortus, either in culture or inside infected HeLa cells or RAW264.7 macrophages. AidB is an acyl-CoA dehydrogenase (ACAD) homolog, similar to E. coli AidB, an enzyme putatively involved in destroying alkylating agents. Accordingly, a B. abortus aidB mutant is more sensitive than the wild-type strain to the lethality induced by methanesulphonic acid ethyl ester (EMS). The exposure to EMS led to a very low frequency of constriction events, suggesting that cell cycle is blocked during alkylation damage. The localization of AidB-YFP at the new poles and at constriction sites seems to be specific for this ACAD homolog since two other ACAD homologs fused to YFP did not show specific localization. The overexpression of aidB, but not the two other ACAD coding sequences, leads to multiple morphological defects.

Conclusions

Data reported here suggest that AidB is a marker of new poles and constriction sites, that could be considered as sites of preparation of new poles in the sibling cells originating from cell division. The possible role of AidB in the generation or the function of new poles needs further investigation.     

Biology and data-intensive scientific discovery in the beginning of the 21st century

The life sciences are poised at the beginning of a paradigm-changing evolution in the way scientific questions are answered. Data-Intensive Science (DIS) promise to provide new ways of approaching scientific challenges and answering questions. This article is a summary of the life sciences issues and challenges as discussed in the DIS workshop in Seattle, September 19-20, 2010.     

Functional characterization and target discovery of glycoside hydrolases from the digestome of the lower termite Coptotermes gestroi

Background

Lignocellulosic materials have been moved towards the forefront of the biofuel industry as a sustainable resource. However, saccharification and the production of bioproducts derived from plant cell wall biomass are complex and lengthy processes. The understanding of termite gut biology and feeding strategies may improve the current state of biomass conversion technology and bioproduct production.

Results

The study herein shows comprehensive functional characterization of crude body extracts from Coptotermes gestroi along with global proteomic analysis of the termite's digestome, targeting the identification of glycoside hydrolases and accessory proteins responsible for plant biomass conversion. The crude protein extract from C. gestroi was enzymatically efficient over a broad pH range on a series of natural polysaccharides, formed by glucose-, xylose-, mannan- and/or arabinose-containing polymers, linked by various types of glycosidic bonds, as well as ramification types. Our proteomic approach successfully identified a large number of relevant polypeptides in the C. gestroi digestome. A total of 55 different proteins were identified and classified into 29 CAZy families. Based on the total number of peptides identified, the majority of components found in the C. gestroi digestome were cellulose-degrading enzymes. Xylanolytic enzymes, mannan- hydrolytic enzymes, pectinases and starch-degrading and debranching enzymes were also identified. Our strategy enabled validation of liquid chromatography with tandem mass spectrometry recognized proteins, by enzymatic functional assays and by following the degradation products of specific 8-amino-1,3,6-pyrenetrisulfonic acid labeled oligosaccharides through capillary zone electrophoresis.

Conclusions

Here we describe the first global study on the enzymatic repertoire involved in plant polysaccharide degradation by the lower termite C. gestroi. The biochemical characterization of whole body termite extracts evidenced their ability to cleave all types of glycosidic bonds present in plant polysaccharides. The comprehensive proteomic analysis, revealed a complete collection of hydrolytic enzymes including cellulases (GH1, GH3, GH5, GH7, GH9 and CBM 6), hemicellulases (GH2, GH10, GH11, GH16, GH43 and CBM 27) and pectinases (GH28 and GH29).     

From forest to farm: systematic review of cultivar feeding by chimpanzees--management implications for wildlife in anthropogenic landscapes

Crop-raiding is a major source of conflict between people and wildlife globally, impacting local livelihoods and impeding conservation. Conflict mitigation strategies that target problematic wildlife behaviours such as crop-raiding are notoriously difficult to develop for large-bodied, cognitively complex species. Many crop-raiders are generalist feeders. In more ecologically specialised species crop-type selection is not random and evidence-based management requires a good understanding of species' ecology and crop feeding habits. Comprehensive species-wide studies of crop consumption by endangered wildlife are lacking but are important for managing human-wildlife conflict. We conducted a comprehensive literature search of crop feeding records by wild chimpanzees (Pan troglodytes), a ripe-fruit specialist. We assessed quantitatively patterns of crop selection in relation to species-specific feeding behaviour, agricultural exposure, and crop availability. Crop consumption by chimpanzees is widespread in tropical Africa. Chimpanzees were recorded to eat a considerable range of cultivars (51 plant parts from 36 species). Crop part selection reflected a species-typical preference for fruit. Crops widely distributed in chimpanzee range countries were eaten at more sites than sparsely distributed crops. We identified 'high' and 'low' conflict crops according to their attractiveness to chimpanzees, taking account of their importance as cash crops and/or staple foods to people. Most (86%) high conflict crops were fruits, compared to 13% of low conflict crops. Some widely farmed cash or staple crops were seldom or never eaten by chimpanzees. Information about which crops are most frequently consumed and which are ignored has enormous potential for aiding on-the-ground stakeholders (i.e. farmers, wildlife managers, and conservation and agricultural extension practitioners) develop sustainable wildlife management schemes for ecologically specialised and protected species in anthropogenic habitats. However, the economic and subsistence needs of local people, and the crop-raiding behaviour of sympatric wildlife, must be considered when assessing suitability of particular crops for conflict prevention and mitigation.     

Seed germination temperatures of eight Mexican Agave species with economic importance

The genetic diversity of Agave plants is threatened by clonal commercial reproduction and climatic change. Sexual reproduction is uncommon and research on seed germination is scarce. The present study evaluated the seed germination of Agave lechuguilla, Agave striata, Agave americana var. marginata, Agave asperrima, Agave cupreata, Agave duranguesis, Agave angustifolia ssp. tequilana and Agave salmiana at constant temperatures (10, 15, 20, 25, 30, 35 and 40°C). Initial imbibition (after the first 12 h) was significantly variable among species, positively correlated with seed weight (r = 0.6560, P < 0.001) and increased with temperature (from 35% at 10°C to 66% at 40°C). Temperature affected maximum imbibition (83–150%) for A. asperrima, A. lechuguilla, A. salmiana and A. striata; other species averaged 110%. Most germination kinetics best fitted a logistic model, whereas only a few treatments fit a Weibull model. The time to germination onset diminished (P < 0.05) from 125–173 h at 15°C to 68–84 h at 25°C, and then ascended to 84–196 h at 35°C. The mean germination rate and seed germination percentage after 312 h peaked at 25°C (0.50–0.95% seeds/h and 85–99%, respectively) and fell (P < 0.05) to near zero at 10 and 40°C. Temperatures of 10, 35 and 40°C were partially lethal to A. asperrima, A. duranguensis and A. salmiana seeds. The time to germination onset, seed germination percentage after 312 h and mean germination rate are best described by a Gaussian distribution, with its optimum at approximately 25°C. Thus, optimum temperatures are related to the ecological characteristics of each species area.     

High frequency of leaf swallowing and its relationship to intestinal parasite expulsion in "village" chimpanzees at Bulindi, Uganda

Self-medication by great apes to control intestinal parasite infections has been documented at sites across Africa. Chimpanzees (Pan troglodytes) swallow the leaves of certain plant species whole, without chewing. Previous studies demonstrated a relationship between chimpanzee leaf swallowing and expulsion of nematode worms (Oesophagostomum sp.) and tapeworms (Bertiella sp.) in dung. We investigated the relationship between leaf swallowing and parasite expulsion in chimpanzees inhabiting a fragmented forest-farm mosaic at Bulindi, Uganda. During 13 months whole undigested leaves occurred in chimpanzee dung at a considerably higher frequency (10.4% of dungs) than at other sites (0.4-4.0%). Leaf swallowing occurred year-round and showed no pronounced seasonality. Chimpanzees egested adults of multiple species of Oesophagostomum (including O. stephanostomum) and proglottids of two tapeworms-Bertiella sp. and probably Raillietina sp. The latter may not be a true infection, but the byproduct of predation on domestic fowl. Compared to previous studies, the co-occurrence of whole leaves and parasites in chimpanzee dung was low. Whereas the presence of leaves in dung increased the probability of adult nematode expulsion, no association between leaf swallowing and the shedding of tapeworm proglottids was apparent. Anthropogenic habitat changes have been linked to alterations in host-parasite interactions. At Bulindi, deforestation for agriculture has increased contact between apes and people. Elevated levels of leaf swallowing could indicate these chimpanzees are especially vulnerable to parasite infections, possibly due to environmental changes and/or increased stress levels arising from a high frequency of contact with humans. Frequent self-medication by chimpanzees in a high-risk environment could be a generalized adaptation to multiple parasite infections that respond differently to the behavior. Future parasitological surveys of apes and humans at Bulindi are needed for chimpanzee health monitoring and management, and to investigate the potential for disease transmission among apes, people, and domestic animals.