bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trojan Horse virus delivering CRISPR-AsCas12f1 controls plant bacterial wilt caused by
Ralstonia solanacearum
Authors: Peng Shiwen , Xu Yanan , Qu Hao , Nong Fushang , Shu Fangling , Yuan Gaoqing , Ruan Lifang , Zheng Dehong 
Published: July 2024

ABSTRACT

Plant bacterial wilt caused by
Ralstonia solanacearum
results in huge losses. Accordingly, developing an effective control method for this disease is urgently required. Filamentous phages, which do not lyse host bacteria and exert minimal burden, offer a potential biocontrol solution. A filamentous phage RSCq that infects
R. solanacearum
was isolated in this study through genome mining. We constructed engineered filamentous phages based on RSCq by employing our proposed approach with wide applicability to non-model phages, enabling the exogenous genes delivery into bacterial cells. CRISPR-AsCas12f1 is a miniature class 2 type V-F CRISPR-Cas system. A CRISPR-AsCas12f1-based gene editing system that targets the key virulence regulator gene
hrpB
was developed, generating the engineered phage RSCqCRISPR-Cas. Similar to the Greek soldiers in the Trojan Horse, our findings demonstrated that the engineered phage-delivered CRISPR-Cas system could disarm the key “weapon,”
hrpB
, of
R. solanacearum
, in medium and plants. Remarkably, pretreatment with RSCqCRISPR-Cas significantly controlled tobacco bacterial wilt, highlighting the potential of engineered filamentous phages as promising biocontrol agents against plant bacterial diseases.

IMPORTANCE
Bacterial disease, one of the major plant diseases, causes huge food and economic losses. Phage therapy, an environmentally friendly control strategy, has been frequently reported in plant bacterial disease control. However, host specificity, sensitivity to ultraviolet light and certain conditions, and bacterial resistance to phage impede the widespread application of phage therapy in crop production. Filamentous phages, which do not lyse host bacteria and exert minimal burden, offer a potential solution to overcome the limitations of lytic phage biocontrol. This study developed a genetic engineering approach with wide applicability to non-model filamentous phages and proved the application possibility of engineered phage-based gene delivery in plant bacterial disease biocontrol for the first.
Transcriptional responses of
Neisseria gonorrhoeae
to glucose and lactate: implications for resistance to oxidative damage and biofilm formation
Authors: Ayala Julio C. , Balthazar Jacqueline T. , Shafer William M. 
Published: July 2024

ABSTRACT

Understanding how bacteria adapt to different environmental conditions is crucial for advancing knowledge regarding pathogenic mechanisms that operate during infection as well as efforts to develop new therapeutic strategies to cure or prevent infections. Here, we investigated the transcriptional response of
Neisseria gonorrhoeae
, the causative agent of gonorrhea, to L-lactate and glucose, two important carbon sources found in the host environment. Our study revealed extensive transcriptional changes that gonococci make in response to L-lactate, with 37% of the gonococcal transcriptome being regulated, compared to only 9% by glucose. We found that L-lactate induces a transcriptional program that would negatively impact iron transport, potentially limiting the availability of labile iron, which would be important in the face of the multiple hydrogen peroxide attacks encountered by gonococci during its lifecycle. Furthermore, we found that L-lactate-mediated transcriptional response promoted aerobic respiration and dispersal of biofilms, contrasting with an anaerobic condition previously reported to favor biofilm formation. Our findings suggest an intricate interplay between carbon metabolism, iron homeostasis, biofilm formation, and stress response in
N. gonorrhoeae
, providing insights into its pathogenesis and identifying potential therapeutic targets.

IMPORTANCE

Gonorrhea is a prevalent sexually transmitted infection caused by the human pathogen
Neisseria gonorrhoeae
, with ca. 82 million cases reported worldwide annually. The rise of antibiotic resistance in
N. gonorrhoeae
poses a significant public health threat, highlighting the urgent need for alternative treatment strategies. By elucidating how
N. gonorrhoeae
responds to host-derived carbon sources such as L-lactate and glucose, this study offers insights into the metabolic adaptations crucial for bacterial survival and virulence during infection. Understanding these adaptations provides a foundation for developing novel therapeutic approaches targeting bacterial metabolism, iron homeostasis, and virulence gene expression. Moreover, the findings reported herein regarding biofilm formation and L-lactate transport and metabolism contribute to our understanding of
N. gonorrhoeae
pathogenesis, offering potential avenues for preventing and treating gonorrhea infections.
A novel hypovirulence-associated Hadaka virus 1 (HadV1-LA6) in
Fusarium oxysporum
f. sp.
cubense
Authors: Lin Yinfu , Pan Guangqun , Qi Yanhua , Wang Bin , Jin Cheng , Fang Wenxia 
Published: July 2024

ABSTRACT

Fusarium oxysporum
f. sp.
cubense
(
Foc
) poses a significant threat to banana crops as a lethal fungal pathogen. The global spread of
Foc
underscores the formidable challenges associated with traditional management methods in combating this pathogen. This study delves into the hypovirulence-associated mycovirus in
Foc
. From
Foc
strain LA6, we isolated and characterized a novel member of the
Hadakaviridae
family, named Hadaka virus 1 strain LA6 (HadV1-LA6). HadV1-LA6 comprises 10 genomic RNA segments, with RNA1 to RNA7 sharing 80.9%–95.0% amino acid sequence identity with known HadV1-7n, while RNA8 to RNA10 display significantly lower identity. HadV1-LA6 demonstrates horizontal transmission capabilities in an all-or-none fashion between different
Foc
strains via coculturing. Phenotypic comparisons highlight that HadV1-LA6 significantly reduces the growth rates of its host fungus under cell wall stress and oxidative stress conditions. Importantly, HadV1-LA6 attenuates
Foc
’s virulence in detached leaves and banana plants. This study represents the first introduction of a novel hypovirulence-associated Hadaka virus 1 in
Foc
.

IMPORTANCE

Fusarium wilt of banana (FWB) is a severe fungal disease caused by soil-borne
Fusarium oxysporum
f. sp.
cubense
(
Foc
). Among various strategies, biocontrol emerges as a safe, ecologically friendly, and cost-effective approach to managing FWB. In this study, we focus on exploring the potential of a novel hypovirulent member of hadakavirid, HadV1-LA6. Previous reports suggest that HadV1 shows no apparent effect on the host. However, through phenotypic assessments, we demonstrate that HadV1-LA6 significantly impedes the growth rates of its host fungus under stress conditions. More importantly, HadV1-LA6 exhibits a remarkable capacity to attenuate
Foc
’s virulence in detached leaves and banana plants. Furthermore, HadV1-LA6 could be horizontally transmitted between different
Foc
strains, presenting a promising resource for revealing the molecular mechanism of the interaction between Hadaka virus 1 and its host.
Spatial patterns of
Hyalomma marginatum
-borne pathogens in the Occitanie region (France), a focus on the intriguing dynamics of
Rickettsia aeschlimannii
Authors: Joly-Kukla Charlotte , Bernard Célia , Bru David , Galon Clémence , Giupponi Carla , Huber Karine , Jourdan-Pineau Hélène , Malandrin Laurence , Rakotoarivony Ignace , Riggi Camille , Vial Laurence , Moutailler Sara , Pollet Thomas 
Published: July 2024

ABSTRACT

Hyalomma marginatum
is an invasive tick species recently established in mainland southern France. This tick is known to host a diverse range of human and animal pathogens. While information about the dynamics of these pathogens is crucial to assess disease risk and develop effective monitoring strategies, few data on the spatial dynamics of these pathogens are currently available. We collected ticks in 27 sites in the Occitanie region to characterize spatial patterns of
H. marginatum
-borne pathogens. Several pathogens have been detected:
Theileria equi
(9.2%),
Theileria orientalis
(0.2%),
Anaplasma phagocytophilum
(1.6%),
Anaplasma marginale
(0.8%), and
Rickettsia aeschlimannii
(87.3%). Interestingly, we found a spatial clustered distribution for the pathogen
R. aeschlimannii
between two geographically isolated areas with infection rates and bacterial loads significantly lower in Hérault/Gard departments (infection rate 78.6% in average) compared to Aude/Pyrénées-Orientales departments (infection rate 92.3% in average). At a smaller scale,
R. aeschlimannii
infection rates varied from one site to another, ranging from 29% to 100%. Overall, such high infection rates (87.3% on average) and the effective maternal transmission of
R. aeschlimannii
might suggest a role as a tick symbiont in
H. marginatum
. Further studies are thus needed to understand both the status and the role of
R. aeschlimannii
in
H. marginatum
ticks.

IMPORTANCE

Ticks are obligatory hematophagous arthropods that transmit pathogens of medical and veterinary importance. Pathogen infections cause serious health issues in humans and considerable economic loss in domestic animals. Information about the presence of pathogens in ticks and their dynamics is crucial to assess disease risk for public and animal health. Analyzing tick-borne pathogens in ticks collected in 27 sites in the Occitanie region, our results highlight clear spatial patterns in the
Hyalomma marginatum
-borne pathogen distribution and strengthen the postulate that it is essential to develop effective monitoring strategies and consider the spatial scale to better characterize the circulation of tick-borne pathogens.
The two alternative NADH:quinone oxidoreductases from
Staphylococcus aureus
: two players with different molecular and cellular roles
Authors: Sena Filipa V. , Sousa Filipe M. , Pereira Ana R. , Catarino Teresa , Cabrita Eurico J. , Pinho Mariana G. , Pinto Francisco R. , Pereira Manuela M. 
Published: July 2024

ABSTRACT

Staphylococcus aureus
is an opportunistic pathogen that has emerged as a major public health threat due to the increased incidence of its drug resistance.
S. aureus
presents a remarkable capacity to adapt to different niches due to the plasticity of its energy metabolism. In this work, we investigated the energy metabolism of
S. aureus
, focusing on the alternative NADH:quinone oxidoreductases, NDH-2s.
S. aureus
presents two genes encoding NDH-2s (NDH-2A and NDH-2B) and lacks genes coding for Complex I, the canonical respiratory NADH:quinone oxidoreductase. This observation makes the action of NDH-2s crucial for the regeneration of NAD
+
and, consequently, for the progression of metabolism. Our study involved the comprehensive biochemical characterization of NDH-2B and the exploration of the cellular roles of NDH-2A and NDH-2B, utilizing knockout mutants (Δ
ndh-2a
and Δ
ndh-2b
). We show that NDH-2B uses NADPH instead of NADH, does not establish a charge-transfer complex in the presence of NADPH, and its reduction by this substrate is the catalytic rate-limiting step. In the case of NDH-2B, the reduction of the flavin is inherently slow, and we suggest the establishment of a charge transfer complex between NADP
+
and FADH
2
, as previously observed for NDH-2A, to slow down quinone reduction and, consequently, prevent the overproduction of reactive oxygen species, which is potentially unnecessary. Furthermore, we observed that the lack of NDH-2A or NDH-2B impacts cell growth, volume, and division differently. The absence of these enzymes results in distinct metabolic phenotypes, emphasizing the unique cellular roles of each NDH-2 in energy metabolism.

IMPORTANCE

Staphylococcus aureus
is an opportunistic pathogen, posing a global challenge in clinical medicine due to the increased incidence of its drug resistance. For this reason, it is essential to explore and understand the mechanisms behind its resistance, as well as the fundamental biological features such as energy metabolism and the respective players that allow
S. aureus
to live and survive. Despite its prominence as a pathogen, the energy metabolism of
S. aureus
remains underexplored, with its respiratory enzymes often escaping thorough investigation.
S. aureus
bioenergetic plasticity is illustrated by its ability to use different respiratory enzymes, two of which are investigated in the present study. Understanding the metabolic adaptation strategies of
S. aureus
to bioenergetic challenges may pave the way for the design of therapeutic approaches that interfere with the ability of the pathogen to successfully adapt when it invades different niches within its host.
Inequalities in children’s tooth decay requiring dental extraction under general anaesthetic: a longitudinal study using linked electronic health records
Authors: Firman Nicola , Dezateux Carol , Muirhead Vanessa 
Published: July 2024

BackgroundDental extraction under general anaesthetic (DGA) is the most severe and irreversible dental treatment for childhood tooth decay. We investigated inequalities in DGA in an ethnically diverse, disadvantaged school-age population and associations of DGA with prior excess weight.MethodsWe identified 608 278 children aged 5–16 years in 2017–2022 from linked hospital and primary care electronic health records (EHRs) for a London, UK region. We estimated ORs (95% CI) for DGA, adjusting for sex, ethnicity, locality and deprivation. We linked 120 985 EHRs to school weight records and estimated HRs (95% CI) for DGA by excess weight (body mass index ≥91st centile) using Cox’s proportional regression.Results3034 children had at least one DGA (0.50%; 95% CI 0.48 to 0.52). Children from white Irish (OR: 1.96; 95% CI 1.17 to 3.29), other Asian (1.23; 95% CI 1.01 to 1.50), Bangladeshi (1.49; 95% CI 1.30 to 1.70) and Pakistani (1.41; 95% CI 1.21 to 1.65) ethnicities were more likely and those from Chinese (0.48; 95% CI 0.27 to 0.86), white and black African (0.59; 95% CI 0.35 to 0.98), other mixed (0.69; 95% CI 0.50 to 0.95), Indian (0.65; 95% CI 0.53 to 0.81), black African (0.79; 95% CI 0.66 to 0.93) and other black (0.62; 95% CI 0.48 to 0.82) ethnicities and living in less deprived areas less likely, to have had a DGA. Five- (HR: 0.80; 95% CI 0.66 to 0.94) and 11- year-olds (0.78; 95% CI 0.62 to 0.99) with excess weight were less likely to have had a DGA.ConclusionWe found marked ethnic and socioeconomic inequalities in childhood DGA. Further research is needed to understand factors mediating inequalities in DGA. These findings emphasise the importance of targeting the wider determinants of inequalities in tooth extraction and ensuring equitable access to preventive and restorative dentistry.
Exploring new physics in the late Universe’s expansion through non-parametric inference
Authors: Sabogal Miguel A. , Akarsu Özgür , Bonilla Alexander , Di Valentino Eleonora , Nunes Rafael C. 
Published: July 2024

AbstractIn this study, we investigate deviations from the Planck-$$\Lambda $$
Λ
CDM model in the late universe ($$z \lesssim 2.5$$

z
≲
2.5

) using the Gaussian Processes method, with minimal assumptions. Our goal is to understand where exploring new physics in the late universe is most relevant. We analyze recent Cosmic Chronometers (CC), Type Ia Supernovae (SN), and Baryon Acoustic Oscillations (BAO) data. By examining reconstructions of the dimensionless parameter $$\delta (z)$$

δ
(
z
)

, which measures deviations of the Hubble parameter from the Planck-$$\Lambda $$
Λ
CDM predictions, we identify intriguing features at low ($$z \lesssim 0.5$$

z
≲
0.5

) and high ($$z \gtrsim 2$$

z
≳
2

) redshifts. Deviations from the Planck-$$\Lambda $$
Λ
CDM model were not significant between $$0.5\lesssim z \lesssim 2$$

0.5
≲
z
≲
2

. Using the combined CC+SN+BAO dataset, we gain insights into dark energy (DE) dynamics, resembling characteristics of omnipotent DE, extending beyond quintessence and phantom models. DE exhibits n-quintessence traits for $$z\gtrsim 2$$

z
≳
2

, transitioning with a singularity around $$z\sim 2$$

z
∼
2

to usual phantom traits in $$1\lesssim z\lesssim 2$$

1
≲
z
≲
2

. DE characteristics differ between scenarios ($$H_0$$

H
0

-SH0ES and $$H_0$$

H
0

-$$\Lambda $$
Λ
&CMB), with $$H_0$$

H
0

-SH0ES leaning towards phantom traits and $$H_0$$

H
0

-$$\Lambda $$
Λ
&CMB towards quintessence. We suggest exploring new physics at $$z\lesssim 0.5$$

z
≲
0.5

and $$1.5\lesssim z\lesssim 2.5$$

1.5
≲
z
≲
2.5

, particularly around $$z = 2$$

z
=
2

, to understand cosmological tensions such as $$H_0$$

H
0

and $$S_8$$

S
8

.
Towards Smartphone-based 3D Hand Pose Reconstruction Using Acoustic Signals
Authors: Wang Shiyang , Wang Xingchen , Jiang Wenjun , Miao Chenglin , Cao Qiming , Wang Haoyu , Sun Ke , Xue Hongfei , Su Lu 
Published: July 2024

Accurately reconstructing 3D hand poses is a pivotal element for numerous Human-Computer Interaction applications. In this work, we propose SonicHand, the first smartphone-based 3D hand pose reconstruction system using purely inaudible acoustic signals. SonicHand incorporates signal processing techniques and a deep learning framework to address a series of challenges. First, it encodes the topological information of the hand skeleton as prior knowledge and utilizes a deep learning model to realistically and smoothly reconstruct the hand poses. Second, the system employs adversarial training to enhance the generalization ability of our system to be deployed in a new environment or for a new user. Third, we adopt a hand tracking method based on channel impulse response estimation. It enables our system to handle the scenario where the hand performs gestures while moving arbitrarily as a whole. We conduct extensive experiments on a smartphone testbed to demonstrate the effectiveness and robustness of our system from various dimensions. The experiments involve 10 subjects performing up to 12 different hand gestures in three distinctive environments. When the phone is held in one of the user’s hands, the proposed system can track joints with an average error of 18.64 mm.
Left Atrial Roof Enlargement Is a Distinct Feature of Heart Failure With Preserved Ejection Fraction
Authors: Backhaus Sören J. , Nasopoulou Anastasia , Lange Torben , Schulz Alexander , Evertz Ruben , Kowallick Johannes T. , Hasenfuß Gerd , Lamata Pablo , Schuster Andreas 
Published: July 2024

BACKGROUND:
It remains unknown to what extent intrinsic atrial cardiomyopathy or left ventricular diastolic dysfunction drive atrial remodeling and functional failure in heart failure with preserved ejection fraction (HFpEF). Computational 3-dimensional (3D) models fitted to cardiovascular magnetic resonance allow state-of-the-art anatomic and functional assessment, and we hypothesized to identify a phenotype linked to HFpEF.

METHODS:
Patients with exertional dyspnea and diastolic dysfunction on echocardiography (E/e′, >8) were prospectively recruited and classified as HFpEF or noncardiac dyspnea based on right heart catheterization. All patients underwent rest and exercise-stress right heart catheterization and cardiovascular magnetic resonance. Computational 3D anatomic left atrial (LA) models were generated based on short-axis cine sequences. A fully automated pipeline was developed to segment cardiovascular magnetic resonance images and build 3D statistical models of LA shape and find the 3D patterns discriminant between HFpEF and noncardiac dyspnea. In addition, atrial morphology and function were quantified by conventional volumetric analyses and deformation imaging. A clinical follow-up was conducted after 24 months for the evaluation of cardiovascular hospitalization.

RESULTS:

Beyond atrial size, the 3D LA models revealed roof dilation as the main feature found in masked HFpEF (diagnosed during exercise-stress only) preceding a pattern shift to overall atrial size in overt HFpEF (diagnosed at rest). Characteristics of the 3D model were integrated into the LA HFpEF shape score, a biomarker to characterize the gradual remodeling between noncardiac dyspnea and HFpEF. The LA HFpEF shape score was able to discriminate HFpEF (n=34) to noncardiac dyspnea (n=34; area under the curve, 0.81) and was associated with a risk for atrial fibrillation occurrence (hazard ratio, 1.02 [95% CI, 1.01–1.04];
P
=0.003), as well as cardiovascular hospitalization (hazard ratio, 1.02 [95% CI, 1.00–1.04];
P
=0.043).

CONCLUSIONS:
LA roof dilation is an early remodeling pattern in masked HFpEF advancing to overall LA enlargement in overt HFpEF. These distinct features predict the occurrence of atrial fibrillation and cardiovascular hospitalization.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03260621.
Visit‐to‐Visit Systolic Blood Pressure Variability Independently Predicts Cardiovascular Events in a Kidney Transplant Recipients' Cohort
Authors: Bussalino Elisabetta , Picciotto Daniela , Macciò Lucia , Parodi Angelica , Gandolfo Maria Teresa , Viazzi Francesca 
Published: July 2024

Background
The predictive role of blood pressure variability for all‐cause mortality and fatal and nonfatal cardiovascular events has been described in the general population and in patients with diabetes, independently of mean BP. Although systolic blood pressure variability has been proposed as an informative measure for predicting clinical outcomes in patients with chronic kidney disease, its role in kidney transplant recipients is still debatable.

Methods and Results

We performed a retrospective, observational, monocentric analysis of all kidney transplant recipients in follow‐up at the outpatient Nephrology Clinic of San Martino Hospital from January 1, 2016 to December 31, 2016, who underwent kidney transplantation >12 months. The primary outcome was a fatal or nonfatal cardiovascular event (myocardial infarction, unstable angina, stroke, and hospitalization for heart failure). Visit‐to‐visit systolic blood pressure variability was expressed as the SD of systolic blood pressure values recorded at baseline and 3 months up to 18 months. Among the 272 patients (mean age, 64±13; 63% men) included in the present analyses, for each increase of 2.7 mm Hg in systolic blood pressure SD, the risk for events increased 3‐fold (hazard ratio [HR], 3.1 [95% CI, 1.19–7.88];
P
=0.02), and patients in the highest tertile of systolic blood pressure SD showed a 4‐fold increased risk (HR, 4.1 [95% CI, 1.34–12.43];
P
=0.01). This relationship was maintained even after incremental adjustment for time‐averaged pulse pressure, age, diabetes, and prior cardiovascular event (HR, 3.2 [95% CI, 1.1–10.0];
P
=0.04).

Conclusions
Long‐term blood pressure variability represents a risk factor for cardiovascular events in kidney transplant recipients, even independently by several confounding factors including blood pressure load.