bluuebunny/crossref_metadata_2025 huggingface dataset:
On the emergence of highly variable distributions in the autonomous system topology
Authors: Fayed Marwan , Krapivsky Paul , Byers John W. , Crovella Mark , Finkel David , Redner Sid
Published: October 2004

Recent studies observe that vertex degree in the autonomous systems (AS) graph exhibits a highly variable distribution [14, 21]. The most prominent explanatory model for this phenomenon is the Barabasi-Albert (B-A) model [5, 2]. A central feature of the B-A model is preferential connectivity --- meaning that the likelihood a new node in a growing graph will connect to an existing node is proportional to the existing node's degree. In this paper we ask whether a more general explanation than the B-A model, and absent the assumption of preferential connectivity, is consistent with empirical data. We are motivated by two observations: first, AS degree and AS size are highly correlated [10]; and second, highly variable AS size can arise simply through exponential growth. We construct a model incorporating exponential growth in the size of the Internet and in the number of ASes, and show that it yields a size distribution exhibiting a power-law tail. In such a model, if an AS's link formation is roughly proportional to its size, then AS out-degree will also show high variability. Moreover, our approach is more flexible than previous work, since the choice of
which
AS to connect to does not impact high variability, thus can be freely specified. We instantiate such a model with empirically derived estimates of historical growth rates and show that the resulting degree distribution is in good agreement with that of real AS graphs.
Automated tools to implement and test Internet systems in reconfigurable hardware
Authors: Lockwood John W. , Neely Chris , Zuver Chris , Lim Dave
Published: October 2004

Tools have been developed to automatically integrate and test networking systems in reconfigurable hardware. These tools dynamically generate circuits for Field Programmable Gate Arrays (FPGAs). A library of hardware-accelerated modules has been developed that processes Internet Protocol (IP) packets, performs header rule matching, scans pocket payloads, and implements per-flow queueing. Other functions can be added to the library as extensible modules.An integration tool was developed to enable a network administrator to specify how a customized system should examine, drop, buffer, and/or modify packets. This tool joins together modules from the library to create a composite circuit that performs multiple functions. The tool allows additional modules to be quickly added to the library and integrated into systems. The integration tool has been used to create circuits that perform Internet firewall, network intrusion detection, network intrusion prevention, and Denial of Service (DoS) attack protection functions.A test tool was developed to automatically verify that circuits created by the integration tool run properly in reconfigurable hardware. Circuits created by the integration tool are deployed into a Field-programmable Port Extender (FPX) platform. As new modules were added to the library, the test tool reconfigured the logic on the FPX, injected traffic, and monitored the resulting packets.By using hardware, not software, networking system can process millions of packets per second. Together, the integration and test tools simplify the otherwise difficult task of developing reconfigurable hardware for networking systems and testing them at Gigabit per second rates.
Virtual routers
Authors: Baumgartner Florian , Braun Torsten , Kurt Eveline , Weyland Attila
Published: October 2004

Virtual routers are software entities, i.e. user space processes, emulating IP routers on one or several (Linux) computers. Virtual routers can be used for both networking research and education. In contrast to simulation, virtual routers process packets in real-time and the virtual router code is similar to code in real routers. In the case of research, larger network test-beds can be built using a relatively small number of computers. New functionalities such as new queuing mechanisms are supported by a modular software architecture and can be tested in a rather safe environment compared to kernel space implementations. Virtual routers can also be used as a tool aiming to allow students to perform virtual experiments within a computer networks course. Students can create and experiment with arbitrary virtual IP network topologies. The web-based user interface allows students to interact remotely with the emulated routers, but simultaneously it is very similar to commonly available configuration interfaces of network devices in reality. This enables students to configure routers like in the real world but also to experiment in a much more robust and safe environment.
Execution-time clocks and Ravenscar kernels
Authors: de la Puente Juan Antonio , Zamorano Juan
Published: October 2004

The kind of high-integrity real-time systems to which the Ada Ravenscar profile is targeted often require overrun detection for enhanced reliability in the time domain Execution-time clocks and timers have been proposed to fulfill this need, but only programming patterns based on asynchronous transfer of control, and thus incompatible with the profile, have been provided up to now. In this paper an assessment of the compatibility of the proposed execution-time mechanisms with the Ravenscar profile is made, and some programming patters for using them are proposed. The patterns are intended to provide basic overrun detection and handling capabilities to high-integrity real-time systems.
DCAP
Authors: Chuah Chen-Nee , Subramanian Lakshminarayanan , Katz Randy H.
Published: October 2004

This paper proposes a detection mechanism called
DCAP
for a network provider to monitor incoming traffic and identify misbehaving flows without having to keep per-flow accounting at any of its routers. Misbehaving flows refer to flows that exceed their stipulated bandwidth limit. Through collaborative aggregate policing at both ingress and egress nodes, DCAP is able to quickly narrow the search to a candidate group that contains the misbehaving flows, and eventually identify the individual culprits. In comparison to per-flow policing, the amount of state maintained at an edge router is reduced from
O
(
n
) to
O
(√
n
), where
n
is the number of admitted flows. Simulation results show that DCAP can successfully detect a majority (64--83%) of the misbehaving flows with almost zero false alarms. Packet losses suffered by innocent flows due to undetected misbehaving activity are insignificant (0.02--0.9%). We also successfully build a prototype that demonstrates how DCAP can be deployed with minimal processing overhead in a soft-QoS architecture.
End-to-end available bandwidth
Authors: Jain Manish , Dovrolis Constantinos
Published: October 2004

The available bandwidth (avail-bw) in a network path is of major importance in congestion control, streaming applications, QoS verification, server selection, and overlay networks. We describe an end-to-end methodology, called Self-Loading Periodic Streams (SLoPS), for measuring avail-bw. The basic idea in SLoPS is that the one-way delays of a periodic packet stream show an increasing trend when the stream's rate is higher than the avail-bw. We implemented SLoPS in a tool called pathload. The accuracy of the tool has been evaluated with both simulations and experiments over real-world Internet paths. Pathload is non-intrusive, meaning that it does not cause significant increases in the network utilization, delays, or losses. We used pathload to evaluate the variability ('dynamics') of the avail-bw in some paths that cross USA and Europe. The avail-bw becomes significantly more variable in heavily utilized paths, as well as in paths with limited capacity (probably due to a lower degree of statistical multiplexing). We finally examine the relation between avail-bw and TCP throughput. A persistent TCP connection can be used to roughly measure the avail-bw in a path, but TCP saturates the path, and increases significantly the path delays and jitter.
From the chair
Authors: Sipior Janice C. , Schatzberg Laurie , Leidner Dorothy , Niederman Fred , Lending Diane
Published: October 2004

I would like to wish all of you a happy, healthy, and prosperous New Year!I would like to thank all of our members and their guests who attended the "Third Annual ACM-SIGMIS Reception," held as an ACM-SIGMIS event on Saturday, December 13, 2003, prior to the International Conference on Information Systems (ICIS2003) in Seattle, Washington, USA. It was great fun seeing all of you! Photos from the event will soon be posted to ACM-SIGMIS's website at: http://www.acm.org/sigmis. This is an annual event, so please mark your calendar now. Next year's reception is planned for Saturday, December 11, 2004, prior to ICIS2004 to be held in Washington, D.C., USA, December 12 - 15, 2004.Please plan to attend our ACM-SIGMIS Computer Personnel Research 2004 (CPR'04) Conference. For more information, please contact the Conference Chair, Mohan Tanniru, University of Arizona, mtanniru@eller.arizona.edu or visit the conference website listed below:

Conference
: ACM-SIGMIS Computer Personnel Research 2004 (CPR'04) Conference

Theme
: "Computer Personnel: Careers, Culture, and Ethics in a Networked Environment"

Dates
: April 22-24, 2004

Location
:Tucson, Arizona, USA

Website
: http://www.eller.arizona.edu/mis/CPR2004.htm

I am pleased to announce the establishment of the annual SIGMIS Magid Igbaria Outstanding Conference Paper of the Year Award, in recognition of the outstanding contributions to MIS and CPR by the late Magid Igbaria, Claremont Graduate School. This award, approved in October 2003 by the ACM awards committee, will be presented for the first time at this year's CPR'04 conference. I would like to express my sincere gratitude to Fred Niederman, Saint Louis University, for all his efforts in establishing this award. I would also like to thank Lorne Olfman, Claremont Graduate School; Tor Guimaraes, Tennessee Technological University; Al Lederer, University of Kentucky; Munir Mandviwalla, Temple University; and Conrad Shayo, California State University for their support.Thank you for your interest and involvement in SIGMIS. We encourage your comments and suggestions. Should you have any questions, ideas, or other input, please feel free to contact any one of us. We look forward to seeing you at ACM-SIGMIS CPR'04!
The research of the distributed stripped storage spatial model
Authors: Wei Qingsong , Chen Bo , Lu Xianliang , Ren Liyong , Zhou Xu
Published: October 2004

This paper presents an efficient method for finding optimized striped storage policy, abstracts and defines performance parameters to describe stripped policy according to basic requirement of distributed backup, and deduces performance evaluation formula upon several spatial storage model, describes the storage model with polyhedron, and researches the performance of various storage policy upon tetrahedron and hexahedron storage model and finds the optimized one.
Minimal host for the KAPSE
Authors: Wilder William L.
Published: October 2004

The concept of a minimal host for the KAPSE is explored and several criteria for categorizing the minimal KAPSE host are collected. This criteria includes the users' view of the environment that the KAPSE has to support, the Instruction Set Architecture of the host, the host's hardware configuration, and the host machine's operating system. Some recommendations as to the actual requirements for the minimal KAPSE host are given and several interesting conclusions about the minimal host for the KAPSE are drawn.
Revisiting fault diagnosis agreement in a new territory
Authors: Wang S. C. , Yan K. Q.
Published: October 2004

In convention, to consensus has been discussed variously. The way of fault masking is commonly used to reach consensus. However, reaching consensus is not enough in a high reliability application. Therefore, in this study, the fault diagnosis agreement is visited. The proposed protocol does not only reach an agreement for healthy processors but also detect and locate the faulty components in a synchronous unreliable network. We also enlarge the fault tolerance capability by allowing both dormant faults and malicious faults exist in a network. That is, the proposed protocol can tolerate, detect and locate the maximum number of faulty components with the dual failure mode to solve the consensus problem and fault diagnosis agreement problem in a synchronous distributed environment by minimum number of rounds of message exchange.
A security scheme for protecting security policies in firewall
Authors: Lee Jung-Seuk , Jeon Jun-Cheol , Yoo Kee-Young
Published: October 2004

This paper discusses the problem of protecting security policies and other related information in security mechanisms, such as the filtering policy of a firewall in distributed or ubiquitous environment. Unauthorized disclosure of such information might reveal the fundamental principles and methods for the protection of the whole network. We discuss the problem with typical protecting method using hash functions and we propose a scheme that protects the rule in firewall using cryptographic algorithm.
A Per-Domain Behavior for circuit emulation in IP networks
Authors: Nichols Kathleen , Jacobson Van , Poduri Kedarnath
Published: October 2004

Circuit networks are expensive to build, difficult to operate, fragile, and not easily scalable. Many network operators would like to carry circuit traffic as an overlay on top of an IP network. With higher bandwidths, faster routers, and Differentiated Services [RFC2474, RFC2475] features in routers, this is now possible. In this paper we describe a simple set of mechanisms that are sufficient to allow an IP cloud to carry circuit replacement traffic. Then, using the framework of [RFC3086] for describing a Per-Domain Behavior (PDB), we explain where these mechanisms should be deployed and quantify how they should be configured in order to construct the appropriate edge-to-edge behavior. This "Virtual Wire" (VW) PDB makes it possible to replace dedicated circuits with IP transport. In the process we attempt to lay to rest two pieces of QoS mythology: first that a Diffserv approach requires substantial over-provisioning compared to int-serv, and second that Diffserv quality of service is inherently loose and not quantitative.
On making SCTP robust to spurious retransmissions
Authors: Ladha Sourabh , Baucke Stephan , Ludwig Reiner , Amer Paul D.
Published: October 2004

Network anomalies such as packet reordering and delay spikes can result in spurious retransmissions and degrade performance of reliable transport protocols such as TCP and SCTP. Past research showed that in certain networks or paths, such anomalies were fairly common. The result was a series of proposals (Eifel, DSACK-based, F-RTO) targeted towards making a transport robust to such events. Most of the proposals focused on TCP and assumed applicability to SCTP. This paper focuses on SCTP and makes three contributions. First, the effect of spurious retransmissions in SCTP is shown to be more aggravated than in TCP, leading to a problem of congestion window overgrowth. Second, it is shown that most but not all of the solution space is shared between TCP and SCTP. An extension to the Eifel algorithm is proposed. Third, a microscopic as well as macroscopic comparison of the Eifel algorithm and the DSACK-based algorithm is presented. Such a comparison will provide implementers and vendors a clearer view of the applicability and tradeoffs involved in different algorithms.
On defining "=" in Ada
Authors: Goodenough John B.
Published: October 2004

It is commonly believed that user-defined equality can only be declared for limited types. Actually it is possible to declare a user-defined equality operator for any type.
The conversion of command & control software to Ada
Authors: Schill John , Smeaton Roger , Jackman Richard
Published: October 2004

An ongoing project to convert an existing command and control software system from Cobol and conventional file management to Ada and a relational database management system is described. This system, known as UNITREP, is a part of the World-Wide Military Command and Control System, or WWMCCS. The Ada model of our proposed UNITREP is presented, and conclusions drawn.
XAda
Authors: Harbaugh Sam
Published: October 2004

A methodology for using Ada as an executable design language is presented. The methodology follows Booch's admonition to "Design a little--Code a little" [BOOCH1] to achieve a progressive demonstration of design correctness. Resource consuming, evolutionary, stubs are used to execute the software design as the design progresses, in order to demonstrate design self-consistency and proper loading on resources such as cpu operations and disk I/O. The methodology continues thru implementation if the programming language is Ada.
ASYMMETRIC CELL DIVISION IN C. ELEGANS: Cortical Polarity and Spindle Positioning
Authors: Cowan Carrie R. , Hyman Anthony A.
Published: October 2004

▪ Abstract  The one-cell Caenorhabditis elegans embryo divides asymmetrically into a larger and smaller blastomere, each with a different fate. How does such asymmetry arise? The sperm-supplied centrosome establishes an axis of polarity in the embryo that is transduced into the establishment of anterior and posterior cortical domains. These cortical domains define the polarity of the embryo, acting upstream of the PAR proteins. The PAR proteins, in turn, determine the subsequent segregation of fate determinants and the plane of cell division. We address how cortical asymmetry could be established, relying on data from C. elegans and other polarized cells, as well as from applicable models. We discuss how cortical polarity influences spindle position to accomplish an asymmetric division, presenting the current models of spindle orientation and anaphase spindle displacement. We focus on asymmetric cell division as a function of the actin and microtubule cytoskeletons, emphasizing the cell biology of polarity.
SPECIFICATION OF TEMPORAL IDENTITY IN THE DEVELOPING NERVOUS SYSTEM
Authors: Pearson Bret J. , Doe Chris Q.
Published: October 2004

▪ Abstract  The nervous system of higher organisms exhibits extraordinary cellular diversity owing to complex spatial and temporal patterning mechanisms. The role of spatial patterning in generating neuronal diversity is well known; here we discuss how neural progenitors change over time to contribute to cell diversity within the central nervous system (CNS). We focus on five model systems: the vertebrate retina, cortex, hindbrain, spinal cord, and Drosophila neuroblasts. For each, we address the following questions: Do multipotent progenitors generate different neuronal cell types in an invariant order? Do changes in progenitor-intrinsic factors or progenitor-extrinsic signals regulate temporal identity (i.e., the sequence of neuronal cell types produced)? What is the mechanism that regulates temporal identity transitions; i.e., what triggers the switch from one temporal identity to the next? By applying the same criteria to analyze each model system, we try to highlight common themes, point out unique attributes of each system, and identify directions for future research.
CONNEXINS AND CELL SIGNALING IN DEVELOPMENT AND DISEASE
Authors: Wei Chih-Jen , Xu Xin , Lo Cecilia W.
Published: October 2004

▪ Abstract  Gap junctions contain hydrophilic membrane channels that allow direct communication between neighboring cells through the diffusion of ions, metabolites, and small cell signaling molecules. They are made up of a hexameric array of polypeptides encoded by the connexin multi-gene family. Cell-cell communication mediated by connexins is crucial to various cellular functions, including the regulation of cell growth, differentiation, and development. Mutations in connexin genes have been linked to a variety of human diseases, including cardiovascular anomalies, peripheral neuropathy, deafness, skin disorders, and cataracts. In addition to their coupling function, recent studies suggest that connexin proteins may also mediate signaling. This could involve interactions with other protein partners that may play a role not only in connexin assembly, trafficking, gating and turnover, but also in the coordinate regulation of cell-cell communication with cell adhesion and cell motility. The integration of these cell functions is likely to be important in the role of gap junctions in development and disease.
THE GENETICS AND MOLECULAR BIOLOGY OF THE SYNAPTONEMAL COMPLEX
Authors: Page Scott L. , Hawley R. Scott
Published: October 2004

▪ Abstract  The synaptonemal complex (SC) is a protein lattice that resembles railroad tracks and connects paired homologous chromosomes in most meiotic systems. The two side rails of the SC, known as lateral elements (LEs), are connected by proteins known as transverse filaments. The LEs are derived from the axial elements of the chromosomes and play important roles in chromosome condensation, pairing, transverse filament assembly, and prohibiting double-strand breaks (DSBs) from entering into recombination pathways that involve sister chromatids. The proteins that make up the transverse filaments of the SC also play a much earlier role in committing a subset of DSBs into a recombination pathway, which results in the production of reciprocal meiotic crossovers. Sites of crossover commitment can be observed as locations where the SC initiates and as immunostaining foci for a set of proteins required for the processing of DSBs to mature crossovers. In most (but not all) organisms it is the establishment of sites marking such crossover-committed DSBs that facilitates completion of synapsis (full-length extension of the SC). The function of the mature full-length SC may involve both the completion of meiotic recombination at the DNA level and the exchange of the axial elements of the two chromatids involved in the crossover. However, the demonstration that the sites of crossover formation are designated prior to SC formation, and the finding that these sites display interference, argues against a role of the mature SC in mediating the process of interference. Finally, in at least some organisms, modifications of the SC alone are sufficient to ensure meiotic chromosome segregation in the complete absence of meiotic recombination.
SIGNALING PATHWAYS IN INTESTINAL DEVELOPMENT AND CANCER
Authors: Sancho Elena , Batlle Eduard , Clevers Hans
Published: October 2004

▪ Abstract  The study of the epithelium of the adult mammalian intestine touches upon many modern aspects of biology. The epithelium is in a constant dialogue with the underlying mesenchyme to control stem cell activity, proliferation in transit-amplifying compartments, lineage commitment, terminal differentiation and, ultimately, cell death. There are spatially distinct compartments dedicated to each of these events. The Wnt, TGF-beta, BMP, Notch, and Par polarity pathways are the major players in homeostatic control of the adult epithelium. Several hereditary cancer syndromes deregulate these same signaling cascades through mutational (in)activation. Moreover, these mutations often also occur in sporadic tumors. Thus symmetry exists between the roles that these signaling pathways play in physiology and in cancer of the intestine. This is particularly evident for the Wnt/APC pathway, for which the mammalian intestine has become one of the most-studied paradigms. Here, we integrate recent knowledge of the molecular inner workings of the prototype signaling cascades with their specific roles in intestinal epithelial homeostasis and in neoplastic transformation of the epithelium.
LAMININ FUNCTIONS IN TISSUE MORPHOGENESIS
Authors: Miner Jeffrey H. , Yurchenco Peter D.
Published: October 2004

▪ Abstract  Significant advances have been made in the application of genetics to probe the functions of basement membrane laminins. These studies have shown that different laminin subunits profoundly affect tissue morphogenesis, starting around the time of embryonic implantation and extending through organogenesis and into the postnatal period. Collectively they have revealed common functions that include the induction and maintenance of cell polarity, the establishment of barriers between tissue compartments, the organization of cells into tissues, and the protection of adherent cells from detachment-induced cell death, anoikis. Interpreted in light of what is known about laminin structure and self-assembly and binding activities, these advances have begun to provide insights into mechanisms of action. In this review we focus on the contributions of the laminins in invertebrate and vertebrate tissue morphogenesis.
RETROVIRUS BUDDING
Authors: Morita Eiji , Sundquist Wesley I.
Published: October 2004

▪ Abstract  Human immunodeficiency virus (HIV) and other retroviruses acquire their envelopes and spread infection by budding through the limiting membranes of producer cells. To facilitate budding, retroviruses usurp a cellular pathway that is normally used to create vesicles that bud into late endosomal compartments called multivesicular bodies (MVB). Research on yeast and human MVB biogenesis has led to the identification of ∼25 human proteins that are required for vesicle formation and for HIV-1 budding, and has produced a working model for sequential recruitment of these proteins during MVB vesicle formation. Retroviruses can redirect this machinery to the plasma membrane and leave the cell in a single step or, alternatively, can bud directly into MVB compartments and then exit cells via the exosome pathway. Remarkably, virus release from both the plasma membrane and MVB compartments can occur directionally into specialized sites of cell-to-cell contact called virological synapses. Thus retroviruses have evolved elaborate mechanisms for escaping the cell and maximizing their chances of infecting a new host.
MECHANISMS OF POLARIZED GROWTH AND ORGANELLE SEGREGATION IN YEAST
Authors: Pruyne David , Legesse-Miller Aster , Gao Lina , Dong Yuqing , Bretscher Anthony
Published: October 2004

▪ Abstract  Cell polarity, as reflected by polarized growth and organelle segregation during cell division in yeast, appears to follow a simple hierarchy. On the basis of physical cues from previous cell cycles or stochastic processes, yeast cells select a site for bud emergence that also defines the axis of cell division. Once polarity is established, rho protein-based signal pathways set up a polarized cytoskeleton by activating localized formins to nucleate and assemble polarized actin cables. These serve as tracks for the transport of secretory vesicles, the segregation of the trans Golgi network, the vacuole, peroxisomes, endoplasmic reticulum, mRNAs for cell fate determination, and microtubules that orient the nucleus in preparation for mitosis, all by myosin-Vs encoded by the MYO2 and MYO4 genes. Most of the proteins participating in these processes in yeast are conserved throughout the kingdoms of life, so the emerging models are likely to be generally applicable. Indeed, several parallels to cellular organization in animals are evident.
ADAPTORS FOR CLATHRIN COATS: Structure and Function
Authors: Owen David J. , Collins Brett M. , Evans Philip R.
Published: October 2004

▪ Abstract  Clathrin-coated vesicles (CCVs) are responsible for the transport of proteins between various compartments of the secretory and endocytic systems. Clathrin forms a scaffold around these vesicles that is linked to membranes by clathrin adaptors. The adaptors simultaneously bind to clathrin and to transmembrane proteins and/or phospholipids and can also interact with each other and with other components of the CCV formation machinery. The result is a collection of proteins that can make multiple, moderate strength (μM Kd) interactions and thereby establish the dynamic regulatable networks to drive vesicle genesis at the correct time and place in the cell. This review focuses on the structure of clathrin adaptors and how these structures provide functional information on the mechanism of CCV formation.
NEW DEVELOPMENTS IN MITOCHONDRIAL ASSEMBLY
Authors: Koehler Carla M.
Published: October 2004

▪ Abstract  The mitochondrion has developed an elaborate translocation system for the import of nuclear-coded proteins and the export of proteins coded on the mitochondrial genome. Precursor proteins contain targeting and sorting information to reach the mitochondrion, whereas the translocons recognize the information and direct the precursor to the correct compartment. The outer membrane contains the TOM (translocase of the outer membrane) complex for translocation and the SAM (sorting and assembly machinery) complex for assembly of outer membrane proteins with complex topologies. At the inner membrane, the TIM23 (translocase of the inner membrane) mediates the import of mitochondrial proteins with a typical N-terminal targeting sequence, and the TIM22 complex mediates the import of polytopic inner membrane proteins. Based on its prokaryotic origin, the inner membrane also contains several components that mediate the export and assembly of proteins from within the matrix. Together the translocation and assembly complexes coordinate assembly of the mitochondrion.
BI-DIRECTIONAL PROTEIN TRANSPORT BETWEEN THE ER AND GOLGI
Authors: Lee Marcus C.S. , Miller Elizabeth A. , Goldberg Jonathan , Orci Lelio , Schekman Randy
Published: October 2004

▪ Abstract  The endoplasmic reticulum (ER) and the Golgi comprise the first two steps in protein secretion. Vesicular carriers mediate a continuous flux of proteins and lipids between these compartments, reflecting the transport of newly synthesized proteins out of the ER and the retrieval of escaped ER residents and vesicle machinery. Anterograde and retrograde transport is mediated by distinct sets of cytosolic coat proteins, the COPII and COPI coats, respectively, which act on the membrane to capture cargo proteins into nascent vesicles. We review the mechanisms that govern coat recruitment to the membrane, cargo capture into a transport vesicle, and accurate delivery to the target organelle.
RNA TRANSLATION IN AXONS
Authors: Piper Michael , Holt Christine
Published: October 2004

▪ Abstract  The cell body has classically been considered the exclusive source of axonal proteins. However, significant evidence has accumulated recently to support the view that protein synthesis can occur in axons themselves, remote from the cell body. Indeed, local translation in axons may be integral to aspects of synaptogenesis, long-term facilitation, and memory storage in invertebrate axons, and for growth cone navigation in response to environmental stimuli in developing vertebrate axons. Here we review the evidence supporting mRNA translation in axons and discuss the potential roles that local protein synthesis may play during development and subsequent neuronal function. We advance the view that local translation provides a rapid supply of nascent proteins in restricted axonal compartments that can potentially underlie long-term responses to transient stimuli.
THE WNT SIGNALING PATHWAY IN DEVELOPMENT AND DISEASE
Authors: Logan Catriona Y. , Nusse Roel
Published: October 2004

▪ Abstract  Tight control of cell-cell communication is essential for the generation of a normally patterned embryo. A critical mediator of key cell-cell signaling events during embryogenesis is the highly conserved Wnt family of secreted proteins. Recent biochemical and genetic analyses have greatly enriched our understanding of how Wnts signal, and the list of canonical Wnt signaling components has exploded. The data reveal that multiple extracellular, cytoplasmic, and nuclear regulators intricately modulate Wnt signaling levels. In addition, receptor-ligand specificity and feedback loops help to determine Wnt signaling outputs. Wnts are required for adult tissue maintenance, and perturbations in Wnt signaling promote both human degenerative diseases and cancer. The next few years are likely to see novel therapeutic reagents aimed at controlling Wnt signaling in order to alleviate these conditions.
PLASMODIUMSPOROZOITE MOLECULAR CELL BIOLOGY
Authors: Kappe Stefan H.I. , Buscaglia Carlos A. , Nussenzweig Victor
Published: October 2004

▪ Abstract  Plasmodium sporozoites display complex phenotypes including gliding motility and invasion of and transmigration through cells in the mosquito vector and the vertebrate host. Sporozoite studies have been difficult to perform because of technical concerns. Nevertheless, they have already provided insights into several aspects of sporozoite biology, shared in part with other apicomplexan invasive stages. Structure/function analysis of the thrombospondin-related anonymous protein paved the way to the understanding of the molecular mechanisms of apicomplexan gliding motility and host cell invasion. Functional studies of circumsporozoite protein revealed its role in Plasmodium sporozoite morphogenesis in addition to its well-known function in host cell invasion. Transcriptional surveys, which facilitate the investigation of gene expression programs that control sporozoite phenotypes, have revealed a high degree of previously unappreciated complexity and novel proteins that mediate sporozoite host cell infection.
MYOSIN VI: Cellular Functions and Motor Properties
Authors: Buss Folma , Spudich Giulietta , Kendrick-Jones John
Published: October 2004

▪ Abstract  Myosin motor proteins use the energy derived from ATP hydrolysis to move cargo along actin tracks. Myosin VI, unlike almost all other myosins, moves toward the minus end of actin filaments and functions in a variety of intracellular processes such as vesicular membrane traffic, cell migration, and mitosis. These diverse roles of myosin VI are mediated by interaction with a number of different binding partners present in multi-protein complexes. Myosin VI can work in vitro as a processive dimeric motor and as a nonprocessive monomeric motor, each with a large working stroke. The possibility that both monomeric and dimeric forms of myosin VI operate in the cell may represent an important regulatory mechanism for controlling the multiple steps in transport pathways where nonprocessive and processive motors are required.
DYNACTIN
Authors: Schroer Trina A.
Published: October 2004

▪ Abstract  Dynactin is a multisubunit protein complex that is required for most, if not all, types of cytoplasmic dynein activity in eukaryotes. Dynactin binds dynein directly and allows the motor to traverse the microtubule lattice over long distances. A single dynactin subunit, p150Glued, is sufficient for both activities, yet dynactin contains several other subunits that are organized into an elaborate structure. It is currently believed that the bulk of the dynactin structure participates in interactions with a wide range of cellular structures, many of which are cargoes of the dynein motor. Genetic studies verify the importance of all elements of dynactin structure to its function. Although dynein can bind some membranous cargoes independently of dynactin, establishment of a fully functional dynein-cargo link appears to depend on dynactin. In this review, I summarize what is presently known about dynactin structure, the cellular structures with which it associates, and the intermolecular interactions that underlie and regulate binding. Although the molecular details of dynactin's interactions with membranous organelles and other molecules are complex, the framework provided here is intended to distill what is presently known and to be of use to dynactin specialists and beginners alike.
G PROTEIN CONTROL OF MICROTUBULE ASSEMBLY
Authors: Zheng Yixian
Published: October 2004

▪ Abstract  Microtubules are dynamic polymers required for many aspects of eukaryotic cell function. The interphase microtubule network is essential for intracellular transport, organization, and cell polarization, whereas the mitotic spindle is required for chromosome segregation and cell division. Studies in different areas such as cell migration, mitosis, and asymmetric cell division have shown that Ran, Rho, and heterotrimeric G proteins regulate many aspects of microtubule functions. This review surveys how G protein–signaling coordinates microtubule polymerization and organization with specific cellular activities.
NUCLEAR RECEPTORS IN MACROPHAGE BIOLOGY: At the Crossroads of Lipid Metabolism and Inflammation
Authors: Castrillo Antonio , Tontonoz Peter
Published: October 2004

▪ Abstract  Macrophages are essential modulators of lipid metabolism and the innate immune system. Lipid and inflammatory pathways induced in activated macrophages are central to the pathogenesis of human diseases including atherosclerosis. Recent work has shown that expression of genes involved in lipid uptake and cholesterol efflux in macrophages is controlled by peroxisome proliferator-activated receptors (PPARs) and liver X receptors (LXRs). Other studies have implicated these same receptors in the modulation of macrophage inflammatory gene expression. Together, these observations position PPARs and LXRs at the crossroads of lipid metabolism and inflammation and suggest that these receptors may serve to integrate these pathways in the control of macrophage gene expression. In this review, we summarize recent work that has advanced our understanding of the roles of PPARs and LXRs in macrophage biology and discuss the implication of these results for cardiovascular physiology and disease.
REGULATION OF MUSCLE MASS BY MYOSTATIN
Authors: Lee Se-Jin
Published: October 2004

▪ Abstract  Myostatin is a secreted protein that acts as a negative regulator of skeletal muscle mass. During embryogenesis, myostatin is expressed by cells in the myotome and in developing skeletal muscle and acts to regulate the final number of muscle fibers that are formed. During adult life, myostatin protein is produced by skeletal muscle, circulates in the blood, and acts to limit muscle fiber growth. The existence of circulating tissue-specific growth inhibitors of this type was hypothesized over 40 years ago to explain how sizes of individual tissues are controlled. Skeletal muscle appears to be the first example of a tissue whose size is controlled by this type of regulatory mechanism, and myostatin appears to be the first example of the long-sought chalone.
THE BUDDING YEAST SPINDLE POLE BODY: Structure, Duplication, and Function
Authors: Jaspersen Sue L. , Winey Mark
Published: October 2004

▪ Abstract  Nucleation of microtubules by eukaryotic microtubule organizing centers (MTOCs) is required for a variety of functions, including chromosome segregation during mitosis and meiosis, cytokinesis, fertilization, cellular morphogenesis, cell motility, and intracellular trafficking. Analysis of MTOCs from different organisms shows that the structure of these organelles is widely varied even though they all share the function of microtubule nucleation. Despite their morphological diversity, many components and regulators of MTOCs, as well as principles in their assembly, seem to be conserved. This review focuses on one of the best-characterized MTOCs, the budding yeast spindle pole body (SPB). We review what is known about its structure, protein composition, duplication, regulation, and functions. In addition, we discuss how studies of the yeast SPB have aided investigation of other MTOCs, most notably the centrosome of animal cells.
THE ENGULFMENT PROCESS OF PROGRAMMED CELL DEATH INCAENORHABDITIS ELEGANS
Authors: Reddien Peter W. , Horvitz H. Robert
Published: October 2004

▪ Abstract  Programmed cell death involves the removal of cell corpses by other cells in a process termed engulfment. Genetic studies of the nematode Caenorhabditis elegans have led to a framework not only for the killing step of programmed cell death but also for the process of cell-corpse engulfment. This work has defined two signal transduction pathways that act redundantly to control engulfment. Signals expressed by dying cells probably regulate these C. elegans pathways. Components of the cell-corpse recognition system of one of the C. elegans pathways include the CED-7 ABC transporter, which likely presents a death ligand on the surface of the dying cell; the CED-1 transmembrane receptor, which recognizes this signal; and the CED-6 adaptor protein, which may transduce a signal from CED-1. The second C. elegans pathway acts in parallel and involves a novel Rac GTPase signaling pathway, with the components CED-2 CrkII, CED-5 DOCK180, CED-12 ELMO, and CED-10 Rac. The cell-corpse recognition system that activates this pathway remains to be characterized. In C. elegans, and possibly in mammals, the process of cell-corpse engulfment promotes the death process itself. The known mechanisms for cell-corpse engulfment leave much to be discovered concerning this fundamental aspect of metazoan biology.
THE ROLE OF KNOX GENES IN PLANT DEVELOPMENT
Authors: Hake Sarah , Smith Harley M.S. , Holtan Hans , Magnani Enrico , Mele Giovanni , Ramirez Julio
Published: October 2004

▪ Abstract  knox genes encode homeodomain-containing transcription factors that are required for meristem maintenance and proper patterning of organ initiation. In plants with simple leaves, knox genes are expressed exclusively in the meristem and stem, but in dissected leaves, they are also expressed in leaf primordia, suggesting that they may play a role in the diversity of leaf form. This hypothesis is supported by the intriguing phenotypes found in gain-of-function mutations where knox gene misexpression affects leaf and petal shape. Similar phenotypes are also found in recessive mutations of genes that function to negatively regulate knox genes. KNOX proteins function as heterodimers with other homeodomains in the TALE superclass. The gibberellin and lignin biosynthetic pathways are known to be negatively regulated by KNOX proteins, which results in indeterminate cell fates.
CORTICAL NEURONAL MIGRATION MUTANTS SUGGEST SEPARATE BUT INTERSECTING PATHWAYS
Authors: Bielas Stephanie , Higginbotham Holden , Koizumi Hiroyuki , Tanaka Teruyuki , Gleeson Joseph G.
Published: October 2004

▪ Abstract  During brain development, neurons migrate great distances from proliferative zones to generate the cortical gray matter. A series of studies has identified genes that are critical for migration and targeting of neurons to specific brain regions. These genes encode three basic groups of proteins and produce three distinct phenotypes. The first group encodes cytoskeletal molecules and produces graded and dosage-dependent effects, with a significant amount of functional redundancy. This group also appears to play important roles during the initiation and ongoing progression of neuronal movement. The second group encodes signaling molecules for which homozygous mutations lead to an inverted cortex. In addition, this group is responsible for movement of neurons through anatomic boundaries to specific cortical layers. The third group encodes enzymatic regulators of glycosylation and appears to delineate where neuronal migration will arrest. There is significant cross-talk among these different groups of molecules, suggesting possible points of pathway convergence.
MEMBRANE TRAFFICKING IN PLANTS
Authors: Jürgens Gerd
Published: October 2004

▪ Abstract  Plant membrane trafficking shares many features with other eukaryotic organisms, including the machinery for vesicle formation and fusion. However, the plant endomembrane system lacks an ER-Golgi intermediate compartment, has numerous Golgi stacks and several types of vacuoles, and forms a transient compartment during cell division. ER-Golgi trafficking involves bulk flow and efficient recycling of H/KDEL-bearing proteins. Sorting in the Golgi stacks separates bulk flow to the plasma membrane from receptor-mediated trafficking to the lytic vacuole. Cargo for the protein storage vacuole is delivered from the endoplasmic reticulum (ER), cis-Golgi, and trans-Golgi. Endocytosis includes recycling of plasma membrane proteins from early endosomes. Late endosomes appear identical with the multivesiculate prevacuolar compartment that lies on the Golgi-vacuole trafficking pathway. In dividing cells, homotypic fusion of Golgi-derived vesicles forms the cell plate, which expands laterally by targeted vesicle fusion at its margin, eventually fusing with the plasma membrane.
Proteins of interstitial cells of Cajal and intestinal smooth muscle, colocalized with caveolin-1
Authors: Cho Woo Jung , Daniel E. E.
Published: October 2004

The murine jejunum and lower esophageal sphincter (LES) were examined to determine the locations of various signaling molecules and their colocalization with caveolin-1 and one another. Caveolin-1 was present in punctate sites of the plasma membranes (PM) of all smooth muscles and diffusely in all classes of interstitial cells of Cajal (ICC; identified by c-kit immunoreactivity), ICC-myenteric plexus (MP), ICC-deep muscular plexus (DMP), ICC-serosa (ICC-S), and ICC-intramuscularis (IM). In general, all ICC also contained the L-type Ca2+(L-Ca2+) channel, the PM Ca2+pump, and the Na+/Ca2+exchanger-1 localized with caveolin-1. ICC in various sites also contained Ca2+-sequestering molecules such as calreticulin and calsequestrin. Calreticulin was present also in smooth muscle, frequently in the cytosol, whereas calsequestrin was present in skeletal muscle of the esophagus. Gap junction proteins connexin-43 and -40 were present in circular muscle of jejunum but not in longitudinal muscle or in LES. In some cases, these proteins were associated with ICC-DMP. The large-conductance Ca2+-activated K+channel was present in smooth muscle and skeletal muscle of esophagus and some ICC but was not colocalized with caveolin-1. These findings suggest that all ICC have several Ca2+-handling and -sequestering molecules, although the functions of only the L-Ca2+channel are currently known. They also suggest that gap junction proteins are located at sites where ultrastructural gap junctions are know to exist in circular muscle of intestine but not in other smooth muscles. These findings also point to the need to evaluate the function of Ca2+sequestration in ICC.
Annexin-1 is an endogenous gastroprotective factor against indomethacin-induced damage
Authors: Zanardo Renata C. O. , Perretti Mauro , Wallace John L.
Published: October 2004

Adherence of neutrophils to the vascular endothelium is an early and critical event in the pathogenesis of gastric injury induced by NSAIDs. Pretreatment with glucocorticoids has been shown to prevent NSAID-induced neutrophil adherence and, in turn, to protect the stomach from injury. Some of the anti-inflammatory effects of glucocorticoids, including inhibition of neutrophil adherence, are mediated via the release of annexin-1. In this study, we assessed the contribution of annexin-1 to the protective actions of a glucocorticoid (dexamethasone) against indomethacin-induced gastric damage. Dexamethasone pretreatment markedly reduced the extent of indomethacin-induced gastric damage in rats. Immunoneutralization of annexin-1 resulted in a reversal of the gastroprotective actions of dexamethasone. Similarly, pretreatment with either of two antagonists of the formyl peptide receptor family, to which annexin-1 binds, reversed the gastroprotective effects of dexamethasone. The inhibitory effects of dexamethasone on indomethacin-induced leukocyte adherence in the mesenteric microcirculation were abolished by pretreatment with an antibody directed against annexin-1 or with an antagonist of the formyl peptide receptors. These results demonstrate that annexin-1 mediates the gastroprotective effects of a glucocorticoid against NSAID-induced damage. We propose that in some circumstances, annexin-1 plays an important role as an endogenous mediator of mucosal defense.