Traditional and emerging roles for the SLC9 Na(+)/H (+) exchangers

The SLC9 gene family encodes Na(+)/H(+) exchangers (NHEs). These transmembrane proteins transport ions across lipid bilayers in a diverse array of species from prokaryotes to eukaryotes, including plants, fungi, and animals. They utilize the electrochemical gradient of one ion to transport another ion against its electrochemical gradient. Currently, 13 evolutionarily conserved NHE isoforms are known in mammals [22, 46, 128]. The SLC9 gene family (solute carrier classification of transporters: www.bioparadigms.org ) is divided into three subgroups [46]. The SLC9A subgroup encompasses plasmalemmal isoforms NHE1-5 (SLC9A1-5) and the predominantly intracellular isoforms NHE6-9 (SLC9A6-9). The SLC9B subgroup consists of two recently cloned isoforms, NHA1 and NHA2 (SLC9B1 and SLC9B2, respectively). The SLC9C subgroup consist of a sperm specific plasmalemmal NHE (SLC9C1) and a putative NHE, SLC9C2, for which there is currently no functional data [46]. NHEs participate in the regulation of cytosolic and organellar pH as well as cell volume. In the intestine and kidney, NHEs are critical for transepithelial movement of Na(+) and HCO3 (-) and thus for whole body volume and acid-base homeostasis [46]. Mutations in the NHE6 or NHE9 genes cause neurological disease in humans and are currently the only NHEs directly linked to human disease. However, it is becoming increasingly apparent that members of this gene family contribute to the pathophysiology of multiple human diseases.

Extended-spectrum cephalosporin-resistant Gram-negative organisms in livestock: an emerging problem for human health?

Escherichia coli, Salmonella spp. and Acinetobacter spp. are important human pathogens. Serious infections due to these organisms are usually treated with extended-spectrum cephalosporins (ESCs). However, in the past two decades we have faced a rapid increasing of infections and colonization caused by ESC-resistant (ESC-R) isolates due to production of extended-spectrum-β-lactamases (ESBLs), plasmid-mediated AmpCs (pAmpCs) and/or carbapenemase enzymes. This situation limits drastically our therapeutic armamentarium and puts under peril the human health. Animals are considered as potential reservoirs of multidrug-resistant (MDR) Gram-negative organisms. The massive and indiscriminate use of antibiotics in veterinary medicine has contributed to the selection of ESC-R E. coli, ESC-R Salmonella spp. and, to less extent, MDR Acinetobacter spp. among animals, food, and environment. This complex scenario is responsible for the expansion of these MDR organisms which may have life-threatening clinical significance. Nowadays, the prevalence of food-producing animals carrying ESC-R E. coli and ESC-R Salmonella (especially those producing CTX-M-type ESBLs and the CMY-2 pAmpC) has reached worryingly high values. More recently, the appearance of carbapenem-resistant isolates (i.e., VIM-1-producing Enterobacteriaceae and NDM-1 or OXA-23-producing Acinetobacter spp.) in livestock has even drawn greater concerns. In this review, we describe the aspects related to the spread of the above MDR organisms among pigs, cattle, and poultry, focusing on epidemiology, molecular mechanisms of resistance, impact of antibiotic use, and strategies to contain the overall problem. The link and the impact of ESC-R organisms of livestock origin for the human scenario are also discussed.

Differential characterization of emerging skin diseases of rainbow trout--a standardized approach to capturing disease characteristics and development of case definitions.

Farmed and wild salmonids are affected by a variety of skin conditions, some of which have significant economic and welfare implications. In many cases, the causes are not well understood, and one example is cold water strawberry disease of rainbow trout, also called red mark syndrome, which has been recorded in the UK since 2003. To date, there are no internationally agreed methods for describing these conditions, which has caused confusion for farmers and health professionals, who are often unclear as to whether they are dealing with a new or a previously described condition. This has resulted, inevitably, in delays to both accurate diagnosis and effective treatment regimes. Here, we provide a standardized methodology for the description of skin conditions of rainbow trout of uncertain aetiology. We demonstrate how the approach can be used to develop case definitions, using coldwater strawberry disease as an example.

A real-time video quality estimator for emerging wireless multimedia systems

Wireless Mesh Networks (WMNs) are increasingly deployed to enable thousands of users to share, create, and access live video streaming with different characteristics and content, such as video surveillance and football matches. In this context, there is a need for new mechanisms for assessing the quality level of videos because operators are seeking to control their delivery process and optimize their network resources, while increasing the user’s satisfaction. However, the development of in-service and non-intrusive Quality of Experience assessment schemes for real-time Internet videos with different complexity and motion levels, Group of Picture lengths, and characteristics, remains a significant challenge. To address this issue, this article proposes a non-intrusive parametric real-time video quality estimator, called MultiQoE that correlates wireless networks’ impairments, videos’ characteristics, and users’ perception into a predicted Mean Opinion Score. An instance of MultiQoE was implemented in WMNs and performance evaluation results demonstrate the efficiency and accuracy of MultiQoE in predicting the user’s perception of live video streaming services when compared to subjective, objective, and well-known parametric solutions.

A century of bovine besnoitiosis: an unknown disease re-emerging in Europe.

Bovine besnoitiosis, which is caused by the cyst-forming apicomplexan parasite Besnoitia besnoiti, is a chronic and debilitating vector-borne disease characterized by both cutaneous and systemic manifestations. In Europe, this parasitic disease appeared in a few restricted areas in France and Portugal since the first recorded cases in the beginning of the 20th century. However, at present, the disease is considered to be re-emerging by the European Food Safety Authority due to an increased number of cases and the geographic expansion of besnoitiosis into cattle herds in several European countries. In this review, we will provide an update of the epidemiology and impact of B. besnoiti infection. Strategies to control this parasitic disease will also be discussed.

A prehistoric thoroughfare between the Ganges and the Himalayas

The greater Himalayan region, including the Tibetan plateau in the north and the Gangetic plain in the south, served as the principal prehistoric thoroughfare for the peopling of East and Southeast Asia. The descendants of ancient migrants through this region ultimately settled lands as far away as New Zealand, Madagascar and the Americas. Several of the keys to understanding the ethnogenesis of human diversity in Asia include the Father Tongue correlation, possible refugia during the Last Glacial Maximum and the hypothesis that language families may have arisen as the result of demographic bottlenecks in prehistory. Ethnolinguistically informed inferences based on Asian Y chromosomal phylogeography permit a reconstruction of episodes of ethnolinguistic prehistory which lie beyond the linguistic event horizon, i.e. beyond the time depth empirically accessible to historical linguistics. The origins of the language families which make up the hypothetical Uralo-Siberian and East Asian linguistic phyla are argued to have lain in the northeastern corner of the Indian subcontinent. Several other Asian language families are shown to be tied to the subcontinent. The Centripetal Migration model, which assumes that migrations in quest of a better life unfolded in both centrifugal and centripetal directions with respect to technologically more advanced centres of civilisation, is opposed to the Farming Language Dispersal theory, which assumes that all linguistic dispersals were driven by agricultural centrifugal migration.

An Emerging Technology: To Model Patient Education for the Dental Hygiene Student

Introduction: Could Livestream Video, an emerging audiovisual media, be used more effectively than the traditional demonstration method of teaching or modeling dental hygiene students on how to provide chairside patient education? [See PDF for complete abstract]

Impact of an abrupt cooling event on interglacial methane emissions in northern peatlands

Rapid changes in atmospheric methane (CH4), temperature and precipitation are documented by Greenland ice core data both for glacial times (the so called Dansgaard-Oeschger (D-O) events) as well as for a cooling event in the early Holocene (the 8.2 kyr event). The onsets of D-O warm events are paralleled by abrupt increases in CH4 by up to 250 ppb in a few decades. Vice versa, the 8.2 kyr event is accompanied by an intermittent decrease in CH4 of about 80 ppb over 150 yr. The abrupt CH4 changes are thought to mainly originate from source emission variations in tropical and boreal wet ecosystems, but complex process oriented bottom-up model estimates of the changes in these ecosystems during rapid climate changes are still missing. Here we present simulations of CH4 emissions from northern peatlands with the LPJ-Bern dynamic global vegetation model. The model represents CH4 production and oxidation in soils and transport by ebullition, through plant aerenchyma, and by diffusion. Parameters are tuned to represent site emission data as well as inversion-based estimates of northern wetland emissions. The model is forced with climate input data from freshwater hosing experiments using the NCAR CSM1.4 climate model to simulate an abrupt cooling event. A concentration reduction of ~10 ppb is simulated per degree K change of mean northern hemispheric surface temperature in peatlands. Peatland emissions are equally sensitive to both changes in temperature and in precipitation. If simulated changes are taken as an analogy to the 8.2 kyr event, boreal peatland emissions alone could only explain 23 of the 80 ppb decline in atmospheric methane concentration. This points to a significant contribution to source changes from low latitude and tropical wetlands to this event.

A functional collagen adhesin gene, acm, in clinical isolates of Enterococcus faecium correlates with the recent success of this emerging nosocomial pathogen.

Enterococcus faecium recently evolved from a generally avirulent commensal into a multidrug-resistant health care-associated pathogen causing difficult-to-treat infections, but little is known about the factors responsible for this change. We previously showed that some E. faecium strains express a cell wall-anchored collagen adhesin, Acm. Here we analyzed 90 E. faecium isolates (99% acm(+)) and found that the Acm protein was detected predominantly in clinically derived isolates, while the acm gene was present as a transposon-interrupted pseudogene in 12 of 47 isolates of nonclinical origin. A highly significant association between clinical (versus fecal or food) origin and collagen adherence (P

POLG DNA testing as an emerging standard of care before instituting valproic acid therapy for pediatric seizure disorders.

PURPOSE: To review our clinical experience and determine if there are appropriate signs and symptoms to consider POLG sequencing prior to valproic acid (VPA) dosing in patients with seizures. METHODS: Four patients who developed VPA-induced hepatotoxicity were examined for POLG sequence variations. A subsequent chart review was used to describe clinical course prior to and after VPA dosing. RESULTS: Four patients of multiple different ethnicities, age 3-18 years, developed VPA-induced hepatotoxicity. All were given VPA due to intractable partial seizures. Three of the patients had developed epilepsia partialis continua. The time from VPA exposure to liver failure was between 2 and 3 months. Liver failure was reversible in one patient. Molecular studies revealed homozygous p.R597W or p.A467T mutations in two patients. The other two patients showed compound heterozygous mutations, p.A467T/p.Q68X and p.L83P/p.G888S. Clinical findings and POLG mutations were diagnostic of Alpers-Huttenlocher syndrome. CONCLUSION: Our cases underscore several important findings: POLG mutations have been observed in every ethnic group studied to date; early predominance of epileptiform discharges over the occipital region is common in POLG-induced epilepsy; the EEG and MRI findings varying between patients and stages of the disease; and VPA dosing at any stage of Alpers-Huttenlocher syndrome can precipitate liver failure. Our data support an emerging proposal that POLG gene testing should be considered in any child or adolescent who presents or develops intractable seizures with or without status epilepticus or epilepsia partialis continua, particularly when there is a history of psychomotor regression.

What is New and Innovative in Emergency Neurosurgery? Emerging Diagnostic Technologies Provide Better Care and Influence Outcome: A Specialist Review

The development of emergency medical services and especially neurosurgical emergencies during recent decades has necessitated the development of novel tools. Although the gadgets that the neurosurgeon uses today in emergencies give him important help in diagnosis and treatment, we still need new technology, which has rapidly developed. This review presents the latest diagnostic tools, which offer precious help in everyday emergency neurosurgery practice. New ultrasound devices make the diagnosis of haematomas easier. In stroke, the introduction of noninvasive new gadgets aims to provide better treatment to the patient. Finally, the entire development of computed tomography and progress in radiology have resulted in innovative CT scans and angiographic devices that advance the diagnosis, treatment, and outcome of the patent. The pressure on physicians to be quick and effective and to avoid any misjudgement of the patient has been transferred to the technology, with the emphasis on developing new systems that will provide our patients with a better outcome and quality of life.

Emerging metabolic targets in the therapy of hematological malignancies

During the last decade, the development of anticancer therapies has focused on targeting neoplastic-related metabolism. Cancer cells display a variety of changes in their metabolism, which enable them to satisfy the high bioenergetic and biosynthetic demands for rapid cell division. One of the crucial alterations is referred to as the "Warburg effect", which involves a metabolic shift from oxidative phosphorylation towards the less efficient glycolysis, independent of the presence of oxygen. Although there are many examples of solid tumors having altered metabolism with high rates of glucose uptake and glycolysis, it was only recently reported that this phenomenon occurs in hematological malignancies. This review presents evidence that targeting the glycolytic pathway at different levels in hematological malignancies can inhibit cancer cell proliferation by restoring normal metabolic conditions. However, to achieve cancer regression, high concentrations of glycolytic inhibitors are used due to limited solubility and biodistribution, which may result in toxicity. Besides using these inhibitors as monotherapies, combinatorial approaches using standard chemotherapeutic agents could display enhanced efficacy at eradicating malignant cells. The identification of the metabolic enzymes critical for hematological cancer cell proliferation and survival appears to be an interesting new approach for the targeted therapy of hematological malignancies.

The effect of abrupt climatic warming on biogeochemical cycling and N2O emissions in a terrestrial ecosystem

The large, rapid increase in atmospheric N2O concentrations that occurred concurrent with the abrupt warming at the end of the Last Glacial period might have been the result of a reorganization in global biogeochemical cycles. To explore the sensitivity of nitrogen cycling in terrestrial ecosystems to abrupt warming, we combined a scenario of climate and vegetation composition change based on multiproxy data for the Oldest Dryas–Bølling abrupt warming event at Gerzensee, Switzerland, with a biogeochemical model that simulates terrestrial N uptake and release, including N2O emissions. As for many central European sites, the pollen record at the Gerzensee is remarkable for the abundant presence of the symbiotic nitrogen fixer Hippophaë rhamnoides (L.) during the abrupt warming that also marks the beginning of primary succession on immature glacial soils. Here we show that without additional nitrogen fixation, climate change results in a significant increase of N2O emissions of approximately factor 3.4 (from 6.4 ± 1.9 to 21.6 ± 5.9 mg N2O–N m− 2 yr− 1). Each additional 1000 mg m− 2 yr− 1 of nitrogen added to the ecosystem through N-fixation results in additional N2O emissions of 1.6 mg N2O–N m− 2 yr− 1 for the time with maximum H. rhamnoides coverage. Our results suggest that local reactions of emissions to abrupt climate change could have been considerably faster than the overall atmospheric concentration changes observed in polar ice. Nitrogen enrichment of soils due to the presence of symbiotic N-fixers during early primary succession not only facilitates the establishment of vegetation on soils in their initial stage of development, but can also have considerable influence on biogeochemical cycles and the release of reactive nitrogen trace gases to the atmosphere.