Random-walk enzymes.

Enzymes that rely on random walk to search for substrate targets in a heterogeneously dispersed medium can leave behind complex spatial profiles of their catalyzed conversions. The catalytic signatures of these random-walk enzymes are the result of two coupled stochastic processes: scanning and catalysis. Here we develop analytical models to understand the conversion profiles produced by these enzymes, comparing an intrusive model, in which scanning and catalysis are tightly coupled, against a loosely coupled passive model.

Analysis of knockout mutants reveals non-redundant functions of poly(ADP-ribose)polymerase isoforms in Arabidopsis.

The enzyme poly(ADP-ribose)polymerase (PARP) has a dual function being involved both in the poly(ADP-ribosyl)ation and being a constituent of the NAD(+) salvage pathway. To date most studies, both in plant and non-plant systems, have focused on the signaling role of PARP in poly(ADP-ribosyl)ation rather than any role that can be ascribed to its metabolic function. In order to address this question we here used a combination of expression, transcript and protein localization studies of all three PARP isoforms of Arabidopsis alongside physiological analysis of the corresponding mutants.

Mental Health Screening Among Adolescents and Young Adults in the Emergency Department.

Objective: To determine if a new, non-validated mental health screener can detect the prevalence of alcohol/drug abuse, traumatic exposure, and behavioral symptoms in adolescents and young adults seeking care in a pediatric emergency department (ED) for medical complaints.

Methods: An 11-item mental health screener (Emergency Department Distress Response Screener [ED-DRS] investigator developed) was created. Patients 12 years or older seen for medical complaints were assessed by physicians using the ED-DRS.

Changes in Right Ventricular Function with Exercise in Healthy Subjects: Optimal Parameters and Effects of Gender and Age.

Background: Right ventricular (RV) function augments with exercise, and loss of this adaptive ability often determines symptoms. Reports on exercise-related changes in RV function in healthy subjects are sparse. In this study, healthy volunteers were prospectively recruited, and changes in RV function with exercise were examined, optimal parameters determined, and the effects of gender and age examined.

Are changes in cerebrovascular autoregulation following cardiac arrest associated with neurological outcome? Results of a pilot study.

Purpose: To investigate the association between impaired cerebrovascular autoregulation (CVAR) and outcome in comatose survivors of cardiac arrest.

Methods: The correlation in the time domain between cerebral tissue oxygenation (cStO2) using near infrared spectroscopy (NIRS) and mean arterial pressure was used to determine the tissue oxygenation index (TOx) as a reflection of normal (TOx<0) or impaired (TOx>0) CVAR. Daily measurements (>1h recording time) were performed in the first three days post cardiac arrest.

A comparison of the chemical and liver extract-induced hepatic differentiation of adipose derived stem cells.

Adipose-derived stem cells (ADSCs) have been put forward as promising therapeutics for end-stage liver disease (ESLD). In the present study, we compared the effects of defined chemicals and liver extract on the hepatic differentiation of ADSCs. ADSCs were isolated according to the method described in our previously published study.

TIGIT-positive circulating follicular helper T cells display robust B-cell help functions: potential role in sickle cell alloimmunization.

T follicular helper cells are the main CD4(+) T cells specialized in supporting B-cell responses, but their role in driving transfusion-associated alloimmunization is not fully characterized. Reports of T follicular helper subsets displaying various markers and functional activities underscore the need for better characterization/identification of markers with defined functions. Here we show that a previously unidentified subset of human circulating T follicular helper cells expressing TIGIT, the T-cell immunoreceptor with Ig and immunoreceptor tyrosine-based inhibitory domains, exhibit strong B-cell help functions.

A Ligand-Based Drug Design. Discovery of 4-Trifluoromethyl-7,8-pyranocoumarin as a Selective Inhibitor of Human Cytochrome P450 1A2.

In humans, cytochrome P450 1A2 is the major enzyme metabolizing environmental arylamines or heterocyclic amines into carcinogens. Since evidence shows that planar triangle-shaped molecules are capable of selectively inhibiting P450 1A2, 16 triangular flavone, and coumarin derivatives were designed and synthesized for these studies. Among these compounds, 7,8-furanoflavone time-dependently inhibits P450 1A2 with a K(I) value of 0.

In vitro immunomodulation for enhancing T cell-based diagnosis of Mycobacterium tuberculosis infection.

Interferon-gamma release assays have limited sensitivity for detecting latent tuberculosis infection. In this study, we determine if the addition of immunomodulators to the QuantiFERON-TB Gold In-Tube (QFT-GIT) increased test sensitivity without compromising specificity. We prospectively compared QFT-GIT results with and without incubation with 2 immunomodulators (lipopolysaccharide [LPS] and polyinosine-polycytidylic acid [PolyIC]) in 2 cohorts-113 culture-confirmed tuberculosis (TB) subjects in Hanoi, Vietnam, and 226 documented QFT-GIT-negative, low TB risk health care workers undergoing annual TB screening at a US academic institution.

A Review of the Toxicity of HIV Medications II: Interactions with Drugs and Complementary and Alternative Medicine Products.

For many patients today, HIV has become a chronic disease. For those patients who have access to and adhere to lifelong antiretroviral (ARV) therapy, the potential for drug-drug interactions has become a real and life-threatening concern. It is known that most ARV drug interactions occur through the cytochrome P450 (CYP) pathway.

Management of patients with a failed kidney transplant: Dialysis reinitiation, immunosuppression weaning, and transplantectomy.

The number of patients reinitiating dialysis after a failed transplant increases over time and has more than doubled between the year 1988 and 2010 (an increase from 2463 to 5588). More importantly, patients returning to dialysis have been shown to have a greater than three-fold increase in the annual adjusted mortality rates compared with those with a functioning graft. Continuation of immunosuppression to preserve residual graft function has been implicated to be a contributing factor, seemingly due to immunosuppression-associated cardiovascular and infectious complications and malignancy risk, among others.

Use of cell lines and primary cultures to explore the capacity of rainbow trout to be a host for frog virus 3 (FV3).

The capacity of rainbow trout, Oncorhynchus mykiss, to be a host for frog virus 3 (FV3) was evaluated at the cellular level. Cell cultures from this species were tested for their ability to express FV3 major capsid protein (MCP) gene, to develop cytopathic effect (CPE), and to produce FV3. After FV3 addition, MCP transcripts were detected in six of six cell lines and in primary macrophage cultures.

Nelfinavir, an HIV protease inhibitor, induces apoptosis and cell cycle arrest in human cervical cancer cells via the ROS-dependent mitochondrial pathway.

HIV protease inhibitors (HIV-PIs) are a class of antiretroviral drugs designed to target the viral protease. Strikingly, these drugs have also been reported to possess antitumor effect. In this study, we evaluated the activity of one HIV-PI, Nelfinavir, against human cervical cancer cells.

Kidney retransplantation for BK virus nephropathy with active viremia without allograft nephrectomy.

BK virus nephropathy is an important cause of kidney allograft failure. Retransplantation has been successfully performed for patients with previous allograft loss due to BK virus nephropathy; however, whether allograft nephrectomy and viral clearance are required prior to retransplantation is controversial. Some recent studies have suggested that retransplantion can be successfully achieved without allograft nephrectomy if viremia is cleared prior to retransplant.

Effects of acupuncture on pain and inflammation in pediatric emergency department patients with acute appendicitis: a pilot study.

Objective: Acupuncture has been shown to treat various medical conditions, including acute and chronic pain, and there is limited evidence that acupuncture produces anti-inflammatory effects. This pilot study evaluated the use of acupuncture to treat pain and determine if acupuncture can reduce the inflammatory response in pediatric patients diagnosed with acute appendicitis.

Design: This pilot study used convenience sampling and was conducted in the Pediatric Emergency Department (PED) of an urban tertiary care children's hospital.

An assessment of antenatal care among Syrian refugees in Lebanon.

Background: After more than three years of violence in Syria, Lebanon hosts over one million Syrian refugees creating significant public health concerns. Antenatal care delivery to tens of thousands of pregnant Syrian refugee women is critical to preventing maternal and fetal mortality but is not well characterized given the multiple factors obtaining health data in a displaced population. This study describes antenatal care access, the scope of existing antenatal care, and antenatal and family planning behaviors and practice among pregnant Syrian refugees in various living conditions and multiple geographic areas of Lebanon.

Drosophila muller f elements maintain a distinct set of genomic properties over 40 million years of evolution.

The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D.

Scripps Genome ADVISER: Annotation and Distributed Variant Interpretation SERver.

Interpretation of human genomes is a major challenge. We present the Scripps Genome ADVISER (SG-ADVISER) suite, which aims to fill the gap between data generation and genome interpretation by performing holistic, in-depth, annotations and functional predictions on all variant types and effects. The SG-ADVISER suite includes a de-identification tool, a variant annotation web-server, and a user interface for inheritance and annotation-based filtration.

Targeting specificity of dendritic cells on breast cancer stem cells: in vitro and in vivo evaluations.

Breast cancer is a leading cause of death in women, and almost all complications are due to chemotherapy resistance. Drug-resistant cells with stem cell phenotypes are thought to cause failure in breast cancer chemotherapy. Dendritic cell (DC) therapy is a potential approach to eradicate these cells.

Overlapping hotspots in CDRs are critical sites for V region diversification.

Activation-induced deaminase (AID) mediates the somatic hypermutation (SHM) of Ig variable (V) regions that is required for the affinity maturation of the antibody response. An intensive analysis of a published database of somatic hypermutations that arose in the IGHV3-23*01 human V region expressed in vivo by human memory B cells revealed that the focus of mutations in complementary determining region (CDR)1 and CDR2 coincided with a combination of overlapping AGCT hotspots, the absence of AID cold spots, and an abundance of polymerase eta hotspots. If the overlapping hotspots in the CDR1 or CDR2 did not undergo mutation, the frequency of mutations throughout the V region was reduced.

Symptom-driven idiopathic disease gene identification.

Purpose: Rare genetic variants are the major cause of Mendelian disorders, yet only half of described genetic diseases have been causally linked to a gene. In addition, the total number of rare genetic diseases is projected to be far greater than that of those already described. Whole-genome sequencing of patients with subsequent genetic and functional analysis is a powerful way to describe these gene anomalies.

Modular architecture of a multi-frequency electrical impedance tomography system: design and implementation.

Electrical impedance tomography (EIT) provides means of imaging the electrical properties distribution of biological tissues and fluids while impedance spectroscopy (IS) allows measuring their frequency response in a more global way. Both require precise and well-integrated instrumentation. In this work, we propose a modular architecture of a multi-frequency EIT (MfEIT) system which has capabilities in implementing both IS and MfEIT.

Senescence-associated β-galactosidase staining in fish cell lines and primary cultures from several tissues and species, including rainbow trout coelomic fluid and milt.

Cell lines and primary cultures from several teleost tissues and species were stained for senescence-associated β-galactosidase (SA β-Gal), revealing four general outcomes. (1) For long-standing fish cell lines that can be considered immortal, little or no SA β-Gal staining was observed, regardless of the culture conditions. (2) For a new walleye cell line from the bulbus arteriosus (WEBA), most cells stained for SA β-Gal even after 40 passages.

Ceo₂ Based Catalysts for the Treatment of Propylene in Motorcycle's Exhaust Gases.

In this work, the catalytic activities of several single metallic oxides were studied for the treatment of propylene, a component in motorcycles' exhaust gases, under oxygen deficient conditions. Amongst them, CeO₂ is one of the materials that exhibit the highest activity for the oxidation of C₃H₆. Therefore, several mixtures of CeO₂ with other oxides (SnO₂, ZrO₂, Co₃O₄) were tested to investigate the changes in catalytic activity (both propylene conversion and CO₂ selectivity).