bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct mutations emerge in the genome of serotype O foot-and-mouth disease virus during persistence in cattle
Authors: Litz Benedikt , Forth Leonie F. , Pfaff Florian , Beer Martin , Eschbaumer Michael 
Published: February 2025

ABSTRACT

Like other RNA viruses, foot-and-mouth disease virus (FMDV) has a high mutation rate. After the acute phase of infection, about half of infected cattle develop a persistent FMDV infection that can last for weeks or months. During this persistent phase, the virus continues to replicate, resulting in the emergence of genomic heterogeneity. We have documented the pattern of mutations in the persistent phase by obtaining consensus-level sequences directly from oropharyngeal fluid (OPF) without prior virus isolation in culture. OPF samples were repeatedly collected from 22 experimentally infected cattle, 20 of which were virus positive in the OPF on day 21 after infection or later. We observed that during the persistent phase, the amount of non-synonymous mutations causing an amino acid change increased over time. Two amino acid changes that showed a striking increase during the persistent phase, VP3 A75T and VP2 Y79H, were present neither in the inoculum nor during the acute phase. Another amino acid change in VP3, R56C, which was previously implicated in FMDV pathogenicity, was already present in the inoculum and dominated toward the end of the trial in most samples. Several other amino acid changes occurred, particularly on the surface of VP2 around residue VP2 79. By functional analysis, we show that the persistent isolates evolve distinctly compared with cell culture adaptation but do not show signs of antigenic escape from neutralizing antibodies. In agreement with previous observations, we conclude that these amino acid changes are indeed associated with persistent infection of cattle with FMDV serotype O.

IMPORTANCE
Our research article describes the genetic changes that occur during the acute and persistent foot-and-mouth disease (FMDV) infection. This is of particular interest to understand viral dynamics within an infected population from which new viral strains could emerge. Especially FMDV, with its high antigenic diversity and very limited cross-reactivity between strains and serotypes, has already demonstrated in the past that new variants can quickly emerge and evade vaccine responses. In our study, we have observed that this dynamic evolution continues during the persistent phase. Persistently infected animals, which are clinically indistinguishable from healthy animals, also pose a reservoir for recombination. A better understanding of viral dynamics is essential for improved vaccines to prevent the emergence of antigenic variants.
Genome-scale CRISPR/Cas9 screening reveals the role of
PSMD4
in colibactin-mediated cell cycle arrest
Authors: Dougherty Michael W. , Hoffmann Ryan M. , Hernandez Maria C. , Airan Yougant , Gharaibeh Raad Z. , Herzon Seth B. , Yang Ye , Jobin Christian 
Published: February 2025

ABSTRACT

Colibactin is a genotoxic secondary metabolite produced by certain
Enterobacteriaceae
strains that populate the intestine and produces a specific mutational signature in human colonocytes. However, the host pathways involved in colibactin response remain unclear. To address this gap, we performed genome-wide CRISPR/Cas9 knockout screens and RNA sequencing utilizing live

pks
+

bacteria and a synthetic colibactin analog. We identified 20 enriched genes with a MAGeCK score of >2.0 in both screens, including proteasomal subunits (e.g.,
PSMG4
and
PSMD4
), RNA processing factors (e.g.,
SF1
and
PRPF8
), and RNA polymerase III (e.g.,
CRCP
), and validated the role of
PSMD4
in colibactin sensitization.
PSMD4
knockout in HEK293T and HT-29 cells promoted cell viability and ameliorated G2-M cell cycle arrest but did not affect the amount of phosphorylated H2AX foci after exposure to synthetic colibactin 742. Consistent with these observations,
PSMD4
−/−
cells had a significantly higher colony formation rate and bigger colony size than control cells after 742 exposure. These findings suggest that
PSMD4
regulates cell cycle arrest following colibactin-induced DNA damage and that cells with
PSMD4
deficiency may continue to replicate despite DNA damage, potentially increasing the risk of malignant transformation.

IMPORTANCE
Colibactin has been implicated as a causative agent of colorectal cancer. However, colibactin-producing bacteria are also present in many healthy individuals, leading to the hypothesis that some aspects of colibactin regulation or host response dictate the molecule’s carcinogenic potential. Elucidating the host-response pathways involved in dictating cell fate after colibactin intoxication has been difficult, partially due to an inability to isolate the molecule. This study provides the first high-throughput CRISPR/Cas9 screening to identify genes conferring colibactin sensitivity. Here, we utilize both bacterial infection and a synthetic colibactin analog to identify genes directly involved in colibactin response. These findings provide insight into how differences in gene expression may render certain individuals more vulnerable to colibactin-initiated tumor formation after DNA damage.
The TgAMPK-TgPFKII axis essentially regulates protein lactylation in the zoonotic parasite
Toxoplasma gondii
Authors: Li Chenghuan , Zhao Yang , Li Qilong , Chen Ran , Feng Ying , Sang Xiaoyu , Li Xiangrui , Shen Bang , Jiang Ning , Chen Qijun 
Published: February 2025

ABSTRACT

Toxoplasma gondii
infects nucleated cells of warm-blooded animals and cause zoonotic toxoplasmosis. Lysine lactylation, as a novel post-translational modification, is essential for epigenetic regulation and cellular processes, and proteomic analyses have shown that lactylated proteins are involved in a wide range of biological processes including energy metabolism, gene regulation, and protein biosynthesis. Additionally, protein lactylation is prevalent in
T. gondii
, while its regulatory mechanisms have not been fully understood. In this study, we investigated the role of
T. gondii
phosphofructokinase-2 (TgPFKII) and the adenosine-5’-monophosphate-activated protein kinase (AMPK) signaling pathway in the invasion, replication, and lactylation regulation of
T. gondii
. We localized TgPFKII in the cytoplasm of
T. gondii
tachyzoites and demonstrated its necessity for parasite growth and protein lactylation through auxin-induced degradation. Our results showed that inhibition of the AMPK pathway led to decreased TgPFKII expression and reduced protein lactylation levels. Furthermore, AMPK-specific inhibitors significantly impaired parasite invasion and proliferation. These findings highlight TgPFKII as a crucial regulator of lactylation and underscore the importance of the AMPK pathway in
T. gondii
’s pathogenic mechanisms, offering potential targets for therapeutic intervention.

IMPORTANCE

Understanding the intricate mechanisms by which
Toxoplasma gondii
invades and proliferates within host cells is essential for developing novel therapeutic strategies against toxoplasmosis. This study focuses on the pivotal roles of
T. gondii
phosphofructokinase-2 (TgPFKII) and the adenosine-5’-monophosphate-activated protein kinase (AMPK) signaling pathway in regulating protein lactylation in association with parasite invasion and growth. By elucidating the cellular localization and functional importance of TgPFKII, as well as its regulation through AMPK-specific inhibitors, we provide comprehensive insights into the metabolic and signaling networks that underpin
T. gondii
pathogenicity. Our findings reveal that TgPFKII is a critical regulator of lactylation and that the AMPK pathway significantly influences
T. gondii
’s ability to invade and replicate within host cells. These insights pave the way for targeted interventions aimed at disrupting key metabolic and signaling pathways in
T. gondii
, potentially leading to more effective treatments for toxoplasmosis.
Supersymmetric $$AdS_6$$ black holes from ISO(3)$$\times $$U(1) F(4) gauged supergravity
Authors: Karndumri Parinya 
Published: February 2025

Abstract
We study supersymmetric

$$AdS_6$$

A
d

S
6

black holes from matter-coupled F(4) gauged supergravity coupled to four vector multiplets with

$$ISO(3)\times U(1)$$

I
S
O
(
3
)
×
U
(
1
)

gauge group. This gauged supergravity admits a maximally supersymmetric

$$AdS_6$$

A
d

S
6

vacuum with

$$SO(3)\subset ISO(3)$$

S
O
(
3
)
⊂
I
S
O
(
3
)

symmetry. We find a number of new supersymmetric

$$AdS_2\times \mathcal {M}_4$$

A
d

S
2

×

M
4

solutions by performing topological twists along

$$\mathcal {M}_4$$

M
4

. For

$$\mathcal {M}_4$$

M
4

being a product of two Riemann surfaces

$$\Sigma \times \widetilde{\Sigma }$$

Σ
×

Σ
~

, we perform a twist by

$$SO(2)\times U(1)$$

S
O
(
2
)
×
U
(
1
)

gauge fields and find

$$AdS_2\times \Sigma \times \widetilde{\Sigma }$$

A
d

S
2

×
Σ
×

Σ
~

solutions for at least one of the Riemann surface being negatively curved. For

$$\mathcal {M}_4$$

M
4

being a Kahler four-cycle

$$\mathcal {M}_{\text {K}4}$$

M

K
4

, a twist by

$$SO(2)\times U(1)$$

S
O
(
2
)
×
U
(
1
)

gauge fields leads to

$$AdS_2\times \mathcal {M}_{\text {K}4}^-$$

A
d

S
2

×

M

K
4

-

solutions for negatively curved

$$\mathcal {M}_{\text {K}4}$$

M

K
4

. Finally, performing a twist by turning on SO(3) gauge fields in the case of

$$\mathcal {M}_4$$

M
4

being a Cayley four-cycle

$$\mathcal {M}_{\text {C}4}$$

M

C
4

also leads to

$$AdS_2\times \mathcal {M}_{\text {C}4}^-$$

A
d

S
2

×

M

C
4

-

solutions for negatively curved

$$\mathcal {M}_{\text {C}4}$$

M

C
4

. We give numerical black hole solutions interpolating between all of these

$$AdS_2\times \mathcal {M}_4$$

A
d

S
2

×

M
4

near horizon geometries and the asymptotically locally

$$AdS_6$$

A
d

S
6

vacuum. It is also possible to uplift all of these solutions to type IIB theory via consistent truncations on

$$S^2\times \Sigma $$

S
2

×
Σ

leading to a new class of supersymmetric

$$AdS_2\times \mathcal {M}_4\times S^2\times \Sigma $$

A
d

S
2

×

M
4

×

S
2

×
Σ

solutions.
Association of Sleep Duration With Serum Estradiol Concentrations Among American Men and Women: Evidence From NHANES 2013–2016
Authors: Zhu Zhisheng , Wu Shiquan , Lin Xingong , Wang Chaoyang , Zhou Xianying 
Published: February 2025

Objective: To evaluate the association between sleep duration with serum estradiol concentrations and its variation by sex and age in American adults.Methods: Data were analyzed for 5406 men and women (≥ 20 years old) who participated in the cycles of the National Health and Nutrition Examination Survey 2013–2016, a cross‐sectional study. Total estradiol (pg/mL) was measured and categorized (low, normal, and high) based on the NHANES protocol. Sleep duration was classified as ≤ 6, 6–9, and ≥ 9 h. Weighted multivariable adjusted and multinomial logistic regression models were conducted to assess these associations.Results: Our multivariable multinomial logistic regression analysis revealed no significant associations between sleep duration and serum estradiol concentrations among both American men and women. Specifically, comparisons of sleep durations (≤ 6 and ≥ 9 h) to the reference group (6–9 h) across various age categories showed odds ratios for low and high estradiol concentrations that remained statistically nonsignificant in fully adjusted models. These findings suggest that, unlike previous studies linking sleep duration with variations in other hormones, estradiol concentrations do not appear to be significantly affected by differences in sleep duration in either sex across all age groups studied.Conclusion: The lack of significant associations between sleep duration and serum estradiol concentrations indicates that sleep duration may not influence estradiol levels in the general population of American men and women. These results underscore the importance of continued research into how sleep influences hormonal balance. However, it is important to note that the NHANES data we used are from a cross‐sectional study, which cannot establish a causal relationship between sleep duration and serum estradiol. Future studies should investigate additional factors, such as genetic predispositions, lifestyle habits, and environmental influences, that may modulate the relationship between sleep and hormone levels.
Prediagnostic Plasma Metabolites Are Associated with Incident Hepatocellular Carcinoma: A Prospective Analysis
Authors: Wilechansky Robert M. , Challa Prasanna K. , Han Xijing , Hua Xinwei , Manning Alisa K. , Corey Kathleen E. , Chung Raymond T. , Zheng Wei , Chan Andrew T. , Simon Tracey G. 
Published: February 2025

Abstract
Despite increasing incidence of hepatocellular carcinoma (HCC) in vulnerable populations, accurate early detection tools are lacking. We aimed to investigate the associations between prediagnostic plasma metabolites and incident HCC in a diverse population. In a prospective, nested case–control study within the Southern Community Cohort Study, we conducted prediagnostic LC/MS metabolomic profiling in 150 incident HCC cases (median time to diagnosis, 7.9 years) and 100 controls with cirrhosis. Logistic regression assessed metabolite associations with HCC risk. Metabolite set enrichment analysis identified enriched pathways, and a random forest classifier was used for risk classification models. Candidate metabolites were validated in the UK Biobank (N = 12 incident HCC cases and 24 cirrhosis controls). In logistic regression analysis, seven metabolites were associated with incident HCC (MeffP &lt; 0.0004), including N-acetylmethionine (OR = 0.46; 95% confidence interval, 0.31–0.66). Multiple pathways were enriched in HCC, including histidine and CoA metabolism (FDR P &lt; 0.001). The random forest classifier identified 10 metabolites for inclusion in HCC risk classification models, which improved HCC risk classification compared with clinical covariates alone (AUC = 0.66 for covariates vs. 0.88 for 10 metabolites plus covariates; P &lt; 0.0001). Findings were consistent in the UK Biobank (AUC = 0.72 for covariates vs. 0.88 for four analogous metabolites plus covariates; P = 0.04), assessed via nuclear magnetic resonance spectroscopy. Prediagnostic metabolites, primarily amino acid and sphingolipid derivatives, are associated with HCC risk and improve HCC risk classification beyond clinical covariates. These metabolite profiles, detectable years before diagnosis, could serve as early biomarkers for HCC detection and risk stratification if validated in larger studies.
Prevention Relevance: Our findings support the need for larger prospective studies examining the role of prediagnostic plasma metabolomics for the preventive management of HCC in diverse patients across multiple etiologies of liver disease. This approach could improve HCC care by identifying metabolic changes years before diagnosis, potentially enhancing screening and early detection practices.
Knudson’s “Two-Hit” Hypothesis and Cancer Predisposition: A Bit More Complicated but Still Going Strong
Authors: Brzezinski Jack J. , Malkin David 
Published: February 2025

Summary:
This study by Treger and colleagues is a comprehensive evaluation of the genome and epigenome of tumors and constitutional tissue from children with Wilms tumor predisposition syndromes that demonstrates that the molecular features of Wilms tumors are dependent on the constitutional milieu of the patient in which they develop.
See related article by Treger et al., p. 286
Hidden in Plain Sight: Clinical Imaging of the Tumor Microenvironment with PET
Authors: Witney Timothy H. 
Published: February 2025

Summary:
PET imaging enables the spatiotemporal assessment of tumor biomarkers. In this issue, Kong and colleagues describe the clinical PET imaging of tumor-associated fibroblasts, which improved the diagnostic accuracy and management of a subset of patients with medullary thyroid carcinoma.
See related article by Kong et al., p. 316
Temporal Dynamics and Representational Consequences of the Control of Processing Conflict between Visual Working Memory and Visual Perception
Authors: Teng Chunyue , Fulvio Jacqueline M. , Pietrelli Mattia , Jiang Jiefeng , Postle Bradley R. 
Published: February 2025

Abstract
Visual working memory (WM) extensively interacts with visual perception. When information between the two processes is in conflict, cognitive control can be recruited to effectively mitigate the resultant interference. The current study investigated the neural bases of the control of conflict between visual WM and visual perception. We recorded the EEG from 25 human participants (13 male) performing a dual task combining visual WM and tilt discrimination, the latter occurring during the WM delay. The congruity in orientation between the memorandum and the discriminandum was manipulated. Behavioral data were fitted to a reinforcement-learning model of cognitive control to derive trial-wise estimates of demand for preparatory and reflexive control, which were then used for EEG analyses. The level of preparatory control was associated with sustained frontal-midline theta activity preceding trial onset, as well as with the strength of the neural representation of the memorandum. Subsequently, discriminandum onset triggered a control prediction error signal that was reflected in a left frontal positivity. On trials when an incongruent discriminandum was not expected, reflexive control that scaled with the prediction error acted to suppress the neural representation of the discriminandum, producing below-baseline decoding of the discriminandum that, in turn, exerted a repulsive serial bias on WM recall on the subsequent trial. These results illustrate the flexible recruitment of two modes of control and how their dynamic interplay acts to mitigate interference between simultaneously processed perceptual and mnemonic representations.
Exploring Dynamic Brain Oscillations in Motor Imagery and Low-frequency Sound
Authors: Dupont William , Poulin-Charronnat Benedicte , Madden-Lombardi Carol , Jacquet Thomas , Pfister Philippe , Dos Anjos Typhanie , Lebon Florent 
Published: February 2025

Abstract
Although both motor imagery (MI) and low-frequency sound listening have independently been shown to modulate brain activity, the potential synergistic effects that may arise from their combined application remains unexplored. Any further modulation derived from this combination may be relevant for motor learning and rehabilitation. We probed neurophysiological activity during these two processes, measuring alpha and beta band power amplitude by means of EEG recordings. Twenty healthy volunteers were instructed to (i) explicitly imagine right finger flexion/extension movements in a kinaesthetic modality, (ii) listen to low-frequency sounds, (iii) imagine right finger movements while listening to low-frequency sounds, or (iv) stay at rest. We observed a bimodal distribution of alpha-band reactivity to the conditions, suggesting the presence of variability in brain activity across participants during both MI and low-frequency sound listening. One group of participants (12 individuals) displayed increased alpha power within contralateral sensorimotor and ipsilateral medial parieto-occipital regions during MI. Another group (eight individuals) exhibited a decrease in alpha and beta band power within sensorimotor areas. Interestingly, low-frequency sound listening elicited a similar pattern of brain activity within both groups. The combination of MI and sound listening did not result in additional changes in alpha and beta power amplitudes, regardless of group (groups based on individual alpha-band reactivity). Altogether, these findings shed significant insight into the brain activity and its variability generated during MI and low-frequency sound listening. The simultaneous engagement of MI and low-frequency sound listening did not further modulate alpha power amplitude, possibly due to concurrent cortical activation. It remains possible that sequential performance of these tasks could elicit additional modulation.
From semantic structure to conventionalization
Authors: Katzir Nicole , Cummins Chris 
Published: February 2025

Abstract
The present study investigates potential differences among 40 quantifier scales regarding measures that may indicate variations in conventionalization among different scales, i.e., the extent to which their terms are stored as scalemates in the mental lexicon. We derive these measures from two experiments and corpus data. In addition to exploring the relationships between these measures, we also investigate their correlation with scalar inference (SI) rates. We compare the quantifier scales to scales from two categories: highly and moderately conventionalized. Our findings indicate that quantifier scales pattern with moderately conventionalized scales in the experimental tasks. Additionally, we identify two significant predictors of SI rates that are not directly derived from the semantics of the quantifiers: confidence in an elicitation task and the observed/expected ratio of sentences in a corpus. Finally, we propose that the semantic and non-semantic features generally align, working together to reinforce the connection between the scalemates.
Exploring the pragmatics of autistic language
Authors: Rebecchi Kevin 
Published: February 2025

Abstract
This article examines the linguistic aspects of autism, focusing specifically on expressive and phatic traits, reevaluating the field of pragmatics. Inspired by the emphasis on inclusion and diverse modes of expression in the Reggio Emilia pedagogy, this study explores the applicability of Reggio Emilia’s pedagogical principles to autism research. The concept of “hundred languages” highlights the multitude of ways in which children can express themselves, think, communicate, and create. By prioritizing inclusive education and recognizing individual differences, the Reggio Emilia approach provides valuable insights for creating inclusive educational environments for autistic individuals. Furthermore, the concept of “hundred languages” aligns with the diverse modes of expression and communication observed in autistic individuals. Emphasis is placed on the pragmatic aspects of language, including social context and the management of similarities and differences in social interactions. This prompts an exploration of how autistic pragmatics may differ from that of non-autistic individuals. The dynamics of linguistic power, wherein individuals in positions of power use language and influence specific segments of the population, raise questions about the impact of power structures on autistic individuals and their language experiences. Moreover, historical descriptions of language in autism provide valuable insights. Observations made by researchers such as Sukhareva, Kanner, Asperger, and Frankl highlight common linguistic peculiarities that cannot be assimilated to deficits or impairments. These descriptions prompt a deeper examination of autistic communication profiles and explain why communication can be more effective between autistic individuals but often more challenging between autistic and non-autistic individuals. This article proposes future research directions, including the study of the “hundred languages” of autism, exploration of the pragmatic aspects of autistic language use, and investigation of the expressive and phatic functions of language in relation to the specialized interests of autistic individuals. These research avenues should aim to enhance our understanding of autistic communication and contribute to the development of effective educational and professional support strategies that encompass and adapt to the unique communication styles and preferences of autistic individuals.