bluuebunny/crossref_metadata_2025_split huggingface dataset:
A systematic identification of resistance determinants to antisense antibiotics suggests adaptation strategies dependent on the delivery peptide
Authors: Mulkern Adam J. , Vu Thu-Hien , Popella Linda , Kerrinnes Tobias , Ðurica-Mitić Svetlana , Barquist Lars , Vogel Jörg , Galardini Marco 
Published: October 2024

AbstractThe rise of antimicrobial resistance (AMR) among human pathogenic microbes is a serious threat to global health, calling for the development of novel treatment strategies. Antibiotics based on programmable antisense oligomers (asobiotics) offer an attractive solution to the “arms-race”, as their specificity can be quickly updated and tailored to target resistant bacteria. In order to understand the genetic architecture of resistance to asobiotics, we employed laboratory evolution assays to identify mutations that decrease susceptibility to antisense peptide nucleic acid (PNA) against four major gram-negative pathogens:Escherichia coli, Klebsiella pneumoniae, Salmonella enterica, andPseudomonas aeruginosa. We observed that the reduction in susceptibility upon asobiotics treatment was dependent on the specific cell penetrating peptide (CPP) being conjugated to the PNAs, suggesting that reduced uptake is a common adaptation strategy only against the (KFF)3-K CPP. We in fact observed thatsbmAwas frequently mutated in all tested species when treated with (KFF)3-K conjugated PNAs. We further identified mutations related to translation, peptide transport and cell envelope, which provide new hypotheses on cellular response to CPP-PNAs conjugates. Furthermore, for (RXR)4XB-acpPwe observed a modest increase in resistance only when mutations in the PNA binding site were induced, which could easily be bypassed by changing the PNA sequence. These findings indicate that the specific identity of the CPP used plays a key role in determining its robustness against the evolution of resistance, and that laboratory evolution can illuminate the remaining gaps in our knowledge on the mechanisms of action of asobiotics.
Pattern-based genome mining guides discovery of the antibiotic indanopyrrole A from a marine streptomycete
Authors: Sweeney Douglas , Bogdanov Alexander , Chase Alexander B. , Castro-Falcón Gabriel , Trinidad-Javier Alma , Dahesh Samira , Nizet Victor , Jensen Paul R. 
Published: October 2024

ABSTRACTTerrestrial actinomycetes in the genusStreptomyceshave long been recognized as prolific producers of small molecule natural products, including many clinically important antibiotics and cytotoxic agents. AlthoughStreptomycescan also be isolated from marine environments, their potential for natural product biosynthesis remains underexplored. The MAR4 clade of largely marine-derivedStreptomyceshas been a rich source of novel halogenated natural products of diverse structural classes. To further explore the biosynthetic potential of this group, we applied pattern-based genome mining leading to the discovery of the first halogenated pyrroloketoindane natural products, indanopyrrole A (1) and B (2), and the bioinformatic linkage of these compounds to an orphan biosynthetic gene cluster (BCG) in 20 MAR4 genomes. Indanopyrrole A displays potent broad-spectrum antibiotic activity against clinically relevant pathogens. A comparison of the putative indanopyrrole BGC with that of the related compound indanomycin provides new insights into the terminal cyclization and offloading mechanisms in pyrroloketoindane biosynthesis. Broader searches of public databases reveal the rarity of this BGC while also highlighting opportunities for discovering additional compounds in this uncommon class.GRAPHICAL ABSTRACT
Replication Kinetics, Pathogenicity and Virus-induced Cellular Responses of Cattle-origin Influenza A(H5N1) Isolates from Texas, United States
Authors: Mostafa Ahmed , Barre Ramya S. , Allué-Guardia Anna , Escobedo Ruby A. , Shivanna Vinay , Rothan Hussin , Castro Esteban M. , Ma Yao , Cupic Anastasija , Jackson Nathaniel , Bayoumi Mahmoud , Torrelles Jordi B , Ye Chengjin , García-Sastre Adolfo , Martinez-Sobrido Luis 
Published: October 2024

AbstractThe host range of HPAIV H5N1 was recently expanded to include ruminants, particularly dairy cattle in the United States. Shortly after, human H5N1 infection was reported in a dairy worker in Texas following exposure to infected cattle. Herein, we rescued the cattle-origin influenza A/bovine/Texas/24-029328-02/2024(H5N1, rHPbTX) and A/Texas/37/2024(H5N1, rHPhTX) viruses, identified in dairy cattle and human, respectively, and their low pathogenic forms, rLPbTX and rLPhTX, with monobasic HA cleavage sites. Intriguingly, rHPhTX replicated more efficiently than rHPbTX in mammalian and avian cells. Still, variations in the PA and NA proteins didn’t affect their antiviral susceptibility to PA and NA inhibitors. Compared to rHPbTX and rLPbTX, the rHPhTX and rLPhTX exhibited higher pathogenicity and efficient replication in infected C57BL/6J mice. The lungs of rHPhTX-infected mice produced higher inflammatory cytokines/chemokines than rHPbTX-infected mice. Our results highlight potential risk of HPAIV H5N1 virus adaptation in human and/or dairy cattle during the current multistate/multispecies outbreak.
The CYK-4 GAP domain regulates cortical targeting of centralspindlin to promote contractile ring assembly and facilitate ring dissolution
Authors: Schlientz Aleesa J , Lee Kian-Yong , Gómez-Cavazos J. Sebastián , Lara-González Pablo , Desai Arshad , Oegema Karen 
Published: October 2024

SUMMARYDuring cytokinesis, an equatorial contractile ring partitions the cell contents. Contractile ring assembly requires an equatorial zone of active GTP-bound RhoA generated by the guanine nucleotide exchange factor ECT21,2. ECT2 is activated by centralspindlin, a complex composed of two molecules each of kinesin-6 and CYK4. During anaphase, Centralspindlin is activated at the central spindle between the separating chromosomes and diffuses to the plasma membrane, where it engages with ECT2 via its N-terminal half3,4. The C-terminal half of CYK4 contains a lipid-binding C1 domain that contributes to plasma membrane targeting5and a GTPase-activating protein (GAP) domain that has an interaction surface for a Rho family GTPase, whose functions have remained unclear1,3,4,6,7. Here, using the one-cell stageC. elegansembryo as a model, we show that RhoA and the Rho-binding interface of the CYK4 GAP domain drive the recruitment of centralspindlin to the equatorial cortex. By contrast, a point mutant that selectively disrupts GAP activity does not prevent cortical centralspindlin recruitment but instead substantially delays dissipation of centralspindlin from the cortex. These findings suggest that positive feedback, in which centralspindlin recruitment promotes the generation of active RhoA and active RhoA drives centralspindlin recruitment, is central to the rapid assembly of the contractile ring within a narrow time window. They also indicate that the CYK4 GAP catalytic activity contributes to release of centralspindlin from the cortex, potentially to ensure timely dissolution of the contractile ring.
Transcriptional profiling of the cortico-accumbal pathway reveals sex-specific alterations underlying stress susceptibility
Authors: Pessoni AM , Blanc-Arabe L , Pancotti L , Mansouri S , D’Angelo M , Huot K , Marroquin Rivera A , Peralta M , Zhao C , Leboulleux Q , Lévesque M , Proulx CD , Labonté B 
Published: October 2024

AbstractAnxiety and depressive disorders, including major depressive disorder (MDD), affect millions of people every year, imposing significant socio-economic burdens. In this scenario, current treatments for MDD show limited efficacy, highlighting the need to better understand its molecular mechanisms. The medial prefrontal cortex (mPFC) has been identified as a critical brain region in MDD pathology, displaying altered activity and morphology. This study targets the mPFC-to-nucleus accumbens (NAc) pathway, which is implicated in the regulation of emotional behavior. We used a pathway-specific approach to uncover transcriptional profiles in mPFC neurons projecting to the NAc in stressed male and female mice. Using the RiboTag technique and RNA sequencing, we identified sex-specific gene expression changes, revealing potential roles in stress susceptibility. Differential expression and weighted gene co-expression network analyses revealed distinct transcriptional responses to chronic stress in males and females. Key findings include the identification of the X-linked lymphocyte-regulated 4B (Xlr4b) gene, within a highly relevant gene module, as a stress susceptibility driver in males. By experimentally overexpressing theXlr4bgene, we characterized its crucial role in regulating neuronal firing and influencing arborization patterns to promote anxiety-like behavior in a sex-specific fashion. These findings suggest that chronic stress induces unique and shared transcriptional alterations in mPFC neurons projecting to the NAc. Some of these alterations change the morphological and functional properties of neuronal pathways ultimately contributing to the differential manifestation of anxiety-like and depressive-like behaviors in male and female mice.
Alternate routes to acetate tolerance lead to varied isoprenol production from mixed carbon sources inPseudomonas putida
Authors: de Siqueira Guilherme M. V. , Srinivasan Aparajitha , Chen Yan , Gin Jennifer W. , Petzold Christopher J. , Lee Taek Soon , Guazzaroni María-Eugenia , Eng Thomas , Mukhopadhyay Aindrila 
Published: October 2024

AbstractLignocellulose is a renewable resource for the production of a diverse array of platform chemicals, including the biofuel isoprenol. While this carbon stream provides a rich source of sugars, other organic compounds, such as acetate, can be used by microbial hosts. Here we examined growth and isoprenol production in aPseudomonas putidastrain pre-tolerized (“PT”) background where its native isoprenol catabolism pathway is deleted, using glucose and acetate as carbon source. We found that PT displays impaired growth in minimal medium containing acetate, and often fails to grow in glucose-acetate medium. Using a mutant recovery-based approach, we generated tolerized strains that overcame these limitations, achieving fast growth and isoprenol production in the mixed carbon feed. Changes in the glucose and acetate assimilation routes, including an upregulation in PP_0154 (SpcC, succinyl-CoA:acetate CoA-transferase) and differential expression of the gluconate assimilation pathways, were key for higher isoprenol titers in the tolerized strains, while a different set of mechanisms were likely enabling tolerance phenotypes in media containing acetate. Among these, a coproporphyrinogen-III oxidase (HemN) was upregulated across all tolerized strains, and in one isolate required for acetate tolerance. Utilizing a defined glucose and acetate mixture ratio reflective of lignocellulosic feedstocks for isoprenol production inP. putidaallowed us to obtain insights into the dynamics and challenges unique to dual carbon source utilization that are obscured when studied separately. Together, this enabled development of aP. putidabioconversion chassis able to use a more complex carbon stream to produce isoprenol.ImportanceAcetate is a relatively abundant component of many lignocellulosic carbon streams and has the potential of being used together with sugars, especially in microbes with versatile catabolism such asP. putida. However, the use of mixed carbon streams necessitates additional optimization. Further, the use ofP. putidafor the production of the biofuel target, isoprenol, requires the use of engineered strains that have additional growth and production constraints when cultivated in acetate and glucose mixtures. In this study we generate acetate tolerantP. putidastrains that overcome these challenges and examine their ability to produce isoprenol. We show that acetate tolerance and isoprenol production, though independent phenotypes can both be optimized in a givenP. putidastrain. Using proteomics and whole genome sequencing we examine the molecular basis of both phenotypes and show that tolerance to acetate can occur via alternate routes and result in different impacts on isoprenol production.
A survey of the mentor-mentee relationship in early career research (ECR): Implications for publishing and career advancement in the STEMM disciplines
Authors: Lordan Ronan , Wride Michael , O’Sullivan Íde 
Published: October 2024

AbstractEarly career researchers (ECRs) are the most abundant workforce in the fields of science, technology, engineering, mathematics, and medicine (STEMM). ECRs are generally mentored by experienced principal investigators (PIs) who direct the research objectives. The ECR mentee- mentor partnership can be mutually beneficial, but it is a critical relationship for ECRs with implications for publishing and career development. In this study, a mixed methods approach involving a survey, X polls (formally Twitter), and semi-structured interviews were used to determine how the ECR mentor-mentee relationship affects ECRs and their perceptions of career development in STEMM. To address this aim, two main research questions were developed: (1) Who do the STEMM ECR mentees and mentors currently perceive to be ECRs? and (2) What characteristics of the ECR mentee-mentor relationship are perceived to be important for ECR publishing practices and career progression? The main survey findings indicate that respondents largely from the life sciences and health field and they consider Ph.D. researchers and postdoctoral researchers as ECRs, but mentors also to a greater extent than mentees perceive new PIs (< 2 years experiences) as ECRs. Survey respondents also mostly agree on publishing practices regarding journal selection criteria such as journal scope and impact factor, although mentees appear to favor journal prestige and open access publishing more than mentors. This is likely due to the importance of visibility early in one’s career. Mentees take the lead in preparing manuscripts for submission, although a minority have described issues regarding authorship disputes. Finally, setting clear expectations, being collegial, mutually respectful, and having regular communication was identified by survey respondents and interviewees as integral features of a healthy ECR mentee- mentor relationship. In conclusion, the mentee-mentor relationship is critically important for ECR career development, and the findings of this study have wider implications for the development of effective ECR mentee and mentor training programs across the STEMM disciplines.
distect: automatic sample-position tracking for X-ray experiments using computer vision algorithms
Authors: Berg Michael , Furrer Dirk , Thominet Vincent , Wang Xiaoqiang , Zeugin Stefan , Grabner Helmut , Stockinger Kurt , Piamonteze Cinthia 
Published: October 2024

Soft X-ray spectroscopy is an important technique for measuring the fundamental properties of materials. However, for measurements of samples in the sub-millimetre range, many experimental setups show limitations. Position drifts on the order of hundreds of micrometres during thermal stabilization of the system can last for hours of expensive beam time. To compensate for drifts, sample tracking and feedback systems must be used. However, in complex sample environments where sample access is very limited, many existing solutions cannot be applied. In this work, we apply a robust computer vision algorithm to automatically track and readjust the sample position in the dozens of micrometres range. Our approach is applied in a complex sample environment, where the sample is in an ultra-high vacuum chamber, surrounded by cooled thermal shields to reach sample temperatures down to 2.5 K and in the center of a superconducting split coil. Our implementation allows sample-position tracking and adjustment in the vertical direction since this is the dimension where drifts occur during sample temperature change in our setup. The approach can be easily extended to 2D. The algorithm enables a factor of ten improvement in the overlap of a series of X-ray absorption spectra in a sample with a vertical size down to 70 µm. This solution can be used in a variety of experimental stations, where optical access is available and sample access by other means is reduced.
Peer support amongst autistic children: an examination of the communication structure in small-group discussions
Authors: Mankinen Senja , Ferreira Juliene Madureira , Mykkänen Arttu 
Published: October 2024

Purpose
Over the past decade, many studies have investigated peer support between neurotypical and neurodivergent children. Less is known about how autistic children support each other in educational contexts, especially in basic education, where child-adult interactions are still predominant. This study aims to investigate whether and how autistic children supported each other in small-group discussions in the first years of basic education. This paper focused on unraveling the communication structures of these supportive events, aiming to understand further how autistic children make sense of social interactions and intersubjective processes that require peer support.

Design/methodology/approach
Building on conversation analysis methods, this paper analyzed the transcripts of the small-group discussions, identifying and analyzing the construction of support in children’s dialogues. Nine Finnish children (7–10 years old) attending mainstream school in Finland under intensified support in part-time special classrooms participated in this study. The study adopted a specific method called Idea Diary to frame the small-group discussions. The teacher guided the conversations, providing a dynamic structure for children’s interactions, but students were encouraged to interact among themselves. This paper recorded 11 sessions within the six-month implementation of the Idea Diary, totaling 240 min of data.

Findings
Results show that the children recognized situations where other children needed support in interactions and intervened in ways that promoted the continuation of the conversation and the clarification of ideas. Autistic children were sensitive to peers’ unspoken needs, capable of identifying subtle nuances of conversation dynamics and able to express support through comments and questions during the small-group discussions.

Originality/value
This study provides insights into the understudied phenomenon of peer support among autistic children in small-group discussions. It contributes to the growing corpus of research dedicated to exploring and revealing social competencies among autistic people. It discusses implications for developing educational practices that foster social interactions respecting the quality of autistic interactions and the interests of autistic students.
The performance evaluation of hybrid roller bearings under lubricant contamination conditions
Authors: Zhao Xudong , Zhang Yimin 
Published: October 2024

Purpose
This paper aims to evaluate the dynamic performance of hybrid roller bearings under lubricant contamination.

Design/methodology/approach
Some steel rollers in traditional cylindrical thrust roller bearings were replaced with ceramic rollers to assemble hybrid roller bearings. Friction experiments were conducted under lubricant contamination using alumina as the contaminant, and simultaneous vibration acceleration signals from the bearings were collected to evaluate their tribological and dynamic performance.

Findings
Under lubricant contamination, hybrid roller bearings with a sufficient number of ceramic rollers exhibit greater wear resistance compared to traditional all-steel bearings. There is a noticeable suppression of energy in both tangential and normal frequency bands of the bearings, with more pronounced suppression observed in higher frequency bands.

Originality/value
This study provides valuable insights for the development of hybrid ceramic bearings.

Peer review
The peer review history for this article is available at: https://publons.com/publon/10.1108/ILT-08-2024-0291/
Position paper: public policy implications in publicly funded infrastructure projects
Authors: Al Naqbi Khalid Khalfan Mohamed , Ojiako Udechukwu , Al-Mhdawi M.K.S. , Chipulu Maxwell , Dweiri Fikri T. , Bashir Hamdi , AlRaeesi Eman Jasim Hussain 
Published: October 2024

PurposeThis essay contributes to the ongoing exposition of a project management-focused understanding of “public policy” implementation. Distinct from previous studies that take a predominantly administrative sciences perspective, the delivery and implementation of publicly funded infrastructure projects as an instrument of public policy is explored through the lens of legal frameworks.Design/methodology/approachWe adopt the explanation-building review approach to provide descriptions and explanations of the relevant enablers and context necessary for the successful delivery and implementation of publicly funded infrastructure projects.FindingsThe ambiguity associated with public policy is more likely to hinder than facilitate the use of publicly funded infrastructure projects as preferred instruments of choice for implementing public policy.Originality/valueDespite substantial interest among academics and practitioners in utilising projects as tools for public policy implementation, thorough discussions on the legal complexities inherent in these projects remain scarce.
Are you happy with your work? Side effects of workloads and work–family conflict in higher education
Authors: Kim Long , Yeo Sook Fern 
Published: October 2024

PurposeLacking lecturers in higher education is an international issue where society faces insufficient educational services to enlighten one’s future, and lecturer work satisfaction also merits higher attention. Work satisfaction is closely associated with turnover rates, lecturer retention, overall university cohesion, lecturers’ well-being, professional teaching improvement and research and publication performances. This study aims to explore how causes of actions (work–family conflict [WFC] and workload) influence consequences (stress and burnout) which affect the overall attitude (lecturer work satisfaction).Design/methodology/approachResearchers collected data from 450 Thai lecturers from different universities via survey questionnaires. Furthermore, a structural equation model method was used to analyze the data.FindingsResults showed that lecturer stress was significantly influenced by WFC and workload. Next, stress, workload and WFC were the main predictors of lecturer burnout. Then, lecturer work satisfaction was significantly influenced by burnout, except stress. Finally, a relationship between lecturer stress and work satisfaction was mediated by burnout.Originality/valueThis research proposes a theoretical mechanism to analyze how causes of actions (WFC and workload) influence consequences (stress and burnout) which lead to a development of lecturer attitude (work satisfaction) in higher education.