Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular mechanisms associated with the resistance of Rhizoctonia solani AG-4 isolates to the succinate dehydrogenase inhibitor, thifluzamide.

Thifluzamide, a succinate dehydrogenase (SDH) inhibitor, possesses high activity against Rhizoctonia. In this study, 144 R. solani AG-4 (4HGI, 4HGII, and 4HGIII) isolates, the predominate pathogen associated with sugar beet seedling damping-off, were demonstrated to be sensitive to thifluzamide with a calculated mean median effective concentration of 0.0682 ± 0.0025 μg/mL. Thifluzamide-resistant isolates were generated using fungicide-amended media, resulting in four AG-4HGI isolates and eight AG-4HGII isolates with stable resistance and almost no loss in fitness. Evaluation of cross-resistance of the twelve thifluzamide-resistant isolates and their corresponding parental-sensitive isolates revealed a moderately positive correlation between thifluzamide resistance and the level of resistance to eight other fungicides from three groups, the exception being fludioxonil. An active efflux of fungicide through ATP-binding cassette and major facilitator superfamily transporters was found to be correlated to the resistance of R. solani AG-4HGII isolates to thifluzamide based on RNA-sequencing and quantitative reverse transcription-PCR analyses. Sequence analysis of sdhA, sdhB, sdhC, and sdhD revealed replacement of isoleucine by phenylalanine at position 61 in SDHC in nine of the twelve generated thifluzamide-resistant isolates. No other mutations were found in any of the other genes. Collectively, the data indicate that the active efflux of fungicide and a point mutation in sdhC may contribute to the resistance of R. solani AG-4HGI and AG-4HGII isolates to thifluzamide in vitro. This is the first characterization of the potential molecular mechanism associated with the resistance of R. solani AG-4 isolates to thifluzamide, and provides practical guidance for the use of this fungicide.
Characterizing preclinical sub‐phenotypic models of acute respiratory distress syndrome: An experimental ovine study

The acute respiratory distress syndrome (ARDS) describes a heterogenous population of patients with acute severe respiratory failure. However, contemporary advances have begun to identify distinct sub‐phenotypes that exist within its broader envelope. These sub‐phenotypes have varied outcomes and respond differently to several previously studied interventions. A more precise understanding of their pathobiology and an ability to prospectively identify them, may allow for the development of precision therapies in ARDS. Historically, animal models have played a key role in translational research, although few studies have so far assessed either the ability of animal models to replicate these sub‐phenotypes or investigated the presence of sub‐phenotypes within animal models. Here, in three ovine models of ARDS, using combinations of oleic acid and intravenous, or intratracheal lipopolysaccharide, we investigated the presence of sub‐phenotypes which qualitatively resemble those found in clinical cohorts. Principal Component Analysis and partitional clustering identified two clusters, differentiated by markers of shock, inflammation, and lung injury. This study provides a first exploration of ARDS phenotypes in preclinical models and suggests a methodology for investigating this phenomenon in future studies.
Novel fluconazole-resistant zoonotic yeast isolated from mastitis

Abstract A hospital-based cross-sectional study was conducted during 2018–2019 to decipher the prevalence of yeast mastitis. The results indicated a 19.68% prevalence of clinical mastitis in bovines. Among them, 5.51% of samples revealed yeasts constituting 1.09% overall prevalence. Candida albicans was recorded as a significant fungal agent involved in clinical bovine mastitis. We record the association of Kodamaea ohmeri in clinical bovine mastitis. On proteomic and molecular confirmation, K. ohmeri isolates were re-identified from phenotypically identified Candida isolates associated with bovine mastitis. After conventional identification, the yeast isolates were re-identified by MALDI-TOF MS-based proteomic approaches. The D1/D2 domains of 26S-rRNA gene and 5.8S-internal transcribed spacer (ITS) rDNA regions based molecular phylogenetic analysis identified the isolates as K. ohmeri. The isolates were resistant to fluconazole. This study reports the first systemic study of K. ohmeri isolates recovered from bovine clinical mastitis, utilizing conventional, automated, proteomic, and genomic approaches followed by antifungal susceptibility. The findings suggest K. ohmeri as a potent opportunistic emerging pathogen of veterinary and public health concern, need for accurate identification of fungal agents from mycotic mastitis, and use of validated antifungal susceptibility assay because of developing resistance to antimycotic agents. Our findings suggest judicious use of fluconazole and alternative antifungal agents may be considered in case of an outbreak.
200-m/500-Mbps underwater wireless optical communication system utilizing a sparse nonlinear equalizer with a variable step size generalized orthogonal matching pursuit.

Linear and nonlinear impairments in underwater wireless optical communication (UWOC) systems caused by the limited bandwidth and nonlinearity of devices severely degrade the system performance. In this paper, we propose a sparse Volterra series model-based nonlinear post equalizer with greedy algorithms to mitigate the nonlinear impairments and the inter-symbol interference (ISI) in a UWOC system. A variable step size generalized orthogonal matching pursuit (VSgOMP) algorithm that combines generalized orthogonal matching pursuit (gOMP) and adaptive step size method is proposed and employed to compress the Volterra equalizer with low computational cost. A maximum data rate of 500 Mbps is realized with the received optical power of -32.5 dBm in a 7-m water tank. In a 50-m swimming pool, a data rate of 500 Mbps over 200-m underwater transmission is achieved with a BER lower than the forward error correction (FEC) threshold of 3.8 × 10-3. The number of kernels of the sparse Volterra equalizer is reduced to 70% of that of the traditional Volterra equalizer without significant BER performance degradation. Compared with orthogonal matching pursuit (OMP) scheme and regularized orthogonal match pursuit (ROMP) scheme, the VSgOMP scheme reduces the running time by 68.6% and 29.2%, respectively. To the best of our knowledge, this is the first time that a sparse Volterra equalizer combined with VSgOMP algorithm is employed for the nonlinear equalization in a long-distance high-speed UWOC system.
Global impacts of invasive species on the tipping points of shallow lakes

There is growing acknowledgement that human‐induced change can push ecosystems beyond tipping points, resulting in the dramatic and sudden loss of vital ecosystem services. Invasive non‐native species (INNS) are spreading rapidly due to anthropogenic activities and climate change and can drive changes to ecosystem functioning by altering abiotic conditions and restructuring native communities. Shallow lake ecosystems are especially vulnerable to perturbation from INNS as they can exist in two alternative stable states: either clear water with an abundance of vegetation or turbid, unvegetated and dominated by phytoplankton. Through a global meta‐analysis of studies observing the effects of INNS on recipient lake ecosystems, we found that certain INNS drive significant changes in the abundance of key taxa and conditions that govern the balance of alternative equilibria in shallow lakes. Invasive fish and crustaceans demonstrated effects likely to lead to early ecosystem collapse to a turbid state and delay ecosystem recovery. Invasive molluscs presented opposite effects, which may delay ecosystem collapse and encourage ecosystem recovery. Our results demonstrate that INNS could significantly alter the tipping points of ecosystem collapse and recovery, and that not all invasive species may initiate system collapse. Our results provide guidance for managers of invaded shallow lake ecosystems, which provide diverse services including sanitation, potable water supply, industrial cooling, aquaculture and recreational resources. Moreover, our approach could be applied to identify key potential drivers of change in other crucial ecosystems which demonstrate alternative equilibria, such as coral reefs and kelp forests.
Modelling the contribution of metacognitions and expectancies to problematic smartphone use

Abstract Background and aims In the current study we have sought to clarify the contribution of metacognitions concerning smartphone use relative to smartphone use expectancies in the relationship between well-established predisposing psychological factors and problematic smartphone use (PSU). We tested a model where psychological distress, impulsivity, and proneness to boredom predict metacognitions about smartphone use and smartphone use expectancies, which in turn predict PSU. Methods A sample of 535 participants (F = 71.2%; mean age = 27.38 ± 9.05 years) was recruited. Results The model accounted for 64% of the PSU variance and showed good fit indices (χ 2 = 16.01, df = 13, P = 0.24; RMSEA [90%CI] = 0.02 [0–0.05], CFI = 0.99; SRMR = 0.03). We found that: (i) when it comes to psychological distress and boredom proneness, negative metacognitions, and both positive and negative expectancies play a mediating role in the association with PSU, with negative metacognitions showing a dominant role; (ii) there is no overlap between positive expectancies and positive metacognitions, especially when it comes to smartphone use as a means for socializing; (iii) impulsivity did not show a significant effect on PSU Direct effects of the predictors on PSU were not found. Discussion and conclusions The current study found additional support for applying metacognitive theory to the understanding of PSU and highlight the dominant role of negative metacognitions about smartphone in predicting PSU.
Activation of the Hypoxia-Inducible Factor Pathway Inhibits Epithelial Sodium Channel–Mediated Sodium Transport in Collecting Duct Principal Cells

Significance Statement The hypoxia-inducible factor (HIF) pathway is a key mediator of cellular adaptation to low oxygen tension. The aldosterone-sensitive distal nephron is the site of active and highly ATP-consuming sodium reabsorption, according to the requirement of sodium balance. The authors found that activation of the HIF pathway in cultured principal cells led to decreased amiloride-sensitive current (reflecting decreased epithelial sodium channel [ENaC] activity) and decreased expression of ENaC subunits, whereas HIF silencing led to increased amiloride-sensitive current and expression of ENaC subunits. Hypoxic control mice displayed decreased γENaC, whereas HIF1α knockout mice displayed increased γENaC. These findings suggest that the HIF pathway controls ENaC expression and activity, and may represent a negative feedback mechanism to prevent hypoxia and/or reactive oxygen species–induced cell damage under sustained stimulation of sodium transport. Background Active sodium reabsorption is the major factor influencing renal oxygen consumption and production of reactive oxygen species (ROS). Increased sodium reabsorption uses more oxygen, which may worsen medullary hypoxia and produce more ROS via enhanced mitochondrial ATP synthesis. Both mechanisms may activate the hypoxia-inducible factor (HIF) pathway. Because the collecting duct is exposed to low oxygen pressure and variations of active sodium transport, we assessed whether the HIF pathway controls epithelial sodium channel (ENaC)–dependent sodium transport. Methods We investigated HIF’s effect on ENaC expression in mpkCCDcl4 cells (a model of collecting duct principal cells) using real-time PCR and western blot and ENaC activity by measuring amiloride-sensitive current. We also assessed the effect of hypoxia and sodium intake on abundance of kidney sodium transporters in wild-type and inducible kidney tubule–specific Hif1α knockout mice. Results In cultured cells, activation of the HIF pathway by dimethyloxalylglycine or hypoxia inhibited sodium transport and decreased expression of βENaC and γENaC, as well as of Na,K-ATPase. HIF1α silencing increased βENaC and γENaC expression and stimulated sodium transport. A constitutively active mutant of HIF1α produced the opposite effect. Aldosterone and inhibition of the mitochondrial respiratory chain slowly activated the HIF pathway, suggesting that ROS may also activate HIF. Decreased γENaC abundance induced by hypoxia in normal mice was abolished in Hif1α knockout mice. Similarly, Hif1α knockout led to increased γENaC abundance under high sodium intake. Conclusions This study reveals that γENaC expression and activity are physiologically controlled by the HIF pathway, which may represent a negative feedback mechanism to preserve oxygenation and/or prevent excessive ROS generation under increased sodium transport.
Direct Observation of Reactive Intermediates by Time-Resolved Spectroscopy Unravels the Mechanism of a Radical-Induced 1,2-Metalate Rearrangement.

Radical-induced 1,2-metalate rearrangements of boronate complexes are an emerging and promising class of reactions that allow multiple new bonds to be formed in a single, tunable reaction step. These reactions involve the addition of an alkyl radical, typically generated from an alkyl iodide under photochemical activation, to a boronate complex to produce an α-boryl radical intermediate. From this α-boryl radical, there are two plausible reaction pathways that can trigger the product forming 1,2-metalate rearrangement: iodine atom transfer (IAT) or single electron transfer (SET). Previous steady-state techniques have struggled to differentiate these pathways. Here we apply state-of-the-art time-resolved infrared absorption spectroscopy to resolve all the steps in the reaction cycle by mapping production and consumption of the reactive intermediates over picosecond to millisecond time scales. We apply this technique to a recently reported reaction involving the addition of an electron-deficient alkyl radical to the strained σ-bond of a bicyclo[1.1. 0]butyl boronate complex to form a cyclobutyl boronic ester. We show that the previously proposed SET mechanism does not adequately account for the observed spectral and kinetic data. Instead, we demonstrate that IAT is the preferred pathway for this reaction and is likely to be operative for other reactions of this type.
Parkinson's disease affects the neural alpha oscillations associated with speech‐in‐noise processing

Parkinson's disease (PD) has increasingly been associated with auditory dysfunction, including alterations regarding the control of auditory information processing. Although these alterations may interfere with the processing of speech in degraded listening conditions, behavioural studies have generally found preserved speech‐in‐noise recognition in PD. However, behavioural speech audiometry does not capture the neurophysiological mechanisms supporting speech‐in‐noise processing. Therefore, the aim of this study was to investigate the neural oscillatory mechanisms associated with speech‐in‐noise processing in PD. Twelve persons with PD and 12 age‐ and gender‐matched healthy controls (HCs) were included in this study. Persons with PD were studied in the medication off condition. All subjects underwent an audiometric screening and performed a sentence‐in‐noise recognition task under simultaneous electroencephalography (EEG) recording. Behavioural speech recognition scores and self‐reported ratings of effort, performance, and motivation were collected. Time‐frequency analysis of EEG data revealed no significant difference between persons with PD and HCs regarding delta‐theta (2–8 Hz) inter‐trial phase coherence to noise and sentence onset. In contrast, significantly increased alpha (8–12 Hz) power was found in persons with PD compared with HCs during the sentence‐in‐noise recognition task. Behaviourally, persons with PD demonstrated significantly decreased speech recognition scores, whereas no significant differences were found regarding effort, performance, and motivation ratings. These results suggest that persons with PD allocate more cognitive resources to support speech‐in‐noise processing. The interpretation of this finding is discussed in the context of a top‐down mediated compensation mechanism for inefficient filtering and degradation of auditory input in PD.
Anti–PD-1 Efficacy in Patients with Metastatic Urothelial Cancer Associates with Intratumoral Juxtaposition of T Helper-Type 1 and CD8+ T cells

Purpose: PD-1 inhibition results in durable antitumor responses in a proportion of patients with metastatic urothelial cancer (mUC). The majority of patients, however, do not experience clinical benefit. In this study, we aimed to identify early changes in T-cell subsets that underlie anti–PD-1 efficacy in patients with mUC. Experimental Design: Paired samples were collected from peripheral blood, plasma, and metastatic lesions of 56 patients with mUC at baseline and weeks 6 and 12 after initiating pembrolizumab treatment (200 mg intravenously, every 3 weeks). Samples were analyzed using multiplex flow cytometry, ELISA, and in situ stainings, including cellular network analysis. Treatment response was evaluated as best overall response according to RECIST v1.1, and patients were classified as responder (complete or partial response) or nonresponder (progressive disease). Results: In responders, baseline fractions of CD4+ T cells expressing cosignaling receptors were higher compared with nonresponders. The fraction of circulating PD-1+ CD4+ T cells decreased at weeks 6 and 12, whereas the fraction of 4-1BB+ CD28+ CD4+ T cells increased at week 12. In metastatic lesions of responders, the baseline density of T helper-type 1 (Th1) cells, defined as T-bet+ CD4+ T cells, was higher as compared to non-responders. Upon treatment, Th1 cells became localized in close proximity to CD8+ T cells, CD11b+ myeloid cells, and tumor cells. Conclusions: A decrease in the fraction of circulating PD-1+ CD4+ T cells, and juxtaposition of Th1, CD8+, and myeloid cells was associated with response to anti–PD-1 treatment in patients with mUC.
Accuracy of intraoperative neuromonitoring during percutaneous cement discoplasty

Abstract Introduction Percutaneous cement discoplasty is a minimally invasive procedure to treat low back pain due to advanced degenerative disc disease in elderly patients. Complications of this procedure has been described such as infection, vertebral fracture, cement leakage and nerve injury. Intraoperative neuromonitoring is used to detect the latter. The objective of this study was to assess the usefulness of neuromonitoring during discoplasty to detect new neurological compromise. Methods 100 consecutive patients were included in this retrospective study, (30 males and 70 females, mean age of 76.3 ± 5.71 years) with mechanical low back pain who underwent percutaneous cement discoplasty. Results Sensitivity to detect neurological injury was 82% (CI 95% 66-98), specificity was of 99% (CI 95%98-100) with a positive predictive value of 0.95 (CI 95% 85-100) and a negative predictive value of 0.97 (CI 95% 95-99). In 5 patients neurological compromise was not detected by neuromonitoring. Discussion Our study showed high sensitivity and specificity of neuromonitoring to detect neurological irritation during percutaneous discoplasty. Intraoperative neuromonitoring resulted an effective assistance during this minimally invasive procedure.
Assembling Native Elementary Cellulose Nanofibrils via a Reversible and Regioselective Surface Functionalization

Selective surface modification of biobased fibers affords effective individualization and functionalization into nanomaterials, as exemplified by the TEMPO-mediated oxidation. However, such a route leads to changes of the native surface chemistry, affecting interparticle interactions and limiting the development of potential supermaterials. Here we introduce a methodology to extract elementary cellulose fibrils by treatment of biomass with N-succinylimidazole, achieving regioselective surface modification of C6-OH, which can be reverted using mild post-treatments. No polymer degradation, cross-linking, nor changes in crystallinity occur under the mild processing conditions, yielding cellulose nanofibrils bearing carboxyl moieties, which can be removed by saponification. The latter offers a significant opportunity in the reconstitution of the chemical and structural interfaces associated with the native states. Consequently, 3D structuring of native elementary cellulose nanofibrils is made possible with the same supramolecular features as the biosynthesized fibers, which is required to unlock the full potential of cellulose as a sustainable building block.
The cellular modifier MOAG‐4/SERF drives amyloid formation through charge complementation

While aggregation‐prone proteins are known to accelerate aging and cause age‐related diseases, the cellular mechanisms that drive their cytotoxicity remain unresolved. The orthologous proteins MOAG‐4, SERF1A, and SERF2 have recently been identified as cellular modifiers of such proteotoxicity. Using a peptide array screening approach on human amyloidogenic proteins, we found that SERF2 interacted with protein segments enriched in negatively charged and hydrophobic, aromatic amino acids. The absence of such segments, or the neutralization of the positive charge in SERF2, prevented these interactions and abolished the amyloid‐promoting activity of SERF2. In protein aggregation models in the nematode worm Caenorhabditis elegans, protein aggregation and toxicity were suppressed by mutating the endogenous locus of MOAG‐4 to neutralize charge. Our data indicate that MOAG‐4 and SERF2 drive protein aggregation and toxicity by interactions with negatively charged segments in aggregation‐prone proteins. Such charge interactions might accelerate primary nucleation of amyloid by initiating structural changes and by decreasing colloidal stability. Our study points at charge interactions between cellular modifiers and amyloidogenic proteins as potential targets for interventions to reduce age‐related protein toxicity.
NHE6 depletion corrects ApoE4-mediated synaptic impairments and reduces amyloid plaque load

Apolipoprotein E4 (ApoE4) is the most important and prevalent risk factor for late-onset Alzheimer’s disease (AD). The isoelectric point of ApoE4 matches the pH of the early endosome (EE), causing its delayed dissociation from ApoE receptors and hence impaired endolysosomal trafficking, disruption of synaptic homeostasis, and reduced amyloid clearance. We have shown that enhancing endosomal acidification by inhibiting the EE-specific sodium-hydrogen exchanger 6 (NHE6) restores vesicular trafficking and normalizes synaptic homeostasis. Remarkably and unexpectedly, loss of NHE6 (encoded by the gene Slc9a6) in mice effectively suppressed amyloid deposition even in the absence of ApoE4, suggesting that accelerated acidification of EEs caused by the absence of NHE6 occludes the effect of ApoE on amyloid plaque formation. NHE6 suppression or inhibition may thus be a universal, ApoE-independent approach to prevent amyloid buildup in the brain. These findings suggest a novel therapeutic approach for the prevention of AD by which partial NHE6 inhibition reverses the ApoE4-induced endolysosomal trafficking defect and reduces plaque load.