Aortobiiliac bypass to the distal external iliac artery versus aortobifemoral bypass: a matched cohort study.

Vascular bypass has long been the standard surgical treatment for symptomatic aortoiliac occlusive disease (AIOD). Conventional wisdom has been that aortobifemoral bypass (ABF) be performed for AIOD because of the inevitable progression of iliac atherosclerosis leading to bypass thrombosis. However, ABF is prone to significant groin incision complications such as infection and lymphocele.

Biochemical reconstitution of hemorrhagic-fever arenavirus envelope glycoprotein-mediated membrane fusion.

The membrane-anchored proteins of enveloped viruses form labile spikes on the virion surface, primed to undergo large-scale conformational changes culminating in virus-cell membrane fusion and viral entry. The prefusion form of these envelope glycoproteins thus represents an important molecular target for antiviral intervention. A critical roadblock to this endeavor has been our inability to produce the prefusion envelope glycoprotein trimer for biochemical and structural analysis.

Inositol pyrophosphates modulate S phase progression after pheromone-induced arrest in Saccharomyces cerevisiae.

Several studies have demonstrated the activation of phosphoinositide-specific phospholipase C (Plc) in nuclei of mammalian cells during synchronous progression through the cell cycle, but the downstream targets of Plc-generated inositol 1,4,5-trisphosphate are poorly described. Phospholipid signaling in the budding yeast Saccharomyces cerevisiae shares similarities with endonuclear phospholipid signaling in mammals, and many recent studies point to a role for inositol phosphates, including InsP(5), InsP(6), and inositol pyrophosphates, in mediating the action of Plc. In this study, we investigated the changes in inositol phosphate levels in α-factor-treated S.

Mouse testing methods in psychoneuroimmunology: an overview of how to measure sickness, depressive/anxietal, cognitive, and physical activity behaviors.

The field of psychoneuroimmunology (PNI) aims to uncover the processes and consequences of nervous, immune, and endocrine system relationships. Behavior is a consequence of such interactions and manifests from a complex interweave of factors including immune-to-neural and neural-to-immune communication. Often the signaling molecules involved during a particular episode of neuroimmune activation are not known but behavioral response provides evidence that bioactives such as neurotransmitters and cytokines are perturbed.

Acquired immunity protects against helminth infection in a natural host population: long-term field and laboratory evidence.

Long-term records of parasite infection are rare for individuals in wild host populations. This study, on an introduced population of Xenopus laevis in Wales, demonstrates powerful control by acquired immunity of the monogenean, Protopolystoma xenopodis. Field evidence was based on a 10 year dataset for 619 individually-marked hosts screened at each capture for patent (egg-producing) infection.

Structural studies and protein engineering of inositol phosphate multikinase.

Inositol phosphates (IPs) regulate vital processes in eukaryotes, and their production downstream of phospholipase C activation is controlled through a network of evolutionarily conserved kinases and phosphatases. Inositol phosphate multikinase (IPMK, also called Ipk2 and Arg82) accounts for phosphorylation of IP(3) to IP(5), as well as production of several other IP molecules. Here, we report the structure of Arabidopsis thaliana IPMKα at 2.

Arenavirus infection induces discrete cytosolic structures for RNA replication.

Arenaviruses are responsible for acute hemorrhagic fevers with high mortality and pose significant threats to public health and biodefense. These enveloped negative-sense RNA viruses replicate in the cell cytoplasm and express four proteins. To better understand how these proteins insinuate themselves into cellular processes to orchestrate productive viral replication, we have identified and characterized novel cytosolic structures involved in arenavirus replication and transcription.

Individually ventilated cages cause chronic low-grade hypoxia impacting mice hematologically and behaviorally.

Use of individually ventilated caging (IVC) systems for mouse-based laboratory investigation has dramatically increased. We found that without mice present, intra-cage oxygen concentration was comparable (21%) between IVC housing and ambient environment caging (AEC) that used wire top lids. However, when mice were housed 4-to-a-cage for 1week, intra-cage oxygen dropped to 20.

Production of a mouse line with a conditional Crim1 mutant allele.

Crim1 is a developmentally expressed, transmembrane protein essential for normal embryonic development. We generated mice engineered to contain a Crim1 conditional null allele by flanking exons three and four of Crim1 with unidirectional LoxP sites. After crossing Crim1+/FLOX mice with a CMV-Cre line, a Crim1+/Δflox colony was established after germline transmission of the deleted allele.

Dissection of the role of the stable signal peptide of the arenavirus envelope glycoprotein in membrane fusion.

The arenavirus envelope glycoprotein (GPC) retains a stable signal peptide (SSP) as an essential subunit in the mature complex. The 58-amino-acid residue SSP comprises two membrane-spanning hydrophobic regions separated by a short ectodomain loop that interacts with the G2 fusion subunit to promote pH-dependent membrane fusion. Small-molecule compounds that target this unique SSP-G2 interaction prevent arenavirus entry and infection.

The curious case of arenavirus entry, and its inhibition.

Arenaviruses comprise a diverse family of enveloped negative-strand RNA viruses that are endemic to specific rodent hosts worldwide. Several arenaviruses cause severe hemorrhagic fevers in humans, including Junín and Machupo viruses in South America and Lassa fever virus in western Africa. Arenavirus entry into the host cell is mediated by the envelope glycoprotein complex, GPC.

A compilation of strategies for implementing clinical innovations in health and mental health.

Efforts to identify, develop, refine, and test strategies to disseminate and implement evidence-based treatments have been prioritized in order to improve the quality of health and mental health care delivery. However, this task is complicated by an implementation science literature characterized by inconsistent language use and inadequate descriptions of implementation strategies. This article brings more depth and clarity to implementation research and practice by presenting a consolidated compilation of discrete implementation strategies, based on a review of 205 sources published between 1995 and 2011.

Roles for nucleotide phosphatases in sulfate assimilation and skeletal disease.

Sulfur is an essential element to all kingdoms of life and is used in essential cellular processes including the synthesis of sulfur-containing amino acids, maintenance of cellular redox states, and incorporation into various metabolites. Inorganic sulfate, the most abundant source of environmental sulfur, is metabolized into two commonly formed nucleotide precursors: adenosine 5’-phosphosulfate (APS) and 3’-phosphoadenosine 5’-phosphosulfate (PAPS). Donation of activated sulfur occurs through a broad range of enzymatic reactions many of which consume PAPS thereby producing 3’-phosphoadenosine 5’-phosphate (PAP).

The biobehavioral and neuroimmune impact of low-dose ionizing radiation.

In the clinical setting, repeated exposures (10-30) to low-doses of ionizing radiation (≤200 cGy), as seen in radiotherapy for cancer, causes fatigue. Almost nothing is known, however, about the fatigue inducing effects of a single exposure to environmental low-dose ionizing radiation that might occur during high-altitude commercial air flight, a nuclear reactor accident or a solar particle event (SPE). To investigate the short-term impact of low-dose ionizing radiation on mouse biobehaviors and neuroimmunity, male CD-1 mice were whole body irradiated with 50 cGy or 200 cGy of gamma or proton radiation.

Environmental constraints influencing survival of an African parasite in a north temperate habitat: effects of temperature on development within the host.

The monogenean Protopolystoma xenopodis has been established in Wales for >40 years following introduction with Xenopus laevis from South Africa. This provides an experimental system for determining constraints affecting introduced species in novel environments. Parasite development post-infection was followed at 15, 20 and 25°C for 15 weeks and at 10°C for ⩾1 year and correlated with temperatures recorded in Wales.

Environmental constraints influencing survival of an African parasite in a north temperate habitat: effects of temperature on egg development.

Factors affecting survival of parasites introduced to new geographical regions include changes in environmental temperature. Protopolystoma xenopodis is a monogenean introduced with the amphibian Xenopus laevis from South Africa to Wales (probably in the 1960s) where low water temperatures impose major constraints on life-cycle processes. Effects were quantified by maintenance of eggs from infections in Wales under controlled conditions at 10, 12, 15, 18, 20 and 25°C.

Contemporary management of diabetic neuropathic foot ulceration: a study of 917 consecutively treated limbs.

Background: For patients with diabetic neuropathic foot ulceration, the current treatment paradigm is heavily weighted toward limb revascularization; aligning incentives to perform more surgery and less ulcer management/prevention. Our purpose was to perform an analysis of functional outcomes to assess this current treatment paradigm.

Study Design: Nine hundred and seventeen neuropathic ulcerated feet in 706 patients with diabetes were analyzed.

A specific interaction of small molecule entry inhibitors with the envelope glycoprotein complex of the Junín hemorrhagic fever arenavirus.

Arenaviruses are responsible for acute hemorrhagic fevers worldwide and are recognized to pose significant threats to public health and biodefense. Small molecule compounds have recently been discovered that inhibit arenavirus entry and protect against lethal infection in animal models. These chemically distinct inhibitors act on the tripartite envelope glycoprotein (GPC) through its unusual stable signal peptide subunit to stabilize the complex against pH-induced activation of membrane fusion in the endosome.

Structure of a zinc-binding domain in the Junin virus envelope glycoprotein.

Arenaviruses cause acute hemorrhagic fevers with high mortality. Entry of the virus into the host cell is mediated by the viral envelope glycoprotein, GPC. In contrast to other class I viral envelope glycoproteins, the mature GPC complex contains a cleaved stable signal peptide (SSP) in addition to the canonical receptor-binding (G1) and transmembrane fusion (G2) subunits.

Prosthetic treatment of hip fractures in the elderly patient.

As the elderly population in our society significantly increases, the incidence of displaced femoral neck fractures will increase proportionally. Three surgical procedures are available to treat such fractures: internal fixation, hemiarthroplasty (unipolar or bipolar), and total hip arthroplasty. Long-term costs and efficacy of these three procedures vary, primarily due to postoperative complications.

Molecular manipulation and analysis of inositol phosphate and pyrophosphate levels in Mammalian cells.

Lipid-derived inositol phosphates (InsPs) comprise a family of second messengers that arise through the action of six classes of InsP kinases, generally referred to as IPKs. Genetic studies have indicated that InsPs play critical roles in embryonic development, but the mechanisms of action for InsPs in mammalian cellular function are largely unknown. This chapter outlines a method for manipulating cellular InsP profiles through the coexpression of a constitutively active G protein and various IPKs.