bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new synthetic protegrin as a promising peptide with antibacterial activity against MDR Gram-negative pathogens
Authors: Moreno-Morales Javier , Guardiola Salvador , Ballesté-Delpierre Clara , Giralt Ernest , Vila Jordi 
Published: August 2022

Abstract

Objectives
Protegrins are a family of natural peptides from the innate immune system of vertebrates, with broad-spectrum antimicrobial activity. However, the toxicity and haemolysis of protegrin-1 (PG-1) at low concentrations renders it useless for therapeutic application. We rationally designed PLP-3, a novel synthetic PG-1-like peptide, comprising key activity features of protegrins in a constrained bicyclic structure. Our main objective was to investigate PLP-3’s activity against MDR strains of Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae and to analyse its haemolysis and cytotoxicity.

Methods
Peptide synthesis was performed via solid phase and intramolecular ligation in solution, and the correct folding of the peptide was verified by circular dichroism. Antimicrobial activity was performed through broth microdilution. The test panel contained 45 bacterial strains belonging to A. baumannii, P. aeruginosa and K. pneumoniae (15 strains per species) comprising colistin-resistant and MDR strains. Cytotoxicity was assessed by XTT cell viability assays using HeLa and A549 cells and haemolysis of human erythrocytes.

Results
PLP-3 was successfully synthesized, and its antiparallel β-sheet conformation was confirmed. Antimicrobial activity screening showed MIC90 values of 2 mg/L for A. baumannii, 16 mg/L for K. pneumoniae and 8 mg/L for P. aeruginosa. The haemolysis IC50 value was 48.53 mg/L. Cytotoxicity against human HeLa and A549 cells showed values of ca. 200 mg/L in both cell lines resulting in a 100-fold selectivity window for bacterial over human cells.

Conclusions
PLP-3 has potent antimicrobial activity, especially against A. baumannii, while maintaining low haemolysis and toxicity against human cell lines at antimicrobial concentrations. These characteristics make PLP-3 a promising peptide with an interesting therapeutic window.
Quaternary organization of the human eEF1B complex reveals unique multi-GEF domain assembly
Authors: Bondarchuk Tetiana V , Shalak Vyacheslav F , Lozhko Dmytro M , Fatalska Agnieszka , Szczepanowski Roman H , Liudkovska Vladyslava , Tsuvariev Oleksandr Yu , Dadlez Michal , El'skaya Anna V , Negrutskii Boris S 
Published: August 2022

Abstract
Protein synthesis in eukaryotic cell is spatially and structurally compartmentalized that ensures high efficiency of this process. One of the distinctive features of higher eukaryotes is the existence of stable multi-protein complexes of aminoacyl-tRNA synthetases and translation elongation factors. Here, we report a quaternary organization of the human guanine-nucleotide exchange factor (GEF) complex, eEF1B, comprising α, β and γ subunits that specifically associate into a heterotrimeric form eEF1B(αβγ)3. As both the eEF1Bα and eEF1Bβ proteins have structurally conserved GEF domains, their total number within the complex is equal to six. Such, so far, unique structural assembly of the guanine-nucleotide exchange factors within a stable complex may be considered as a ‘GEF hub’ that ensures efficient maintenance of the translationally active GTP-bound conformation of eEF1A in higher eukaryotes.
3D (x-y-t) Raman imaging of tomato fruit cuticle: Microchemistry during development
Authors: González Moreno Ana , Domínguez Eva , Mayer Konrad , Xiao Nannan , Bock Peter , Heredia Antonio , Gierlinger Notburga 
Published: August 2022

Abstract
The cuticle is a protective extracellular matrix that covers the above-ground epidermis of land plants. Here, we studied the cuticle of tomato (Solanum lycopersicum L.) fruits in situ using confocal Raman microscopy. Microsections from cuticles isolated at different developmental stages were scanned to visualize cuticle components with a spatial resolution of 342 nm by univariate and multivariate data analysis. Three main components, cutin, polysaccharides, and aromatics, were identified, with the latter exhibiting the strongest Raman scattering intensity. Phenolic acids and flavonoids were differentiated within the cuticle, and three schematic cuticle models were identified during development. Phenolic acids were found across the entire cuticle at the earliest stage of development, i.e. during the formation of the procuticle layer. Based on a mixture analysis with reference component spectra, the phenolic acids were identified as mainly esterified p-coumaric acid together with free p-hydroxybenzoic acid. During the cell expansion period of growth, phenolic acids accumulated in an outermost layer of the cuticle and in the middle region of the pegs. In these stages of development, cellulose and pectin were detected next to the inner cuticle region, close to the epidermal cell where flavonoid impregnation started during ripening. In the first ripening stage, chalconaringenin was observed, while methoxylated chalcones were chosen by the algorithm to fit the mature cuticle spectra. The colocation of carbohydrates, esterified p-coumaric acid, and methoxylated chalconaringenin suggests that the latter two link polysaccharide and cutin domains. Elucidating the different distribution of aromatics within the cuticle, suggests important functions: (1) overall impregnation conferring mechanical and thermal functions (2) the outermost phenolic acid layer displaying UV-B protection of the plant tissue.
AtPRMT5-mediated AtLCD methylation improves Cd2+ tolerance via increased H2S production in Arabidopsis
Authors: Cao Haiyan , Liang Yali , Zhang Liping , Liu Zhiqiang , Liu Danmei , Cao Xiaofeng , Deng Xian , Jin Zhuping , Pei Yanxi 
Published: August 2022

Abstract
Arabidopsis (Arabidopsis thaliana) PROTEIN ARGININE METHYLTRANSFERASE5 (PRMT5), a highly conserved arginine (Arg) methyltransferase protein, regulates multiple aspects of the growth, development, and environmental stress responses by methylating Arg in histones and some mRNA splicing-related proteins in plants. Hydrogen sulfide (H2S) is a recently characterized gasotransmitter that also regulates various important physiological processes. l-cysteine desulfhydrase (LCD) is a key enzyme of endogenous H2S production. However, our understanding of the upstream regulatory mechanisms of endogenous H2S production is limited in plant cells. Here, we confirmed that AtPRMT5 increases the enzymatic activity of AtLCD through methylation modifications during stress responses. Both atprmt5 and atlcd mutants were sensitive to cadmium (Cd2+), whereas the overexpression (OE) of AtPRMT5 or AtLCD enhanced the Cd2+ tolerance of plants. AtPRMT5 methylated AtLCD at Arg-83, leading to a significant increase in AtLCD enzymatic activity. The Cd2+ sensitivity of atprmt5-2 atlcd double mutants was consistent with that of atlcd plants. When AtPRMT5 was overexpressed in the atlcd mutant, the Cd2+ tolerance of plants was significantly lower than that of AtPRMT5-OE plants in the wild-type background. These results were confirmed in pharmacological experiments. Thus, AtPRMT5 methylation of AtLCD increases its enzymatic activity, thereby strengthening the endogenous H2S signal and ultimately improving plant tolerance to Cd2+ stress. These findings provide further insights into the substrates of AtPRMT5 and increase our understanding of the regulatory mechanism upstream of H2S signals.
Chronic Pelvic Pain Profiles in Women Seeking Care in a Tertiary Pelvic Pain Clinic
Authors: Li Rui , Kreher Donna A , Gubbels Ashley L , Palermo Tonya M 
Published: August 2022

Abstract

Objective
Female chronic pelvic pain (CPP) has multiple pain generators and significant psychosocial sequalae. Biopsychosocial-based phenotyping could help identify clinical heterogeneity that may inform tailored patient treatment. This study sought to identify distinct CPP profiles based on routinely collected clinical information and evaluate the validity of the profiles through associations with social histories and subsequent health care utilization.

Methods
Women (18–77 years, n = 200) seeking care for CPP in a tertiary gynecological pelvic pain clinic between 2017 and 2020 were included. Baseline data of pain intensity, interference, catastrophizing, acceptance, overlapping pelvic pain syndromes, and co-occurring psychiatric disorders were subject to a partition around medoids clustering to identify patient profiles. Profiles were compared across social history and subsequent treatment modality, prescribed medications, and surgeries performed.

Results
Two profiles with equal proportion were identified. Profile 1 was vulvodynia and myofascial pelvic pain-dominant characterized by lower pain burden and better psychological functioning. Profile 2 was visceral pain-dominant featuring higher pain interference and catastrophizing, lower pain acceptance, and higher psychiatric comorbidity. Patients in Profile 2 had 2–4 times higher prevalence of childhood and adulthood abuse history (all P &lt; .001), were more likely to subsequently receive behavioral therapy (46% vs 27%, P = .005) and hormonal treatments (34% vs 21%, P = .04), and were prescribed more classes of medications for pain management (P = .045) compared to patients in Profile 1.

Conclusions
Treatment-seeking women with CPP could be separated into two groups distinguished by pain clusters, pain burden, pain distress and coping, and co-occurring mental health disorders.
Tofacitinib to Treat Severe Acute Refractory Colitis in a Teenager: Case Report and Review of the Literature
Authors: Girard Chloé , Dirks Martha , Deslandres Colette 
Published: August 2022

Objectives:
Acute severe colitis (ASC) may occur within 3 months of ulcerative colitis diagnosis in 9%–15% of children and the rate of colectomy is up to 40%–50% within 5 years after an ASC. The aim of this publication is to present recent and relevant data on the success of medical treatment with tofacitinib in ASC.

Methods:
We report a challenging case of a teenage boy with ASC at diagnosis and conduct a discussion after a review of the literature regarding the use of tofacitinib in inflammatory bowel disease, especially in pediatric patients and in ASC.

Results:
The patient was hospitalized for 10 weeks and was refractory to conventional therapies: intravenous corticosteroids, infliximab, methotrexate, and vedolizumab. He received 7 blood transfusions and also presented with a severe malnutrition requiring a total parenteral nutrition. Tofacitinib was considered as a medical last resort before colectomy and was started at week 8. Thirteen days after starting tofacitinib, he was asymptomatic and was discharged on tofacitinib as sole treatment. By week 9 of tofacitinib, a colonoscopy showed both endoscopic and histological remission. He has remained in clinical remission at 6-month follow-up.

Conclusions:
Tofacitinib may be an alternative medical treatment to avoid colectomy in ASC. It is a small molecule with a rapid onset and few severe adverse events. It has been used for ASC in adult patients, allowing to avoid colectomy in more than 60%. To our knowledge, this is one of the few pediatric patients with refractory ASC at initial diagnosis who responded to tofacitinib.
Specialized germline P-bodies are required to specify germ cell fate in C. elegans embryos
Authors: Cassani Madeline , Seydoux Geraldine 
Published: August 2022

ABSTRACTIn animals with germ plasm, specification of the germline involves “germ granules”, cytoplasmic condensates that enrich maternal transcripts in the germline founder cells. In C. elegans embryos, P granules enrich maternal transcripts, but surprisingly P granules are not essential for germ cell fate specification. Here we describe a second condensate in the C. elegans germ plasm. Like canonical P-bodies found in somatic cells, “germline P-bodies” contain regulators of mRNA decapping and deadenylation and, in addition, the intrinsically-disordered proteins MEG-1 and MEG-2 and the TIS11-family RNA-binding protein POS-1. Embryos lacking meg-1 and meg-2 do not stabilize P-body components, miss-regulate POS-1 targets, miss-specify the germline founder cell, and do not develop a germline. Our findings suggest that specification of the germ line involves at least two distinct condensates that independently enrich and regulate maternal mRNAs in the germline founder cells.
TMsDP: two-stage density peak clustering based on multi-strategy optimization
Authors: Ma Jie , Hao Zhiyuan , Hu Mo 
Published: August 2022

PurposeThe density peak clustering algorithm (DP) is proposed to identify cluster centers by two parameters, i.e. ρ value (local density) and δ value (the distance between a point and another point with a higher ρ value). According to the center-identifying principle of the DP, the potential cluster centers should have a higher ρ value and a higher δ value than other points. However, this principle may limit the DP from identifying some categories with multi-centers or the centers in lower-density regions. In addition, the improper assignment strategy of the DP could cause a wrong assignment result for the non-center points. This paper aims to address the aforementioned issues and improve the clustering performance of the DP.Design/methodology/approachFirst, to identify as many potential cluster centers as possible, the authors construct a point-domain by introducing the pinhole imaging strategy to extend the searching range of the potential cluster centers. Second, they design different novel calculation methods for calculating the domain distance, point-domain density and domain similarity. Third, they adopt domain similarity to achieve the domain merging process and optimize the final clustering results.FindingsThe experimental results on analyzing 12 synthetic data sets and 12 real-world data sets show that two-stage density peak clustering based on multi-strategy optimization (TMsDP) outperforms the DP and other state-of-the-art algorithms.Originality/valueThe authors propose a novel DP-based clustering method, i.e. TMsDP, and transform the relationship between points into that between domains to ultimately further optimize the clustering performance of the DP.
Stakeholder perceptions of mentoring in developing girls’ STEM identities: “you do not have to be the textbook scientist with a white coat”
Authors: Millar Victoria , Hobbs Linda , Speldewinde Christopher , van Driel Jan 
Published: August 2022

PurposeGirls are underrepresented in many school science, technology, engineering and mathematics (STEM) subjects, leading to ongoing gender disparity in STEM careers. This issue is not new and has seen a range of initiatives implemented in an attempt to increase girls’ STEM participation. In Australia, a number of these initiatives have emphasised role models and mentors. This paper seeks to understand the influence of role models and mentors on girls’ STEM identities.Design/methodology/approachThis paper presents qualitative research undertaken with STEM experts into the influences on girls’ STEM identities. Data were collected through three phases involving semi-structured interviews, a forum and focus groups. Thematic analysis identified the importance of mentoring and role modelling in shaping girls’ STEM participation and identities.FindingsThis paper provides a basis for rethinking how and when role models and mentors can assist girls in making decisions about STEM. In particular, it reveals the need for role models and mentors to consider the role of relatability in developing girls’ STEM identities and the need to do this at multiple points throughout girls’ lives.Originality/valueThis article captures the perspectives of multiple experts involved in a variety of STEM professions on the topic of how mentors and role models can influence girls to consider STEM professions. Utilising the concept of identity, this paper sheds new light on girls’ interactions with role models and mentors and the value of storying in role modelling and mentoring relationships as an important component of girls’ identity work in relation to STEM.
University-Affiliated Research Centers: evasive entrepreneurship within the DOD
Authors: Reilly Chandler 
Published: August 2022

PurposeThe Department of Defense (DOD) has long partnered with universities and other nonprofit organizations to perform early-stage, military-related research using research centers established under long-term contracts known as Federally Funded Research and Development Centers (FFRDCs). Over the last 25 years, there has been a shift in the type of arrangement used to University Affiliated Research Centers (UARCs) that this paper argues is the result of bureaucrats acting as evasive entrepreneurs in response to changing regulations.Design/methodology/approachExtending the theory of evasive entrepreneurship to bureaucrats, the author shows how regulations increase the cost of bureaucratic action and incentivize the creation of substitute actions to avoid those regulatory costs and capture benefits. Qualitative evidence from DOD documents is used to support the contention that UARCs serve the same function as FFRDCs. Quantitative evidence on the number of FFRDCs and UARCs and their funding illustrates how bureaucrats respond to political restrictions.FindingsBureaucrats have little to no recourse to respond to budgetary cuts or spending ceilings. In the case of FFRDCs, spending ceilings were introduced starting in the 1960s and led to a decline in the number of DOD FFRDCs. Bureaucrats can however strategically evade new regulations by reorganizing transactions justified by existing federal law that contradicts new regulations. Once FFRDCs were federally regulated in 1990 there were strong incentives to create substitute arrangements leading to the creation of UARCs in 1996 that have ultimately replaced FFRDCs as the research center of choice for the DOD.Originality/valueThe article makes three contributions. First, it applies the concept of evasive entrepreneurship to a political context and then use that framework to understand the creation and establishment of the DOD's UARCS. Second, the organizational features and purpose of UARCs are analyzed. Third, the evidence provided shows how regulations resulted in a shift in the DOD's R&D strategy toward working with universities.
Big data from customers and non-customers through crowdsourcing, citizen science and crowdfunding
Authors: Cappa Francesco 
Published: August 2022

Purpose
The unprecedented growth in the volume, variety and velocity with which data is generated and collected over the last decade has led to the spread of big data phenomenon. Organizations have become increasingly involved in the collection and analysis of big data to improve their performance. Whereas the focus thus far has mainly been on big data collected from customers, the topic of how to collect data also from those who are not yet customers has been overlooked. A growing means of interacting with non-customers is through crowd-based phenomena, which are therefore examined in this study as a way to further collect big data. Therefore, this study aims to demonstrate the importance of jointly considering these phenomena under the proposed framework.

Design/methodology/approach
This study seeks to demonstrate that organizations can collect big data from a crowd of customers and non-customers through crowd-based phenomena such as crowdsourcing, citizen science and crowdfunding. The conceptual analysis conducted in this study produced an integrated framework through which companies can improve their performance.

Findings
Grounded in the resource-based view, this paper argues that non-customers can constitute a valuable resource insofar as they can be an additional source of big data when participating in crowd-based phenomena. Companies can, in this way, further improve their performance.

Originality/value
This study advances scientific knowledge of big data and crowd-based phenomena by providing an overview of how they can be jointly applied to further benefit organizations. Moreover, the framework posited in this study is an endeavour to stimulate further analyses of these topics and provide initial suggestions on how organizations can jointly leverage crowd-based phenomena and big data.
Embedded librarianship and Greek academic libraries
Authors: Kyprianos Konstantinos 
Published: August 2022

PurposeThe purpose of this study is to provide a detailed overview of the role and participation of embedded librarians in the academic e-classroom. More specifically, this paper reflects the perceptions of Greek academic librarians regarding the use of learning management systems (LMSs). Furthermore, it seeks to highlight the most popular software, to list the services provided through LMSs and to determine the level of librarians’ engagement with LMSs. Finally, it investigates the challenges and benefits of their use.Design/methodology/approachSurvey research was used as the methodological design. An adequate questionnaire was created for the collection of quantitative data to study the activities and experiences of academic embedded librarians.FindingsAccording to the study findings, a considerable percentage of academic librarians use the potential of LMSs, indicating that embedded librarianship is the future for Greek academic libraries. However, it seems that LMSs are not fully exploited even during the pandemic when the libraries remained closed.Research limitations/implicationsThis study was exploratory in nature and thus its scope was limited. It was limited to embedded librarianship in academic libraries.Practical implicationsEmbedded librarianship comes with many challenges for its practitioners; yet, it also has the potential to connect libraries and librarians directly to the overall institutional aims and enhance their positions in the academy.Originality/valueThe role and participation of embedded librarians in Greek academic institutions is a research area that has not been fully investigated. Therefore, this paper can give insights into this critical issue, especially during a pandemic.
Ceasefire monitoring under fire: TheOSCE, technology, and the 2022 war in Ukraine
Authors: Verjee Aly 
Published: August 2022

AbstractThis Policy Insight discusses what was the world's largest dedicated third‐party ceasefire monitoring operation, the Special Monitoring Mission (SMM), which, until the Russian invasion in early 2022, oversaw a ceasefire in Ukraine. Although it may now seem obvious to conclude that the SMM failed to deter conflict escalation, this once‐heralded, ‘model’ mission provides insights for the design and implementation of other ceasefire monitoring efforts. This Policy Insight argues that the limitations and differing interpretations of the SMM's mandate, an inability to attribute responsibility for violations, and a failure to act in response to violations substantially weakened the practice of ceasefire monitoring in Ukraine. Still, important lessons can be identified for future monitoring work, whether in Ukraine or elsewhere, including agreeing on the mechanisms for consequences when violations occur, better understanding the limitations of remote sensing technology in monitoring, and establishing more robust planning for mission suspension, evacuation, and termination.