A Malus crabapple chalcone synthase gene, McCHS, regulates red petal color and flavonoid biosynthesis.

Chalcone synthase is a key and often rate-limiting enzyme in the biosynthesis of anthocyanin pigments that accumulate in plant organs such as flowers and fruits, but the relationship between CHS expression and the petal coloration level in different cultivars is still unclear. In this study, three typical crabapple cultivars were chosen based on different petal colors and coloration patterns. The two extreme color cultivars, 'Royalty' and 'Flame', have dark red and white petals respectively, while the intermediate cultivar 'Radiant' has pink petals.

An innovative, multi-arm, complete phase 1b study of the novel anti-cancer agent tasisulam in patients with advanced solid tumors.

Background: This phase Ib study used a parallel, multi-arm design to examine tasisulam-sodium (hereafter tasisulam), a drug with complex pharmacology, combined with standard chemotherapies in patients with advanced solid tumors, with the ultimate goal of accelerating drug development.

Methods: Patients received escalating doses of tasisulam (3 + 3 schema; target Cmax 300-400 μg/mL) every 28 days plus 1,000 mg/m(2) gemcitabine HCl (days 1 and 15), 60 mg/m(2) docetaxel, 200 mg/m(2)/day temozolomide, 75 mg/m(2) cisplatin, or 150 mg/day erlotinib. Following dose-escalation, patients were enrolled into specific tumor subtype arms, chosen based on the established activity of the standard agent.

A simple and sensitive turn-on fluorescence probe for detection of cetyltrimethylammonium bromide in aqueous samples.

The interaction of acid (PTCA) with cetyltrimethylammonium bromide (CTAB) has been studied by fluorescence spectroscopy. The fluorescence of PTCA can be greatly enhanced by the addition of CTAB, due to the formation a fluorescent supramolecular compound. Under optimum conditions, the enhancement intensity of fluorescence was proportional to the concentration of CTAB over a range of 0-4.

CREB SUMOylation by the E3 ligase PIAS1 enhances spatial memory.

cAMP-responsive element binding protein (CREB) phosphorylation and signaling plays an important role in long-term memory formation, but other posttranslational modifications of CREB are less known. Here, we found that CREB1Δ, the short isoform of CREB, could be sumoylated by the small ubiquitin-like modifier (SUMO) E3 ligase protein inhibitor of activated STAT1 (PIAS1) at Lys271 and Lys290 and PIAS1 SUMOylation of CREB1Δ increased the expression level of CREB1Δ. CREB1Δ could also be sumoylated by other PIAS family proteins, but not by the E3 ligases RanBP2 and Pc2 or by the E2 ligase Ubc9.

Thyroid hormone enhanced human hepatoma cell motility involves brain-specific serine protease 4 activation via ERK signaling.

Background: The thyroid hormone, 3, 3', 5-triiodo-L-thyronine (T3), has been shown to modulate cellular processes via interactions with thyroid hormone receptors (TRs), but the secretory proteins that are regulated to exert these effects remain to be characterized. Brain-specific serine protease 4 (BSSP4), a member of the human serine protease family, participates in extracellular matrix remodeling. However, the physiological role and underlying mechanism of T3-mediated regulation of BSSP4 in hepatocellular carcinogenesis are yet to be established.

A genome-wide association study on chronic HBV infection and its clinical progression in male Han-Taiwanese.

It is common to observe the clustering of chronic hepatitis B surface antigen (HBsAg) carriers in families. Intra-familial transmission of hepatitis B virus (HBV) could be the reason for the familial clustering of HBsAg carriers. Additionally, genetic and gender factors have been reported to be involved.

Myocyte-mediated arginase expression controls hyperargininemia but not hyperammonemia in arginase-deficient mice.

Human arginase deficiency is characterized by hyperargininemia and infrequent episodes of hyperammonemia that cause neurological impairment and growth retardation. We previously developed a neonatal mouse adeno-associated viral vector (AAV) rh10-mediated therapeutic approach with arginase expressed by a chicken β-actin promoter that controlled plasma ammonia and arginine, but hepatic arginase declined rapidly. This study tested a codon-optimized arginase cDNA and compared the chicken β-actin promoter to liver- and muscle-specific promoters.

Establishment of bovine trophoblast stem-like cells from in vitro-produced blastocyst-stage embryos using two inhibitors.

The trophoblast (TR) is the first to differentiate during mammalian embryogenesis and play a pivotal role in the development of the placenta. We used a dual inhibitor system (PD0325901 and CHIR99021) with mixed feeders to successfully obtain bovine trophoblast stem-like (bTS) cells, which were similar in phenotype to mouse trophoblast stem cells (TSCs). The bTS cells that were generated using this system continually proliferated, displayed a normal diploid karyotype, and had no signs of altered morphology or differentiation even after 150 passages.

qFibrosis: a fully-quantitative innovative method incorporating histological features to facilitate accurate fibrosis scoring in animal model and chronic hepatitis B patients.

Background & Aims: There is increasing need for accurate assessment of liver fibrosis/cirrhosis. We aimed to develop qFibrosis, a fully-automated assessment method combining quantification of histopathological architectural features, to address unmet needs in core biopsy evaluation of fibrosis in chronic hepatitis B (CHB) patients.

Methods: qFibrosis was established as a combined index based on 87 parameters of architectural features.

Correlation of MR elastography with morphometric quantification of liver fibrosis (Fibro-C-Index) in chronic hepatitis B.

Purpose: We evaluated the correlation of MR Elastography (MRE) with morphometric assessment of liver fibrosis in chronic hepatitis B (CHB).

Methods: Thirty-two patients with CHB underwent both MRE and a liver biopsy within a 6-month interval. MRE was performed using standard MRE sequence on a 1.

Identification of properties important to protein aggregation using feature selection.

Background: Protein aggregation is a significant problem in the biopharmaceutical industry (protein drug stability) and is associated medically with over 40 human diseases. Although a number of computational models have been developed for predicting aggregation propensity and identifying aggregation-prone regions in proteins, little systematic research has been done to determine physicochemical properties relevant to aggregation and their relative importance to this important process. Such studies may result in not only accurately predicting peptide aggregation propensities and identifying aggregation prone regions in proteins, but also aid in discovering additional underlying mechanisms governing this process.

Lethal phenotype in conditional late-onset arginase 1 deficiency in the mouse.

Human arginase deficiency is characterized by hyperargininemia and infrequent episodes of hyperammonemia, which lead to neurological impairment with spasticity, loss of ambulation, seizures, and severe mental and growth retardation; uncommonly, patients suffer early death from this disorder. In a murine targeted knockout model, onset of the phenotypic abnormality is heralded by weight loss at around day 15, and death occurs typically by postnatal day 17 with hyperargininemia and markedly elevated ammonia. This discrepancy between the more attenuated juvenile-onset human disease and the lethal neonatal murine model has remained suboptimal for studying and developing therapy for the more common presentation of arginase deficiency.

Low rates of short- and long-term graft loss after kidney-pancreas transplant from a single center.

Importance: Since the 1980s, pancreas transplant has become the most effective treatment strategy to restore euglycemia in patients with type 1 diabetes mellitus. However, technical complications and BK virus nephropathy continue to be important causes of early and late graft loss. These and other complications lead to cited 1- and 3-year graft survival rates of 74% and 67% (pancreas) and 81% and 73% (kidney).

A lead (II) 3D coordination polymer based on a marine cyclic peptide motif.

The crystal structure of a naturally occurring cyclic tetrapeptide cyclo(Gly-L-Ser-L-Pro-L-Glu) [cyclo(GSPE)] was obtained. The conformation of synthesized cyclo(GSPE) fixes the coordination to lead ion in a 1:1 ratio. This cyclo(GSPE)-Pb complex was constructed as an asymmetric 3D network in the crystalline state.

Associations between hemodialysis access type and clinical outcomes: a systematic review.

Clinical practice guidelines recommend an arteriovenous fistula as the preferred vascular access for hemodialysis, but quantitative associations between vascular access type and various clinical outcomes remain controversial. We performed a systematic review of cohort studies to evaluate the associations between type of vascular access (arteriovenous fistula, arteriovenous graft, and central venous catheter) and risk for death, infection, and major cardiovascular events. We searched MEDLINE, EMBASE, and article reference lists and extracted data describing study design, participants, vascular access type, clinical outcomes, and risk for bias.

Depletion of albumin and immunoglobulin G from human serum using epitope-imprinted polymers as artificial antibodies.

Serum is a readily available source for noninvasive studies in clinical research, but it contains abundant proteins such as albumin and immunoglobulin G that can hinder the presence of low-abundant proteins as well as decrease sample loading capacity of analytical methods. Therefore, depletion of these two proteins is required to observe low-abundance serum proteins. Molecularly imprinted polymers are template-induced artificial antibodies with the ability to recognize and selectively bind the target molecule.

Retroperitoneal pelvic packing for haemodynamically unstable pelvic fractures in children and adolescents: a level-one trauma-centre experience.

Purpose: This study aims to review the outcomes of haemodynamically unstable paediatric patients with pelvic fractures undergoing protocol intervention of retroperitoneal pelvic packing (RPP) with external fixation and angiography.

Methods: From 2004 to 2011, consecutive patients younger than 19 years treated in our centre for haemodynamically unstable pelvic fractures were retrospectively reviewed. From 2008, protocol intervention triad of external fixation, RPP, and angiography with embolization was implemented.

Efficient induction of pluripotent stem cells from menstrual blood.

The technology to reprogram human somatic cells back to pluripotency allows the production of patient-specific induced pluripotent stem cells (iPSCs) and holds a great promise for regenerative medicine. Choosing the most suitable cell type for induction and reducing the risk of viral transgene activation, especially oncogene activation, are important for iPSC research. To date, human dermal fibroblasts (HDFs) are the most frequent cell source used for iPSC generation, but they have several limitations.

Macrophage heterogeneity and cholesterol homeostasis: classically-activated macrophages are associated with reduced cholesterol accumulation following treatment with oxidized LDL.

Macrophages are centrally involved during atherosclerosis development and are the predominant cell type that accumulates cholesterol in the plaque. Macrophages however, are heterogeneous in nature reflecting a variety of microenvironments and different phenotypes may be more prone to contribute towards atherosclerosis progression. Using primary human monocyte-derived macrophages, we sought to evaluate one aspect of atherogenic potential of different macrophage phenotypes by determining their propensity to associate with and accumulate oxidized low density lipoprotein (oxLDL).

Changes in intracellular redox status influence multidrug resistance in gastric adenocarcinoma cells.

Multidrug resistance (MDR) to chemotherapeutic agents is a major obstacle for the treatment of various types of cancers. The exact mechanism of MDR has not yet been fully clarified, although it has been frequently associated with the variation of intracellular redox status. The levels of intracellular glutathione (GSH) are considered to play a vital role in the regulation of the intracellular redox status.

Pneumatic compression devices during hemodialysis: a randomized crossover trial.

Background: Maintenance of central blood volume (CBV) is essential for hemodynamic stability during hemodialysis (HD), though preservation of CBV is poorly understood. Pneumatic compression devices (PCDs) during HD may help maintain CBV.

Methods: We performed a randomized, crossover trial to determine the effect of PCDs on CBV during HD.

Phase 2 randomized study of enzastaurin (LY317615) for lung cancer prevention in former smokers.

Background: Chemoprevention for lung cancer with nutraceutical or anti-inflammatory agents has had mixed clinical benefit. Novel targeted agents hold the promise of greater efficacy and selectivity. The authors of this report evaluated enzastaurin, a selective protein kinase C-β (PKC-β) inhibitor with antiproliferative and proapoptotic properties, in former smokers.

Phase II study of gemcitabine and bevacizumab as first-line treatment in taxane-pretreated, HER2-negative, locally recurrent or metastatic breast cancer.

Background: In first-line treatment of metastatic breast cancer, the best use of the available therapeutic agents is unclear. This study evaluated the efficacy and safety of combined therapy with bevacizumab and gemcitabine.

Patients: Women who were to undergo first-line treatment for locoregionally recurrent or metastatic breast cancer were eligible.

Conservative management of L-asparaginase-induced hypertriglyceridemia in an adult patient: a case report and review of the literature.

Background: L-Asparaginase (L-Asp) may induce hypertriglyceridemia; however, this has been mainly observed among pediatric patients. Treatment for L-Asp-induced hypertriglyceridemia is not standardized, ranging from fasting and diet restriction to the invasive plasmapheresis procedure.

Case Report: We describe a 53-year-old male patient who presented with L-Asp-induced severe hypertriglyceridemia.

The impact of irritable bowel syndrome on health-related quality of life: a Singapore perspective.

Background: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder. The prevalence of IBS in Asian countries varies from 2.9% to 15.