bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transient infection of
Euprymna scolopes
with an engineered D-alanine auxotroph of
Vibrio fischeri
Authors: Coppinger Macey , Yang Liu , Popham David L. , Ruby Edward , Stabb Eric V. 
Published: September 2024

ABSTRACT

The symbiosis between
Vibrio fischeri
and the Hawaiian bobtail squid,
Euprymna scolopes
, is a tractable and well-studied model of bacteria-animal mutualism. Here, we developed a method to transiently colonize
E. scolopes
using D-alanine (D-ala) auxotrophy of the symbiont, controlling the persistence of viable infection by supplying or withholding D-ala. We generated alanine racemase (
alr
) mutants of
V. fischeri
that lack avenues for mutational suppression of auxotrophy or reversion to prototrophy. Surprisingly, an ∆
alr
mutant did not require D-ala to grow in a minimal medium, a phenomenon requiring
metC
, which encodes cystathionine β-lyase. Likewise, overexpression of
metC
suppressed D-ala auxotrophy in a rich medium. To block potential mechanisms of suppression, we combined the ∆
alr
mutation with deletions of
metC
and/or
bsrF
, which encodes a broad-spectrum racemase and investigated the suppression rates of four D-ala auxotrophic strains. We then focused on ∆
alr
∆
bsrF
mutant MC13, which has a suppression rate of <10
−9
. When D-ala was removed from a growing culture of MC13, cells rounded and lysed within 40 minutes. Transient colonization of
E. scolopes
was achieved by inoculating squid in seawater containing MC13 and D-ala, and then transferring the squid into water lacking D-ala, which resulted in loss of viable symbionts within hours. Interestingly, the symbionts within crypt 3 persisted longer than those of crypt 1, suggesting a difference in bacterial growth rate in distinct crypt environments. Our study highlights a new approach for inducing transient colonization and provides insight into the biogeography of the
E. scolopes
light organ.

IMPORTANCE

The importance of this study is multi-faceted, providing a valuable methodological tool and insight into the biology of the symbiosis between
Vibrio fischeri
and
Euprymna scolopes
. First, the study sheds light on the critical role of D-ala for bacterial growth, and the underpinnings of D-ala synthesis. Our observations that
metC
obviates the need for D-ala supplementation of an
alr
mutant in minimal medium and that MetC-dependent growth correlates with D-ala in peptidoglycan, corroborate and extend previous findings in
Escherichia coli
regarding a role of MetC in D-ala production. Second, our isolation of robust D-ala auxotrophs led us to a novel method for studying the squid-
Vibrio
symbiosis, allowing for transient colonization without the use of antibiotics, and revealed intriguing differences in symbiont growth parameters in distinct light organ crypts. This work and the methodology developed will contribute to our understanding of the persistence and dynamics of
V. fischeri
within its host.
Structural and functional diversity of Resistance-Nodulation-Division (RND) efflux pump transporters with implications for antimicrobial resistance
Authors: Kavanaugh Logan G. , Dey Debayan , Shafer William M. , Conn Graeme L. 
Published: September 2024

SUMMARY
The discovery of bacterial efflux pumps significantly advanced our understanding of how bacteria can resist cytotoxic compounds that they encounter. Within the structurally and functionally distinct families of efflux pumps, those of the Resistance-Nodulation-Division (RND) superfamily are noteworthy for their ability to reduce the intracellular concentration of structurally diverse antimicrobials. RND systems are possessed by many Gram-negative bacteria, including those causing serious human disease, and frequently contribute to resistance to multiple antibiotics. Herein, we review the current literature on the structure-function relationships of representative transporter proteins of tripartite RND efflux pumps of clinically important pathogens. We emphasize their contribution to bacterial resistance to clinically used antibiotics, host defense antimicrobials and other biocides, as well as highlighting structural similarities and differences among efflux transporters that help bacteria survive in the face of antimicrobials. Furthermore, we discuss technical advances that have facilitated and advanced efflux pump research and suggest future areas of investigation that will advance antimicrobial development efforts.
Jet Fuel as a Source of Soil Pollution: A Review
Authors: Koroleva T. V. , Semenkov I. N. , Lednev S. A. , Soldatova O. S. 
Published: September 2024

Abstract
Kerosene is widely used in various types of anthropogenic activities. Its environmental safety is mainly discussed in the context of aerospace activities. At all stages of its life cycle, aerospace activity impacts the environment. In aviation, the pollution of atmospheric air and terrestrial ecosystems is caused, first of all, by jet fuel and the products of its incomplete combustion and is technologically specified for a number of models in the case of fuel leak during an emergency landing. In the rocket and space activities, jet fuel enters terrestrial ecosystems as a result of fuel spills from engines and fuel tanks at the crash sites of the first stages of launch vehicles. The jet fuel from the second and third stages of launch vehicles does not enter terrestrial ecosystems. The fuel components have been studied in sufficient detail. However, the papers with representative data sets and their statistical processing not only for the kerosene content, but also for the total petroleum hydrocarbons in the soils affected by aerospace activity are almost absent. Nevertheless, the available data and results of mathematical modeling allow us to assert that an acceptable level of hydrocarbons, not exceeding the assimilation potential, enters terrestrial ecosystems during a regular aerospace activity. Thus, the incoming amount of jet fuel disappears rapidly enough without causing any irreversible damage.
Investigating the impact of multidisciplinary prehabilitation on deconditioning in patients eligible for haematopoietic allogenic stem cell transplantation: protocol for a feasibility trial
Authors: Naumann Karlee , Singh Ben , Bushaway Samuel , Crane Rhiannon , Deepak Swapna , Hartland Amie , Konstantopoulos Peter , Mansell Ella , Marinelli Vanessa , Pallotta Vanessa , Tolfts Annabel , Virieux Alison , Wall Michelle , Wilksch Sarah , Zhuang Mabel , Atkinson Morgan , Maher Carol 
Published: September 2024

BackgroundAssessing multidisciplinary prehabilitation strategies becomes crucial to pre-emptively counter the physical, psychological and social negative impacts experienced during an allogenic haematopoietic stem cell transplant (allo-HSCT) among acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) patients. Current evidence is restricted to studies during induction chemotherapy, omitting rehabilitation interventions and predominantly using exercise-only approaches without a multidisciplinary framework. The aim of this study is to investigate the feasibility, safety and preliminary efficacy of multidisciplinary prehabilitation in adults offered allo-HSCT.Methods and analysisThis 8-week single-group pre-post feasibility study aims to pilot a multidisciplinary prehabilitation intervention for participants undergoing allo-HSCT, with a focus on feasibility and safety. Participants, aged 18 or older, diagnosed with AML or MDS, and offered allo-HSCT, will be recruited between June 2023 and July 2024. The multidisciplinary prehabilitation intervention, conducted by the cancer allied health team at the Royal Adelaide Hospital, includes exercise physiology, physiotherapy, dietetics, social work, occupational therapy and psychology interventions. Consistent with a multidisciplinary treatment approach, each component is tailored to address different aspects of patient care, and adherence calculations will assess patient engagement and compliance. In addition, participants will continue to receive usual care from cancer allied health staff. The primary outcome of the study is to assess the feasibility of a multidisciplinary prehabilitation intervention by evaluating intervention uptake, retention, adherence, acceptability and safety. Secondary outcomes are leg strength, upper-body strength, aerobic fitness, falls risk, anthropometry, nutritional status, quality of life, anxiety, depression, self-efficacy for coping with cancer and distress.Ethics and disseminationEthics approval for this study has been provided by the Central Adelaide Local Health Network (HREC 2022/HRE00284). Recruitment for the study commenced in June 2023 and will continue until July 2024. The methods have been designed and are reported according to the SPIRIT and CONSORT-pilot study checklist.Trial registration numberThe Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12623000052639.
Current situation and relationship between occupational stress, burn-out and sleep quality among ambulance drivers: a cross-sectional study
Authors: Zhang Jianfei , Tan Kaixi , Xiao Xia , Tang Yujun , Tong Jing , Ling Lin 
Published: September 2024

ObjectiveTo understand the current status of occupational stress, occupational burn-out and sleep quality among ambulance drivers in Hengyang, China and to analyse the relationship between occupational stress, occupational burn-out and sleep quality of ambulance drivers.DesignA cross-sectional study.SettingPrehospital emergency centre of third-class hospital in Hengyang, China.ParticipantsFrom October 2023 to December 2023, a cross-sectional survey was conducted, with 213 ambulance drivers from Hengyang, China, selected as participants.MethodsGeneral demographic questionnaires, the Chinese Occupational Stress Inventory, the Maslach Burnout Inventory and the Pittsburgh Sleep Quality Index were used for data collection and analysis.ResultsOccupational stress among ambulance drivers was positively correlated with occupational burn-out and sleep quality (r=0.528, 0.447, both p<0.01) while occupational burn-out was positively correlated with sleep quality (r=0.394, p<0.01). Occupational burn-out partially mediated the relationship between occupational stress and sleep quality among ambulance drivers, with a mediation effect value of 0.168, accounting for 26.09% of the total effect.ConclusionThe sleep quality of ambulance drivers in Hengyang, China is suboptimal, with occupational stress directly predicting sleep quality. Occupational burn-out plays a partial positive mediating role between occupational stress and sleep quality among ambulance drivers. Reducing occupational stress and burn-out is beneficial for improving the sleep quality of ambulance drivers.
Loss of Annexin A1 in macrophages restrains efferocytosis and remodels immune microenvironment in pancreatic cancer by activating the cGAS/STING pathway
Authors: Hou Zelin , Lu Fengchun , Lin Jiajing , Wu Yuwei , Chen Linjin , Fang Haizong , Chen Linlin , Zhang Shihan , Huang Heguang , Pan Yu 
Published: September 2024

ObjectivePancreatic cancer is an incurable malignant disease with extremely poor prognosis and a complex tumor microenvironment. We sought to characterize the role of Annexin A1 (ANXA1) in pancreatic cancer, including its ability to promote efferocytosis and antitumor immune responses.MethodsThe tumor expression of ANXA1 and cleaved Caspase-3 (c-Casp3) and numbers of tumor-infiltrating CD68+macrophages in 151 cases of pancreatic cancer were examined by immunohistochemistry and immunofluorescence. The role of ANXA1 in pancreatic cancer was investigated using myeloid-specific ANXA1-knockout mice. The changes in tumor-infiltrating immune cell populations induced by ANXA1 deficiency in macrophages were assessed by single-cell RNA sequencing and flow cytometry.ResultsANXA1 expression in pancreatic cancer patient samples correlated with the number of CD68+macrophages. The percentage of ANXA1+tumor-infiltrating macrophages negatively correlated with c-Casp3 expression and was significantly associated with worse survival. In mice, myeloid-specific ANXA1 deficiency inhibited tumor growth and was accompanied by the accumulation of apoptotic cells in pancreatic tumor tissue caused by inhibition of macrophage efferocytosis, which was dependent on cGAS-STING pathway-induced type I interferon signaling. ANXA1 deficiency significantly remodeled the intratumoral lymphocyte and macrophage compartments in tumor-bearing mice by increasing the number of effector T cells and pro-inflammatory macrophages. Furthermore, combination therapy of ANXA1 knockdown with gemcitabine and anti-programmed cell death protein-1 antibody resulted in synergistic inhibition of pancreatic tumor growth.ConclusionThis research uncovers a novel role of macrophage ANXA1 in pancreatic cancer. ANXA1-mediated regulation of efferocytosis by tumor-associated macrophages promotes antitumor immune response via STING signaling, suggesting potential treatment strategies for pancreatic cancer.
Bounds on ultralight bosons from the Event Horizon Telescope observation of Sgr A$$^*$$
Authors: Saha Akash Kumar , Parashari Priyank , Maity Tarak Nath , Dubey Abhishek , Bouri Subhadip , Laha Ranjan 
Published: September 2024

AbstractRecent observation of Sagittarius A$$^*$$

∗

(Sgr A$$^*$$

∗

) by the Event Horizon Telescope (EHT) collaboration has uncovered various unanswered questions in black hole (BH) physics. Besides, it may also probe various beyond the Standard Model (BSM) scenarios. One of the most profound possibilities is the search for ultralight bosons (ULBs) using BH superradiance (SR). EHT observations imply that Sgr A$$^*$$

∗

has a non-zero spin. Using this observation, we derive bounds on the mass of ULBs with purely gravitational interactions. Considering self-interacting ultralight axions, we constrain new regions in the parameter space of decay constant, for a certain spin of Sgr A$$^*$$

∗

. Future observations of various spinning BHs can improve the present constraints on ULBs.
Abstract A001: PAX3-FOXO1-induced transcriptional dysregulation in rhabdomyosarcoma
Authors: Stevens Bradley T. , Zhang Yang , Larsen Randolph K. , Adkins Grace E. , Hopkins Jack D. , Kimbrough Darden W. , Garcia Matthew R. , Hatley Mark E. , Abraham Brian J. 
Published: September 2024

Abstract
The survival rate for high-risk rhabdomyosarcoma (RMS) has not increased above 20% in the last thirty years. This insufficiency persists despite thorough molecular characterization of existing models and patient tumors, which has demonstrated that the most challenging RMS tumors harbor chromosomal translocations generating PAX3-FOXO1 (P3F) or PAX7-FOXO1 (P7F) oncofusion transcription factors. The presence of P3/7F largely explains the alveolar subtype of RMS. However, the molecular mechanisms by which P3/7F drives tumor onset and the extent to which they are required after establishment of RMS remain unclear. In recent work, we challenged the dogma that fusion-positive RMS arises from incompletely differentiated muscle cells by demonstrating that P3F-bearing endothelial precursors form RMS tumors ex vivo and in vivo. This observation proposes an explanation for why RMS is observed throughout the body including in sites devoid of skeletal muscle. Here, we describe a novel constructionist model of RMS in which the P3F protein is added to induced pluripotent stem cell-derived endothelial precursors. The inducible alveolar rhabdomyosarcoma (iARMS) system faithfully recapitulates tumor-relevant aspects of RMS biology, including histology, tumor-formation, and the upregulation of signature expression programs. P3F expression during endothelial-directed differentiation blocked endothelial maturation and reprogrammed cell identity toward skeletal muscle-like cells that form ARMS tumors in mice. The iARMS system reproducibly generates RMS over a 15-day timecourse, providing a unique model to examine gene-regulatory dynamics induced by P3F during RMS transformation. In addition to the expected upregulation of hallmark RMS factors, including MYOD1 and MYF6, we observed a cadre of additional transcription factor proteins that were induced and may contribute to transformation, as well as signature endothelial genes that became downregulated. P3F activated a set of enhancers that drove these expression patterns. P3F induced specific genetic dependencies in iARMS cells as observed in knockout screens. Our results define the fundamental cell identity changes underpinning P3F-induced transformation into FP-RMS and nominate collaborative transcription and non-transcription proteins that might be vulnerable to therapeutic attack.
Citation Format: Bradley T. Stevens, Yang Zhang, Randolph K. Larsen, Grace E. Adkins, Jack D. Hopkins, Darden W. Kimbrough, Matthew R. Garcia, Mark E. Hatley, Brian J. Abraham. PAX3-FOXO1-induced transcriptional dysregulation in rhabdomyosarcoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr A001.
Abstract A007 DNA damage response deficiency enhances neuroblastoma progression and sensitivity to combination PARP and ATR inhibition
Authors: Hayes Madeline N. , Cohen-Gogo Sarah , Kee Lynn , Layeghifard Mehdi , Valencia-Sama Ivette , Rajaselvam Anisha , Kaplan David , Villani Anita , Shlien Adam , Morgenstern Daniel A. , Irwin Meredith S 
Published: September 2024

Abstract
Background: Significant progress has been made in identifying mutations and defining biological heterogeneity in neuroblastoma (NB) using high-throughput sequencing approaches. However, functional roles for many specific genetic alterations in NB initiation, growth, and metastasis remain to be fully defined. Pathogenic and/or likely pathogenic (P/LP) alterations in genes involved in DNA Damage Response (DDR) pathways were identified in approximately 30% of patients enrolled in the SickKids Cancer Sequencing Program (KiCS). Despite being well studied in many adult cancers, roles for DDR disruption and potential therapeutic implications remains poorly understood for NB and other pediatric solid tumors. Aims: We aimed to define roles for DDR-deficiency in NB progression and assess the therapeutic potential of targeted agents using patient-specific DDR loss-of-function NB models. Methods: We incorporated loss-of-function mutations in atm, brca2, palb2, and bard1 into an established zebrafish MYCN-driven model of human NB and characterized tumor progression, transcriptional signatures, and response to candidate therapeutics in vivo. Human cell lines with DDR protein knock-down were used to assess candidate drug combinations in vitro. Results: Mutations in DDR genes were found to enhance tumor penetrance and metastasis in MYCN-driven zebrafish NB, and resulted in upregulation of proliferation, cell cycle checkpoint, and DNA damage repair transcriptional signatures. Zebrafish DDR-deficient NB and human NB cells with DDR protein knock-down were sensitive to the poly(ADP-ribose)-polymerase (PARP) inhibitor olaparib, and this effect was further enhanced by inhibition of the ataxia telangiectasia and rad3 related (ATR) kinase. Conclusions: Our data supports an in vivo functional role for DDR-deficiency in NB, as well as potential molecular vulnerabilities. Pre-clinical assessments in vitro and in vivo suggest therapeutic potential for combination PARP + ATR inhibition in NB patients with alterations in DDR genes.
Citation Format: Madeline N. Hayes, Sarah Cohen-Gogo, Lynn Kee, Mehdi Layeghifard, Ivette Valencia-Sama, Anisha Rajaselvam, David Kaplan, Anita Villani, Adam Shlien, Daniel A. Morgenstern, Meredith S Irwin. DNA damage response deficiency enhances neuroblastoma progression and sensitivity to combination PARP and ATR inhibition [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr A007.
Abstract A028 Unraveling the complex interplay of genetic, environmental, and lifestyle factors in cancer predisposition: A comprehensive review and analysis
Authors: David Peter Oloche O. 
Published: September 2024

Abstract
Cancer Predisposition is a complex and multifaceted topic that continues to intrigue researchers and scientists for decades. This thesis delves into the intricate web of factors that contribute to an individual's predisposition to cancer, aiming to unravel the mysteries surrounding this phenomenon. Through a comprehensive review of existing literature and cutting-edge research findings, the paper explores the genetic, environmental, and lifestyle factors that play a crucial role in predisposing individuals to cancer. By examining the interplay between genetic mutations, familial history, and environmental exposures, this study sheds light on the intricate mechanisms underlying cancer predisposition. Furthermore, the thesis investigates the role of epigenetic modifications, immune system dysregulation, and metabolic abnormalities in shaping an individual's susceptibility to cancer. The intricate interactions between these factors and their collective impact on cancer risk are analyzed, providing valuable insights into the underlying causes of cancer predisposition. By synthesizing the latest research findings in the field, this thesis offers a comprehensive overview of the complex nature of cancer predisposition and its multifactorial etiology. Ultimately, this study aims to contribute to our understanding of the intricate interplay between genetics, environment, and lifestyle in shaping an individual's susceptibility to cancer, paving the way for targeted prevention and personalized treatment strategies in the fight against this devastating disease.
Citation Format: Peter Oloche O. David. Unraveling the complex interplay of genetic, environmental, and lifestyle factors in cancer predisposition: A comprehensive review and analysis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr A028.