Holding the inflammatory system in check: NLRs keep it cool.
This report aims to review the literature regarding several members of the nucleotide-binding domain, leucine-rich repeat-containing receptor (NLR) family of pattern recognition sensors/receptors that serve as checkpoints for inflammation. Understanding the negative regulation of inflammation is highly relevant to the development of therapeutics for inflammatory as well as infectious diseases.
PMID: 25750733 [PubMed] (Source: F1000 Medicine Reports)
Source: F1000 Medicine Reports - March 12, 2015 Category: Biomedical Science Tags: F1000Prime Rep Source Type: research
Potential mechanisms to explain how LABAs and PDE4 inhibitors enhance the clinical efficacy of glucocorticoids in inflammatory lung diseases.
In this report, we provide a state-of-the-art appraisal, including unresolved and controversial issues, of how cAMP-elevating drugs and inhaled glucocorticoids interact at a molecular level to deliver enhanced anti-inflammatory benefit over inhaled glucocorticoid monotherapy. We also speculate on ways to further exploit this desirable interaction. Critical discussion of how these two drug classes regulate gene transcription, often in a synergistic manner, is a particular focus. Indeed, because interplay between glucocorticoid receptor and cAMP signaling pathways may contribute to the superiority of inhaled glucocorticoid/L...
Source: F1000 Medicine Reports - March 12, 2015 Category: Biomedical Science Tags: F1000Prime Rep Source Type: research
Solving the puzzle of autoimmunity: critical questions.
Authors: Smilek DE, St Clair EW
Abstract
Despite recent advances in delineating the pathogenic mechanisms of autoimmune disease, the puzzle that reveals the true picture of these diverse immunological disorders is yet to be solved. We know that the human leukocyte antigen (HLA) loci as well as many different genetic susceptibility loci with relatively small effect sizes predispose to various autoimmune diseases and that environmental factors are involved in triggering disease. Models for mechanisms of disease become increasingly complex as relationships between components of both the adaptive and innate im...
Source: F1000 Medicine Reports - March 12, 2015 Category: Biomedical Science Tags: F1000Prime Rep Source Type: research
Autophagy in cancer.
Authors: Zhi X, Zhong Q
Abstract
Autophagy is a catabolic degradation process in which cellular proteins and organelles are engulfed by double-membrane autophagosomes and degraded in lysosomes. Autophagy has emerged as a critical pathway in tumor development and cancer therapy, although its precise function remains a conundrum. The current consensus is that autophagy has a dual role in cancer. On the one hand, autophagy functions as a tumor suppressor mechanism by preventing the accumulation of damaged organelles and aggregated proteins. On the other hand, autophagy is a key cell survival mechanism for est...
Source: F1000 Medicine Reports - March 12, 2015 Category: Biomedical Science Tags: F1000Prime Rep Source Type: research
New tangles in the auxin signaling web.
Authors: Wright RC, Nemhauser JL
Abstract
Plants use auxin to relay critical information that shapes their growth and development. Auxin perception and transcriptional activation are mediated by the degradation of Aux/IAA repressor proteins. Degradation of Aux/IAAs relieves repression on Auxin Response Factors (ARFs), which bind DNA sequences called Auxin Response Elements (AuxREs). In most higher plant genomes, multiple paralogs exist for each part of the auxin nuclear signaling pathway. This potential combinatorial diversity in signaling pathways likely contributes to the myriad of context-specific respo...
Source: F1000 Medicine Reports - March 12, 2015 Category: Biomedical Science Tags: F1000Prime Rep Source Type: research
Sublingual thyroid ectopy: similarities and differences with Kallmann syndrome.
Authors: Van Vliet G, Deladoëy J
Abstract
Permanent primary congenital hypothyroidism (CH), the commonest cause of preventable intellectual disability, is due to defects in the embryonic development of the thyroid in the vast majority of cases. These defects are collectively called thyroid dysgenesis. The thyroid may be absent (athyreosis) but, more commonly, a sublingual thyroid ectopy without lateral lobes, is the only thyroid tissue present. Such an ectopy presumably results from an arrest in the downward migration of the median anlage. Thyroid ectopy almost always occurs in a sporadic fashion. However...
Source: F1000 Medicine Reports - March 12, 2015 Category: Biomedical Science Tags: F1000Prime Rep Source Type: research
Empiric/pre-emptive anti-Candida therapy in non-neutropenic ICU patients.
Authors: Timsit JF, Chemam S, Bailly S
Abstract
The potential of the systemic antifungal treatment of non-immunocompromised patients with sepsis, extra-digestive Candida colonization and multiple organ failure is unknown, although it represents three out of four antifungal treatments prescribed in intensive care units. It may allow an early treatment of invasive fungal infection at incubation phase, but exposes patients to unnecessary antifungal treatments with subsequent costs and antifungal selection pressure. As early diagnostic tests for invasive candidiasis are still considered insufficient, the poten...
Source: F1000 Medicine Reports - March 12, 2015 Category: Biomedical Science Tags: F1000Prime Rep Source Type: research
Treatment of distant metastases from follicular cell-derived thyroid cancer.
Authors: Schlumberger M, Leboulleux S
Abstract
Distant metastases from thyroid cancer of follicular origin are uncommon. Treatment includes levothyroxine administration at suppressive doses, focal treatment modalities with surgery, external radiation therapy and thermal ablation, and radioiodine in patients with uptake of (131)I in their metastases. Two thirds of distant metastases will become refractory to radioiodine at some point, and when there is a significant tumor burden and documented progression on imaging, a treatment with a kinase inhibitor may provide benefits.
PMID: 25750740 [PubMed] ...
Source: F1000 Medicine Reports - March 12, 2015 Category: Biomedical Science Tags: F1000Prime Rep Source Type: research
Root hair growth: it's a one way street.
Authors: Mendrinna A, Persson S
Abstract
Over the last few decades, our understanding of directed cell growth in different organisms has substantially improved. Tip-growing cells in plants elongate rapidly via targeted deposition of cell wall and membrane material at the cell apex, and use turgor pressure as a driving force for expansion. This type of polar growth requires a high degree of coordination between a plethora of cellular and extracellular components and compounds, including calcium dynamics, apoplastic reactive oxygen species and pH, the cytoskeleton, and vesicular trafficking. In this review, ...
Source: F1000 Medicine Reports - March 12, 2015 Category: Biomedical Science Tags: F1000Prime Rep Source Type: research
Recent advances in the diagnosis and management of pre-eclampsia.
This article summarizes new developments in diagnosis with a focus on angiogenic biomarkers for prediction of disease onset, and recent advances in management strategies for patients with pre-eclampsia.
PMID: 25750742 [PubMed] (Source: F1000 Medicine Reports)
Source: F1000 Medicine Reports - March 12, 2015 Category: Biomedical Science Tags: F1000Prime Rep Source Type: research
H2A.Z: a molecular rheostat for transcriptional control.
Authors: Subramanian V, Fields PA, Boyer LA
Abstract
The replacement of nucleosomal H2A with the histone variant H2A.Z is critical for regulating DNA-mediated processes across eukaryotes and for early development of multicellular organisms. How this variant performs these seemingly diverse roles has remained largely enigmatic. Here, we discuss recent mechanistic insights that have begun to reveal how H2A.Z functions as a molecular rheostat for gene control. We focus on specific examples in metazoans as a model for understanding how H2A.Z integrates information from histone post-translational modifications,...
Source: F1000 Medicine Reports - February 25, 2015 Category: Biomedical Science Tags: F1000Prime Rep Source Type: research
Neural crest migration: trailblazing ahead.
Authors: Kulesa PM, McLennan R
Abstract
Embryonic cell migration patterns are amazingly complex in the timing and spatial distribution of cells throughout the vertebrate landscape. However, advances in in vivo visualization, cell interrogation, and computational modeling are extracting critical features that underlie the mechanistic nature of these patterns. The focus of this review highlights recent advances in the study of the highly invasive neural crest cells and their migratory patterns during embryonic development. We discuss these advances within three major themes and include a description of compu...
Source: F1000 Medicine Reports - February 25, 2015 Category: Biomedical Science Tags: F1000Prime Rep Source Type: research
Recent advances in the management of resistant hypertension.
Authors: Manolis AJ, Kallistratos MS, Doumas M, Pagoni S, Poulimenos L
Abstract
And suddenly, following the preliminary results of renal denervation and carotid baroreceptor stimulation, a big interest in resistant hypertension rose, and all interventionists, many of them with no previous experience with hypertension, fell in love with hypertension and especially resistant hypertension. In the European Society of Hypertension/International Society of Hypertension (ESH/ISH) 2014 Joint Hypertension meeting in Athens, there were no more than four to five sessions related to resistant hypertension and renal de...
Source: F1000 Medicine Reports - February 25, 2015 Category: Biomedical Science Tags: F1000Prime Rep Source Type: research
Spinal muscular atrophy: from tissue specificity to therapeutic strategies.
Authors: Iascone DM, Henderson CE, Lee JC
Abstract
Spinal muscular atrophy (SMA) is the most frequent genetic cause of death in infants and toddlers. All cases of spinal muscular atrophy result from reductions in levels of the survival motor neuron (SMN) protein, and so SMN upregulation is a focus of many preclinical and clinical studies. We examine four issues that may be important in planning for therapeutic success. First, neuromuscular phenotypes in the SMNΔ7 mouse model closely match those in human patients but peripheral disease manifestations differ, suggesting that endpoints other than mouse lifes...
Source: F1000 Medicine Reports - February 25, 2015 Category: Biomedical Science Tags: F1000Prime Rep Source Type: research
Managing anxiety associated with neurodegenerative disorders.
Authors: Gomoll BP, Kumar A
Abstract
Anxiety is a common symptom among patients with cognitive impairment. The presence of anxiety is correlated with poorer outcomes; despite this, there is limited research on anxiety related to neurodegenerative disorder. In this article, we discuss the prevalence of anxiety and factors involved in the etiology of anxiety in patients with diagnosed neurodegenerative disorders and related states of cognitive impairment as well as the evidence for currently available methods of evaluating and treating these symptoms. Specific treatments are highlighted in light of current e...
Source: F1000 Medicine Reports - February 25, 2015 Category: Biomedical Science Tags: F1000Prime Rep Source Type: research
