bluuebunny/crossref_metadata_2025_split huggingface dataset:
Directional stepping model for yeast dynein: Longitudinal- and side- step distributions
Authors: Fayer Itay , Granek Rony 
Published: May 2019

AbstractWe deduce the directional step distribution of yeast dynein motor protein on the microtubule surface by combing intrinsic features of the dynein and microtubule. These include the probability distribution of the separation vector between the two microtubule binding domains (MTBDs), the angular probability distribution of a single MTBD translation, the existence of a microtubule seam defect, microtubule binding sites, and theoretical extension that accounts for a load force on the motor. Our predictions are in excellent accord with the measured longitudinal step size distributions at various load forces. Moreover, we predict the side-step distribution and its dependence on longitudinal load forces, which shows a few surprising features. First, the distribution is broad. Second, in the absence of load, we find a small right-hand bias. Third, the side-step bias is susceptible to the longitudinal load force; it vanishes at a load equal to the motor stalling force and changes to a left-hand bias above that value. Fourth, our results are sensitive to the ability of the motor to explore the seam several times during its walk. While available measurements of side-way distribution are limited, our findings are amenable to experimental check and, moreover, suggest a diversity of results depending on whether the microtubule seam is viable to motor sampling.Significance StatementThe function of microtubule (MT) associated protein motors, kinesin and dynein, is essential for a myriad of intracellular processes. Different measurements on yeast cytoplasmic-dynein stepping characteristics appear to be unrelated to each other. We provide a unified physical-statistical model that combines these seemingly independent features with a theoretical expression that accounts for the exertion of a longitudinal load force, to yield the longitudinal step distribution at various load forces. The latter is in excellent accord with the measured distributions. Moreover, we deduce the side-step distribution, which surprisingly is susceptible to longitudinal load forces and comprises a right or left bias. This side-way bias is consistent with observations of helical motion of a nanoparticle carried by a number of motors.
PUMILIO, but not RBMX, binding is required for regulation of genomic stability by noncoding RNA NORAD
Authors: Elguindy Mahmoud M. , Kopp Florian , Goodarzi Mohammad , Rehfeld Frederick , Thomas Anu , Chang Tsung-Cheng , Mendell Joshua T. 
Published: May 2019

ABSTRACTNORAD is a highly-conserved and abundant long noncoding RNA (lncRNA) that is required for maintenance of genomic stability in mammals. Although initial characterization of NORAD established it as a negative regulator of PUMILIO (PUM) proteins in the cytoplasm, a nuclear role for NORAD in genome maintenance through an interaction with the RNA binding protein RBMX has also been reported. Here we addressed the relative contributions of NORAD:PUM and NORAD:RBMX interactions to the regulation of genomic stability by this lncRNA. Extensive RNA FISH and fractionation experiments established that NORAD localizes predominantly to the cytoplasm with or without DNA damage. Moreover, genetic rescue experiments demonstrated that PUM binding is required for maintenance of genomic stability by NORAD whereas binding of RBMX is dispensable for this function. These data therefore establish an essential role for the NORAD:PUM interaction in genome maintenance and provide a foundation for further mechanistic dissection of this pathway.
Epigenomic profiling discovers trans-lineage SOX2 partnerships driving tumor heterogeneity in lung squamous cell carcinoma
Authors: Sato Takashi , Yoo Seungyeul , Kong Ranran , Fridrikh Maya , Sinha Abhilasha , Chandramani-Shivalingappa Prashanth , Patel Ayushi , Nagano Osamu , Masuko Takashi , Beasley Mary Beth , Powell Charles A. , Zhu Jun , Watanabe Hideo 
Published: May 2019

AbstractMolecular characterization of lung squamous cell carcinoma (LUSC), a major subtype of lung cancer, has not sufficiently improved its non-stratified treatment strategies over decades. Accumulating evidence suggests that lineage-specific transcriptional regulators control differentiation states during cancer evolution, and underlie their distinct biological behaviors. In this study, by investigating the super-enhancer landscape of LUSC, we identified a previously undescribed ‘neural’ subtype defined by Sox2 and a neural lineage factor Brn2, as well as the classical LUSC subtype defined by Sox2 and its classical squamous partner p63. Robust protein-protein interaction and genomic co-occupancy of Sox2 and Brn2, in place for p63 in the classical LUSC, indicated their transcriptional cooperation imparting this unique lineage state in the ‘neural’ LUSC. Forced expression of p63 downregulated Brn2 in the ‘neural’ LUSC cells and invoked the classical LUSC lineage with more squamous/epithelial features, which were accompanied by increased activities of ErbB/Akt and MAPK-ERK pathways suggesting differential dependency. Collectively, our data demonstrate heterogeneous cell lineage states of LUSC featured by Sox2 cooperation with Brn2 or p63, for which distinct therapeutic approaches may be warranted.
Cataract-associated deamidations on the surface of γS-crystallin increase protein unfolding and flexibility at distant regions
Authors: Forsythe Heather M. , Vetter Calvin , Jara Kayla Ann , Reardon Patrick N. , David Larry L. , Barbar Elisar J. , Lampi Kirsten J. 
Published: May 2019

AbstractDeamidation is a major age-related modification in the human lens that is highly prevalent in crystallins isolated from cataractous lenses. However, the mechanism by which deamidation causes proteins to become insoluble is not known, because of only subtle structural changes observed in vitro. We have identified Asn14 and Asn76 of γS-crystallin as highly deamidated in insoluble proteins. These sites are on the surface of the N-terminal domain and were mimicked by replacing the Asn with Asp residues. We used heteronuclear NMR spectroscopy to measure their amide hydrogen exchange and 15N relaxation dynamics to identify regions with significantly increased dynamics compared to wildtype-γS. Changes in dynamics were localized to the C-terminal domain, particularly to helix and surface loops distant from the mutation sites. Thus, a potential mechanism for γS deamidation-induced insolubilization in cataractous lenses is altered dynamics due to local regions of unfolding and increased flexibility.
Nup93 and CTCF co-modulate spatiotemporal dynamics and function of the HOXA gene cluster during differentiation
Authors: Labade Ajay S. , Salvi Adwait , Karmodiya Krishanpal , Sengupta Kundan 
Published: May 2019

ABSTRACTNucleoporins regulate nuclear transport. In addition, nucleoporins also modulate chromatin organization and gene expression. Here we investigated the role of nucleoporin Nup93, in regulating HOXA gene expression during differentiation. ChIP-Seq analysis revealed that Nup93 associates with genes involved in development and differentiation. Furthermore, Nup93 occupancy significantly overlaps with CTCF. Interestingly, Nup93 and CTCF show antagonistic roles in regulating 3’ and 5’ end HOXA genes in undifferentiated cells. The HOXA gene locus untethered from the nuclear periphery upon Nup93 but not CTCF depletion, consistent with its upregulation. Remarkably, occupancy of Nup93 and CTCF on HOXA gene locus progressively declined during differentiation but was restored in differentiated cells, consistent with the rerepression and re-localization of the HOXA gene locus with the nuclear periphery upon differentiation. In summary, Nup93 is a key modulator of the spatiotemporal dynamics and function of the HOXA gene locus during differentiation.
Mastitis risk effect on the economic consequences of paratuberculosis control in dairy cattle: A stochastic modeling study
Authors: Chiu L. J. Verteramo , Tauer L. W. , Gröhn Y.T. , Smith R. L. 
Published: May 2019

ABSTRACTThe benefits and efficacy of control programs for herds infected with Mycobacterium avium subsp. paratuberculosis (MAP) have been investigated under various contexts. However, most previous research investigated paratuberculosis control programs in isolation, without modeling the potential association with other dairy diseases. This paper evaluated the benefits of MAP control programs when the herd is also affected by mastitis, a common disease causing the largest losses in dairy production. The effect of typically suggested MAP controls were estimated under the assumption that MAP infection increased the rate of clinical mastitis. We evaluated one hundred twenty three control strategies comprising various combinations of testing, culling, and hygiene, and found that the association of paratuberculosis with mastitis alters the ranking of specific MAP control programs, but only slightly alters the cost-effectiveness of particular MAP control components, as measured by the distribution of net present value of a representative U.S. dairy operation. In particular, although testing and culling for MAP resulted in a reduction in MAP incidence, that control led to lower net present value (NPV) per cow. When testing was used, ELISA was more cost-effective than alternative testing regimes, especially if mastitis was explicitly modeled as more likely in MAP-infected animals, but ELISA testing was only significantly associated with higher NPV if mastitis was not included in the model at all. Additional hygiene was associated with a lower NPV per cow, although it lowered MAP prevalence. Overall, the addition of an increased risk of mastitis in MAP-infected animals did not change model recommendations as much as failing to consider mastitis at all.
Intrinsically disordered proteins and structured proteins with intrinsically disordered regions have different functional roles in the cell
Authors: Deiana Antonio , Forcelloni Sergio , Porrello Alessandro , Giansanti Andrea 
Published: May 2019

AbstractMany studies about classification and the functional annotation of intrinsically disordered proteins (IDPs) are based on either the occurrence of long disordered regions or the fraction of disordered residues in the sequence. Taking into account both criteria we separate the human proteome, taken as a case study, into three variants of proteins: i) ordered proteins (ORDPs), ii) structured proteins with intrinsically disordered regions (IDPRs), and iii) intrinsically disordered proteins (IDPs). The focus of this work is on the different functional roles of IDPs and IDPRs, which up until now have been generally considered as a whole. Previous studies assigned a large set of functional roles to the general category of IDPs. We show here that IDPs and IDPRs have non-overlapping functional spectra, play different roles in human diseases, and deserve to be treated as distinct categories of proteins. IDPs enrich only a few classes, functions, and processes: nucleic acid binding proteins, chromatin binding proteins, transcription factors, and developmental processes. In contrast, IDPRs are spread over several functional protein classes and GO annotations which they partly share with ORDPs. As regards to diseases, we observe that IDPs enrich only cancer-related proteins, at variance with previous results reporting that IDPs are widespread also in cardiovascular and neurodegenerative pathologies. Overall, the operational separation of IDPRs from IDPs is relevant towards correct estimates of the occurrence of intrinsically disordered proteins in genome-wide studies and in the understanding of the functional spectra associated to different flavors of protein disorder.
Corporate governance and corporate internet reporting in sub-Saharan Africa:the case of Kenya and Tanzania
Authors: Waweru Nelson , Mangena Musa , Riro George 
Published: May 2019

PurposeThis paper aims to investigate corporate internet reporting (CIR) by Kenyan and Tanzanian listed companies and whether the level of CIR is related to corporate governance structures.Design/methodology/approachThe authors collect data over a four-year period from companies listed on the Nairobi Securities Exchange and the Dar es Salaam Securities Exchange. Panel data models (random effects) are used for the analysis.FindingsThe results indicate that the level of CIR in both countries is high, but the highest in Kenya. The authors find that CIR increases with foreign ownership, audit committee independence and financial expertise but decreases with domestic ownership concentration. They also show that the effects of ownership concentration are moderated by country-specific factors. Overall, the results demonstrate that effective governance structures may lead to higher levels CIR in sub-Saharan Africans.Originality/valueThis study extends, as well as contributes to the existing literature by the examining the corporate governance-disclosure nexus relating to CIR in sub-Saharan Africa. These findings have policy implications for African countries looking to attract foreign investment.
Corporate governance in Ghana
Authors: Amartey Larry Amartei , Yu Mei , Chukwu-lobelu Osita 
Published: May 2019

Purpose
This study aims to examine the mechanisms that were being used to enhance board accountability of Ghanaian listed banks, and how board accountability can be improved.

Design/methodology/approach
The 2011 and 2016 annual reports of listed banks on the Ghana Stock Exchange were examined, and a survey questionnaire was sent to board members of nine banks.

Findings
The results show that the directors of Ghanaian listed banks prioritise a shareholder approach to accountability, with a shift towards stakeholders. Audit committees, external audits and internal audits were the main mechanisms used by these banks to enhance board accountability. Some of these mechanisms were not used effectively by a number of these banks.

Practical implications
Board accountability can be improved by appointing very competent people to the board, the national adoption of a mandatory code of corporate governance, regular rotation of external auditors and requiring non-executive directors to stand for re-election more frequently. Our research identifies weaknesses of accountability mechanisms and offers timely recommendations for banks and regulators to build stronger corporate governance systems.

Originality/value
This study obtained valuable opinions of the boards of directors, provides insights on boards of Ghanaian listed banks and contributes to the literature of corporate governance and accountability in Africa.
Losing metrics … finding heart
Authors: Day Julia K. 
Published: May 2019

PurposeThis paper aims to provide an example of ways in which research plans may shift and how the research team dealt with necessary changes as they unfolded; within this context, the authors encourage the use of qualitative and narrative methods prior to and during the design process to better understand the population for which they are designing. Second, the stories from this case study illustrate the importance of understanding the overall context in design solutions, understanding the value of working with residents during the design process and using design as a tool for advocacy and empathy.Design/methodology/approachInitially, a traditional mixed method approach was developed to study the feasibility of tiny homes in homeless populations. Responding to unforeseen circumstances, the research team shifted to more appropriate narrative research methods, capturing a profile of the community. The paper shares narrative accounts from the tiny home village residents.FindingsOverall, the stories from the Portland visit illustrate the importance of social impact and the understanding of the overall context in design. This study also advocates the use of qualitative interview and narrative methods in design research, especially when used to better understand the “houseless” or other special populations.Research limitations/implicationsThere were limitations to the research that likely affected the outcomes and the results. The most apparent limitation was the unanticipated shift in methodology that occurred during the research study, which is also arguably one of the best strengths. Also, because of the qualitative nature of this research, the results are not generalizable to a broader context and only valuable or applicable to special cases.Practical implicationsThe true human condition of displaced people is often misrepresented in the minds of those who are unaffected. Designers are uniquely qualified to help solve seemingly unsolvable problems but must do so with caution.Social implicationsFor those taking on the challenge of designing for disadvantaged communities, this paper reveals that design research is more than just a problem to solve through habitable boxes. This study brings to light several social, economic and design complications that may arise in this vein of research.Originality/valueThis research methodology was unexpectedly altered when unforeseen events necessitated a shift in the research plan. This process revealed that sensitive social issues can be difficult to navigate and must be treated with utmost respect and flexibility. Issues such as affordable housing, homelessness and sustainability are all examples of wicked problems, which designers are uniquely qualified to help solve but must do so with caution and a true understanding of context. Many lessons were learned through this process.
NHS Inquiries and the Problem of Culture
Authors: Goodwin Dawn 
Published: May 2019

AbstractIf inquiries are about learning the lessons of the past, why do they appear to find the same failings time and again? Bristol, Mid Staffordshire, Morecambe Bay, Liverpool Community Health are all examples of where culture went wrong. The lack of learning from inquiries is a prominent concern and one raised elsewhere in this issue. In this article, I explore why it might be that culture is repeatedly found to be the cause of healthcare failures. I start by reviewing perspectives on what culture is and the degree to which it is possible change it. I examine how culture was described in the Bristol, Mid Staffordshire, Morecambe Bay and Liverpool inquiries and question whether these are the same cultures, with the same problems, or whether they are different. I discuss possible explanations for apparent similarities, describe how cultural change occurs and conclude by drawing out the implications of focussing on culture as a threat to patient safety.
Public Involvement in NHS Inquiries
Authors: Carlyle Ruth 
Published: May 2019

AbstractOpportunities for engaging the public have changed over the fifty years since the inquiry into the Ely Hospital, Cardiff. NHS inquiries, and inquiries more widely, tend to be called where events have led to public concern and loss of public confidence. Involvement of the public could therefore be assumed to form a part of restoring that public confidence. This paper explores the mechanisms for public involvement in NHS inquiries over the past fifty years, assessing the roles played by the public. It uses the framework outlined by Geoffrey Howe to examine how members of the public have been involved in four NHS inquiries. Findings suggest that the roles and mechanisms have varied, but that understanding the extent of public involvement is a dimension to assessing each of the potential functions of an NHS inquiry.
How migration policies moderate the diffusion of terrorism
Authors: BÖHMELT TOBIAS , BOVE VINCENZO 
Published: May 2019

AbstractThere is an ongoing debate among practitioners and scholars about the security consequences of transnational migration. Yet, existing work has not, so far, fully taken into account the policy instruments states have at their disposal to mitigate these risks, and reliable evidence is lacking for the effectiveness of such measures. This article addresses both shortcomings as whether and to what extent national migration policies affect the diffusion of terrorism via population movements are analysed. Spatial analyses report robust support for a moderating influence of states’ policies: while terrorism can travel from one country to another via larger migration populations, this only applies to target countries with extremely lax regulations and control mechanisms. This research sheds new light on the security implications of population movements, and it crucially adds to our understanding of governments’ instruments for addressing migration challenges as well as their effectiveness.
Disinfectant and Antimicrobial Susceptibility Profiles of Campylobacter coli Isolated in 1998 to 1999 and 2015 from Swine and Commercial Pork Chops
Authors: Beier Ross C. , Harvey Roger B. , Hernandez Charles A. , Andrews Kathleen , Droleskey Robert E. , Hume Michael E. , Davidson Maureen K. , Bodeis‐Jones Sonya , Young Shenia , Anderson Robin C. , Nisbet David J. 
Published: May 2019

AbstractSusceptibility profiles were determined for 111 Campylobacter coli strains obtained in 1998 to 1999 and 2015 from market age pigs and pork chops against 22 disinfectants and 9 antimicrobials. Resistance to tetracycline (TET) was observed in 44.4% of 1998 to 1999 strains, and the antibiotic resistance profile was TET. But strains obtained in 2015 from swine and retail pork chops had 75% TET resistance and the antibiotic resistance profile was TET, followed by azithromycin‐erythromycin‐TET‐telithromycin‐clindamycin. Antimicrobial resistance increased in 2015 strains. All strains were resistant to triclosan, and 84.1% and 95.8% of strains in 1998 to 1999 and 2015, respectively, were chlorhexidine resistant. All strains were susceptible to benzalkonium chloride. There was a shift toward higher susceptibility to chlorhexidine, triclosan, P‐128, OdoBan, CPB, and CPC in 2015 swine and pork chop strains compared with 1998 to 1999 strains. The disinfectants Tek‐Trol and providone‐iodine, tris(hydroxylmethyl)nitromethane (THN) and formaldehyde demonstrated the highest susceptibilities. Didecyldimethylammonium chloride (C10AC) appeared to be about equally effective as benzyldimethyltetradecylammonium chloride (C14BAC) for inhibiting C. coli, and both were more effective than C8AC and C12BAC, but C16BAC was not efficient at inhibiting C. coli. The BACs, C12BAC and C14BAC, were the most effective ingredients in DC&R. Also, C12BAC and C14BAC, or these two in synergy with C10AC were responsible for inhibition of C. coli at high P‐128 MICs. No cross‐resistance was observed between antibiotics and disinfectants. The continued use of THN and formaldehyde in DC&R should be evaluated since these components are not effective, and their inclusion adds unwanted chemicals in the environment.Practical ApplicationCampylobacter species cause diarrheal disease throughout the world. Disinfectants are often used on the farm, in veterinary medicine, by the food processing industry, in restaurants, and in consumer's homes. Limited information is available in the literature showing how disinfectants or disinfectant components may affect the many different foodborne pathogens, and, specifically, Campylobacter coli studied here. The knowledge generated in this study concerning the interactions of a broad array of disinfectants against C. coli may well affect the types of disinfectants and disinfectant formulations allowable for use by medical personnel, producers, food processors, restaurants, and consumers.