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1.  Recent advances in understanding Golgi biogenesis 
The Golgi complex is a central processing station for proteins traversing the secretory pathway, yet we are still learning how this compartment is constructed and how cargo moves through it. Recent experiments suggest a key role for Ras-like Rab GTPases and provide important new ideas for how the Golgi may function.
PMCID: PMC2897732  PMID: 20625450
2.  Recent advances in polyubiquitin chain recognition 
F1000 biology reports  2010;2(20):1-5.
Polyubiquitin chains are regulatory signals for a wide array of biological processes. Recent structural studies reveal novel modes of polyubiquitin chain recognition and implicate the diverse repertoire of interactions in providing the specificity of polyubiquitin recognition.
PMCID: PMC2847284  PMID: 20357899
3.  Recent advances in pancreas development: from embryonic pathways to programming renewable sources of beta cells 
F1000 biology reports  2010;2(17):1-4.
In recent years, there has been significant progress in understanding the detailed mechanisms of pancreas development. These studies have in turn influenced research aimed at producing pancreatic islet cells from stem cells. Here, we review recent progress in both of these areas.
PMCID: PMC2863342  PMID: 20445833
4.  RNA pseudoknots: folding and finding 
RNA pseudoknots are important for function. Three-dimensional structural information is available, insights into factors affecting pseudoknot stability are being reported, and computer programs are available for predicting pseudoknots.
PMCID: PMC2873773  PMID: 20495679
5.  Understanding lipid rafts and other related membrane domains 
Evidence in support of the classical lipid raft hypothesis has remained elusive. Data suggests that transmembrane proteins and the actin-containing cortical cytoskeleton can organize lipids into short-lived nanoscale assemblies that can be assembled into larger domains under certain conditions. This supports an evolving view in which interactions between lipids, cholesterol, and proteins create and maintain lateral heterogeneity in the cell membrane.
PMCID: PMC2894464  PMID: 20606718
6.  Mechanisms of growth cone repulsion 
Research conducted in the last century suggested that chemoattractants guide cells or their processes to appropriate locations during development. Today, we know that many of the molecules involved in cellular guidance can act as chemorepellents that prevent migration into inappropriate territories. Here, we review some of the early seminal experiments and our current understanding of the underlying molecular mechanisms.
PMCID: PMC2919842  PMID: 20711492
7.  Antigen presentation to B cells 
B cells are capable of mounting responses to a bewildering range of potentially pathogenic antigens through the production of high-affinity antibodies and the establishment of immunological memory. Thus, regulated B-cell activation is critical for protection against a variety of bacterial and viral infections, as well as cancers. Here, we discuss a number of recent imaging studies that have provided new insights into the variety of mechanisms by which B-cell activation is initiated in the lymph node in vivo.
PMCID: PMC3026618  PMID: 21283653
8.  Closing in on the link between apoptosis and autophagy 
While there is a clear connection between apoptosis and autophagy, the mechanisms that regulate the interaction have been difficult to identify. The initial clue to the link was the observation that Bcl-2 was located at the endoplasmic reticulum (ER), where it could prevent some forms of apoptosis and also bind to the autophagy regulatory protein Beclin-1. However, both of these enigmatic observations have been united with the discovery of the nutrient-deprivation autophagy factor-1 (NAF-1) protein. As an ER-localized protein that enhances the interaction of Bcl-2 and Beclin-1 and that also binds to the pro-apoptotic protein Bik, NAF-1 is perfectly placed to be a central regulator of the switch between autophagy and apoptosis.
PMCID: PMC3026626  PMID: 21283600
9.  Modeling complex neuropsychiatric disease with induced pluripotent stem cells 
The study of neuropsychiatric diseases and the development of effective treatments have been limited by a lack of appropriate models. Induced pluripotent stem cells (iPSCs) represent a potentially limitless supply of patient-specific cells for the study of neuropsychiatric disorders. In this review, we will discuss the potential and limitations of iPSCs for the development of cell-based models of neuropsychiatric diseases and the identification of novel therapeutics.
PMCID: PMC3026614  PMID: 21283649
10.  Coordinating changes in cell adhesion and phenotype during EMT-like processes in cancer 
Understanding the progression of a primary cancer to the metastatic stage has been the focus of extensive research for years. Commonly accepted concepts in this process (i.e., that of genetic instability and loss of normal cellular constraints on growth and motility) are well established. Other important paradigms, such as the necessary change from an epithelial cell phenotype displaying cell-cell adhesions to a singular and motile mesenchymal-like cell phenotype (possibly derived from a stem cell-like cell) via a process similar to epithelial to mesenchymal transition (EMT), are less well understood. In this review we will address studies linking EMT and cancer stem cells during cancer development and observations that are challenging these concepts.
PMCID: PMC3026620  PMID: 21283595
11.  The case for resequencing studies of Arabidopsis thaliana accessions: mining the dark matter of natural genetic variation 
Ultra-high-throughput sequencing (UHTS) techniques are evolving rapidly and may soon become an affordable and routine tool for sequencing plant DNA, even in smaller plant biology labs. Here we review recent insights into intraspecific genome variation gained from UHTS, which offers a glimpse of the rather unexpected levels of structural variability among Arabidopsis thaliana accessions. The challenges that will need to be addressed to efficiently assemble and exploit this information are also discussed.
PMCID: PMC3026625  PMID: 21283599
12.  Creating transplant tolerance by taming adverse intragraft innate immunity 
Certain forms of inflammation of an allograft are highly detrimental to the induction and maintenance of transplant tolerance as they foster stable commitment to graft-destructive, not graft-protective, forms of T-cell immunity. Hence, a reduction in adverse tissue inflammation may prove crucial in facilitating the induction and maintenance of a long-lasting state of transplant tolerance.
PMCID: PMC3026643  PMID: 21283601
13.  Does GSK-3 provide a shortcut for PI3K activation of Wnt signalling? 
Glycogen synthase kinase-3 (GSK-3) is a well-established downstream component of the phosphatidylinositol 3-kinase (PI3K) signalling pathway but is also a key enzyme in negatively regulating the canonical Wnt/β-catenin signalling pathway. Several recent studies argue that PKB (protein kinase B)-mediated inhibition of GSK-3 leads to β-catenin accumulation, but whether cross-talk actually exists between these two pathways is controversial. To elucidate the mechanisms of shared signalling components, further studies taking into account different components of the PI3K signalling pathway and different pools of GSK-3 or β-catenin are required.
PMCID: PMC3026644  PMID: 21283602
14.  The role of microRNAs in acute myeloid leukemia 
MicroRNAs (miRs) are short (18-22 nucleotides) non-coding RNAs that are important in regulating gene expression. MiR expression is deregulated in many types of cancers, including leukemias. In acute myeloid leukemia (AML), the expression of specific miRs has been linked with both prognostically and cytogenetically defined subgroups. Recent studies have shown that deregulation of miR expression is not simply a consequence of AML but a potential contributer to leukemogenesis. This commentary will focus on select findings that describe the different mechanistic roles for miRs in the development of leukemia.
PMCID: PMC2998852  PMID: 21170374
15.  Life and destruction: ubiquitin-mediated proteolysis in aging and longevity 
The ubiquitin/proteasome system (UPS) regulates the turnover of improperly folded and damaged proteins to maintain protein homeostasis (proteostasis), cellular function, and viability. It is commonly thought that an age-related impairment of the UPS affects general proteostasis networks, which causes enhanced protein aggregation and contributes to normal aging. Recent studies identified the existence of ubiquitin-dependent degradation pathways that specifically control lifespan regulators, suggesting additional roles for ubiquitylation in aging and longevity.
PMCID: PMC2998811  PMID: 21151840
16.  Fibrosis: recent advances in myofibroblast biology and new therapeutic perspectives 
The crucial role of the myofibroblast in wound healing and fibrosis development is well established. This review discusses the mechanisms of myofibroblast action and the new findings that may develop into therapeutic strategies during the next few years.
PMCID: PMC2998803  PMID: 21170369
17.  Developments in low-resolution biological X-ray crystallography 
Despite the recent substantial technological developments in X-ray crystallography, solving and refining structures at low resolutions remain substantial challenges. Many macromolecular crystals, especially those of large molecules or multicomponent assemblies, diffract X-rays to resolutions that are worse than 3.5Å. This report summarizes several recent advances aiding low resolution crystallographic work.
PMCID: PMC2998839  PMID: 21170372
18.  Beta cell antigens in type 1 diabetes: triggers in pathogenesis and therapeutic targets 
Recognition of pancreatic beta cell antigens by autoreactive T lymphocytes plays a central role in the pathogenesis of insulin-dependent type 1 diabetes. Recent results suggest that non-conventional antigenic epitope processing and presentation may contribute to triggering and maintaining autoreactive responses. Moreover, promising results raise hope that autoantigens may become safe and specific therapeutics for type 1 diabetes in the future.
PMCID: PMC2981181  PMID: 21173836
19.  Treating aging: progress toward dietary restriction mimetics 
During the last decade, biogerontologists have labored to understand the biological basis of the aging process by studying the genes and signaling pathways that regulate it. But the last year has seen a breakthrough in a different direction: toward treatments that might slow aging by mimicking the effects of dietary restriction.
PMCID: PMC2981192  PMID: 21173839
20.  Role of endoplasmic reticulum domains in determining secretion routes 
Distinct domains of the endoplasmic reticulum (ER) can function as entry points into different protein-sorting routes. In addition to using the classical ER-Golgi pathway, one of these unconventional routes utilizes different combinations of machinery of the classical secretory pathway and components of the autophagosomal system.
PMCID: PMC2981193  PMID: 21173840
21.  New genetic resources for mammalian developmental biologists 
The utilization of homologous recombination in embryonic stem cells as a means to generate mice carrying pre-determined modifications of genomic sequences has revolutionized the study of developmental biology. Recognizing the potential efficiencies that can be obtained by high-throughput production at centralized technology centers, a number of large-scale efforts for generating mice with targeted mutations have been funded. These programs are reaching fruition, and a variety of libraries of embryonic stem cells with defined mutations are now available.
PMCID: PMC2989628  PMID: 21173845
22.  All for one, and one for all: the clonality of the intestinal stem cell niche 
Intestinal epithelia are maintained by intestinal stem cells (ISCs) that divide to replace dying absorptive and secretory cells that make up this tissue. Lineage labeling studies, both in vertebrates and Drosophila, have revealed the relationships between ISCs and their progeny. In addition, a number of signaling pathways involved in ISC proliferation and differentiation have been identified. Further studies will clarify the signals originating from the ISC niche and determine the processes that control the number and uniform distribution of niches throughout the epithelium.
PMCID: PMC2989629  PMID: 21173846
23.  How do RNA sequence, DNA sequence, and chromatin properties regulate splicing? 
Recent genome-wide studies have revealed a remarkable correspondence between nucleosome positions and exon-intron boundaries, and several studies have implicated specific histone modifications in regulating alternative splicing. In addition, recent progress in cracking the ‘splicing code’ shows that sequence motifs carried on the nascent RNA molecule itself are sufficient to accurately predict tissue-specific alternative splicing patterns. Together, these studies shed light on the complex interplay between RNA sequence, DNA sequence, and chromatin properties in regulating splicing.
PMCID: PMC2989630  PMID: 21173847
24.  Hebb and the art of spine remodeling 
The notion that synaptic remodeling underlies certain forms of learning is one of the main tenets of Hebb's inspiring theories dating from the 1940s. Until recently, however, direct evidence for tight relationships between synaptic remodeling and behavior has been scarce. Fascinating data from recent studies on the remodeling of postsynaptic structures known as dendritic spines indicates that such relationships might be more complex than initially expected.
PMCID: PMC2989625  PMID: 21173842
25.  Do PAKs make good drug targets? 
p21-activated kinases (PAKs) act downstream of Rho-family GTPase and are linked to steps in both cancer initiation and progression. There are six mammalian PAK isoforms that are divided into two groups, and for different reasons both groups are attractive targets for cancer therapy. We describe the background and recent development of a PAK inhibitor, PF-3758309, which exhibits relatively good selectivity and high potency for PAKs. Experiments using PF-3758309 confirm that inhibiting PAK is a beneficial strategy to combat some tumors, and this activity is likely related to modulation of both cell proliferation and survival. The genetic loss of NF2 (neurofibromatosis type 2) leading to increased cell proliferation through a Ras-Rac-PAK pathway may represent a good test system to analyze this new PAK inhibitor.
PMCID: PMC2989626  PMID: 21173843

Results 1-25 (97)