Effects of equine-assisted activities on attention and quality of life in children with cerebral palsy in a randomized trial: examining the comorbidity with attention-deficit/hyperactivity disorder.

Background: Attention problems and decreased quality of life are frequently accompanied in Cerebral Palsy (CP), which can negatively affect rehabilitation of physical disability. However, the majority of affected children remain untreated in the aspects of attention or psychosocial factors. Equine-Assisted Activities and Therapies (EAAT) use horse as a therapeutic modality including grooming as well as mounted riding activities in which patients exercise and experience mounted stimulation.

PGC1/PPAR drive cardiomyocyte maturation at single cell level via YAP1 and SF3B2.

Cardiomyocytes undergo significant structural and functional changes after birth, and these fundamental processes are essential for the heart to pump blood to the growing body. However, due to the challenges of isolating single postnatal/adult myocytes, how individual newborn cardiomyocytes acquire multiple aspects of the mature phenotype remains poorly understood. Here we implement large-particle sorting and analyze single myocytes from neonatal to adult hearts.

PKG1α Cysteine-42 Redox State Controls mTORC1 Activation in Pathological Cardiac Hypertrophy.

Rationale: Stimulated PKG1α (protein kinase G-1α) phosphorylates TSC2 (tuberous sclerosis complex 2) at serine 1365, potently suppressing mTORC1 (mechanistic [mammalian] target of rapamycin complex 1) activation by neurohormonal and hemodynamic stress. This reduces pathological hypertrophy and dysfunction and increases autophagy. PKG1α oxidation at cysteine-42 is also induced by these stressors, which blunts its cardioprotective effects.

PKG1-modified TSC2 regulates mTORC1 activity to counter adverse cardiac stress.

The mechanistic target of rapamycin complex-1 (mTORC1) coordinates regulation of growth, metabolism, protein synthesis and autophagy. Its hyperactivation contributes to disease in numerous organs, including the heart, although broad inhibition of mTORC1 risks interference with its homeostatic roles. Tuberin (TSC2) is a GTPase-activating protein and prominent intrinsic regulator of mTORC1 that acts through modulation of RHEB (Ras homologue enriched in brain).

Marked disparity of microRNA modulation by cGMP-selective PDE5 versus PDE9 inhibitors in heart disease.

MicroRNAs (miRs) posttranscriptionally regulate mRNA and its translation into protein, and are considered master controllers of genes modulating normal physiology and disease. There is growing interest in how miRs change with drug treatment, and leveraging this for precision guided therapy. Here we contrast 2 closely related therapies, inhibitors of phosphodiesterase type 5 or type 9 (PDE5-I, PDE9-I), given to mice subjected to sustained cardiac pressure overload (PO).

Identification of new PDE9A isoforms and how their expression and subcellular compartmentalization in the brain change across the life span.

3',5'-Cyclic nucleotide phosphodiesterases (PDEs) degrade 3',5' cyclic adenonosine monophosphate (cAMP) and 3',5' cyclic guanosine monophosphate (cGMP), with PDE9A having the highest affinity for cGMP. We show PDE9A6 and 3 novel PDE9 isoforms (PDE9X-100, PDE9X-120, and PDE9X-175) are reliably detected in the brain and lung of mice, whereas PDE9A2 and other isoforms are found elsewhere. PDE9A localizes to the membrane in all organs except the bladder, where it is cytosolic.

Comparison of Impact of Monocular and Integrated Binocular Visual Fields on Vision-related Quality of Life.

Purpose Of The Study: The purpose of the study was to investigate the relationship between vision-related quality of life (VRQOL) and mean deviation (MD) of the monocular visual field and integrated binocular visual field (IBVF).

Methods: One hundred eighty VFs (90 pairs) obtained from 90 patients with normal tension glaucoma were included. VRQOL was evaluated using the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25).

Clinical factors affecting intraocular pressure change after orbital decompression surgery in thyroid-associated ophthalmopathy.

Objective: To report the physiological monitoring of intraocular pressure (IOP) during the postoperative periods after orbital decompression surgery and ascertain the correlation between the clinical factors and IOP changes.

Methods: The medical records of 113 orbits from 60 patients who underwent orbital decompression surgery were reviewed retrospectively. IOP measurement during the postoperative periods was classified based on the postoperative day: week 1 (1-7 days), month 1 (8-41 days), month 2 (42-70 days), month 3 (71-97 days), month 4 (98-126 days), and final (after 127 days).

Precardiac deletion of Numb and Numblike reveals renewal of cardiac progenitors.

Cardiac progenitor cells (CPCs) must control their number and fate to sustain the rapid heart growth during development, yet the intrinsic factors and environment governing these processes remain unclear. Here, we show that deletion of the ancient cell-fate regulator Numb (Nb) and its homologue Numblike (Nbl) depletes CPCs in second pharyngeal arches (PA2s) and is associated with an atrophic heart. With histological, flow cytometric and functional analyses, we find that CPCs remain undifferentiated and expansive in the PA2, but differentiate into cardiac cells as they exit the arch.

Gold nanoparticles-based colorimetric assay for cathepsin B activity and the efficiency of its inhibitors.

Cathepsin B has been suggested to be a prognostic marker of melanoma, glioma, and a variety of cancers such as brain, breast, colon, esophageal, gastric, lung, ovarian, and thyroid cancers. Cathepsin B inhibitors have also been considered as anticancer drug candidates; hence, there has been a growing need for a probe which enables the selective and simple detection of cathepsin B and its inhibitors. For the purpose of selective assay, a cathepsin B-specific substrate, N,N'-diBoc-dityrosine-glycine-phenylalanine-3-(methylthio)propylamine (DBDY-Gly-Phe-MTPA) was synthesized in this study.

Cardiomyocyte-specific transforming growth factor β suppression blocks neutrophil infiltration, augments multiple cytoprotective cascades, and reduces early mortality after myocardial infarction.

Rationale: Wound healing after myocardial infarction involves a highly regulated inflammatory response that is initiated by the appearance of neutrophils to clear out dead cells and matrix debris. Neutrophil infiltration is controlled by multiple secreted factors, including the master regulator transforming growth factor β (TGFβ). Broad inhibition of TGFβ early postinfarction has worsened post-myocardial infarction remodeling; however, this signaling displays potent cell specificity, and targeted suppression particularly in the myocyte could be beneficial.

Combined TRPC3 and TRPC6 blockade by selective small-molecule or genetic deletion inhibits pathological cardiac hypertrophy.

Chronic neurohormonal and mechanical stresses are central features of heart disease. Increasing evidence supports a role for the transient receptor potential canonical channels TRPC3 and TRPC6 in this pathophysiology. Channel expression for both is normally very low but is increased by cardiac disease, and genetic gain- or loss-of-function studies support contributions to hypertrophy and dysfunction.

Hyperactive adverse mechanical stress responses in dystrophic heart are coupled to transient receptor potential canonical 6 and blocked by cGMP-protein kinase G modulation.

Rationale: The heart is exquisitely sensitive to mechanical stimuli to adapt rapidly to physiological demands. In muscle lacking dystrophin, such as Duchenne muscular dystrophy, increased load during contraction triggers pathological responses thought to worsen the disease. The relevant mechanotransducers and therapies to target them remain unclear.

New strategy for selective and sensitive assay of cathepsin B using a dityrosine-based material.

The increasing number of reports for disease-related proteases has necessitated materials for the fast, sensitive, and specific assessment of protease activities. The purpose of this study was to synthesize and test a dityrosine-based substrate for the selective assay of a specific cysteine cathepsin. DBDY-Gly-INH)2 was synthesized from the conjugation of N,N'-diBoc-dityrosine (DBDY) with two molecules of glycine and isoniazid (INH) for this purpose.

Pathological cardiac hypertrophy alters intracellular targeting of phosphodiesterase type 5 from nitric oxide synthase-3 to natriuretic peptide signaling.

Background: In the normal heart, phosphodiesterase type 5 (PDE5) hydrolyzes cGMP coupled to nitric oxide- (specifically from nitric oxide synthase 3) but not natriuretic peptide (NP)-stimulated guanylyl cyclase. PDE5 is upregulated in hypertrophied and failing hearts and is thought to contribute to their pathophysiology. Because nitric oxide signaling declines whereas NP-derived cGMP rises in such diseases, we hypothesized that PDE5 substrate selectivity is retargeted to blunt NP-derived signaling.

A dityrosine-based substrate for a protease assay: application for the selective assessment of papain and chymopapain activity.

N,N'-diBoc-dityrosine (DBDY), which was synthesized by the oxidative C-C coupling of 2 N-Boc-L-tyrosine molecules, was conjugated with two isoniazid (INH) molecules. Due to the quenching effect of INH, DBDY-(INH)(2) lacks the fluorescence of DBDY. As such, it was tested for use in the detection of proteases by measuring fluorescence recovery.

Thrombospondin-4 is required for stretch-mediated contractility augmentation in cardiac muscle.

Rationale: One of the physiological mechanisms by which the heart adapts to a rise in blood pressure is by augmenting myocyte stretch-mediated intracellular calcium, with a subsequent increase in contractility. This slow force response was first described over a century ago and has long been considered compensatory, but its underlying mechanisms and link to chronic adaptations remain uncertain. Because levels of the matricellular protein thrombospondin-4 (TSP4) rapidly rise in hypertension and are elevated in cardiac stress overload and heart failure, we hypothesized that TSP4 is involved in this adaptive mechanism.

Electrical bistabilities and memory stabilities of nonvolatile bistable devices fabricated utilizing C(60) molecules embedded in a polymethyl methacrylate layer.

Current-voltage (I-V) measurements on Al/fullerene (C(60)) molecules embedded in polymethyl methacrylate/Al devices at 300 K showed a current bistability due to the existence of the C(60) molecules. The on/off ratio of the current bistability for the memory devices was as large as 10(3). The retention time of the devices was above 2.

Oxidation of 17alpha-ethinylestradiol with Mn(III) and product identification.

With increasing concern about the contamination of aquatic environments by estrogenic pollutants, removal of synthetic estrogens such as 17alpha-ethinylestradiol (EE2) has been widely studied, especially with respect to the treatment methods. However, the degradation products have rarely been identified. The purpose of this study was to identify structurally the oxidation products of EE2.

Entangled photon absorption in an organic porphyrin dendrimer.

Two-photon absorption spectroscopy is an intensity dependent nonlinear effect related to the excitation of virtual intermediate states. The classical two-photon absorption has an extremely low efficiency which is quantified by its cross-section (delta approximately 10(-48) cm4 s at 800 nm). To overcome this limitation, we demonstrate a novel effect of the two-photon absorption method utilizing the high degree of quantum optical correlation between photon pairs created by the process of spontaneous parametric downconversion.

Thapsigargin resistance in human prostate cancer cells.

Background: Thapsigargin (TG) is a potent inhibitor of sarcoplasmic/endoplasmic reticulum Ca2+ ATPases (SERCAs). TG-based prodrugs are being developed for the treatment of prostate cancer (PC). To develop optimal TG-based therapeutics it is important to understand the mechanisms of resistance to TG that may potentially occur in cancer cells.

Measuring properties of superposed light beams carrying different frequencies.

When two electromagnetic fields of different frequencies are physically superposed, the linear superposition equation implies that the fields readjust themselves into a new mean frequency whose common amplitude undulates at half their difference frequency. Neither of these mathematical frequencies are measurable quantities. We present a set of experiments underscoring that optical fields do not interfere with each other or modify themselves into a new frequency even when they are physically superposed.

Endoplasmic reticulum calcium pool depletion-induced apoptosis is coupled with activation of the death receptor 5 pathway.

Thapsigargin (TG), by inducing perturbations in cellular Ca(2+) homeostasis, has been shown to induce apoptosis. The molecular mechanisms of Ca(2+) perturbation-induced apoptosis are not fully understood. In this study, we demonstrate for the first time that TG-mediated perturbations in Ca(2+) homeostasis are coupled with activation of the death receptor 5 (DR5)-dependent apoptotic pathway in human cancer cells.