Measuring Fishing Capacity and Utilization with Commonly Available Data: An Application to Alaska Fisheries

Due to a lack of data on vessel costs, earnings, and input use, many of the capacity assessment models developed in the economics literature cannot be applied in U.S. fisheries. This incongruity between available data and model requirements underscores the need for developing applicable methodologies. This paper presents a means of assessing fishing capacity and utilization (for both vessels and fish stocks) with commonly available data, while avoiding some of the shortcomings associated with competing “frontier” approaches (such as data envelopment analy

Reprogramming human T cell function and specificity with non-viral genome targeting.

Decades of work have aimed to genetically reprogram T cells for therapeutic purposes1,2 using recombinant viral vectors, which do not target transgenes to specific genomic sites3,4. The need for viral vectors has slowed down research and clinical use as their manufacturing and testing is lengthy and expensive. Genome editing brought the promise of specific and efficient insertion of large transgenes into target cells using homology-directed repair5,6. Here we developed a CRISPR-Cas9 genome-targeting system that does not require viral vectors, allowing rapid and efficient insertion of large DNA sequences (greater than one kilobase) at specific sites in the genomes of primary human T cells, while preserving cell viability and function. This permits individual or multiplexed modification of endogenous genes. First, we applied this strategy to correct a pathogenic IL2RA mutation in cells from patients with monogenic autoimmune disease, and demonstrate improved signalling function. Second, we replaced the endogenous T cell receptor (TCR) locus with a new TCR that redirected T cells to a cancer antigen. The resulting TCR-engineered T cells specifically recognized tumour antigens and mounted productive anti-tumour cell responses in vitro and in vivo. Together, these studies provide preclinical evidence that non-viral genome targeting can enable rapid and flexible experimental manipulation and therapeutic engineering of primary human immune cells

Peripheral arterial disease: A high risk – but neglected – disease population

Peripheral arterial disease (PAD) is a common, progressive manifestation of atherothrombotic vascular disease, which should be managed no different to cardiac disease. Indeed, there is growing evidence that PAD patients are a high risk group, although still relatively under-detected and under treated. This is despite the fact that PAD patients are an increased mortality rate comparable to those with pre-existing or established cardiovascular disease [myocardial infarction, stroke]. With a holistic approach to atherothrombotic vascular disease, our management of PAD can only get better

CRL4^(AMBRA1) targets Elongin C for ubiquitination and degradation to modulate CRL5 signaling

Multi‐subunit cullin‐RING ligases (CRLs) are the largest family of ubiquitin E3 ligases in humans. CRL activity is tightly regulated to prevent unintended substrate degradation or autocatalytic degradation of CRL subunits. Using a proteomics strategy, we discovered that CRL4^(AMBRA1) (CRL substrate receptor denoted in superscript) targets Elongin C (ELOC), the essential adapter protein of CRL5 complexes, for polyubiquitination and degradation. We showed that the ubiquitin ligase function of CRL4^(AMBRA1) is required to disrupt the assembly and attenuate the ligase activity of human CRL5^(SOCS3) and HIV‐1 CRL5^(VIF) complexes as AMBRA1 depletion leads to hyperactivation of both CRL5 complexes. Moreover, CRL4^(AMBRA1) modulates interleukin‐6/STAT3 signaling and HIV‐1 infectivity that are regulated by CRL5^(SOCS3) and CRL5^(VIF), respectively. Thus, by discovering a substrate of CRL4^(AMBRA1), ELOC, the shared adapter of CRL5 ubiquitin ligases, we uncovered a novel CRL cross‐regulation pathway

The Power of the Stakeholders' Voice: The Effects of Social Media Activism on Stock Markets

This is the author accepted manuscript. The final version is available fromWiley via the DOI in this record.Building on social movement theory, this study assesses the influence of social media activism on the stock market performance of targeted firms. We focus on information published on Twitter by two critical stakeholders: consumer associations and trade unions. To the extent that social media represent a valid medium to mobilize stakeholders' activism, protests on Twitter may damage firm reputation, leading to capital market reactions. Using a corpus of over 1.5 million tweets referring to Spanish listed banks, we study the impact of activism by looking at targeted firms' abnormal variations in price and trading volume. Our findings suggest that the Twitter activism of key stakeholders has a significant impact on investors' decisions. Further, our empirical analyses indicate that the mechanisms affecting investors' behavior differ depending on the characteristics of the stakeholder group. Hence, this study contributes to understanding how social movements influence corporate behavior via social media

Evidence for compensatory upregulation of expressed X-linked genes in mammals, Caenorhabditis elegans and Drosophila melanogaster

Many animal species use a chromosome-based mechanism of sex determination, which has led to the coordinate evolution of dosage-compensation systems. Dosage compensation not only corrects the imbalance in the number of X chromosomes between the sexes but also is hypothesized to correct dosage imbalance within cells that is due to monoallelic X-linked expression and biallelic autosomal expression, by upregulating X-linked genes twofold (termed ‘Ohno’s hypothesis’). Although this hypothesis is well supported by expression analyses of individual X-linked genes and by microarray-based transcriptome analyses, it was challenged by a recent study using RNA sequencing and proteomics. We obtained new, independent RNA-seq data, measured RNA polymerase distribution and reanalyzed published expression data in mammals, C. elegans and Drosophila. Our analyses, which take into account the skewed gene content of the X chromosome, support the hypothesis of upregulation of expressed X-linked genes to balance expression of the genome

CRL4^(AMBRA1) targets Elongin C for ubiquitination and degradation to modulate CRL5 signaling

Multi‐subunit cullin‐RING ligases (CRLs) are the largest family of ubiquitin E3 ligases in humans. CRL activity is tightly regulated to prevent unintended substrate degradation or autocatalytic degradation of CRL subunits. Using a proteomics strategy, we discovered that CRL4^(AMBRA1) (CRL substrate receptor denoted in superscript) targets Elongin C (ELOC), the essential adapter protein of CRL5 complexes, for polyubiquitination and degradation. We showed that the ubiquitin ligase function of CRL4^(AMBRA1) is required to disrupt the assembly and attenuate the ligase activity of human CRL5^(SOCS3) and HIV‐1 CRL5^(VIF) complexes as AMBRA1 depletion leads to hyperactivation of both CRL5 complexes. Moreover, CRL4^(AMBRA1) modulates interleukin‐6/STAT3 signaling and HIV‐1 infectivity that are regulated by CRL5^(SOCS3) and CRL5^(VIF), respectively. Thus, by discovering a substrate of CRL4^(AMBRA1), ELOC, the shared adapter of CRL5 ubiquitin ligases, we uncovered a novel CRL cross‐regulation pathway

Reoperative Complications after Primary Orthotopic Liver Transplantation: A Contemporary Single-Center Experience in the Post–Model for End-Stage Liver Disease Era

BackgroundData on complications requiring reoperation after orthotopic liver transplantation (OLT) are limited. We sought to describe the spectrum of reoperative complications after OLT, evaluate the associations with graft and patient survival, and identify predictors of need for reoperation.Study designWe retrospectively studied adult patients who underwent primary OLT at our institution from February 2002 to July 2012. The primary outcomes included occurrence of a reoperative complication. Secondary outcomes were graft and patient survival. Multivariable logistic regression analysis was used to model the associations of recipient, donor, and operative variables with reoperation.ResultsOf 1,620 patients, 470 (29%) had complications requiring reoperation. The most common reoperative complication was bleeding (17.3%). Compared with patients not requiring reoperation, patients with reoperative complications had greater Model for End-Stage Liver Disease scores and need for pretransplantation hospitalization, mechanical ventilation, vasopressors, and renal replacement therapy; considerably longer cold and warm ischemia times and greater intraoperative blood transfusion requirements; and substantially worse 1-, 3-, and 5-year graft and patient survival rates. In multivariable analysis, predictors of reoperative complications included intraoperative transfusion of packed RBCs (odds ratio [OR] = 2.21; 95% CI, 1.91-2.56), donor length of hospitalization >8 days (OR = 1.87; 95% CI, 1.28-2.73), recipient pretransplantation mechanical ventilation (OR = 1.65; 95% CI, 1.21-2.24), cold ischemia time >9 hours (OR = 1.63; 95% CI, 1.23-2.17), warm ischemia time >55 minutes (OR = 1.58; 95% CI, 1.02-2.44), earlier major abdominal surgery (OR = 1.41; 95% CI, 1.03-1.92), and elevated donor serum sodium (OR = 1.17; 95% CI, 1.03-1.31).ConclusionsPatients who require reoperation for complications after OLT have high pretransplantation acuity and inferior post-transplantation survival. We identified factors associated with reoperative complications to guide perioperative donor-recipient matching and improve outcomes