bluuebunny/crossref_metadata_2025_split huggingface dataset:
The landscape of antibody binding affinity in SARS-CoV-2 Omicron BA.1 evolution
Authors: Moulana Alief , Dupic Thomas , Phillips Angela M. , Chang Jeffrey , Roffler Anne A. , Greaney Allison J. , Starr Tyler N. , Bloom Jesse D. , Desai Michael M. 
Published: September 2022

ABSTRACTThe Omicron BA.1 variant of SARS-CoV-2 escapes convalescent sera and monoclonal antibodies that are effective against earlier strains of the virus. This immune evasion is largely a consequence of mutations in the BA.1 receptor binding domain (RBD), the major antigenic target of SARS-CoV-2. Previous studies have identified several key RBD mutations leading to escape from most antibodies. However, little is known about how these escape mutations interact with each other and with other mutations in the RBD. Here, we systematically map these interactions by measuring the binding affinity of all possible combinations of these 15 RBD mutations (215= 32,768 genotypes) to four monoclonal antibodies (LY-CoV016, LY-CoV555, REGN10987, and S309) with distinct epitopes. We find that BA.1 can lose affinity to diverse antibodies by acquiring a few large-effect mutations and can reduce affinity to others through several small-effect mutations. However, our results also reveal alternative pathways to antibody escape that do not include every large-effect mutation. Moreover, epistatic interactions are shown to constrain affinity decline in S309 but only modestly shape the affinity landscapes of other antibodies. Together with previous work on the ACE2 affinity landscape, our results suggest that escape of each antibody is mediated by distinct groups of mutations, whose deleterious effects on ACE2 affinity are compensated by another distinct group of mutations (most notably Q498R and N501Y).
Structural Premise of Selective Deubiquitinase USP30 Inhibition by Small-Molecule Benzosulfonamides
Authors: O’Brien Darragh P , Jones Hannah BL , Guenther Franziska , Murphy Emma J , England Katherine S , Anderson Malcolm , Brennan Paul , Davis John B , Pinto-Fernández Adán , Turnbull Andrew P , Kessler Benedikt M 
Published: September 2022

ABSTRACTDampening functional levels of the mitochondrial deubiquitylating enzyme USP30 has been suggested as an effective therapeutic strategy against neurodegenerative disorders such as Parkinson’s Disease. USP30 inhibition may counteract the deleterious effects of impaired turnover of damaged mitochondria which is inherent to both familial and sporadic forms of the disease. Small-molecule inhibitors targeting USP30 are currently in development, but little is known about their precise nature of binding to the protein. We have integrated biochemical and structural approaches to gain novel mechanistic insights into USP30 inhibition by a small-molecule benzosulfonamide containing compound,39. Activity-based protein profiling (ABPP) mass spectrometry confirmed target engagement, the high selectivity, and potency of39for USP30 against 49 other deubiquitylating enzymes in a neuroblastoma cell line.In vitrocharacterization of39enzyme kinetics infers slow and tight binding behavior, which is comparable with features of covalent modification of USP30. Finally, we blended hydrogen-deuterium exchange mass spectrometry and computational docking to elucidate the molecular architecture and geometry of USP30 complex formation with39, identifying structural rearrangements at the cleft of the USP30 thumb and palm subdomains. These studies suggest that39binds to the thumb-palm cleft that guides the ubiquitin C-terminus into the active site, thereby preventing ubiquitin binding and isopeptide bond cleavage, and confirming its importance in the inhibitory process. Our data will pave the way for the design and development of next-generation inhibitors targeting USP30 and associated deubiquitinylases.
Creating an atlas of the bone microenvironment during oral inflammatory-related bone disease using single-cell profiling
Authors: Fan Yi , Lyu Ping , Bi Ruiye , Cui Chen , Xu Ruoshi , Rosen Clifford J. , Yuan Quan , Zhou Chenchen 
Published: September 2022

AbstractOral inflammatory diseases such as apical periodontitis are common bacterial infectious diseases that may affect the periapical alveolar bone tissues. A protective healing process occurs simultaneously with the inflammatory tissue destruction, in which mesenchymal stem cells (MSCs) play a primary role. However, a systematic and precise description of the cellular and molecular composition of the microenvironment of bone affected by inflammation is lacking. In this study, we created a single cell atlas of cell populations that compose alveolar bone in healthy and inflammatory disease states. We investigated changes in expression frequency and patterns related to apical periodontitis, as well as the interactions between MSCs and immunocytes. Our results highlight an enhanced self-supporting network and osteogenic potential within MSCs during apical periodontitis-associated inflammation. MSCs not only differentiated towards osteoblast lineage cells, but also expressed higher levels of osteogenic related markers, including SPARC and Col1α1. This was confirmed by lineage tracing in transgenic mouse models and human samples from oral inflammatory-related alveolar bone lesions. In summary, the current study provides an in-depth description of the microenvironment of MSCs and immunocytes in both healthy and disease states. We also identified key apical periodontitis-associated MSC subclusters and their biomarkers, which could further our understanding of the healing process and the underlying mechanisms of oral inflammatory-related bone disease. Taken together, these results enhance our understanding of heterogeneity and cellular interactions of alveolar bone cells under pathogenic and inflammatory conditions. We provide these data as a tool for investigators not only to better appreciate the repertoire of progenitors that are stress responsive but importantly to help design new therapeutic targets to restore bone lesions caused by apical periodontitis and other inflammatory-related bone diseases.
IL-10 suppresses T cell expansion while promoting tissue-resident memory cell formation during SARS-CoV-2 infection in rhesus macaques
Authors: Nelson Christine E. , Foreman Taylor W. , Kauffman Keith D. , Sakai Shunsuke , Gould Sydnee T. , Fleegle Joel D. , Gomez Felipe ,   NIAID/DIR Tuberculosis Imaging Program, Le Nouën Cyril , Liu Xueqiao , Burdette Tracey L. , Garza Nicole L. , Lafont Bernard A. P. , Brooks Kelsie , Arlehamn Cecilia S. Lindestam , Weiskopf Daniela , Sette Alessandro , Hickman Heather D. , Buchholz Ursula J. , Johnson Reed F. , Brenchley Jason M. , Via Laura E. , Barber Daniel L. 
Published: September 2022

ABSTRACTThe pro- and anti-inflammatory pathways that determine the balance of inflammation and viral control during SARS-CoV-2 infection are not well understood. Here we examine the roles of IFNγ and IL-10 in regulating inflammation, immune cell responses and viral replication during SARS-CoV-2 infection of rhesus macaques. IFNγ blockade tended to decrease lung inflammation based on 18FDG-PET/CT imaging but had no major impact on innate lymphocytes, neutralizing antibodies, or antigen-specific T cells. In contrast, IL-10 blockade transiently increased lung inflammation and enhanced accumulation of virus-specific T cells in the lower airways. However, IL-10 blockade also inhibited the differentiation of virus-specific T cells into airway CD69+CD103+ TRM cells. While virus-specific T cells were undetectable in the nasal mucosa of all groups, IL-10 blockade similarly reduced the frequency of total TRM cells in the nasal mucosa. Neither cytokine blockade substantially affected viral load and infection ultimately resolved. Thus, in the macaque model of mild COVID-19, the pro- and anti-inflammatory effects of IFNγ and IL-10 have no major role in control of viral replication. However, IL-10 has a key role in suppressing the accumulation of SARS-CoV-2-specific T cells in the lower airways, while also promoting TRM at respiratory mucosal surfaces.
Characterization of the cytopathic effect of monkeypox virus isolated from clinical specimens and differentiation from common viral exanthems
Authors: Ma Angela , Langer Janine , Hanson Kimberly E. , Bradley Benjamin T. 
Published: September 2022

AbstractWhile the practice of viral culture has largely been replaced by nucleic acid amplification tests, circumstances still exist in which the availability of viral culture will allow for the diagnosis of infections not included in a provider’s differential diagnosis. Here, we examine the cytopathic effect (CPE) and clinical data associated with eighteen cases of monkeypox virus (MPXV) isolated from nineteen clinical samples submitted for viral culture. During the study period a total of 3,468 viral cultures were performed with herpes simplex virus most commonly isolated (646/3,468; 18.6%), followed by monkeypox virus (19/3,468; 0.6%) and varicella zoster virus (12/3,468; 0.4%). Most MPXV-positive samples were obtained from males (14/19) and taken from genital (7/19) or rectal lesions (5/19). Cycle threshold values of tested samples ranged from 15.3 to 29.0. Growth of MPXV in cell culture was rapid, yielding detectable CPE at a median of 2 days (range: 1-4) often with >50% of the monolayer affected in RMK, BGM, A549, and MRC-5 cell lines. As clinical features of MPXV, HSV, and VZV lesions may overlap, CPE patterns were comparted between viruses. HSV CPE developed in a similar time frame (median: 2 days, range: 1-7) but was more often negative in RMK cells relative to MPXV. VZV grew more slowly (median: 9 days, range: 5-11) and demonstrated CPE affecting ≤25% of cell monolayers when positive. Viral culture remains an important tool for the detection of rare or emerging viral pathogens, particularly when high viral load specimens are easily obtained.
HLA variants and TCR diversity against SARS-CoV-2 in the pre-COVID-19 era
Authors: Buhler Stéphane , Sollet Zuleika Calderin , Bettens Florence , Schaefer Antonia , Ansari Marc , Ferrari-Lacraz Sylvie , Villard Jean 
Published: September 2022

AbstractHLA antigen presentation and T-cell immunity are critical to control viral infection such as SARS-CoV-2. This study performed on samples collected in the pre-COVID-19 era demonstrates that individuals are fully equiped at the genetic level in terms of TCR repertoire and HLA variants to recognize and kill SARS-CoV-2 infected cells. HLA diversity, heterologous immunity and random somatic TCR recombination could explain these observations.
How do non-economic goals and priorities affect family firm’s propensity to innovate in automation? The role of ownership, board of director, young successor and generation
Authors: Bannò Mariasole , D'Allura Giorgia Maria , Filippi Emilia , Trento Sandro 
Published: September 2022

PurposeThis study examines the propensity to innovate in automation of family firms (FFs) based on the socio-emotional wealth (SEW) perspective.Design/methodology/approachThis study’s analysis is based on three aspects. First, the authors consider three main non-economic goals and priorities of FFs: the family’s relationship with employees (read as to care for their satisfaction and well-being); the inner pride of building and maintaining the family and firm image and reputation; and the inner feeling to be socially responsible. Second, the authors consider how these goals and priorities vary among FFs according to four dimensions: family ownership, the presence of family members on the board of directors, the involvement of young successors, and the presence of founding and later generations. Finally, the consequences of automation are considered: lower firm employment, lower employees’ satisfaction and well-being, and higher firm productivity. The analysis is based on a sample of 4,150 Italian firms.FindingsThe analysis revealed that FFs are less prone to innovate in automation than non-FFs. Specifically, family ownership, the presence of family members on the board of directors, and the presence of founding generation are negatively associated with innovation in automation. Instead, the involvement of young successors and the presence of later generation are positively associated with innovation in automation.Originality/valueTo the authors’ knowledge, this study is the first investigation that, based on SEW, examines how FFs act on the decision to innovate in automation, thereby providing empirical evidence.
Living heritage sites in the M'zab valley (Algeria): community and continuity
Authors: Rezaei Naimeh , Khouadja Abdelaziz 
Published: September 2022

PurposeThe ancient settlements of the M'zab Valley in Algeria, called ksour, are still being used by local inhabitants a thousand years after their construction. The main objective of this study was to discover why, despite the formation of new residential areas, these settlements have been able to survive and maintain their original functions.Design/methodology/approachThe authors used the concept of living heritage sites as an analytical framework. The field data were collected through semi-structured interviews and analyzed through qualitative content analysis.FindingsThis study revealed that the reasons for the survival of these settlements were cultural and social rather than physical. Four main factors play a role in the survival of these settlements: (1) solidarity and unity among the inhabitants, (2) built environment as an ancestral heritage and a symbol of identity, (3) comfort and convenience in ksour and (4) social control and adherence to tradition. However, some concerns have arisen in recent decades that may endanger the viability of these settlements in the future, requiring more attention from the government.Originality/valueWhile previous studies on urban heritage and World Heritage Sites (WHSs) have mainly focused on tourism development and conservation issues, this paper emphasized a less-studied aspect of these sites, i.e. continuity and sustainability. All previous studies on the WHSs of the M'zab Valley have addressed the traditional architecture and the climatic design of houses without sufficiently addressing other factors that have contributed to the sustainability and resilience of these settlements.
Examining resilience: the role of creativity-oriented high-performance work practices and role clarity
Authors: Aparna S.M. , Sahney Sangeeta 
Published: September 2022

PurposeThe paper aims to highlight the understated role of creativity in R&D organizations by exploring the effect of creativity-oriented high-performance work practices (CHPWPs) on resilience. The moderator effect of role clarity (RC) on the association between CHPWPs and resilience is examined.Design/methodology/approachThe study proposes a simple moderation model to understand the relationship, and specifically hierarchical regression analysis (SPSS 22.0) and SPSS PROCESS Macro has been used to test the hypotheses.FindingsFindings revealed that the implementation of CHPWPs would significantly improve resilience. The benefits of CHPWPs on resilience get compromised as the organizations lay stress on higher levels of RC.Practical implicationsIndian R&D organizations must emphasize upon enhancing resilience through a set of CHPWPs. Rather than laying greater stress on RC, these organizations should build a creative climate characterized by experimentation, freedom and a free flow of ideas.Originality/valueThe current study makes a valuable contribution by highlighting the importance of creativity and resilience in organizations. Although conceptual studies highlight the importance of creativity in R&D organizations, this has been was greatly neglected. The current study adds value to the existing literature by deepening the authors’ understanding of the role of CHPWPs in enhancing resilience, the latter being a subject of huge focus of organizations during the pandemic.
Dynamic responses of energy prices to oil price shocks
Authors: Miller Tom W. 
Published: September 2022

PurposeThis study examines the dynamic responses of five different daily energy prices to a pulse shock affecting the daily price of oil.Design/methodology/approachDaily data for energy prices from the Federal Reserve Economic Data (FRED) database for January 7, 1997, through February 8, 2021, are analyzed. A bivariate structural vector error correction model and generalized autoregressive conditionally heteroscedastic model are combined and extended by adding the volatility of the growth rate of daily oil prices as an explanatory variable for the growth rates of energy prices. This model is estimated and used to generate impulse responses for energy prices.FindingsThe empirical results show that the levels of the daily energy prices examined have unit roots, are integrated of order one, are cointegrated, and generally revert slowly to their long-term equilibrium relationships with the price of oil. The growth rates for the daily energy prices have autoregressive conditional heteroscedasticity, generally are positively related to the volatility of daily oil prices, respond quickly to a pulse shock to daily oil prices, and have cumulative responses that last at least one month.Originality/valueThis paper allows for simultaneous estimation of extended bivariate structural vector error correction and generalized autoregressive conditionally heteroscedastic models that include the volatility of oil as an explanatory variable and uses these models to generated cumulative impulse responses for the growth rates of daily energy prices to oil price shocks.
Stewardship theory of corporate governance and succession planning in family businesses of UAE: views of the owners
Authors: Jasir Mohamed , Khan Naimat U. , Barghathi Yasser 
Published: September 2022

Purpose
This paper aims to explore corporate governance (CG) and succession planning in family-owned businesses in the United Arab Emirates (UAE).

Design/methodology/approach
Semi-structured interviews are conducted with 16 owners and heirs of UAE family businesses. The interviews – face-to-face and asynchronous electronic – are conducted instead of a questionnaire to get an in-depth analysis of the topic in the context of both medium- and large-sized family businesses.

Findings
The responses are mixed with regard to governance challenges (duality, gender, internal control, transparency, etc.). The majority of the interviewees indicate that succession planning remains one of the biggest challenges for family businesses in the UAE. Fifteen of the sixteen interviewees document that a sound succession strategy must be in place to ensure the continuity of the business and prevent future disputes among potential successors. Similarly, the respondents also emphasise the importance of transparency and accountability for the sustainability of family businesses. The sustainability of family businesses relies on many aspects, such as national regulations, corporate systems and the succession process. Finally, most of the respondents from medium-sized companies opined that incorporating CG is a time-consuming and expensive process.

Practical implications
The interviewees supported stewardship theory in case family members are occupying positions on the board as they have more long-term commitment and a greater sense of belonging to the business (socio-emotional wealth) compared to non-family members. The interviewees acknowledge that the lack of professionalism and conflicts of interest among family members can be offset by recruiting non-family members.

Originality/value
Family businesses are particularly significant in the Arab world as they account for over 60% of gross domestic product (GDP) and use above 80% of the workforce which make them interesting research subject. In addition, this paper explores the CG challenges faced by both large- and medium-sized family businesses in the UAE within the theoretical framework of stewardship theory.
Predicting spatio‐temporal population patterns of Borrelia burgdorferi, the Lyme disease pathogen
Authors: Tran Tam , Prusinski Melissa A. , White Jennifer L. , Falco Richard C. , Kokas John , Vinci Vanessa , Gall Wayne K. , Tober Keith J. , Haight Jamie , Oliver JoAnne , Sporn Lee Ann , Meehan Lisa , Banker Elyse , Backenson P. Bryon , Jensen Shane T. , Brisson Dustin 
Published: September 2022

Abstract

The causative bacterium of Lyme disease, Borrelia burgdorferi, expanded from an undetected human pathogen into the etiologic agent of the most common vector‐borne disease in the United States over the last several decades. Systematic field collections of the tick vector reveal increases in the geographic range and prevalence of B. burgdorferi–infected ticks that coincided with increases in human Lyme disease incidence across New York State.

We investigate the impact of environmental features on the population dynamics of B. burgdorferi. Analytical models developed using field collections of nearly 19,000 nymphal Ixodes scapularis and spatially and temporally explicit environmental features accurately explained the variation in the nymphal infection prevalence of B. burgdorferi across space and time.

Importantly, the model identified environmental features reflecting landscape ecology, vertebrate hosts, climatic metrics, climate anomalies and surveillance efforts that can be used to predict the biogeographical patterns of B. burgdorferi–infected ticks into future years and in previously unsampled areas.

Forecasting the distribution and prevalence of a pathogen at fine geographic scales offers a powerful strategy to mitigate a serious public health threat.

Synthesis and applications. A decade of environmental and tick data was collected to create a model that accurately predicts the infection prevalence of Borrelia burgdorferi over space and time. This predictive model can be extrapolated to create a high‐resolution risk map of the Lyme disease pathogen for future years that offers an inexpensive approach to improve both ecological management and public health strategies to mitigate disease risk.
Control on moisture distribution and protein changes of Antarctic krill meat by antifreeze protein during multiple freeze–thaw cycles
Authors: Diao Huayu , Lin Songyi , Li Dongmei , Li Shuang , Feng Qi , Sun Na 
Published: September 2022

AbstractControl on the moisture distribution, protein structure changes, and protein degradation of Antarctic krill meat during freeze–thaw (F–T) cycles by presoaking with antifreeze protein (AFP) was investigated. The results from the thawing loss rate and cooking loss rate indicated that 0.1% was the optimal AFP concentration. Magnetic resonance imaging and low‐field nuclear magnetic resonance results showed that AFP inhibited the changes in moisture distribution and maintained the moisture in Antarctic krill meat. The contents of nonprotein nitrogen and trichloroacetic acid‐soluble peptides indicated that AFP reduced protein degradation. Further, SDS‐PAGE showed that AFP reduced the degradation of actin, troponin T, and myosin light chain. The results of fluorescence spectra, circular dichroism, and chemical bond contents indicated that AFP reduced the damage of the protein tertiary and secondary structures of Antarctic krill meat by holding it in a weak polar environment. This study supplied basic theory for the quality control of Antarctic krill meat.Practical ApplicationProtein degradation, moisture distribution, and protein structure changes occurred to Antarctic krill meat during freeze–thaw cycles due to ice crystal growth and recrystallization, which leads to the decrease in quality. Antifreeze protein has been proven to avoid ice crystals’ growth and inhibit ice recrystallization. During freeze–thaw cycles, the moisture distribution of Antarctic krill meat treated with antifreeze protein was more uniform, the degree of protein degradation was lower, and the protein structure was protected. This study demonstrated the potential of antifreeze protein as a water and protein protectant of Antarctic krill meat during freeze–thaw cycles.