Fluorescent biosensors illuminate calcium levels within defined beta-cell endosome subpopulations.

Live cell imaging has revealed that calcium ions (Ca(2+)) pass in and out of many cellular organelles. However, technical hurdles have limited measurements of Ca(2+) in acidic organelles, such as endosomes. Although evidence hints that endosomes play a role in Ca(2+) signaling, direct measurements within endosomal lumina represent one of the final frontiers in organelle imaging.

Activity and well-being of older adults: does cognitive impairment play a role?

This analysis assesses the activity level of 324 older adults and the relationship of activity to quality of life with a specific emphasis on the role of cognitive ability. Although the number of older adults with cognitive impairment continues to grow, few studies have examined the variation in activity and quality of life based on the older adults' cognitive status. Results indicated that cognitively impaired older adults were less active than their nonimpaired peers; however, correlations revealed that regardless of impairment status, more activity was related to a higher quality of life.

The Effects of Age on the Neural Correlates of Recollection Success, Recollection-Related Cortical Reinstatement, and Post-Retrieval Monitoring.

Functional magnetic resonance imaging (fMRI) was used to investigate whether age-related differences in episodic memory performance are accompanied by a reduction in the specificity of recollected information. We addressed this question by comparing recollection-related cortical reinstatement in young and older adults. At study, subjects viewed objects and concrete words, making 1 of 2 different semantic judgments depending on the study material.

On-road heavy-duty vehicle emissions monitoring system.

The introduction of particulate and oxides of nitrogen (NOx) after-treatment controls on heavy-duty vehicles has spurred the need for fleet emissions data to monitor their reliability and effectiveness. The University of Denver has developed a new method for rapidly measuring heavy-duty vehicles for gaseous and particulate fuel specific emissions. The method was recently used to collect 3088 measurements at a Port of Los Angeles location and a weigh station on I-5 in northern California.

PWD/PhJ mice have a genetically determined increase in nutrient-stimulated insulin secretion.

PWD/PhJ (PWD) is a wild-derived inbred mouse strain unrelated to commonly studied strains, such as C57BL/6J (B6). A chromosome substitution panel with PWD chromosomes transferred into the B6 background is commercially available and will facilitate genetic analysis of this strain. We have previously shown that the PWD strain is a model of primary fasting hyperinsulinemia.

Molecular characterization of the cytochrome b gene and in vitro atovaquone susceptibility of Plasmodium falciparum isolates from Kenya.

The prevalence of a genetic polymorphism(s) at codon 268 in the cytochrome b gene, which is associated with failure of atovaquone-proguanil treatment, was analyzed in 227 Plasmodium falciparum parasites from western Kenya. The prevalence of the wild-type allele was 63%, and that of the Y268S (denoting a Y-to-S change at position 268) mutant allele was 2%. There were no pure Y268C or Y268N mutant alleles, only mixtures of a mutant allele(s) with the wild type.

A Survey of Imidacloprid Levels in Water Sources Potentially Frequented by Honeybees () in the Eastern USA.

Imidacloprid, a water-soluble neonicotinoid pesticide used globally in many applications, has been the subject of numerous studies (1) to determine its sublethal effects (5-100 ppb, LD ∼200 ppb) on honeybees. This study was undertaken to determine, by ELISA assay, the presence of imidacloprid in water sources potentially frequented by honeybees in urban, suburban, and rural environments across the state of Maryland. Eighteen sites (six samples/site) were chosen which spanned diverse habitats including golf courses, nursery, livestock and crop farms, residential neighborhoods, and cityscapes.

Episodic retrieval involves early and sustained effects of reactivating information from encoding.

Several fMRI studies have shown a correspondence between the brain regions activated during encoding and retrieval, consistent with the view that memory retrieval involves hippocampally-mediated reinstatement of cortical activity. With the limited temporal resolution of fMRI, the precise timing of such reactivation is unclear, calling into question the functional significance of these effects. Whereas reactivation influencing retrieval should emerge with neural correlates of retrieval success, that signifying post-retrieval monitoring would trail retrieval.

A feature analysis of lower solubility proteins in three eukaryotic systems.

Unlabelled: Because misfolded and damaged proteins can form potentially harmful aggregates, all living organisms have evolved a wide variety of quality control mechanisms. However, the timely clearance of aggregation-prone species may not always be achieved, potentially leading to the accumulation of low solubility proteins. At the same time, promiscuity, which can be a driving force for aggregation, is also important to the functionality of certain proteins which have a large number of interaction partners.

Islet cell research brings hope for a diabetes cure: meeting report from the 6(th) annual islet society meeting in Stellenbosch, South Africa.

The International Diabetes Federation predicts that, over the next twenty years, the largest increase in the prevalence of diabetes will be in the Africa region. Recognizing an unmet need for more focus on Africa and engagement with African scholars, the Islet Society held its 6th annual meeting July 20-21, 2014 in Stellenbosch, South Africa. Here, we present a report that covers the presentations and discussion points from that meeting.

Five-year tracking of Plasmodium falciparum allele frequencies in a holoendemic area with indistinct seasonal transitions.

Background: The renewed malaria eradication efforts require an understanding of the seasonal patterns of frequency of polymorphic variants in order to focus limited funds productively. Although cross-sectional studies in holoendemic areas spanning a single year could be useful in describing parasite genotype status at a given point, such information is inadequate in describing temporal trends in genotype polymorphisms. For Plasmodium falciparum isolates from Kisumu District Hospital, Plasmodium falciparum chloroquine-resistance transporter gene (Pfcrt-K76T) and P.

A practical guide to genetic engineering of pancreatic β-cells in vivo: getting a grip on RIP and MIP.

In vivo gene manipulation is a cornerstone approach in modern physiology. Cre-Lox technology has been extensively used to delete genes and activate reporters in pancreatic β-cells, bringing new insight into the pathophysiology of diabetes. In all cases, it is important to understand the expression domain of the specific reporter-Cre combination in order to correctly interpret the data.

Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells.

Transplantation of pancreatic progenitors or insulin-secreting cells derived from human embryonic stem cells (hESCs) has been proposed as a therapy for diabetes. We describe a seven-stage protocol that efficiently converts hESCs into insulin-producing cells. Stage (S) 7 cells expressed key markers of mature pancreatic beta cells, including MAFA, and displayed glucose-stimulated insulin secretion similar to that of human islets during static incubations in vitro.

Physician's emerging roles relating to trends in health information technology.

Objective: To determine the new roles that physicians will adopt in the near future to adjust to accelerating trends from managed care to outcome-based practice to health care reform to health information technology to the evolving role of health consumers.

Methods: Trends and related developments concerning the changing roles of physicians based on prior literature reviews.

Results: Six possible roles, traditional, gatekeeper, coach, navigator, informatician and one voice among many, are discussed in terms of physician's centrality, patient autonomy, decision-making and uncertainty, information seeking, satisfaction and outcomes, particularly those related to compliance.

Evaluation of the resistance to cyclic fatigue among ProTaper Next, ProTaper Universal, and Vortex Blue rotary instruments.

Introduction: The purpose of this study was to compare the fracture resistance to cyclic fatigue of ProTaper Next (PTN; Dentsply Tulsa Dental Specialties, Tulsa, OK), ProTaper Universal (PTU, Dentsply Tulsa Dental Specialties), and Vortex Blue (VB, Dentsply Tulsa Dental Specialties) rotary instruments.

Methods: Twenty instruments each of PTN X1-X5, PTU S1-F5, and VB 20/04-50/04 were rotated until fracture in a simulated canal of 90° and a 5-mm radius using a custom-made testing platform. The number of cycles to fracture (NCF) was calculated.

Neural reinstatement and the amount of information recollected.

Recent functional neuroimaging studies have attempted to understand the cognitive and neural bases of episodic memory retrieval, as well as the extent to which different retrieval judgments reflect qualitative as opposed to continuous changes in neural signals. The present study addressed this issue by investigating the reinstatement of episodic content according to the amount of information available at retrieval. Subjects encoded a series of words in the context of three distinct tasks, while a manipulation of presentation duration (4 or 8s) was also employed.

The Synthetic Biology Open Language (SBOL) provides a community standard for communicating designs in synthetic biology.

The re-use of previously validated designs is critical to the evolution of synthetic biology from a research discipline to an engineering practice. Here we describe the Synthetic Biology Open Language (SBOL), a proposed data standard for exchanging designs within the synthetic biology community. SBOL represents synthetic biology designs in a community-driven, formalized format for exchange between software tools, research groups and commercial service providers.

Polymorphisms in Pfmdr1, Pfcrt, and Pfnhe1 genes are associated with reduced in vitro activities of quinine in Plasmodium falciparum isolates from western Kenya.

In combination with antibiotics, quinine is recommended as the second-line treatment for uncomplicated malaria, an alternative first-line treatment for severe malaria, and for treatment of malaria in the first trimester of pregnancy. Quinine has been shown to have frequent clinical failures, and yet the mechanisms of action and resistance have not been fully elucidated. However, resistance is linked to polymorphisms in multiple genes, including multidrug resistance 1 (Pfmdr1), the chloroquine resistance transporter (Pfcrt), and the sodium/hydrogen exchanger gene (Pfnhe1).

Generation and characterization of a mouse model harboring the exon-3 deletion in the cardiac ryanodine receptor.

A large genomic deletion in human cardiac ryanodine receptor (RYR2) gene has been detected in a number of unrelated families with various clinical phenotypes, including catecholaminergic polymorphic ventricular tachycardia (CPVT). This genomic deletion results in an in-frame deletion of exon-3 (Ex3-del). To understand the underlying disease mechanism of the RyR2 Ex3-del mutation, we generated a mouse model in which the RyR2 exon-3 sequence plus 15-bp intron sequences flanking exon-3 were deleted.

The use of a prodrug approach to minimize potential CNS exposure of next generation quinoline methanols while maintaining efficacy in in vivo animal models.

The use of mefloquine (MQ) for antimalarial treatment and prophylaxis has diminished largely in response to concerns about its neurologic side effects. An analog campaign designed to maintain the efficacy of MQ while minimizing blood-brain barrier (BBB) penetration has resulted in the synthesis of a prodrug with comparable-to-superior in vivo efficacy versus mefloquine in a P. berghei mouse model while exhibiting a sixfold reduction in CNS drug levels.

A stepwise approach to the interpretation of pulmonary function tests.

Office-based pulmonary function testing, also known as spirometry, is a powerful tool for primary care physicians to diagnose and manage respiratory problems. An obstructive defect is indicated by a low forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ratio, which is defined as less than 70% or below the fifth percentile based on data from the Third National Health and Nutrition Examination Survey (NHANES III) in adults, and less than 85% in patients five to 18 years of age. If an obstructive defect is present, the physician should determine if the disease is reversible based on the increase in FEV1 or FVC after bronchodilator treatment (i.

Goals, symptoms, signs, and treatments among women with pelvic floor disorders.

Objective: This study aimed to identify associations between patient-centered goals and pelvic floor measures and treatment choice.

Methods: A retrospective study of women seen for a pelvic floor disorder by a single surgeon in a specialty clinic from January 2008 to December 2009 was done. Goals were categorized as information-seeking, improving across any of 6 pelvic floor symptom categories, and "other.