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By illustrating how practitioners can use a simple conceptual template to customise HMMs for their specific systems of interest, revealing methodological links between existing applications, and highlighting some practical considerations and limitations of these approaches, our goal is to help establish HMMs as a fundamental inferential tool for ecologists.Three decades ago a series of parallel circuits were described involving the frontal cortex and deep grey matter structures, with putative roles in control of motor and oculomotor function, cognition, behaviour and emotion. The circuit comprising the dorsolateral prefrontal cortex, caudate, globus pallidus and thalamus has a putative role in regulating executive functions. The aim of this study is to investigate effective connectivity (EC) of the dorsolateral-prefrontal circuit and its association with PASAT-3 performance in people with multiple sclerosis(MS). We use Granger causality analysis of resting-state functional MRI from 52 people with MS and 36 healthy people to infer that reduced EC in the afferent limb of the dorsolateral prefrontal circuit occurs in the people with MS with cognitive dysfunction (left p = .006; right p = .029), with bilateral EC reductions in this circuit resulting in more severe cognitive dysfunction than unilateral reductions alone (p = .002). We show that reduced EC in the afferent limb of the dorsolateral prefrontal circuit mediates the relationship between cognitive performance and macrostrucutral and microstructural alterations of white matter tracts in components of the circuit. Specificity is shown by the absence of any relationship between cognition and EC in the analogous and anatomically proximal motor circuit. We demonstrate good stability of the EC measures in people with MS over an interval averaging 8-months. #link# Key positive and negative results are replicated in an independent cohort of people with MS. Our findings identify the dorsolateral prefrontal circuit as a potential target for therapeutic strategies aimed at improving cognition in people with MS.The rapid spread of SARS-CoV-2 and its threat to health systems worldwide have led governments to take acute actions to enforce social distancing. Previous studies used complex epidemiological models to quantify the effect of lockdown policies on infection rates. However, these rely on prior assumptions or on official regulations. Here, we use country-specific reports of daily mobility from people cellular usage to model social distancing. buy Withaferin A -driven model enabled the extraction of lockdown characteristics which were crossed with observed mortality rates to show that (i) the time at which social distancing was initiated is highly correlated with the number of deaths, r2 = 0.64, while the lockdown strictness or its duration is not as informative; (ii) a delay of 7.49 days in initiating social distancing would double the number of deaths; and (iii) the immediate response has a prolonged effect on COVID-19 death toll.
The role of structural abnormalities in high hyperdiploidy (HeH) has been debatable, with few studies that addressed recurrent translocations with concurrent HeH (t-HeH). We aimed at the characterization of HeH cases in pediatric B-acute lymphoblastic leukemia (B-ALL) patients with special emphasis on the structural abnormalities including t-HeH.
Our study included all patients diagnosed with HeH over the period from January 2016 to April 2019 presenting to the Pediatric Oncology Department, National Cancer Institute, Cairo University.
Among 480 de novo B-ALL pediatric patients, HeH was detected in eighty (16.7%) cases with a median age of 5years. t-HeH was identified in 17/480 (3.5%) cases 9(1.9%) with t(12;21), 7(1.5%) with t(9;22), and 1(0.2%) with t(4;11). Duplication (1q) was the most prevalent structural abnormality in c-HeH (hyperdiploidy without recurrent translocations) (n=12,15%). Children ≥10years or presenting with white blood cells (WBC) ≥50×10
/L) had an inferior 3year-overall survival as compared to younger children (P=.003), and to lower WBC (P=.02). Duplication (1q) was an independent adverse parameter on the disease-free survival (DFS) of c-HeH patients (P=.004).
Older age and WBC≥50×10
/L were adverse prognostic factors. Duplication (1q) is correlated with lower DFS in c-HeH patients. t-HeH has distinct patterns of chromosomal gain.
Older age and WBC ≥ 50 × 109 /L were adverse prognostic factors. Duplication (1q) is correlated with lower DFS in c-HeH patients. t-HeH has distinct patterns of chromosomal gain.The current standard cisplatin regimen for concurrent chemoradiation therapy (CCRT) involves generalized static administration of cisplatin without considering patient characteristics and patient/tumor responses during treatment. We aimed to evaluate the oncological feasibility of individualized/dynamic cisplatin regimens for definitive CCRT in patients with head and neck squamous cell carcinoma (HNSCC). This prospective, single-center study enrolled patients with biopsy-confirmed HNSCC for whom CCRT was indicated as the primary treatment. Concurrent with radiation therapy (RT), patients received individualized and dynamically modified cisplatin chemotherapy based on patient characteristics, such as age and Eastern Cooperative Oncology Group performance status (PS), and patient/tumor treatment responses. The primary endpoints of the study were grade ≥3 toxicity and progression-free survival (PFS). The study enrolled 150 patients; 146 (97.3%) received ≥2 cycles of cisplatin in addition to scheduled RT. Incidence of any grade 3-4 toxicities was 40.7% (61/150). During the 40.1 ± 25.1-month follow-up period, the 2-year locoregional control, distant control, PFS, disease-specific survival, and overall survival were 81.7%, 89.2%, 73.0%, 89.2%, and 86.1%, respectively. The treatment compliance and grade ≥3 toxicities did not differ between patients aged less then 70 years and ≥70 years, or those with PS 0 and PS 1-2, respectively. CCRT using individualized, dynamic cisplatin regimens based on patient age, PS, and patient/tumor responses during treatment was oncologically safe and effective for treating patients with HNSCC, including those aged ≥70 years and with PS 1-2.We demonstrate hydrogen-bonded structures of water in self-organized subnanoporous water treatment membranes obtained using synchrotron-based high-resolution soft X-ray emission spectroscopy. The ion selectivity of these water treatment membranes is usually understood by the size compatibility of nanochannels in the membrane with the Stokes radius of hydrated ions, or by electrostatic interaction between charges inside the nanochannels and such ions. However, based on a comparison between the hydrogen-bonded structures of water molecules in the nanochannels of the water treatment membrane and those surrounding the ions, we propose a definite contribution of structural consistency among the associated hydrogen-bonded water molecules to the ion selectivity. Our observation delivers a novel concept to the design of water treatment membranes where water molecules in the nanochannel can be regarded as a part of the material that controls the ion selectivity.
The Asian citrus psyllid Diaphorina citri has developed high levels of resistance to many insecticides, and understanding its resistance mechanism will aid in the chemical control of this species. Nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome P450 reductase (CPR) is crucial in cytochrome P450 function, and in some insects CPR knockdown has increased their susceptibility to insecticides. However, the CPR from D. link2 citri has not been characterized and its function is undescribed.
The CPR gene of D. citri (DcCPR) was cloned and sequenced. The expression level of DcCPR, determined by reverse-transcription quantitative polymerase chain reaction (RT-qPCR) analysis, was highest in the midgut and in nymphs. After feeding on double-stranded RNA for 72 h, the DcCPR messenger RNA level in D. citri adults decreased by 68.4%, and the susceptibility of D. citri to imidacloprid and thiamethoxam significantly increased. Meanwhile, after DcCPR silencing, the specific activities of DcCPR protein and P450s were significantly reduced by 41.6% and 44.7%, respectively. The subsequent western blot analysis and quantification of band intensity also showed that DcCPR content significantly decreased, consistent with the results of the specific activity test. In a eukaryotic expression assay, the viability of cells expressing DcCPR was significantly higher than the viability of cells expressing green fluorescent protein (GFP) when cells were exposed to imidacloprid or thiamethoxam.
These results indicate that DcCPR contributes to D. citri susceptibility to imidacloprid and thiamethoxam.
These results indicate that DcCPR contributes to D. citri susceptibility to imidacloprid and thiamethoxam.Systemic acquired resistance (SAR) is a broad-spectrum disease resistance response that can be induced upon infection from pathogens or by chemical treatment, such as with benzo-(1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester (BTH). SAR involves priming for more robust activation of defence genes upon pathogen attack. Whether priming for SAR would involve components of RNA silencing remained unknown. Here, we show that upon leaf infiltration of water, BTH-primed Arabidopsis thaliana plants accumulate higher amounts of mRNA of ARGONAUTE (AGO)2 and AGO3, key components of RNA silencing. The enhanced AGO2 expression is associated with prior-to-activation trimethylation of lysine 4 in histone H3 and acetylation of histone H3 in the AGO2 promoter and with induced resistance to the yellow strain of cucumber mosaic virus (CMV[Y]). The results suggest that priming A. thaliana for enhanced defence involves modification of histones in the AGO2 promoter that condition AGO2 for enhanced activation, associated with resistance to CMV(Y). Consistently, the fold-reduction in CMV(Y) coat protein accumulation by BTH pretreatment was lower in ago2 than in wild type, pointing to reduced capacity of ago2 to activate BTH-induced CMV(Y) resistance. A role of AGO2 in pathogen-induced SAR is suggested by the enhanced activation of AGO2 after infiltrating systemic leaves of plants expressing a localized hypersensitive response upon CMV(Y) infection. In addition, local inoculation of SAR-inducing Pseudomonas syringae pv. maculicola causes systemic priming for enhanced AGO2 expression. Together our results indicate that defence priming targets the AGO2 component of RNA silencing whose enhanced expression is likely to contribute to SAR.The perception of facial and vocal stimuli is driven by sensory input and cognitive top-down influences. Important top-down influences are attentional focus and supramodal social memory representations. The present study investigated the neural networks underlying these top-down processes and their role in social stimulus classification. In a neuroimaging study with 45 healthy participants, we employed a social adaptation of the Implicit Association Test. Attentional focus was modified via the classification task, which compared two domains of social perception (emotion and gender), using the exactly same stimulus set. Supramodal memory representations were addressed via congruency of the target categories for the classification of auditory and visual social stimuli (voices and faces). Functional magnetic resonance imaging identified attention-specific and supramodal networks. link3 Emotion classification networks included bilateral anterior insula, pre-supplementary motor area, and right inferior frontal gyrus. They were pure attention-driven and independent from stimulus modality or congruency of the target concepts.
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