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1.
Child Abuse Negl ; 154: 106887, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38981310

ABSTRACT

BACKGROUND: In child welfare, caseloads are frequently far higher than optimal. Not all cases are created equal; however, little is known about which combination and interaction of factors make caseloads more challenging and impact child and family outcomes. OBJECTIVE: This study aims to identify which case, provider, and organizational factors most strongly differentiate between families with favorable and less-than-positive treatment outcomes. PARTICIPANTS AND SETTING: Participants were 25 family advocacy program providers and 17 supervisors at 11 Department of the Air Force installations. METHODS: Following informed consent, participants completed demographic and caseload questionnaires, and we collected information about organizational factors. Providers were sent a weekly case update and burnout questionnaire for seven months. We used linear mixed-effects model tree (LMM tree) algorithms to determine the provider, client, and organizational characteristics that best distinguish between favorable vs. unfavorable outcomes. RESULTS: The LMM tree predicting provider-rated treatment success yielded three significant partitioning variables: (a) commander involvement, (b) case complexity, and (c) % of clients in a high-risk field. The LMM predicting client-rated treatment progress yielded seven significant partitioning variables: (a) command involvement; (b) ease of reaching tenant unit command; (c) # of high-risk cases; (d) % of clients receiving Alcohol and Drug Abuse Prevention and Treatment services; (e) ease of reaching command; (f) % of clients with legal involvement; (g) provider age. CONCLUSIONS: This study is a first step toward developing a dynamic caseload management tool. An intelligent, algorithm-informed approach to case assignment could help child welfare agencies operate in their typically resource-scarce contexts in a manner that improves outcomes.

2.
Bioorg Med Chem ; 109: 117798, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38906068

ABSTRACT

N-(Benzothiazole-2-yl)pyrrolamide DNA gyrase inhibitors with benzyl or phenethyl substituents attached to position 3 of the benzothiazole ring or to the carboxamide nitrogen atom were prepared and studied for their inhibition of Escherichia coli DNA gyrase by supercoiling assay. Compared to inhibitors bearing the substituents at position 4 of the benzothiazole ring, the inhibition was attenuated by moving the substituent to position 3 and further to the carboxamide nitrogen atom. A co-crystal structure of (Z)-3-benzyl-2-((4,5-dibromo-1H-pyrrole-2-carbonyl)imino)-2,3-dihydrobenzo[d]-thiazole-6-carboxylic acid (I) in complex with E. coli GyrB24 (ATPase subdomain) was solved, revealing the binding mode of this type of inhibitor to the ATP-binding pocket of the E. coli GyrB subunit. The key binding interactions were identified and their contribution to binding was rationalised by quantum theory of atoms in molecules (QTAIM) analysis. Our study shows that the benzyl or phenethyl substituents bound to the benzothiazole core interact with the lipophilic floor of the active site, which consists mainly of residues Gly101, Gly102, Lys103 and Ser108. Compounds with substituents at position 3 of the benzothiazole core were up to two orders of magnitude more effective than compounds with substituents at the carboxamide nitrogen. In addition, the 6-oxalylamino compounds were more potent inhibitors of E. coli DNA gyrase than the corresponding 6-acetamido analogues.


Subject(s)
DNA Gyrase , Escherichia coli , Topoisomerase II Inhibitors , Topoisomerase II Inhibitors/pharmacology , Topoisomerase II Inhibitors/chemistry , Topoisomerase II Inhibitors/chemical synthesis , DNA Gyrase/metabolism , DNA Gyrase/chemistry , Binding Sites , Escherichia coli/enzymology , Escherichia coli/drug effects , Structure-Activity Relationship , Benzothiazoles/chemistry , Benzothiazoles/pharmacology , Benzothiazoles/chemical synthesis , Adenosine Triphosphate/metabolism , Adenosine Triphosphate/chemistry , Molecular Structure , Quantum Theory , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Models, Molecular
3.
Sci Rep ; 14(1): 13928, 2024 06 17.
Article in English | MEDLINE | ID: mdl-38886476

ABSTRACT

Respiratory syncytial virus is the major cause of acute lower respiratory tract infections in young children, causing extensive mortality and morbidity globally, with limited therapeutic or preventative options. Cathelicidins are innate immune antimicrobial host defence peptides and have antiviral activity against RSV. However, upper respiratory tract cathelicidin expression and the relationship with host and environment factors in early life, are unknown. Infant cohorts were analysed to characterise early life nasal cathelicidin levels, revealing low expression levels in the first week of life, with increased levels at 9 months which are comparable to 2-year-olds and healthy adults. No impact of prematurity on nasal cathelicidin expression was observed, nor were there effects of sex or birth mode, however, nasal cathelicidin expression was lower in the first week-of-life in winter births. Nasal cathelicidin levels were positively associated with specific inflammatory markers and demonstrated to be associated with microbial community composition. Importantly, levels of nasal cathelicidin expression were elevated in infants with mild RSV infection, but, in contrast, were not upregulated in infants hospitalised with severe RSV infection. These data suggest important relationships between nasal cathelicidin, upper airway microbiota, inflammation, and immunity against RSV infection, with interventional potential.


Subject(s)
Cathelicidins , Respiratory Syncytial Virus Infections , Respiratory Syncytial Virus Infections/immunology , Respiratory Syncytial Virus Infections/metabolism , Humans , Female , Male , Infant , Infant, Newborn , Respiratory Syncytial Virus, Human/immunology , Nasal Mucosa/metabolism , Nasal Mucosa/virology , Nasal Mucosa/immunology
4.
Cell ; 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38917788

ABSTRACT

Fewer than 200 proteins are targeted by cancer drugs approved by the Food and Drug Administration (FDA). We integrate Clinical Proteomic Tumor Analysis Consortium (CPTAC) proteogenomics data from 1,043 patients across 10 cancer types with additional public datasets to identify potential therapeutic targets. Pan-cancer analysis of 2,863 druggable proteins reveals a wide abundance range and identifies biological factors that affect mRNA-protein correlation. Integration of proteomic data from tumors and genetic screen data from cell lines identifies protein overexpression- or hyperactivation-driven druggable dependencies, enabling accurate predictions of effective drug targets. Proteogenomic identification of synthetic lethality provides a strategy to target tumor suppressor gene loss. Combining proteogenomic analysis and MHC binding prediction prioritizes mutant KRAS peptides as promising public neoantigens. Computational identification of shared tumor-associated antigens followed by experimental confirmation nominates peptides as immunotherapy targets. These analyses, summarized at https://targets.linkedomics.org, form a comprehensive landscape of protein and peptide targets for companion diagnostics, drug repurposing, and therapy development.

5.
Child Dev ; 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38888101

ABSTRACT

Healthy Indigenous child development is grounded in Indigenous ways of knowing and being. Attachment theory has been influential in understanding the significance of parenting for infant development in Western science but has focused on child-caregiver bonds predominantly within the parent-child dyad. To bring forth Indigenous perspectives regarding understandings of parenting, the attachment bond, and the well-being of Indigenous children, we conducted semi-structured interviews with 28 members of a Northwest tribal community (21 female) in spring and summer 2020. Themes included Community caregiving, Family value systems, Bonding, Traditional teachings, and Historical trauma. The need to expand the lens of attachment theory beyond the dyad is clear. Implications for improving the child welfare system and prevention programs within Indigenous communities are discussed.

6.
Nat Commun ; 15(1): 4927, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38862545

ABSTRACT

It is now widely recognised that the environment in space activates a diverse set of genes involved in regulating fundamental cellular pathways. This includes the activation of genes associated with blood homoeostasis and erythropoiesis, with a particular emphasis on those involved in globin chain production. Haemoglobin biology provides an intriguing model for studying space omics, as it has been extensively explored at multiple -omic levels, spanning DNA, RNA, and protein analyses, in both experimental and clinical contexts. In this study, we examined the developmental expression of haemoglobin over time and space using a unique suite of multi-omic datasets available on NASA GeneLab, from the NASA Twins Study, the JAXA CFE study, and the Inspiration4 mission. Our findings reveal significant variations in globin gene expression corresponding to the distinct spatiotemporal characteristics of the collected samples. This study sheds light on the dynamic nature of globin gene regulation in response to the space environment and provides valuable insights into the broader implications of space omics research.


Subject(s)
Hemoglobins , Humans , Hemoglobins/metabolism , Hemoglobins/genetics , Space Flight , Gene Expression Regulation , Erythropoiesis/genetics , Gene Expression Profiling/methods
7.
Euro Surveill ; 29(25)2024 Jun.
Article in English | MEDLINE | ID: mdl-38904114

ABSTRACT

BackgroundTo be better prepared for emerging wildlife-borne zoonoses, we need to strengthen wildlife disease surveillance.AimThe aim of this study was to create a topical overview of zoonotic pathogens in wildlife species to identify knowledge gaps and opportunities for improvement of wildlife disease surveillance.MethodsWe created a database, which is based on a systematic literature review in Embase focused on zoonotic pathogens in 10 common urban wildlife mammals in Europe, namely brown rats, house mice, wood mice, common voles, red squirrels, European rabbits, European hedgehogs, European moles, stone martens and red foxes. In total, we retrieved 6,305 unique articles of which 882 were included.ResultsIn total, 186 zoonotic pathogen species were described, including 90 bacteria, 42 helminths, 19 protozoa, 22 viruses and 15 fungi. Most of these pathogens were only studied in one single animal species. Even considering that some pathogens are relatively species-specific, many European countries have no (accessible) data on zoonotic pathogens in these relevant animal species. We used the Netherlands as an example to show how this database can be used by other countries to identify wildlife disease surveillance gaps on a national level. Only 4% of all potential host-pathogen combinations have been studied in the Netherlands.ConclusionsThis database comprises a comprehensive overview that can guide future research on wildlife-borne zoonotic diseases both on a European and national scale. Sharing and expanding this database provides a solid starting point for future European-wide collaborations to improve wildlife disease surveillance.


Subject(s)
Animals, Wild , Zoonoses , Animals , Animals, Wild/microbiology , Europe/epidemiology , Zoonoses/epidemiology , Databases, Factual , Humans , Rats , Sciuridae/microbiology , Hedgehogs/microbiology , Rabbits , Mice , Population Surveillance , Foxes/microbiology , Foxes/parasitology
8.
Commun Med (Lond) ; 4(1): 106, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38862781

ABSTRACT

BACKGROUND: Spaceflight poses a unique set of challenges to humans and the hostile spaceflight environment can induce a wide range of increased health risks, including dermatological issues. The biology driving the frequency of skin issues in astronauts is currently not well understood. METHODS: To address this issue, we used a systems biology approach utilizing NASA's Open Science Data Repository (OSDR) on space flown murine transcriptomic datasets focused on the skin, biochemical profiles of 50 NASA astronauts and human transcriptomic datasets generated from blood and hair samples of JAXA astronauts, as well as blood samples obtained from the NASA Twins Study, and skin and blood samples from the first civilian commercial mission, Inspiration4. RESULTS: Key biological changes related to skin health, DNA damage & repair, and mitochondrial dysregulation are identified as potential drivers for skin health risks during spaceflight. Additionally, a machine learning model is utilized to determine gene pairings associated with spaceflight response in the skin. While we identified spaceflight-induced dysregulation, such as alterations in genes associated with skin barrier function and collagen formation, our results also highlight the remarkable ability for organisms to re-adapt back to Earth via post-flight re-tuning of gene expression. CONCLUSION: Our findings can guide future research on developing countermeasures for mitigating spaceflight-associated skin damage.


Spaceflight is a hostile environment which can lead to health problems in astronauts, including in the skin. It is not currently well understood why these skin problems occur. Here, we analyzed data from the skin of space flown mice and astronauts to try and identify possible explanations for these skin problems. It appears that changes in the activation of genes related to damage to DNA, skin barrier health, and mitochondria (the energy-producing parts of cells) may play a role in these skin problems. Further research will be needed to confirm exactly how these changes influence skin health, which could lead to solutions for preventing and managing such issues in astronauts.

9.
Nat Commun ; 15(1): 4954, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38862516

ABSTRACT

Spaceflight induces an immune response in astronauts. To better characterize this effect, we generated single-cell, multi-ome, cell-free RNA (cfRNA), biochemical, and hematology data for the SpaceX Inspiration4 (I4) mission crew. We found that 18 cytokines/chemokines related to inflammation, aging, and muscle homeostasis changed after spaceflight. In I4 single-cell multi-omics data, we identified a "spaceflight signature" of gene expression characterized by enrichment in oxidative phosphorylation, UV response, immune function, and TCF21 pathways. We confirmed the presence of this signature in independent datasets, including the NASA Twins Study, the I4 skin spatial transcriptomics, and 817 NASA GeneLab mouse transcriptomes. Finally, we observed that (1) T cells showed an up-regulation of FOXP3, (2) MHC class I genes exhibited long-term suppression, and (3) infection-related immune pathways were associated with microbiome shifts. In summary, this study reveals conserved and distinct immune disruptions occurring and details a roadmap for potential countermeasures to preserve astronaut health.


Subject(s)
Single-Cell Analysis , Space Flight , Transcriptome , Animals , Female , Male , Humans , Mice , Astronauts , Cytokines/metabolism , T-Lymphocytes/immunology , Sex Factors , Gene Expression Profiling , Oxidative Phosphorylation
10.
J Forensic Sci ; 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38940006

ABSTRACT

DNA typing of latent fingerprints is highly desirable to increase chances of individualization. We recovered DNA from Cyanoacrylate (CA) fumed fingerprints and used both GlobalFiler™ and ForenSeq™ DNA Signature Prep kits for DNA typing. For GlobalFiler™, samples were processed using a protocol modified for Low Template (LT)-DNA samples (half-volume reactions, 30 cycles) while for ForenSeq™ DNA Signature Prep, samples were processed using a standard protocol and fluorometer-based library quantitation. We evaluated genotyping success and quality of profiles in terms of completeness, Peak Height Ratio/Allele Coverage Ratio, presence of PCR artifacts and drop-in alleles. With GlobalFiler™, average autosomal STR (aSTR) profile completeness was 44.4% with 2-20 pg, 54.3% with 22-60 pg, and 95% with 64-250 pg DNA input. CODIS uploadable profiles were obtained in 2/10, 3/11, and 11/12 samples in these ranges. With ForenSeq™ DNA Signature Prep, average aSTR profile completeness was 19.7% with 1-20 pg and 45.2% with 22-47 pg but increased to 78.3% with 68-122 pg and 86.7% with 618-1000 pg DNA input. Uploadable profiles were obtained in 0/12, 4/11, 4/7, and 3/3 samples for these ranges. Results show very high sensitivity using both kits. Half-volume reactions and 30 cycles had minimal negative effect on Globalfiler™ profile quality, providing support for wider use after validation experiments to routinely improve results from LT samples. A standard protocol for the ForenSeq™ DNA Signature Prep kit was also highly successful with LT DNA obtained from CA-fumed fingerprints with additional information from isometric STR alleles and other markers.

12.
Article in English | MEDLINE | ID: mdl-38733515

ABSTRACT

Anticoagulation therapy is standard for conditions like atrial fibrillation, venous thromboembolism, and valvular heart disease, yet it is unclear if there are ethnoracial disparities in its quality and delivery in the United States. For this scoping review, electronic databases were searched for publications between January 1, 2011 - March 30, 2022. Eligible studies included all study designs, any setting within the United States, patients prescribed anticoagulation for any indication, outcomes reported for ≥ 2 distinct ethnoracial groups. The following four research questions were explored: Do ethnoracial differences exist in 1) access to guideline-based anticoagulation therapy, 2) quality of anticoagulation therapy management, 3) clinical outcomes related to anticoagulation care, 4) humanistic/educational outcomes related to anticoagulation therapy. A total of 5374 studies were screened, 570 studies received full-text review, and 96 studies were analyzed. The largest mapped focus was patients' access to guideline-based anticoagulation therapy (88/96 articles, 91.7%). Seventy-eight articles made statistical outcomes comparisons among ethnoracial groups. Across all four research questions, 79 articles demonstrated favorable outcomes for White patients compared to non-White patients, 38 articles showed no difference between White and non-White groups, and 8 favored non-White groups (the total exceeds the 78 articles with statistical outcomes as many articles reported multiple outcomes). Disparities disadvantaging non-White patients were most pronounced in access to guideline-based anticoagulation therapy (43/66 articles analyzed) and quality of anticoagulation management (19/21 articles analyzed). Although treatment guidelines do not differentiate anticoagulant therapy by ethnoracial group, this scoping review found consistently favorable outcomes for White patients over non-White patients in the domains of access to anticoagulation therapy for guideline-based indications and quality of anticoagulation therapy management. No differences among groups were noted in clinical outcomes, and very few studies assessed humanistic or educational outcomes.

13.
Biol Trace Elem Res ; 2024 May 17.
Article in English | MEDLINE | ID: mdl-38758479

ABSTRACT

The success of arsenic trioxide (ATO) in acute promyelocytic leukemia has driven a plethora studies to investigate its efficacy in other malignancies. However, the inherent toxicity of ATO limits the expansion of its clinical applications. Such toxicity may be linked to ATO-induced metabolic derangements of endogenous substrates. Therefore, the primary objective of this study was to investigate the effect of ATO on the hepatic formation of arachidonic acid (AA) metabolites, hydroxyeicosatetraenoic acids (HETEs), as well as their most notable producing machinery, cytochrome P450 (CYP) enzymes. For this purpose, C57BL/6 mice were intraperitoneally injected with 8 mg/kg ATO for 6 and 24 h. Total RNA was extracted from harvested liver tissues for qPCR analysis of target genes. Hepatic microsomal proteins underwent incubation with AA, followed by identification/quantification of the produced HETEs. ATO downregulated Cyp2e1, while induced Cyp2j9 and most of Cyp4a and Cyp4f, and this has resulted in a significant increase in 17(S)-HETE and 18(R)-HETE, while significantly decreased 18(S)-HETE. Additionally, ATO induced Cyp4a10, Cyp4a14, Cyp4f13, Cyp4f16, and Cyp4f18, resulting in a significant elevation in 20-HETE formation. In conclusion, ATO altered hepatic AA metabolites formation through modulating the underlying network of CYP enzymes. Modifying the homeostatic production of bioactive AA metabolites, such as HETEs, may entail toxic events that can, at least partly, explain ATO-induced hepatotoxicity. Such modification can also compromise the overall body tolerability to ATO treatment in cancer patients.

16.
ISME J ; 18(1)2024 Jan 08.
Article in English | MEDLINE | ID: mdl-38718148

ABSTRACT

Nutrient-induced blooms of the globally abundant freshwater toxic cyanobacterium Microcystis cause worldwide public and ecosystem health concerns. The response of Microcystis growth and toxin production to new and recycled nitrogen (N) inputs and the impact of heterotrophic bacteria in the Microcystis phycosphere on these processes are not well understood. Here, using microbiome transplant experiments, cyanotoxin analysis, and nanometer-scale stable isotope probing to measure N incorporation and exchange at single cell resolution, we monitored the growth, cyanotoxin production, and microbiome community structure of several Microcystis strains grown on amino acids or proteins as the sole N source. We demonstrate that the type of organic N available shaped the microbial community associated with Microcystis, and external organic N input led to decreased bacterial colonization of Microcystis colonies. Our data also suggest that certain Microcystis strains could directly uptake amino acids, but with lower rates than heterotrophic bacteria. Toxin analysis showed that biomass-specific microcystin production was not impacted by N source (i.e. nitrate, amino acids, or protein) but rather by total N availability. Single-cell isotope incorporation revealed that some bacterial communities competed with Microcystis for organic N, but other communities promoted increased N uptake by Microcystis, likely through ammonification or organic N modification. Our laboratory culture data suggest that organic N input could support Microcystis blooms and toxin production in nature, and Microcystis-associated microbial communities likely play critical roles in this process by influencing cyanobacterial succession through either decreasing (via competition) or increasing (via biotransformation) N availability, especially under inorganic N scarcity.


Subject(s)
Microbiota , Microcystins , Microcystis , Nitrogen , Microcystis/metabolism , Microcystis/growth & development , Microcystins/metabolism , Nitrogen/metabolism , Amino Acids/metabolism
17.
JMIR Form Res ; 8: e48767, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38625729

ABSTRACT

BACKGROUND: Hydroxyurea is an evidence-based disease-modifying therapy for sickle cell disease (SCD) but is underutilized. The Integration of Mobile Health into Sickle Cell Disease Care to Increase Hydroxyurea Utilization (meSH) multicenter study leveraged mHealth to deliver targeted interventions to patients and providers. SCD studies often underenroll; and recruitment strategies in the SCD population are not widely studied. Unanticipated events can negatively impact enrollment, making it important to study strategies that ensure adequate study accrual. OBJECTIVE: The goal of this study was to evaluate enrollment barriers and the impact of modified recruitment strategies among patients and providers in the meSH study in response to a global emergency. METHODS: Recruitment was anticipated to last 2 months for providers and 6 months for patients. The recruitment strategies used with patients and providers, new recruitment strategies, and recruitment rates were captured and compared. To document recruitment adaptations and their reasons, study staff responsible for recruitment completed an open-ended 9-item questionnaire eliciting challenges to recruitment and strategies used. Themes were extrapolated using thematic content analysis. RESULTS: Total enrollment across the 7 sites included 89 providers and 293 patients. The study acceptance rate was 85.5% (382/447) for both patients and providers. The reasons patients declined participation were most frequently a lack of time and interest in research, while providers mostly declined because of self-perceived high levels of SCD expertise, believing they did not need the intervention. Initially, recruitment involved an in-person invitation to participate during clinic visits (patients), staff meetings (providers), or within the office (providers). We identified several important recruitment challenges, including (1) lack of interest in research, (2) lack of human resources, (3) unavailable physical space for recruitment activities, and (4) lack of documentation to verify eligibility. Adaptive strategies were crucial to alleviate enrollment disruptions due to the COVID-19 pandemic. These included remote approaching and consenting (eg, telehealth, email, and telephone) for patients and providers. Additionally, for patients, recruitment was enriched by simplification of enrollment procedures (eg, directly approaching patients without a referral from the provider) and a multitouch method (ie, warm introductions with flyers, texts, and patient portal messages). We found that patient recruitment rates were similar between in-person and adapted (virtual with multitouch) approaches (167/200, 83.5% and 126/143, 88.1%, respectively; P=.23). However, for providers, recruitment was significantly higher for in-person vs remote recruitment (48/50, 96% and 41/54, 76%, respectively, P<.001). CONCLUSIONS: We found that timely adaptation in recruitment strategies secured high recruitment rates using an assortment of enriched remote recruitment strategies. Flexibility in approach and reducing the burden of enrollment procedures for participants aided enrollment. It is important to continue identifying effective recruitment strategies in studies involving patients with SCD and their providers and the impact and navigation of recruitment challenges. TRIAL REGISTRATION: ClinicalTrials.Gov NCT03380351; https://clinicaltrials.gov/study/NCT03380351. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/16319.

18.
Curr Biol ; 34(9): 1930-1939.e4, 2024 05 06.
Article in English | MEDLINE | ID: mdl-38636515

ABSTRACT

Substantial progress has been made in understanding the genetic architecture of phenotypes involved in a variety of evolutionary processes. Behavioral genetics remains, however, among the least understood. We explore the genetic architecture of spatial cognitive abilities in a wild passerine bird, the mountain chickadee (Poecile gambeli). Mountain chickadees cache thousands of seeds in the fall and require specialized spatial memory to recover these caches throughout the winter. We previously showed that variation in spatial cognition has a direct effect on fitness and has a genetic basis. It remains unknown which specific genes and developmental pathways are particularly important for shaping spatial cognition. To further dissect the genetic basis of spatial cognitive abilities, we combine experimental quantification of spatial cognition in wild chickadees with whole-genome sequencing of 162 individuals, a new chromosome-scale reference genome, and species-specific gene annotation. We have identified a set of genes and developmental pathways that play a key role in creating variation in spatial cognition and found that the mechanism shaping cognitive variation is consistent with selection against mildly deleterious non-coding mutations. Although some candidate genes were organized into connected gene networks, about half do not have shared regulation, highlighting that multiple independent developmental or physiological mechanisms contribute to variation in spatial cognitive abilities. A large proportion of the candidate genes we found are associated with synaptic plasticity, an intriguing result that leads to the hypothesis that certain genetic variants create antagonism between behavioral plasticity and long-term memory, each providing distinct benefits depending on ecological context.


Subject(s)
Cognition , Gene Regulatory Networks , Animals , Feeding Behavior , Spatial Memory , Songbirds/genetics , Songbirds/physiology , Passeriformes/genetics , Passeriformes/physiology
19.
Microbiol Spectr ; 12(6): e0001524, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38682907

ABSTRACT

Gastric cancer is the fifth most diagnosed cancer in the world. Infection by the bacteria Helicobacter pylori (HP) is associated with approximately 75% of gastric cancer cases. HP infection induces chronic gastric inflammation, damaging the stomach and fostering carcinogenesis. Most mechanistic studies on gastric cancer initiation are performed in mice and utilize either mouse-adapted strains of HP or the natural mouse pathogen Helicobacter felis (HF). Here, we identified the differences in gastric inflammation, atrophy, and metaplasia associated with HP and HF infection in mice. PMSS1 HP strain or the CS1 HF strain were co-cultured with mouse peritoneal macrophages to assess their immunostimulatory effects. HP and HF induced similar cytokine production from cultured mouse peritoneal macrophages revealing that both bacteria exhibit similar immunostimulatory effects in vitro. Next, C57BL/6J mice were infected with HP or HF and were assessed 2 months post-infection. HP-infected mice caused modest inflammation within both the gastric corpus and antrum, and did not induce significant atrophy within the gastric corpus. In contrast, HF induced significant inflammation throughout the gastric corpus and antrum. Moreover, HF infection was associated with significant atrophy of the chief and parietal cell compartments and induced the expression of pyloric metaplasia (PM) markers. HP is poorly immunogenic compared to HF. HF induces dramatic CD4+ T cell activation, which is associated with increased gastric cancer risk in humans. Thus, HP studies in mice are better suited for studies on colonization, while HF is more strongly suited for studies on the effects of gastric inflammation on tumorigenesis. . IMPORTANCE: Mouse infection models with Helicobacter species are widely used to study Helicobacter pathogenesis and gastric cancer initiation. However, Helicobacter pylori is not a natural mouse pathogen, and mouse-adapted H. pylori strains are poorly immunogenic. In contrast, Helicobacter felis is a natural mouse pathogen that induces robust gastric inflammation and is often used in mice to investigate gastric cancer initiation. Although both bacterial strains are widely used, their disease pathogenesis in mice differs dramatically. However, few studies have directly compared the pathogenesis of these bacterial species in mice, and the contrasting features of these two models are not clearly defined. This study directly compares the gastric inflammation, atrophy, and metaplasia development triggered by the widely used PMSS1 H. pylori and CS1 H. felis strains in mice. It serves as a useful resource for researchers to select the experimental model best suited for their studies.


Subject(s)
Gastric Mucosa , Helicobacter Infections , Helicobacter felis , Helicobacter pylori , Metaplasia , Mice, Inbred C57BL , Animals , Helicobacter pylori/immunology , Helicobacter pylori/pathogenicity , Helicobacter Infections/microbiology , Helicobacter Infections/pathology , Helicobacter Infections/immunology , Mice , Helicobacter felis/pathogenicity , Metaplasia/microbiology , Metaplasia/pathology , Gastric Mucosa/pathology , Gastric Mucosa/microbiology , Gastric Mucosa/immunology , Gastritis/microbiology , Gastritis/pathology , Stomach Neoplasms/microbiology , Stomach Neoplasms/pathology , Inflammation/microbiology , Inflammation/pathology , Female , Cytokines/metabolism , Disease Models, Animal , Stomach/pathology , Stomach/microbiology
20.
J Allergy Clin Immunol Glob ; 3(2): 100244, 2024 May.
Article in English | MEDLINE | ID: mdl-38577482

ABSTRACT

A case report detailing, for the first time, a case of laboratory-confirmed zoster in an astronaut on board the International Space Station is presented. The findings of reduced T-cell function, cytokine imbalance, and increased stress hormones which preceded the event are detailed. Relevance for deep space countermeasures is discussed.

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