Angiotensin-converting enzyme 2 is an essential regulator of heart function

Ace2 maps to a defined quantitative trait locus (QTL) on the X chromosome in three different rat models of hypertension. In all hypertensive rat strains, ACE2 mRNA and protein expression were markedly reduced, suggesting that ace2 is a candidate gene for this QTL. Targeted disruption of ACE2 in mice results in a severe cardiac contractility defect, increased angiotensin II levels, and upregulation of hypoxia-induced genes in the heart. These genetic data for ACE2 show that it is an essential regulator of heart function in vivo.

On the TRAIL to apoptosis

Apoptosis in mammalian cells can be initiated through two major interrelated pathways, one involving engagement of the TNF family of death receptors, the other involving the release of cytochrome c from mitochondria. Unlike other members of the TNF ligand family, TNF-related apoptosis-inducing ligand (TRAIL) preferentially induces apoptosis in tumor cell lines, but not in normal cells, suggesting that TRAIL could potentially represent a powerful cancer therapeutic.

Novel synthetic amino acid copolymers that inhibit autoantigen-specific T cell responses and suppress experimental autoimmune encephalomyelitis

Poly (Y, F, A, K) (YFAK) inhibited binding of the biotinylated MBP 86-100 epitope to HLA-DR2 molecules more efficiently than did either unlabeled MBP 85-99 or any other copolymer. Most importantly, these novel copolymers suppressed experimental autoimmune encephalomyelitis.

Targeted adenoviral gene transfer to the kidney

In vivo administration of the chimeric adenoviral vector into the renal artery of the rat resulted in significantly enhanced β-galactosidase expression in the vascular endothelium of the kidney compared with an adenoviral vector containing the native adenoviral fiber protein (AdZ).

Calcium signaling: A tale for all seasons

The rapid advancement of the Calcuim signal field has now swollen the literature to a size where it would be impossible to cover all of it in a few pages. Because a number of comprehensive reviews are available, this contribution will focus only on the most significant recent advances.

A vaccine against atherosclerosis

The development of a vaccine to prevent the build-up of atherosclerotic plaque has come a step closer. Researchers at the Cedars-Sinai Medical Center (Los Angeles, CA, USA) and Lund University (Malmo, Sweden) have tested a peptidebased vaccine that reduces arterial plaque formation in mice by up to 70%.

Nonremodeling Properties of Matrix Metalloproteinases

Recently, a number of contributions have shown that in addition to chronic remodeling reactions, MMPs(Matrix Metalloproteinases) are involved in acute biological reactions associated with discrete cell signaling such as regulation of vascular reactivity,leukocyte activation,and platelet function.

Young Adult Bone Marrow–Derived Endothelial Precursor Cells Restore Aging-Impaired Cardiac Angiogenic Function

Delivery of young bone marrow–derived stem cells offers a novel approach for restoring the impaired senescent cardiac angiogenic function that may underlie the increased morbidity and mortality associated with ischemic heart disease in older individuals.

New Treatments for COPD

Chronic Obstructive Pulmonary Disease (COPD),is one of the most common diseases in the world, and there is a global increase in prevalence.A better understanding of the cellular and molecular mechanisms that are involved in the underlying inflammatory and destructive processes has revealed several new targets for which drugs are now in development, and the prospects for finding new treatments are good.

The impact of pharmacogenetics and pharmacogenomics on drug discovery

The implementation of molecular genetics and biology will provide us with better ways to treat illnesses, and has already begun to do so in an incremental and evolutionary fashion.Advances are most likely to be made in the area of pharmacodynamics, as we learn to differentiate broader conventional clinical diagnoses into separate molecular subtypes.

Gene Therapy to Protect Haematopoietic Cell From Cytotoxic Cancer Drugs

Several gene-therapy vectors have been developed with the aim of expressing drug-resistance genes specifically in bonemarrow stem cells, so protecting them from chemotherapeutics. The feasibility of this approach has been established in animal model systems, and recent advances in the design of genetherapy vectors offer promise for future clinical applications.

Cardiomyocyte Cell Cycle Regulation

Although rapid progress is being made in many areas of molecular cardiology, issues pertaining to the origins of heart-forming cells, the mechanisms responsible for cardiogenic induction, and the pathways that regulate cardiomyocyte proliferation during embryonic and adult life remain unanswered.

Functional Significance of Prorenin Internalization in the Rat Heart

One mechanism of internalization recently described involves the mannose-6-phosphate receptor and requires glycosylation of renin. Based on previous observations, we considered the existence of another pathway of uptake, not requiring glycosylation and predominantly involving prorenin.

G Protein Pathways

The heterotrimeric guanine nucleotide–binding proteins (G proteins) are signal transducers that communicate signals from many hormones, neurotransmitters, chemokines, and autocrine and paracrine factors. The extracellular signals are received by members of a large superfamily of receptors with seven membrane-spanning regions that activate the G proteins, which route the signals to several distinct intracellular signaling pathways.

Encoding Microcarriers: Present and Future Technologies

In answer to the ever-increasing need to carry out many assays simultaneously in drug screening and drug discovery, several microcarrier-based multiplex technologies have arisen in the past fewyears.In this article, the methods that have been developed for the encoding of microcarriers are reviewed and discussed.

Angiogenesis Modulation in Cancer Research:Novel Clinic Approaches

The modulation of tumour angiogenesis using novel agents has become a highly active area of investigation in cancer research, from the bench to the clinic.Here, we discuss methods for monitoring the biological activity of angiogenic modulators, and innovative approaches to trial design that might facilitate the integration of these agents into anticancer therapy.

PI 3-Kinases and PTEN: How Opposites Chemoattract

Phosphatidylinositol lipids, such as PI(4,5)P2 and PI(3,4,5)P3, are key mediators in diverse intracellular signaling pathways. Two recent reports examine how the metabolism of these lipids by phosphatidylinositol 3-kinases and the PTEN 3-phosphoinositide phosphase may coordinate G protein coupled signaling pathways during eukaryotic chemotaxis.

T Lymphocytes in Atherosclerosis

The presence of activated T lymphocytes in all stages of human atherosclerotic lesion development implies their involvement in this vascular disease process. However, the specific role T lymphocytes play in atherogenesis remains unclear.

New vaccine development

This review describes recent developments in the basic science underpinning the development of new vaccines and summarises the potential of the vaccines to treat and prevent a wide range of infectious and non-infectious diseases.

Specialized DNA Polymerases, Cellular Survival,and the Genesis of Mutations

Cell death caused by arrested replication of damaged or structurally altered DNA can be avoided in prokaryotic and eukaryotic cells by multiple DNA polymerases that are specialized to bypass DNA damage. The low fidelity of some of these specialized polymerases when copying undamaged DNA may be physiologically functional, including generating immunoglobulin diversity.

At the Center of Eukaryotic Life

The ribosomal RNA genes encode the enzymatic scafold of the ribosome and thereby perform perhaps the most basic of all housekeeping functions. However,recent data suggests that they might also control important aspects of cell behavior.

Comparative assessment of large-scale data sets of protein–protein interactions

Recently, large-scale approaches have predicted many new protein interactions in yeast. To measure their accuracy and potential as well as to identify biases, strengths and weaknesses, we compare the methods with each other and with a reference set of previously reported protein interactions.

Combinatorial Synthesis of Genetic Networks

Creation and analysis of synthetic networks, composed of well-characterized genetic elements, provide a framework for theoretical modeling. Here, with the use of a combinatorial method, a library of networks with varying connectivity was generated in E. coli.

T-cell antigen receptor signal transduction

T-cell activation by foreign antigen induces antigen specific T-cell clonal expansion and differentiation and this response is regulated by signal transduction pathways initiated by antigen receptors and costimulatory molecules.This review will cover recent progress from biochemistry, genetics and cell biology towards understanding the signal transduction pathways that control T-cell activation.

Coronary Anomalies: Incidence, Pathophysiology, and Clinical Relevance

Although the medical community and general public are increasingly aware that coronary anomalies can be fatal (typically in young, previously “healthy” athletes), the reasons for the sudden fatal event and the frequency with which it occurs are generally unclear. To promote a less casual approach to this subject, we review some basic, substantive, and methodological questions about coronary anomalies.

Lipases and HDL metabolism

HDL metabolism is recognized as a potential target for therapeutic intervention of atherosclerotic vascular diseases. Here,we focus on new developments and insights into the role of secreted lipases on HDL metabolism and their relationship to atherosclerosis.

Centrosomes and cancer: lessons from a TACC

The recent discovery that many cancer cells have centrosomal abnormalities suggests a link between centrosomes and cancer. Members of the transforming acidic coiled-coil (TACC) family of proteins have been implicated in cancer and are concentrated at centrosomes, where they regulate microtubule stability.

Molecules in focus: Clusterin

Clusterin is an enigmatic glycoprotein with a nearly ubiquitous tissue distribution and an apparent involvement in biological processes ranging from mammary gland involution to neurodegeneration in Alzheimer’s disease.

Translational Control of the Embryonic Cell Cycle

The synthesis and destruction of cyclin B drives mitosis in eukaryotic cells. Cell cycle progression is also regulated at the level of cyclin B translation.Observations suggest that regulated cyclin B1 mRNA translation is essential for the embryonic cell cycle.

Views of Transcription Initiation

Initiation of transcription is the first step in gene expression and a major point of regulation. Recent structure studies reveal the nature of the initiating complex and suggest new ways of accomplishing the processes required for initiation.