| November 30,2002 |
Signaling PAthway Database
(SPAD) - an upcoming online database on signal transduction |
| |
The Signaling PAthway
Database (SPAD) is an integrated database for genetic information
and signal transduction systems created by the Graduate School
of Genetic Resources Technology of the Kyushu University in Japan.
It provides information on interactions between protein and protein,
protein and DNA and information on sequences of DNA proteins.
Information is passed on via clickable signal transduction pathway
maps which are supported by additional text information. |
| November 29,2002 |
Protein Nitration in
Cardiovascular Diseases |
| |
The nitration of protein
tyrosine residues has been used as a footprint for in vivo production
of radical and nonradical reactive species. Tyrosine nitration
may alter protein function and metabolism and therefore, provides
for further dysfunctional changes. This review focuses on an appearance
of tyrosine nitrated proteins in cardiovascular tissues under
different settings of cardiovascular disease. |
| November 28,2002 |
Orchestrating the unfolded
protein response in health and disease |
| |
The ER has evolved highly
specific signaling pathways to ensure that its protein-folding
capacity is not overwhelmed. These pathways are collectively termed
the unfolded protein response (UPR).Here, the author summarize
current discoveries that have offered insights into the complex
regulation of the UPR and its relevance to human physiology and
disease. |
| November 27,2002 |
The Genetics of RNA Silencing |
| |
The underlying mechanisms
in distinct RNA silencing phenomena in different genetic systems
are very similar. There are common RNA intermediates, and similar
genes are required in RNA silencing pathways in protozoa, plants,
fungi, and animals, thus indicating an ancient pathway. This chapter
gives an overview of both biochemical and genetic approaches leading
to the current understanding of the molecular mechanism of RNA
silencing and its probable biological function. |
| November 26,2002 |
Targeted Drug Delivery
via Endocytosis Pathway |
| |
The membrane transferrin
receptor mediated endocytosis or internalization of the complex
of transferrin bound iron and the transferrin receptor is the
major route of cellular iron uptake. This efficient cellular uptake
pathway has been exploited for the site-specific delivery not
only of anticancer drugs and proteins, but also of therapeutic
genes into proliferating malignant cells that overexpress the
transferrin receptors. |
| November 25,2002 |
Computational systems biology |
| |
To understand complex
biological systems requires the integration of experimental and
computational research — in other words a systems biology approach.
Computational biology, through pragmatic modelling and theoretical
exploration, provides a powerful foundation from which to address
critical scientific questions head-on. |
| November 24,2002 |
Apoptosis-inducing factor
(AIF): key to the conserved caspase-independent pathways of cell
death? |
| |
Apoptosis-inducing factor
(AIF), is a phylogenetically old flavoprotein which, in healthy
cells, is confined to the mitochondrial intermembrane space. Upon
lethal signaling, AIF translocates, via the cytosol, to the nucleus
where it binds to DNA and provokes caspaseindependent chromatin
condensation.Recent studies suggest AIF to be a major factor determining
caspase-independent neuronal death, emphasizing the central role
of mitochondria in the control of physiological and pathological
cell demise. |
| November 23,2002 |
Single-neuron mnemonics |
| |
How can you remember what
you’ve just read or seen or done? The issue of short-term memory
has vexed neuroscientists for more than half a century; a new
study adds an unexpected piece to the puzzle. |
| November 22,2002 |
Rules for Making Human
Tumor Cells |
| |
Recent successes in the
experimental transformation of human cells indicate that the disruption
of a limited number of cellular regulatory pathways is sufficient
to impart a tumorigenic phenotype to a wide variety of normal
cells. These results, in turn, suggest a series of genetic and
cellular principles that may govern the formation of most, if
not all, types of human cancers. Rous sarcoma virus to transform
the chicken cells that it infected. |
| November 21,2002 |
Structure and Function
of Natural Killer Cell Receptors :Multiple Molecular Solutions
to Self, Nonself Discrimination |
| |
Considerable progress
has recently been made in our understanding of molecular recognition
by such molecules based on the determination of their three-dimensional
structure, either in isolation or in complex with their MHC-I
ligands. Those best studied are the receptors that are expressed
on natural killer (NK) cells, but others are found on populations
of T cells and other hematopoietic cells. |
| November 20,2002 |
A new generation of HIV
vaccines |
| |
New strategies for vaccine
development have gained momentum over the past decade.These new
vaccines include DNA vaccines and live viral vectors, and have
been based on the generation of high levels of antiviral T cells.
These vaccines do not prevent infection, but rather control virus
replication with a rapid expansion and then contraction of antiviral
T cells in response to the challenge infection. |
| November 19,2002 |
Regulatory Principles
of Developmental Signaling |
| |
We review the mechanisms
by which signaling between cells is regulated so that a cell receives
the right amount of signal, at the right time, to achieve its
intended developmental fate and position.We emphasize the different
regulatory strategies that operate for threshold as opposed to
concentration-dependent (morphogen) signaling. |
| November 18,2002 |
Linkage Analysis in Psychiatric
Disorders: The Emerging Picture |
| |
In this review, the genetic
epidemiology of these behavioral psychiatric disorders is covered
as well as linkage findings on chromosomes 4, 12, 13, 18, 21,
and 22 in bipolar disorder and on chromosomes 1, 6, 8, 10, 13,
15, and 22 in schizophrenia. The sequencing of the human genome
and identification of numerous SNPs should substantially enhance
the ability of investigators to identify disease-causing genes
in these areas of the genome. |
| November 17,2002 |
T Cell Memory |
| |
Typical immune responses
lead to prominent clonal expansion of antigen-specific T and B
cells followed by differentiation into effector cells. Most effector
cells die at the end of the immune response but some of these
cells survive and form long-lived memory cells. The factors controlling
the formation and survival of memory T cells are reviewed. |
| November 16,2002 |
The Language of Genes |
| |
Linguistic metaphors have
been woven into the fabric of molecular biology since its inception.
The determination of the human genome sequence has brought these
metaphors to the forefront of the popular imagination, with the
natural extension of the notion of DNA as language to that of
the genome as the ‘book of life’. |
| November 15,2002 |
Amyloid Precursor Protein,
Presenilins, and α-Synuclein: Molecular Pathogenesis and Pharmacological
Applications in Alzheimer’s Disease |
| |
The autosomal dominant
inherited forms of early-onset Alzheimer’s disease are caused
by mutations in the genes encoding APP, presenilin-1,and presenilin-2.Alzheimer’s
disease and Parkinson’s disease are associated with the cerebral
accumulation of Aβ and α-synuclein, respectively2. This review
covers the trafficking and processing of APP, amyloid cascade
hypothesis in AD pathogenesis, physiological and pathological
roles of presenilins, molecular characteristics of α-synuclein,
their interactions, and therapeutic strategies for AD. |
| November 14,2002 |
A Stem Cell Molecular
Signature |
| |
Mechanisms regulating
self-renewal and cell fate decisions in mammalian stem cells are
poorly understood. We determined global gene expression profiles
for mouse and human hematopoietic stem cells and other stages
of the hematopoietic hierarchy. |
| November 13,2002 |
Regulation of endothelial
cell apoptosis in atherothrombosism |
| |
The present review article
summarizes the current findings and discusses the potential role
of endothelial cell apoptosis for coronary artery disease progression.The
article focuses on the regulation of endothelial cell apoptosis
by the redox balance, which is mainly determined by reactive oxygen
species and activation as well as injury. |
| November 12,2002 |
New genome-wide methods
bring more power to yeast as a model organism |
| |
Recent developments in
genetic research using S. cerevisiaehave provided rapid new methods
for identifying the genes that control cellular responses to treatment
with a wide variety of agents. This increases the power of yeast
as a model system for studying human cellular responses to these
agents, and for identifying human genes that are important in
DNA repair and cancer. |
| November 11,2002 |
Lipoprotein lipase: the
regulation of tissue specific expression and its role in lipid
and energy metabolism |
| |
The aim of this review
is to summarize and discuss recent advances in the understanding
of the physiological role of lipoprotein lipase in lipid and energy
metabolism.Studies on the transcriptional and the posttranscriptional
level of lipoprotein lipase expression have provided new insights
into the complex mechanisms that are involved in the regulation
of the enzyme. |
| November 10,2002 |
Life’s Complexity Pyramid |
| |
Cells and microorganisms
have an impressive capacity for adjusting their intracellular
machinery, and we arrive at a major issue of contemporary cell
biology: our need to comprehend the staggering complexity, versatility,
and robustness of living systems.Viewing the cell as a network
of genes and proteins offers a viable strategy for addressing
the complexity of living systems. |
| November 9,2002 |
Cyclooxygenase-2 and
atherosclerosis |
| |
Cyclooxygenase regulates
the production of eicosanoids, which modulate physiologic processes
in the vessel wall contributing to atherosclerosis and thrombosis,
including platelet aggregation, control of vascular tone, and
the local inflammatory response.Concerns have been raised that
cyclooxygenase-2 inhibitors may increase thrombotic cardiovascular
events by disturbing the balance between platelet thromboxane
A2 and endothelial prostacyclin. |
| November 8,2002 |
Designing Peptide Receptor
Agonists and Antagonists |
| |
A search for systematic
structure-based or ligand-based approaches to designing analogues
that act as agonists and antagonists of the native ligands has
been an important concern. Today, a robust strategy has been developed
for the design of peptides as drugs, drug candidates and biological
tools. This strategy includes structural, conformational, dynamic
and topographical considerations. |
| November 7,2002 |
Innate Immune Recognition |
| |
The innate immune system
is a universal and ancient form of host defense against infection.
Innate immune recognition relies on a limited number of germline-encoded
receptors. Toll-like receptors play a major role in the pathogen
recognition and initiation of inflammatory and immune responses. |
| November 6,2002 |
Molecular Physiology
of P2X Receptors |
| |
P2X receptors are membrane
ion channels that open in response to the binding of extracellular
ATP.P2X receptors are abundantly distributed, and functional responses
are seen in neurons, glia, epithelia, endothelia, bone, muscle,
and hemopoietic tissues. |
| November 5,2002 |
The cellular and molecular
basis of store-operated calcium entry |
| |
The activation of ‘store-operated
channels’ (SOCs) — remains a molecular and mechanistic mystery.
Here we review new insights into the exchange of signals between
the endoplasmic reticulum (ER) and plasma membrane that result
in activation of calcium entry channels mediating crucial long-term
calcium signals. |
| November 4,2002 |
Molecular Mechanisms
For Genomic Disorders |
| |
Genomic rearrangements
play a major role in the pathogenesis of hu-man genetic diseases.
Nonallelic homologous recombination (NAHR) between low-copy repeats
(LCRs) that flank unique genomic segments results in changes of
genome organization and can cause a loss or gain of genomic segments.
These LCRs appear to have arisen recently during primate speciation
via paralogous segmental duplication, thus making the human species
particularly susceptible to genomic rearrangements. Genomic disorders
are defined as a group of diseases that result from genomic rear-rangements,
mostly mediated by NAHR.Molecular investigations of genomic disorders
have revealed genome architectural features associated with susceptibility
to rearrange-ments and the recombination mechanisms responsible
for such rearrangements. |
| November 3,2002 |
Developmental Genomic
Approaches in Model Organisms |
| |
A number of researchers
have begun to apply DNA microarrays and other functional genomics
approaches to study development. Here we review recent studies
that take the first steps toward relating genome-wide information
to developmental events, we discuss recent genomics approaches
taken in animal model systems used to study human disease, and
we outline methods that may be useful for constructing genome-wide
maps of developmental processes. |
| November 2,2002 |
A Cell Biological Perspective
on Alzheimer's Disease |
| |
The amyloid precursor
protein and the proteases cleaving this protein are important
players in the pathogenesis of Alzheimer’s disease via the generation
of the amyloid peptide. We discuss the cell biology behind the
amyloid and tangle hypoth-esis for Alzheimer’s disease, drawing
on the many links to the fields of cell biology and developmental
biology that have been established in the recent years. |
| November 1,2002 |
Membrane Fusion
In Eukaryotic Cells |
| |
Membrane fusion is a fundamental
biochemical reaction and the final step in all vesicular trafficking
events. The purpose of this review is to highlight common features
of different fusion reactions and the concepts that emerged from
them but also to stress the differences and challenge parts of
the current hypotheses. This review covers only the endoplasmic
fusion reactions, i.e., reactions initiated by contacts of membranes
with their cyto-plasmic faces. Ectoplasmic fusion events, which
depend on an initial contact of the fusion partners via the membrane
surfaces exposed to the surrounding medium are not discussed,
nor are topics such as the entry of enveloped viruses, formation
of syncytia, gamete fusion, or vesicle scission (a fusion reaction
that leads to the fission of, e.g., transport vesicles). |
