bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Rrp2-RpoN-RpoS pathway plays an important role in the blood-brain barrier transmigration of the Lyme disease pathogen
Authors: Alanazi Fuad , Raghunandanan Sajith , Priya Raj , Yang X. Frank 
Published: October 2023

ABSTRACT

Lyme disease, caused by
Borrelia
(or
Borreliella
)
burgdorferi
, is a complex multisystemic disorder that includes Lyme neuroborreliosis resulting from the invasion of both the central and peripheral nervous systems. However, factors that enable the pathogen to cross the blood-brain barrier (BBB) and invade the central nervous system (CNS) are still not well understood. The objective of this study was to identify the
B. burgdorferi
factors required for BBB transmigration. We utilized a transwell BBB model based on human brain-microvascular endothelial cells and focused on investigating the Rrp2-RpoN-RpoS pathway, a central regulatory pathway that is essential for mammalian infection by
B. burgdorferi
. Our results demonstrated that the Rrp2-RpoN-RpoS pathway is crucial for BBB transmigration. Furthermore, we identified OspC, a major surface lipoprotein controlled by the Rrp2-RpoN-RpoS pathway, as a significant contributor to BBB transmigration. Constitutive production of OspC in a mutant defective in the Rrp2-RpoN-RpoS pathway did not rescue the impairment in BBB transmigration, indicating that this pathway controls additional factors for this process. Two other major surface lipoproteins controlled by this pathway, DbpA/B and BBK32, appeared to be dispensable for BBB transmigration. In addition, both the surface lipoprotein OspA and the Rrp1 pathway, which are required
B. burgdorferi
colonization in the tick vector, were found not required for BBB transmigration. Collectively, our findings using
in vitro
transwell assays uncover another potential role of the Rrp2-RpoN-RpoS pathway in BBB transmigration of
B. burgdorferi
and invasion into the CNS.
Detoxification of reactive oxygen species by the hyaluronic acid capsule of group A
Streptococcus
Authors: Wilde Shyra , Dash Ananya , Johnson Anders , Mackey Kialani , Okumura Cheryl Y. M. , LaRock Christopher N. 
Published: October 2023

ABSTRACT

The pro-inflammatory cytokine IL-6 regulates antimicrobial responses that are broadly crucial in the defense against infection. Our prior work shows that IL-6 promotes the killing of the M4 serotype group A
Streptococcus
(GAS) but does not impact the globally disseminated M1T1 serotype associated with invasive infections. Using
in vitro
and
in vivo
infection models, we show that IL-6 induces phagocyte reactive oxygen species (ROS) that are responsible for the differential susceptibility of M4 and M1T1 GAS to IL-6-mediated defenses. Clinical isolates naturally deficient in capsule, or M1T1 strains deficient in capsule production, are sensitive to this ROS killing. The GAS capsule is made of hyaluronic acid, an antioxidant that detoxifies ROS and can protect acapsular M4 GAS when added exogenously. During
in vitro
interactions with macrophages and neutrophils, acapsular GAS can also be rescued with the antioxidant N-acetylcysteine, suggesting this is a major virulence contribution of the capsule. In an intradermal infection model with

gp91
phox

-/-
(chronic granulomatous disease [CGD]) mice, phagocyte ROS production had a modest effect on bacterial proliferation and the cytokine response but significantly limited the size of the bacterial lesion in the skin. These data suggest that the capsule broadly provides enhanced resistance to phagocyte ROS but is not essential for invasive infection. Since capsule-deficient strains are observed across several GAS serotypes and are competent for transmission and both mild and invasive infections, additional host or microbe factors may contribute to ROS detoxification during GAS infections.
A cost-free CURE: using bioinformatics to identify DNA-binding factors at a specific genomic locus
Authors: Schmidt Casey A. , Hodkinson Lauren J. , Comstra H. Skye , Khan Samia , Torres Henrik , Rieder Leila E. 
Published: October 2023

ABSTRACT
Research experiences provide diverse benefits for undergraduates. Many academic institutions have adopted course-based undergraduate research experiences (CUREs) to improve student access to research opportunities. However, potential instructors of a CURE might still face financial or practical hurdles that prevent implementation. Bioinformatics research offers an alternative that is free, safe, compatible with remote learning, and may be more accessible for students with disabilities. Here, we describe a bioinformatics CURE that leverages publicly available datasets to discover novel proteins that target an instructor-determined genomic locus of interest. We use the free, user-friendly bioinformatics platform Galaxy to map ChIP-seq datasets to a genome, which removes the computing burden from students. Both faculty and students directly benefit from this CURE, as faculty can perform candidate screens and publish CURE results. Students gain not only basic bioinformatics knowledge, but also transferable skills, including scientific communication, database navigation, and primary literature experience. The CURE is flexible and can be expanded to analyze different types of high-throughput data or to investigate different genomic loci in any species.
Draft genome sequence of
Pseudomonas
sp. ER28, a cyclohexane pentanoic acid degrader isolated from oil sands process-affected water from Alberta, Canada
Authors: Goff Kira L. , Gauthier Jeff , Gieg Lisa M. , Kukavica-Ibrulj Irena , Ramos-Padrón Esther , Lewenza Shawn , Levesque Roger C. 
Published: October 2023

ABSTRACT

We report the draft genome sequence of
Pseudomonas
sp. ER28, capable of utilizing the model naphthenic acid, cyclohexane pentanoic acid, as its sole carbon source. It was recovered from oil sands process-affected water containing cyclic and acyclic naphthenic acids. The genome size is 5.7 Mbp, and the G + C content is 60%.
Machine-learning analysis of cross-study samples according to the gut microbiome in 12 infant cohorts
Authors: Vänni Petri , Tejesvi Mysore V. , Paalanne Niko , Aagaard Kjersti , Ackermann Gail , Camargo Carlos A. , Eggesbø Merete , Hasegawa Kohei , Hoen Anne G. , Karagas Margaret R. , Kolho Kaija-Leena , Laursen Martin F. , Ludvigsson Johnny , Madan Juliette , Ownby Dennis , Stanton Catherine , Stokholm Jakob , Tapiainen Terhi 
Published: October 2023

ABSTRACT
Combining and comparing microbiome data from distinct infant cohorts has been challenging because such data are inherently multidimensional and complex. Here, we used an ensemble of machine-learning (ML) models and studied 16S rRNA amplicon sequencing data from 4,099 gut microbiome samples representing 12 prospectively collected infant cohorts. We chose the childbirth delivery mode as a starting point for such analysis because it has previously been associated with alterations in the gut microbiome in infants. In cross-study ensemble models, Bacteroides was the most important feature in all machine-learning models. The predictive capacity by taxonomy varied with age. At the age of 1–2 months, gut microbiome data were able to predict delivery mode with an area under the curve of 0.72 to 0.83. In contrast, ML models trained on taxa were not able to differentiate between the modes of delivery, in any of the cohorts, when the infants were between 3 and 12 months of age. Moreover, no ML model, alternately trained on the functional pathways of the infant gut microbiome, could consistently predict mode of delivery at any infant age. This study shows that infant gut microbiome data sets can be effectively combined with the application of ML analysis across different study populations.

IMPORTANCE
There are challenges in merging microbiome data from diverse research groups due to the intricate and multifaceted nature of such data. To address this, we utilized a combination of machine-learning (ML) models to analyze 16S sequencing data from a substantial set of gut microbiome samples, sourced from 12 distinct infant cohorts that were gathered prospectively. Our initial focus was on the mode of delivery due to its prior association with changes in infant gut microbiomes. Through ML analysis, we demonstrated the effective merging and comparison of various gut microbiome data sets, facilitating the identification of robust microbiome biomarkers applicable across varied study populations.
Characterization of spatial lipidomic signatures in tick-bitten guinea pig skin as a model for host-vector-pathogen interaction profiling
Authors: Scott Alison J. , Smith Alexis A. , Heeren Ron M. A. , Pal Utpal , Ernst Robert K. 
Published: October 2023

ABSTRACT

Spatially aware
de novo
discovery methods are essential tools for therapeutic target identification in complex interphylum interactions such as arthropods and mammals. Notably, the methods should ideally be species agnostic, showing unique features of all interacting species. We evaluated the possibilities for matrix-assisted desorption/ionization mass spectrometry imaging (MALDI-MSI, referred to here as MSI) as a spatial “omics” method to simultaneously profile both an arthropod vector (
Ixodes
tick) and a mammalian skin (guinea pig) in a bite model. We demonstrated the feasibility of MSI using gelatin-stabilized sample mounting that allowed for serial sectioning and mapping lipids in control and bitten skin, including the tick body and embedded mouthparts. We identified unique lipid ion patterns and observed lipid reorganization beneath the bite site consistent with histological changes. Furthermore, several ions were observed in the tick body with lower intensity in the dermis and control skin, suggesting the transmission of lipids from the tick to mammalian skin. These results establish a multi-system approach for discovering cross-species molecular interactions that can be further developed as targets to disrupt the vector-host interface.

IMPORTANCE
Here, we demonstrate the adaptability of spatial “omics” methods to identify interphylum processes regulated at the vector-host interface of ticks during a mammalian blood meal. This approach enables a better understanding of complex bipartite or tripartite molecular interactions between hosts, arthropod vectors and transmitted pathogens, and contributes toward the development of spatially aware therapeutic target discovery and description.
Clinically relevant mutations in the PhoR sensor kinase of host-adapted
Mycobacterium abscessus
isolates impact response to acidic pH and virulence
Authors: Belardinelli Juan M. , Arora Divya , Avanzi Charlotte , Wheat William H. , Bryant Josephine M. , Spencer John S. , Blundell Tom L. , Parkhill Julian , Floto R. Andres , Jackson Mary 
Published: October 2023

ABSTRACT

Functional genomics analysis of
Mycobacterium abscessus
clinical isolates from chronically infected patients to identify genes under strong evolutionary pressure during lung adaptation identified
phoR
as one of the most frequently mutated.
phoR
encodes the histidine kinase (HK) of the two-component regulatory system (TCS) PhoPR. While PhoPR has been extensively studied in
Mycobacterium tuberculosis
for its role in virulence, little is known about the function of this TCS and the signals governing its activation in
M. abscessus
. We here show that acidic pH leads to the upregulation of
phoP
in
M. abscessus
and that clinically relevant non-synonymous mutations identified in PhoR exacerbate this response. PhoR modulates the ability of its cognate response regulator, PhoP, to autoregulate itself by controlling its dephosphorylation. At low pH, the phosphatase activity of PhoR is reduced and the build-up of phospho-PhoP that ensues results in the upregulation of
phoP
that accompanies the induction of a defined set of genes, many of which are thought to play a role in virulence and host adaptation. In line with the idea that
M. abscessus
isolates expressing clinically relevant PhoR variants may be better prepared for survival within the host, we find these strains to be less efficiently internalized by macrophages and to display enhanced intracellular survival.

IMPORTANCE

Difficult-to-treat pulmonary infections caused by nontuberculous mycobacteria of the
Mycobacterium abscessus
group have been steadily increasing in the USA and globally. Owing to the relatively recent recognition of
M. abscessus
as a human pathogen, basic and translational research to address critical gaps in diagnosis, treatment, and prevention of diseases caused by this microorganism has been lagging behind that of the better-known mycobacterial pathogen,
Mycobacterium tuberculosis
. To begin unraveling the molecular mechanisms of pathogenicity of
M. abscessus
, we here focus on the study of a two-component regulator known as PhoPR which we found to be under strong evolutionary pressure during human lung infection. We show that PhoPR is activated at acidic pH and serves to regulate a defined set of genes involved in host adaptation. Accordingly, clinical isolates from chronically infected human lungs tend to hyperactivate this regulator enabling
M. abscessus
to escape macrophage killing.
Systematic investigation of the emerging pathogen of
Tsukamurella
species in a Chinese tertiary teaching hospital
Authors: Yu Shuying , Ding Xiaoqi , Hua Kexin , Zhu Huiqing , Zhang Qingshui , Song Xinuo , Xie Xiuli , Huang Rong , Xu Yingchun , Zhang Li , Yi Qiaolian , Zhao Ying 
Published: October 2023

ABSTRACT

Tsukamurella
species have been clinically regarded as rare but emerging opportunistic pathogens causing various infections in humans.
Tsukamurella
pneumonia has often been misdiagnosed as pulmonary tuberculosis due to its clinical presentation resembling tuberculosis-like syndromes.
Tsukamurella
species have also been confused in the laboratory with other phylogenetic bacteria, such as
Gordonia
. This study aimed to investigate the clinical, microbiological, and molecular characteristics; species distribution; and antimicrobial susceptibility of
Tsukamurella
species. Immunodeficiency and chronic pulmonary disease appeared to be risk factors for
Tsukamurella
pneumonia, and the presence of bronchiectasis and pulmonary nodules on imaging was highly correlated with this infection. The study confirmed that
groEL
(heat shock protein 60) and
secA
(the secretion ATPase) genes are reliable for identifying
Tsukamurella
species. Additionally, the
ssrA
(stable small RNA) gene showed promise as a tool for discriminating between different
Tsukamurella
species with the shortest sequence length. In terms of antimicrobial susceptibility, quinolones, trimethoprim/sulfamethoxazole, amikacin, minocycline, linezolid, and tigecycline demonstrated potent
in vitro
activity against
Tsukamurella
isolates in our study. The study also proposed a resistance mechanism involving a substitution (S91R) within the quinolone-resistance-determining region of the
gyrA
gene, which confers resistance to levofloxacin and ciprofloxacin. Furthermore, we found that disk diffusion testing is not suitable for testing the susceptibilities of
Tsukamurella
isolates to ciprofloxacin, imipenem, and minocycline. In conclusion, our systematic investigation may contribute to a better understanding of this rare pathogen.

Tsukamurella
species are rare but emerging human pathogens that share remarkable similarities with other mycolic acid–containing genera of the order Actinomycetales, especially
Mycobacterium tuberculosis
. Consequently, misdiagnosis and therapeutic failures can occur in clinical settings. Despite the significance of accurate identification, antimicrobial susceptibility, and understanding the resistance mechanism of this important genus, our knowledge in these areas remains fragmentary and incomplete. In this study, we aimed to address these gaps by investigating promising identification methods, the antimicrobial susceptibility patterns, and a novel quinolone resistance mechanism in
Tsukamurella
species, utilizing a collection of clinical isolates. The findings of our study will contribute to improve diagnosis and successful management of infections caused by
Tsukamurella
species, as well as establishing well-defined performance and interpretive criteria for antimicrobial susceptibility testing.
Culture-independent analyses of carrion beetle (Coleoptera: Silphidae) secretion bacterial communities
Authors: Pratt Carrie J. , Meili Casey H. , Youssef Noha H. , Hoback W. Wyatt 
Published: October 2023

ABSTRACT
In the central plains of North America, the beetle family Silphidae comprised two subfamilies, Silphinae and Nicrophorinae, differentiated by reproductive behaviors. Silphinae, known as carrion beetles, feed on carrion and fly larvae and produce free-living larvae that receive no parental care. Adult Nicrophorinae, known as burying beetles, prepare a vertebrate carcass into a brood ball and provide biparental care to their offspring. Preparation of a brood ball involves coating the carcass in antimicrobial oral and anal secretions. These secretions contain a community of microbes, referred to as the secretion microbiome, which inhibit carcass microbe succession, preventing normal decomposition. Here, the secretion microbiomes of five species of Nicrophorinae and two species of Silphinae, both sampled from Oklahoma, with additional Nicrophorinae from Nebraska, were characterized using culture-independent analyses to understand and decipher factors shaping diversity and community structure. We identify the core secretion microbiome across Silphidae and show that, while the host subfamily, secretion type, and collection locality had no significant effect on the bacterial community alpha diversity, these factors significantly influenced bacterial community structure. Global and local tests of phylogenetic associations identified 14 genera with phylogenetic signals to the host subfamily and species. Description of the bacterial communities present in silphid secretions furthers our understanding of how these beetles interact with microbes for carcass nutrient processing. Future culture-dependent studies from silphid secretions may identify novel antimicrobials and nontoxic compounds that can act as meat preservatives or sources for antimicrobials.

IMPORTANCE
The manuscript explores the secretion bacterial community of carrion and burying beetles of the central plains of North America. A core secretion microbiome of 11 genera is identified. The host subfamily, secretion type, and collection locality significantly affects the secretion microbiome. Future culture-dependent studies from silphid secretions may identify novel antimicrobials and nontoxic compounds that can act as meat preservatives or sources for antimicrobials.
Antifungal and antibiofilm activities of chromones against nine
Candida
species
Authors: Lee Jin-Hyung , Kim Yong-Guy , Kim Yeseul , Lee Jintae 
Published: October 2023

ABSTRACT

Candida
species are the most common cause of fungal infections, and thus the emergence of antifungal-resistant species and biofilm formation by
Candida
further threatens the limited availability of antifungal agents. We investigated the antifungal and antibiofilm activities of 27 chromones against nine
Candida
species, including
Candida albicans, Candida glabrata
,
Candida parapsilosis
, and
Candida auris
. Four chromone-3-carbonitriles exhibited good antifungal activity with minimum inhibitory concentrations from 5 to 50 µg/mL and significantly inhibited biofilm formation by
C. albicans
. Furthermore, these four chromone-3-carbonitriles markedly inhibited cell aggregation and hypha formation, which are virulence factors and prerequisites for
C. albicans
biofilm formation. Transcriptomic analyses showed that the most active 6-bromochromone-3-carbonitrile downregulated the expressions of hypha-forming and biofilm-related genes (
TEC1
and
UME6
) but upregulated the hyphal regulator
UCF1
. Toxicity assays conducted using plant and nematode models showed that the four chromone-3-carbonitriles were non-to-mildly toxic. This study suggests that chromones bearing the 3-carbonitrile motif should be considered potential antifungal agents against
Candida
species.

IMPORTANCE

The persistence of
Candida
infections is due to its ability to form biofilms that enable it to resist antifungals and host immune systems. Hence, inhibitions of the biofilm formation and virulence characteristics of
Candida
sp. provide potential means of addressing these infections. Among various chromone derivatives tested, four chromone-3-carbonitriles showed antifungal, antibiofilm, and antivirulence activities against several
Candida
species. Their mode of action has been partially revealed, and their toxicity is reported here using nematode and plant models.
Prevalence of neural tube defects in England prior to the mandatory fortification of non-wholemeal wheat flour with folic acid: a population-based cohort study
Authors: Broughan Jennifer M , Martin Danielle , Higgins Thomas , Swan Gillian , Cullum Adrienne , Kurinczuk Jennifer J , Draper Elizabeth S , Luyt Karen , Wellesley Diana G , Stevens Sarah , Tedstone Alison , Rankin Judith 
Published: October 2023

ObjectivesTo determine the baseline trends in the total birth prevalence of neural tube defects (NTDs) in England (2000–2019) to enable the impact of folic acid fortification of non-wholemeal wheat flour to be monitored.DesignPopulation-based, observational study using congenital anomaly (CA) registration data for England curated by the National Congenital Anomaly and Rare Disease Registration Service (NCARDRS).SettingRegions of England with active registration in the time period.ParticipantsBabies that were liveborn or stillborn and pregnancies that resulted in a termination of pregnancy or a late miscarriage (20–23 weeks’ gestation) with an NTD.Main outcome measuresTotal birth prevalence of anencephaly, spina bifida and all NTDs in England. Poisson regression analysis was used to evaluate time trends with regional register as a random effect. The progress of national registration across England was assessed.ResultsThere were 4541 NTD pregnancies out of 3 637 842 births in England; 1982 anencephaly and 2127 spina bifida. NTD prevalence was 12.5 (95% CI 12.1 to 12.9) per 10 000 total births. NTD prevalence per 10 000 total births was significantly higher in 2015–2019 (13.6, 95% CI 12.9 to 14.4) compared with 2010–2014 (12.1, 95% CI 11.7 to 12.5). An increasing trend in NTDs overall was detected (incidence rate ratio (IRR) 1.01, 1.00 to 1.02), although further analysis determined this effect was confined to 2015–2019 (compared against 2000–2004, IRR 1.14, 1.04 to 1.24). The birth prevalence of anencephaly reflected this pattern. The prevalence of spina bifida remained relatively stable over time.ConclusionsBaseline NTD prevalence for England has been established. National and standardised CA registration is in place, facilitating the systematic and consistent monitoring of pre-fortification and post-fortification NTD trends and evaluating the impact of fortification on NTD prevalence.
Revisiting $$\Xi _{Q}-\Xi _{Q}^{\prime }$$ mixing in QCD sum rules
Authors: Sun Xiao-Yu , Zhang Fu-Wei , Shi Yu-Ji , Zhao Zhen-Xing 
Published: October 2023

AbstractIn this work, we perform a QCD sum rules analysis on $$\Xi _{Q}-\Xi _{Q}^{\prime }$$

Ξ
Q

-

Ξ

Q

′

mixing. Contributions from up to dimension-6 four-quark operators are considered. However, it turns out that only dimension-4 and dimension-5 operators contribute, which reveals the non-perturbative nature of mixing. In particular, we observe that only the diagrams with the two light quarks participating in gluon exchange contribute to the mixing. Our results indicate that the mixing angle $$\theta _{c}=(1.2\sim 2.8)^{\circ }$$

θ
c

=

(
1.2
∼
2.8
)

∘

for the $$Q=c$$

Q
=
c

case and $$\theta _{b}=(0.28\sim 0.34)^{\circ }$$

θ
b

=

(
0.28
∼
0.34
)

∘

for the $$Q=b$$

Q
=
b

case. Our prediction of $$\theta _{c}$$

θ
c

is consistent with the most recent Lattice QCD result within error. Such a small mixing angle seems unlikely to resolve the tension between the recent experimental measurement from Belle and Lattice QCD calculation for the semileptonic decay $$\Xi _{c}^{0}\rightarrow \Xi ^{-} e^{+}\nu _{e}$$

Ξ

c

0

→

Ξ
-

e
+

ν
e

.