Miracle-dz/UniFAR-FTUs huggingface dataset:
The root-knot nematode effector MiEFF18 interacts with the plant core spliceosomal protein SmD1 required for giant cell formation.

The root-knot nematode Meloidogyne incognita secretes specific effectors (MiEFF) and induces the redifferentiation of plant root cells into enlarged multinucleate feeding "giant cells" essential for nematode development. Immunolocalisations revealed the presence of the MiEFF18 protein in the salivary glands of M. incognita juveniles. In planta, MiEFF18 localizes to the nuclei of giant cells demonstrating its secretion during plant-nematode interactions. A yeast two-hybrid approach identified the nuclear ribonucleoprotein SmD1 as a MiEFF18 partner in tomato and Arabidopsis. SmD1 is an essential component of the spliceosome, a complex involved in pre-mRNA splicing and alternative splicing. RNA-seq analyses of Arabidopsis roots ectopically expressing MiEFF18 or partially impaired in SmD1 function (smd1b mutant) revealed the contribution of the effector and its target to alternative splicing and proteome diversity. The comparison with Arabidopsis galls data showed that MiEFF18 modifies the expression of genes important for giant cells ontogenesis, indicating that MiEFF18 modulates SmD1 functions to facilitate giant cell formation. Finally, Arabidopsis smd1b mutants exhibited less susceptibility to M. incognita infection, and the giant cells formed on these mutants displayed developmental defects, suggesting that SmD1 plays an important role in the formation of giant cells and is required for successful nematode infection.
Bioanalytical Assay Development and Validation for the Pharmacokinetic Study of GMC1, a Novel FKBP52 Co-chaperone Inhibitor for Castration Resistant Prostate Cancer

Background: GMC1 (2-(1H-benzimidazol-2-ylsulfanyl)-N-[(Z)-(4-methoxyphenyl) methylideneamino] acetamide) effectively inhibits androgen receptor function by binding directly to FKBP52. This is a novel mechanism for the treatment of castration resistant prostate cancer (CRPC). Methods: an LC-MS/MS method was developed and validated to quantify GMC1 in plasma and urine from pharmacokinetics studies in rats. An ultra-high-performance liquid chromatography (UHPLC) system equipped with a Waters XTerra MS C18 column was used for chromatographic separation by gradient elution with 0.1% (v/v) formic acid in water and methanol. A Sciex 4000 QTRAP® mass spectrometer was used for analysis by multiple reaction monitoring (MRM) in positive mode; the specific ions [M+H]+ m/z 340.995 → m/z 191.000 and [M+H]+ m/z 266.013 → m/z 234.000 were monitored for GMC1 and internal standard (albendazole), respectively. Results: GMC1 and albendazole had retention times of 1.68 and 1.66 min, respectively. The calibration curves for the determination of GMC1 in rat plasma and urine were linear from 1–1000 ng/mL. The LC-MS/MS method was validated with intra- and inter-day accuracy and precision within the 15% acceptance limit. The extraction recovery values of GMC1 from rat plasma and urine were greater than 95.0 ± 2.1% and 97.6 ± 4.6%, respectively, with no significant interfering matrix effect. GMC1 is stable under expected sample handling, storage, preparation and LC-MS/MS analysis conditions. Conclusions: Pharmacokinetic evaluation of GMC1 revealed that the molecule has a biexponential disposition in rats, is distributed rapidly and extensively, has a long elimination half-life, and appears to be eliminated primarily by first order kinetics.
Protective Vaccination Reshapes Hepatic Response to Blood-Stage Malaria of Genes Preferentially Expressed by NK Cells

The role of natural killer (NK) cells in the liver as first-line post infectionem (p.i.) effectors against blood-stage malaria and their responsiveness to protective vaccination is poorly understood. Here, we investigate the effect of vaccination on NK cell-associated genes induced in the liver by blood-stage malaria of Plasmodium chabaudi. Female Balb/c mice were vaccinated at weeks 3 and 1 before being infected with 106 P. chabaudi-parasitized erythrocytes. Genes preferentially expressed by NK cells were investigated in livers of vaccination-protected and non-protected mice on days 0, 1, 4, 8, and 11 p.i. using microarrays, qRT-PCR, and chromosome landscape analysis. Blood-stage malaria induces expression of specific genes in the liver at different phases of infection, i.e., Itga1 in expanding liver-resident NK (lrNK) cells, Itga2 in immigrating conventional NK (cNK) cells; Eomes and Tbx21 encoding transcription factors; Ncr1, Tnfsf10, Prf1, Gzma, Gzmb, Gzmc, Gzmm, and Gzmk encoding cytolytic effectors; natural killer gene complex (NKC)-localized genes encoding the NK cell receptors KLRG1, KLRK1, KLRAs1, 2, 5, 7, KLRD1, KLRC1, KLRC3, as well as the three receptors KLRB1A, KLRB1C, KLRB1F and their potential ligands CLEC2D and CLEC2I. Vaccination enhances this malaria-induced expression of genes, but impairs Gzmm expression, accelerates decline of Tnfsf10 and Clec2d expression, whereas it accelerates increased expression of Clec2i, taking a very similar time course as that of genes encoding plasma membrane proteins of erythroblasts, whose malaria-induced extramedullary generation in the liver is known to be accelerated by vaccination. Collectively, vaccination reshapes the response of the liver NK cell compartment to blood-stage malaria. Particularly, the malaria-induced expansion of lrNK cells peaking on day 4 p.i. is highly significantly (p < 0.0001) reduced by enhanced immigration of peripheral cNK cells, and KLRB1F:CLEC2I interactions between NK cells and erythroid cells facilitate extramedullary erythroblastosis in the liver, thus critically contributing to vaccination-induced survival of otherwise lethal blood-stage malaria of P. chabaudi.
Arbuscular mycorrhizal fungi enhance mineralization of organic phosphorus (P) by carrying bacteria along their extraradical hyphae.

Arbuscular mycorrhizal (AM) fungi gain access to nutrient patches outside the rhizosphere by producing an extensive network of fine hyphae. Here, we focused on establishing the mechanism by which AM fungal hyphae reach discrete organic patches with a cohort of functional bacteria transported in a biofilm on their surface. We investigated the mechanisms and impact of the translocation of phosphate solubilizing bacteria (PSB) along AM fungal hyphae in bespoke microcosms. An in vitro culture experiment was also conducted to determine the direct impact of hyphal exudates of AM fungi upon the growth of PSB. The extraradical hyphae of AM fungi can transport PSB to organic phosphorus (P) patches and enhance organic P mineralization both under in vitro culture and soil conditions. Bacteria move in a thick water film formed around fungal hyphae. However, the bacteria cannot be transferred to the organic P patch without an energy source in the form of hyphal exudates. Our results could be harnessed to better manage plant microbe interactions and improve the ability of biological inocula involving AM fungi and bacteria to enhance the sustainability of agricultural crops in P limited conditions.
A Global Interconnected Observer for Attitude and Gyro Bias Estimation with Vector Measurements

This paper proposes a novel interconnected observer to get good estimates of attitude and gyro bias from high-noise vector measurements. The observer is derived based on the theory of nonlinear and linear cascade systems, and its error dynamics have the properties of global exponential stability and robustness to bounded noise. These properties ensure the convergence and boundedness of the attitude and gyro bias estimation errors. To obtain higher estimation accuracy, an approach to calculate time-varying gains for the proposed auxiliary observer is designed under the premise of considering noise terms in the rate gyro and vector sensors. The simulation results show that when the vector sensors’ outputs contain high-level noise, the proposed observer with time-varying gains yields better performance in both the transient and steady-state phases.
The Role of Toll-Like Receptors in Retroviral Infection

Toll-like receptors (TLRs) are key pathogen sensing receptors that respond to diverse microbial ligands, and trigger both innate and adaptive immune responses to infection. Since their discovery, a growing body of evidence has pointed to an important role for TLRs in retroviral infection and pathogenesis. These data suggest that multiple TLRs contribute to the anti-retroviral response, and that TLR engagement by retroviruses can have complex and divergent outcomes for infection. Despite this progress, numerous questions remain about the role of TLRs in retroviral infection. In this review, I summarize existing evidence for TLR-retrovirus interactions and the functional roles these receptors play in immunity and pathogenesis, with particular focus on human immunodeficiency virus (HIV).
The seed germination spectrum of alpine plants: a global meta-analysis.

Assumptions about the germination ecology of alpine plants are presently based on individual species and local studies. A current challenge is to synthesize, at the global level, the alpine seed ecological spectrum. We performed a meta-analysis of primary data from laboratory experiments conducted across four continents (excluding the tropics) and 661 species, to estimate the influence of six environmental cues on germination proportion, mean germination time and germination synchrony; accounting for possible effects of seed morphology (mass, embryo:seed ratio) and phylogeny. Most alpine plants show physiological seed dormancy, a strong need for cold stratification, warm-cued germination and positive germination responses to light and alternating temperatures. Species restricted to the alpine belt have a higher preference for warm temperatures and a stronger response to cold stratification than species whose distribution extends also below the treeline. Seed mass, embryo size and phylogeny have strong constraining effects on germination responses to the environment. Globally, overwintering and warm-cued germination are key drivers of germination in alpine habitats. The interplay between germination physiology and seed morphological traits further reflects pressures to avoid frost or drought stress. Our results indicate the convergence, at the global level, of the seed germination spectrum of alpine species.
Bile Ductal Transcriptome Identifies Key Pathways and Hub Genes in Clonorchis sinensis-Infected Sprague-Dawley Rats

Clonorchis sinensis is a food-borne trematode that infects more than 15 million people. The liver fluke causes clonorchiasis and chronical cholangitis, and promotes cholangiocarcinoma. The underlying molecular pathogenesis occurring in the bile duct by the infection is little known. In this study, transcriptome profile in the bile ducts infected with C. sinensis were analyzed using microarray methods. Differentially expressed genes (DEGs) were 1,563 and 1,457 at 2 and 4 weeks after infection. Majority of the DEGs were temporally dysregulated at 2 weeks, but 519 DEGs showed monotonically changing expression patterns that formed seven distinct expression profiles. Protein-protein interaction (PPI) analysis of the DEG products revealed 5 sub-networks and 10 key hub proteins while weighted co-expression network analysis (WGCNA)-derived gene-gene interaction exhibited 16 co-expression modules and 13 key hub genes. The DEGs were significantly enriched in 16 Kyoto Encyclopedia of Genes and Genomes pathways, which were related to original systems, cellular process, environmental information processing, and human diseases. This study uncovered a global picture of gene expression profiles in the bile ducts infected with C. sinensis, and provided a set of potent predictive biomarkers for early diagnosis of clonorchiasis.
Effect of Cadmium Toxicity on Growth, Oxidative Damage, Antioxidant Defense System and Cadmium Accumulation in Two Sorghum Cultivars

Heavy metal stress is a leading environmental issue reducing crop growth and productivity, particularly in arid and semi-arid agro-ecological zones. Cadmium (Cd), a non-redox heavy metal, can indirectly increase the production of reactive oxygen species (ROS), inducing cell death. A pot experiment was conducted to investigate the effects of different concentrations of Cd (0, 5, 25, 50, 100 µM) on physiological and biochemical parameters in two sorghum (Sorghum bicolor L.) cultivars: JS-2002 and Chakwal Sorghum. The results showed that various concentrations of Cd significantly increased the Cd uptake in both cultivars; however, the uptake was higher in JS-2002 compared to Chakwal Sorghum in leaf, stem and root. Regardless of the cultivars, there was a higher accumulation of the Cd in roots than in shoots. The Cd stress significantly reduced the growth and increased the electrolyte leakage (EL), hydrogen peroxide (H2O2) concentration and malondialdehyde (MDA) content in both cultivars, but the Chakwal Sorghum showed more pronounced oxidative damage than the JS-2002, as reflected by higher H2O2, MDA and EL. Moreover, Cd stress, particularly 50 µM and 100 µM, decreased the activity of different antioxidant enzymes, including superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT). However, the JS-2002 exhibited higher SOD, POD and CAT activities than the Chakwal Sorghum under different Cd-levels. These findings revealed that JS-2002 had a stronger Cd enrichment capacity and also exhibited a better tolerance to Cd stress due to its efficient antioxidant defense system than Chakwal Sorghum. The present study provides the available information about Cd enrichment and tolerance in S. bicolor, which is used as an important agricultural crop for livestock feed in arid and semi-arid regions.
Long‐term plant community trajectories suggest divergent responses of native and non‐native perennials and annuals to vegetation removal and seeding treatments

Land managers frequently apply vegetation removal and seeding treatments to restore ecosystem function following woody plant encroachment, invasive species spread, and wildfire. However, the long‐term outcome of these treatments is unclear due to a lack of widespread monitoring. We quantified how vegetation removal (via wildfire or management) with or without seeding and environmental conditions related to plant community composition change over time in 491 sites across the intermountain western United States. Most community metrics took over 10 years to reach baseline conditions posttreatment, with the slowest recovery observed for native perennial cover. Total cover was initially higher in sites with seeding after vegetation removal than sites with vegetation removal alone, but increased faster in sites with vegetation removal only. Seeding after vegetation removal was associated with rapidly increasing non‐native perennial cover and decreasing non‐native annual cover. Native perennial cover increased in vegetation removal sites irrespective of seeding and was suppressed by increasing non‐native perennial cover. Seeding was associated with higher non‐native richness across the monitoring period as well as initially higher, then declining, total and native species richness. Several cover and richness recovery metrics were positively associated with mean annual precipitation and negatively associated with mean annual temperature, whereas relationships with weather extremes depended on the lag time and season. Our results suggest that key plant groups, such as native perennials and non‐native annuals, respond to restoration treatments at divergent timescales and with different sensitivities to climate and weather variation.
Morfometría de semillas en la cactácea amenazada de extinción Astrophytum myriostigma Lemaire

Se presenta un estudio morfometrico y microestructural en semillas de una poblacion de la cactacea amenazada Astrophytum myriostigma Lem. , removida en su totalidad en el sitio por saqueo. Se incluyen resultados que separan tamanos de semillas y embriones (grandes y pequenos) asi como promedios para ambos. Se realizo una descripcion de caracteristicas en la semilla obtenidas mediante estereoscopia. Se incluye una descripcion detallada de la forma y color, asi como microestructural del funiculo, capa funicular y otras estructuras que le acompanan
Outpatient surgical management of non‐melanoma skin cancers of the head and neck in a regional centre: an analysis of costs and outcomes

Non‐melanoma skin cancer is the most commonly diagnosed malignancy in Australia. Lesions of the head and neck are often outside the scope of primary care providers. The challenges of cancer care in regional Australia necessitate careful resource planning. This study presents an outpatient model that minimizes health service cost with local general practitioner follow‐up.
Boosting template-based SSVEP decoding by cross-domain transfer learning

Objective. This study aims to establish a generalized transfer-learning framework for boosting the performance of steady-state visual evoked potential (SSVEP)-based brain–computer interfaces (BCIs) by leveraging cross-domain data transferring. Approach. We enhanced the state-of-the-art template-based SSVEP decoding through incorporating a least-squares transformation (LST)-based transfer learning to leverage calibration data across multiple domains (sessions, subjects, and electroencephalogram montages). Main results. Study results verified the efficacy of LST in obviating the variability of SSVEPs when transferring existing data across domains. Furthermore, the LST-based method achieved significantly higher SSVEP-decoding accuracy than the standard task-related component analysis (TRCA)-based method and the non-LST naive transfer-learning method. Significance. This study demonstrated the capability of the LST-based transfer learning to leverage existing data across subjects and/or devices with an in-depth investigation of its rationale and behavior in various circumstances. The proposed framework significantly improved the SSVEP decoding accuracy over the standard TRCA approach when calibration data are limited. Its performance in calibration reduction could facilitate plug-and-play SSVEP-based BCIs and further practical applications.
What Type of Patients Did PARAGON-HF Select? Insights from a Real-World Prospective Cohort of Patients with Heart Failure and Preserved Ejection Fraction

The PARAGON-HF clinical trial suggested that sacubitril/valsartan may become a treatment option for particular subgroups of patients with heart failure and preserved ejection fraction (HFpEF). However, the proportion of real-world HFpEF patients who are theoretically superimposable with the PARAGON-HF population is yet unknown. The present study was performed to define the proportion of real-world PARAGON-HF-like patients and to describe their clinical characteristics and long-term prognosis in comparison with those who would not meet PARAGON-HF criteria. We systematically applied PARAGON-HF inclusion and exclusion criteria to a total of 427 HFpEF patients who have been participating in a prospective national registry between December 2010 and December 2019. In total, only 170 (39.8%) registry patients were theoretically eligible for PARAGON-HF. Patients not meeting inclusion criteria (41.0%) were less impaired with respect to exercise capacity (median 6-min walk distance: 385 m (IQR: 300–450) versus 323 m (IQR: 240–383); p < 0.001) had lower pulmonary pressures (mean pulmonary artery pressure (mPAP): 31.2 mmHg, standard deviation (SD): ±10.2 versus 32.8 mmHg, SD: ±9.7; p < 0.001) and better outcomes (log-rank: p < 0.001) as compared to the PARAGON-like cohort. However, patients theoretically excluded from the trial (19.2%) were those with most advanced heart failure symptoms (median 6-min walk test: 252 m (IQR: 165–387); p < 0.001), highest pulmonary pressures (mPAP: 38.2 mmHg, SD: ±12.4; p < 0.001) and worst outcome (log-rank: p = 0.037). We demonstrate here that < 40% of real-world HFpEF patients meet eligibility criteria for PARAGON-HF. We conclude that despite reasons for optimism after PARAGON-HF, a large proportion of HFpEF patients will remain without meaningful treatment options.
Clinical Evaluation of Basal-Bolus Therapy Delivered by the V-Go® Wearable Insulin Delivery Device in Patients with Type 2 Diabetes: A Retrospective Analysis

Insulin therapy is frequently required to achieve glycemic targets (A1c) in type 2 diabetes (T2D); however, clinicians and patients face barriers with the complexities of multiple daily injection regimens. Patch-like wearable insulin devices, such as V-Go, may simplify and optimize this complexity. This study evaluated the change in A1C and insulin total daily dose (TDD) in a suboptimally-controlled (not achieving A1C targets) T2D population after switching to V-Go. A retrospective chart analysis at a diabetes clinic was performed to evaluate change in A1c measurements from baseline (V-Go initiation) to end of study observation. Of the 139 patients enrolled, A1C significantly decreased from baseline (−1.5 ± 1.79%; p < 0.001). Patients prescribed insulin at baseline (n = 122) used significantly less insulin TDD (−8 u/day; p = 0.006). The percentage of patients meeting the target of A1C < 8% increased from 14% at baseline to 48% at study completion (p = 0.008). Patients prescribed a basal-bolus regimen prior to V-Go achieved an A1C reduction of 1.5 ± 2.0% (p < 0.0001) and experienced the greatest reduction in TDD (−24 u/day; p < 0.0001). Thus, patients switching to V-Go from a variety of therapies at baseline experienced reductions in A1C while using less insulin, with a reduction in clinically relevant hypoglycemia, indicating the potential benefit of V-Go in optimizing and simplifying T2D care.
Asymmetric Total Synthesis of Dankasterones A and B and Periconiastone A Through Radical Cyclization.

We describe herein the assembly of the cis -decalin framework through radical cyclization initiated by metal-catalyzed hydrogen atom transfer (MHAT), further applied it in the asymmetric synthesis of dankasterones A and B and periconiastone A. Position-selective C-H oxygenation allowed for installation of the necessary functionality. A radical rearrangement was adopted to create 13(14→8) abeo -8-ergostane skeleton. Interconversion of dankasterone B and periconiastone A was realized through biomimetic intramolecular aldol and retro-aldol reactions. The MHAT-based approach, serves as a new dissection means, is complementary to the conventional ways to establish cis -decalin framework.
Tracking Quantitative Characteristics of Cutting Maneuvers with Wearable Movement Sensors during Competitive Women’s Ultimate Frisbee Games

(1) Ultimate frisbee involves frequent cutting motions, which have a high risk of anterior cruciate ligament (ACL) injury, especially for female players. This study investigated the in-game cutting maneuvers performed by female ultimate frisbee athletes to understand the movements that could put them at risk of ACL injury. (2) Lower-body kinematics and movement around the field were reconstructed from wearable lower-body inertial sensors worn by 12 female players during 16 league-sanctioned ultimate frisbee games. (3) 422 cuts were identified from speed and direction change criteria. The mean cut had approach speed of 3.4 m/s, approach acceleration of 3.1 m/s2, cut angle of 94 degrees, and ground-contact knee flexion of 34 degrees. Shallow cuts from 30 to 90 degrees were most common. Speed and acceleration did not change based on cut angle. Players on more competitive teams had higher speed and acceleration and reduced knee flexion during cutting. (4) This study demonstrates that a lower-body set of wearable inertial sensors can successfully track an athlete’s motion during real games, producing detailed biomechanical metrics of behavior and performance. These in-game measurements can be used to specify controlled cutting movements in future laboratory studies. These studies should prioritize higher-level players since they may exhibit higher-risk cutting behavior.