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Purpose: Faculty research is frequently the basis of pay, tenure, and promotion decisions in the university arena. Meanwhile, perceptions regarding the quantity and quality of the research produced by a faculty is often the basis of departmental, college, and university reputation. The journal in which research findings are published is often used to assess the overall research quality. In order to better benchmark journal quality, this report provides findings of a meticulous investigation of leading journals in the finance, information systems and management science disciplines. It examines four different citation-based measures of quality and four journal characteristics that are exogenous to the quality of any individual piece of research. In unison, these investigative paths provide a clearer understanding of journal quality across the business realm, and hence of the quality of research appearing in business journals. Design: This study assists in the development of an accurate perception regarding business research through a careful analysis of the popular Journal Citation Reports (JCR) impact factor across leading journals in three diverse business disciplines. By considering three newer journal quality metrics, a.) SCImago Journal Rank (SJR), b.) Source Normalized Impact per Paper (SNIP), and c.) Percentage of articles cited, this research builds on past research. Top-tier journals in finance, information systems, and operations research and management science (referred to here as “management science ”) are compared to evaluate the consistency of these measures across disciplines. The differences in journal characteristics and their impact on the citation-rate based measures of quality are also analyzed. Further, the potential impact of a discipline-based variation in the acceptance rate, issue frequency, the time since journal inception, and total reviewers are put forth as additional potential exogenous factors that may influence the perception of the overall journal quality. T-tests are applied for discipline comparisons, while correlation and multiple regression are employed in the analysis of journal characteristics. Findings: There is a significant difference in the JCR impact measures of high-quality finance and management science journals versus high-quality information systems journals. However, only the JCR measures for finance journals correlate with a variety of journal-specific factors, including the journal's acceptance rate and frequency of issue. The SJR measures for finance and management science journals are, on the other hand, consistently higher than information systems journals, though the SJR value of any individual journal can be quite volatile. Most importantly, finance and management journals also report significant relations between the SJR measures and the journal's acceptance rate and year of initial issue. By comparison, the SNIP metric rates suggest that information systems and management science journals have higher quality. Moreover, underscoring the SNIP metrics for both the base years of the current study, articles in leading information systems and management journals are cited over twelve percentage points more than those in finance journals. Overall, results show that given the metric, the measured variance in the quality of finance, information systems, and management science journals is correlated with the identified journal-specific factors. Research limitations: The present research is limited to three business disciplines, making the examination of journals in other business disciplines a logical extension of it. Whereas this research takes journal quality as fixed, one could also evaluate a quality measures reaction to a variation in journal characteristics (i.e. changes in acceptance rates). Furthermore, one could include other measures of journal quality, comprising the h-index or the more recently-released CiteScore metric. Such research would not only build on the present research, but also improve the accuracy of scholarly outlets and consequently the research quality. Practical implications: Discipline-specific traits should be considered, and adjusted for, when making inferences about the long-term value of recently-published research. Our investigation demonstrates that citation-based research measures and journal-specific factors vary systematically across disciplines, which is why discipline-specific differences in journal characteristics, leading to the differences in citation-based quality measures, need to be considered, when making inferences about the long-term value of recently-published research. As a result, this research has significant implications for the basis upon which recommendations regarding salary adjustments, retention, and promotion are made. Social implications: Research quantity and quality are two hallmarks of leading research institutions. Assessing research quality is very problematic, because its definition has changed from being based on the review process (i.e. “blind refereed”) to currently standing on acceptance rates and impact factors. Furthermore, the impact factor construct has been a lightning rod of controversy among researchers and administrators. Even journals themselves argue over which metric to employ, in the end supporting those putting them in the best light. This research assesses how impact factors and journal characteristics, which may influence the impact factors, vary by business discipline. The research is especially important and relevant to the authors who separately chair faculty departments that include finance, information systems, and management science, and are therefore in roles requiring an assessment of faculty research productivity, including quality. Originality/value: This study is a detailed analysis of bibliographic aspects of the top-tier journals in three quantitative business areas. In addition to the popular JCR, SJR, and SNIP measures of performance, our analysis studies the seldomexamined percentage of articles cited metric. articles-citation metrics. A deeper understanding of citation-based measures is obtained through an evaluation of changes in how journals have been rated on these metrics over time. Our research shows firstly, that there are discipline-related systematic differences in both citation-based research measures and journal-specific factors, and secondly, that these discipline-specific traits should be considered when making inferences about the long-term value of recently published research. Furthermore, discipline-specific differences in journal characteristics, leading to the differences in citation-based quality measures, should in any case be considered when making personnel and remuneration decisions.

Autosomal dominant mutations of the RNA/DNA binding protein FUS are linked to familial amyotrophic lateral sclerosis (FALS); however, it is not clear how FUS mutations cause neurodegeneration. Using transgenic mice expressing a common FALS-associated FUS mutation (FUS-R521C mice), we found that mutant FUS proteins formed a stable complex with WT FUS proteins and interfered with the normal interactions between FUS and histone deacetylase 1 (HDAC1). Consequently, FUS-R521C mice exhibited evidence of DNA damage as well as profound dendritic and synaptic phenotypes in brain and spinal cord. To provide insights into these defects, we screened neural genes for nucleotide oxidation and identified brain-derived neurotrophic factor (Bdnf) as a target of FUS-R521C-associated DNA damage and RNA splicing defects in mice. Compared with WT FUS, mutant FUS-R521C proteins formed a more stable complex with Bdnf RNA in electrophoretic mobility shift assays. Stabilization of the FUS/Bdnf RNA complex contributed to Bdnf splicing defects and impaired BDNF signaling through receptor TrkB. Exogenous BDNF only partially restored dendrite phenotype in FUS-R521C neurons, suggesting that BDNF-independent mechanisms may contribute to the defects in these neurons. Indeed, RNA-seq analyses of FUS-R521C spinal cords revealed additional transcription and splicing defects in genes that regulate dendritic growth and synaptic functions. Together, our results provide insight into how gain-of-function FUS mutations affect critical neuronal functions.

The California Verbal Learning Test, Second Edition (CVLT-II) and the Virtual Environment Grocery Store (VEGS) use list learning and recognition tasks to assess episodic memory. This study aims to: (1) Replicate prior construct validity results among a new sample of young adults and healthy older adults; (2) Extend this work to a clinical sample of older adults with a neurocognitive diagnosis; (3) Compare CVLT-II and VEGS performance among these groups; and (4) Validate the independence of CVLT and VEGS episodic memory performance measures from executive functioning performance measures. Typically developing young adults (n = 53) and older adults (n = 85), as well as older adults with a neurocognitive diagnosis (n = 18), were administered the CVLT-II, VEGS, and D-KEFS CWIT. Results found that (1) the relationship of the VEGS and CVLT-II measures was highly correlated on all variables, (2) compared to the CVLT-II, participants (particularly older adults) recalled fewer items on the VEGS, and (3) the CVLT-II and VEGS were generally independent of D-KEFS CWIT. It appeared that the VEGS may be more difficult than the CVLT-II, possibly reflecting the word length effect. Performance may have also been impacted by the presence of everyday distractors in the virtual environment.

Algorithms designed to identify canonical yeast prions predict that around 250 human proteins, including several RNA-binding proteins associated with neurodegenerative disease, harbour a distinctive prion-like domain (PrLD) enriched in uncharged polar amino acids and glycine. PrLDs in RNA-binding proteins are essential for the assembly of ribonucleoprotein granules. However, the interplay between human PrLD function and disease is not understood. Here we define pathogenic mutations in PrLDs of heterogeneous nuclear ribonucleoproteins (hnRNPs) A2B1 and A1 in families with inherited degeneration affecting muscle, brain, motor neuron and bone, and in one case of familial amyotrophic lateral sclerosis. Wild-type hnRNPA2 (the most abundant isoform of hnRNPA2B1) and hnRNPA1 show an intrinsic tendency to assemble into self-seeding fibrils, which is exacerbated by the disease mutations. Indeed, the pathogenic mutations strengthen a 'steric zipper' motif in the PrLD, which accelerates the formation of self-seeding fibrils that cross-seed polymerization of wild-type hnRNP. Notably, the disease mutations promote excess incorporation of hnRNPA2 and hnRNPA1 into stress granules and drive the formation of cytoplasmic inclusions in animal models that recapitulate the human pathology. Thus, dysregulated polymerization caused by a potent mutant steric zipper motif in a PrLD can initiate degenerative disease. Related proteins with PrLDs should therefore be considered candidates for initiating and perhaps propagating proteinopathies of muscle, brain, motor neuron and bone.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease primarily affecting motor neurons. Mutations in the gene encoding TDP-43 cause some forms of the disease, and cytoplasmic TDP-43 aggregates accumulate in degenerating neurons of most individuals with ALS. Thus, strategies aimed at targeting the toxicity of cytoplasmic TDP-43 aggregates may be effective. Here, we report results from two genome-wide loss-of-function TDP-43 toxicity suppressor screens in yeast. The strongest suppressor of TDP-43 toxicity was deletion of DBR1, which encodes an RNA lariat debranching enzyme. We show that, in the absence of Dbr1 enzymatic activity, intronic lariats accumulate in the cytoplasm and likely act as decoys to sequester TDP-43, preventing it from interfering with essential cellular RNAs and RNA-binding proteins. Knockdown of Dbr1 in a human neuronal cell line or in primary rat neurons is also sufficient to rescue TDP-43 toxicity. Our findings provide insight into TDP-43-mediated cytotoxicity and suggest that decreasing Dbr1 activity could be a potential therapeutic approach for ALS.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease primarily affecting motor neurons. Mutations in the gene encoding TDP-43 cause some forms of the disease, and cytoplasmic TDP-43 aggregates accumulate in degenerating neurons of

Objective There are many uncertainties surrounding the aetiology, treatment and sequelae of hyperemesis gravidarum (HG). Prioritising research questions could reduce research waste, helping researchers and funders direct attention to those questions which most urgently need addressing. The HG priority setting partnership (PSP) was established to identify and rank the top 25 priority research questions important to both patients and clinicians.Methods Following the James Lind Alliance (JLA) methodology, an HG PSP steering group was established. Stakeholders representing patients, carers and multidisciplinary professionals completed an online survey to gather uncertainties. Eligible uncertainties related to HG. Uncertainties on nausea and vomiting of pregnancy and those on complementary treatments were not eligible. Questions were verified against the evidence. Two rounds of prioritisation included an online ranking survey and a 1-hour consensus workshop.Results 1009 participants (938 patients/carers, 118 professionals with overlap between categories) submitted 2899 questions. Questions originated from participants in 26 different countries, and people from 32 countries took part in the first prioritisation stage. 66 unique questions emerged, which were evidence checked according to the agreed protocol. 65 true uncertainties were narrowed via an online ranking survey to 26 unranked uncertainties. The consensus workshop was attended by 19 international patients and clinicians who reached consensus on the top 10 questions for international researchers to address. More patients than professionals took part in the surveys but were equally distributed during the consensus workshop. Participants from low-income and middle-income countries noted that the priorities may be different in their settings.Conclusions By following the JLA method, a prioritised list of uncertainties relevant to both HG patients and their clinicians has been identified which can inform the international HG research agenda, funders and policy-makers. While it is possible to conduct an international PSP, results from developed countries may not be as relevant in low-income and middle-income countries.

Skd3 (encoded by human CLPB) is a mitochondrial AAA+ protein comprised of an N-terminal ankyrin-repeat domain and a C-terminal HCLR-clade nucleotide-binding domain. The function of Skd3 has long remained unknown due to challenges in purifying the protein to high quality and near homogeneity. Recently we described Skd3 as a human mitochondrial protein disaggregase that solubilizes proteins in the mitochondrial intermembrane space. This protocol overcomes the challenges associated with purifying Skd3 and allows for in depth in vitro study of Skd3 activity. Tobacco etch virus (TEV) protease is required in the purification of Skd3. Thus, we also describe how to purify high quality TEV protease for use in the purification of Skd3, other purification protocols, and in vitro assays requiring TEV protease.

The study of RNA-binding proteins (RBP) offers insight into the mechanisms of pathologic protein aggregation in neurodegenerative diseases. We developed a protocol for purifying an RBP FUS and a nuclear import receptor (NIR) Kapβ2 and testing the ability of Kapβ2 to mitigate FUS aggregation and liquid-liquid phase separation.