bluuebunny/crossref_metadata_2025_split huggingface dataset:
The human cytomegalovirus protein UL116 interacts with the viral ER resident glycoprotein UL148 and promotes the incorporation of gH/gL complexes into virions
Authors: Siddiquey Mohammed N.A. , Schultz Eric P. , Yu Qin , Amendola Diego , Vezzani Giacomo , Yu Dong , Maione Domenico , Lanchy Jean-Marc , Ryckman Brent J. , Merola Marcello , Kamil Jeremy P. 
Published: November 2020

ABSTRACTHeterodimers of glycoproteins H (gH) and L (gL) comprise a basal element of the viral membrane fusion machinery conserved across herpesviruses. In human cytomegalovirus (HCMV), a glycoprotein encoded byUL116noncovalently assembles onto gH at a position similar to that occupied by gL, forming a heterodimer that is incorporated into virions. However, physiological roles for UL116 or its complex with gH remain to be identified. Here, we show that UL116 promotes the expression of gH/gL complexes and is required for the efficient production of infectious cell-free virions.UL116-nullmutants show a 10-fold defect in production of infectious cell-free virions from infected fibroblasts and epithelial cells. This defect is accompanied by reduced expression of the two disulfide-linked gH/gL complexes that play crucial roles in viral entry: the heterotrimer of gH/gL with glycoprotein O (gO) and the pentameric complex of gH/gL with UL128, UL130, and UL131. Furthermore, gH/UL116 complexes comprise a substantial constituent of virions since an abundant gH species not covalently linked to other glycoproteins, which has long been observed in the literature, is readily detected from wild-type but notUL116-nullvirions.Interestingly, UL116 co-immunoprecipitates with UL148, a viral ER resident glycoprotein previously shown to attenuate ER-associated degradation (ERAD) of gO, and we observe elevated levels of UL116 inUL148-nullvirions.Collectively, our findings suggest that UL116 may serve as a chaperone for gH to support the assembly, maturation, and incorporation of gH/gL complexes into virions.IMPORTANCEHCMV is a betaherpesvirus that causes dangerous opportunistic infections in immunocompromised patients, as well as in the immune-naive fetus and preterm infants. The potential of the virus to enter new host cells is governed in large part by two alternative viral glycoprotein H (gH) / glycoprotein L (gL) complexes that play important roles in entry: gH/gL/gO and gH/gL/UL128-131. A recently identified virion gH complex, comprised of gH bound to UL116, adds a new layer of complexity to the mechanisms that contribute to HCMV infectivity. Here, we show that UL116 promotes the expression of gH/gL complexes, and that UL116 interacts with the viral ER-resident glycoprotein UL148, a factor that supports the expression of gH/gL/gO. Overall, our results suggest that UL116 is a chaperone for gH. These findings have important implications for understanding of HCMV cell tropism as well as for the development of vaccines against the virus.
Comparative efficacy of the novel diarylquinoline TBAJ-587 and bedaquiline against a resistantRv0678mutant in a mouse model of tuberculosis
Authors: Xu Jian , Converse Paul J. , Upton Anna M. , Mdluli Khisimuzi , Fotouhi Nader , Nuermberger Eric L. 
Published: November 2020

AbstractSince its conditional approval in 2012, bedaquiline (BDQ) has been a valuable tool for treatment of drug-resistant tuberculosis. More recently, a novel short-course regimen combining BDQ with pretomanid and linezolid won approval to treat highly drug-resistant tuberculosis. Clinical reports of emerging BDQ resistance have identified mutations inRv0678that de-repress the expression of the MmpL5/MmpS5 efflux transporter as the most common cause. Because the effect of these mutations on bacterial susceptibility to BDQ is relatively small (e.g., 2-8× MIC shift), increasing the BDQ dose would increase antibacterial activity but also pose potential safety concerns, including QTc prolongation. Substitution of BDQ with another diarylquinoline with superior potency and/or safety has the potential to overcome these limitations. TBAJ-587 has greaterin vitropotency than BDQ, including againstRv0678mutants, and may offer a larger safety margin. Using a mouse model of tuberculosis and different doses of BDQ and TBAJ-587, we found that against wild-typeM. tuberculosisH37Rv and an isogenicRv0678mutant, TBAJ-587 has greater efficacy against both strains than BDQ, whether alone or in combination with pretomanid and either linezolid or moxifloxacin and pyrazinamide. TBAJ-587 also reduced the emergence of resistance to diarylquinolines and pretomanid.
Regular universal screening for SARS-CoV-2 infection may not allow reopening of society after controlling a pandemic wave
Authors: Bootsma MCJ , Kretzschmar ME , Rozhnova G , Heesterbeek JAP , Kluytmans JAJW , Bonten MJM 
Published: November 2020

AbstractBackgroundTo limit societal and economic costs of lockdown measures, public health strategies are needed that control the spread of SARS-CoV-2 and simultaneously allow lifting of disruptive measures. Regular universal random screening of large proportions of the population regardless of symptoms has been proposed as a possible control strategy.MethodsWe developed a mathematical model that includes test sensitivity depending on infectiousness for PCR-based and antigen-based tests, and different levels of onward transmission for testing and non-testing parts of the population. Only testing individuals participate in high-risk transmission events, allowing more transmission in case of unnoticed infection. We calculated the required testing interval and coverage to bring the effective reproduction number due to universal random testing (Rrt) below 1, for different scenarios of risk behavior of testing and non-testing individuals.FindingsWith R0 = 2.5, lifting all control measures for tested subjects with negative test results would require 100% of the population being tested every three days with a rapid test method with similar sensitivity as PCR-based tests. With remaining measures in place reflecting Re = 1.3, 80% of the population would need to be tested once a week to bring Rrt below 1. With lower proportions tested and with lower test sensitivity, testing frequency should increase further to bring Rrt below 1. With similar Re values for tested and non-tested subjects, and with tested subjects not allowed to engage in higher risk events, at least 80% of the populations needs to test every five days to bring Rrt below. The impact of the test-sensitivity on the reproduction number is far less than the frequency of testing.InterpretationRegular universal random screening followed by isolation of infectious individuals is not a viable strategy to reopen society after controlling a pandemic wave of SARS-CoV-2. More targeted screening approaches are needed to better use rapid testing such that it can effectively complement other control measures.FundingRECOVER (H2020-101003589) (MJMB), ZonMw project 10430022010001 (MK, HH), FCT project 131_596787873 (GR). ZonMw project 91216062 (MK)
Salivary CGRP as diagnostic and migraine attack phase monitor biomarker: CGRP (in)dependent attacks
Authors: Alpuente Alicia , Gallardo Victor J , Asskour Laila , Caronna Edoardo , Torres-Ferrus Marta , Pozo-Rosich Patricia 
Published: November 2020

ABSTRACTObjectiveTo assess saliva as a substrate to measure CGRP by comparing interictal levels of CGRP in patients with episodic migraine and controls; and to evaluate saliva CGRP temporal profile during migraine attacks.MethodsThis prospective observational study included women with episodic migraine and healthy controls. Participants collected daily saliva samples for 30 consecutive days and 3 additional ones during migraine attacks. 4 timepoints were considered: interictal (72h headache-free), preictal (PRE-24h before the attack), ictal (0h,2h,8h), postictal (POST-24h after the attack). CGRP levels were quantified by ELISA.Results35 women (22 patients, 13 controls) were included. Statistically significant differences were found in interictal salivary levels of CGRP between patients and controls (median[IQR]: 98.0 [86.7] vs. 42.2 [44.7] pg/mL; p=0.010). An increase in CGRP levels during migraine attacks was detected (median[IQR]: preictal 113.5 [137.8], 0h 164.6 [204.5], 2h 101.7 [159.1], 8h 82.6 [166.2], postictal 79.6 [124.3] pg/ml; p<0.001). Patients were classified as having CGRP-dependent (80.0%) and non-CGRP dependent migraine attacks (20.0%) according to the magnitude of change between preictal and ictal phase (0h). Accompanying symptoms were different depending on the type of attack. In the longitudinal analysis, we observed that the amount of CGRP measured during attacks were phase dependent and it was influenced by the frequency of monthly headache days (p=0.02).InterpretationPatients with episodic migraine have higher interictal salivary levels of CGRP than controls. These levels usually increase during a migraine attack, however, not every attack is CGRP-dependent, which in turn, might explain different underline pathophysiology and response to acute and preventive treatment.
Biomarkers of lesion severity in a rodent model of nonarteritic anterior ischemic optic neuropathy (rNAION)
Authors: Guo Yan , Mehrabian Zara , Johnson Mary A. , Miller Neil R. , Henderson Amanda D. , Hamlyn John , Bernstein Steven L. 
Published: November 2020

AbstractThe rodent model of nonarteritic anterior ischemic optic neuropathy (rNAION) is similar in many of its pathophysiological responses to clinical NAION. However, little is known of the parameters associated with rNAION induction severity and if pre- or early post-induction biomarkers can be identified that enable prediction of lesion severity and ultimate loss of retinal ganglion cells (RGCs). Adult male Sprague-Dawley outbred rats were evaluated for various parameters including physiological characteristics (heart rate, respiratory rate, temperature, hematocrit), optic nerve head (ONH) appearance, pre- and post-induction mean diameter, and intravenous fluorescein and indocyanine green angiographic patterns of vascular leakage at 5 hours post-induction, performed using a spectral domain-optical coherence tomography (SD-OCT) instrument. These parameters were correlated with ultimate RGC loss by Brn3a (+) immunohistology. RGC loss also was correlated with the relative level of laser exposure. The severity of ONH edema 2d, but not 5hr, post induction was most closely associated with the degree of RGC loss, revealing a threshold effect, and consistent with a compartment syndrome where a minimum level of capillary compression within a tight space is responsible for damage. RGC loss increased dramatically as the degree of laser exposure increased. Neither physiological parameters nor the degree of capillary leakage 5hr post induction were informative as to the ultimate degree of RGC loss. Similar to human NAION, the rNAION model exhibits marked variability in lesion severity. Unlike clinical NAION, pre-induction ONH diameter likely does not contribute to ultimate lesion severity; however, cross-sectional ONH edema can be used as a biomarker 1-2d post-induction to determine randomization of subjects prior to inclusion in specific neuroprotection or neuroregeneration studies.
Everything you wanted to know about Mayaro virus but were afraid to ask: Characterization and lifecycle of Mayaro virus in vertebrate and invertebrate cellular backgrounds
Authors: Pujhari Sujit , Brustolin Marco , Heu Chan C. , Smithwick Ronald , Larrosa Mireia , Hafenstein Susan , Rasgon Jason L. 
Published: November 2020

AbstractMayaro virus (MAYV) is an emerging new world alphavirus (genusAlphavirus, familyTogaviridae)that causes acute multiphasic febrile illness, skin rash, polyarthritis, and occasional severe clinical phenotypes. The virus lifecycle alternates between invertebrate and vertebrate hosts. Here we characterize the replication features, cell entry, life cycle, and virus-related cell pathology of MAYV using vertebrate and invertebratein vitromodels. Electron dense clathrin-coated pits in infected cells, and reduced viral production in the presence of dynasore, ammonium chloride, and bafilomycin, indicates that viral entry occurs through pH-dependent endocytosis. Increase in FITC-dextran uptake (an indicator of macropinocytosis) in MAYV-infected cells, and dose-dependent infection inhibition by 5-(N-ethyl-N-isopropyl) amiloride (a macropinocytosis inhibitor), indicated that macropinocytosis is an additional entry mechanism of MAYV in vertebrate cells. Acutely infected vertebrate and invertebrate cells formed cytoplasmic or membrane-associated extracytoplasmic replication complexes. Mosquito cells showed modified hybrid cytoplasmic vesicles that supported virus replication, nucleocapsid production, and maturation. Mature virus particles were released from cells by both exocytosis and budding from the cell membrane. MAYV replication was cytopathic and associated with induction of apoptosis by the intrinsic pathway, and later by the extrinsic pathway in infected vertebrate cells. Given that MAYV is expanding its geographical existence as a potential public health problem, this study lays the foundation of biological understanding valuable for therapeutic and preventive interventions.
Grit: the good, the bad and the ugly
Authors: Arli Denni , Tjiptono Fandy , Tkaczynski Aaron , Bakpayev Marat 
Published: November 2020

PurposeThe concept of grit has been receiving increased attention in recent years. Grit is a trait that enables individuals to persevere while facing challenges and obstacles in life, sometimes “winning at any cost”. The purpose of the study is to understand how ethical views may vary among different groups of people segmented on grittiness. Our key argument is that grittier segment is more inclined towards Machiavellian factors (amorality, desire for control, desire for status, distrust of others) and materialism.Design/methodology/approachData derived from self-administered questionnaires completed by convenience samples of Indonesians living in Daerah Istimewa Yogyakarta (DIY), a region commonly considered as the miniature of Indonesia. Turning to market segmentation tools (n = 467), we first segment people based on their level of grittiness and, subsequently, investigate each segment's perception towards various Machiavellian factors (amorality, desire for control, distrust of others) and materialistic attitudes.FindingsThe study identified three segments of grittiness: The Least Gritty (the Good), The More Gritty (the Bad) and The Most Gritty (the Ugly). The results of this study showed the dark side of grit. Individuals with higher grit traits are more likely to behave unethically which could be referred to as “bad” and “ugly”. To help them succeed, cheating and lying are more likely considered acceptable by gritty individuals compared to less gritty “good” individuals.Practical implicationsMerely focussing on grit–be it grit promotion or training–may produce individuals who achieve success at all costs and disregard ethical values. An implication from the study is not to discourage developing grit in individuals but instead to add and emphasise ethical components. This implication is especially critical for educators and managers developing grit as a part of their activities.Originality/valueThe results of this study will have important theoretical implications and managerial implications educators balancing the consequences of teaching grit, but also for managers interested in understanding employees' level of grit within their workplaces along with ethical considerations.
Contributions of Chinese doctoral recipients from foreign universities to agricultural economic research and education in North America and China
Authors: Wang Qingbin , Wang H. Holly , Zhang Junbiao 
Published: November 2020

PurposeThis paper traces the timeline and milestones of Chinese graduate students in agricultural economics and related fields at foreign universities, with an emphasis on North American universities, since the early 1980s, and assesses the contributions of Chinese doctoral recipients from foreign universities to agricultural economic research and education in North America and China.Design/methodology/approachData from department and college websites, associations of agricultural economics, university libraries and databases of theses and dissertations and selected agricultural economic journals in English and Chinese are used to attain the above purposes through graphical and bibliometric analyses.FindingsFirst, the numbers of Chinese doctoral recipients and tenure-track and tenured faculty in agricultural economics at North American universities have increased steadily and significantly. Second, Chinese scholars in North America have achieved tremendous success in agricultural economic research via high-quality publications, prestigious awards, editorship of top journals, leadership in professional organizations, etc. Third, more Chinese doctoral recipients overseas have increasingly returned to China and are playing important roles in China’s agricultural economic research, education and international collaboration. Fourth, the publications of overseas Chinese scholars in Chinese journals and those of their counterparts working in China on topics beyond China are relatively limited and more collaboration may enhance the global impacts of Chinese agricultural economists.Research limitations/implicationsThis research is limited by data availability and quality and the data problems are discussed in the paper.Originality/valueThis is likely the first study to assess the contributions of Chinese doctoral recipients from foreign universities to agricultural economic research and education in China and abroad.
Knowledge management processes, innovation capability and organizational performance
Authors: Migdadi Mahmoud Mohammad 
Published: November 2020

PurposeThe purpose of this study is to introduce a unified framework which integrates knowledge management processes (knowledge creation, sharing, storage and documentation and acquisition), innovation capability (product, process, marketing and organizational and organizational performance (operational, financial and product quality). Then empirically test the effect of knowledge management processes (KMP) on innovation capability (IC), the effect of IC on organizational performance (OP) and the impact of KMP on OP through the mediator (IC).Design/methodology/approachA questionnaire was designed and addressed to the general managers of the Jordanian companies making up the target population. Statistical techniques employed included confirmatory factor analysis and structural equation modeling (SEM) using AMOS 24 to test the hypotheses.FindingsThe results show that KMP influences IC, IC affects OP and KMP impacts OP through the mediator (IC).Research limitations/implicationsThe use of longitudinal data and comparisons with this study would provide further insights that would assist in generalizing knowledge related to the relationships among KMP, IC and Os' P.Practical implicationsIf organizations fully comprehend KMP and IC, they would be able to implement them successfully, creating value for their companies and improving OP.Originality/valueThe existing research on KMP and IC is primarily conceptual and descriptive in nature, and empirical research confirming the real impact of KMP when developing IC is lacking. Also. the relationship between innovation capabilities and OP has not been adequately studied. Hence, this study introduces a conceptual framework which integrates KMP, IC and OP and simultaneously empirically tests the relationships among them.
The dark side of effectuation in a key account management relationship
Authors: McGowan Phillip , Simms Chris , Pickernell David , Zisakis Konstantios 
Published: November 2020

Purpose
The purpose of this paper is to consider the impact of effectuation when used by small suppliers within key account management (KAM) relationships.

Design/methodology/approach
An exploratory longitudinal case study approach was used to examine a single small supplier operating in the snack foods sector of the UK foods industry, as it entered into a new KAM relationship with a major retailer and undertook four new product development projects.

Findings
Findings suggest effectuation may positively moderate the ability of a small supplier to enter into a KAM relationship by enabling it to obtain resources and limit risk. However, once within the relationship, the use of effectuation may negatively impact success by increasing the potential for failure to co-create new product development, leading to sub-optimal products, impacting buyer confidence and trust. Furthermore, a failed KAM relationship may impact other customers through attempts to recover revenues by selling these products, which may promote short-term success but, in the long-term, lead to cascading sales failure.

Research limitations/implications
It cannot be claimed that the findings of just one case study represent all small suppliers or KAM relationships. Furthermore, the case presented specifically concerns buyer-supplier relationships within the food sector.

Practical implications
This study appears to suggest caution be exercised when applying effectuation to enter into a KAM relationship, as reliance on effectual means to garner required resources may lead to the production of sub-optimal products, which are rejected by the customer. Additionally, a large customer considering entering into a KAM relationship with a small supplier should take care to ensure their chosen partner has all resources needed to successfully deliver as required or be prepared to provide sufficient support to avoid the production of sub-optimal products.

Originality/value
Findings suggest the use of effectuation within a KAM relationship has the potential to develop a dark side within business-to-business buyer-supplier relationships through unintentional breaches of trust by the selling party.
Sustainable housing development: the legitimacy-seeking perspective
Authors: Cheah Chee Wei , Low Brian , Lee Christina Kwai-Choi 
Published: November 2020

Purpose
Rapid urbanization and the influx of rural residents to urban cities has led to the growth of informal settlements globally. Drawing on institutional theory, this paper aims to examine institutional actors’ legitimacy seeking behaviour to housing issues and their responses to regulative, normative and cultural pressures.

Design/methodology/approach
The qualitative case-study research approach is adopted by conducting 25 in-depth interviews that involved purposefully chosen institutional actors in the housing sector. Online observations and documents are used to support the interview data.

Findings
Thematic analysis of data gathered suggests that these actors, guided by sensemaking, invest in relationship-building to attain market, social, relational and political legitimacy. The relationship-building also leads to the legitimation of institutional actors’ existence via an eclectic mix of economic, social and political actions.

Originality/value
The results not only guide policymakers faced with potentially conflicting demands to legitimize sustainable housing developments policy that could benefit the urban poor’s shelter needs but also to consider the interactive and dynamic processes of stakeholders’ pressures, in a highly regulated housing environment.