Dissecting the Hydrolytic Activities of Sarcoplasmic Reticulum ATPase in the Presence of Acetyl Phosphate

Sarcoplasmic reticulum vesicles and purified Ca$^{2+}$-ATPase hydrolyze acetyl phosphate both in the presence and absence of Ca$^{2+}$. The Ca$^{2+}$-independent activity was fully sensitive to vanadate, insensitive to thapsigargin, and proceeded without accumulation of phosphorylated enzyme. Acetyl phosphate hydrolysis in the absence of Ca$^{2+}$ was activated by dimethyl sulfoxide. The Ca$^{2+}$-dependent activity was partially sensitive to vanadate, fully sensitive to thapsigargin, and associated with steady phosphoenzyme accumulation. The Ca$^{2+}$/P(i) coupling ratio at neutral pH sustained by 10 mm acetyl phosphate was 0.57. Addition of 30% dimethyl sulfoxide completely blocked Ca$^{2+}$ transport and partially inhibited the hydrolysis rate. Uncoupling induced by dimethyl sulfoxide included the accumulation of vanadate-insensitive phosphorylated enzyme. When acetyl phosphate was the substrate, the hydrolytic pathway was dependent on experimental conditions that might or might not allow net Ca$^{2+}$ transport. The interdependence of both Ca$^{2+}$-dependent and Ca$^{2+}$-independent hydrolytic activities was demonstrated

On the chronological structure of the solutrean in Southern Iberia

The Solutrean techno-complex has gained particular significance over time for representing a clear demographic and techno-typological deviation from the developments occurred during the course of the Upper Paleolithic in Western Europe. Some of Solutrean's most relevant features are the diversity and techno-typological characteristics of the lithic armatures. These have been recurrently used as pivotal elements in numerous Solutrean-related debates, including the chronological organization of the techno-complex across Iberia and Southwestern France. In Southern Iberia, patterns of presence and/or absence of specific point types in stratified sequences tend to validate the classical ordering of the techno-complex into Lower, Middle and Upper phases, although some evidence, namely radiocarbon determinations, have not always been corroborative. Here we present the first comprehensive analysis of the currently available radiocarbon data for the Solutrean in Southern Iberia. We use a Bayesian statistical approach from 13 stratified sequences to compare the duration, and the start and end moments of each classic Solutrean phase across sites. We conclude that, based on the current data, the traditional organization of the Solutrean cannot be unquestionably confirmed for Southern Iberia, calling into doubt the status of the classically defined type-fossils as precise temporal markers.Fundacao para a Ciencia e Tecnologia [PTDC/HAH/64184/2006, PTDC/HIS-ARQ/117540/2010, SFRH/BD/65527/2009, SFRH/BPD/96277/2013]; National Geographic Society [8045-06]; Wenner-Gren Foundation for Anthropological Research [8290

Natural History of MYH7-Related Dilated Cardiomyopathy

BACKGROUND: Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. OBJECTIVE: We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. METHODS: We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 ± 19.2 years) recruited from 29 international centers. RESULTS: At initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% ± 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of ≤35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. CONCLUSIONS: MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare

Genetically elevated high-density lipoprotein cholesterol through the cholesteryl ester transfer protein gene does not associate with risk of Alzheimer's disease

Introduction: There is conflicting evidence whether high-density lipoprotein cholesterol (HDL-C) is a risk factor for Alzheimer's disease (AD) and dementia. Genetic variation in the cholesteryl ester transfer protein (CETP) locus is associated with altered HDL-C. We aimed to assess AD risk by genetically predicted HDL-C. Methods: Ten single nucleotide polymorphisms within the CETP locus predicting HDL-C were applied to the International Genomics of Alzheimer's Project (IGAP) exome chip stage 1 results in up 16,097 late onset AD cases and 18,077 cognitively normal elderly controls. We performed instrumental variables analysis using inverse variance weighting, weighted median, and MR-Egger. Results: Based on 10 single nucleotide polymorphisms distinctly predicting HDL-C in the CETP locus, we found that HDL-C was not associated with risk of AD (P > .7). Discussion: Our study does not support the role of HDL-C on risk of AD through HDL-C altered by CETP. This study does not rule out other mechanisms by which HDL-C affects risk of AD

Plant fibre reinforced polymers: where do we stand in terms of tensile properties?

Plant fibres have a unique set of properties ranging from being stiff and brittle, such as hemp and flax, to more ductile, such as coir, c ombining these properties with their cost and availability makes them attractive alternative reinforcements for the production of greener composites . This article reviews the tensile properties of various plant fibre or plant based natural fibre - reinforced polymer s reported in the literature . We critically discuss the use of plant fibres as reinforcement for the production of bio - based , renewable or green polymer composites , showing t he evolution of the properties of plant fibre composites. The reported tensile properties of plant fibre - reinforced polymer composites are compared against various renewable and n on - renewable engineering/commodity polymers as well as the tensile properties of commercially available randomly oriented glass fibre - reinforced polymers (GFRP). G reen composites containing random short plant fibres do have similar properties to randomly oriented GFRP at a lower overall part weight. U nidirectional plant fibre - reinf orced polymers offer better performance than randomly oriented GFRP and could have the potential to be adapted in applications requiring even higher mechanical performance, especially in areas where the use of costly synthetic fibres might be less attracti ve . Furthermore, plant fibres can also be regarded as effective fillers to replace more expensive polymer s and improve the green credential s of final composite parts. These features may motivate the industry to introduce more plant fibre - based products to the market

Ultra-permeable zeolitic imidazolate frameworks-intercalated graphene oxide membranes for unprecedented ultrafast molecular separation

Membranes with ultrafast solvent transport for precise molecular separations are desired to reduce the energy consumption in the separation processes. Graphene oxide (GO)-based membranes have tremendous potential for precise molecular filtration. However, the construction of well-defined interlayer channels that overcome permeance-rejection trade-off is still fundamentally challenging. In this work, molecule selective GO/MOF membranes with ultrafast diffusion nanochannels were fabricated via in situ self-assembly of zeolitic imidazolate framework-8 (ZIF-8) in the GO interlayers using a facile vacuum-assisted filtration method. The obtained lamellar GO/MOF membranes with well-defined nanochannels showed unprecedented ultrafast solvent transport, with acetone and methanol permeance up to ~10,000 L m−2 h−1 bar−1 and ~6,800 L m−2 h−1 bar−1, respectively. More importantly, these membranes provided smart, selective separation performance for various binary dye mixtures with separation efficiencies higher than 95%, achieving precise separation of small organic molecules at a transport rate which is over two orders of magnitude higher than that of reported organic solvent nanofiltration membranes. Their high permeation flux as well as precise size-selective molecular recognition make them a promising candidate for energy-efficient molecular separations