Experimental acute pancreatitis is enhanced in mice with tissue nonspecific alkaline phoshatase haplodeficiency due to modulation of neutrophils and acinar cells

Tissue nonspecific alkaline phosphatase (TNAP) has a well established role in bone homeostasis and in hepatic/biliary conditions. In addition, TNAP is expressed in the inflamed intestine and is relevant to T and B lymphocyte function. TNAP KO mice are only viable for a few days, but TNAP^+/? haplodeficient mice are viable. Acute pancreatitis was induced by repeated caerulein injection in WT and TNAP^+/? mice. TNAP^+/? mice presented an increased expression of Cxcl2, Ccl2, Selplg (P-selectin ligand), Il6 and Il1b in the pancreas. Freshly isolated acinar cells showed a dramatic upregulation of Cxcl1, Cxcl2, Ccl2, Il6, Selpg or Bax in both pancreatitis groups. TNAP^+/? cells displayed a 2-fold higher expression of Cxcl2, and a smaller increase in Il6. These findings could be partly replicated by in vitro treatment of primary acinar cells with caerulein. Furthermore, the proinflammatory effect on acinar cells could be partially reproduced in wild type cells treated with the TNAP inhibitor levamisole. TNAP mRNA levels were also markedly upregulated by pancreatitis in acinar cells. Neutrophil infiltration (MRP8+ cells) and activation (IL-6 and TNF production in LPS treated primary neutrophils) were increased in TNAP^+/? vs WT mice. Neutrophil depletion greatly attenuated inflammation, indicating that this cell type is mainly responsible for the higher inflammatory status of TNAP^+/? mice. In conclusion, our results show that altered TNAP expression results in heightened pancreatic inflammation, which may be explained by an augmented response of neutrophils and by a higher sensitivity of acinar cells to caerulein injury.     

Relationship between myological variables and different take-off and landing behaviours in frogs

Although landing behaviour in anurans differs significantly among species, a take-off behaviour seems to be largely conserved in the evolution of frogs and toads. The ancestral mode of landing is hypothesized to involve the body crash-landing on the substrate, after which the anuran cycles the limbs forward and then backward to their resting position. The part of the body that first contacts the substrate may vary among taxa. The limbs and pectoral girdle muscles as well as those of the caudopelvic region, involved with landing and take-off behaviours, are investigated. The existence of a relationship exists between myology and different take-off and landing behaviours is explored. The results suggest that most of the muscles involved in both take-off and landing are conserved morphologically, with only few differing, depending on the locomotor behaviour. Two muscles tend to be longer; the m. coracobrachialis, which is involved with landing, and the m. coccygeosacralis, related to the take-off.     

Characterization of aerobic heterotrophic bacteria in cold and nutrient-poor freshwater ecosystems

Aerobic heterotrophic bacteria present in the surface water of three cold and nutrient-poor lakes in the Chilean Patagonia (Alto Reino, Las Dos Torres and Venus) were analysed for genetic similarity and metabolic diversity using 16S ribosomal DNA and the Biolog EcoPlate^TM system, respectively. Bacterial fingerprints of water samples in enriched and non-enriched nutrient broth demonstrated a >50% fingerprinting similarity between the lakes. Metabolic activity was also similar. However, the Biolog EcoPlate^TM system carbon substrates revealed functional diversity. Lake Las Dos Torres showed the most fingerprinting similarity between enriched and non-enriched cold water samples. The amounts of living and viable bacteria were also higher in this lake’s water sample, suggesting a predominance of facultative oligotrophic groups. DNA sequencing analysis demonstrated the presence of phylum Bacteroidetes in Lake Alto Reino; phyla Bacteroidetes and Gammaproteobacteria in Lake Las Dos Torres; and phyla Bacteroidetes, Alphaproteobacteria, and Gammaproteobacteria in Lake Venus. Although each lake had a unique bacterial community structure, the different bacterial groups may be performing similar metabolic functions, given the similarity in extreme environmental conditions.     

Chromatin condensation and differential sensitivity of mammalian and insect cells to DNA strand breaks induced by bleomycin

Bleomycin (BLM) induces DNA damage in living cells. In this report we analyzed the role of chromatin compactness in the differential response of mosquito (ATC-15) and mammalian (CHO) cells to DNA strand breaks induced by BLM. We used cells unexposed and exposed to sodium butyrate (NaB), which induces chromatin decondensation. By nucleoid sedimentation assay and digestions of nuclei with DNAse I, untreated mosquito cells (no BLM; no NaB) were shown to have more chromatin condensation than untreated CHO cells. By alkaline unwinding ATC-15 cells treated with NaB showed more BLM-induced DNA strand breaks than NaB-untreated CHO cells. The time-course of BLM-induced DNA damage to nuclear DNA was similar for NaB-untreated mammalian and insect cells, but with mosquito cells showing less DNA strand breaks, both at physiological temperatures and at 4 °C. However, when DNA repair was inhibited by low temperatures and chromatin was decondensed by NaB treatments, differences in BLM-induced DNA damage between these cells lines were no longer observed. In both cell lines, NaB did not affect BLM action on cell growth and viability. On the other hand, the low sensitivity of ATC-15 cells to BLM was reflected in their better growth efficiency. These cells exhibited a satisfactory growth at BLM doses that produced a permanent arrest of growth in CHO cells. The data suggest that mosquito cells might have linker DNAs shorter than those of mammalian cells, which would result in the observed both greater chromatin condensation and greater resistance to DNA damage induced by BLM as compared to CHO cells.     

An Entangled Model for Sustainability Indicators

Nowadays the challenge for humanity is to find pathways towards sustainable development. Decision makers require a set of sustainability indicators to know if the sustainability strategies are following those pathways. There are more than one hundred sustainability indicators but they differ on their relative importance according to the size of the locality and change on time. The resources needed to follow these sustainability indicators are scarce and in some instances finite, especially in smaller regions. Therefore strategies to select set of these indicators are useful for decision makers responsible for monitoring sustainability. In this paper we propose a model for the identification and selection of a set of sustainability indicators that adequately represents human systems. In developing this model, we applied evolutionary dynamics in a space where sustainability indicators are fundamental entities interconnected by an interaction matrix. we used a fixed interaction that simulates the current context for the city of Cuernavaca, México as an example. We were able to identify and define relevant sets indicators for the system by using the Pareto principle. In this case we identified a set of sixteen sustainability indicators with more than 80% of the total strength. This set presents resilience to perturbations. For the Tangled Nature framework we provided a manner of treating different contexts (i.e., cities, counties, states, regions, countries, continents or the whole planet), dealing with small dimensions. This model provides decision makers with a valuable tool to select sustainability indicators set for towns, cities, regions, countries, continents or the entire planet according to a coevolutionary framework. The social legitimacy can arise from the fact that each individual indicator must be selected from those that are most important for the subject community.     

A halotolerant and thermotolerant <Emphasis Type="Italic">Bacillus</Emphasis> sp. degrades hydrocarbons and produces tensio-active emulsifying agent

A Bacillus sp. strain DHT, isolated from oil-contaminated soil, grew and produced biosurfactant when cultured in variety of substrate at salinities of up to 100 g l⁻¹ and temperatures up to 45°C. It was capable of utilizing crude oil, fuels, various pure alkanes and PAHs as a sole carbon and energy source across a wide range of temperature and salinity. Over the range evaluated, the degradation of hydrocarbon and biosurfactant production was not influenced by salinity (0–10% wv⁻¹) and temperature (30–45°C). The biosurfactant produced by the organism emulsified a range of hydrocarbons with hexadecane as the best substrate and toluene as the poorest. From 16S rDNA analysis, strain DHT was related to Bacillus licheniformis.     

Patient and observer reported outcome measures to evaluate health-related quality of life in inherited metabolic diseases: a scoping review

Background

Health-related Quality of Life (HrQoL) is a multidimensional measure, which has gained clinical and social relevance. Implementation of a patient-centred approach to both clinical research and care settings, has increased the recognition of patient and/or observer reported outcome measures (PROMs or ObsROMs) as informative and reliable tools for HrQoL assessment. Inherited Metabolic Diseases (IMDs) are a group of heterogeneous conditions with phenotypes ranging from mild to severe and mostly lacking effective therapies. Consequently, HrQoL evaluation is particularly relevant.

Objectives

We aimed to: (1) identify patient and/or caregiver-reported HrQoL instruments used among IMDs; (2) identify the main results of the application of each HrQoL tool and (3) evaluate the main limitations of HrQoL instruments and study design/methodology in IMDs.

Methods

A scoping review was conducted using methods outlined by Arksey and O’Malley. Additionally, we critically analysed each article to identify the HrQoL study drawbacks.

Results

Of the 1954 studies identified, 131 addressed HrQoL of IMDs patients using PROMs and/or ObsROMs, both in observational or interventional studies. In total, we identified 32 HrQoL instruments destined to self- or proxy-completion; only 2% were disease-specific. Multiple tools (both generic and disease-specific) proved to be responsive to changes in HrQoL; the SF-36 and PedsQL questionnaires were the most frequently used in the adult and pediatric populations, respectively. Furthermore, proxy data often demonstrated to be a reliable approach complementing self-reported HrQoL scores. Nevertheless, numerous limitations were identified especially due to the rarity of these conditions.

Conclusions

HrQoL is still not frequently assessed in IMDs. However, our results show successful examples of the use of patient-reported HrQoL instruments in this field. The importance of HrQoL measurement for clinical research and therapy development, incites to further research in HrQoL PROMs’ and ObsROMs’ creation and validation in IMDs.