bluuebunny/crossref_metadata_2025 huggingface dataset:
PGAM5 degrades PDCoV N protein and activates type I interferon to antagonize viral replication
Authors: Yang Xinyu , Kong Ning , Qin Wenzhen , Zhai Xueying , Song Yiyi , Tong Wu , Li Liwei , Liu Changlong , Zheng Hao , Yu Hai , Zhang Wen , Tong Guangzhi , Shan Tongling
Published: October 2023

In recent years, porcine deltacoronavirus (PDCoV) has become a new intestinal coronavirus in pigs, rapidly spreading across multiple countries and causing significant financial losses in the global pig industry. Currently, no effective commercial vaccine is available to prevent this virus’ spread. Thus, it becomes crucial to investigate the interaction between the virus and its host to acquire valuable insights into the underlying mechanisms of viral replication and develop innovative strategies for preventing and controlling PDCoV. This study specifically focuses on exploring the regulatory effects of PGAM5, a mitochondrial protein, during viral proliferation. Our findings suggest that PDCoV infection hinders the expression of PGAM5 in LLC-PK1 cells. Additionally, it was also found that PGAM5 facilitates the degradation of the PDCoV N protein via the interaction with it, thereby inhibiting viral proliferation. Notably, the degradation of the PDCoV N protein by PGAM5 is mediated through its interaction with the cargo receptor P62 and the E3 ubiquitination ligase STUB1 during the protein degradation process. Furthermore, our results demonstrate that PGAM5 enhances the phosphorylation of IRF7, resulting in increased expression of type I interferon through its interaction with MyD88 and TRAF3, ultimately inhibiting PDCoV replication. Collectively, these findings elucidate the antiviral mechanism of PGAM5, which involves the degradation of the PDCoV N protein and activation of type I interferon to counteract viral replication. The obtained results emphasize the potential of PGAM5 as the novel target for preventing and treating PDCoV.

IMPORTANCE

As a member of the δ-coronavirus family, porcine deltacoronavirus (PDCoV) is a vital reason for diarrhea in piglets, which can contribute to high morbidity and mortality rates. Initially identified in Hong Kong in 2012, the virus has rapidly spread worldwide. During PDCoV infection, the virus employs evasion mechanisms to evade host surveillance, while the host mounts corresponding responses to impede viral replication. Our research has revealed that PDCoV infection down-regulates the expression of PGAM5 to promote virus replication. In contrast, PGAM5 degrades PDCoV N through autophagy by interacting with the cargo receptor P62 and the E3 ubiquitination ligase STUB1. Additionally, PGAM5 interacts with MyD88 and TRAF3 to activate the IFN signal pathway, resulting in the inhibition of viral replication.
Regulation of the WNT-CTNNB1 signaling pathway by severe fever with thrombocytopenia syndrome virus in a cap-snatching manner
Authors: Jiang Xia-Ming , Xin Qi-Lin , Liu Kai , Peng Xue-Fang , Han Shuo , Zhang Ling-Yu , Liu Wei , Xiao Geng-Fu , Li Hao , Zhang Lei-Ke
Published: October 2023

The segmented negative-strand RNA viruses (sNSVs) include highly pathogenic human and animal viruses such as Lassa virus (LASV), severe fever with thrombocytopenia syndrome virus (SFTSV), and influenza A virus (IAV). One of the conserved mechanisms at the stage of genome transcription of sNSVs is the cap-snatching process, providing druggable targets for the development of antivirals. SFTSV is an emerging tick-borne sNSV that causes severe hemorrhagic fever with a high fatality rate of 12%–50%. Here, we determined the correlation between death outcome and downregulation of the WNT-CTNNB1 signaling pathway through transcriptomic analysis of blood samples collected from SFTS patients. We further demonstrated that SFTSV affected this pathway by downregulating the mRNA levels of a series of pathway-related genes, including
CTNNB1
. Loss-of-function mutations or inhibitors targeting SFTSV cap-snatching activity effectively alleviated the inhibition of the WNT-CTNNB1 signaling pathway. Exogenous activation of the WNT-CTNNB1 signaling pathway enhanced SFTSV replication, while inhibition of this pathway reduced SFTSV replication. Treatment with a WNT-CTNNB1 signaling pathway inhibitor attenuated viral replication and decreased fatality in mice. Notably, downregulation of the WNT-CTNNB1 signaling pathway was also observed for other sNSVs, including LASV and IAV. These results suggested that RNAs related to the WNT-CTNNB1 signaling pathway might be utilized as a primer “pool” in a cap-snatching manner for viral transcription, which provides effective targets for the development of broad-spectrum antivirals against sNSVs.

IMPORTANCE

One of the conserved mechanisms at the stage of genome transcription of segmented negative-strand RNA viruses (sNSVs) is the cap-snatching process, which is vital for sNSVs transcription and provides drugable targets for the development of antivirals. However, the specificity of RNAs snatched by sNSV is still unclear. By transcriptomics analysis of whole blood samples from SFTS patients, we found WNT-CTNNB1 signaling pathway was regulated according to the course of the disease. We then demonstrated that L protein of severe fever with thrombocytopenia syndrome virus (SFTSV) could interact with mRNAs of WNT-CTNNB1 signaling pathway-related gene, thus affecting WNT-CTNNB1 signaling pathway through its cap-snatching activity. Activation of WNT-CTNNB1 signaling pathway enhanced SFTSV replication, while inhibition of this pathway decreased SFTSV replication
in vitro
and
in vivo
. These findings suggest that WNT-associated genes may be the substrate for SFTSV “cap-snatching”, and indicate a conserved sNSVs replication mechanism involving WNT-CTNNB1 signaling.
A novel RofA-family transcriptional regulator, GadR, controls the development of acid resistance in
Listeria monocytogenes
Authors: Wu Jialun , McAuliffe Olivia , O'Byrne Conor P.
Published: October 2023

Stomach acid provides a significant innate barrier to the entry of the food-borne pathogen
Listeria monocytogenes
into the human gastrointestinal tract. A key determinant of acid resistance in this bacterium is the conserved glutamate decarboxylase system, GadD2 (encoded by the
gadT2D2
operon), which helps to maintain the intracellular pH during exposure to gastric acid. In this study, we identified a premature stop codon in a gene located immediately downstream of the
gadT2D2
operon that was highly linked to an acid-sensitive phenotype. When this open reading frame was restored through homologous recombination, an acid-resistant phenotype was restored. Through a series of genetic, transcriptomic, and survival experiments, we established that this gene, which we designated
gadR
, encodes a transcriptional regulator of the
gadT2D2
operon. GadR belongs to the RofA family of regulators, primarily found in streptococci, where they are involved in regulating virulence. The data further showed that
gadR
plays a critical role in the development of acid resistance in response to mild acid exposure, a response that is known as the adaptive acid tolerance response (ATR). A deletion analysis of the
gadT2D2
promoter region identified two 18-bp palindromic sequences that are required for the GadR-mediated induction of
gadT2D2
, suggesting that they act as binding sites for GadR. Overall, this study uncovers a new RofA-like regulator of acid resistance in
L. monocytogenes
, which plays a significant role in both growth phase-dependent acid resistance and ATR and accounts for previously observed strain-to-strain differences in survival at low pH.

IMPORTANCE

The ability to survive the acidic conditions found in the stomach is crucial for the food-borne pathogen
Listeria monocytogenes
to gain access to the mammalian gastrointestinal tract. Little is currently known about how acid resistance is regulated in this pathogen and why this trait is highly variable between strains. Here, we used comparative genomics to identify a novel RofA-family transcriptional regulator, GadR, that controls the development of acid resistance. The RofA family of regulators was previously found only in a small group of bacterial pathogens, including streptococci, where they regulate virulence properties. We show that
gadR
encodes the dominant regulator of acid resistance in
L. monocytogenes
and that its sequence variability accounts for previously observed differences between strains in this trait. Together, these findings significantly advance our understanding of how this important pathogen copes with acid stress and suggest a potential molecular target to aid its control in the food chain.
Ubiquitination of Sec22b by a novel
Legionella pneumophila
ubiquitin E3 ligase
Authors: Ma Kelong , Shu Rundong , Liu Hongtao , Fu Jiaqi , Luo Zhao-Qing , Qiu Jiazhang
Published: October 2023

Legionella pneumophila
is a facultative intracellular pathogen that causes legionellosis. The key to its virulence is the delivery of hundreds of effector proteins into host cells via the
d
efective in
o
rganelle
t
rafficking/
i
ntra
c
ellular
m
ultiplication type IV secretion system. These effectors modulate numerous host signaling pathways to create a niche called the

L
egionella

-
c
ontaining
v
acuole (LCV) permissive for its intracellular replication. Previous investigation revealed that exploitation of the host ubiquitin system is among the most important strategies used by
L. pneumophila
to coopt host processes for its benefit. Here, we show that the effector
Legionella
ubiquitin ligase gene 15 (Lug15) (Lpg2327), which has no detectable homology with any enzyme involved in ubiquitin signaling, is an E3 ligase. In
L. pneumophila
-infected cells, Lug15 is localized on the LCV and impacts its association with polyubiquitinated proteins. We also demonstrate that Sec22b is ubiquitinated and recruited to the LCV by Lug15. Thus, our results establish Lug15 as a novel E3 ligase that functions to recruit a SNARE protein to remodel the
L. pneumophila
phagosome.

IMPORTANCE

Protein ubiquitination is one of the most important post-translational modifications that plays critical roles in the regulation of a wide range of eukaryotic signaling pathways. Many successful intracellular bacterial pathogens can hijack host ubiquitination machinery through the action of effector proteins that are injected into host cells by secretion systems.
Legionella pneumophila
is the etiological agent of legionellosis that is able to survive and replicate in various host cells. The
d
efective in
o
rganelle
t
rafficking (Dot)/
i
ntra
c
ellular
m
ultiplication (Icm) type IV secretion system of
L. pneumophila
injects over 330 effectors into infected cells to create an optimal environment permissive for its intracellular proliferation. To date, at least 26 Dot/Icm substrates have been shown to manipulate ubiquitin signaling via diverse mechanisms. Among these, 14 are E3 ligases that either cooperate with host E1 and E2 enzymes or adopt E1/E2-independent catalytic mechanisms. In the present study, we demonstrate that the
L. pneumophila
effector
Legionella
ubiquitin ligase gene 15 (Lug15) is a novel ubiquitin E3 ligase. Lug15 is involved in the remodeling of LCV with polyubiquitinated species. Moreover, Lug15 catalyzes the ubiquitination of host SNARE protein Sec22b and mediates its recruitment to the LCV. Ubiquitination of Sec22b by Lug15 promotes its noncanonical pairing with plasma membrane-derived syntaxins (e.g., Stx3). Our study further reveals the complexity of strategies utilized by
L. pneumophila
to interfere with host functions by hijacking host ubiquitin signaling.
An isothermal CRISPR-based diagnostic assay for
Neisseria gonorrhoeae
and
Chlamydia trachomatis
detection
Authors: Luo Hao , Zeng Lihong , Yin Xiaona , Pan Yuying , Yang Jianjiang , Liu Mingjing , Qin Xiaolin , Feng Zhanqin , Chen Wentao , Zheng Heping
Published: October 2023

The occurrence of
Chlamydia trachomatis
(CT) and
Neisseria gonorrhoeae
(NG) is increasing worldwide, particularly in low- and middle-income countries. In cases where most infections are asymptomatic and remain in a coinfection condition. It may cause missed detections or the severe subsequent symptoms. Accurate diagnosis and convenient screening are essential for disease control. However, molecular diagnostics for CT/NG predominantly rely on polymerase chain reaction (PCR)-based detection, which requires special devices and conditions. Here, we developed an isothermal CRISPR-based CT/NG dual-target detection system by pairing recombinase polymerase amplification (RPA) and CRISPR-Cas12a/13a detection. Multiplex RPA can amplify NG and CT simultaneously, and a single-pot reaction with the Cas12a/13a can be performed for further recognizing the amplified target, driving the cleavage of the corresponding fluorescence reporter separately; thus, the signal can be monitored in different channels. This CRISPR-based CT/NG detection system achieved analytical sensitivities of 10° copies/μL for both synthetic CT/NG dsDNA and exhibited no cross-reaction with other species. In tests on 88 clinical samples, our CRISPR-based assay showed excellent agreement with the commercial assay Roche Cobas 4800 (100% accuracy for NG, 94.32% accuracy for CT, and 97.73% accuracy for CT/NG coinfection) and showed higher positive percent agreement, negative percent agreement, and accuracy than those reported for TaqMan PCR in a previous study. In addition, the results of this CRISPR-based system could be acquired within 75 min. Our isothermal diagnostic method with promising performance provides more convenience than PCR-based methods for detection and screening.

IMPORTANCE

A method for
Neisseria gonorrhoeae
(NG)/
Chlamydia trachomatis
(CT) detection is developed using multiplex-recombinase polymerase amplification and Cas12a/Cas13a. This method can detect NG and CT simultaneously with high sensitivity and specificity. This method has great potential to be further developed into larger-scale screening and point-of-care testing (POCT).
Identification and production of novel potential pathogen-specific biomarkers for diagnosis of histoplasmosis
Authors: Puerta-Arias Juan David , Isaza Agudelo Juan Pablo , Naranjo Preciado Tonny Williams
Published: October 2023

Immunological assays based on the detection of circulating fungal biomarkers are helpful in clinical practice for diagnosing invasive fungal infections. Some of these targeting antigenic components are common to several different fungi. Histoplasmosis is a mycosis caused by the dimorphic fungus
Histoplasma capsulatum
, which in recent years has gained significant relevance due to the increase in the population susceptible to developing severe clinical forms, including those living with HIV/AIDS. Immunological tests that detect cell wall polysaccharide antigens are among the most used laboratory techniques for diagnosing this mycosis. However, none have shown adequate performance, and cross-reactivity with other fungal pathogens may be observed. Considering that there is a real need to improve the sensitivity and specificity of current diagnostic methods, we explored a novel strategy for the identification of
H. capsulatum-
specific antigens (
Hc_Ags
) that could be detected in clinical samples during infection based on a computational analysis model that included the application of bioinformatics tools and the analysis of experimental data from transcriptomics and proteomics. The
Hc_Ags
identified were expressed and purified by eukaryotic and prokaryotic systems. First, the
Hc_Ags
were used in an in-house immunization model in mice (BALB/c) to obtain
Hc_Ag
-specific polyclonal antibodies (
Hc_Ag_PAb
). Then, the presence of these antigens in
H. capsulatum
-yeast culture extracts and the specificity of
Hc_Ag_PAb
against culture extracts of
Candida albicans
,
Aspergillus fumigatus
,
Cryptococcus neoformans
,
Fusarium
spp., and
Paracoccidioides brasiliensis
were confirmed. Finally, we demonstrated the immunoreactivity of these
Hc_Ag
-specific polyclonal antibodies with urine samples from patients previously diagnosed with histoplasmosis.

IMPORTANCE

Histoplasmosis is considered one of the most important mycoses due to the increasing number of individuals susceptible to develop severe clinical forms, particularly those with HIV/AIDS or receiving immunosuppressive biological therapies, the high mortality rates reported when antifungal treatment is not initiated in a timely manner, and the limitations of conventional diagnostic methods. In this context, there is a clear need to improve the capacity of diagnostic tools to specifically detect the fungal pathogen, regardless of the patient’s clinical condition or the presence of other co-infections. The proposed novel pathogen-specific biomarkers have the potential to be used in immunodiagnostic platforms and antifungal treatment monitoring in histoplasmosis. In addition, the bioinformatics strategy used in this study could be applied to identify potential diagnostic biomarkers in other models of fungal infection of public health importance.
Longitudinal analysis of vaginal microbiota during IVF fresh embryo transfer and in early pregnancy
Authors: Väinämö Sofia , Saqib Schahzad , Kalliala Ilkka , Kervinen Kaisa , Luiro Kaisu , Niinimäki Maarit , Halttunen-Nieminen Mervi , Virtanen Seppo , Nieminen Pekka , Salonen Anne , Holster Tiina
Published: October 2023

Non-
Lactobacillus
-dominated vaginal microbiota has been associated with poor gynecologic health and complications during pregnancy. Lactobacilli and especially
Lactobacillus crispatus
associate with good reproductive health and dominate the microbiota during healthy pregnancy. We examined whether the composition of vaginal microbiota at the time of fresh embryo transfer (ET) has an impact on the success of
in vitro
fertilization (IVF) and whether vaginal microbiota changes from IVF-ET to early pregnancy within individuals. Vaginal swab samples were collected from subfertile women at the time of IVF-ET (
n
= 76) and at the eighth gestational week (
n
= 21) from those who achieved clinical pregnancy. The microbiota composition was analyzed using 16S rRNA gene amplicon sequencing.
L. crispatus
was more abundant among the 30 women who achieved clinical pregnancy (46.9% vs. 19.1%,
q
= 0.039) and the 26 women who had live birth (43.3% vs. 23.1%,
q
= 0.32) compared to those who did not. Lactobacilli, mainly
L. crispatus
(76.2%), dominated all early pregnancy samples. Microbiota remained the same, i.e.,
Lactobacillus
-dominated type in 52% (11/21), shifted from one
Lactobacillus-
dominated type to another in 24% (5/21), or shifted from mixed community to
Lactobacillus
-dominated type in 24% (5/21) women, but never from
Lactobacillus
dominance to non-lactobacilli dominance. Our results emphasize the role of
L. crispatus
in the success of IVF-ET and in early pregnancy. During pregnancy, the microbiota shifted toward
L. crispatus
dominance even if it was undetectable before pregnancy, indicating that most women hold a reservoir of this beneficial
Lactobacillus
in their reproductive tract.

IMPORTANCE

Infertility is a global public health issue which leads many couples to seek fertility treatments, of which
in vitro
fertilization (IVF) is considered to be the most effective. Still, only about one-third of the women achieve live birth after the first IVF embryo transfer (IVF-ET). Factors affecting embryo implantation are poorly known, but the female reproductive tract microbiota may play a key role. Our study confirms the beneficial role of vaginal lactobacilli, especially
Lactobacillus crispatus,
in the probability of achieving clinical pregnancy and live birth following IVF-ET. Our findings regarding the intra-individual shift of vaginal microbiota between non-pregnancy and pregnancy states are novel and provide new information about the dynamics of microbiota in the early steps of human reproduction. These findings may help clinicians in their attempts to optimize the conditions for ET by microbiota screening or modulation and timing the ET when the microbiota is the most favorable.
Phylogenomic analysis of the understudied
Neisseriaceae
species reveals a poly- and paraphyletic
Kingella
genus
Authors: Morreale Daniel P. , St Geme III Joseph W. , Planet Paul J.
Published: October 2023

Taxonomic classification and phylogenetic analysis of the
Neisseriaceae
family have focused on the pathogens
Neisseria meningitidis
and
Neisseria gonorrhoeae
. Less is known about the relationships of commensal
Neisseria
species and other
Neisseriaceae
genera, raising the possibility that the phylogeny of this family may not agree with current taxonomy. In this study, we used available nucleotide sequences and a phylogenetic approach to assess the
Kingella
genus and its relatives. We found that this genus is both paraphyletic and polyphyletic.
Kingella potus
is more closely related to
Neisseria bacilliformis
than to other
Kingella
species. The
Alysiella
and
Simonsiella
genera form a distinct clade within the
Kingella
genus that is closely related to the pathogens
K. kingae
and
K. negevensis
. We find a phylogenetic relationship between
Conchiformibius
,
Alysiella
,
Simonsiella
, and
Kingella
, which we name the CASK clade. Finally, we define the gene sets that differentiate each genus of the CASK clade from one another and from the rest of the
Neisseriaceae
family.

IMPORTANCE

Understanding the evolutionary relationships between the species in the
Neisseriaceae
family has been a persistent challenge in bacterial systematics due to high recombination rates in these species. Previous studies of this family have focused on
Neisseria meningitidis
and
N. gonorrhoeae
. However, previously understudied
Neisseriaceae
species are gaining new attention, with
Kingella kingae
now recognized as a common human pathogen and with
Alysiella
and
Simonsiella
being unique in the bacterial world as multicellular organisms. A better understanding of the genomic evolution of the
Neisseriaceae
can lead to the identification of specific genes and traits that underlie the remarkable diversity of this family.
Comparison of phage-derived recombinases for genetic manipulation of
Pseudomonas
species
Authors: Kalb Madison J. , Grenfell Andrew W. , Jain Abhiney , Fenske-Newbart Jane , Gralnick Jeffrey A.
Published: October 2023

Several strains in the
Pseudomonas
genus are categorized as plant growth-promoting rhizobacteria (PGPR). Although several of these strains are strong candidates for applications as biofertilizers or biopesticides, genome editing approaches are generally limited and require further development. Editing genomes in PGPR could enable more robust agricultural applications, persistence, and biosafety measures. In this study, we investigate the use of five phage-encoded recombinases to develop a recombineering workflow in three PGPR strains:
Pseudomonas protegens
Pf-5,
Pseudomonas protegens
CHA0, and
Pseudomonas putida
KT2440. Using point mutations in the
rpoB
gene, we reach maximum recombineering efficiencies of 1.5 × 10
−4
, 3 × 10
−4
, and 5 × 10
−5
, respectively, in these strains using λ-Red Beta recombinase from
Escherichia coli
. We further examine recombineering efficiencies across these strains as a function of selected mutation, editing template concentration, and phosphorothiolate bond protection. This work validates the use of these tools across several environmentally and biotechnologically relevant strains to expand the possibilities of genetic manipulation in the
Pseudomonas
genus.

IMPORTANCE

The
Pseudomonas
genus contains many members currently being investigated for applications in biodegradation, biopesticides, biocontrol, and synthetic biology. Though several strains have been identified with beneficial properties, chromosomal manipulations to further improve these strains for commercial applications have been limited due to the lack of efficient genetic tools that have been tested across this genus. Here, we test the recombineering efficiencies of five phage-derived recombinases across three biotechnologically relevant
Pseudomonas
strains:
P. putida
KT2440,
P. protegens
Pf-5, and
P. protegens
CHA0. These results demonstrate a method to generate targeted mutations quickly and efficiently across these strains, ideally introducing a method that can be implemented across the
Pseudomonas
genus and a strategy that may be applied to develop analogous systems in other nonmodel bacteria.
Virulence factors and antimicrobial resistance profiles of
Campylobacter
isolates recovered from consecutively reused broiler litter
Authors: Woyda Reed , Oladeinde Adelumola , Endale Dinku , Strickland Timothy , Plumblee Lawrence Jodie , Abdo Zaid
Published: October 2023

Campylobacter
infections are a leading cause of bacterial diarrhea in humans globally. Infections are due to consumption of contaminated food products and are highly associated with chicken meat, with chickens being an important reservoir for
Campylobacter
. Here, we characterized the genetic diversity of
Campylobacter jejuni
(
C. jejuni
) and
Campylobacter coli
(
C. coli
) detected in broiler chicken litter over three consecutive flocks and determined their antimicrobial resistance (ARM) and virulence factor (VF) profiles.
Campylobacter
was detected in 9.38% (27/288) of litter samples collected. Antimicrobial susceptibility testing and whole genome sequencing were performed on
C. jejuni
(
n
= 39) and
C. coli
(
n
= 5) isolates.
Campylobacter
virulence factors differed within and across broiler houses but were explained by the broiler flock cohort raised on litter,
Campylobacter
species and
Campylobacter
multilocus sequence type (MLST). Virulence factors involved in the ability to invade and colonize host tissues and evade host defenses were present in
C. jejuni
isolates (ST-464) from flock cohorts 1 and 2 but absent in
C. jejuni
isolates (ST-48) from flock cohort 3.
C. jejuni
isolates from house three harbored a significantly higher proportion of virulence genes with functions related to glycosylation and immune evasion than
C. jejuni
isolates from houses 1 and 2 (
P
< 0.01). All
C. jejuni
isolates were susceptible to all antibiotics tested while
C. coli
(
n
= 4) were resistant to tetracycline and harbored the tetracycline resistant ribosomal protection protein (TetO). Our results suggest that house environment and broiler management practices imposed selective pressures on virulence factors and antimicrobial resistance genes of
Campylobacter
.

IMPORTANCE

Campylobacter
is a leading cause of foodborne illness in the United States due to consumption of contaminated or mishandled food products, often associated with chicken meat.
Campylobacter
is common in the microbiota of avian and mammalian gut; however, acquisition of antimicrobial resistance genes (ARGs) and virulence factors (VFs) may result in strains that pose significant threat to public health. Although there are studies investigating the genetic diversity of
Campylobacter
strains isolated from post-harvest chicken samples, there are limited data on the genome characteristics of isolates recovered from preharvest broiler production. Here, we show that
Campylobacter jejuni
and
Campylobacter coli
differ in their carriage of antimicrobial resistance and virulence factors may also differ in their ability to persist in litter during consecutive grow-out of broiler flocks. We found that presence/absence of virulence factors needed for evasion of host defense mechanisms and gut colonization played an integral role in differentiating
Campylobacter
strains.
A structural foundation for studying chlamydial polymorphic membrane proteins
Authors: Debrine Abigail M. , Karplus P. Andrew , Rockey Daniel D.
Published: October 2023

Polymorphic membrane proteins (Pmps) are chlamydial cell surface proteins with signature repeating FxxN and GGA (I, V, L) tetrapeptide motifs. These autotransporter proteins are key immune targets and mediators of host-microbe interactions but by unknown mechanisms. AlphaFold predictions reveal that Pmp passenger domains have two distinct β-helical parts: a C-terminal globular “Pmp middle region” that forms six β-helical rungs, and an N-terminal highly-regular “Pmp repeat region” that is from 9 to 25 rungs long. In the repeat region, paired FxxN and GGA (I, V, L) motifs – or close variants – are fully buried and packed together to form novel β-helical rungs from which variable-length loops extend out from one face. Similar motifs in proteins from diverse organisms are predicted to form analogous structures. In Pmps, the structures imply that the tetrapeptide motifs are not directly involved in host-cell adhesion, but position protein loops on a common face where they can interact with ligands important for infection. These structural descriptions provide a guide for mutagenesis studies to identify those parts of Pmps involved in infection.

IMPORTANCE

Infections by bacteria in the genus
Chlamydia
cause a range of widespread and potentially debilitating conditions in humans and other animals. We analyzed predicted structures of a family of proteins that are potential vaccine targets found in all
Chlamydia
spp. Our findings deepen the understanding of protein structure, provide a descriptive framework for discussion of the protein structure, and outline regions of the proteins that may be key targets in host-microbe interactions and anti-chlamydial immunity.
Supplemental Material: Precursors to a continental-arc ignimbrite flare-up: Early central volcanoes of the San Juan Mountains, Colorado, USA
Authors: Lipman Peter , al. et
Published: October 2023

Table S1: Summary of 40Ar/39Ar and U-Pb zircon age determinations, pre-ignimbrite volcanoes of the eastern San Juan region. Table S2: New and published X-ray fluorescence (XRF) rock analyses, pre-ignimbrite volcanoes of the San Juan region. Table S3 and figures: Analytical data—new 40Ar/39Ar age determinations. Table S4: Analytical data—new U-Pb zircon age determinations. Table S5: Multimineral age comparisons—single samples and multiple samples from the same locality. Table S6: Groundmass-mineral age comparisons. 
Similarities and Differences in Photochemistry of Type I and Type II Rhodopsins
Authors: Ostrovsky Mikhail A. , Smitienko Olga A. , Bochenkova Anastasia V. , Feldman Tatiana B.
Published: October 2023

The diversity of the retinal-containing proteins (rhodopsins) in nature is extremely large. Fundamental similarity of the structure and photochemical properties unites them into one family. However, there is still a debate about the origin of retinal-containing proteins: divergent or convergent evolution? In this review, based on the results of our own and literature data, a comparative analysis of the similarities and differences in the photoconversion of the rhodopsin of types I and II is carried out. The results of experimental studies of the forward and reverse photoreactions of the bacteriorhodopsin (type I) and visual rhodopsin (type II) rhodopsins in the femto- and picosecond time scale, photo-reversible reaction of the octopus rhodopsin (type II), photovoltaic reactions, as well as quantum chemical calculations of the forward photoreactions of bacteriorhodopsin and visual rhodopsin are presented. The issue of probable convergent evolution of type I and type II rhodopsins is discussed.
The Electronic Structure, Thermoelectric, and Optical Properties of Heusler Alloys Mn2MeAl (Me = Ti, V, Cr)
Authors: Shreder E. I. , Filanovich A. N. , Chernov E. D. , Lukoyanov A. V. , Marchenkov V. V. , Stashkova L. A.
Published: October 2023

The results of calculations of the electronic structure, thermoelectric characteristics, and experimental study of the thermoelectric, electrical, and optical properties of Mn2MeAl Heusler alloys (Me = Ti, V, Cr) are presented. The agreement between theory and experiment in the sign of the Seebeck coefficient is shown. The obtained pattern of the band spectrum allows us to qualitatively explain the peculiarities of the temperature dependences of the electrical resistance and the permittivity dispersion.
Peculiarities of the Behavior of Point Defects under the Optoplastic Effect in Copper
Authors: Malinskii T. V. , Rogalin V. E. , Shur V. Ya. , Kuznetsov D. K.
Published: October 2023

The authors previously discovered a new optoplastic effect and observed it under the action of a nanosecond UV laser pulse irradiation of subcritical intensity. In this paper it is shown that under this effect no micropores arise in the subsurface layer of metal. This proves the statement that swelling of metal under laser impact of moderate (subcritical) intensity occurs due to interstitial atoms migrating to the surface and not due to melting with formation of bubbles. At a abrupt cooling (for ~20 μs) interstitial atoms migrate to the surface by the Schottky mechanism due to abnormal mass transfer and the less mobile vacancies have no time to coagulate with formation of micropores in the time of the process.
Advances in the management of systemic lupus erythematosus
Authors: Morand Eric F , Fernandez-Ruiz Ruth , Blazer Ashira , Niewold Timothy B
Published: October 2023

Systemic lupus erythematosus (SLE) is a severe multisystem autoimmune disease that can cause injury in almost every body system. While considered a classic example of autoimmunity, it is still relatively poorly understood. Treatment with immunosuppressive agents is challenging, as many agents are relatively non-specific, and the underlying disease is characterized by unpredictable flares and remissions. This State of The Art Review provides a comprehensive current summary of systemic lupus erythematosus based on recent literature. In basic and translational science, this summary includes the current state of genetics, epigenetics, differences by ancestry, and updates about the molecular and immunological pathogenesis of systemic lupus erythematosus. In clinical science, the summary includes updates in diagnosis and classification, clinical features and subphenotypes, and current guidelines and strategies for treatment. The paper also provides a comprehensive review of the large number of recent clinical trials in systemic lupus erythematosus. Current knowns and unknowns are presented, and potential directions for the future are suggested. Improved knowledge of immunological pathogenesis and the molecular differences that exist between patients should help to personalize treatment, minimize side effects, and achieve better outcomes in this difficult disease.
Novel prognostic biomarkers in decompensated cirrhosis: a systematic review and meta-analysis
Authors: Juanola Adrià , Ma Ann Thu , de Wit Koos , Gananandan Kohilan , Roux Olivier , Zaccherini Giacomo , Jiménez César , Tonon Marta , Solé Cristina , Villaseca Clara , Uschner Frank E , Graupera Isabel , Pose Elisa , Moreta Maria José , Campion Daniela , Beuers Ulrich , Mookerjee Rajeshawar P , Francoz Claire , Durand Francois , Vargas Victor , Piano Salvatore , Alonso Sonia , Trebicka Jonel , Laleman Wim , Asrani Sumeet K , Soriano German , Alessandria Carlo , Serra-Burriel Miquel , Morales-Ruiz Manuel , Torres Ferran , Allegretti Andrew S , Krag Aleksander , Caraceni Paolo , Watson Hugh , Abraldes Juan G , Solà Elsa , Kamath Patrick S , Hernaez Ruben , Ginès Pere
Published: October 2023

Background

Patients with decompensated cirrhosis experience high mortality rates. Current prognostic scores, including the model for end-stage liver disease (MELD), may underperform in settings other than in those they were initially developed. Novel biomarkers have been proposed to improve prognostication accuracy and even to predict development of complications.

Methods

We performed a systematic review and meta-analysis on novel urine and blood biomarkers and their ability to predict 90-day mortality in patients with decompensated cirrhosis. Secondary outcomes included 28-day and 1-year mortality, and development of acute-on-chronic liver failure, acute kidney injury and other complications. To overcome differences in units, temporal changes in assays and reporting heterogeneity, we used the ratio of means (RoM) as measure of association for assessing strength in predicting outcomes. An RoM>1 implies that the mean biomarker level is higher in those that develop the outcome than in those that do not.

Results

Of 6629 unique references, 103 were included, reporting on 29 different biomarkers, with a total of 31 362 biomarker patients. Most studies were prospective cohorts of hospitalised patients (median Child-Pugh-Turcotte score of 9 and MELD score of 18). The pooled 90-day mortality rate was 0.27 (95% CI 0.24 to 0.29). The RoM for predicting 90-day mortality was highest for interleukin 6 (IL-6) (2.56, 95% CI 2.39 to 2.74), followed by urinary neutrophil gelatinase-associated lipocalin (uNGAL) (2.42, 95% CI 2.20 to 2.66) and copeptin (2.33, 95% CI 2.17 to 2.50). These RoMs were all higher than for MELD (1.44, 95% CI 1.42 to 1.46).

Conclusion

Novel biomarkers, including IL-6, uNGAL and copeptin, can probably improve prognostication of patients with decompensated cirrhosis compared with MELD alone.
Design and performance of the ENUBET monitored neutrino beam
Authors: Acerbi F. , Angelis I. , Bomben L. , Bonesini M. , Bramati F. , Branca A. , Brizzolari C. , Brunetti G. , Calviani M. , Capelli S. , Carturan S. , Catanesi M. G. , Cecchini S. , Charitonidis N. , Cindolo F. , Cogo G. , Collazuol G. , Corso F. Dal , Delogu C. , De Rosa G. , Falcone A. , Goddard B. , Gola A. , Guffanti D. , Halić L. , Iacob F. , Jollet C. , Kain V. , Kallitsopoulou A. , Kliček B. , Kudenko Y. , Lampoudis Ch. , Laveder M. , Legou P. , Longhin A. , Ludovici L. , Lutsenko E. , Magaletti L. , Mandrioli G. , Marangoni S. , Margotti A. , Mascagna V. , Mauri N. , McElwee J. , Meazza L. , Meregaglia A. , Mezzetto M. , Nessi M. , Paoloni A. , Pari M. , Papaevangelou T. , Parozzi E. G. , Pasqualini L. , Paternoster G. , Patrizii L. , Pozzato M. , Prest M. , Pupilli F. , Radicioni E. , Ruggeri A. C. , Saibene G. , Sampsonidis D. , Scian C. , Sirri G. , Stipčević M. , Tenti M. , Terranova F. , Torti M. , Tzamarias S. E. , Vallazza E. , Velotti F. , Votano L.
Published: October 2023

The ENUBET project is aimed at designing and experimentally demonstrating the concept of monitored neutrino beams. These novel beams are enhanced by an instrumented decay tunnel, whose detectors reconstruct large-angle charged leptons produced in the tunnel and give a direct estimate of the neutrino flux at the source. These facilities are thus the ideal tool for high-precision neutrino cross-section measurements at the GeV scale because they offer superior control of beam systematics with respect to existing facilities. In this paper, we present the first end-to-end design of a monitored neutrino beam capable of monitoring lepton production at the single particle level. This goal is achieved by a new focusing system without magnetic horns, a 20 m normal-conducting transfer line for charge and momentum selection, and a 40 m tunnel instrumented with cost-effective particle detectors. Employing such a design, we show that percent precision in cross-section measurements can be achieved at the CERN SPS complex with existing neutrino detectors.
Prosthesis Options for Proximal Interphalangeal Joint Arthroplasty in Osteoarthritis: A Systematic Review and Meta-Analysis
Authors: DARWISH Ibrahim , IMANI Sahand , BABA Mohammed
Published: October 2023

Background: Literature investigating the long-term outcomes of prosthesis options for proximal interphalangeal (PIP) joint arthroplasty is scarce, with most reports combining indications and underlying pathologies in analyses. In this study, we aim to compare silicone, pyrocarbon and metal prostheses in PIP joint arthroplasty for primary degenerative osteoarthritis (OA).

Methods: A review of scientific literature published between 1990 and 2021 was conducted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Relevant studies were screened and the appropriate data was extracted. An evaluation of clinical outcomes (range of motion [ROM] and pain), complications (reoperation) and survival rates for each prosthesis was performed.

Results: Twelve studies were included for analysis with a total of 412 PIP joints. ROM was 66.6°, 55.8° and 46.4° for metal, silicone and pyrocarbon implants, respectively. Silicone implants had the best pain score on the visual analogue scale (1.2) followed by the pyrocarbon (2.6) and metal (3.9) groups. Complication rates were lowest in silicone implants (11.3%) compared to 18.5% in pyrocarbon and 22.4% in metal prostheses. Survival did not differ significantly amongst the three groups.

Conclusions: Our findings suggest that for patients with primary degenerative OA, PIP joint arthroplasty using a silicone prosthesis can provide greater pain relief with lower complication rates compared to other implant options.

Level of Evidence: Level III (Therapeutic)
Explicit State Representation Guided Video-based Pedestrian Attribute Recognition
Authors: Lu Wei-Qing , Hu Hai-Miao , Yu Jinzuo , Zhang Shifeng , Wang Hanzi
Published: October 2023

The pedestrian attribute recognition aims to generate a structured description of pedestrians, which serves an important role in surveillance. Current works usually assume that the images and the specific pedestrian states, including pedestrian occlusion and pedestrian orientation, are given. However, we argue that the current works ignore the guidance of the pedestrian state and cannot achieve the appropriate performance since the appearance feature will become unreliable due to the variance of the pedestrian state, which is common in practice. Therefore, this paper proposes the Explicit State Representation (ExSR) Guided Pedestrian Attribute Recognition to improve the accuracy through state learning and attribute fusion among frames. Firstly, the pedestrian state is explicitly represented by concatenating the pedestrian orientation and occlusion, which can be accurately determined via analyzing the pose. Secondly, the state-aware pedestrian attribute fusion method is proposed and divided into two cases, namely the inter-state case and the intra-state case. In the intra-state case, the appearance feature will remain stable and the attribute relations are propagated to refine. The method of exploiting attribute relations within a single frame is the Graph Neural Network. In the inter-state case, the state changes, the attribute relationship propagation is prevented, and the advantages of attribute recognition in each frame are complemented to make a reliable judgment on the invisible region. The experimental results demonstrate that the ExSR outperforms the state-of-the-art methods on two public databases, benefiting from the explicit introduction of the state into the attribute recognition.
Towards a Causal Decision-Making Framework for Recommender Systems
Authors: Cavenaghi Emanuele , Zanga Alessio , Stella Fabio , Zanker Markus
Published: October 2023

Causality is gaining more and more attention in the machine learning community and consequently also in recommender systems research. The limitations of learning offline from observed data are widely recognized, however, applying debiasing strategies like Inverse Propensity Weighting does not always solve the problem of making wrong estimates. This concept paper contributes a summary of debiasing strategies in recommender systems and the design of several toy examples demonstrating the limits of these commonly applied approaches. Therefore, we propose to map the causality frameworks of potential outcomes and structural causal models onto the recommender systems domain in order to foster future research and development. For instance, applying causal discovery strategies on offline data to learn the causal graph in order to compute counterfactuals or improve debiasing strategies.
A Comprehensive Survey on Automated Machine Learning for Recommendations
Authors: Chen Bo , Zhao Xiangyu , Wang Yejing , Fan Wenqi , Guo Huifeng , Tang Ruiming
Published: October 2023

Deep recommender systems (DRS) are critical for current commercial online service providers, which address the issue of information overload by recommending items that are tailored to the user’s interests and preferences. They have unprecedented feature representations effectiveness and the capacity of modeling the non-linear relationships between users and items. Despite their advancements, DRS models, like other deep learning models, employ sophisticated neural network architectures and other vital components that are typically designed and tuned by human experts. This article will give a comprehensive summary of automated machine learning (AutoML) for developing DRS models. We first provide an overview of AutoML for DRS models and the related techniques. Then we discuss the state-of-the-art AutoML approaches that automate the feature selection, feature embeddings, feature interactions, and model training in DRS. We point out that the existing AutoML-based recommender systems are developing to amulti-componentjoint search withabstractsearch space andefficientsearch algorithm. Finally, we discuss appealing research directions and summarize the survey.
Web3 Metaverse: State-of-the-Art and Vision
Authors: Chen Hongzhou , Duan Haihan , Abdallah Maha , Zhu Yufeng , Wen Yonggang , Saddik Abdulmotaleb El , Cai Wei
Published: October 2023

The metaverse, as a rapidly evolving socio-technical phenomenon, exhibits significant potential across diverse domains by leveraging Web3 (a.k.a. Web 3.0) technologies such as blockchain, smart contracts, and non-fungible tokens (NFTs). This survey aims to provide a comprehensive overview of the Web3 metaverse from a human-centered perspective. We (i) systematically review the development of the metaverse over the past 30 years, highlighting the balanced contributions from its core components: Web3, immersive convergence, and crowd intelligence communities, (ii) define the metaverse that integrates the Web3 community as the Web3 metaverse and propose an analysis framework from the community, society, and human layers to describe the features, missions, and relationships for each community and their overlapping sections, (iii) survey the state-of-the-art of the Web3 metaverse from a human-centered perspective, namely, the identity, field, and behavior aspects, and (iv) provide supplementary technical reviews. To the best of our knowledge, this work represents the first systematic, interdisciplinary survey on the Web3 metaverse. Specifically, we commence by discussing the potential for establishing decentralized identities (DID) utilizing mechanisms such as profile picture (PFP) NFTs, domain name NFTs, and soulbound tokens (SBTs). Subsequently, we examine land, utility, and equipment NFTs within the Web3 metaverse, highlighting interoperable and full on-chain solutions for existing centralization challenges. Lastly, we spotlight current research and practices about individual, intra-group, and inter-group behaviors within the Web3 metaverse, such as Creative Commons Zero license (CC0) NFTs, decentralized education, decentralized science (DeSci), and decentralized autonomous organizations (DAO). Furthermore, we share our insights into several promising directions, encompassing three key socio-technical facets of Web3 metaverse development.
Impaired hemodynamic renal reserve response following recovery from established acute kidney injury and improvement by hydrodynamic isotonic fluid delivery
Authors: Ullah Md Mahbub , Collett Jason A. , Bacallao Robert L. , Basile David P.
Published: October 2023

Despite the apparent recovery of renal filtration function following acute kidney injury (AKI) in rats, the renal hemodynamic reserve response is significantly attenuated, suggesting that clinical evaluation of this parameter may provide information on the potential development of chronic kidney disease. Treatments such as hydrodynamic isotonic fluid delivery, or other treatments in the early post-AKI period, could minimize chronic inflammation or loss of microvessels with the potential to promote a more favorable outcome on long-term function.