Several studies have reported maternal and paternal age as risk factors for having a child with Autism Spectrum Disorder (ASD), yet the results remain inconsistent. We used data for 68 age- and sex-matched case-control pairs collected from Jamaica. Using Multivariate General Linear Models (MGLM) and controlling for parity, gestational age, ...

The µ-conopeptide family is defined by its ability to block voltage-gated sodium channels (VGSCs), a property that can be used for the development of myorelaxants and analgesics. We characterized the pharmacology of a new µ-conopeptide (µ-CnIIIC) on a range of preparations and molecular targets to assess its potential as a ...

Ca(v) 3.2 T-type calcium channels, targeted by H(2) S, are involved in neuropathic hyperalgesia in rats and ascorbic acid inhibits Ca(v) 3.2 channels. Therefore, we evaluated the effects of intraplantar (i.pl.) administration of ascorbic acid or topical application of disodium isostearyl 2-O-L-ascorbyl phosphate (DI-VCP), a skin-permeable ascorbate derivative on hyperalgesia ...

We have developed a novel method for genetic characterization of single cells by integrating microfluidic stretching of chromosomal DNA and fiber fluorescence in situ hybridization (FISH). In this method, individually isolated cell nuclei were immobilized in a microchannel. Chromosomal DNA was released from the nuclei and stretched by a pressure-driven ...

Lipoxidation-derived reactive carbonyl species (RCS) such as 4-hydroxy-2-nonenal (HNE) react with proteins to form advanced lipoxidation end products (ALEs), which have been implicated in both atherosclerosis and renal disease. L-carnosine acts as an endogenous HNE scavenger, but it is rapidly inactivated by carnosinase. This study aimed at assessing the effect ...

Translational animal models are essential in the prediction of the efficacy and side effects of new chemical entities. We have carried out a thorough study of three distinct disease-modifying antirheumatic drugs (DMARDs) in an adjuvant-induced arthritis (AIA) model in the rat and critically appraised the results in the context of ...

  To provide an initial abuse liability assessment of an electronic cigarette (EC) in current tobacco cigarette smokers.   The first of four within-subject sessions was an EC sampling session that involved six, 10-puff bouts (30 seconds inter-puff interval), each bout separated by 30 minutes. In the remaining three sessions ...

There are sparse data on outcome of lupus nephritis from developing countries. This study looks at outcome in Asian Indians. This retrospective study included patients at a single center over 20 years. Patients were treated as per standard protocols. The primary outcome measure was chronic renal failure or death; the ...

To assess the impact of thrombospondin 1(TSP1) deficiency on choroidal neovascularization (CNV)and to determine whether administration of a TSP1 antiangiogenic mimetic peptide attenuates CNV. The impact of TSP1 deficiency on laser induced CNV was assessed using wild-type (TSP1 +/+) and TSP1-deficient (TSP1 −/−) mice. Three laser burns were placed in ...

To investigate whether the severity of cystoid macular edema (CME) in neonates who were 31 to 36 weeks' postmenstrual age, as viewed by spectral-domain optical coherence tomography (SD-OCT)imaging, predicts the severity of retinopathy of prematurity(ROP) or is related to systemic health. Of 62 prematurely born neonates in a prospective institutional ...

APOE ε4 status has been associated with greater cortical amyloid deposition, whereas exercise has been associated with less in cognitively normal adults. The primary objective here was to examine whether physical exercise moderates the association between APOE genotype and amyloid deposition in cognitively normal adults. APOE genotyping data and answers ...

Several genetic causes of familial Parkinson's disease (PD) have now been identified and include mutations of genes encoding mitochondrial proteins. Mitochondrial complex I toxins can induce dopaminergic cell death and produce a parkinsonian state. Importantly, defects of mitochondrial function have been identified in postmortem substantia nigra from pathologically proven cases ...

To demonstrate a unique abnormality of the pupillary light reflex in patients with autoimmune autonomic ganglionopathy (AAG). Case series. Autonomic clinics at 2 university hospitals (University of Texas Southwestern Medical Center and Beth Israel Deaconess Medical Center). Seven patients with antibody-positive AAG. All patients with AAG underwent either monocular or ...

Several genetic risk variants for ankylosing spondylitis (AS) have been identified in genome-wide association studies. Our objective was to examine whether familial AS cases have a higher genetic load of these susceptibility variants. Overall, 502 AS patients were examined, consisting of 312 patients who had first-degree relatives (FDRs) with AS ...

To investigate which anthropometric adiposity measure has the strongest association with cardiovascular disease (CVD) risk factors in Caucasian men and women without a history of CVD. Systematic review and meta-analysis. We searched databases for studies reporting correlations between anthropometric adiposity measures and CVD risk factors in Caucasian subjects without a ...

To estimate the cost-effectiveness of visual acuity screening performed in primary care settings and of dilated eye evaluations performed by an eye care professional among new Medicare enrollees with no diagnosed eye disorders. Medicare currently reimburses visual acuity screening for new enrollees during their initial preventive primary care health check, ...

To determine the prognostic significance of data collected early after starting certolizumab pegol (CZP) to predict low disease activity (LDA) at week 52. Data from 703 CZP-treated patients in the Rheumatoid Arthritis Prevention of Structural Damage 1 (RAPID 1) trial through week 12 were used as variables to predict LDA ...

Pseudoxanthoma elasticum (PXE) manifests with cutaneous lesions consisting of yellowish papules coalescing into plaques of inelastic skin. Histopathology demonstrates accumulation of pleiomorphic elastic structures with progressive mineralization. The classic form of PXE is caused by mutations in the ABCC6 gene. A 2-year-old patient with PXE of the neck, inguinal folds ...

Maintaining adequate numbers of spermatogonial stem cells is required for the production of the millions of sperm required for male fertility. To date, however, the mechanisms that regulate the size of this pool in the adult are poorly defined. Glial cell line-derived neurotrophic factor (GDNF) is required for establishing this ...

Properdin deficiency is a rare immunological disorder inherited as an X-chromosomal recessive trait. Properdin deficiency poses a significant risk for severe meningococcal infections. About 20 mutations have been reported to underlie properdin deficiency. Here we report a large Finnish family with a novel mutation in the properdin gene (CFP). Based ...

Ghrelin is secreted mainly in the stomach and plays a role in food intake regulation. Morbidly obese (MO) individuals report a decline in appetite after sleeve gastrectomy (SG), presumably due, in part, to ghrelin cell removal. Ghrelin cell distribution and expression were determined in three areas of resected stomach specimens ...

MicroRNAs (miRNAs) are short noncoding RNAs, which post-transcriptionally regulate gene expression. miRNAs are transcribed as precursors and matured to active forms by a series of enzymes, including Dicer. miRNAs are important in governing cell differentiation, development, and disease. We have recently developed a feeder- and serum-free protocol for direct derivation ...

Reactive oxygen species (ROS) such as superoxide, hydrogen peroxide, and peroxynitrite are generated ubiquitously by all mammalian cells and have been understood for many decades as inflicting cell damage and as causing cancer by oxidation and nitration of macromolecules, including DNA, RNA, proteins, and lipids. RECENT ADVANCES: A current concept ...

  Most, but not all, epidemiological studies suggest a cardioprotective association for low to moderate average alcohol consumption. The objective was to quantify the dose-response relationship between average alcohol consumption and ischaemic heart disease (IHD) stratified by sex and IHD end-point (mortality versus morbidity).   A systematic search of published ...

Abstract Helicobacter pylori infection plays a crucial role in the pathogenesis of gastric extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT). However, the host response to this infection is also important in the development of the disease. In particular, NADPH oxidases (NOXs) which generate reactive oxygen species are known ...

Small interfering RNAs (siRNAs) have been used extensively in reverse genetic research, and many have made their way into clinical trials. The most widely used siRNA structure consists of double-stranded RNA with 19 base pairs and 2-nucleotide overhangs at the 3'-end of both strands (19+2). Although widely used, this symmetric ...

Oxygen is a pulmonary vasodilator, but data suggest high O(2) concentrations impede that response. We previously reported 24 h of 100% O(2) increased phosphodiesterase 5 (PDE5) activity in fetal pulmonary artery smooth muscle cells (FPASMC) and in ventilated neonatal lambs. PDE5 degrades cyclic GMP (cGMP) and inhibits nitric oxide (NO)-mediated cGMP-dependent ...

Accumulating evidence shows that hydrogen sulfide may function as a signaling molecule in processes such as neuromodulation in the brain and smooth muscle relaxation in the vascular system. It also has a cytoprotective effect, since it can protect neurons and cardiac muscle from oxidative stress and ischemia-reperfusion injury, respectively. Hydrogen ...

The popularity of running as a recreational sport for health gains has steadily increased. Runners may acquire several types of injuries including hip osteoarthritis (OA). Running is possible with mild forms of OA if proper joint mechanics, neuromuscular control, and technique are present. Recent literature will be discussed that builds ...

The vasculature, an organ that penetrates every other organ, is ideally poised to be the site where pools of stem cells are placed, to be deployed and committed in response to feedback regulation, and to respond to demands for new vascular structures. These pools of multipotent cells are often under ...

Hip resurfacing (HR) has become a widely used surgical intervention for younger patients requiring hip joint arthroplasty. While case reports have been published describing rehabilitation programs following HR, there has yet to be established rehabilitation guidelines. Through experience and clinical reasoning, the following guidelines have been developed based on the ...

Intracellular amyloid beta (Aβ) oligomers and extracellular Aβ plaques are key players in the progression of sporadic Alzheimer's disease (AD). Still, the molecular signals triggering Aβ production are largely unclear. We asked whether mitochondrion-derived reactive oxygen species (ROS) are sufficient to increase Aβ generation and thereby initiate a vicious cycle ...

On the one hand, redox emerges as a key mechanism in regulating intra- and intercellular signaling and homeostatic systems. On the other hand, cells of the B lineage provide powerful systems to unravel the intra- and intercellular mechanisms that coordinate the processes of development and terminal differentiation. RECENT ADVANCES: This ...

Nascent polypeptides entering the endoplasmic reticulum (ER) are co- and post-translationally modified by N-glycosylation and the oxidation/isomerization of cysteine residues followed by folding with the aid of molecular chaperones. Only properly folded proteins reach their final destination. The oxidative environment in the ER enables ER-resident oxidoreductases to facilitate disulfide bond ...

Prolonged hyperoxia exposure generates excessive reactive oxygen species (ROS) and potentially leads to oxidative injury in every organ. We have previously generated Drosophila melanogaster flies that tolerate extreme oxidative stress (90%-95% O₂), a lethal condition to naive flies, through a long-term laboratory selection. We found that hyperoxia-selected (S(O2)A) flies had ...

Accurate computation of free energy changes upon molecular binding remains a challenging problem, and changes in configurational entropy are especially difficult due to the potentially large numbers of local minima, anharmonicity, and high-order coupling among degrees of freedom. Here we propose a new method to compute molecular entropies based on ...

To investigate the impact of manipulating stomatal density, a collection of Arabidopsis epidermal patterning factor (EPF) mutants with an approximately 16-fold range of stomatal densities (approx. 20-325% of that of control plants) were grown at three atmospheric carbon dioxide (CO(2)) concentrations (200, 450 and 1000 ppm), and 30 per cent ...

Rubisco, the most abundant enzyme on the Earth and responsible for all photosynthetic carbon fixation, is often thought of as a highly conserved and sluggish enzyme. Yet, different algal Rubiscos demonstrate a range of kinetic properties hinting at a history of evolution and adaptation. Here, we show that algal Rubisco ...

Savannahs are a mixture of trees and grasses often occurring as alternate states to closed forests. Savannah fires are frequent where grass productivity is high in the wet season. Fires help maintain grassy vegetation where the climate is suitable for woodlands or forests. Saplings in savannahs are particularly vulnerable to ...

The colonization and radiation of multicellular plants on land that started over 470 Ma was one of the defining events in the history of this planet. For the first time, large amounts of primary productivity occurred on the continental surface, paving the way for the evolution of complex terrestrial ecosystems ...

Exciting evidence from diverse fields, including physiology, evolutionary biology, palaeontology, geosciences and molecular genetics, is providing an increasingly secure basis for robustly formulating and evaluating hypotheses concerning the role of atmospheric carbon dioxide (CO(2)) in the evolution of photosynthetic eukaryotes. Such studies span over a billion years of evolutionary change, ...

The geochemical carbon cycle is strongly influenced by life on land, principally through the effects of carbon sequestration and the weathering of calcium and magnesium silicates in surface rocks and soils. Knowing the time of origin of land plants and animals and also of key organ systems (e.g. plant vasculature, ...

Tectonic processes drive megacycles of atmospheric carbon dioxide (CO(2)) concentration, c(a), that force large fluctuations in global climate. With a period of several hundred million years, these megacycles have been linked to the evolution of vascular plants, but adaptation at the subcellular scale has been difficult to determine because fossils ...

In response to short-term fluctuations in atmospheric CO(2) concentration, c(a), plants adjust leaf diffusive conductance to CO(2), g(c), via feedback regulation of stomatal aperture as part of a mechanism for optimizing CO(2) uptake with respect to water loss. The operational range of this elaborate control mechanism is determined by the ...

C(4) photosynthesis has evolved more than 60 times as a carbon-concentrating mechanism to augment the ancestral C(3) photosynthetic pathway. The rate and the efficiency of photosynthesis are greater in the C(4) than C(3) type under atmospheric CO(2) depletion, high light and temperature, suggesting these factors as important selective agents. This ...

Variation in atmospheric [CO(2)] is a prominent feature of the environmental history over which vascular plants have evolved. Periods of falling and low [CO(2)] in the palaeo-record appear to have created selective pressure for important adaptations in modern plants. Today, rising [CO(2)] is a key component of anthropogenic global environmental ...

Oxygenic photosynthesis evolved at least 2.4 Ga; all oxygenic organisms use the ribulose bisphosphate carboxylase-oxygenase (Rubisco)-photosynthetic carbon reduction cycle (PCRC) rather than one of the five other known pathways of autotrophic CO(2) assimilation. The high CO(2) and (initially) O(2)-free conditions permitted the use of a Rubisco with a high maximum ...

Global weathering of calcium and magnesium silicate rocks provides the long-term sink for atmospheric carbon dioxide (CO(2)) on a timescale of millions of years by causing precipitation of calcium carbonates on the seafloor. Catchment-scale field studies consistently indicate that vegetation increases silicate rock weathering, but incorporating the effects of trees ...

AIM: In the pathogenesis of diabetic retinopathy, retinal mitochondria are damaged, superoxide levels are elevated, and mitochondrial DNA (mtDNA) biogenesis is impaired. mtDNA has a noncoding region, displacement loop (D-loop), which has essential transcription and replication elements, and this region is highly vulnerable to oxidative damage. The aim of this ...

We have developed fluorescence triple correlation spectroscopy (F3CS) as an extension of the widely used fluorescence microscopy technique fluorescence correlation spectroscopy. F3CS correlates three signals at once and provides additional capabilities for the study of systems with complex stoichiometry, kinetic processes, and irreversible reactions. A general theory of F3CS was ...