SGLT2 inhibitors attenuate endothelial to mesenchymal transition and cardiac fibroblast activation.

Beneficial effects of sodium glucose co-transporter 2 inhibitors (SGLT2is) in cardiovascular diseases have been extensively reported leading to the inclusion of these drugs in the treatment guidelines for heart failure. However, molecular actions especially on non-myocyte cells remain uncertain. We observed dose-dependent inhibitory effects of two SGLT2is, dapagliflozin (DAPA) and empagliflozin (EMPA), on inflammatory signaling in human umbilical vein endothelial cells.

120-GBaud 16-QAM silicon photonics IQ modulator for data center interconnection.

We demonstrated all-silicon IQ modulators (IQMs) operating at 120-GBaud 16-QAM with suitable bandwidth, and output power. We required optical signal-to-noise-ratio (rOSNR) that have promising potential to be used in 800-Gbps small-form-factor pluggable transceivers for data center interconnection. First, we tested an IQM chip using discrete drivers and achieved a per-polarization TX output power of -18.

From data to interpretable models: machine learning for soil moisture forecasting.

Soil moisture is critical to agricultural business, ecosystem health, and certain hydrologically driven natural disasters. Monitoring data, though, is prone to instrumental noise, wide ranging extrema, and nonstationary response to rainfall where ground conditions change. Furthermore, existing soil moisture models generally forecast poorly for time periods greater than a few hours.

Deciphering Pro-angiogenic Transcription Factor Profiles in Hypoxic Human Endothelial Cells by Combined Bioinformatics and Modeling.

Background: Constant supply of oxygen is crucial for multicellular tissue homeostasis and energy metabolism in cardiac tissue. As a first response to acute hypoxia, endothelial cells (ECs) promote recruitment and adherence of immune cells to the dysbalanced EC barrier by releasing inflammatory mediators and growth factors, whereas chronic hypoxia leads to the activation of a transcription factor (TF) battery, that potently induces expression of growth factors and cytokines including platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF). We report a hypoxia-minded, targeted bioinformatics approach aiming to identify and validate TFs that regulate angiogenic signaling.

The long non-coding RNA NRON promotes the development of cardiac hypertrophy in the murine heart.

Physiological and pathological cardiovascular processes are tightly regulated by several cellular mechanisms. Non-coding RNAs, including long non-coding RNAs (lncRNAs), represent one important class of molecules involved in regulatory processes within the cell. The lncRNA non-coding repressor of NFAT (NRON) was described as a repressor of the nuclear factor of activated T cells (NFAT) in different in vitro studies.

Reconstruction of the miR-506-Quaking axis in Idiopathic Pulmonary Fibrosis using integrative multi-source bioinformatics.

The family of RNA-binding proteins (RBP) functions as a crucial regulator of multiple biological processes and diseases. However, RBP function in the clinical setting of idiopathic pulmonary fibrosis (IPF) is still unknown. We developed a practical in silico screening approach for the characterization of RBPs using multi-sources data information and comparative molecular network bioinformatics followed by wet-lab validation studies.

Alternative strategies in cardiac preclinical research and new clinical trial formats.

An efficient and safe drug development process is crucial for the establishment of new drugs on the market aiming to increase quality of life and life-span of our patients. Despite technological advances in the past decade, successful launches of drug candidates per year remain low. We here give an overview about some of these advances and suggest improvements for implementation to boost preclinical and clinical drug development with a focus on the cardiovascular field.

The kinesin motor Klp98A mediates apical to basal Wg transport.

Development and tissue homeostasis rely on the tight regulation of morphogen secretion. In the wing imaginal disc epithelium, Wg secretion for long-range signal transduction occurs after apical Wg entry into the endosomal system, followed by secretory endosomal transport. Although Wg release appears to occur from the apical and basal cell sides, its exact post-endocytic fate and the functional relevance of polarized endosomal Wg trafficking are poorly understood.

Interaction of Hydrogen with MB (M = Ba, Ca, La, and Sr) Surfaces from First Principles.

We show results of basic energetics and interacting behavior of hydrogen with metal hexaboride surfaces using a combination of self-consistent density functional calculations and dynamics based on the Car-Parrinello method. Our results show that hydrogen is strongly attracted to localized exposed boron atoms and interactions with the terminal cations are strictly repulsive. From these, preliminary local adsorption energy calculations suggest that a single hydrogen molecule per surface unit-cell is possible (one ML).

A functional promoter variant of the human formimidoyltransferase cyclodeaminase (FTCD) gene is associated with working memory performance in young but not older adults.

Objective: The central role of working memory in IQ and the high heritability of working memory performance motivated interest in identifying the specific genes underlying this heritability. The (formimidoyltransferase cyclodeaminase) gene was identified as a candidate gene for allelic association with working memory in part from genetic mapping studies of mouse Morris water maze performance.

Method: The present study tested variants of this gene for effects on a delayed match-to-sample task of a large sample of younger and older participants.

Influence of postnatal glucocorticoids on hippocampal-dependent learning varies with elevation patterns and administration methods.

Recent interest in the lasting effects of early-life stress has expanded to include effects on cognitive performance. An increase in circulating glucocorticoids is induced by stress exposure and glucocorticoid effects on the hippocampus likely underlie many of the cognitive consequences. Here we review studies showing that corticosterone administered to young rats at the conclusion of the stress-hyporesponsiveness period affects later performance in hippocampally-mediated trace eyeblink conditioning.

Data collection strategies for time-resolved X-ray free-electron laser diffraction, and 2-color methods.

We compare three schemes for time-resolved X-ray diffraction from protein nanocrystals using an X-ray free-electron laser. We find expressions for the errors in structure factor measurement using the Monte Carlo pump-probe method of data analysis with a liquid jet, the fixed sample pump-probe (goniometer) method (both diffract-and-destroy, and below the safe damage dose), and a proposed two-color method. Here, an optical pump pulse arrives between X-ray pulses of slightly different energies which hit the same nanocrystal, using a weak first X-ray pulse which does not damage the sample.

A generalized method for the inversion of cohesive energy curves from isotropic and anisotropic lattice expansions.

Cohesive energy curves contain important information about energetics of atomic interactions in crystalline materials, and these are more often obtained using ab initio methods such as density functional theory. Decomposing these curves into the different interatomic contributions is of great value to evaluate and characterize the energetics of specific types of atom-atom interactions. In this work, we present and discuss a generalized method for the inversion of cohesive energy curves of crystalline materials for pairwise interatomic potentials extraction using detailed geometrical descriptions of the atomic interactions to construct a list of atomic displacements and degeneracies, which is modified using a Gaussian elimination process to isolate the pairwise interactions.

Expression, purification and crystallization of CTB-MPR, a candidate mucosal vaccine component against HIV-1.

CTB-MPR is a fusion protein between the B subunit of cholera toxin (CTB) and the membrane-proximal region of gp41 (MPR), the transmembrane envelope protein of Human immunodeficiency virus 1 (HIV-1), and has previously been shown to induce the production of anti-HIV-1 antibodies with antiviral functions. To further improve the design of this candidate vaccine, X-ray crystallography experiments were performed to obtain structural information about this fusion protein. Several variants of CTB-MPR were designed, constructed and recombinantly expressed in Escherichia coli.

Serial time-resolved crystallography of photosystem II using a femtosecond X-ray laser.

Photosynthesis, a process catalysed by plants, algae and cyanobacteria converts sunlight to energy thus sustaining all higher life on Earth. Two large membrane protein complexes, photosystem I and II (PSI and PSII), act in series to catalyse the light-driven reactions in photosynthesis. PSII catalyses the light-driven water splitting process, which maintains the Earth's oxygenic atmosphere.

Time-resolved protein nanocrystallography using an X-ray free-electron laser.

We demonstrate the use of an X-ray free electron laser synchronized with an optical pump laser to obtain X-ray diffraction snapshots from the photoactivated states of large membrane protein complexes in the form of nanocrystals flowing in a liquid jet. Light-induced changes of Photosystem I-Ferredoxin co-crystals were observed at time delays of 5 to 10 µs after excitation. The result correlates with the microsecond kinetics of electron transfer from Photosystem I to ferredoxin.

Signal, noise, and resolution in correlated fluctuations from snapshot small-angle x-ray scattering.

It has been suggested that the three-dimensional structure of one particle may be reconstructed using the scattering from many identical, randomly oriented copies ab initio, without modeling or a priori information. This may be possible if these particles are frozen in either space or time, so that the conventional two-dimensional small-angle x-ray scattering (SAXS) distribution contains fluctuations and is no longer isotropic. We consider the magnitude of the correlated fluctuation SAXS (CFSAXS) signal for typical x-ray free-electron laser (XFEL) beam conditions and compare this against the errors derived with the inclusion of Poisson photon counting statistics.

Phasing of coherent femtosecond X-ray diffraction from size-varying nanocrystals.

The scattering between Bragg reflections from nanocrystals is used to aid solution of the phase problem. We describe a method for reconstructing the charge density of a typical molecule within a single unit cell, if sufficiently finely-sampled "snap-shot" diffraction data (as provided a free-electron X-ray laser) are available from many nanocrystals of different sizes lying in random orientations. By using information on the particle-size distribution within the patterns, this digital method succeeds, using all the data, without knowledge of the distribution of particle size or requiring atomic-resolution data.

Structure-factor analysis of femtosecond microdiffraction patterns from protein nanocrystals.

A complete set of structure factors has been extracted from hundreds of thousands of femtosecond single-shot X-ray microdiffraction patterns taken from randomly oriented nanocrystals. The method of Monte Carlo integration over crystallite size and orientation was applied to experimental data from Photosystem I nanocrystals. This arrives at structure factors from many partial reflections without prior knowledge of the particle-size distribution.

Femtosecond X-ray protein nanocrystallography.

X-ray crystallography provides the vast majority of macromolecular structures, but the success of the method relies on growing crystals of sufficient size. In conventional measurements, the necessary increase in X-ray dose to record data from crystals that are too small leads to extensive damage before a diffraction signal can be recorded. It is particularly challenging to obtain large, well-diffracting crystals of membrane proteins, for which fewer than 300 unique structures have been determined despite their importance in all living cells.

Accuracy of diagnoses delivered by an automated hand-held nerve conduction device in comparison to standard electrophysiological testing in patients with unilateral leg symptoms.

Introduction: Automated hand-held nerve conduction study (NCS) devices are being marketed for use in the diagnosis of lumbosacral radiculopathy (LSR). In this study we compared the specificity and sensitivity of a hand-held NCS device for the detection of LSR with standard electrodiagnostic study (EDX).

Methods: Fifty patients referred to a tertiary referral electromyography (EMG) laboratory for testing of predominantly unilateral leg symptoms (weakness, sensory complaints, and/or pain) were included in the investigation.