Inspiratory muscle training reduces blood lactate concentration during volitional hyperpnoea

Although reduced blood lactate concentrations ([lac−]B) have been observed during whole-body exercise following inspiratory muscle training (IMT), it remains unknown whether the inspiratory muscles are the source of at least part of this reduction. To investigate this, we tested the hypothesis that IMT would attenuate the increase in [lac−]B caused by mimicking, at rest, the breathing pattern observed during high-intensity exercise. Twenty-two physically active males were matched for 85% maximal exercise minute ventilation (V˙Emax) and divided equally into an IMT or a control group. Prior to and following a 6 week intervention, participants performed 10 min of volitional hyperpnoea at the breathing pattern commensurate with 85% V˙Emax

Presence and Persistence of Ebola or Marburg Virus in Patients and Survivors: A Rapid Systematic Review

Background: The 2013-15 Ebola outbreak was unprecedented due to sustainedtransmission within urban environments and thousands of survivors. In 2014 the World Health Organization stated that there was insufficient evidence to give definitive guidance about which body fluids are infectious and when they pose a risk to humans. We report a rapid systematic review of published evidence on the presence of filoviruses in body fluids of infected people and survivors. Methods: Scientific articles were screened for information about filovirus in human body fluids. The aim was to find primary data that suggested high likelihood of actively infectious filovirus in human body fluids (viral RNA). Eligible infections were from Marburg virus (MARV or RAVV) and Zaire, Sudan, Taï Forest and Bundibugyo species of Ebola. [1] Cause of infection had to be laboratory confirmed (in practice either tissue culture or RT-PCR tests), or evidenced by compatible clinical history with subsequent positivity for filovirus antibodies or inflammatory factors. Data were extracted and summarized narratively. Results: 6831 unique articles were found, and after screening, 33 studies were eligible. For most body fluid types there were insufficient patients to draw strong conclusions, and prevalence of positivity was highly variable. Body fluids taken >16 days after onset were usually negative. In the six studies that used both assay methods RT-PCR tests for filovirus RNA gave positive results about 4 times more often than tissue culture. Conclusions: Filovirus was reported in most types of body fluid, but not in every sample from every otherwise confirmed patient. Apart from semen, most non-blood, RT-PCR positive samples are likely to be culture negative and so possibly of low infectious risk. Nevertheless, it is not apparent how relatively infectious many body fluids are during or after illness, even when culture-positive, not least because most test results come from more severe cases. Contact with blood and blood-stained body fluids remains the major risk for disease transmission because of the known high viral loads in blood

Aurora kinase-C-T191D is constitutively active mutant

<p>Abstract</p> <p>Background</p> <p>Aurora kinases (Aurora-A, B and C) belong to a family of conserved serine/threonine kinases which are key regulators of cell cycle progression. Aurora-A and Aurora-B are expressed in somatic cells and involved in cell cycle regulation while aurora-C is meiotic chromosome passenger protein. As Aurora kinase C is rarely expressed in normal somatic cells and has been found over expressed in many cancer lines. It is suggested that Aurora-C-T191D is not hyperactive mutant.</p> <p>Result</p> <p>Aurora-C-T191D variant form was investigated and compared with wild type. The overexpression of Aurora-C-T191D was observed that it behaves like Aurora-C wild type (aurC-WT). Both Aurora-C-T191D and aurC-WT induce abnormal cell division resulting in centrosome amplification and multinucleation in transiently transfected cells as well as in stable cell lines. Similarly, Aurora-C-T191D and aurC-WT formed foci of colonies when grown on soft agar, indicating that a gain of Aurora-C activity is sufficient to transform cells. Furthermore, we reported that NIH-3 T3 stable cell lines overexpressing Aurora-C-T191D and its wild type partner induced tumour formation when injected into nude mice, demonstrating the oncogenic activity of enzymatically active Aurora kinase C. Interestingly enough tumour aggressiveness was positively correlated with the rate of kinase activity, making Aurora-C a potential anti-cancer therapeutic target.</p> <p>Conclusion</p> <p>These findings proved that Aurora C-T191D is not hyperactive but is constitutively active mutant.</p

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Early Evolution of Conserved Regulatory Sequences Associated with Development in Vertebrates

Comparisons between diverse vertebrate genomes have uncovered thousands of highly conserved non-coding sequences, an increasing number of which have been shown to function as enhancers during early development. Despite their extreme conservation over 500 million years from humans to cartilaginous fish, these elements appear to be largely absent in invertebrates, and, to date, there has been little understanding of their mode of action or the evolutionary processes that have modelled them. We have now exploited emerging genomic sequence data for the sea lamprey, Petromyzon marinus, to explore the depth of conservation of this type of element in the earliest diverging extant vertebrate lineage, the jawless fish (agnathans). We searched for conserved non-coding elements (CNEs) at 13 human gene loci and identified lamprey elements associated with all but two of these gene regions. Although markedly shorter and less well conserved than within jawed vertebrates, identified lamprey CNEs are able to drive specific patterns of expression in zebrafish embryos, which are almost identical to those driven by the equivalent human elements. These CNEs are therefore a unique and defining characteristic of all vertebrates. Furthermore, alignment of lamprey and other vertebrate CNEs should permit the identification of persistent sequence signatures that are responsible for common patterns of expression and contribute to the elucidation of the regulatory language in CNEs. Identifying the core regulatory code for development, common to all vertebrates, provides a foundation upon which regulatory networks can be constructed and might also illuminate how large conserved regulatory sequence blocks evolve and become fixed in genomic DNA

Reduced Exercise Tolerance and Pulmonary Capillary Recruitment with Remote Secondhand Smoke Exposure

RATIONALE: Flight attendants who worked on commercial aircraft before the smoking ban in flights (pre-ban FAs) were exposed to high levels of secondhand smoke (SHS). We previously showed never-smoking pre-ban FAs to have reduced diffusing capacity (Dco) at rest. METHODS: To determine whether pre-ban FAs increase their Dco and pulmonary blood flow (Qc) during exercise, we administered a symptom-limited supine-posture progressively increasing cycle exercise test to determine the maximum work (watts) and oxygen uptake (VO2) achieved by FAs. After 30 min rest, we then measured Dco and Qc at 20, 40, 60, and 80 percent of maximum observed work. RESULTS: The FAs with abnormal resting Dco achieved a lower level of maximum predicted work and VO2 compared to those with normal resting Dco (mean±SEM; 88.7±2.9 vs. 102.5±3.1%predicted VO2; p = 0.001). Exercise limitation was associated with the FAs' FEV(1) (r = 0.33; p = 0.003). The Dco increased less with exercise in those with abnormal resting Dco (mean±SEM: 1.36±0.16 vs. 1.90±0.16 ml/min/mmHg per 20% increase in predicted watts; p = 0.020), and amongst all FAs, the increase with exercise seemed to be incrementally lower in those with lower resting Dco. Exercise-induced increase in Qc was not different in the two groups. However, the FAs with abnormal resting Dco had less augmentation of their Dco with increase in Qc during exercise (mean±SEM: 0.93±0.06 vs. 1.47±0.09 ml/min/mmHg per L/min; p<0.0001). The Dco during exercise was inversely associated with years of exposure to SHS in those FAs with ≥10 years of pre-ban experience (r = -0.32; p = 0.032). CONCLUSIONS: This cohort of never-smoking FAs with SHS exposure showed exercise limitation based on their resting Dco. Those with lower resting Dco had reduced pulmonary capillary recruitment. Exposure to SHS in the aircraft cabin seemed to be a predictor for lower Dco during exercise