Miracle-dz/UniFAR-FTUs huggingface dataset:
Plasmid composition and the chpG gene determine the virulence level of Clavibacter capsici natural isolates in pepper

Abstract The gram‐positive bacterial species Clavibacter capsici causes necrosis and canker in pepper plants. Genomic and functional analyses of C. capsici type strain PF008 have shown that multiple virulence genes exist in its two plasmids. We aimed to identify the key determinants that control the virulence of C. capsici. Pepper leaves inoculated with 54 natural isolates exhibited significant variation in the necrosis. Six isolates showed very low virulence, but their population titres in plants were not significantly different from those of the highly virulent isolates. All six isolates lacked the pCM1Cc plasmid that carries chpG, which has been shown to be required for virulence and encodes a putative serine protease, but two of them, isolates 1,106 and 1,207, had the intact chpG elsewhere in the genome. Genomic analysis of these two isolates revealed that chpG was located in the pCM2Cc plasmid, and two highly homologous regions were present next to the chpG locus. The chpG expression in isolate 1,106 was not induced in plants. Introduction of chpG of the PF008 strain into the six low‐virulence isolates restored their virulence to that of PF008. Our findings indicate that there are at least three different variant groups of C. capsici and that the plasmid composition and the chpG gene are critical for determining the virulence level. Moreover, our findings also indicate that the virulence level of C. capsici does not directly correlate with bacterial titres in plants.
Hepatitis C Virus Entry: An Intriguingly Complex and Highly Regulated Process

Hepatitis C virus (HCV) is a major cause of chronic hepatitis and liver disease worldwide. Its tissue and species tropism are largely defined by the viral entry process that is required for subsequent productive viral infection and establishment of chronic infection. This review provides an overview of the viral and host factors involved in HCV entry into hepatocytes, summarizes our understanding of the molecular mechanisms governing this process and highlights the therapeutic potential of host-targeting entry inhibitors.
U-net-based Deformation Vector Field Estimation for Motion-Compensated 4D-CBCT Reconstruction.

PURPOSE For four-dimensional cone-beam computed tomography (4D-CBCT), its image quality is usually degraded by insufficient projections at each respiratory phase after phase-sorting. Recently, we developed a simultaneous motion estimation and image reconstruction (SMEIR) technique, which can improve lung 4D-CBCT reconstruction quality by incorporating an inter-phase motion model generated as deformation-vector-fields (DVFs). SMEIR uses an intensity-driven 2D-3D deformation technique to estimate these DVFs by intensity-matching 2D projections. However, 2D-3D deformation may fail to generate accurate intra-lung DVFs, since the motion of intricate, small lung structures only leads to subtle intensity variations on 2D projections that are insufficient to drive accurate DVF optimization. This study is to develop convolutional neural network (CNN)-based methods to fine-tune the 2D-3D deformation DVFs to improve the efficiency and accuracy of 4D-CBCT reconstruction. METHODS We built two U-net based architectures for this study. The first architecture (U-net-3C) uses 2D-3D deformation-estimated DVFs (in three cardinal directions) as the input with three channels (3C), and outputs fine-tuned DVFs. For the second architecture (U-net-4C), the reference phase CBCT image reconstructed by SMEIR was added as an additional input channel (4C) to represent patient-specific heterogeneous properties of the lung. The output fine-tuned high-quality DVFs of both models were input again into the SMEIR workflow, as an optimized motion model, to generate the final 4D-CBCT. Both methods were evaluated on 11 lung patient cases, using 5-fold cross-validation. We also reconstructed 4D-CBCTs by the original SMEIR and the SMEIR-Bio (SMEIR with biomechanical modeling) algorithms for comparison. The 4D-CBCT accuracy was quantitatively assessed through metrics including root-mean-square-error (RMSE), universal-quality-index (UQI) and normalized-cross- correlation (NCC). The DVF accuracy was evaluated by manually-tracked lung landmarks. We also evaluated our proposed methods on SPARE challenge dataset based on reconstructed 4D-CBCT quality using metrics above. RESULTS The average (± standard deviation) residual DVF errors of SMEIR-U-net-3C, SMEIR-U-net-4C, SMEIR- Bio and SMEIR were 3.88 ± 3.12 mm, 3.71 ± 2.90 mm, 3.75 ± 3.40 mm, and 5.73 ± 4.61 mm, respectively. The SMEIR-U-net-3C and SMEIR-U-net-4C generated images of generally improved RMSE, UQI and NCC as compared to the other methods. Compared with SMERI-U-net-3C, SMEIR-U-net-4C has slightly higher 4D-CBCT reconstruction and DVF estimation accuracy. For SPARE dataset, the UQI for SMEIR-U-net-3C, SMEIR-U-net-4C, SMEIR-Bio and SMEIR were 0.96, 0.97, 0.96 and 0.94. CONCLUSION The CNN-based models can achieve fast (~10 s) and accurate DVF fine-tuning to improve the efficiency and accuracy of 4D-CBCT reconstruction.
Kinetics of the conformational cycle of Hsp70 reveals the importance of the dynamic and heterogeneous nature of Hsp70 for its function

Significance Heat shock protein 70 kDa (Hsp70) plays a central role in maintaining protein homeostasis. It cooperates with cochaperone Hsp40, which stimulates Hsp70 ATPase activity and presents protein substrates to Hsp70 to assist refolding. The mechanism by which Hsp40 regulates the intramolecular and intermolecular changes of Hsp70 is still largely unknown. Here, by bulk and single-molecule FRET, we report the conformational dynamics of Hsp70 and its regulation by Hsp40 as well as the kinetics of the multistep Hsp70–Hsp40 functional cycle. We show that Hsp40 modulates the conformations of ATP-bound Hsp70 to a domain-undocked ATPase-stimulated state, and facilitates the formation of a heterotetrameric Hsp70–Hsp40 complex. Our findings provide insights into the functional mechanism of this core chaperone machinery. Hsp70 is a conserved molecular chaperone that plays an indispensable role in regulating protein folding, translocation, and degradation. The conformational dynamics of Hsp70 and its regulation by cochaperones are vital to its function. Using bulk and single-molecule fluorescence resonance energy transfer (smFRET) techniques, we studied the interdomain conformational distribution of human stress-inducible Hsp70A1 and the kinetics of conformational changes induced by nucleotide and the Hsp40 cochaperone Hdj1. We found that the conformations between and within the nucleotide- and substrate-binding domains show heterogeneity. The conformational distribution in the ATP-bound state can be induced by Hdj1 to form an “ADP-like” undocked conformation, which is an ATPase-stimulated state. Kinetic measurements indicate that Hdj1 binds to monomeric Hsp70 as the first step, then induces undocking of the two domains and closing of the substrate-binding cleft. Dimeric Hdj1 then facilitates dimerization of Hsp70 and formation of a heterotetrameric Hsp70–Hsp40 complex. Our results provide a kinetic view of the conformational cycle of Hsp70 and reveal the importance of the dynamic nature of Hsp70 for its function.
Reactive dicarbonyl compounds cause Calcitonin Gene-Related Peptide release and synergize with inflammatory conditions in mouse skin and peritoneum

The plasmas of diabetic or uremic patients and of those receiving peritoneal dialysis treatment have increased levels of the glucose-derived dicarbonyl metabolites like methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG). The elevated dicarbonyl levels can contribute to the development of painful neuropathies. Here, we used stimulated immunoreactive Calcitonin Gene–Related Peptide (iCGRP) release as a measure of nociceptor activation, and we found that each dicarbonyl metabolite induces a concentration-, TRPA1-, and Ca2+-dependent iCGRP release. MGO, GO, and 3-DG were about equally potent in the millimolar range. We hypothesized that another dicarbonyl, 3,4-dideoxyglucosone-3-ene (3,4-DGE), which is present in peritoneal dialysis (PD) solutions after heat sterilization, activates nociceptors. We also showed that at body temperatures 3,4-DGE is formed from 3-DG and that concentrations of 3,4-DGE in the micromolar range effectively induced iCGRP release from isolated murine skin. In a novel preparation of the isolated parietal peritoneum PD fluid or 3,4-DGE alone, at concentrations found in PD solutions, stimulated iCGRP release. We also tested whether inflammatory tissue conditions synergize with dicarbonyls to induce iCGRP release from isolated skin. Application of MGO together with bradykinin or prostaglandin E2 resulted in an overadditive effect on iCGRP release, whereas MGO applied at a pH of 5.2 resulted in reduced release, probably due to an MGO-mediated inhibition of transient receptor potential (TRP) V1 receptors. These results indicate that several reactive dicarbonyls activate nociceptors and potentiate inflammatory mediators. Our findings underline the roles of dicarbonyls and TRPA1 receptors in causing pain during diabetes or renal disease.
Development of a Sensitive and Reliable UHPLC-MS/MS Method for the Determination of Multiple Urinary Biomarkers of Mycotoxin Exposure

A variety of mycotoxins from different sources frequently contaminate farm products, presenting a potential toxicological concern for animals and human. Mycotoxin exposure has been the focus of attention for governments around the world. To date, biomarkers are used to monitor mycotoxin exposure and promote new understanding of their role in chronic diseases. The goal of this research was to develop and validate a sensitive UHPLC-MS/MS method using isotopically-labeled internal standards suitable for accurate determination of 18 mycotoxin biomarkers, including fumonisins, ochratoxins, Alternaria and emerging Fusarium mycotoxins (fumonisin B1, B2, and B3, hydrolyzed fumonisin B1 and B2, ochratoxin A, B, and alpha, alternariol, alternariol monomethyl ether, altenuene, tentoxin, tenuazonic acid, beauvericin, enniatin A, A1, B, and B1) in human urine. After enzymatic digestion with β-glucuronidase, human urine samples were cleaned up using HLB solid phase extraction cartridges prior to instrument analysis. The multi-mycotoxin and analyte-specific method was validated in-house, providing satisfactory results. The method provided good linearity in the tested concentration range (from LOQ up to 25–500 ng/mL for different analytes), with R2 from 0.997 to 0.999. The limits of quantitation varied from 0.0002 to 0.5 ng/mL for all analytes in urine. The recoveries for spiked samples were between 74.0% and 133%, with intra-day precision of 0.5%–8.7% and inter-day precision of 2.4%–13.4%. This method was applied to 60 urine samples collected from healthy volunteers in Beijing, and 10 biomarkers were found. At least one biomarker was found in all but one of the samples. The high sensitivity and accuracy of this method make it practical for human biomonitoring and mycotoxin exposure assessment.
Helicobacter pylori CagA oncoprotein interacts with SHIP2 to increase its delivery into gastric epithelial cells

Chronic infection with Helicobacter pylori cagA‐positive strains is causally associated with the development of gastric diseases, most notably gastric cancer. The cagA‐encoded CagA protein, which is injected into gastric epithelial cells by bacterial type IV secretion, undergoes tyrosine phosphorylation at the Glu‐Pro‐Ile‐Tyr‐Ala (EPIYA) segments (EPIYA‐A, EPIYA‐B, EPIYA‐C, and EPIYA‐D), which are present in various numbers and combinations in its C‐terminal polymorphic region, thereby enabling CagA to promiscuously interact with SH2 domain‐containing host cell proteins, including the prooncogenic SH2 domain‐containing protein tyrosine phosphatase 2 (SHP2). Perturbation of host protein functions by aberrant complex formation with CagA has been considered to contribute to the development of gastric cancer. Here we show that SHIP2, an SH2 domain‐containing phosphatidylinositol 5′‐phosphatase, is a hitherto undiscovered CagA‐binding host protein. Similar to SHP2, SHIP2 binds to the Western CagA‐specific EPIYA‐C segment or East Asian CagA‐specific EPIYA‐D segment through the SH2 domain in a tyrosine phosphorylation‐dependent manner. In contrast to the case of SHP2, however, SHIP2 binds more strongly to EPIYA‐C than to EPIYA‐D. Interaction with CagA tethers SHIP2 to the plasma membrane, where it mediates production of phosphatidylinositol 3,4‐diphosphate [PI(3,4)P2]. The CagA‐SHIP2 interaction also potentiates the morphogenetic activity of CagA, which is caused by CagA‐deregulated SHP2. This study indicates that initially delivered CagA interacts with SHIP2 and thereby strengthens H. pylori‐host cell attachment by altering membrane phosphatidylinositol compositions, which potentiates subsequent delivery of CagA that binds to and thereby deregulates the prooncogenic phosphatase SHP2.
Results from a cluster-randomized trial to evaluate a microfinance and peer health leadership intervention to prevent HIV and intimate partner violence among social networks of Tanzanian men

Despite calls to engage men in HIV and intimate partner violence (IPV) prevention efforts, effective approaches to reach and engage men in low-resource, high-HIV prevalence settings are limited. We identified and engaged social networks of mostly young men in a study designed to evaluate the efficacy of a combined microfinance and peer health leadership intervention to prevent HIV and IPV. We conducted a cluster-randomized trial among 60 social networks locally referred to as “camps” within Dar es Salaam, Tanzania. Camps were randomly assigned (1:1) to a microfinance and peer health leadership intervention or a control condition that received a brief delayed intervention after the study’s conclusion. Allocation was not masked to participants or researchers. Behavioral assessments were conducted at baseline and 30-months post-intervention launch, with biological samples drawn at 30-months to test for sexually-transmitted infections (STIs). Primary outcomes included prevalence of STIs and past-year IPV perpetration. Secondary outcomes included STI sexual risk behaviors and past-year HIV testing. Proximal intervention targets included inequitable gender norm attitudes and hope. A modified Poisson regression approach was used to estimate intention-to-treat intervention effects on outcomes assessed at the 30-month follow-up. We enrolled 1,258 men within 60 camps. Of these men, 1,029 (81.8%) completed the 30-month follow-up. There were no differences by condition in STI prevalence, IPV perpetration, or sexual risk behaviors at the 30-month follow-up. Intervention participants reported greater levels of past-year HIV testing, controlling for baseline testing (aRR 1.13 95% CI 1.005–1.28). They also reported significantly lower levels of inequitable gender norm attitudes (adjusted effect -0.11, 95% CI -0.21–0.003). We successfully engaged and retained social networks of men in this multilevel intervention study. While we did not see an effect on the primary outcomes, our intervention successfully improved HIV testing and reduced inequitable gender norm attitudes.
Citrate and Polyvinylpyrrolidone Stabilized Silver Nanoparticles as Selective Colorimetric Sensor for Aluminum (III) Ions in Real Water Samples

The use of silver nanoparticles stabilized with citrate and polyvinylpyrrolidone as a sensor for aluminum ions determination is proposed in this paper. These non-functionalized and specific nanoparticles provide a highly selective and sensitive detection system for aluminum in acidic solutions. The synthesized nanoparticles were characterized by transmission electron microscopy. Surface plasmon band deconvolution analysis was applied to study the interaction between silver nanoparticles and aluminum ions in solution. The interaction band in the UV-visible region was used as an analytical signal for quantitation purposes. The proposed detection system offers an effective AND wide linearity range (0.1–103 nM), specificity for Al(III) in THE presence of other metallic ions in solution, as well as high sensitivity (limit of detection = 40.5 nM). The proposed silver-nanoparticles-based sensor WAS successfully used for detecting Al(III) in real water samples.
Phytohormone dynamics in developing endosperm influence rice grain shape and quality.

Hormones are important signaling molecules regulating developmental processes and responses to environmental stimuli in higher plants. Rice endosperm, the portion of the seed surrounding the embryo, is the main determinant of rice grain shape and yield; however, the dynamics and exact functions of phytohormones in developing endosperm remain elusive. Through a systemic study including transcriptome analysis, hormone measurement, and transgene-based endosperm-specific expression of phytohormone biosynthetic enzymes, we demonstrated that dynamic phytohormone levels play crucial roles in the developing rice endosperm, particularly in regard to grain shape and quality. We detected diverse, differential, and dramatically changing expression patterns of genes related to hormone biosynthesis and signaling during endosperm development, especially at early developmental stages. Liquid chromatography measurements confirmed the dynamic accumulation of hormones in developing endosperm. Further transgenic analysis performed on plants expressing hormone biosynthesis genes driven by an endosperm-specific promoter revealed differential effects of the hormones, especially auxin and brassinosteroids, in regulating grain shape and quality. Our studies help elucidate the distinct roles of hormones in developing endosperm and provide novel and useful tools for influencing crop seed shape and yield. This article is protected by copyright. All rights reserved.
Adaptation of the “active communication education” programme into Spanish for older adults with hearing loss

Abstract Objective: To adapt the Active Communication Education (ACE) programme into Spanish. In addition, this study aimed at determining the effects of the adapted ACE programme on the social/emotional impacts of hearing loss and hearing functioning in a group of older adults with hearing loss who do not wear hearing aids. Design: This was an exploratory cohort study. Study group participants received the newly adapted ACE programme and control group participants received a cognitive stimulation programme. The Shortened Hearing Handicap Inventory for the Elderly in Spanish (HHIE-S) and the Spanish version of the Amsterdam Inventory for Auditory Disability and Handicap (S-AIADH) were carried out before and after each programme. Study sample: Sixty-six older adults with hearing loss and who did not wear hearing aids were randomly assigned to either an ACE group (n = 30) or a cognitive stimulation group (n = 36). Results: Participants who received the ACE programme showed a significantly larger improvement for the S-AIADH than did the cognitive stimulation group participants. Conclusions: The ACE programme has been adapted into Spanish for use with Chilean older adults with hearing loss. The results show that older adults report better functioning in listening situations after attending the sessions of the adapted ACE programme.
Forecasts of mortality and economic losses from poor water and sanitation in sub-Saharan Africa

This paper presents country-level estimates of water, sanitation and hygiene (WASH)-related mortality and the economic losses associated with poor access to water and sanitation infrastructure in sub-Saharan Africa (SSA) from 1990 to 2050. We examine the extent to which the changes that accompany economic growth will “solve” water and sanitation problems in SSA and, if so, how long it will take. Our simulations suggest that WASH-related mortality will continue to differ markedly across countries in sub-Saharan Africa. In many countries, expected economic growth alone will not be sufficient to eliminate WASH-related mortality or eliminate the economic losses associated with poor access to water and sanitation infrastructure by 2050. In other countries, WASH-related mortality will sharply decline, although the economic losses associated with the time spent collecting water are forecast to persist. Overall, our findings suggest that in a subset of countries in sub-Saharan Africa (e.g., Angola, Niger, Sierra Leone, Chad and several others), WASH-related investments will remain a priority for decades and require a long-term, sustained effort from both the international community and national governments.
Fucoidans: Downstream Processes and Recent Applications

Fucoidans are multifunctional marine macromolecules that are subjected to numerous and various downstream processes during their production. These processes were considered the most important abiotic factors affecting fucoidan chemical skeletons, quality, physicochemical properties, biological properties and industrial applications. Since a universal protocol for fucoidans production has not been established yet, all the currently used processes were presented and justified. The current article complements our previous articles in the fucoidans field, provides an updated overview regarding the different downstream processes, including pre-treatment, extraction, purification and enzymatic modification processes, and shows the recent non-traditional applications of fucoidans in relation to their characters.
Confirmation of 123I-FP-CIT SPECT Quantification Methods in Dementia with Lewy Bodies and Other Neurodegenerative Disorders

Our rationale was to conduct a retrospective study comparing 3 123I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (123I-FP-CIT) SPECT quantitative methods in patients with neurodegenerative syndromes as referenced to neuropathologic findings. Methods: 123I-FP-CIT-SPECT and neuropathologic findings among patients with neurodegenerative syndromes from the Mayo Alzheimer Disease Research Center and Mayo Clinic Study of Aging were examined. Three 123I-FP-CIT SPECT quantitative assessment methods—MIMneuro, DaTQUANT, and manual region-of-interest creation on a workstation—were compared with neuropathologic findings describing the presence or absence of Lewy body disease (LBD). Striatum-to-background ratios (SBRs) generated by DaTQUANT were compared with the calculated SBRs of the manual method and MIMneuro. The left and right SBRs for caudate, putamen, and striatum were evaluated with the manual method. For DaTQUANT and MIMneuro, the left, right, total, and average SBRs and z scores for whole striatum, caudate, putamen, anterior putamen, and posterior putamen were calculated. Results: The cohort included 24 patients (20 [83%] male, mean age for all patients at death, 75.4 ± 10.0 y). The antemortem clinical diagnoses were Alzheimer disease dementia (n = 6), probable dementia with Lewy bodies (n = 12), mixed Alzheimer disease dementia and probable dementia with Lewy bodies (n = 1), Parkinson disease with mild cognitive impairment (n = 2), corticobasal syndrome (n = 1), idiopathic rapid-eye-movement sleep behavior disorder (n = 1), and behavioral-variant frontotemporal dementia (n = 1). Seventeen (71%) had LBD. All 3 123I-FP-CIT SPECT quantitative methods had an area under the receiver-operating-characteristics curve ranging from more than 0.93 to up to 1.000 (P < 0.001) and showed excellent discrimination between LBD and non-LBD patients in each region assessed (P < 0.001). There was no significant difference between the accuracy of the regions in discriminating the 2 groups, with good discrimination for both caudate and putamen. Conclusion: All 3 123I-FP-CIT SPECT quantitative methods showed excellent discrimination between LBD and non-LBD patients in each region assessed, using both SBRs and z scores.