bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oxamic transcarbamylase of
Escherichia coli
is encoded by the three genes
allFGH
(formerly
fdrA, ylbE
, and
ylbF
)
Authors: Kim Nam Yeun , Kim Ok Bin 
Published: June 2024

ABSTRACT

Escherichia coli
uses allantoin as the sole nitrogen source during anaerobic growth. In the final step of allantoin degradation, oxamic transcarbamylase (OXTCase) converts oxalurate to carbamoyl phosphate (CP) and oxamate. The activity of this enzyme was first measured in
Streptococcus allantoicus
in the 1960s, but no OXTCase enzyme or the encoding gene(s) have been found in any strain. This study discovered that
allFGH
(
fdrA
,
ylbE
, and
ylbF
) are the genes that encode the global orphan enzyme OXTCase. The three genes form an operon together with
allK
(
ybcF
), encoding catabolic carbamate kinase. The
allFGHK
operon is located directly downstream of the
allECD
operon that encodes enzymes for the preceding steps of OXTCase. The OXTCase kinetic parameters were analyzed using the purified protein composed of AllF-AllG-AllH (FdrA-YlbE-YlbF); for the substrate CP,
K

M

and
V
max
were 1.3 mM and 15.4 U/mg OXTCase, respectively, and for the substrate oxamate, they were 36.9 mM and 27.0 U/mg OXTCase. In addition, the OXTCase encoded by the three genes is a novel transcarbamylase that shows no similarity with known enzymes of the transcarbamylase family such as aspartate transcarbamylase, ornithine transcarbamylase, and YgeW transcarbamylase. The present study elucidated the anaerobic allantoin degradation pathway of
E. coli
. Therefore, we suggest that the genes
fdrA
,
ylbE
, and
ylbF
are renamed
allF
,
allG
, and
allH
, respectively.

IMPORTANCE

The anaerobic allantoin degradation pathway of
Escherichia coli
includes a global orphan enzyme, oxamic transcarbamylase (OXTCase), which converts oxalurate to carbamoyl phosphate and oxamate. This study found that the
allFGH
(
fdrA
,
ylbE
, and
ylbF
) genes encode OXTCase. The OXTCase activity and kinetics were successfully determined with purified recombinant AllF-AllG-AllH (FdrA-YlbE-YlbF). This OXTCase is a novel transcarbamylase that shows no similarity with known enzymes of the transcarbamylase family such as aspartate transcarbamylase (ATCase), ornithine transcarbamylase (OTCase), and YgeW transcarbamylase (YTCase). In addition, OXTCase activity requires three genes, whereas ATCase is encoded by two genes, and OTCase and YTCase are encoded by a single gene. The current study discovered OXTCase, the last unknown step in allantoin degradation, and this enzyme is a new member of the transcarbamylase group that was previously unknown.
A simple and sensitive test for
Candida auris
colonization, surveillance, and infection control suitable for near patient use
Authors: Banik Sukalyani , Ozay Burcu , Trejo Marisol , Zhu YanChun , Kanna Charan , Santellan Cynthia , Shaw Bennett , Chandrasekaran Sukantha , Chaturvedi Sudha , Vejar Lindy , Chakravorty Soumitesh , Alland David , Banada Padmapriya 
Published: June 2024

ABSTRACT

Candida auris
is a multidrug-resistant fungal pathogen with a propensity to colonize humans and persist on environmental surfaces.
C. auris
invasive fungal disease is being increasingly identified in acute and long-term care settings. We have developed a prototype cartridge-based
C. auris
surveillance assay (CaurisSurV cartridge; “research use only”) that includes integrated sample processing and nucleic acid amplification to detect
C. auris
from surveillance skin swabs in the GeneXpert instrument and is designed for point-of-care use. The assay limit of detection (LoD) in the skin swab matrix was 10.5 and 14.8 CFU/mL for non-aggregative (AR0388) and aggregative (AR0382) strains of
C. auris
, respectively. All five known clades of
C. auris
were detected at 2-3-5× (31.5–52.5 CFU/mL) the LoD. The assay was validated using a total of 85 clinical swab samples banked at two different institutions (University of California Los Angeles, CA and Wadsworth Center, NY). Compared to culture, sensitivity was 96.8% (30/31) and 100% (10/10) in the UCLA and Wadsworth cohorts, respectively, providing a combined sensitivity of 97.5% (40/41), and compared to PCR, the combined sensitivity was 92% (46/50). Specificity was 100% with both clinical (
C. auris
negative matrix,
N
= 31) and analytical (non-
C
.
auris
strains,
N
= 32) samples. An additional blinded study with
N
= 60 samples from Wadsworth Center, NY yielded 97% (29/30) sensitivity and 100% (28/28) specificity. We have developed a completely integrated, sensitive, specific, and 58-min prototype test, which can be used for routine surveillance of
C. auris
and might help prevent colonization and outbreaks in acute and chronic healthcare settings.

IMPORTANCE

This study has the potential to offer a better solution to healthcare providers at hospitals and long-term care facilities in their ongoing efforts for effective and timely control of
Candida auris
infection and hence quicker response for any potential future outbreaks.
Nervous necrosis virus capsid protein and Protein A dynamically modulate the fish cGAS-mediated IFN signal pathway to facilitate viral evasion
Authors: Huang Siyou , Yang Linwei , Zheng Rui , Weng Shaoping , He Jianguo , Xie Junfeng 
Published: June 2024

ABSTRACT

Nervous necrosis virus (NNV), an aquatic RNA virus belonging to
Betanodavirus
, infects a variety of marine and freshwater fishes, leading to massive mortality of cultured larvae and juveniles and substantial economic losses. The enzyme cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) is widely recognized as a central component in the innate immune response to cytosolic DNA derived from different pathogens. However, little is known about the response of cGAS to aquatic RNA viruses. This study found that
Epinephelus coioides
cGAS (EccGAS) overexpression inhibited NNV replication, whereas EccGAS silencing promoted NNV replication. The anti-NNV activity of EccGAS was involved in interferon (IFN) signaling activation including tumor necrosis factor receptor-associated factor family member-associated NF-kappa-B activator-binding kinase 1 (TBK1) phosphorylation, interferon regulatory factor 3 (IRF3) nuclear translocation, and the subsequent induction of IFNc and ISGs. Interestingly, NNV employed its capsid protein (CP) or Protein A (ProA) to negatively or positively modulate EccGAS-mediated IFN signaling by simultaneously targeting EccGAS. CP interacted with EccGAS via the arm-P, S-P, and SD structural domains and promoted its polyubiquitination with K48 and K63 linkages in an EcUBE3C (the ubiquitin ligase)-dependent manner, ultimately leading to EccGAS degradation. Conversely, ProA bound to EccGAS and inhibited its ubiquitination and degradation. In regulating EccGAS protein content, CP’s inhibitory action was more pronounced than ProA’s protective effect, allowing successful NNV replication. These novel findings suggest that NNV CP and ProA dynamically modulate the EccGAS-mediated IFN signaling pathway to facilitate the immune escape of NNV. Our findings shed light on a novel mechanism of virus-host interaction and provide a theoretical basis for the prevention and control of NNV.

IMPORTANCE
As a well-known DNA sensor, cGAS is a pivotal component in innate anti-viral immunity to anti-DNA viruses. Although there is growing evidence regarding the function of cGAS in the resistance to RNA viruses, the mechanisms by which cGAS participates in RNA virus-induced immune responses in fish and how aquatic viruses evade cGAS-mediated immune surveillance remain elusive. Here, we investigated the detailed mechanism by which EccGAS positively regulates the anti-NNV response. Furthermore, NNV CP and ProA interacted with EccGAS, regulating its protein levels through ubiquitin-proteasome pathways, to dynamically modulate the EccGAS-mediated IFN signaling pathway and facilitate viral evasion. Notably, NNV CP was identified to promote the ubiquitination of EccGAS via ubiquitin ligase EcUBE3C. These findings unveil a novel strategy for aquatic RNA viruses to evade cGAS-mediated innate immunity, enhancing our understanding of virus-host interactions.
Bloodmeals fuel dengue virus replication in the female mosquito
Aedes aegypti
Authors: Huang Yu-Ning , Lee Kuan-Ying , Shiao Shin-Hong , Chen Chun-Hong , Yu Guann-Yi , Yu Ming-Jiun 
Published: June 2024

ABSTRACT

Vector competence defines the ability of a vector to acquire, host, and transmit a pathogen. Understanding the molecular determinants of the mosquitos’ competence to host dengue virus (DENV) holds promise to prevent its transmission. To this end, we employed RNA-seq to profile mRNA transcripts of the female
Aedes aegypti
mosquitos feeding on naïve vs viremic mouse. While most transcripts (12,634) did not change their abundances, 360 transcripts showed decreases. Biological pathway analysis revealed representatives of the decreased transcripts involved in the wnt signaling pathway and hippo signaling pathway. One thousand three hundred fourteen transcripts showed increases in abundance and participate in 21 biological pathways including amino acid metabolism, carbon metabolism, fatty acid metabolism, and oxidative phosphorylation. Inhibition of oxidative phosphorylation with antimycin A reduced oxidative phosphorylation activity and ATP concentration associated with reduced DENV replication in the
Aedes aegypti
cells. Antimycin A did not affect the amounts of the non-structural proteins 3 and 5, two major components of the replication complex. Ribavirin, an agent that reduces GTP concentration, recapitulated the effects of reduced ATP concentration on DENV replication. Knocking down one of the oxidative phosphorylation components, ATP synthase subunit β, reduced DENV replication in the mosquitos. In summary, our results suggest that DENV enhances metabolic pathways in the female
Aedes aegypti
mosquitos to supply nutrients and energy for virus replication. ATP synthase subunit β knockdown might be exploited to reduce the mosquitos’ competence to host and transmit DENV.

IMPORTANCE
Through evolution, the mosquito-borne viruses have adapted to the blood-feeding behaviors of their opportunist hosts to fulfill a complete lifecycle in humans and mosquitos. Disruption in the mosquitos’ ability to host these viruses offers strategies to prevent diseases caused by them. With the advent of genomic tools, we discovered that dengue virus (DENV) benefited from the female mosquitos’ bloodmeals for metabolic and energetic supplies for replication. Chemical or genetic disruption in these supplies reduced DENV replication in the female mosquitos. Our discovery can be exploited to produce genetically modified mosquitos, in which DENV infection leads to disruption in the supplies and thereby reduces replication and transmission. Our discovery might be extrapolated to prevent mosquito-borne virus transmission and the diseases they cause.
Stability and gene strand bias of lambda prophages and chromosome organization in
Escherichia coli
Authors: Li Xintian , Gallardo Oscar , August Elias , Dassa Bareket , Court Donald L. , Stavans Joel , Arbel-Goren Rinat 
Published: June 2024

ABSTRACT

Temperate phage-mediated horizontal gene transfer is a potent driver of genetic diversity in the evolution of bacteria. Most lambdoid prophages in
Escherichia coli
are integrated into the chromosome with the same orientation with respect to the direction of chromosomal replication, and their location on the chromosome is far from homogeneous. To better understand these features, we studied the interplay between lysogenic and lytic states of phage lambda in both native and inverted integration orientations at the wild-type integration site as well as at other sites on the bacterial chromosome. Measurements of free phage released by spontaneous induction showed that the stability of lysogenic states is affected by location and orientation along the chromosome, with stronger effects near the origin of replication. Competition experiments and range expansions between lysogenic strains with opposite orientations and insertion loci indicated that there are no major differences in growth. Moreover, measurements of the level of transcriptional bursts of the
cI
gene coding for the lambda phage repressor using single-molecule fluorescence
in situ
hybridization resulted in similar levels of transcription for both orientations and prophage location. We postulate that the preference for a given orientation and location is a result of a balance between the maintenance of lysogeny and the ability to lyse.

IMPORTANCE

The integration of genetic material of temperate bacterial viruses (phages) into the chromosomes of bacteria is a potent evolutionary force, allowing bacteria to acquire in one stroke new traits and restructure the information in their chromosomes. Puzzlingly, this genetic material is preferentially integrated in a particular orientation and at non-random sites on the bacterial chromosome. The work described here reveals that the interplay between the maintenance of the stability of the integrated phage, its ability to excise, and its localization along the chromosome plays a key role in setting chromosomal organization in
Escherichia coli
.
Biological characteristics of manganese transporter MntP in
Klebsiella pneumoniae
Authors: Peng Wei , Xu Yafei , Yin Yilin , Xie Jichen , Ma Renhui , Song Guoyuan , Zhang Zhiqiang , Quan Qiuhang , Jiang Qinggen , Li Moran , Li Bei 
Published: June 2024

ABSTRACT

Klebsiella pneumoniae
is an important opportunistic pathogen that causes a variety of infections. It is critical for bacteria to maintain metal homeostasis during infection. By using an isogenic
mntP
deletion mutant of
K. pneumoniae
strain NTUH-K2044, we found that MntP was a manganese efflux pump. Manganese increased the tolerance to oxidative stress, and oxidative stress could increase the intracellular manganese concentration. In oxidative stress, the
mntP
deletion mutant exhibited significantly higher sensitivity to manganese. Furthermore, iron could increase the tolerance of the
mntP
deletion mutant to manganese. Inductively coupled plasma mass spectrometry analysis revealed that the
mntP
deletion mutant had higher intracellular manganese and iron concentrations than wild-type and complementary strains. These findings suggested that iron could increase manganese tolerance in
K. pneumoniae
. This work elucidated the role of MntP in manganese detoxification and Mn/Fe homeostasis in
K. pneumoniae
.

IMPORTANCE

Metal homeostasis plays an important role during the process of bacterial infection. Herein, we revealed that MntP was involved in intracellular manganese homeostasis. Manganese promoted resistance to oxidative stress in
Klebsiella pneumoniae
. Furthermore, we demonstrated that the
mntP
deletion mutant exhibited significantly lower survival under manganese and H
2
O
2
conditions. Oxidative stress increased the intracellular manganese content of the
mntP
deletion mutant. MntP played a critical role in maintaining intracellular manganese and iron concentrations. MntP contributed to manganese detoxification and Mn/Fe homeostasis in
K. pneumoniae
.
Integrative RNA-seq and ChIP-seq analysis unveils metabolic regulation as a conserved antiviral mechanism of chicken p53
Authors: Cui Lu , Li Xuefeng , Chen Zhijie , Liu Zheyi , Zhang Yu , Han Zongxi , Liu Shengwang , Li Hai 
Published: June 2024

ABSTRACT

The tumor suppressor p53, primarily functioning as a transcription factor, has exhibited antiviral capabilities against various viruses in chickens, including infectious bursal disease virus (IBDV), avian leukosis virus subgroup J (ALV-J), and avian infectious laryngotracheitis virus (ILTV). Nevertheless, the existence of a universal antiviral mechanism employed by chicken p53 (chp53) against these viruses remains uncertain. This study conducted a comprehensive comparison of molecular networks involved in chp53’s antiviral function against IBDV, ALV-J, and ILTV. This was achieved through an integrated analysis of ChIP-seq data, examining chp53’s genome-wide chromatin occupancy, and RNA-seq data from chicken cells infected with these viruses. The consistent observation of chp53 target gene enrichment in metabolic pathways, confirmed via ChIP-qPCR, suggests a ubiquitous regulation of host cellular metabolism by chp53 across different viruses. Further genome binding motif conservation analysis and transcriptional co-factor prediction suggest conserved transcriptional regulation mechanism by which chp53 regulates host cellular metabolism during viral infection. These findings offer novel insights into the antiviral role of chp53 and propose that targeting the virus-host metabolic interaction through regulating p53 could serve as a universal strategy for antiviral therapies in chickens.

IMPORTANCE
The current study conducted a comprehensive analysis, comparing molecular networks underlying chp53’s antiviral role against infectious bursal disease virus (IBDV), avian leukosis virus subgroup J (ALV-J), and avian infectious laryngotracheitis virus (ILTV). This was achieved through a combined assessment of ChIP-seq and RNA-seq data obtained from infected chicken cells. Notably, enrichment of chp53 target genes in metabolic pathways was consistently observed across viral infections, indicating a universal role of chp53 in regulating cellular metabolism during diverse viral infections. These findings offer novel insights into the antiviral capabilities of chicken p53, laying a foundation for the potential development of broad-spectrum antiviral therapies in chickens.
Recognition of Neogene tin mineralization in the Southeast Asian tin belt
Authors: Huang Wen-Qing , Pan Jun-Yi , Ni Pei , Zhou Jun-Gui , Shui Ting , Chen Hui , Fan Ming-Sen , Cui Jian-Ming 
Published: June 2024

Abstract
The Southeast (SE) Asian tin belt is a major tin producer globally, with a prolonged mineralization history from the Permian to Paleogene (ca. 285–45 Ma). Tin deposits in this region are typically associated with tectonic settings that involve subduction and collision of the Paleo-, Meso-, and Neo-Tethys slabs. Ca. 40 Ma, a notable transition occurred in the tectonic regime of SE Tibet, with the Neo-Tethys subduction giving way to lateral extrusion of the Indochina block along major strike-slip faults. Previously, it was believed that this shift had brought tin mineralization to a halt. In this study, we present in situ laser ablation–inductively coupled plasma–mass spectrometry U-Pb cassiterite ages of 21–19 Ma from the Yunling tin deposit located in western Yunnan, China.
Yunling produces gem-quality cassiterite that is transparent but contains low U contents, which renders usual U-Pb dating techniques unusable. To address this, a customized dating protocol involving cathodoluminescence (CL) imaging and testing of U distribution on crystallographically well-defined cassiterite crystals was applied. The study revealed two types of primary microstructures in cassiterite: volumetrically dominant concentric oscillatory growth zones and subordinate CL-dark sector zones. The U content shows a preferential enrichment in the CL-dark sector zones, typically tens of parts per million (ppm), which is two orders of magnitude greater than the U content in the concentric zone. This is significant, as the dating results (21–19 Ma) obtained through the targeted selection of CL-dark sector zones represent the youngest tin mineralization event in the SE Asian tin belt. Additionally, these results challenge the established belief that the ore-hosting Indosinian granite, dated to ca. 215 Ma, was related to Sn mineralization in the Yunling area. We suggest that emplacement of the early Neogene Sn mineralization at Yunling may be genetically connected to extensive delamination of the lithosphere in southeastern Tibet. The lithospheric delamination led to the upwelling and decompression partial melting of the asthenosphere, which provides a plausible explanation for the high temperature required for the release of Sn from biotite-dehydration melting of sedimentary protolith. The study also highlights the potential of Oligocene–Miocene-aged granites situated in the Sanjiang Tethys and adjacent areas of western Yunnan as prospective exploration targets for tin mineralization.
Severe psychiatric disorders are associated with increased risk of dementia
Authors: Stevenson-Hoare Joshua , Legge Sophie E , Simmonds Emily , Han Jun , Owen Michael J , O’Donovan Michael , Kirov George , Escott-Price Valentina 
Published: June 2024

BackgroundIndividuals with psychiatric disorders have an increased risk of developing dementia. Most cross-sectional studies suffer from selection bias, underdiagnosis and poor population representation, while there is only limited evidence from longitudinal studies on the role of anxiety, bipolar and psychotic disorders. Electronic health records (EHRs) permit large cohorts to be followed across the lifespan and include a wide range of diagnostic information.ObjectiveTo assess the association between four groups of psychiatric disorders (schizophrenia, bipolar disorder/mania, depression and anxiety) with dementia in two large population-based samples with EHR.MethodsUsing EHR on nearly 1 million adult individuals in Wales, and from 228 937 UK Biobank participants, we studied the relationships between schizophrenia, mania/bipolar disorder, depression, anxiety and subsequent risk of dementia.FindingsIn Secure Anonymised Information Linkage, there was a steep increase in the incidence of a first diagnosis of psychiatric disorder in the years prior to the diagnosis of dementia, reaching a peak in the year prior to dementia diagnosis for all psychiatric diagnoses. Psychiatric disorders, except anxiety, were highly significantly associated with a subsequent diagnosis of dementia: HRs=2.87, 2.80, 1.63 for schizophrenia, mania/bipolar disorder and depression, respectively. A similar pattern was found in the UK Biobank (HRs=4.46, 3.65, 2.39, respectively) and anxiety was also associated with dementia (HR=1.34). Increased risk of dementia was observed for all ages at onset of psychiatric diagnoses when these were divided into 10-year bins.ConclusionsPsychiatric disorders are associated with an increased risk of subsequent dementia, with a greater risk of more severe disorders.Clinical implicationsA late onset of psychiatric disorders should alert clinicians of possible incipient dementia.