bluuebunny/crossref_metadata_2025 huggingface dataset:
The embryonic zebrafish brain is exclusively colonized by
pu.1
-dependent and lymphatic-independent population of microglia
Authors: Yu Tao , Chen Jiahao , Wang Yuexin , Xu Jin
Published: August 2024

Microglia, the crucial immune cells inhabiting the central nervous system (CNS), perform a range of vital functions, encompassing immune defense and neuronal regulation. Microglia subsets with diverse functions and distinct developmental regulations have been identified recently. It is generally accepted that all microglia originate from hematopoiesis and depend on the myeloid transcription factor PU.1. However, a recent study reported the existence of

mrc1
+

microglia in zebrafish embryos, which are seemingly independent of Pu.1 and reliant on lymphatic vessels, sparking great interest in the possibility of lymphatic-originated microglia. To address this, we took advantage of a
pu.1
knock-in zebrafish allele for a detailed investigation. Our results conclusively showed that almost all zebrafish embryonic microglia (~95% on average) express
pu.1
. Further, lineage tracing and mutant analysis revealed that these microglia neither emerged from nor depended on lymphatic vessels. In essence, our study refutes the presence of
pu.1
-independent but lymphatic-dependent microglia.
The uniqueness of human vulnerability to brain aging in great ape evolution
Authors: Vickery Sam , Patil Kaustubh R. , Dahnke Robert , Hopkins William D. , Sherwood Chet C. , Caspers Svenja , Eickhoff Simon B. , Hoffstaedter Felix
Published: August 2024

Aging is associated with progressive gray matter loss in the brain. This spatially specific, morphological change over the life span in humans is also found in chimpanzees, and the comparison between these great ape species provides a unique evolutionary perspective on human brain aging. Here, we present a data-driven, comparative framework to explore the relationship between gray matter atrophy with age and recent cerebral expansion in the phylogeny of chimpanzees and humans. In humans, we show a positive relationship between cerebral aging and cortical expansion, whereas no such relationship was found in chimpanzees. This human-specific association between strong aging effects and large relative cortical expansion is particularly present in higher-order cognitive regions of the ventral prefrontal cortex and supports the “last-in-first-out” hypothesis for brain maturation in recent evolutionary development of human faculties.
Inhibiting endothelial
Rhoj
blocks profibrotic vascular intussusception and angiocrine factors to sustain lung regeneration
Authors: Ma Jie , Zhang Liyin , Zhang Xu , Zhang Lanlan , Zhang Hua , Zhu Yulei , Huang Xingming , Zhang Ting , Tang Xiangdong , Wang Yuan , Chen Lu , Pu Qiang , Yang Liming , Cao Zhongwei , Ding Bi-Sen
Published: August 2024

Lung regeneration after fibrosis requires formation of functional new vasculature, which is essential for gas exchange and cellular cross-talk with other lung cells. It remains unknown how the lung vasculature can be regenerated without fibrosis. Here, we tested the role of N6-methyladenosine (m6A) modification of
forkhead box protein O1
(
Foxo1
) mRNA in lung regeneration after pneumonectomy (PNX) in mice, a model for lung regrowth after surgical resection. Endothelial cell (EC)–specific knockout of
methyltransferase-like 3
(
Mettl3
) and
Foxo1
caused nonproductive intussusceptive angiogenesis (IA), which impaired regeneration and enhanced fibrosis. This nonproductive IA was characterized by enhanced endothelial proliferation and increased vascular splitting with increased numbers of pillar ECs. Endothelial-selective knockout of
Mettl3
in mice stimulated nonproductive IA and up-regulation of profibrotic factors after PNX, promoting regeneration to fibrotic transition. EC-specific mutation of m6A modification sites in the
Foxo1
gene in mice revealed that endothelial
Mettl3
modified A504 and A2035 sites in the
Foxo1
mRNA to maintain pro-regenerative endothelial glycolysis, ensuring productive IA and lung regeneration without fibrosis. Suppression of
Mettl3-Foxo1
signaling stimulated a subset of hyperglycolytic and hyperproliferative
6-phosphofructo-2-kinase/fructose-2
,
6-biphosphatase 3
(
Pfkfb3
)
+
,
Ras homolog family member J
(
Rhoj
)
+
, and
platelet-derived growth factor subunit B
(
Pdgfb
)
+
ECs in both human and mouse lungs with fibrosis. Inhibiting this
Pfkfb3
+
Rhoj
+
Pdgfb
+
EC subset normalized IA, alleviated fibrosis, and restored regeneration in bleomycin (BLM)–injured mouse lungs. We found that m6A modification of
Foxo1
in the mouse vasculature promoted lung regeneration over fibrosis after PNX and BLM injury.
An autoimmune transcriptional circuit drives FOXP3
+
regulatory T cell dysfunction
Authors: Sumida Tomokazu S. , Lincoln Matthew R. , He Liang , Park Yongjin , Ota Mineto , Oguchi Akiko , Son Raku , Yi Alice , Stillwell Helen A. , Leissa Greta A. , Fujio Keishi , Murakawa Yasuhiro , Kulminski Alexander M. , Epstein Charles B. , Bernstein Bradley E. , Kellis Manolis , Hafler David A.
Published: August 2024

Autoimmune diseases, among the most common disorders of young adults, are mediated by genetic and environmental factors. Although CD4
+
FOXP3
+
regulatory T cells (T
regs
) play a central role in preventing autoimmunity, the molecular mechanism underlying their dysfunction is unknown. Here, we performed comprehensive transcriptomic and epigenomic profiling of T
regs
in the autoimmune disease multiple sclerosis (MS) to identify critical transcriptional programs regulating human autoimmunity. We found that up-regulation of a primate-specific short isoform of PR domain zinc finger protein 1 (PRDM1-S) induces expression of serum and glucocorticoid-regulated kinase 1 (SGK1) independent from the evolutionarily conserved long
PRDM1
, which led to destabilization of forkhead box P3 (FOXP3) and T
reg
dysfunction. This aberrant
PRDM1-S/SGK1
axis is shared among other autoimmune diseases. Furthermore, the chromatin landscape profiling in T
regs
from individuals with MS revealed enriched activating protein–1 (AP-1)/interferon regulatory factor (IRF) transcription factor binding as candidate upstream regulators of
PRDM1-S
expression and T
reg
dysfunction. Our study uncovers a mechanistic model where the evolutionary emergence of
PRDM1-S
and epigenetic priming of AP-1/IRF may be key drivers of dysfunctional T
regs
in autoimmune diseases.
Adjuvants restore colistin sensitivity in mouse models of highly colistin-resistant isolates, limiting bacterial proliferation and dissemination
Authors: Koller Beverly H. , Jania Leigh A. , Li Haoting , Barker William T. , Melander Roberta J. , Melander Christian
Published: August 2024

Antimicrobial resistance (AMR) has led to a marked reduction in the effectiveness of many antibiotics, representing a substantial and escalating concern for global health. Particularly alarming is resistance in Gram-negative bacteria due to the scarcity of therapeutic options for treating infections caused by these pathogens. This challenge is further compounded by the rising incidence of resistance to colistin, an antibiotic traditionally considered a last resort for the treatment of multi-drug resistant (MDR) Gram-negative bacterial infections. In this study, we demonstrate that adjuvants restore colistin sensitivity
in vivo
. We previously reported that the salicylanilide kinase inhibitor IMD-0354, which was originally developed to inhibit the human kinase IKKβ in the NFκB pathway, is a potent colistin adjuvant. Subsequent analog synthesis using an amide isostere approach led to the creation of a series of novel benzimidazole compounds with enhanced colistin adjuvant activity. Herein, we demonstrate that both IMD-0354 and a lead benzimidazole effectively restore colistin susceptibility in mouse models of highly colistin-resistant
Klebsiella pneumoniae
and
Acinetobacter baumannii
-induced peritonitis. These novel adjuvants show low toxicity
in vivo
, significantly reduce bacterial load, and prevent dissemination that could otherwise result in systemic infection.
The novel MFS efflux pump SxtP, regulated by the LysR-type transcriptional activator SxtR, is involved in the susceptibility to sulfamethoxazole/trimethoprim (SXT) and the pathogenesis of
Acinetobacter baumannii
Authors: Gaona Marc , Corral Jordi , Campoy Susana , Barbé Jordi , Pérez−Varela María , Aranda Jesús
Published: August 2024

Acinetobacter baumannii
is a notorious opportunistic pathogen responsible for healthcare-associated infections worldwide. Efflux pumps play crucial roles in mediating antimicrobial resistance, motility, and virulence. In this study, we present the identification and characterization of the new
A. baumannii
efflux pump SxtP belonging to the MFS superfamily (
m
ajor
f
acilitator
s
uperfamily), along with its associated activator
L
ysR
-
type
t
ranscriptional
r
egulator (LTTR) SxtR, demonstrating their roles in sulfamethoxazole/trimethoprim (also known as co-trimoxazole or SXT) resistance, surface-associated motility and virulence.
Retrospective validation study of a machine learning-based software for empirical and organism-targeted antibiotic therapy selection
Authors: Tejeda Maria Isabel , Fernández Javier , Valledor Pablo , Almirall Cristina , Barberán José , Romero-Brufau Santiago
Published: August 2024

Errors in antibiotic prescriptions are frequent, often resulting from the inadequate coverage of the infection-causative microorganism. The efficacy of iAST, a machine-learning-based software offering empirical and organism-targeted antibiotic recommendations, was assessed. The study was conducted in a 12-hospital Spanish institution. After model fine-tuning with 27,531 historical antibiograms, 325 consecutive patients with acute infections were selected for retrospective validation. The primary endpoint was comparing each of the top three of iAST’s antibiotic recommendations’ success rates (confirmed by antibiogram results) with the antibiotic prescribed by the physicians. Secondary endpoints included examining the same hypothesis within specific study population subgroups and assessing antibiotic stewardship by comparing the percentage of antibiotics recommended that belonged to different World Health Organization AWaRe groups within each arm of the study. All of iAST first three recommendations were non-inferior to doctor prescription in the primary endpoint analysis population as well as the secondary endpoint. The overall success rate of doctors’ empirical treatment was 68.93%, while that of the first three iAST options was 91.06% (
P
< 0.001), 90.63% (
P
< 0.001), and 91.06% (
P
< 001), respectively. For organism-targeted therapy, the doctor’s overall success rate was 84.16%, and that of the first three ranked iAST options was 97.83% (
P
< 0.001), 94.09% (
P
< 0.001), and 91.30% (
P
< 0.001), respectively. In empirical therapy, compared to physician prescriptions, iAST demonstrated a greater propensity to recommend access antibiotics, fewer watch antibiotics, and higher reserve antibiotics. In organism-targeted therapy, iAST advised a higher utilization of access antibiotics. The present study demonstrates iAST accuracy in predicting antibiotic susceptibility, showcasing its potential to promote effective antibiotic stewardship.

CLINICAL TRIALS

This study is registered with

ClinicalTrials.gov
as
NCT06174519

.
Application of machine-learning models to predict the ganciclovir and valganciclovir exposure in children using a limited sampling strategy
Authors: Ponthier Laure , Franck Bénédicte , Autmizguine Julie , Labriffe Marc , Ovetchkine Philippe , Marquet Pierre , Åsberg Anders , Woillard Jean-Baptiste
Published: August 2024

Intravenous ganciclovir and oral valganciclovir display significant variability in ganciclovir pharmacokinetics, particularly in children. Therapeutic drug monitoring currently relies on the area under the concentration-time (AUC). Machine-learning (ML) algorithms represent an interesting alternative to Maximum-a-Posteriori Bayesian-estimators for AUC estimation. The goal of our study was to develop and validate an ML-based limited sampling strategy (LSS) approach to determine ganciclovir AUC
0–24
after administration of either intravenous ganciclovir or oral valganciclovir in children. Pharmacokinetic parameters from four published population pharmacokinetic models, in addition to the World Health Organization growth curve for children, were used in the mrgsolve R package to simulate 10,800 pharmacokinetic profiles of children. Different ML algorithms were trained to predict AUC
0–24
based on different combinations of two or three samples. Performances were evaluated in a simulated test set and in an external data set of real patients. The best estimation performances in the test set were obtained with the Xgboost algorithm using a 2 and 6 hours post dose LSS for oral valganciclovir (relative mean prediction error [rMPE] = 0.4% and relative root mean square error [rRMSE] = 5.7%) and 0 and 2 hours post dose LSS for intravenous ganciclovir (rMPE = 0.9% and rRMSE = 12.4%). In the external data set, the performance based on these two sample LSS was acceptable: rMPE = 0.2% and rRMSE = 16.5% for valganciclovir and rMPE = −9.7% and rRMSE = 17.2% for intravenous ganciclovir. The Xgboost algorithm developed resulted in a clinically relevant individual estimation using only two blood samples. This will improve the implementation of AUC-targeted ganciclovir therapeutic drug monitoring in children.
Analytical and clinical validation of direct detection of antimicrobial resistance markers by plasma microbial cell-free DNA sequencing
Authors: Christians Fred C. , Akhund-Zade Jamilla , Jarman Kristin , Venkatasubrahmanyam Shivkumar , Noll Nicholas , Blauwkamp Timothy A. , Bercovici Sivan , Zielinska Aga , Carr Amy L. , Craney Arryn , Pike Matthew , Farrell John Joseph , Dadwal Sanjeet , Wood James B. , Matkovich Efrat , McAdams Staci , Nolte Frederick S.
Published: August 2024

Sequencing of plasma microbial cell-free DNA (mcfDNA) has gained increased acceptance as a valuable adjunct to standard-of-care testing for diagnosis of infections throughout the body. Here, we report the analytical and clinical validation of a novel application of mcfDNA sequencing, the non-invasive detection of seven common antimicrobial resistance (AMR) genetic markers in 18 important pathogens. The AMR markers include SCC
mec
,
mecA, mecC
,
vanA, vanB
,
bla
CTX-M
, and
bla
KPC
. The AMR markers were computationally linked to the pathogens detected. Analytical validation showed high reproducibility (100%), inclusivity (54 to 100%), and exclusivity (100%). Clinical accuracy was assessed with 114 unique plasma samples from patients at seven study sites with concordant culture results for target bacteria from a variety of specimen types and correlated with available phenotypic antimicrobial susceptibility test results and genotypic results. The positive percent agreement (PPA), negative percent agreement (NPA), and diagnostic yield (DY) were estimated for each AMR marker. DY was defined as the percentage of tests that yielded an actionable result of either detected or not detected. The results for the combination of SCC
mec
and
mecA
for staphylococci were PPA 19/20 (95.0%), NPA 21/22 (95.4%), DY 42/60 (70.0%);
vanA
for enterococci were PPA 3/3 (100%), NPA 2/2 (100%), DY 5/6 (83.3%);
bla
CTX-M
for gram-negative bacilli were PPA 5/6 (83.3%), NPA 29/29 (100%), DY 35/49 (71.4%); and
bla
KPC
for gram-negative bacilli were PPA 0/2 (0%), NPA: 23/23 (100%), DY 25/44 (56.8%). The addition of AMR capability to plasma mcfDNA sequencing should provide clinicians with an effective new culture-independent tool for optimization of therapy.

IMPORTANCE

This manuscript is ideally suited for the Innovative Diagnostic Methods sections as it reports the analytical and clinical validation of a novel application of plasma microbial cell-free DNA sequencing for direct detection of seven selected antimicrobial resistance markers in 18 target pathogens. Clearly, it has potential clinical utility in optimizing therapy and was incorporated into the Karius test workflow in September 2023. In addition, the workflow could readily be adapted to expand the number of target bacteria and antimicrobial resistance markers as needed.
Comparison of the sensitivity and specificity of commercial anti-dengue virus IgG tests to identify persons eligible for dengue vaccination
Authors: Medina Freddy A. , Vila Frances , Adams Laura E. , Cardona Jaime , Carrion Jessica , Lamirande Elaine , Acosta Luz N. , De León-Rodríguez Carlos M. , Beltran Manuela , Grau Demian , Rivera-Amill Vanessa , Balmaseda Angel , Harris Eva , Madewell Zachary J. , Waterman Stephen H. , Paz-Bailey Gabriela , Whitehead Stephen , Muñoz-Jordán Jorge L.
Published: August 2024

The Advisory Committee on Immunization Practices (ACIP) recommended that dengue pre-vaccination screening tests for Dengvaxia administration have at least 98% specificity and 75% sensitivity. This study evaluates the performance of commercial anti-DENV IgG tests to identify tests that could be used for pre-vaccination screening. First, for seven tests, we evaluated sensitivity and specificity in early convalescent dengue virus (DENV) infection, using 44 samples collected 7–30 days after symptom onset and confirmed by RT-PCR. Next, for the five best-performing tests and two additional tests (with and without an external test reader) that became available later, we evaluated performance to detect past dengue infection among a panel of 44 specimens collected in 2018–2019 from healthy 9- to 16-year-old children from Puerto Rico. Finally, a full-scale evaluation was done with the four best-performing tests using 400 specimens from the same population. We used virus focus reduction neutralization test and an in-house DENV IgG ELISA as reference standards. Of seven tests, five showed ≥75% sensitivity in detecting anti-DENV IgG in early convalescent specimens with low cross-reactivity to the Zika virus. For the detection of previous DENV infections, the tests with the highest performance were the Euroimmun NS1 IgG ELISA (sensitivity 84.5%, specificity 97.1%) and CTK Dengue IgG rapid test R0065C with the test reader (sensitivity 76.2% specificity 98.1%). There are IgG tests available that can be used to accurately classify individuals with previous DENV infection as eligible for dengue vaccination to support safe vaccine implementation.

IMPORTANCE

The Advisory Committee on Immunization Practices (ACIP) has set forth recommendations that dengue pre-vaccination screening tests must exhibit at least 98% specificity and 75% sensitivity. Our research rigorously assesses the performance of various commercial tests against these benchmarks using well-characterized specimens from Puerto Rico. The findings from our study are particularly relevant given FDA approval and ACIP recommendation of Sanofi Pasteur’s Dengvaxia vaccine, highlighting the need for accurate pre-vaccination screening tools.
Coxsackievirus group B3 regulates ASS1-mediated metabolic reprogramming and promotes macrophage inflammatory polarization in viral myocarditis
Authors: Liu Qiong , Shang Yinpan , Tao Ziwei , Li Xuan , Shen Lu , Zhang Hanchi , Liu Zhili , Rao Zhirong , Yu Xiaomin , Cao Yanli , Zeng Lingbing , Huang Xiaotian
Published: August 2024

Coxsackievirus group B3 (CVB3) belongs to the genus
Enteroviruses
of the family
Picornaviridae
and is the main pathogen underlying viral myocarditis (VMC). No specific therapeutic is available for this condition. Argininosuccinate synthase 1 (ASS1) is a key enzyme in the urea cycle that converts citrulline and aspartic acid to argininosuccinate. Here, we found that CVB3 and its capsid protein VP2 inhibit the autophagic degradation of ASS1 and that CVB3 consumes citrulline to upregulate ASS1, triggers urea cycle metabolic reprogramming, and then activates macrophages to develop pro-inflammatory polarization, thereby promoting the occurrence and development of VMC. Conversely, citrulline supplementation to prevent depletion can downregulate ASS1, rescue macrophage polarization, and alleviate the pathogenicity of VMC. These findings provide a new perspective on the occurrence and development of VMC, revealing ASS1 as a potential new target for treating this disease.

IMPORTANCE

Viral myocarditis (VMC) is a common and potentially life-threatening myocardial inflammatory disease, most commonly caused by CVB3 infection. So far, the pathogenesis of VMC caused by CVB3 is mainly focused on two aspects: one is the direct myocardial injury caused by a large number of viral replication in the early stage of infection, and the other is the local immune cell infiltration and inflammatory damage of the myocardium in the adaptive immune response stage. There are few studies on the early innate immunity of CVB3 infection in myocardial tissue, but the appearance of macrophages in the early stage of CVB3 infection suggests that they can play a regulatory role as early innate immune response cells in myocardial tissue. Here, we discovered a possible new mechanism of VMC caused by CVB3, revealed new drug targets for anti-CVB3, and discovered the therapeutic potential of citrulline for VMC.
Requirement of the N-terminal region of nonstructural protein 1 in cis for SARS-CoV-2 defective RNA replication
Authors: Terasaki Kaori , Makino Shinji
Published: August 2024

SARS-CoV-2 belongs to the family
Coronaviridae
and carries a single-stranded positive-sense RNA genome. During coronavirus (CoV) replication, defective or defective interfering RNAs that lack a large portion of the genome often emerge. These defective RNAs typically carry the necessary RNA elements that are required for replication and packaging. We identified the minimum requirement of the 5′ proximal region necessary for viral RNA replication by using artificially generated SARS-CoV-2 minigenomes. The minigenomes consist of the 5′-proximal region, an open reading frame (ORF) that encodes a fusion protein consisting of the N-terminal of viral NSP1 and a reporter gene, and the 3′ untranslated region of the SARS-CoV-2 genome. We used a modified SARS-CoV-2 variant to support replication of the minigenomes. A minigenome carrying the 5′ proximal 634 nucleotides replicated, whereas those carrying shorter than 634 nucleotides did not, demonstrating that the entire 265 nt-long 5′ untranslated region and N-terminal portion of the NSP1 coding region are required for the minigenome replication. Minigenome RNAs carrying a specific amino acid substitution or frame shift insertions in the partial NSP1 coding sequence abrogated minigenome replication. Introduction of synonymous mutations in the minigenome RNAs also affected the replication efficiency of the minigenomes. These data suggest that the expression of the N-terminal portion of NSP1 and the primary sequence of the 5′ proximal 634 nucleotides are important for minigenome replication.

IMPORTANCE

SARS-CoV-2, the causative agent of COVID-19, is highly transmissible and continues to have a significant impact on public health and the global economy. While several vaccines mitigate the severe consequences of SARS-CoV-2 infection, mutant viruses with reduced reactivity to current vaccines continue to emerge and circulate. This study aimed to identify the minimal 5′ proximal region of SARS-CoV-2 genomic RNA required for SARS-CoV-2 defective RNA replication and investigate the importance of an ORF encoded in these defective RNAs. Identifying cis-acting replication signals of SARS-CoV-2 genomic RNA is critical for the development of antivirals that target these signals. Additionally, replication-competent defective RNAs can serve as therapeutic reagents to interfere with SARS-CoV-2 replication. Our findings provide valuable insights into the mechanisms of SARS-CoV-2 RNA replication and the development of reagents that suppress SARS-CoV-2 replication.
Liquid-liquid phase separation is essential for reovirus viroplasm formation and immune evasion
Authors: He Libo , Wang Qian , Wang Xuyang , Zhou Fang , Yang Cheng , Li Yongming , Liao Lanjie , Zhu Zuoyan , Ke Fei , Wang Yaping
Published: August 2024

Grass carp reovirus (GCRV) is the most virulent pathogen in the genus
Aquareovirus
, belonging to the family
Spinareoviridae
. Members of the
Spinareoviridae
family are known to replicate and assemble in cytoplasmic inclusion bodies termed viroplasms; however, the detailed mechanism underlying GCRV viroplasm formation and its specific roles in virus infection remains largely unknown. Here, we demonstrate that GCRV viroplasms form through liquid-liquid phase separation (LLPS) of the nonstructural protein NS80 and elucidate the specific role of LLPS during reovirus infection and immune evasion. We observe that viroplasms coalesce within the cytoplasm of GCRV-infected cells. Immunofluorescence and transmission electron microscopy indicate that GCRV viroplasms are membraneless structures. Live-cell imaging and fluorescence recovery after photobleaching assay reveal that GCRV viroplasms exhibit liquid-like properties and are highly dynamic structures undergoing fusion and fission. Furthermore, by using a reagent to inhibit the LLPS process and constructing an NS80 mutant defective in LLPS, we confirm that the liquid-like properties of viroplasms are essential for recruiting viral dsRNA, viral RdRp, and viral proteins to participate in viral genome replication and virion assembly, as well as for sequestering host antiviral factors for immune evasion. Collectively, our findings provide detailed insights into reovirus viroplasm formation and reveal the specific functions of LLPS during virus infection and immune evasion, identifying potential targets for the prevention and control of this virus.

IMPORTANCE

Grass carp reovirus (GCRV) poses a significant threat to the aquaculture industry, particularly in China, where grass carp is a vital commercial fish species. However, detailed information regarding how GCRV viroplasms form and their specific roles in GCRV infection remains largely unknown. We discovered that GCRV viroplasms exhibit liquid-like properties and are formed through a physico-chemical biological phenomenon known as liquid-liquid phase separation (LLPS), primarily driven by the nonstructural protein NS80. Furthermore, we confirmed that the liquid-like properties of viroplasms are essential for virus replication, assembly, and immune evasion. Our study not only contributes to a deeper understanding of GCRV infection but also sheds light on broader aspects of viroplasm biology. Given that viroplasms are a universal feature of reovirus infection, inhibiting LLPS and then blocking viroplasms formation may serve as a potential pan-reovirus inhibition strategy.
Chlamydia trachomatis
modulates the expression of JAK-STAT signaling components to attenuate the type II interferon response of epithelial cells
Authors: Fontanilla Francis L. , Ibana Joyce A. , Carabeo Rey A. , Brinkworth Amanda J.
Published: August 2024

Chlamydia trachomatis
has adapted to subvert signaling in epithelial cells to ensure successful intracellular development. Interferon-γ (IFNγ) produced by recruited lymphocytes signals through the JAK/STAT pathway to restrict chlamydial growth in the genital tract. However, during
Chlamydia
infection
in vitro
, addition of IFNγ does not fully induce nuclear localization of its transcription factor STAT1 and expression of its target gene, IDO1. We hypothesize that this altered interferon response is a result of
Chlamydia
targeting components of the IFNγ-JAK/STAT pathway. To assess the ability of replicating
Chlamydia
to dampen interferon signaling, HEp2 human epithelial cells were infected with
C. trachomatis
serovar L2 for 24 hours prior to exposure to physiologically relevant levels of IFNγ (500 pg/mL). This novel approach enabled us to observe reduced phospho-activation of both STAT1 and its kinase Janus Kinase 2 (JAK2) in infected cells compared with mock-infected cells. Importantly, basal JAK2 and STAT1 transcript and protein levels were dampened by infection even in the absence of interferon, which could have implications for cytokine signaling beyond IFNγ. Additionally, target genes IRF1, GBP1, APOL3, IDO1, and SOCS1 were not fully induced in response to IFNγ exposure. Infection-dependent decreases in transcript, protein, and phosphoprotein were rescued when
de novo
bacterial protein synthesis was inhibited with chloramphenicol, restoring expression of IFNγ-target genes. Similar
Chlamydia
-dependent dampening of STAT1 and JAK2 transcript levels was observed in infected HeLa and END1 endocervical cells and in HEp2s infected with
C. trachomatis
serovar D, suggesting a conserved mechanism of dampening the interferon response by reducing the availability of key signaling components.

IMPORTANCE

As an obligate intracellular pathogen that has evolved to infect the genital epithelium,
Chlamydia
has developed strategies to prevent detection and antimicrobial signaling in its host to ensure its survival and spread. A major player in clearing
Chlamydia
infections is the inflammatory cytokine interferon-γ (IFNγ), which is produced by immune cells that are recruited to the site of infection. Reports of IFNγ levels in endocervical specimens from
Chlamydia
-infected patients range from 1 to 350 pg/mL, while most
in vitro
studies of the effects of IFNγ on chlamydial growth have used 15–85-fold higher concentrations. By using physiologically relevant concentrations of IFNγ, we were able to assess
Chlamydia
’s ability to modulate its signaling. We found that
Chlamydia
decreases the expression of multiple components that are required for inducing gene expression by IFNγ, providing a possible mechanism by which
Chlamydia trachomatis
can attenuate the immune response in the female genital tract to cause long-term infections.
Draft genome of
Thermoanaerobacter thermohydrosulfuricus
strain AK152, a novel thermophilic and anaerobic bacterium isolated from a hot spring in Iceland
Authors: Abraham Clay A. , Bradley Kevin M. , Scully Sean Michael , Orlygsson Johann , Dube Derek , Benner Steven A.
Published: August 2024

We present the draft genome of the bacterium
Thermoanaerobacter thermohydrosulfuricus
strain AK152, a thermophilic, endospore–spore-forming, anaerobe isolated from a hot spring in Grensdalur, in Southwestern Iceland. This assembled genome will lay the foundation for identifying the carboxylic and amino acid fermentation pathways, suggesting biotechnological applications for this strain.
Late Cretaceous – Early Tertiary Deformation, North Greenland
Authors: soper N.J. , Higgins A.K.
Published: August 2024

Northern Greenland underwent within-plate deformations in Tertiary time in response to a rather complex and incompletely understood displacement history associated with the opening of Labrador Sea – Baffin Bay, the Arctic Ocean basins, and the North Atlantic. Because post-Ellesmerian cover sequences are not widely preserved in the region, it is frequently difficult to differentiate these “Eurekan” structures from earlier deformations, or to establish their precise age. Nonetheless, three sets of structures and two geotectonically important magmatic events of Cretaceous-Paleogene age have been recognized Fig. 16.1. Since these have been subject to speculative and often conflicting geotectonic interpretations, in this account we concentrate on the available factual information, following the review by Soper et al. (1982) and references therein, plus new information derived from 1984 fieldwork. We allude briefly to geotectonic implications, referring the reader to the Nares Strait symposium volume (Dawes and Kerr, 1982) for fuller discussion.

A dense swarm of approximately north-south trending (coast-normal) dolerite dykes occurs along the north coast of Greenland between about 38°W and 48°W (Nansen Land, westernmost Johannes V. Jensen Land and the intervening islands). Scattered examples are also present throughout Johannes V. Jensen Land. The swarm is most dense at sea level, approaching 50 per cent of the rock in places, with individual dykes up to 25 m in width and occasionally much larger. Dyke density diminishes both upward and to the south, the swarm being confined to the region north of the Harder Fjord fault zone (see below). The dykes cut lower Paleozoic
Supplemental Material: Ultrahigh-pressure to high-pressure eclogite in Cuban ophiolitic mélange reveals proto-Caribbean spreading ridge subduction
Authors: Rui Hui-Chao , Yang Jing-Sui , al. et
Published: August 2024

Analytical data (Tables S1–S11).
Natural Products on Inflammatory Bowel Disease: Role of Gut Microbes
Authors: Cheng Wen-Wen , Liu Bao-Hong , Hou Xiao-Ting , Meng Huan , Wang Dan , Zhang Cheng-Hao , Yuan Shuo , Zhang Qing-Gao
Published: August 2024

Inflammatory bowel disease (IBD) refers to long-term medical conditions that involve inflammation of the digestive tract, and the global incidence and prevalence of IBD are on the rise. Gut microbes play an important role in maintaining the intestinal health of the host, and the occurrence, development, and therapeutic effects of IBD are closely related to the structural and functional changes of gut microbes. Published studies have shown that the natural products from traditional Chinese medicine have direct or indirect regulatory impacts on the composition and metabolism of the gut microbes. In this review, we summarize the research progress of several groups of natural products, i.e., flavonoids, alkaloids, saponins, polysaccharides, polyphenols, and terpenoids, for the therapeutic activities in relieving IBD symptoms. The role of gut microbes and their intestinal metabolites in managing the IBD is presented, with focusing on the mechanism of action of those natural products. Traditional Chinese medicine alleviated IBD symptoms by regulating gut microbes, providing important theoretical and practical basis for the treatment of variable inflammatory intestinal diseases.
Ginsenoside Rg2 Attenuates Aging-Induced Liver Injury via Inhibiting Caspase 8-Mediated Pyroptosis, Apoptosis and Modulating Gut Microbiota
Authors: Gao Xu-Fei , Ji Bao-Yu , Zhang Jun-Jie , Wang Zi , Jiang Shuang , Hu Jun-Nan , Gong Xiao-Jie , Zhang Jing-Tian , Tsopmejio Ivan Stève Nguepi , Li Wei
Published: August 2024

Aging is an irresistible natural law of the progressive decline of body molecules, organs, and overall function with the passage of time, resulting in eventual death. World Health Organization data show that aging is correlated with a wide range of common chronic diseases in the elderly, and is an essential driver of many diseases. Panax Ginseng C.A Meyer is an ancient herbal medicine, which has an effect of “long service, light weight, and longevity” recorded in the ancient Chinese medicine book “Compendium of Materia Medica.” Ginsenoside Rg2, the main active ingredient of ginseng, also exerts a marked effect on the treatment of liver injury. However, it remains unclear whether Rg2 has the potential to ameliorate aging-induced liver injury. Hence, exploring the hepatoprotective properties of Rg2 and its possible molecular mechanism by Senescence Accelerate Mouse Prone 8 (SAMP8) and gut microbiota. Our study demonstrated that Rg2 can inhibit pyroptosis and apoptosis through caspase 8, and regulate the gut-liver axis to alleviate liver inflammation by changing the composition of gut microbiota, thus improving aging-induced liver injury. These findings provide theoretical support for the pharmacological effects of ginsenosides in delaying aging-induced liver injury.
Investigating the invariant solutions of (1+1)-dimensional Sawada–Kotera model using Lie symmetries analysis
Authors: Nadeem Muhammad , Jabeen Shamoona , Arqub Omar Abu
Published: August 2024

Here attention is focused on the (1+1)-dimensional Sawada–Kotera (SK) model that is prominent in mathematical physics and engineering to analyze plasmas and coherent systems for communication. Our techniques offer fresh perspectives on the model’s attributes and structure, deepening our comprehension of the underlying dynamics. First, the SK model is reduced to ordinary differential equations by constructing the Lie symmetries and using the associated transformation. Graphs are used to build and display invariant solutions. This strategy has caused the revelation of novel constant solutions that have not been found in the previous works. We offer new understandings of nature and changes observed during the SK derivation by taking advantage of the Lie symmetries powerful tools. Next, the fluctuating layout of proposed framework is examined from several perspectives such as sensitivity and bifurcation analysis. We examined the bifurcation analysis of planar dynamical system by using bifurcation theory. We also include an external periodic perturbation term that breaks regular patterns in the perturbed dynamical system. Graphical structures are provided to display the invariant solutions. The sensitivity of the SK model is determined to be strong after sensitivity analysis under different initial conditions. These results are fascinating, fresh, and conceptually useful for understanding the suggested framework. In mathematics and the applied sciences, forecasting and learning about new technologies are greatly aided by the dynamic aspect of system processing.
A Modified Stress-Strength Reliability Function for Discrete Family of Distributions
Authors: Bhattacharya Rahul , Bhattacharjee Mayukh
Published: August 2024

A modified definition of the stress-strength reliability function is proposed for discrete family of distributions. The newly introduced definition is utilized to derive expressions of the reliability function as well as its Uniformly Minimum Variance Unbiased Estimator (UMVUE) and unbiased estimator of the variance of the UMVUE for different members of the discrete Power Series family of Distributions (PSD). The performance of the UMVUE is compared with the corresponding Maximum Likelihood (ML) estimator in terms of relevant measures. The modified definition is further applied in the context of engineering data and real-world football data to demonstrate its usefulness.
Random self-similar series over a rotation
Authors: Brémont Julien
Published: August 2024

We study the law of random self-similar series defined above an irrational rotation on the Circle. This provides a natural class of continuous singular non-Rajchman measures.
Commuting graph of non-abelian groups of order p4 with center having p elements
Authors: Malviy Siddharth , Kakkar Vipul
Published: August 2024

Let [Formula: see text] be a non-abelian group and [Formula: see text] We define the commuting graph [Formula: see text] with vertex set [Formula: see text] and two distinct vertices [Formula: see text] and [Formula: see text] of [Formula: see text] are connected by an edge when they commute in [Formula: see text]. In this article, certain distance and detour distance properties of commuting graph of non-abelian groups of order [Formula: see text] with center having [Formula: see text] elements, where [Formula: see text] is an odd prime have been studied. Metric dimensions, resolving polynomials and spectral properties of such graphs have also been effectively computed.
A new coding algorithm using Fibonacci numbers, linear mappings, and change of basis
Authors: İrge Vedat , Soykan Yüksel
Published: August 2024

In this paper, we present a new encryption and decryption algorithm that includes Fibonacci numbers, linear mappings, and change of basis.
ℓ-LCP of 𝔽q-linear codes over 𝔽qm
Authors: Hossain Md Ajaharul , Bandi Ramakrishna
Published: August 2024

In this paper, we present an isomorphism that connects a code of length [Formula: see text] over [Formula: see text] to a code of length [Formula: see text] over [Formula: see text]. We define criteria for identifying linear complementary pair (LCP) and linear complementary dual (LCD) codes by utilizing this isomorphism. We also introduce the notion of [Formula: see text]-LCP of codes into the LCP framework and give a necessary and sufficient condition for their characterization. We also provide a necessary and sufficient condition for the existence of an maximum distance separable (MDS) [Formula: see text]-LCP of codes. These insights into the structural properties of codes offer promising avenues for their application in various fields, particularly in the realm of finite fields.
Biodegradation as More-than-Human Unmaking
Authors: Bell Fiona , Campo Woytuk Nadia , Søndergaard Marie Louise Juul , Alistar Mirela
Published: August 2024

In this work, we introduce biodegradation as a process of more-than-human unmaking. We begin by positioning biodegradation amongst related works in design research before presenting a circular process of making and unmaking biomaterials and living organisms through biodegradation. To exemplify this process, we detail two existing works—ReClaym and Biomenstrual—that exemplify how biodegradability can be explored in design through different biomaterials, methods, and contexts. By diffractively reading these projects through one another, we identify six themes and corresponding suggestions for researchers engaging with biodegradation. Lastly, we discuss the broader design implications and limitations, as well as the more-than-human values that emerge from designing for biodegradation via biomaterials. Through this, we aim to provide design researchers with practical tools and insights for engaging with biodegradation to unmake anthropocentric hierarchies between humans, non-humans, and biomaterials, which in turn can promote environmental sustainability and support more-than-human collaboration and care.
A Partial Offline Payment System for Connecting the Unconnected Using Internet of Things: A Survey
Authors: S Sravan S , Mandal Susmita , Alphonse PJA , Ramesh P L
Published: August 2024

The digital revolution in finance has bypassed many in rural areas due to limited access to technology and infrastructure. While real-time Internet banking is not feasible, a new approach is needed to create a secure, low-cost banking ecosystem for these unconnected populations. Existing offline payment mechanisms, prevalent in countries like India, offer some solutions but may still be expensive for rural communities. Researchers are exploring cost-effective solutions based on the Internet of Things (IoT). This study explores various IoT and non-IoT-based offline digital banking solutions to identify potential ways to provide digital payment options for the unconnected rural population.
Creating High-quality 3D Content by Bridging the Gap Between Text-to-2D and Text-to-3D Generation
Authors: Ma Yiwei , Fan Yijun , Ji Jiayi , Wang Haowei , Yin Haibing , Sun Xiaoshuai , Ji Rongrong
Published: August 2024

In recent times, automatic text-to-3D content creation has made significant progress, driven by the development of pretrained 2D diffusion models. Existing text-to-3D methods typically optimize the 3D representation to ensure that the rendered image aligns well with the given text, as evaluated by the pretrained 2D diffusion model. Nevertheless, a substantial domain gap exists between 2D images and 3D assets, primarily attributed to variations in camera-related attributes and the exclusive presence of foreground objects. Consequently, employing 2D diffusion models directly for optimizing 3D representations may lead to suboptimal outcomes. To address this issue, we present X-Dreamer, a novel approach for high-quality text-to-3D content creation that effectively bridges the gap between text-to-2D and text-to-3D synthesis. The key components of X-Dreamer are two innovative designs: Camera-Guided Low-Rank Adaptation (CG-LoRA) and Attention-Mask Alignment (AMA) Loss. CG-LoRA dynamically incorporates camera information into the pretrained diffusion models by employing camera-dependent generation for trainable parameters. This integration makes the 2D diffusion model camera-sensitive. AMA loss guides the attention map of the pretrained diffusion model using the binary mask of the 3D object, prioritizing the creation of the foreground object. This module ensures that the model focuses on generating accurate and detailed foreground objects. Extensive evaluations demonstrate the effectiveness of our proposed method compared to existing text-to-3D approaches. Our project webpage:
https://anonymous-11111.github.io/
. Our code is available at
https://github.com/xmu-xiaoma666/X-Dreamer
.
Book to the Future!
Authors: Sturdee Miriam
Published: August 2024

Lou Rosenfeld, Founder of UX Book Publisher and Conference Producer Rosenfeld Media, is Doing His Best to Be Thoughtful about AI (But He's Still Worried Nonetheless)
PEPT: Expert Finding Meets Personalized Pre-Training
Authors: Peng Qiyao , Xu Hongyan , Wang Yinghui , Liu Hongtao , Huo Cuiying , Wang Wenjun
Published: August 2024

Finding experts is essential in Community Question Answering (CQA) platforms as it enables the effective routing of questions to potential users who can provide relevant answers. The key is to personalized learning expert representations based on their historical answered questions, and accurately matching them with target questions. Recently, the applications of Pre-Trained Language Models (PLMs) have gained significant attraction due to their impressive capability to comprehend textual data, and are widespread used across various domains. There have been some preliminary works exploring the usability of PLMs in expert finding, such as pre-training expert or question representations. However, these models usually learn pure text representations of experts from histories, disregarding personalized and fine-grained expert modeling. For alleviating this, we present a personalized pre-training and fine-tuning paradigm, which could effectively learn expert interest and expertise simultaneously. Specifically, in our pre-training framework, we integrate historical answered questions of one expert with one target question, and regard it as a candidate-aware expert-level input unit. Then, we fuse expert IDs into the pre-training for guiding the model to model personalized expert representations, which can help capture the unique characteristics and expertise of each individual expert. Additionally, in our pre-training task, we design (1) a question-level masked language model task to learn the relatedness between histories, enabling the modeling of question-level expert interest; (2) a vote-oriented task to capture question-level expert expertise by predicting the vote score the expert would receive. Through our pre-training framework and tasks, our approach could holistically learn expert representations including interests and expertise. Our method has been extensively evaluated on six real-world CQA datasets, and the experimental results consistently demonstrate the superiority of our approach over competitive baseline methods.
Feature-Enhanced Neural Collaborative Reasoning for Explainable Recommendation
Authors: Zhang Xiaoyu , Shi Shaoyun , Li Yishan , Ma Weizhi , Sun Peijie , Zhang Min
Published: August 2024

Providing reasonable explanations for a specific suggestion given by the recommender can help users trust the system more. As logic rule-based inference is concise, transparent, and aligned with human cognition, it can be adopted to improve the interpretability of recommendation models. Previous work that interprets user preference with logic rules merely focuses on the construction of rules while neglecting the usage of feature embeddings. This limits the model in capturing implicit relationships between features. In this article, we aim to improve both the effectiveness and explainability of recommendation models by simultaneously representing logic rules and feature embeddings. We propose a novel model-intrinsic explainable recommendation method named
Feature-Enhanced Neural Collaborative Reasoning (FENCR)
. The model automatically extracts representative logic rules from massive possibilities in a data-driven way. In addition, we utilize feature interaction-based neural modules to represent logic operators on embeddings. Experiments on two large public datasets show our model outperforms state-of-the-art neural logical recommendation models. Further case analyses demonstrate that
FENCR
can derive reasonable rules, indicating its high robustness and expandability.

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