The role of RNA binding proteins in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the leading causes of overall cancer deaths worldwide with limited therapeutic options. Due to the heterogeneity of HCC pathogenesis, the molecular mechanisms underlying HCC development are not fully understood. Emerging evidence indicates that RNA-binding proteins (RBPs) play a vital role throughout hepatocarcinogenesis.

Hepatic Stellate Cells and Hepatocarcinogenesis.

Hepatic stellate cells (HSCs) are a significant component of the hepatocellular carcinoma (HCC) tumor microenvironment (TME). Activated HSCs transform into myofibroblast-like cells to promote fibrosis in response to liver injury or chronic inflammation, leading to cirrhosis and HCC. The hepatic TME is comprised of cellular components, including activated HSCs, tumor-associated macrophages, endothelial cells, immune cells, and non-cellular components, such as growth factors, proteolytic enzymes and their inhibitors, and other extracellular matrix (ECM) proteins.

AGO2 Mediates mRNA Stability in Hepatocellular Carcinoma.

Deregulated RNA-binding proteins (RBP), such as Argonaute 2 (AGO2), mediate tumor-promoting transcriptomic changes during carcinogenesis, including hepatocellular carcinoma (HCC). While AGO2 is well characterized as a member of the RNA-induced silencing complex (RISC), which represses gene expression through miRNAs, its role as a bona fide RBP remains unclear. In this study, we investigated AGO2's role as an RBP that regulates the transcript to promote HCC.

Collapse of generalized Euler and surface quasigeostrophic point vortices.

Point-vortex models are presented for the generalized Euler equations, which are characterized by a fractional Laplacian relation between the active scalar and the stream function. Special focus is given to the case of the surface quasigeostrophic (SQG) equations, for which the existence of finite-time singularities is still a matter of debate. Point-vortex trajectories are expressed using Nambu dynamics.

Efficacy and safety of epratuzumab in patients with moderate/severe flaring systemic lupus erythematosus: results from two randomized, double-blind, placebo-controlled, multicentre studies (ALLEVIATE) and follow-up.

Objective: To evaluate epratuzumab treatment in patients with moderately-to-severely active SLE in two international, randomized, controlled trials (ALLEVIATE-1 and -2) and an open-label extension study (SL0006).

Methods: Ninety ALLEVIATE patients (43% BILAG A, median BILAG score 12.0) received standard of care plus 10 total doses of placebo (n = 37) or 360 mg/m(2) (n = 42) or 720 mg/m(2) (n = 11) epratuzumab, administered across 12-week cycles for up to 48 weeks, with BILAG assessments every 4 weeks.

Efficacy and safety of epratuzumab in patients with moderate/severe active systemic lupus erythematosus: results from EMBLEM, a phase IIb, randomised, double-blind, placebo-controlled, multicentre study.

Objective: To identify a suitable dosing regimen of the CD22-targeted monoclonal antibody epratuzumab in adults with moderately to severely active systemic lupus erythematosus (SLE).

Methods: A phase IIb, multicentre, randomised controlled study (NCT00624351) was conducted with 227 patients (37-39 per arm) receiving either: placebo, epratuzumab 200 mg cumulative dose (cd) (100 mg every other week (EOW)), 800 mg cd (400 mg EOW), 2400 mg cd (600 mg weekly), 2400 mg cd (1200 mg EOW), or 3600 mg cd (1800 mg EOW). The primary endpoint (not powered for significance) was the week 12 responder rate measured using a novel composite endpoint, the British Isles Lupus Assessment Group (BILAG)-based Combined Lupus Assessment (BICLA).

A showcase of torus canards in neuronal bursters.

Rapid action potential generation - spiking - and alternating intervals of spiking and quiescence - bursting - are two dynamic patterns commonly observed in neuronal activity. In computational models of neuronal systems, the transition from spiking to bursting often exhibits complex bifurcation structure. One type of transition involves the torus canard, which we show arises in a broad array of well-known computational neuronal models with three different classes of bursting dynamics: sub-Hopf/fold cycle bursting, circle/fold cycle bursting, and fold/fold cycle bursting.

Inactivation of Rb in stromal fibroblasts promotes epithelial cell invasion.

Stromal-derived growth factors are required for normal epithelial growth but are also implicated in tumour progression. We have observed inactivation of the retinoblastoma protein (Rb), through phosphorylation, in cancer-associated fibroblasts in oro-pharyngeal cancer specimens. Rb is well known for its cell-autonomous effects on cancer initiation and progression; however, cell non-autonomous functions of Rb are not well described.

An elementary model of torus canards.

We study the recently observed phenomena of torus canards. These are a higher-dimensional generalization of the classical canard orbits familiar from planar systems and arise in fast-slow systems of ordinary differential equations in which the fast subsystem contains a saddle-node bifurcation of limit cycles. Torus canards are trajectories that pass near the saddle-node and subsequently spend long times near a repelling branch of slowly varying limit cycles.

Efficacy of NNRTI-based antiretroviral therapy initiated during acute HIV infection.

Objective: Characterize responses to non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral treatment (ART) initiated during acute HIV infection (AHI).

Design: This was a prospective, single-arm evaluation of once-daily, co-formulated emtricitabine/tenofovir/efavirenz initiated during AHI.

Methods: The primary endpoint is the proportion of responders with HIV RNA less than 200 copies/ml by week 24.

Exposure to indoor biomass fuel pollutants and asthma prevalence in Southeastern Kentucky: results from the Burden of Lung Disease (BOLD) study.

Background: Asthma is a chronic inflammatory respiratory disease, characterized by episodic and reversible airflow obstruction and airway hyperresponsiveness and is influenced by both genetic and environmental factors.

Methods: The Burden of Obstructive Lung Disease (BOLD) survey was used to determine the prevalence of self-reported asthma in a target population of 325,000 adults aged > or =40 in Southeastern Kentucky. Postbronchodilator spirometry was used to classify subjects based on lung function.

SOCS2 can enhance interleukin-2 (IL-2) and IL-3 signaling by accelerating SOCS3 degradation.

Cytokine responses can be regulated by a family of proteins termed suppressors of cytokine signaling (SOCS) which can inhibit the JAK/STAT pathway in a classical negative-feedback manner. While the SOCS are thought to target signaling intermediates for degradation, relatively little is known about how their turnover is regulated. Unlike other SOCS family members, we find that SOCS2 can enhance interleukin-2 (IL-2)- and IL-3-induced STAT phosphorylation following and potentiate proliferation in response to cytokine stimulation.

A retrospective study of standing gastrocnemius-soleus stretching versus night splinting in the treatment of plantar fasciitis.

Plantar fasciitis is the most common cause of heel pain, yet the conservative treatment of plantar fasciitis is not standardized. This open retrospective study compared the effects of standing gastrocnemius-soleus stretching to a prefabricated night splint. One hundred and sixty patients with unilateral or bilateral plantar fasciitis were evaluated and treated according to the standard regimen in addition to either night splints or stretching.