Parkinson's disease-associated mutations in the GTPase domain of LRRK2 impair its nucleotide-dependent conformational dynamics.

Mutation in leucine-rich repeat kinase 2 (LRRK2) is a common cause of familial Parkinson's disease (PD). Recently, we showed that a disease-associated mutation R1441H rendered the GTPase domain of LRRK2 catalytically less active and thereby trapping it in a more persistently "on" conformation. However, the mechanism involved and characteristics of this on conformation remained unknown.

IL-33-mediated IL-13 secretion by ST2+ Tregs controls inflammation after lung injury.

Acute respiratory distress syndrome is an often fatal disease that develops after acute lung injury and trauma. How released tissue damage signals, or alarmins, orchestrate early inflammatory events is poorly understood. Herein we reveal that IL-33, an alarmin sequestered in the lung epithelium, is required to limit inflammation after injury due to an unappreciated capacity to mediate Foxp3+ Treg control of local cytokines and myeloid populations.

Effects of norfloxacin exposure on neurodevelopment of zebrafish (Danio rerio) embryos.

In view of the wide application of fluoroquinolones (FQs), a group of broad-spectrum synthetic antibacterial agents, and their large ingress into the environment, the toxic effects on non-target organisms caused by FQs have received great attention. In this study, we used zebrafish embryo as a model, measured the general toxic effects of norfloxacin, a commonly used FQs, and investigated the effects of norfloxacin on the neurodevelopment of zebrafish embryos. Our data showed that norfloxacin significantly inhibited the hatching rate of zebrafish embryos, and increased the mortality and malformation rate of the embryos.

The Parkinson's disease-associated mutation N1437H impairs conformational dynamics in the G domain of LRRK2.

Parkinson disease-associated mutations within the GTPase domain Ras of complex proteins (ROC) of leucine rich repeat kinase 2 (LRRK2) result in an abnormal over-activation of its kinase domain. However, the mechanisms involved remain unclear. Recent study has shown that LRRK2 G-domain cycles between monomeric and dimeric conformations upon binding to GTP or guanosine diphosphate, and that the Parkinson's disease (PD)-associated R1441C/G/H mutations impair the G-domain monomer-dimer dynamics and trap the G-domain in a constitutive monomeric conformation.

Roco Proteins and the Parkinson's Disease-Associated LRRK2.

Small G-proteins are structurally-conserved modules that function as molecular on-off switches. They function in many different cellular processes with differential specificity determined by the unique effector-binding surfaces, which undergo conformational changes during the switching action. These switches are typically standalone monomeric modules that form transient heterodimers with specific effector proteins in the 'on' state, and cycle to back to the monomeric conformation in the 'off' state.

Prostate cancer tends to metastasize in the bone-mimicking microenvironment via activating NF-κB signaling.

Prostate cancer preferentially metastasizes to the bone. However, the underlying molecular mechanisms are still unclear. To explore the effects of a bone-mimicking microenvironment on PC3 prostate cancer cell growth and metastasis, we used osteoblast differentiation medium (ODM; minimal essential medium alpha supplemented with L-ascorbic acid) to mimic the bone microenvironment.

Analysis of Intravenous Urography Findings in a Tertiary Reference Center.

Objective: To analyze intravenous urography (IVU) findings in a tertiary reference center.

Materials And Methods: A retrospective, observational study was conducted in a tertiary reference center. The radiology reports of 1,470 patients subjected to IVU in the period from January 2008 to December 2012 were retrieved from the tertiary reference center databases.

Tumor microenvironment promotes prostate cancer cell dissemination via the Akt/mTOR pathway.

Metastasis causes high mortality in various malignancies, including prostate cancer (PCa). Accumulating data has suggested that cancer cells spread from the primary tumor to distant sites at early stage, which is characterized by disseminated tumor cells (DTCs). However, lack of direct evidence of partial localized PCa cells occurring epithelial-to-mesenchymal transition (EMT) and disseminating to distant sites (e.

A Novel Nonelectrosurgical Technique for Incising the Pylorus in Laparoscopic Pyloromyotomy.

Objective: Since the loss of the protected arthrotomy knife several years ago, pediatric surgeons have struggled to find a safe, reliable, and inexpensive way to incise the pyloric serosa before spreading the muscle. The most widely accepted method of cutting the serosa is with electrocautery, although some still question its safety. We introduce a novel technique of incising the serosa with a percutaneously inserted needle without the use of electrocautery.

Conditional deletion of ELL2 induces murine prostate intraepithelial neoplasia.

Elongation factor, RNA polymerase II, 2 (ELL2) is an RNA Pol II elongation factor with functional properties similar to ELL that can interact with the prostate tumor suppressor EAF2. In the prostate, is an androgen response gene that is upregulated in benign prostatic hyperplasia (BPH). We recently showed that ELL2 loss could enhance prostate cancer cell proliferation and migration, and that gene expression was downregulated in high Gleason score prostate cancer specimens.

Cancer metastasis: issues and challenges.

Metastasis is the major cause of treatment failure in cancer patients and of cancer-related deaths. This editorial discusses how cancer metastasis may be better perceived and controlled. Based on big-data analyses, a collection of 150 important pro-metastatic genes was studied.

Negative effects of retinoic acid on stem cell niche of mouse incisor.

The continuous growth of mouse incisors depends on epithelial stem cells (SCs) residing in the SC niche, called labial cervical loop (LaCL). The homeostasis of the SCs is subtly regulated by complex signaling networks. In this study, we focus on retinoic acid (RA), a derivative of Vitamin A and a known pivotal signaling molecule in controlling the functions of stem cells (SCs).

Inflammatory regulatory T cells in the microenvironments of ulcerative colitis and colon carcinoma.

Foxp3(+)CD4(+) regulatory T (Treg) cells are thought to express negligible levels of effector cytokines, and inhibit immune responses and inflammation. Here, we have identified a population of IL-8(+)Foxp3(+)CD4(+) T cells in human peripheral blood, which is selectively increased in the microenvironments of ulcerative colitis and colon carcinoma. Phenotypically, this population is minimally overlapping with IL-17(+)Foxp3(+)CD4(+) T cells, and is different from IL-8(-)Foxp3(+)CD4(+) T cells in the same microenvironment.

Expression profiles of retinoic acid synthetases ALDH1As and metabolic enzymes CYP26s in adult and embryonic zebrafish (Danio rerio).

Retinoic acid (RA) plays a crucial role in cellular proliferation, differentiation, and apoptosis. The physiological activity of RA begins early in development and continues throughout an organism's life. RA distribution is tightly controlled by the RA synthetases ALDH1As and the metabolic enzymes CYP26s.

Associations of depression with impaired glucose regulation, newly diagnosed diabetes and previously diagnosed diabetes in Chinese adults.

Aim: To examine the association between depression and impaired glucose regulation, newly diagnosed diabetes and previously diagnosed diabetes in middle-aged and elderly Chinese people, and whether depression was associated with different treatment regimens or durations of diabetes.

Methods: A cross-sectional study was performed among 229,047 adults living in the community aged ≥ 40 years from 25 centres in China. The self-reported depression rating scale Patient Health Questionnaire 9 (PHQ-9) was used to diagnose probable and sub-threshold depression.

Curative effect of combined lamivudine, adefovir dipivoxil, and stem cell transplantation on decompensated hepatitis B cirrhosis.

This study assessed the clinical efficacy of lamivudine and adefovir dipivoxil combined with autologous bone marrow stem cell transplantation as treatment for patients with hepatitis B and decompensated liver cirrhosis. In total, 77 patients with hepatitis B and decompensated liver cirrhosis were randomly divided into two groups. Under general symptomatic and supportive treatment, the patients in group A (37 cases) were treated with lamivudine and adefovir dipivoxil, whereas those in group B (40 cases) were treated with autologous bone marrow stem cell transplantation in combination with lamivudine and adefovir dipivoxil.

The relationship between insulin-sensitive obesity and cardiovascular diseases in a Chinese population: results of the REACTION study.

Objective: Obesity and insulin resistance are risk factors for cardiovascular diseases. Whether insulin-sensitive obese individuals are at higher risk for cardiovascular diseases is still debated. We aim to investigate whether insulin-sensitive obesity associates with prevalent cardiovascular diseases and 10-year coronary heart disease (CHD) risk.

High frequency of suboptimal serum vitamin B12 level in adults in Jordan.

Objective: To assess the prevalence of functional vitamin B12 deficiency status in an adult Jordanian seemingly healthy population.

Methods: We carried out this study in the Department of Physiology, Faculty of Medicine, Jordanian University of Science and Technology, Jordan from September 2004 to January 2005. We included a randomly selected sample of 216 healthy adult volunteers (male 124, female 92, aged 19-50 years) from north Jordan.