Role and origin of the centriole]

The centriole could constitute a system of inertia in the cell, providing the system of references controlling the movement of the cell. It would ensure equally the coherence of cell metabolism and its stability. The origin and functioning of the centriole would be linked to a singel physical phenomenon.     

Expanding the roles of chromatin insulators in nuclear architecture,chromatin organization and genome function

Of the numerous classes of elements involved in modulating eukaryotic chromosome structure and function, chromatin insulators arguably remain the most poorly understood in their contribution to these processes in vivo. Indeed, our view of chromatin insulators has evolved dramatically since their chromatin boundary and enhancer blocking properties were elucidated roughly a quarter of a century ago as a result of recent genome-wide, high-throughput methods better suited to probing the role of these elements in their native genomic contexts. The overall theme that has emerged from these studies is that chromatin insulators function as general facilitators of higher-order chromatin loop structures that exert both physical and functional constraints on the genome. In this review, we summarize the result of recent work that supports this idea as well as a number of other studies linking these elements to a diverse array of nuclear processes, suggesting that chromatin insulators exert master control over genome organization and behavior.     

Heavy and light roles: myosin in the morphogenesis of the heart

Myosin is an essential component of cardiac muscle, from the onset of cardiogenesis through to the adult heart. Although traditionally known for its role in energy transduction and force development, recent studies suggest that both myosin heavy-chain and myosin light-chain proteins are required for a correctly formed heart. Myosins are structural proteins that are not only expressed from early stages of heart development, but when mutated in humans they may give rise to congenital heart defects. This review will discuss the roles of myosin, specifically with regards to the developing heart. The expression of each myosin protein will be described, and the effects that altering expression has on the heart in embryogenesis in different animal models will be discussed. The human molecular genetics of the myosins will also be reviewed.     

How human and nature shake hands: The role of no-conspiracy in physical theories

No-conspiracy is the requirement that measurement settings should be probabilistically independent of the elements of reality responsible for the measurement outcomes. In this paper we investigate what role no-conspiracy generally plays in a physical theory; how it influences the semantical role of the event types of the theory; and how it relates to such other concepts as separability, compatibility, causality, locality and contextuality.     

Physiological roles of glycerol-transporting aquaporins: the aquaglyceroporins

A subclass of aquaporin (AQP) water channels, termed aquaglyceroporins, are also able to transport glycerol and perhaps urea and other small solutes. Although extensive data exist on the physiological roles of aquaporin-facilitated water transport, until recently the biological significance of glycerol transport by the mammalian aquaglyceroporins has been unknown. There is now compelling evidence for involvement of aquaglyceroporin- facilitated glycerol transport in skin hydration and fat cell metabolism. Mice deficient in AQP3 have dry skin, reduced skin elasticity and impaired epidermal biosynthesis. Mice lacking AQP7 manifest progressive adipocyte fat accumulation and hypertrophy. These skin and fat phenotypes are attributable to impaired glycerol transport. A potential implication of these findings is the possibility of modulation of aquaglyceroporin expression or function in the therapy of skin diseases and obesity. Received 20 January 2006; received after revision 21 February 2006; accepted 20 March 2006     

Breast cancer stem cell: the roles and therapeutic implications

Breast cancers have been increasingly recognized as malignancies displaying frequent inter- and intra-tumor heterogeneity. This heterogeneity is represented by diverse subtypes and complexity within tumors, and impinges on response to therapy, metastasis, and prognosis. Cancer stem cells (CSCs), a subpopulation of cancer cells endowed with self-renewal and differentiation capacity, have been suggested to contribute to tumor heterogeneity. The CSC concept posits a hierarchical organization of tumors, at the apex of which are stem cells that drive tumor initiation, progression, and recurrence. In breast cancer, CSCs have been proposed to contribute to malignant progression, suggesting that targeting breast cancer stem cells (BCSCs) may improve treatment efficacy. Currently, several markers have been reported to identify BCSCs. However, there is objective variability with respect to the frequency and phenotype of BCSCs among different breast cancer cell lines and patients, and the regulatory mechanisms of BCSCs remain unclear. In this review, we summarize current literature about the diversity of BCSC markers, the roles of BCSCs in tumor development, and the regulatory mechanisms of BCSCs. We also highlight the most recent advances in BCSC targeting therapies and the challenges in translating the knowledge into clinical practice.     

The nuclear envelope: emerging roles in development and disease

The chromosomes of eukaryotic cells are separated from the cytoplasm by the nuclear envelope. The nuclear envelope includes two riveted membranes, plus embedded pore complexes that mediate nuclear import and export. In this sense, the nuclear envelope is truly a border zone. However, the envelope also links directly to chromosomes, and anchors two major infrastructures--the nuclear lamina and Tpr filaments--to the nuclear perimeter. Proteins of the nuclear envelope mediate a variety of fundamental activities, including DNA replication, gene expression and silencing, chromatin organization, cell division, apoptosis, sperm nuclear remodeling, the behavior of pronuclei, cell fate determination, nuclear migration and cell polarity. Furthermore, mutations in nuclear lamins and lamin-binding proteins cause tissue-specific inherited diseases. This special issue of Cell and Molecular Life Sciences is devoted to recent major advances in the characterization of nuclear envelope proteins and their roles. We offer here an overview of the topics covered in this issue of CMLS, and also discuss the emerging recognition that the nuclear envelope is an organelle critical for a wide range of genetic and developmental activity in multicellular organisms.     

Organization and expression of the poxvirus genome

Summary Poxviruses comprise a large group of very complex animal DNA viruses which replicate in the cytoplasm of infected cells. Vaccinia virus, the most studied poxvirus, has a linear, double stranded DNA genome with an approximate molecular weight of 120×10⁶ (180 kilobase pairs). The two strands of the DNA molecule are naturally cross-linked at both termini. In addition, the vaccinia virus genome contains very long inverted terminal repetitions of approximately 10 kilobase pairs which are further characterized by the presence of direct tandem repeats of a 70-base-pair sequence arranged in two blocks of 13 and 17 copies, respectively. A central region of the genome is highly conserved between different orthopoxviruses. In contrast, the ends are hypervariable and may contain extensive deletions and complex, symmetrical sequences rearrangements. Vaccinia virus gene expression is divided into two stages. Early in infection, RNA complementary to one half of one strand-equivalent of the genome is transcribed within subviral particles by the virion-associated RNA polymerase. Later in infection, after DNA replication, RNA complementary to one entire strand-equivalent is transcribed. RNA made late in infection is very heterogeneous in length and a large fraction of it contains self-complementary sequences. Late genes are clustered near the central region of the genome. Vaccinia virus mRNAs do not appear to be synthesized by a splicing mechanism.     

Vaults and the major vault protein: Novel roles in signal pathway regulation and immunity

The unique and evolutionary highly conserved major vault protein (MVP) is the main component of ubiquitous, large cellular ribonucleoparticles termed vaults. The 100 kDa MVP represents more than 70% of the vault mass which contains two additional proteins, the vault poly (ADP-ribose) polymerase (vPARP) and the telomerase-associated protein 1 (TEP1), as well as several short untranslated RNAs (vRNA). Vaults are almost ubiquitously expressed and, besides chemotherapy resistance, have been implicated in the regulation of several cellular processes including transport mechanisms, signal transmissions and immune responses. Despite a growing amount of data from diverse species and systems, the definition of precise vault functions is still highly complex and challenging. Here we review the current knowledge on MVP and vaults with focus on regulatory functions in intracellular signal transduction and immune defence. Received 27 June 2008; received after revision 25 July 2008; accepted 30 July 2008     

Stress proteins in neural cells: functional roles in health and disease

Heat shock proteins (HSPs) or stress proteins participate in protein synthesis, protein folding, transport and translocalization processes. Stress situations trigger a heat shock response leading to their induction. Similarly, they can be upregulated by impairment of the proteasomal degradation pathway. The upregulation of stress proteins is an important step in prevention of protein aggregation and misfolding after stress, and also is essential during development and differentiation. A number of HSPs are constitutively or inducibly expressed in the nervous system and connected to protection of nerve cells and glia. The cytoskeleton is affected by stress, and HSPs have been shown to interact with the cytoskeleton in normal cells and to assist proper assembly, spatial organization and cross-linking properties. The integrity of the cytoskeleton is disturbed in many neurodegenerative disorders, and filamentous cytoplasmic inclusion bodies, containing a variety of HSPs, are observed. This review summarizes the recent literature on the presence and induction of HSPs in neural cells, and their possible functional roles in health and disease are discussed.