Crystal Structure of the Human Cannabinoid Receptor CB2.

The cannabinoid receptor CB2 is predominately expressed in the immune system, and selective modulation of CB2 without the psychoactivity of CB1 has therapeutic potential in inflammatory, fibrotic, and neurodegenerative diseases. Here, we report the crystal structure of human CB2 in complex with a rationally designed antagonist, AM10257, at 2.8 Å resolution.

Cancer3D 2.0: interactive analysis of 3D patterns of cancer mutations in cancer subsets.

Our knowledge of cancer genomics exploded in last several years, providing us with detailed knowledge of genetic alterations in almost all cancer types. Analysis of this data gave us new insights into molecular aspects of cancer, most important being the amazing diversity of molecular abnormalities in individual cancers. The most important question in cancer research today is how to classify this diversity to identify subtypes that are most relevant for treatment and outcome prediction for individual patients.

Transesophageal Echocardiography Diagnosis of Tricuspid Valve Injury During AngioVac Percutaneous Pulmonary Embolectomy.

• Imaging evidence of right ventricular dysfunction predicts risk in pulmonary embolism. • Catheter techniques are an alternative to systemic lysis or surgical embolectomy. • Catheter embolectomy may be enhanced by transesophageal echocardiographic imaging.

Cocaine reward is reduced by decreased expression of receptor-type protein tyrosine phosphatase D (PTPRD) and by a novel PTPRD antagonist.

Receptor-type protein tyrosine phosphatase D (PTPRD) is a neuronal cell-adhesion molecule/synaptic specifier that has been implicated in addiction vulnerability and stimulant reward by human genomewide association and mouse cocaine-conditioned place-preference data. However, there have been no reports of effects of reduced expression on cocaine self-administration. There have been no reports of PTPRD targeting by any small molecule.

The cost-effectiveness of alternative vision screening models among preschool children in rural China.

Purpose: To explore the accuracy and cost-effectiveness of three vision screening models among preschool children in rural China.

Methods: Vision screening was carried out among children aged 4-5 years in 65 preschools in two counties in Northwest China, using Crowded Single Lea Symbols to test visual acuity. Children were assigned randomly by school to one of three screening models: screening by teachers (15 schools, 1835 children), local optometrists (30 schools, 1718 children) or volunteers (20 schools, 2183 children).

Identification of discrete, intermingled hypocretin neuronal populations.

Neurons in the lateral hypothalamic area that express hypocretin (Hcrt) neuropeptides help regulate many behaviors including wakefulness and reward seeking. These neurons project throughout the brain, including to neural populations that regulate wakefulness, such as the locus coeruleus (LC) and tuberomammilary nucleus (TMN), as well as to populations that regulate reward, such as the nucleus accumbens (NAc) and ventral tegmental area (VTA). To address the roles of Hcrt neurons in seemingly disparate behaviors, it has been proposed that Hcrt neurons can be anatomically subdivided into at least two distinct subpopulations: a "medial group" that projects to the LC and TMN, and a "lateral group" that projects to the NAc and VTA.

Genome-wide survey of remote homologues for protein domain superfamilies of known structure reveals unequal distribution across structural classes.

Domains are the basic building blocks of proteins which can combine to give rise to different domain architectures. Annotation of domains in a sequence is the first step towards understanding the biological function. Since there are a limited number of folds and evolutionarily related proteins have a similar structure, function can be inferred through remote homology.

Cultural affordance, social relationships, and narratives of independence: Understanding the meaning of social care for adults with intellectual disabilities from minority ethnic groups in the UK.

To explore the perspective of adults with intellectual disabilities from minority ethnic groups, on their relationship with social care services. Thirty-two adults took part in semi-structured interviews. Transcripts were analyzed within a Pluralist framework, adopting the structure of Template Analysis and then drawing on phenomenological, narrative, and discursive approaches.

Analysis of the androgen receptor-regulated lncRNA landscape identifies a role for ARLNC1 in prostate cancer progression.

The androgen receptor (AR) plays a critical role in the development of the normal prostate as well as prostate cancer. Using an integrative transcriptomic analysis of prostate cancer cell lines and tissues, we identified ARLNC1 (AR-regulated long noncoding RNA 1) as an important long noncoding RNA that is strongly associated with AR signaling in prostate cancer progression. Not only was ARLNC1 induced by the AR protein, but ARLNC1 stabilized the AR transcript via RNA-RNA interaction.

Effect of a Local Vision Care Center on Eyeglasses Use and School Performance in Rural China: A Cluster Randomized Clinical Trial.

Importance: Visual impairment is common among children in rural China, but fewer than one-third of children with poor vision own and wear eyeglasses.

Objective: To study the effect of hospital-based vision centers on academic performance, ownership of eyeglasses, and eyeglasses-wearing behavior in rural Chinese children.

Design, Setting, And Participants: Cluster randomized, investigator-masked, clinical trial from September 2014 through June 2015.

Synthesis of C -labeled, dual-target inhibitor of cannabinoid-1 receptor (CB R) and inducible nitric oxide synthase (iNOS).

Cannabinoid-1 receptor (CB R) antagonists/inverse agonists have great potential in the treatment of metabolic disorders like dyslipidemia, type 2 diabetes, and nonalcoholic steatohepatitis. Cannabinoid-1 receptor inverse agonists have also been reported to be effective in mitigating fibrotic disorders in murine models. Inducible nitric oxide synthase is another promising target implicated in fibrotic and inflammatory disorders.

Health Seeking Behavior among Rural Left-Behind Children: Evidence from Shaanxi and Gansu Provinces in China.

More than 60 million children in rural China are “left-behind”—both parents live and work far from their rural homes and leave their children behind. This paper explores differences in how left-behind and non-left-behind children seek health remediation in China’s vast but understudied rural areas. This study examines this question in the context of a program to provide vision health care to myopic rural students.

Higher Mallampati Scores Are Not Associated with More Adverse Events During Pediatric Procedural Sedation and Analgesia.

Introduction: Procedural sedation and analgesia (PSA) is used by non-anesthesiologists (NAs) outside of the operating room for several types of procedures. Adverse events during pediatric PSA that pose the most risk to patient safety involve airway compromise. Higher Mallampati scores may indirectly indicate children at risk for airway compromise.

Tet2 Rescues Age-Related Regenerative Decline and Enhances Cognitive Function in the Adult Mouse Brain.

Restoring adult stem cell function provides an exciting approach for rejuvenating the aging brain. However, molecular mechanisms mediating neurogenic rejuvenation remain elusive. Here we report that the enzyme ten eleven translocation methylcytosine dioxygenase 2 (Tet2), which catalyzes the production of 5-hydroxymethylcytosine (5hmC), rescues age-related decline in adult neurogenesis and enhances cognition in mice.

Chiropractic Management Using Multimodal Therapies on 2 Pediatric Patients With Constipation.

Objective: The purpose of this case report is to describe chiropractic management of 7-month-old male twins who had had constipation since birth.

Clinical Features: Identical male twins presented with the chief complaint of constipation and bloating. Both patients were born premature after 29 weeks of gestation and had invasive abdominal surgeries in the right lower quadrant resulting in healed postsurgical scars.

Oncogenic Role of THOR, a Conserved Cancer/Testis Long Non-coding RNA.

Large-scale transcriptome sequencing efforts have vastly expanded the catalog of long non-coding RNAs (lncRNAs) with varying evolutionary conservation, lineage expression, and cancer specificity. Here, we functionally characterize a novel ultraconserved lncRNA, THOR (ENSG00000226856), which exhibits expression exclusively in testis and a broad range of human cancers. THOR knockdown and overexpression in multiple cell lines and animal models alters cell or tumor growth supporting an oncogenic role.

Insulin Access to Skeletal Muscle is Preserved in Obesity Induced by Polyunsaturated Diet.

Objective: Diets high in saturated fat induce obesity and insulin resistance and impair insulin access to skeletal muscle, leading to reduced insulin levels at the muscle cell surface available to bind insulin receptors and induce glucose uptake. In contrast, diets supplemented with polyunsaturated fat improve insulin sensitivity (SI) and reduce the risk for type 2 diabetes. It was hypothesized that a diet high in polyunsaturated fat would preserve SI and insulin access to muscle, as compared with a diet high in saturated fat.

One Ion to Rule Them All: Combined Antibacterial, Osteoinductive and Anticancer Properties of Selenite-Incorporated Hydroxyapatite.

Although hydroxyapatite (HAp) has been doped with dozens of different ions, the quest for an ion imparting a combination of properties conducive to bone healing is still ongoing. Because of its protean potency and the similarity in size and shape to the phosphate tetrahedron, selenite ion presents a natural ionic substitute in HAp. The incorporation of selenite into synthetic HAp using two different methods - co-precipitation and ion-exchange sorption - was studied for its effect on crystal properties and on a triad of biological responses: antibacterial, anticancer and osteoinductive.

Antifungal response of oral-associated candidal reference strains (American Type Culture Collection) by supercritical fluid extract of nutmeg seeds for geriatric denture wearers: An screening study.

Objectives: Since time immemorial, plants have continued to play a predominant role in the maintenance of human health as sources of medicinal compounds. Several effective antifungal agents are available for oral infections; the failure is not uncommon because isolates of may exhibit resistance to the drug during therapy. The present study aimed to identify an alternative, inexpensive, simple, and effective method of preventing and controlling the candidal infection.

Development of Glatopa® (Glatiramer Acetate): The First FDA-Approved Generic Disease-Modifying Therapy for Relapsing Forms of Multiple Sclerosis.

The multiple sclerosis (MS) treatment landscape in the United States has changed dramatically over the past decade. While many disease-modifying therapies (DMTs) have been approved by the US Food and Drug Administration (FDA) for the treatment of relapsing forms of MS, DMT costs continue to rise. The availability of generics and biosimilars in the MS-treatment landscape is unlikely to have a major impact on clinical benefit.

Indirect Regulation of Endogenous Glucose Production by Insulin: The Single Gateway Hypothesis Revisited.

On the basis of studies that investigated the intraportal versus systemic insulin infusion and transendothelial transport of insulin, we proposed the "single gateway hypothesis," which supposes an indirect regulation of hepatic glucose production by insulin; the rate-limiting transport of insulin across the adipose tissue capillaries is responsible for the slow suppression of free fatty acids (FFAs), which in turn is responsible for delayed suppression of hepatic endogenous glucose production (EGP) during insulin infusion. Preventing the fall in plasma FFAs during insulin infusion either by administering intralipids or by inhibiting adipose tissue lipolysis led to failure in EGP suppression, thus supporting our hypothesis. More recently, mice lacking hepatic Foxo1 in addition to Akt1 and Akt2 (L-AktFoxo1TKO), all required for insulin signaling, surprisingly showed normal glycemia.

Synthesis of S-2-((S)-3-(4-chlorophenyl)-N'-((4-chlorophenyl)sulfonyl)-4-phenyl-4,5-dihydro-1H-pyrazole-1-carboximidamido)-3-(methyl-d )butanamide-d , octadeuterated JD5037.

JD5037 (1) is a potent and selective, peripherally acting inverse agonist of the cannabinoid (CB R) receptor. Peripheral CB receptor antagonists/inverse agonists have great potential in the treatment of metabolic disorders like type 2 diabetes, obesity, and nonalcoholic steatohepatitis. We report the synthesis of octadeuterated [ H ]-JD5037 (S, S) (8) along with its (S, R) diastereomer (13) from commercially available L-valine-d starting material.