Hematopoietic transcription factor mutations and inherited platelet dysfunction.
Authors: Songdej N, Rao AK
Abstract
The molecular and genetic mechanisms in most patients with inherited platelet dysfunction are unknown. There is increasing evidence that mutations in hematopoietic transcription factors are major players in the pathogenesis of defective megakaryopoiesis and platelet dysfunction in patients with inherited platelet disorders. These hematopoietic transcription factors include RUNX1, FLI1, GATA-1, and GFI1B. Mutations involving these transcription factors affect diverse aspects of platelet production and function at the genetic and molecular levels, culminating in clinical m...
Source: F1000 Medicine Reports - June 23, 2015 Category: Biomedical Science Tags: F1000Prime Rep Source Type: research
Plasmodesmata spread their influence.
In this report, I review recent findings that broaden the potential impact of these channels, by revealing their contribution to auxin movement and as potential sites of receptor signaling. These discoveries should prompt a reassessment of symplasmic connectivity and its importance to plant development, defense, and physiology.
PMID: 25926976 [PubMed] (Source: F1000 Medicine Reports)
Source: F1000 Medicine Reports - May 1, 2015 Category: Biomedical Science Tags: F1000Prime Rep Source Type: research
Angiogenesis versus arteriogenesis: neuropilin 1 modulation of VEGF signaling.
Authors: Kofler NM, Simons M
Abstract
In development and disease, vascular endothelial growth factor (VEGF) regulates the expansion of the vascular tree. In response to hypoxia, VEGF promotes new capillary formation through the process of angiogenesis by inducing endothelial cell sprouting, proliferation, and migration. Wound healing, tissue regeneration, and tumor growth depend on angiogenesis for adequate nutrient and oxygen delivery. Under different conditions, VEGF promotes arterial growth, modulates lumen expansion, and induces collateral vessel formation, events collectively referred to as arteriogen...
Source: F1000 Medicine Reports - May 1, 2015 Category: Biomedical Science Tags: F1000Prime Rep Source Type: research
Evolutionary models of in-group favoritism.
Authors: Masuda N, Fu F
Abstract
In-group favoritism is the tendency for individuals to cooperate with in-group members more strongly than with out-group members. Similar concepts have been described across different domains, including in-group bias, tag-based cooperation, parochial altruism, and ethnocentrism. Both humans and other animals show this behavior. Here, we review evolutionary mechanisms for explaining this phenomenon by covering recently developed mathematical models. In fact, in-group favoritism is not easily realized on its own in theory, although it can evolve under some conditions. We also...
Source: F1000 Medicine Reports - May 1, 2015 Category: Biomedical Science Tags: F1000Prime Rep Source Type: research
Recent advances in understanding/management of non-alcoholic steatohepatitis.
Authors: Pacana T, Sanyal AJ
Abstract
Non-alcoholic steatohepatitis (NASH) can lead to advanced fibrosis, hepatocellular carcinoma, and end-stage liver disease requiring liver transplantation. A myriad of pathways and genetic influence contribute to NASH pathogenesis and liver disease progression. Diagnosing patients with NASH and advanced fibrosis is critical prior to treatment and prognostication. There has been ongoing interest in developing non-invasive biomarkers and tools for identifying NASH and advanced fibrosis. To date, there has been no approved therapy for NASH. Recently, the FLINT (Farnesoid X...
Source: F1000 Medicine Reports - May 1, 2015 Category: Biomedical Science Tags: F1000Prime Rep Source Type: research
Duality of lipid mediators in host response against Mycobacterium tuberculosis: good cop, bad cop.
Authors: Dietzold J, Gopalakrishnan A, Salgame P
Abstract
Lipid mediators play an important role in infection- and tissue injury-driven inflammatory responses and in the subsequent inhibition and resolution of the response. Here, we discuss recent findings that substantiate how Mycobacterium tuberculosis promotes its survival in the host by dysregulation of lipid mediator balance. By inhibiting prostaglandin E2 (PGE2) and enhancing lipoxin production, M. tuberculosis induces necrotic death of the macrophage, an environment that favors its growth. These new findings provide opportunities for developing and ...
Source: F1000 Medicine Reports - May 1, 2015 Category: Biomedical Science Tags: F1000Prime Rep Source Type: research
The hunt for origins of DNA replication in multicellular eukaryotes.
Authors: Urban JM, Foulk MS, Casella C, Gerbi SA
Abstract
Origins of DNA replication (ORIs) occur at defined regions in the genome. Although DNA sequence defines the position of ORIs in budding yeast, the factors for ORI specification remain elusive in metazoa. Several methods have been used recently to map ORIs in metazoan genomes with the hope that features for ORI specification might emerge. These methods are reviewed here with analysis of their advantages and shortcomings. The various factors that may influence ORI selection for initiation of DNA replication are discussed.
PMID: 25926981 [PubM...
Source: F1000 Medicine Reports - May 1, 2015 Category: Biomedical Science Tags: F1000Prime Rep Source Type: research
Post-transcriptional regulation of early embryogenesis.
Authors: Weil TT
Abstract
Gene expression is controlled by diverse mechanisms before, during, and after transcription. Chromatin modification factors as well as transcriptional repressors, silencers, and enhancers all feed into how eukaryotes transcribe RNA in the nucleus. However, there is increasing evidence that post-transcriptional regulation of gene expression is as widespread as transcriptional control if not more so. Studies of specific transcripts in oocytes and embryos are at the core of our mechanistic understanding of many post-transcriptional events. Coupled with genome-wide and large-scale exp...
Source: F1000 Medicine Reports - May 1, 2015 Category: Biomedical Science Tags: F1000Prime Rep Source Type: research
Lateral root initiation in Arabidopsis thaliana: a force awakens.
Authors: Vermeer JE, Geldner N
Abstract
Osmotically driven turgor pressure of plant cells can be higher than that of a car tire. It puts tremendous forces onto cell walls and drives cell growth and changes in cell shape. This has given rise to unique mechanisms to control organ formation compared to metazoans. The fascinating interplay between forces and local cellular reorganization is still poorly understood. Growth of lateral roots is a prominent example of a developmental process in which mechanical forces between neighboring cells are generated and must be dealt with. Lateral roots initiate from a sin...
Source: F1000 Medicine Reports - May 1, 2015 Category: Biomedical Science Tags: F1000Prime Rep Source Type: research
Recent advances in managing and understanding menstrual disorders.
Authors: Bahamondes L, Ali M
Abstract
Menstrual disorders are a major reason for gynaecological consultations worldwide and, unfortunately there are many different definitions and classifications of this condition. Clear definitions and terminology are necessary for scientific literature, particularly for clinicians, and for clinical trials comparing two treatments. The International Federation of Gynaecology and Obstetrics (FIGO) Menstrual Disorders Working Group has proposed abandoning the use of one common term, dysfunctional uterine bleeding (DUB), while continuing to use the terms abnormal uterine ble...
Source: F1000 Medicine Reports - May 1, 2015 Category: Biomedical Science Tags: F1000Prime Rep Source Type: research
Drug-induced liver injury: the dawn of biomarkers?
Authors: Weiler S, Merz M, Kullak-Ublick GA
Abstract
Drug-induced liver injury (DILI) is a potentially fatal adverse event with significant medical and economic impact. Many drugs, especially anti-infective, neurologic or pain-modifying substances, act as hepatotoxins. With cardiovascular toxicity, liver toxicity is one of the two leading causes for drug withdrawal from the market. The liver can be affected directly, in a predictable and dose-dependent manner, or idiosyncratically, independent of the dose and therefore unpredictable. Currently DILI is a diagnosis of exclusion that physicians have to bear i...
Source: F1000 Medicine Reports - May 1, 2015 Category: Biomedical Science Tags: F1000Prime Rep Source Type: research
The rapidly changing world of food allergy in children.
In this report, we aim to discuss recent advances in the diagnosis, management, and treatment modalities of food allergy in children.
PMID: 25926986 [PubMed] (Source: F1000 Medicine Reports)
Source: F1000 Medicine Reports - May 1, 2015 Category: Biomedical Science Tags: F1000Prime Rep Source Type: research
Unique among ciliopathies: primary ciliary dyskinesia, a motile cilia disorder.
Authors: Praveen K, Davis EE, Katsanis N
Abstract
Primary ciliary dyskinesia (PCD) is a ciliopathy, but represents the sole entity from this class of disorders that results from the dysfunction of motile cilia. Characterized by respiratory problems appearing in childhood, infertility, and situs defects in ~50% of individuals, PCD has an estimated prevalence of approximately 1 in 10,000 live births. The diagnosis of PCD can be prolonged due to a lack of disease awareness, coupled with the fact that symptoms can be confused with other more common genetic disorders, such as cystic fibrosis, or environmental i...
Source: F1000 Medicine Reports - May 1, 2015 Category: Biomedical Science Tags: F1000Prime Rep Source Type: research
The phosphoinositide 3-kinase pathway and therapy resistance in cancer.
Authors: Brown KK, Toker A
Abstract
The phosphoinositide 3-kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) signaling network is a master regulator of processes that contribute to tumorigenesis and tumor maintenance. The PI3K pathway also plays a critical role in driving resistance to diverse anti-cancer therapies. This review article focuses on mechanisms by which the PI3K pathway contributes to therapy resistance in cancer, and highlights potential combination therapy strategies to circumvent resistance driven by PI3K signaling. In addition, resistance mechanisms that limit the clinical efficacy ...
Source: F1000 Medicine Reports - March 12, 2015 Category: Biomedical Science Tags: F1000Prime Rep Source Type: research
Structure and mechanism of ABC transporters.
Authors: Wilkens S
Abstract
All living organisms depend on primary and secondary membrane transport for the supply of external nutrients and removal or sequestration of unwanted (toxic) compounds. Due to the chemical diversity of cellular molecules, it comes as no surprise that a significant part of the proteome is dedicated to the active transport of cargo across the plasma membrane or the membranes of subcellular organelles. Transport against a chemical gradient can be driven by, for example, the free energy change associated with ATP hydrolysis (primary transport), or facilitated by the potential energy...
Source: F1000 Medicine Reports - March 12, 2015 Category: Biomedical Science Tags: F1000Prime Rep Source Type: research
