bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficient indexing of peptides for database search using Tide
Authors: Adoquaye Acquaye Frank Lawrence Nii , Kertesz-Farkas Attila , Noble William Stafford 
Published: October 2022

AbstractThe first step in the analysis of protein tandem mass spectrometry data typically involves searching the observed spectra against a protein database. During database search, the search engine must digest the proteins in the database into peptides, subject to digestion rules that are under user control. The choice of these digestion parameters, as well as selection of post-translational modifications (PTMs), can dramatically affect the size of the search space and hence the statistical power of the search. The Tide search engine separates the creation of the peptide index from the database search step, thereby saving time by allowing a peptide index to be reused in multiple searches. Here we describe an improved implementation of the indexing component of Tide that consumes around four times less resources (CPU and RAM) than the previous version and can generate arbitrarily large peptide databases, limited by only the amount of available disk space. We use this improved implementation to explore the relationship between database size and the parameters controlling digestion and PTMs, as well as database size and statistical power. Our results can help guide practitioners in proper selection of these important parameters.
What’s the matter with MICs: The contribution of nutrients and limiting resources to the pharmacodynamics of antibiotics and bacteria
Authors: Berryhill Brandon A. , Gil-Gil Teresa , Manuel Joshua A. , Smith Andrew P. , Margollis Ellie , Baquero Fernando , Levin Bruce R. 
Published: October 2022

AbstractThe minimum inhibitory concentration (MIC) of an antibiotic required to prevent replication is used both as a measure of the susceptibility/resistance of bacteria to that drug and as the single pharmacodynamic parameter for the rational design of antibiotic treatment regimes. MICs are estimated in vitro under conditions optimal for the action of the antibiotic. However, bacteria rarely grow in these optimal conditions. Using a mathematical model of the pharmacodynamics of antibiotics, we make predictions about the nutrient dependency of bacterial growth in the presence of antibiotics. We test these predictions with experiments in a rich media and a glucose-limited minimal media with Escherichia coli and eight different antibiotics. Our experiments uncover properties that question the sufficiency of using MICs and simple pharmacodynamic functions as measures of the pharmacodynamics of antibiotics under the nutritional conditions of infected tissues. To an extent that varies among drugs: (i) The estimated MICs obtained in rich media are greater than those estimated in minimal media. (ii) Exposure to these drugs increases the time before logarithmic growth starts, their lag. (iii) The stationary phase density of E. coli populations declines with greater sub-MIC antibiotic concentrations. We postulate a mechanism to account for the relationship between the sub-MIC concentration of antibiotics and the stationary phase density of bacteria and provide evidence in support of this hypothesis. We discuss the implications of these results to our understanding of the MIC as the unique pharmacodynamic parameter used to design protocols for antibiotic treatment.
Aldehyde inactivation of the RicR regulon sensitizesMycobacterium tuberculosisto copper
Authors: Limón Gina , Samhadaneh Nora M. , Pironti Alejandro , Darwin K. Heran 
Published: October 2022

ABSTRACTMycobacterium tuberculosisis a major human pathogen and the causative agent of tuberculosis disease. WhileM. tuberculosiscan persist in the presence of host-derived antimicrobials like nitric oxide and copper, bacteria defective for proteasome activity are highly sensitive to these molecules, making the proteasome an attractive target for drug development. Previous work linked nitric oxide susceptibility with the accumulation of at least one aldehyde in anM. tuberculosismutant lacking proteasomal degradation. In this study, we show that this aldehyde accumulation is also responsible for copper sensitivity in this strain. Furthermore, we show the exogenous addition of aldehydes to wild-typeM. tuberculosiscultures sensitizes bacteria to copper. We determined that aldehydes directly affect the activity of two members of the RicR (regulatedincopperrepressor) regulon, resulting in the reduced production and function of critical copper-responsive proteins. This study is the first to mechanistically describe how aldehydes can renderM. tuberculosissusceptible to an existing host defense, and could support a broader role for aldehydes in controllingM. tuberculosisinfections.IMPORTANCEM. tuberculosisis a leading cause of death by a single infectious agent, causing 1.5 million deaths annually. An effective vaccine forM. tuberculosisinfections is currently lacking, and prior infection does not typically provide robust immunity to subsequent infections. Nonetheless, immunocompetent humans can controlM. tuberculosisinfections for decades. For these reasons, a clear understanding of how mammalian immunity inhibits mycobacterial growth is warranted. In this study, we show aldehydes can increaseM. tuberculosissusceptibility to copper. Given that activated macrophages produce increased amounts of aldehydes during infection, we propose host-derived aldehydes target critical bacterial survival pathways, making aldehydes a previously unappreciated antimicrobial defense.
The Formation of Biogenic Guanine Crystals Closely Resembles Melanosome Morphogenesis
Authors: Wagner Avital , Upcher Alexander , Maria Raquel , Magnesen Thorolf , Zelinger Einat , Raposo Graça , Palmer Benjamin A. 
Published: October 2022

AbstractAnimals precisely control the morphology and assembly of highly reflective guanine crystals to produce diverse optical phenomena used in coloration and vision. However, little is known about how organisms regulate crystallization to produce optically useful crystal morphologies which express highly reflective crystal faces. Guanine crystals form inside iridosome vesicles within specialized chromatophore cells called iridophores. By following the formation of iridosomes in developing scallop eyes we show that, despite their different physical properties, the morphogenesis of iridosomes bears a striking resemblance to melanosome morphogenesis in vertebrates. A key finding is that pre-assembled intravesicular fibrillar sheets template crystal nucleation, growth, and orientation, dictating the formation of optically functional, but thermodynamically disfavored plate-like habits. The common control mechanisms for melanin and guanine formation inspire new approaches for manipulating the morphologies and properties of molecular materials.
Optogenetic Miro cleavage reveals direct consequences of real-time loss of function inDrosophila
Authors: Mattedi Francesca , Lloyd-Morris Ethlyn , Hirth Frank , Vagnoni Alessio 
Published: October 2022

ABSTRACTMiro GTPases control mitochondrial morphology, calcium homeostasis and regulate mitochondrial distribution by mediating their attachment to the kinesin and dynein motor complex. It is not clear, however, how Miro proteins spatially and temporally integrate their function as acute disruption of protein function has not been performed. To address this issue, we have developed an optogenetic loss of function ’Split-Miro’ allele for precise control of Miro-dependent mitochondrial functions inDrosophila. Rapid optogenetic cleavage of Split-Miro leads to a striking rearrangement of the mitochondrial network, which is mediated by mitochondrial interaction with the microtubules. Unexpectedly, this treatment did not impact the ability of mitochondria to buffer calcium or their association with the endoplasmic reticulum. While Split-Miro overexpression is sufficient to augment mitochondrial motility, sustained photocleavage shows Split-Miro is surprisingly dispensable to maintain elevated mitochondrial processivity. In adult fly neuronsin vivo, Split-Miro photocleavage affects both mitochondrial trafficking and neuronal activity. Furthermore, functional replacement of endogenous Miro with Split-Miro identifies its essential role in the regulation of locomotor activity in adult flies, demonstrating the feasibility of tuning animal behaviour by real-time loss of protein function.
Identification of BcenGI15 genomic island harboring ST839 clone in a population of Burkholderia cenocepacia complex from a major tertiary care hospital in Northern India
Authors: Saroha Tanu , Singh Charu , Kumar Sunil , Kumar Rajesh , Patil Prashant P. , Singhal Lipika , Gautam Vikas , Patil Prabhu B. 
Published: October 2022

ABSTRACTIntroductionBurkholderia cepacia complex (Bcc) is a non-fermenting Gram-negative bacilli (NFGNB) cluster with high genome plasticity and large genome size. As a major nosocomial pathogen, it is known to cause bacteremia, infections in cystic fibrosis patients. One of the factors contributing to multidrug resistance, virulence, and fitness is through chromosomally encoded genetic elements. They carry advantageous genes benefitting the host, thus its crucial to understand their stability and transfer in population. In an earlier study, we have reported a novel genomic island BcenGI15 in a unique clone of Bcc, ST824, involved in a major sepsis outbreak of a pediatric ward in an Indian hospital. In the present study, we have carried out screening of this genomic island by polymerase chain reaction (PCR) in an extensive collection of Bcc isolates from a major tertiary care hospital in Northern part of India.Materials and methods90 isolates obtained from routine patient specimens over a period of 9 years revived from glycerol stock and identified as Burkholderia cenocepacia based on conventional biochemical tests, recA PCR-based restriction fragment length polymorphism (RFLP), and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Isolates were screened for genomic island BcenGI15 via PCR using attL gene primers. Island positive isolates were subjected to multilocus sequence typing (MLST) and antibiotic susceptibility testing.ResultsThe PCR in 16/90 (17.77%) isolates came positive for the presence of BcenGI15. Multi-locus sequence typing (MLST) revealed that all the positive isolates are clonal and belong to a dominant sequence type (ST) ST839.ConclusionMLST data analysis suggested presence of BcenGI15 in two different STs (ST824, ST839) from hospitals in north and west part of India. This suggests probable movement and selection for this element in Indian population of Bcc isolates.
Ultra High-Plex Spatial Proteogenomic Investigation of Giant Cell Glioblastoma Multiforme Immune Infiltrates Reveals Distinct Protein and RNA Expression Profiles
Authors: Bonnett Shilah A. , Rosenbloom Alyssa , Ong Giang , Conner Mark , Rininger Aric , Newhouse Daniel , New Felicia , Phan Chi , Ilcisin Saskia , Sato Hiromi , Lyssand John , Geiss Gary , Beechem Joseph M. 
Published: October 2022

AbstractA deeper understanding of complex biological processes, including tumor development and immune response, requires ultra high-plex, spatial interrogation of multiple “omes”. Here we present the development and implementation of a novel spatial proteogenomic (SPG) assay on the GeoMx® Digital Spatial Profiler platform with NGS readout that enables ultra high-plex digital quantitation of proteins (> 100-plex) and RNA (whole transcriptome, > 18,000-plex) from a single FFPE sample. This study highlighted the high concordance,R> 0.85, and <11% change in sensitivity between SPG assay and the single analyte –assays on various cell lines and tissues from human and mouse. Furthermore, we demonstrate that the SPG assay was reproducible across multiple users. When used in conjunction with advanced cellular neighborhood segmentation, distinct immune or tumor RNA and protein targets were spatially resolved within individual cell subpopulations in human colorectal cancer and non-small cell lung cancer. We used the SPG assay to interrogate 23 different glioblastoma multiforme samples across 4 pathologies. The study revealed distinct clustering of both RNA and protein based on pathology and anatomic location. The in-depth investigation of giant cell glioblastoma multiforme revealed distinct protein and RNA expression profiles compared to that of the more common glioblastoma multiforme. More importantly, the use of spatial proteogenomics allowed simultaneous interrogation of critical protein post-translational modifications alongside whole transcriptomic profiles within the same distinct cellular neighborhoods.
Human sialidase activity is vital for dengue virus serotype 2 infection
Authors: St Clair Laura A. , Pujari Padmasri G. , Perera Rushika 
Published: October 2022

AbstractThe human sialidase enzymes (or neuraminidases, NEU1-4) are glycoside hydrolases that catalyze the removal of sialic acid residues from glycoconjugates, including many bioactive glycoproteins and glycolipids. Through their physiochemical effect on glycoconjugates, sialic acid residues are thought to play vital roles in the control of cellular signaling. In previous studies, it was demonstrated that NEU1-4 activity was increased in cells infected with dengue virus serotype 2 (DENV2). Additionally, it was demonstrated that the DENV2 NS1 protein was sufficient for inducing increased NEU1-4 activity in both in vivo and in vitro models, and that this increased activity was linked to endothelial hyperpermeability and vascular leakage, a hallmark of severe dengue disease. However, the role of increased NEU1-4 activity in the viral lifecycle was not understood. Here, we used siRNA-mediated loss of function studies to evaluate the effect of inhibition of sialidase activity on the DENV2 lifecycle. Our analyses uncovered that apart from their importance for viral pathogenesis, NEU1-4 activity was vital for DENV2 viral replication and egress. Moreover, we characterized the inter-relationship between NEU 1-4, and determined that there was a transcriptional dependency of NEU1-3 on NEU4.
Long-term passaging of replication competent pseudo-typed SARS-CoV-2 reveals the antiviral breadth of monoclonal and bispecific antibody cocktails
Authors: Ma Hang , Zong Huifang , Liu Junjun , Yue Yali , Ke Yong , Liao Yunji , Tang Haoneng , Wang Lei , Wang Shusheng , Yuan Yunsheng , Wu Mingyuan , Bian Yanlin , Zhang Baohong , Yin Haiyang , Jiang Hua , Sun Tao , Han Lei , Xie Yueqing , Zhu Jianwei 
Published: October 2022

AbstractThe continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants poses challenges to the effectiveness of neutralizing antibodies. Rational design of antibody cocktails is a realizable approach addressing viral immune evasion. However, evaluating the breadth of antibody cocktails is essential for understanding the development potential. Here, based on a replication competent vesicular stomatitis virus model that incorporates the spike of SARS-CoV-2 (VSV-SARS-CoV-2), we evaluated the breadth of a number of antibody cocktails consisting of monoclonal antibodies and bispecific antibodies by long-term passaging the virus in the presence of the cocktails. Results from over two-month passaging of the virus showed that 9E12+10D4+2G1 and 7B9-9D11+2G1 from these cocktails were highly resistant to random mutation, and there was no breakthrough after 30 rounds of passaging. As a control, antibody REGN10933 was broken through in the third passage. Next generation sequencing was performed and several critical mutations related to viral evasion were identified. These mutations caused a decrease in neutralization efficiency, but the reduced replication rate and ACE2 susceptibility of the mutant virus suggested that they might not have the potential to become epidemic strains. The 9E12+10D4+2G1 and 7B9-9D11+2G1 cocktails that picked from the VSV-SARS-CoV-2 system efficiently neutralized all current variants of concern and variants of interest including the most recent variants Delta and Omicron, as well as SARS-CoV-1. Our results highlight the feasibility of using the VSV-SARS-CoV-2 system to develop SARS-CoV-2 antibody cocktails and provide a reference for the clinical selection of therapeutic strategies to address the mutational escape of SARS-CoV-2.
Moderating the connections: media coverage and firm market value
Authors: Gama Marina Amado Bahia , Lana Jeferson , Bueno Giovana , Marcon Rosilene , Bandeira-de-Mello Rodrigo 
Published: October 2022

Purpose
The purpose of this paper is to explore how a politically connected firm moderates the relationship between media coverage and market value. More specifically, the authors are interested in the interplay of an external corporate governance (CG) mechanism with an internal one. By interacting different mechanisms, this paper advances the empirical setting of application and functions of the corporate governance.

Design/methodology/approach
This paper tests the hypotheses presented using panel data with a fixed-effect model, by assembling and exploiting a unique, hand-collected set of data on media coverage consisting of over 164,000 media reports and a politically connected board of directors comprising over 12,000 CVs tracked from 2010 to 2014. Data is originally from Brazil, a country where political connections are highly used by firms and that has been a place of much research on corporate political activity.

Findings
The results of this paper suggest that a politically connected board of directors can mitigate the negative effects of media coverage on market value. Overall, the results imply that the validity of a CG mechanism might be affected by other mechanisms.

Research limitations/implications
The findings of this paper imply the need for research focusing on the mutual effects of different CG mechanisms. While CG is understood as a set of mechanisms, new research could focus on the interplay of these mechanisms.

Practical implications
The findings suggest that the presence of former politicians and government officers on the board dissipates bad news reported by the media and boosts market value when media is positive. To maximize investment returns, investors should analyze firms' political human capital.

Originality/value
To the best of the authors’ knowledge, this paper is the first to develop hypotheses on the moderation effects of a politically connected board on the relation between media coverage and market value. This is relevant because this brings insights on how firms could jointly manage these mechanisms.
“Power of words”: impact, concerns and applications of nonviolent communication training
Authors: Korlipara Madhuri , Shah Hardik 
Published: October 2022

PurposeThe purpose of this study is to evaluate the effectiveness of a training program on nonviolent communication (NVC) and assess its impact, concerns and applicability to the context of work. This study also focuses on the factors that influence the retention and application of the skills acquired during the training after three months of completion of the program.Design/methodology/approachThis study uses a qualitative approach. Purposive sampling was used, and 14 semi-structured interviews were conducted to study the impact of an NVC training program titled “Power of words”. Thematic analysis based on Kirkpatrick’s model of training evaluation was used to arrive at the findings.FindingsNVC training was found to have created a sustainable shift in perspective and behaviour of the participants; however, the learning and application of the NVC skills were found to be dependent on individual and contextual factors. The role of the facilitator was found to be crucial in creating safe spaces that were essential for open sharing and effective practice. NVC was found to be easier to apply to contexts of personal relationships; however, in a work context, it holds immense scope to create both organisational- and employee-level outcomes.Research limitations/implicationsThis study has implications for developing theory on NVC and its consequences to humanistic management and employee thriving.Practical implicationsThis study has implications for developing theory on NVC and its consequences for humanistic management and employee thriving. This study has practical implications for humanising communication at work and also has implications for leaders, managers, coaches, counsellors, HR professionals and OD professionals, to improve employee or client experiences. This study also has implications for the potential community development.Social implicationsThis study also has implications for the potential community development as a consequence of NVC training.Originality/valueThe research on the application of NVC training to context of work is very limited, and also, there is very limited research on both the effectiveness of online training and the retention and application of the learning after three months of completion of the program. This study fills these gaps.
The importance of knowledge management in gastronomy: a chef’s future career, the next generations of chefs and trends
Authors: Bressan Alessandro , Duarte Alonso Abel , Kim Vu Oanh Thi , Tran Luong Ngoc , Tran Thanh Duc 
Published: October 2022

PurposeThe purpose of this study is to shed new light on empirical and conceptual aspects related to chefs’ careers and the hospitality sector. The study examines how the future of the chef’s profession is perceived, how future generations of chefs could be developed and the main emerging trends within the chef’s scene.Design/methodology/approachSemi-structured, face-to-face, online and telephone interviews were conducted with 34 chefs operating in Australia and 35 in Vietnam.FindingsThe findings reveal ten dimensions that strongly adhere to knowledge management (KM) and the notions of the knowledge-based view of the firm. In addition, numerous differences in how the two groups perceived aspects of their careers transpire. Based on these findings, a conceptual framework was developed, with important theoretical and practical implications.Practical implicationsThe importance of KM through talent development, mentoring, creating a learning environment and enhancing problem-solving skills is highlighted.Originality/valueWhile scholarly works emphasise chefs’ value, importance and contributions, little is known about the links between their careers and KM. Furthermore, almost no study has compared chefs across geographic/cultural domains. The study addresses these research gaps and contributes to the conceptual understanding of KM within the chefs’ domain.