A decreasing glacier mass balance gradient from the edge of the Upper Tarim Basin to the Karakoram during 2000-2014

In contrast to the glacier mass losses observed at other locations around the world, some glaciers in the High Mountains of Asia appear to have gained mass in recent decades. However, changes in digital elevation models indicate that glaciers in Karakoram and Pamir have gained mass, while recent laser altimetry data indicate mass gain centred on West Kunlun. Here, we obtain results that are essentially consistent with those from altimetry, but with two-dimensional observations and higher resolution. We produced elevation models using radar interferometry applied to bistatic data gathered between 2011 and 2014 and compared them to a model produced from bistatic data collected in 2000. The glaciers in West Kunlun, Eastern Pamir and the northern part of Karakoram experienced a clear mass gain of 0.043 ± 0.078~0.363 ± 0.065 m w.e. yr−1. The Karakoram showed a near-stable mass balance in its western part (−0.020 ± 0.064 m w.e. yr−1), while the Eastern Karakoram showed mass loss (−0.101 ± 0.058 m w.e. yr−1). Significant positive glacier mass balances are noted along the edge of the Upper Tarim Basin and indicate a decreasing gradient from northeast to southwest

Eucapnic Voluntary Hyperpnea: Gold Standard for Diagnosing Exercise-Induced Bronchoconstriction in Athletes?

In athletes, a secure diagnos is of exercise-induced bronchoconstriction (EIB) is dependent on objective testing. Evaluating spirometric indices of airflow before and following an exercise bout is intuitively the optimal means for the diagnosis; however, this approach is recognized as having several key limitations. Accordingly, alternative indirect bronchoprovocation tests have been recommended as surrogate means for obtaining a diagnosis of EIB. Of these tests, it is often argued that the eucapnic voluntary hyperpnea (EVH) challenge represents the ‘gold standard’. This article provides a state-of-the-art review of EVH, including an overview of the test methodology and its interpretation. We also address the performance of EVH against the other functional and clinical approaches commonly adopted for the diagnosis of EIB. The published evidence supports a key role for EVH in the diagnostic algorithm for EIB testing in athletes. However, its wide sensitivity and specificity and poor repeatability preclude EVH from being termed a ‘gold standard’ test for EIB

Comparative Expression Profiling of Leishmania: Modulation in Gene Expression between Species and in Different Host Genetic Backgrounds

The single-celled parasite Leishmania, transmitted by sand flies in more than 88 tropical and sub-tropical countries globally, infects man and other mammals, causing a spectrum of diseases called the leishmaniases. Over 12 million people are currently infected worldwide with 2 million new cases reported each year. The type of leishmaniasis that develops in the mammalian host is dependent on the species of infecting parasite and the immune response to infection (that can be influenced by host genetic variation). Our research is focused on identifying parasite factors that contribute to pathogenicity in the host and understanding how these might differ between parasite species that give rise to the different clinical forms of leishmaniasis. Molecules of this type might lead to new therapeutic tools in the longer term. In this paper, we report a comparative analysis of gene expression profiles in three Leishmania species that give rise to different types of disease, focusing on the intracellular stages that reside in mammalian macrophages. Our results show that there are only a small number of differences between these parasite species, with host genetics playing only a minor role in influencing the parasites' response to their intracellular habitat. These small changes may be significant, however, in determining the clinical outcome of infection

Danger- and pathogen-associated molecular patterns recognition by pattern-recognition receptors and ion channels of the transient receptor potential family triggers the inflammasome activation in immune cells and sensory neurons.

An increasing number of studies show that the activation of the innate immune system and inflammatory mechanisms play an important role in the pathogenesis of numerous diseases. The innate immune system is present in almost all multicellular organisms and its activation occurs in response to pathogens or tissue injury via pattern-recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs). Intracellular pathways, linking immune and inflammatory response to ion channel expression and function, have been recently identified. Among ion channels, the transient receptor potential (TRP) channels are a major family of non-selective cation-permeable channels that function as polymodal cellular sensors involved in many physiological and pathological processes.In this review, we summarize current knowledge of interactions between immune cells and PRRs and ion channels of TRP families with PAMPs and DAMPs to provide new insights into the pathogenesis of inflammatory diseases. TRP channels have been found to interfere with innate immunity via both nuclear factor-kB and procaspase-1 activation to generate the mature caspase-1 that cleaves pro-interleukin-1ß cytokine into the mature interleukin-1ß.Sensory neurons are also adapted to recognize dangers by virtue of their sensitivity to intense mechanical, thermal and irritant chemical stimuli. As immune cells, they possess many of the same molecular recognition pathways for danger. Thus, they express PRRs including Toll-like receptors 3, 4, 7, and 9, and stimulation by Toll-like receptor ligands leads to induction of inward currents and sensitization in TRPs. In addition, the expression of inflammasomes in neurons and the involvement of TRPs in central nervous system diseases strongly support a role of TRPs in inflammasome-mediated neurodegenerative pathologies. This field is still at its beginning and further studies may be required.Overall, these studies highlight the therapeutic potential of targeting the inflammasomes in proinflammatory, autoinflammatory and metabolic disorders associated with undesirable activation of the inflammasome by using specific TRP antagonists, anti-human TRP monoclonal antibody or different molecules able to abrogate the TRP channel-mediated inflammatory signals