A Platform for Generation of Chamber-Specific Cardiac Tissues and Disease Modeling

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Within-plant distribution and emission of sesquiterpenes from Copaifera officinalis

Copaifera officinalis, the diesel tree, is known for massive production of oleoresin, mainly composed of sesquiterpene hydrocarbons. In this study, composition of these sesquiterpenes and their concentrations in leaves, stems and roots of C. officinalis at two developmental stages, including the three-week old (TW) seedlings and two-year old (TY) trees, were determined. The leaves of TW seedlings and TY trees contained similar number of sesquiterpenes, which also had comparable concentrations. The stems of TW seedlings had higher concentrations of sesquiterpenes than those of TY trees. In contrast, the number of sesquiterpene species and their concentrations in the roots of TW seedlings were much lower than those in the roots of TY trees. Cluster analysis of sesquiterpenes estimated that there are at least four terpene synthase genes involved in the production of sesquiterpenes in C. officinalis. Because sesquiterpenes are highly volatile, emissions of sesquiterpenes from healthy and wounded TW seedlings were examined using headspace analysis. Whereas very low emission of sesquiterpenes was detected from undamaged plants, the physically injured seedlings emitted a large number of sesquiterpenes, the quality and the relative quantity of which were similar to those in leaves determined using organic extraction. The implications of our findings to the biosynthetic pathways leading to the production of sesquiterpenes as well as their biological roles in C. officinalis are discussed.     

Handedness and Grooming in Pan troglodytes: Comparative Analysis Between Findings in Captive and Wild Individuals

Grooming is a complex set of motor actions, common in highly social primates. We tested for asymmetries in hand use during unimanual and bimanual allogrooming in 215 captive chimpanzees. In addition to hand use, we coded in the ethogram whether the manual grooming action co-occurred with the use of the mouth. Overall, grooming did not elicit strong handedness at the individual level, but there is a small yet significant population-level right-hand bias for bimanual grooming. Mouth use during grooming had no influence on hand use. A comparison of the findings with previously published data on handedness for grooming in wild chimpanzees suggests that wild apes are more right-handed than captive individuals are for allogrooming. Collectively, the results suggest that role differentiation of the hands is an important factor in the assessment of handedness for grooming, and perhaps additional manual actions of chimpanzees and other primates.     

Ubiquitin ligase Smurf1 mediates tumor necrosis factor-induced systemic bone loss by promoting proteasomal degradation of bone morphogenetic signaling proteins

Chronic inflammatory disorders, such as rheumatoid arthritis, are often accompanied by systemic bone loss, which is thought to occur through inflammatory cytokine-mediated stimulation of osteoclast resorption and inhibition of osteoblast function. However, the mechanisms involved in osteoblast inhibition remain poorly understood. Here we test the hypothesis that increased Smad ubiquitin regulatory factor 1 (Smurf1)-mediated degradation of the bone morphogenetic protein pathway signaling proteins mediates reduced bone formation in inflammatory disorders. Osteoblasts derived from bone marrow or long bone samples of adult tumor necrosis factor (TNF) transgenic (TNF-Tg) mice were used in this study. TNF decreased the steady-state levels of Smad1 and Runx2 protein similarly to those in long bones of TNF-Tg mice. In the presence of the proteasome inhibitor MG132, TNF increased accumulation of ubiquitinated Smad1 protein. TNF administration over calvarial bones caused decreases in Smad1 and Runx2 protein levels and mRNA expression of osteoblast marker genes in wild-type, but not in Smurf1(-/-) mice. Vertebral bone volume and strength of TNF-Tg/Smurf1(-/-) mice were examined by a combination of micro-CT, bone histomorphometry, and biomechanical testing and compared with those from TNF-Tg littermates. TNF-Tg mice had significantly decreased bone volume and biomechanical properties, which were partially rescued in TNF-Tg/Smurf1(-/-) mice. We conclude that in chronic inflammatory disorders where TNF is increased, TNF induces the expression of ubiquitin ligase Smurf1 and promotes ubiquitination and proteasomal degradation of Smad1 and Runx2, leading to systemic bone loss. Inhibition of ubiquitin-mediated Smad1 and Runx2 degradation in osteoblasts could help to treat inflammation-induced osteoporosis.     

tRNA genes and retroelements in the yeast genome.

A survey of tRNA genes and retroelements (Ty) in the genome of the yeast Saccharomyces cerevisiae is presented. Aspects of genomic organization and evolution of these genetic entities and their interplay are discussed. Attention is also given to the relationship between tRNA gene multiplicity and codon selection in yeast and the role of Ty elements.     

Sensitivity of spatially offset Raman spectroscopy (SORS) to subcortical bone tissue

The development of spatially offset Raman spectroscopy (SORS) has enabled deep, non‐invasive chemical characterization of turbid media. Here, we use SORS to measure subcortical bone tissue and depth‐resolved biochemical variability in intact, exposed murine bones. We also apply the technique to study a mouse model of the genetic bone disorder osteogenesis imperfecta. The results suggest that SORS is more sensitive to disease‐related biochemical differences in subcortical trabecular bone and marrow than conventional Raman measurements.     

Scanning orientation and polarization effects for XRQA radiochromic film

Gafchromic XRQA radiochromic film, is an effective tool for quality assurance and dose assessment in kilovoltage radiotherapy and diagnostic applications. Like other Gafchromic film products, XRQA film exhibits a variation in dose to reflected optical density response with angle of rotation when analysed with a light source that is partially or fully polarised such as a desktop scanner. Although warnings are not given on manufacturers specifications, this can affect dosimetry accuracy and we recommend that it is essential to scan all XRQA films in the same orientation. The effect is not as pronounced as EBT Gafchromic film. The magnitude of this variation has been measured and shown to be up to 16 ± 2% (1SD) using a fully linear polarised light source was seen with a 90° angle rotation. This would be the maximum variation seen on a desktop scanner with a fully polarised light source. For our standard desktop scanner (Epson v700) a mean variation of 2 ± 1% from 0 cGy to 20 cGy applied dose was measured as compared to 8 ± 2% for EBT Gafchromic. We recommend that to decrease uncertainty in dose measurement, accurate alignment of the calibration films to experimental films be performed on a regular basis. This is especially important if your desktop scanner has a high degree of polarization of its light source.     

Mesenchymal Stromal (Stem) Cell Therapy Fails to Improve Outcomes in Experimental Severe Influenza

Rationale

Severe influenza remains a major public health threat and is responsible for thousands of deaths annually. Increasing antiviral resistance and limited effectiveness of current therapies highlight the need for new approaches to influenza treatment. Extensive pre-clinical data have shown that mesenchymal stromal (stem) cell (MSC) therapy can induce anti-inflammatory effects and enhance repair of the injured lung. We hypothesized that MSC therapy would improve survival, dampen lung inflammation and decrease acute lung injury (ALI) in a murine model of severe influenza.

Methods

C57Bl/6 mice were infected with influenza A/PuertoRico/8/34 (mouse-adapted H1N1) or influenza A/Mexico/4108/2009 (swine-origin pandemic H1N1) and administered human or mouse MSCs via the tail vein, either pre- or post- infection. MSC efficacy was evaluated as both an independent and adjunctive treatment strategy in combination with the antiviral agent, oseltamivir. Weight loss and survival were monitored. Inflammatory cells, cytokine/chemokines (IFN-γ, CXCL10, CCL2 and CCL5) and markers of ALI (total protein and IgM), were measured in bronchoalveolar lavage fluid and lung parenchyma.

Results

Administration of murine MSCs or human MSCs in a prophylactic or therapeutic regimen failed to improve survival, decrease pulmonary inflammation/inflammatory cell counts or prevent ALI in influenza virus-infected mice. MSCs administered in combination with oseltamivir also failed to improve outcomes.

Conclusions

Despite similarities in the clinical presentation and pathobiology of ALI and severe influenza, our findings suggest that MSC therapy may not be effective for prevention and/or treatment of acute severe influenza.     

National mapping of schistosomiasis,soil-transmitted helminthiasis and anaemia in Yemen: Towards better national control and elimination

BackgroundSchistosomiasis (SCH) and soil-transmitted helminthiasis (STH) are known to be endemic in Yemen. However, the distribution of both diseases had not previously been assessed by a well-structured national mapping study covering all governorates. The main aim of this study was, therefore, to map the prevalence of SCH and STH in Yemen in order to better inform implementation of effective national control and elimination interventions. The assessment of the distribution of anaemia was also included as a well-known consequence of infection with both SCH and STH. Secondarily, the study aimed to provide a broad indication of the impact of large-scale treatment on the distribution of infection.Methodology and principal findingsTo achive these aims, 80,432 children (10–14 years old) from 2,664 schools in 332 of Yemen’s 333 districts were included, in 2014, into this national cross-sectional survey. Countrywide, 63.3% (210/332) and 75.6% (251/332) of districts were found to be endemic for SCH and STH respectively. More districts were affected by intestinal than urogenital SCH (54.2% and 31.6% respectively). SCH infection was mostly mild and moderate, with no districts reporting high infection. One quarter (24.4%) of Yemeni districts had high or moderate levels of Ascaris lumbricoides infection. Infection with Trichuris trichiura was the second most common STH (44.9% of districts infected) after A. lumbricoides (68.1%). Hookworm was the least prevalent STH (9.0%).Anaemia was prevalent in 96.4% of districts; it represented a severe public health problem (prevalence ≥ 40%) in 26.5% of districts, and a mild to moderate problem in two thirds of the districts (33.7% and 36.1% respectively).ConclusionThis study provided the first comprehensive mapping of SCH, STH, and anaemia across the country. This formed the basis for evaluating and continuing the national control and elimination programme for these neglected tropical diseases in Yemen.