bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Moderate Versus Vigorous Exercise Intensity on Body Composition in Young Untrained Adults: The Activating Brown Adipose Tissue Through Exercise (ACTIBATE) Randomized Controlled Trial
Authors: Amaro-Gahete Francisco J. , Ruiz-Ruiz María , Cano-Nieto Amalia , Sanchez-Delgado Guillermo , Alcantara Juan M.A. , Acosta Francisco M. , Labayen Idoia , Ortega Francisco B. , Ruiz Jonatan R. 
Published: September 2023

The present study aimed to investigate the effect of a 24-week aerobic + resistance training programs at moderate versus vigorous intensity on body composition, and the persistence of the changes after a 10-month free-living period, in young untrained adults. This report is based on a secondary analysis from the activating brown adipose tissue through exercise (ACTIBATE) single-center unblinded randomized controlled trial. A total of 144 young adults (65.6% women) aged 18–25 years were randomly allocated to three different groups: (a) aerobic + resistance exercise training program based on the international physical activity recommendations at vigorous intensity (Ex-Vigorous group), (b) at moderate intensity (Ex-Moderate group), and (c) control group (no exercise). Body composition outcomes were determined by a dual-energy X-ray absorptiometry scanner. Both Ex-Vigorous and Ex-Moderate decreased body weight, fat mass, and visceral adipose tissue mass in a similar manner (all p < .04). After a 10-month free-living period, these parameters returned to baseline levels in both exercise groups (all ps < .03). No differences between the exercise groups and the control group were noted in lean mass changes (all ps > .1). A 24-week aerobic + resistance training intervention based on the international physical activity recommendations was enough to improve body weight, fat mass, and visceral adipose tissue mass in untrained young adults, independently of the exercise intensity (moderate vs. vigorous).
Delayed host mortality and immune response upon infection with
P. aeruginosa
persister cells
Authors: Hastings Cody J. , Keledjian Maya V. , Musselman Laura Palanker , Marques Cláudia N. H. 
Published: September 2023

ABSTRACT

Chronic infections are a heavy burden on healthcare systems worldwide. Persister cells are thought to be largely responsible for chronic infection due to their tolerance to antimicrobials and recalcitrance to innate immunity factors.
Pseudomonas aeruginosa
is a common and clinically relevant pathogen that contains stereotypical persister cells. Despite their importance in chronic infection, there have been limited efforts to study persister cell infections
in vivo. Drosophila melanogaster
has a well-described innate immune response similar to that of vertebrates and is a good candidate for the development of an
in vivo
model of infection for persister cells. Similar to what is observed in other bacterial strains, in this work we found that infection with
P. aeruginosa
persister cells resulted in a delayed mortality phenotype in
Caenorhabditis elegans
,
Arabidopsis thaliana
, and
D. melanogaster
compared to infection with regular cells. An in-depth characterization of infected
D. melanogaster
found that bacterial loads differed between persister and regular cells’ infections during the early stages. Furthermore, hemocyte activation and antimicrobial peptide expression were delayed/reduced in persister infections over the same time course, indicating an initial suppression of, or inability to elicit, the fly immune response. Overall, our findings support the use of
D. melanogaster
as a model in which to study persister cells
in vivo,
where this bacterial subpopulation exhibits delayed virulence and an attenuated immune response.
Mutations in the C-terminal region of the bacteriophage exclusion protein PglX can selectively inactivate restriction in
Salmonella
Authors: Wozniak Christopher E. , Hughes Kelly T. , Liou Theodore G. 
Published: September 2023

ABSTRACT

Salmonella enterica
serovar Typhimurium strain LT2 is protected by two DNA restriction-modification systems (HsdRMS and Mod-Res) and a Type I bacteriophage exclusion (BREX) system (BrxA-L). The LB5000 strain was constructed to inactivate restriction but not methylation in all three systems and has been available for decades (L. R. Bullas and J. I. Ryu, J Bacteriol 156:471–474, 1983,
https://doi.org/10.1128/jb.156.1.471-474.1983
). However, this strain had been heavily mutagenized and contains hundreds of other mutations, including a few in DNA repair genes. Here, we describe the development of a strain that is only mutated for DNA restriction by the three systems and remains competent for DNA modification. We transferred mutations specific to DNA restriction from LB5000 to a wild-type LT2 background. The
hsdR
and
res
mutations affected only restriction in the wild-type background, but the
brxC
and
pglZ
mutations for the poorly understood BREX system also reduced modification. Amino acids in an unannotated conserved region of PglX in the BREX system were then randomized. Mutations were identified that specifically affected restriction at 37°C but were found to be temperature sensitive for restriction and methylation when tested at 30°C and 42°C. These mutations in PglX are consistent with a domain that communicates DNA methylation information to other BREX effector proteins. Finally, mutations generated in the specificity domain of PglX may have changed the DNA binding site recognized by the BREX system.

IMPORTANCE

The restriction system mutants constructed in this study will be useful for cloning DNA and transferring plasmids from other bacterial species into
Salmonella
. We verified which mutations in strain LB5000 resulted in loss of restriction for each restriction-modification system and the BREX system by moving these mutations to a wild-type
Salmonella
background. The methylase PglX was then mutagenized, which adds to our knowledge of the BREX system that is found in many bacteria but is not well understood. These PglX mutations affected restriction and methylation at different temperatures, which suggests that the C-terminal region of PglX may coordinate interactions between the methylase and other BREX system proteins.
Fly-CURE, a multi-institutional CURE using
Drosophila
, increases students' confidence, sense of belonging, and persistence in research
Authors: Merkle Julie A. , Devergne Olivier , Kelly Seth M. , Croonquist Paula A. , Evans Cory J. , Hwalek Melanie A. , Straub Victoria L. , Hamill Danielle R. , Peister Alexandra , Puthoff David P. , Saville Ken J. , Siders Jamie L. , Villanueva Gonzalez Zully J. , Wittke-Thompson Jacqueline K. , Bieser Kayla L. , Stamm Joyce , Vrailas-Mortimer Alysia D. , Kagey Jacob D. 
Published: September 2023

ABSTRACT

The Fly-CURE is a genetics-focused multi-institutional Course-Based Undergraduate Research Experience (CURE) that provides undergraduate students with hands-on research experiences within a course. Through the Fly-CURE, undergraduate students at diverse types of higher education institutions across the United States map and characterize novel mutants isolated from a genetic screen in
Drosophila melanogaster
. To date, more than 20 mutants have been studied across 20 institutions, and our scientific data have led to eleven publications with more than 500 students as authors. To evaluate the impact of the Fly-CURE experience on students, we developed and validated assessment tools to identify students’ perceived research self-efficacy, sense of belonging in science, and intent to pursue additional research opportunities. Our data, collected over three academic years and involving 14 institutions and 480 students, show gains in these metrics after completion of the Fly-CURE across all student subgroups analyzed, including comparisons of gender, academic status, racial and ethnic groups, and parents’ educational background. Importantly, our data also show differential gains in the areas of self-efficacy and interest in seeking additional research opportunities between Fly-CURE students with and without prior research experience, illustrating the positive impact of research exposure (dosage) on student outcomes. Altogether, our data indicate that the Fly-CURE experience has a significant impact on students’ efficacy with research methods, sense of belonging to the scientific research community, and interest in pursuing additional research experiences.
Identification of tanshinone I as cap-dependent endonuclease inhibitor with broad-spectrum antiviral effect
Authors: He Xiaoxue , Yang Fan , Wu Yan , Lu Jia , Gao Xiao , Zhu Xuerui , Yang Jie , Liu Shuwen , Xiao Gengfu , Pan Xiaoyan 
Published: September 2023

ABSTRACT

The cap-snatching mechanism mediated by cap-dependent endonuclease, which is common among the negative-stranded, segmented RNA viruses in
Orthomyxoviridae
,
Bunyaviridae,
and
Arenaviridae
, is crucial for viral transcription and replication and is thus an attractive target for antiviral drug development. Herein, tanshinone I and its analog tanshinone IIA were identified as candidate compounds with broad-spectrum antiviral activities against bandaviruses, including severe fever with thrombocytopenia syndrome virus, Heartland virus, and Guertu virus. Additionally, the broad-spectrum antiviral activity was observed in influenza A virus and arenavirus. Further study demonstrated that tanshinone I exhibited potent antiviral activity
in vitro
and significantly reduced the viral loads
in vivo
. The underlying mechanism was speculated to involve tanshinone I binding to the active pocket of the L protein endonuclease domain to inhibit cap cleavage. This study reports candidate broad-spectrum antiviral compounds against negative-stranded, segmented RNA viruses, highlighting the endonuclease involved in the cap-snatching process as a reliable antiviral target for discovering broad-spectrum antivirals.

IMPORTANCE
The spread of avian-borne, tick-borne, and rodent-borne pathogens has the potential to pose a serious threat to human health, and candidate vaccines as well as therapeutics for these pathogens are urgently needed. Tanshinones, especially tanshinone I, were identified as a cap-dependent endonuclease inhibitor with broad-spectrum antiviral effects on negative-stranded, segmented RNA viruses including bandavirus, orthomyxovirus, and arenavirus from natural products, implying an important resource of candidate antivirals from the traditional Chinese medicines. This study supplies novel candidate antivirals for the negative-stranded, segmented RNA virus and highlights the endonuclease involved in the cap-snatching process as a reliable broad-spectrum antiviral target.
Metabolic engineering of
Paracoccus denitrificans
for dual degradation of sulfamethoxazole and ammonia nitrogen
Authors: Zhou Shenghu , Zhu Rongrong , Niu Xiaoqian , Zhao Yunying , Deng Yu 
Published: September 2023

ABSTRACT

Sulfamethoxazole (SMX), as one of the most widely used sulfonamide antibiotics, has been frequently detected in the aqueous environment, posing potential risks to the environment and human health. Although microbial degradation methods have been widely applied, some issues remain, including low degradation efficiency and poor environmental adaptability. In this regard, constructing efficient degrading bacteria by metabolic engineering is an ideal solution to these challenges. In this study, we used
Paracoccus denitrificans
DYTN-1, a superior nitrogen removal environment strain, as chassis to construct an SMX degradation pathway, obtaining a new bacteria for simultaneous degradation of SMX and removal of ammonia nitrogen. In doing this, we first identified and characterized four native promoters of
P. denitrificans
DYTN-1 with gradient strength to control the expression of the SMX degradation pathway. After degradation pathway expression level optimization and FMN reductase optimization, SMX degradation efficiency was significantly improved. The constructed
P. d-
pIAB
4
-P

CS
-sutR

strain exhibited superior co-degradation of SMX and ammonia nitrogen contaminants with degradation rates of 44% and 71%, respectively. This study could pave the way for SMX degradation engineered strain design and evolution of environmental bioremediation.

IMPORTANCE

The abuse of sulfamethoxazole (SMX) had led to an increased accumulation in the environment, resulting in the disruption of the structure of microbial communities, further disrupting the bio-degradation process of other pollutants, such as ammonia nitrogen. To solve this challenge, we first identified and characterized four native promoters of
Paracoccus denitrificans
DYTN-1 with gradient strength to control the expression of the SMX degradation pathway. Then SMX degradation efficiency was significantly improved with degradation pathway expression level optimization and FMN reductase optimization. Finally, the superior nitrogen removal environment strain,
P. denitrificans
DYTN-1, obtained an SMX degradation function. This pioneering study of metabolic engineering to enhance the SMX degradation in microorganisms could pave the way for designing the engineered strains of SMX and nitrogen co-degradation and the environmental bioremediation.
Emerging
Aeromonas
enteric infections: their association with inflammatory bowel disease and novel pathogenic mechanisms
Authors: Lee Seul A. , Liu Fang , Yuwono Christopher , Phan Monique , Chong Sarah , Biazik Joanna , Tay Alfred Chin Yen , Janitz Michael , Riordan Stephen M. , Lan Ruiting , Wehrhahn Michael C. , Zhang Li 
Published: September 2023

ABSTRACT

Aeromonas
species are emerging human enteric pathogens. This study examines the isolation of
Aeromonas
and other enteric bacterial pathogens from patients with and without inflammatory bowel disease (IBD). This study also investigates the intestinal epithelial pathogenic mechanisms of
Aeromonas veronii
. The isolation rates of seven enteric bacterial pathogens from 2,279 patients with IBD and 373,276 non-IBD patients were compared. An
A. veronii
strain (AS1) isolated from intestinal biopsies of a patient with IBD was used for pathogenic mechanism investigation, and
Escherichia coli
K12 was used as a bacterial control. HT-29 cells were used as a model of human intestinal epithelium. A significantly higher isolation of
Aeromonas
species was found in patients with IBD as compared to non-IBD patients (
P
= 0.0001, odds ratio = 2.11).
A. veronii
upregulated 177 inflammatory genes and downregulated 52 protein-coding genes affecting chromatin assembly, multiple small nuclear RNAs, multiple nucleolar RNAs, and 55 cytoplasmic tRNAs in HT-29 cells. These downregulation effects were unique to
A. veronii
and not observed in HT-29 cells infected with
E. coli
K12.
A. veronii
induced intestinal epithelial apoptosis involving the intrinsic pathway.
A. veronii
caused epithelial microvilli shortening and damage and epithelial production of IL-8. In conclusion, this study for the first time reports the association between IBD and
Aeromonas
enteric infection detected by bacterial cultivation. This study also reports that
A. veronii
damages intestinal epithelial cells via multiple mechanisms, of which the downregulating cytoplasmic tRNA, small nuclear RNA, and small nucleolar RNA are novel bacterial pathogenic mechanisms.

IMPORTANCE

This study for the first time reports the association between inflammatory bowel disease (IBD) and
Aeromonas
enteric infection detected by bacterial pathogen cultivation, highlighting the need of clinical and public health attention. The finding that patients with IBD are more susceptible to
Aeromonas
enteric infection suggests that detection of
Aeromonas
enteric infection should be routinely performed for the diagnosis and treatment of IBD. This study also reports novel bacterial pathogenic mechanisms employed by
Aeromonas veronii
. Through comparative transcriptomic analysis and other techniques, this study revealed the pathogenic mechanisms by which
A. veronii
causes damage to intestinal epithelial cells. Among the various pathogenic mechanisms identified, the downregulating tRNA, small nuclear and nucleolar RNAs in human intestinal epithelial cells are novel bacterial pathogenic mechanisms.
Whole-genome sequencing provides insights into a novel species:
Providencia hangzhouensis
associated with urinary tract infections
Authors: Dong Xu , Yu Yuyun , Liu Jiaying , Cao Dan , Xiang Yanghui , Bi Kefan , Yuan Xin , Li Shengchao , Wu Tiantian , Zhang Ying 
Published: September 2023

ABSTRACT

Providencia rettgeri
is a clinically significant opportunistic pathogen that is involved in urinary tract infections. Due to the resolution limitations of identification, distinguishing
P. rettgeri
from closely related species is challenging by commercial biochemical test systems. Here, we first reported a novel species,
Providencia hangzhouensis
, which had been misidentified as
P. rettgeri
. Exhibiting ≤91.97% average nucleotide identity (ANI) and ≤46.10% in silico DNA-DNA hybridization values with all known
Providencia
species,
P. hangzhouensis
falls well beneath the established species-defining thresholds. We conducted a population genomics analysis of
P. hangzhouensis
isolates worldwide. Our study revealed that
P. hangzhouensis
has emerged in many countries and has formed several transmission clusters. We found that
P. hangzhouensis
shared the highest ANI values (91.54% and 91.97%) with
P. rettgeri
and
P. huaxiensis
, respectively. The pan-genome analysis revealed that these three species possessed a similar component of pan-genomes. Two genes associated with metabolism,
folE2
and
ccmM
, were identified to be specific to
P. hangzhouensis
. Furthermore, we also observed that carbapenem-resistance genes frequently occur in
P. hangzhouensis
with the
bla
IMP-27
being the most prevalent (46.15%; 36/78). The emergence of
P. hangzhouensis
is often accompanied by extended-spectrum β-lactamase and carbapenem-resistance genes, and calls for tailored surveillance of this species as a clinically relevant species in the future.

IMPORTANCE

Our study has identified and characterized a novel species,
Providencia hangzhouensis
, which is associated with urinary tract infections and was previously misidentified as
Providencia rettgeri
. Through this study, we have identified specific genes unique to
P. hangzhouensis
, which could serve as marker genes for rapid PCR identification. Additionally, our findings suggest that the emergence of
P. hangzhouensis
is often accompanied by extended-spectrum β-lactamase and carbapenem-resistance genes, emphasizing the need for attention to clinical management and the importance of accurate species identification and proper drug use.
Genomic epidemiology of
Neisseria gonorrhoeae
in Shenzhen, China, during 2019–2020: increased spread of ceftriaxone-resistant isolates brings insights for strengthening public health responses
Authors: Wang Di , Li Yamei , Zhang Chi , Zeng Yaling , Peng Junping , Wang Feng 
Published: September 2023

ABSTRACT

The antimicrobial resistance (AMR) in gonorrhea poses global threat of increasing public health concern. In response to this concern, molecular surveillance has been widely utilized to detail the changes in the evolution and distribution of
Neisseria gonorrhoeae
during AMR transmission. In this study, we performed a comprehensive molecular surveillance of 664
N
.
gonorrhoeae
isolates collected in Shenzhen, one of the cities with the largest mobile population in China, 2019–2020. In 2020, ceftriaxone showed an unprecedented high resistance rate of 24.87%, and 67.83% of the ceftriaxone-resistant (Cro-R) isolates harbored a nonmosaic
penA
allele. The Cro-R isolates with nonmosaic
penA
alleles showed a tremendous increasing trend from 0.00% in 2014 to 20.45% in 2020, which proves the need for monitoring nonmosaic
penA
-related resistance. Importantly, genotyping indicated that multilocus sequence typing ST11231 (35.71%) had a notable rate of ceftriaxone resistance, which might become the focus of future surveillance. Whole-genome sequencing analysis showed that the internationally spreading FC428 clones have circulated in Shenzhen region with typical ceftriaxone resistance (MIC ≥ 0.5 mg/L) maintained. Our surveillance combined with genomic analysis provides current information to update gonorrhea management guidelines and emphasizes that continuous AMR surveillance for
N. gonorrhoeae
is essential.

IMPORTANCE

We conducted a comprehensive molecular epidemiology analysis for antimicrobial-resistant
Neisseria gonorrhoeae
in Shenzhen during 2019–2020, which provided important data for personalized treatment and adjustment of monitoring strategy. Briefly, the proportion of ceftriaxone-resistant (Cro-R) isolates reached a stunning prevalence rate of 24.87% in 2020. A typical increment of Cro-R isolates with nonmosaic
penA
alleles proves the necessity of monitoring nonmosaic AMR mechanism and involving it into developing molecular detection methods. Whole-genome sequencing analysis showed that the international spreading FC428 clone has been circulating in Shenzhen with typical ceftriaxone resistance (MIC ≥ 0.5 mg/L) maintained. In summary, we conducted a comprehensive epidemiology study, providing significant data for therapy management. Our results not only improve the understanding of the distribution and transmission of AMR in
N. gonorrhoeae
but also provide effective AMR data for improving surveillance strategies in China.
Heterologous expression of
mtf
and
mtc
genes of
Pseudanabaena foetida
var.
intermedia
is sufficient to produce 2-methylisoborneol in
Escherichia coli
Authors: Dayarathne Kaushalya , Ishikawa Toshiki , Watanabe Satoru , Ishikawa Yuuma , Aikeranmu Kadeer , Kitagawaa Hina , Komatsubara Natsumi , Yamaguchi Masatoshi , Kawai-Yamada Maki 
Published: September 2023

ABSTRACT

Microbial volatile metabolite 2-methylisoborneol (2-MIB) causes odor and taste issues in drinking water, making it unappealing for human consumption. It has been suggested that 2-MIB biosynthesis consists of two main steps, namely, methylation of geranyl diphosphate into 2-methyl geranyl diphosphate by geranyl diphosphate methyl transferase (GPPMT) and subsequent cyclization into 2-MIB by 2-MIB synthase (MIBS).
Pseudanabaena foetida
var.
intermedia
is a 2-MIB-producing cyanobacterium whose GPPMT and MIBS enzymes are encoded by adjacent
mtf
and
mtc
genes
.
The present study identified a 2-MIB-related gene cluster composed of
cnb
A,
mtf
,
mtc
, and
cnb
B genes in
P
.
foetida
var.
intermedia
. The two homologous cyclic nucleotide-binding protein genes,
cnb
A and
cnb
B, were detected adjacent to the
mtf
and
mtc
genes, respectively. The nucleotide sequence of the
cnb
A-
mtf-mtc-cnb
B gene cluster showed 99.55% identity with 2-MIB synthesis-associated gene cluster of
Pseudanabaena
sp. dqh15. RT-PCR results revealed that
mtf
and
mtc
genes are co-expressed, while
cnb
A and
cnb
B genes are expressed independently in
P
.
foetida
var.
intermedia
. To investigate whether only
mtf
and
mtc
genes are sufficient for 2-MIB synthesis, the two-gene unit (
mtf-mtc
) was introduced into
Escherichia coli
strain JM109 via overexpression vector pYS1C. Gas chromatograph-mass spectrometry results showed that the
E. coli
strain transformed with
mtf-mtc
was able to produce 2-MIB. The intracellular 2-MIB level in
P
.
foetida
var.
intermedia
was higher than the extracellular 2-MIB level, while the transformed
E. coli
strain showed an opposite trend. Growth inhibition was observed in the 2-MIB-producing transformed
E. coli
strain.

IMPORTANCE

Contamination of drinking water with odiferous microbial metabolite 2-MIB is a worldwide concern. Removal of 2-MIB from drinking water burdens the water purification process. Therefore, it is important to search for alternative methods, such as suppressing the production of 2-MIB by aquatic microorganisms. For that, it is necessary to expand the current knowledge about the mechanism of 2-MIB synthesis at the genetic level. This study revealed that
mtf
and
mtc
genes of the 2-MIB-related gene cluster are transcribed as a single unit in
P
.
foetida
var.
intermedia
, and the expression of both
mtf
and
mtc
genes is essential and sufficient for 2-MIB synthesis in
E. coli
heterologous gene expression system.