Diverse specificity of cellulosome attachment to the bacterial cell surface.

During the course of evolution, the cellulosome, one of Nature's most intricate multi-enzyme complexes, has been continuously fine-tuned to efficiently deconstruct recalcitrant carbohydrates. To facilitate the uptake of released sugars, anaerobic bacteria use highly ordered protein-protein interactions to recruit these nanomachines to the cell surface. Dockerin modules located within a non-catalytic macromolecular scaffold, whose primary role is to assemble cellulosomal enzymatic subunits, bind cohesin modules of cell envelope proteins, thereby anchoring the cellulosome onto the bacterial cell.

Enhancing the pharmaceutical properties of protein drugs by ancestral sequence reconstruction.

Optimization of a protein's pharmaceutical properties is usually carried out by rational design and/or directed evolution. Here we test an alternative approach based on ancestral sequence reconstruction. Using available genomic sequence data on coagulation factor VIII and predictive models of molecular evolution, we engineer protein variants with improved activity, stability, and biosynthesis potential and reduced inhibition by anti-drug antibodies.

Outcomes after retroflexed gracilis muscle flap for vascular infections in the groin.

Objective: Multiple catheterizations and procedures on the femoral arteries can increase the risk of infection and eventual destruction of the overlying skin and subcutaneous tissue. Without adequate tissue coverage, vascular structures are exposed and, thus, vulnerable to disruption. This can lead to loss of limb and/or life and carries a significant mortality.

Use of a Novel Accounting and Grouping Method for Major Trunk Injury-Analysis of Data from a Statewide Trauma Financial Survey.

Major trunk trauma is common and costly, but comparisons of costs between trauma centers (TCs) are rare. Understanding cost is essential to improve quality, manage trauma service lines, and to facilitate institutional commitment for trauma. We have used results of a statewide trauma financial survey of Levels I to IV TC to develop a useful grouping method for costs and clinical characteristics of major trunk trauma.

The Selective Maintenance of Allelic Variation Under Generalized Dominance.

Simple models of viability selection acting on variation at a single diploid locus only maintain multiple alleles for very restricted sets of fitnesses. Most of these models assume that fitnesses are independent, even if the genotypes share alleles. Here, we extend this result to a model with generalized dominance interactions, in which fitnesses are strongly affected by what we call the "primary effects" of the genotype's component alleles, so that genotypes with shared alleles have correlated fitnesses.

Cervical polyps: Is histologic evaluation necessary?

Objective: The aim of this study was to examine a series of clinically identified cervical polyps and determine the incidence of significant histologic and concurrent cytologic findings.

Methods: Consecutive cervical polyps from January 2000 through September 2012 were retrieved from the hospital laboratory information system. Histologic evaluation of these polyps was performed, followed by a chart review of clinical findings and correlation with the immediately prior or concurrently collected cervical Papanicolaou (Pap) test results, when available.

Femoral cam deformity due to anterior capsular force: A theoretical model with MRI and cadaveric correlation.

Background: Cam deformity is associated with epiphyseal extension onto the anterosuperior femoral head-neck before physeal closure. A century ago, anatomists speculated that this femoral prominence acts as a pulley bar to withstand capsular compression in hip extension with pressure concentrated where the zona orbicularis (ZO) joins the iliofemoral ligament (IFL). An animal model has shown that growth plates deflect laterally and distally when exposed to forces perpendicular to growth.

State of the art: gene therapy of haemophilia.

Clinical gene therapy has been practiced for more than a quarter century and the first products are finally gaining regulatory/marketing approval. As of 2016, there have been 11 haemophilia gene therapy clinical trials of which six are currently open. Each of the ongoing phase 1/2 trials is testing a variation of a liver-directed adeno-associated viral (AAV) vector encoding either factor VIII (FVIII) or factor IX (FIX) .

Evaluation of Antibiotics Active against Methicillin-Resistant Staphylococcus aureus Based on Activity in an Established Biofilm.

We used in vitro and in vivo models of catheter-associated biofilm formation to compare the relative activity of antibiotics effective against methicillin-resistant Staphylococcus aureus (MRSA) in the specific context of an established biofilm. The results demonstrated that, under in vitro conditions, daptomycin and ceftaroline exhibited comparable activity relative to each other and greater activity than vancomycin, telavancin, oritavancin, dalbavancin, or tigecycline. This was true when assessed using established biofilms formed by the USA300 methicillin-resistant strain LAC and the USA200 methicillin-sensitive strain UAMS-1.

Pathologic features of aggressive vulvar carcinoma are associated with epithelial-mesenchymal transition.

Factors contributing to aggressive behavior in vulvar squamous cell carcinoma (vSCC) are poorly defined; however, a recent study has shown that vSCCs with an infiltrative pattern of invasion and fibromyxoid stroma are associated with worse outcomes than tumors with a pushing or nested pattern of invasion and lymphoplasmacytic stroma. Epithelial-mesenchymal transition (EMT) has been associated with tumor progression in a number of malignancies, and this study proposes that EMT contributes to tumor aggressiveness in this subset of vSCC. Immunohistochemistry was used to detect nuclear localization of β-catenin, loss of E-cadherin, and presence of vimentin in 58 cases of vSCC.

Host and ecology both play a role in shaping distribution of digenean parasites of New Zealand whelks (Gastropoda: Buccinidae: Cominella).

Digenean parasites infecting four Cominella whelk species (C. glandiformis, C. adspersa, C.

Bioengineering and serum free expansion of blood-derived γδ T cells.

Background Aims: Cellular immunotherapy relies on several highly variable patient-specific parameters, such as (i) cell number before and after expansion, (ii) targeting of cells to tumors, (iii) cell survival and function after infusion, and (iv) on- and off-target adverse events. Cellular approaches such as the specific expansion of γδ T cells as opposed to αβ T cells are being pursued. γδ T cells are reasonable candidates for immunotherapy because they (i) possess intrinsic anti-tumorigenicity, (ii) require no priming, (iii) direct tumor killing via recognition of stress-responsive ligands, and (iv), as we now show, can be expanded to clinical cell doses in current Good Manufacturing Practice serum-free media (SFM).

Phylogeographic patterns in New Zealand and temperate Australian cantharidines (Mollusca: Gastropoda: Trochidae: Cantharidinae): Trans-Tasman divergences are ancient.

Current taxonomic treatments of New Zealand and temperate Australian members of the gastropod subfamily Cantharidinae imply that species on either side of the Tasman Sea are closely related and, in some cases, congeneric. Such a close relationship, however, entails a relatively recent divergence of Australian and New Zealand lineages, which seems inconsistent with what is known about cantharidine larval development in general. In order to address these issues, mitochondrial and nuclear DNA sequences were used to ascertain how cantharidine genera became established over the wide geographical range of temperate Australia and New Zealand, including their subantarctic islands.

The Evolution of Sex-Specific Dominance in Response to Sexually Antagonistic Selection.

Arguments about the evolutionary modification of genetic dominance have a long history in genetics, dating back more than 100 years. Mathematical investigations have shown that modifiers of the level of dominance at the locus of interest can spread at a reasonable rate only if heterozygotes at that locus are common. One hitherto neglected scenario is that of sexually antagonistic selection, which not only is ubiquitous in sexual species but also can generate stable high frequencies of heterozygotes that would appear to facilitate the spread of such modifiers.

Atrial Fibrillation and Atrial Flutter in Pregnant Women-A Population-Based Study.

Background: The goal of this study was to determine the prevalence of atrial fibrillation and atrial flutter (AF) in pregnant women and to examine the impact of AF on maternal and fetal outcomes.

Methods And Results: Between January 1, 2003 and December 31, 2013, there were 264 730 qualifying pregnancies (in 210 356 women) in the Kaiser Permanente Southern California hospitals, among whom AF was noted in 157 pregnancies (129 women; 61.3 per 100 000 women, or 59.

Radiographic failure and rates of re-operation after acromioclavicular joint reconstruction: a comparison of surgical techniques.

Aims: To compare radiographic failure and re-operation rates of anatomical coracoclavicular (CC) ligament reconstructional techniques with non-anatomical techniques after chronic high grade acromioclavicular (AC) joint injuries.

Patients And Methods: We reviewed chronic AC joint reconstructions within a region-wide healthcare system to identify surgical technique, complications, radiographic failure and re-operations. Procedures fell into four categories: (1) modified Weaver-Dunn, (2) allograft fixed through coracoid and clavicular tunnels, (3) allograft loop coracoclavicular fixation, and (4) combined allograft loop and synthetic cortical button fixation.

For Host's Sake: The Pluses of Parasite Preservation.

Conservation biologists now realize that parasites of endangered hosts should be conserved for their own sake and as part of their host's natural environment. But parasites should also be conserved because parasitic exposure might be crucial to the host's development of a fully functional immune system and hence to the survival of the host.

Design, fabrication and perivascular implantation of bioactive scaffolds engineered with human adventitial progenitor cells for stimulation of arteriogenesis in peripheral ischemia.

Cell therapy represents a promising option for revascularization of ischemic tissues. However, injection of dispersed cells is not optimal to ensure precise homing into the recipient's vasculature. Implantation of cell-engineered scaffolds around the occluded artery may obviate these limitations.

Human papillomavirus type 16 viral load is decreased following a therapeutic vaccination.

In the dose-escalation phase of a Phase I clinical trial in which six subjects each were vaccinated with PepCan at the 50, 100, 250, and 500 μg per peptide dose, the 50 μg dose showed the best histological regression rate. Ten additional subjects were vaccinated at this dose in the final dose phase. As with the dose-escalation phase, no dose-limiting toxicities were observed.

Rationalising the role of Keratin 9 as a biomarker for Alzheimer's disease.

Keratin 9 was recently identified as an important component of a biomarker panel which demonstrated a high diagnostic accuracy (87%) for Alzheimer's disease (AD). Understanding how a protein which is predominantly expressed in palmoplantar epidermis is implicated in AD may shed new light on the mechanisms underlying the disease. Here we use immunoassays to examine blood plasma expression patterns of Keratin 9 and its relationship to other AD-associated proteins.

Precision-scored parental report questions and HL-scaled tympanometry as informative measures of hearing in otitis media 1: Large-sample evidence on determinants and complementarity to pure-tone audiometry.

Introduction: In otitis media with effusion (OME), hearing loss is a core sign/symptom and basis of concern, with absolute pure-tone threshold sensitivity (in dB HL) by air-conduction providing the default measure of hearing. However several fundamental problems limiting the value of HL measures in otitis media are insufficiently appreciated. To appraise the joint value and implications of multiple hearing measures towards more comprehensive hearing assessment in OM, we examine in two related articles the interrelations and common or diverging determinants of three measures, two of them objective: binaural HL, and ACET (the published quasi-continuous scaling of binaural tympanometry to HL).

Delayed management of Grade III blunt aortic injury: Series from a Level I trauma center.

Background: Blunt aortic injuries (BAIs) are traditionally treated as surgical emergencies, with the majority of repairs performed in an urgent fashion within 24 hours, irrespective of the grade of aortic injury. These patients are often underresuscitated and often have multiple other trauma issues that need to be addressed. This study reviews a single center's experience comparing urgent (<24 hours) thoracic endovascular aneurysm repair (TEVAR) versus delayed (>24 hours) TEVAR for Grade III BAI.

Effects of FVIII immunity on hepatocyte and hematopoietic stem cell-directed gene therapy of murine hemophilia A.

Immune responses to coagulation factors VIII (FVIII) and IX (FIX) represent primary obstacles to hemophilia treatment. Previously, we showed that hematopoietic stem cell (HSC) retroviral gene therapy induces immune nonresponsiveness to FVIII in both naive and preimmunized murine hemophilia A settings. Liver-directed adeno-associated viral (AAV)-FIX vector gene transfer achieved similar results in preclinical hemophilia B models.

XerC Contributes to Diverse Forms of Staphylococcus aureus Infection via agr-Dependent and agr-Independent Pathways.

We demonstrate that mutation of xerC, which reportedly encodes a homologue of an Escherichia coli recombinase, limits biofilm formation in the methicillin-resistant Staphylococcus aureus strain LAC and the methicillin-sensitive strain UAMS-1. This was not due to the decreased production of the polysaccharide intracellular adhesin (PIA) in either strain because the amount of PIA was increased in a UAMS-1xerC mutant and undetectable in both LAC and its isogenic xerC mutant. Mutation of xerC also resulted in the increased production of extracellular proteases and nucleases in both LAC and UAMS-1, and limiting the production of either class of enzymes increased biofilm formation in the isogenic xerC mutants.

Regulatory Mutations Impacting Antibiotic Susceptibility in an Established Staphylococcus aureus Biofilm.

We previously determined the extent to which mutations of different Staphylococcus aureus regulatory loci impact biofilm formation as assessed under in vitro conditions. Here we extend these studies to determine the extent to which those regulatory loci that had the greatest effect on biofilm formation also impact antibiotic susceptibility. The experiments were done under in vitro and in vivo conditions using two clinical isolates of S.