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The present study focused on three autochthonous varieties of apple trees belonging to the old Tuscany germplasm (central Italy), Chitignano, Mora and Ruggine, and aimed to (a) evaluate the presence of the four main latent viruses of apple trees (apple chlorotic leaf spot virus [ACLSV], apple mosaic virus [ApMV], apple stem grooving virus [ASGV] and apple stem pitting virus [ASPV]) and (b) elucidate the biochemical and physiological responses of apple leaves and fruits challenged by ACLSV (the only virus detected). Indeed, despite no visible symptoms being reported, more than half of the assayed trees tested positive for ACLSV, although it occurred only in Mora and Ruggine. ACLSV impaired the photosynthetic performance of apple trees, especially in Ruggine leaves, but variety‐specific responses in terms of reorganization of photosynthetic pigment and primary metabolites were reported. Mora showed a higher ability to trigger the de‐epoxidation state of xanthophylls and to accumulate α‐tocopherol, while d‐glucose and sucrose increased only in infected Ruggine leaves, probably as a signalling response and/or an osmotic adjustment of this variety under ACLSV infection. Unexpectedly, ACLSV infection slightly increased pome size, but it dramatically reduced their quality (i.e., soluble solids content), again especially in Ruggine, the only variety where reductions of d‐fructose, d‐glucose and malic acid contents were reported. Overall, the evidence here reported could offer valuable insights to effectively cope with the detrimental viral diseases affecting this species and to protect the production of one of the most consumed and appreciated fruits in the world. [ABSTRACT FROM AUTHOR]

The flagellar MS‐ring, uniquely constituted by FliF, is essential for flagellar biogenesis and functionality in several bacteria. The aim of this study was to dissect the role of FliF in the Gram‐positive and peritrichously flagellated Bacillus cereus. We demonstrate that fliF forms an operon with the upstream gene fliE. In silico analysis of B. cereus ATCC 14579 FliF identifies functional domains and amino acid residues that are essential for protein functioning. The analysis of a ΔfliF mutant of B. cereus, constructed in this study using an in frame markerless gene replacement method, reveals that the mutant is unexpectedly able to assemble flagella, although in reduced amounts compared to the parental strain. Nevertheless, motility is completely abolished by fliF deletion. FliF deprivation causes the production of submerged biofilms and affects the ability of B. cereus to adhere to gastrointestinal mucins. We additionally show that the fliF deletion does not compromise the secretion of the three components of hemolysin BL, a toxin secreted through the flagellar type III secretion system. Overall, our findings highlight the important role of B. cereus FliF in flagella‐related functions, being the protein required for complete flagellation, motility, mucin adhesion, and pellicle biofilms. [ABSTRACT FROM AUTHOR]

Background: His‐Bundle pacing (HBP) is an emerging technique for physiological pacing. However, its effects on right ventricle (RV) performance are still unknown. Methods: We enrolled consecutive patients with an indication for pacemaker (PM) implantation to compare HBP versus RV pacing (RVP) effects on RV performance. Patients were evaluated before implantation and after 6 months by a transthoracic echocardiogram. Results: A total of 84 patients (age 75.1±7.9 years, 64% male) were enrolled, 42 patients (50%) underwent successful HBP, and 42 patients (50%) apical RVP. At follow up, we found a significant improvement in RV‐FAC (Fractional Area Change)% [baseline: HBP 34 IQR (31–37) vs. RVP 33 IQR (29.7–37.2),p =.602; 6‐months: HBP 37 IQR (33–39) vs. RVP 30 IQR (27.7–35), p <.0001] and RV‐GLS (Global Longitudinal Strain)% [baseline: HBP –18 IQR (–20.2 to –15) vs. RVP –16 IQR (–18.7 to –14), p =.150; 6‐months: HBP –20 IQR(–23 to –17) vs. RVP –13.5 IQR (–16 to –11), p <.0001] with HBP whereas RVP was associated with a significant decline in both parameters. RVP was also associated with a significant worsening of tricuspid annular plane systolic excursion (TAPSE) (p <.0001) and S wave velocity (p <.0001) at follow up. Conversely from RVP, HBP significantly improved pulmonary artery systolic pressure (PASP) [baseline: HBP 38 IQR (32–42) mmHg vs. RVP 34 IQR (31.5–37) mmHg,p =.060; 6‐months: HBP 32 IQR (26–38) mmHg vs. RVP 39 IQR (36–41) mmHg, p <.0001] and tricuspid regurgitation (p =.005) irrespectively from lead position above or below the tricuspid valve. Conclusions: In patients undergoing PM implantation, HBP ensues a beneficial and protective impact on RV performance compared with RVP. [ABSTRACT FROM AUTHOR]

The autonomic nervous system (ANS) is known to play an important role in the genesis and maintenance of atrial fibrillation (AF). Biomolecular and genetic mechanisms, anatomical knowledges with recent diagnostic techniques acquisitions, both invasive and non‐invasive, have enabled greater therapeutic goals in patients affected by AF related to ANS imbalance. Catheter ablation of ganglionated plexi (GP) in the left and right atrium has been proposed in varied clinical conditions. Moreover interesting results arise from renal sympathetic denervation and vagal nerve stimulation. Despite all this, in the scenario of ANS modulation translational strategies we necessary must consider the treatment or correction of dynamic factors such as obesity, obstructive sleep apnea, lifestyle, food, and stress. Finally, new antiarrhythmic drugs, gene therapy and "ablatogenomic" could be represent exciting future therapeutic perspectives. [ABSTRACT FROM AUTHOR]

Due to its complex epidemiological cycle, including several polyphagous insect vectors and host plants, and the absence of efficient control strategies, Bois Noir (BN) disease of grapevine is encroaching wider territories in the main viticultural areas worldwide. Molecular approaches allowed to increase the knowledge about its etiological agent (Bois Noir phytoplasma, BNp; 'Candidatus Phytoplasma solani' species), revealing interesting features concerning BNp population structure and dynamics and transmission routes in vineyard agro‐ecosystems. In the present study, a multilocus sequence typing approach (vmp1 and stamp genes) was utilised for describing the genetic diversity among BNp strain populations in 17 vineyards localised in two distinct geographic areas in Tuscany (central Italy). The results confirmed that BNp ecology in Tuscan vineyards is mainly associated to the bindweed‐related host system, and allowed the identification of 14 BNp vmp1/stamp genotypes. Interestingly, the prevalent genotype (Vm43/St10) was never found in grapevines outside of Tuscany. Moreover, statistical analyses showed significant differences between the composition of BNp strain populations identified in grapevines from north‐western and central‐eastern Tuscany. These results reinforce the hypothesis that distinct geographic areas, probably associated with different ecological niches, can drive the selection of BNp strains, also favouring the entrance of unusual 'Ca. Phytoplasma solani' genotypes in vineyards. Multi‐locus sequence typing allowed the identification of 14 BNp vmp1/stamp genotypes in Tuscan vineyards, mainly associated to bindweed‐related host system. [ABSTRACT FROM AUTHOR]

Diagnostic tests for grapevine viruses subjected to phytosanitary rules involve a heavy workload for plant protection services and laboratories. Propagation schemes enable nurseries, where mother plants (MPs) are cultivated, to be linked to batches of certified plants (CPs). This approach entails post‐production checks of MPs once infection occurs in CPs. However, this traceability system is not tight and follow ups are demanding. This study assessed radio frequency identification (RFID) tagging of plants in terms of its ability to reduce laboratory workloads for nursery health checks. RFID‐tagged plants (RFID‐CPs) were produced from individually tagged MPs (RFID‐MPs) or row‐tagged MPs (RFID‐ROW, a less expensive approach). In a 10‐year case study, the health status of CPs and RFID‐CPs were assessed and the occurrence of infections then led to health checks in MPs, RFID‐MPs or RFID‐ROWs. Laboratory workloads were evaluated by considering two sampling methods (single or pool sampling). Using single sampling, the workload was reduced by 93–98% in RFID‐ROW or RFID‐MP checks compared to the conventional approach. Considerable reductions in workload due to the tagging system (93–96%) were also observed using pool sampling. Traceability of CPs and MPs using RFID reduces laboratory workloads, and supports emergency measures that can be taken to stop any unsafe sales of plants after a virus outbreak. [ABSTRACT FROM AUTHOR]

The terminal N-Boc protected diamino PAMAM 7 was condensed (EDC-DMAP) with two units of mycophenolic acid (MPA) giving the N-Boc protected dendron 8 in a good yield (76%). The ammonium trifluoroacetate 9 was prepared from 8 by acid treatment (TFA-THF-H2O) and was split into two equal parts. The first half was treated with di-2-pyridyl thionocarbonate (DPT) in the presence of Et3N to give the corresponding isothiocyanate 10. This was reacted with the second half of 9 providing the symmetrical dendrimer 11 (68% yield), exposing four MPA units around the thioureido-PAMAM core. [ABSTRACT FROM AUTHOR]

Objectives: To assess the reliability of data in electronic health records (EHRs) for measuring processes of care among primary care physicians (PCPs) and examine the relationship between these measures and clinical outcomes.Data Sources/study Setting: EHR data from 15,370 patients with diabetes, 49,561 with hypertension, in a group practice serving four Northern California counties.Study Design/methods: Exploratory factor analysis (EFA) and multilevel analyses of the relationships between processes of care variables and factor scales with control of hemoglobin A1c, blood pressure (BP), and low density lipoprotein (LDL) among patients with diabetes and BP among patients with hypertension.Principal Findings: Volume of e-messages, number of days to the third-next-available appointment, and team communication emerged as reliable factors of PCP processes of care in EFA (Cronbach's alpha=0.73, 0.62, and 0.91). Volume of e-messages was associated with higher odds of LDL control (≤100) (OR=1.13, p<.05) among patients with diabetes. Frequent in-person visits were associated with better BP (OR=1.02, p<.01) and LDL control (OR=1.01, p<.01) among patients with diabetes, and better BP control (OR=1.04, p<.01) among patients with hypertension.Conclusions: The EHR offers process of care measures which can augment patient-reported measures of patient-centeredness. Two of them are significantly associated with clinical outcomes. Future research should examine their association with additional outcomes. [ABSTRACT FROM AUTHOR]

Objectives. To assess the reliability of data in electronic health records (EHRs) for measuring processes of care among primary care physicians (PCPs) and examine the relationship between these measures and clinical outcomes. Data Sources/Study Setting. EHR data from 15,370 patients with diabetes, 49,561 with hypertension, in a group practice serving four Northern California counties. Study Design/Methods. Exploratory factor analysis (EFA) and multilevel analyses of the relationships between processes of care variables and factor scales with control of hemoglobin A1c, blood pressure (BP), and low density lipoprotein (LDL) among patients with diabetes and BP among patients with hypertension. Principal Findings. Volume of e-messages, number of days to the third-next-available appointment, and team communication emerged as reliable factors of PCP processes of care in EFA (Cronbach's alpha = 0.73, 0.62, and 0.91). Volume of e-messages was associated with higher odds of LDL control (≤100) (OR = 1.13, p < .05) among patients with diabetes. Frequent in-person visits were associated with better BP (OR = 1.02, p < .01) and LDL control (OR = 1.01, p < .01) among patients with diabetes, and better BP control (OR = 1.04, p < .01) among patients with hypertension. Conclusions. The EHR offers process of care measures which can augment patient-reported measures of patient-centeredness. Two of them are significantly associated with clinical outcomes. Future research should examine their association with additional outcomes. [ABSTRACT FROM AUTHOR]

ABSTRACT This study aims to describe the morphology of Didelphis sp. male genital organs (penis, testes, epididymis, ductus deferens, prostate, and bulbourethral gland). Ten male animals were used, eight for macroscopic and light microscopy analysis, and two for scanning electron microscopy. The testes and epididymis showed similarity to other eutherian mammals. The bifid penis showed the urethra ending in the medial region where the bifurcation begins, occurring in each segment extension of the urethral groove until the beginning of the glans. Histologically, the penis consists of a cavernous and spongy body, covered by stratified squamous epithelium with loose connective tissue. The urethra was lined by transitional stratified epithelium. In the prostate, prostatic segments were found consisting of tubular glands in a radial arrangement around the urethra, coated externally by a dense connective tissue associated with a relatively thick layer of smooth muscle arranged in two layers that surround the glandular tissue. The animals had three pairs of bulbourethral glands placed at the membranous and cavernous urethra junction with descending and parallel excretory ducts ending caudally in the urethral lumen. Microsc. Res. Tech. 76:388-397, 2013. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Emotional cues contain important information about the intentions and feelings of others. Despite a wealth of research into children's understanding of facial signals of emotions, little research has investigated the developmental trajectory of interpreting affective cues in the voice. In this study, 48 children ranging between 5 and 10 years were tested using forced-choice tasks with non-verbal vocalizations and emotionally inflected speech expressing different positive, neutral and negative states. Children as young as 5 years were proficient in interpreting a range of emotional cues from vocal signals. Consistent with previous work, performance was found to improve with age. Furthermore, the two tasks, examining recognition of non-verbal vocalizations and emotionally inflected speech, respectively, were sensitive to individual differences, with high correspondence of performance across the tasks. From this demonstration of children's ability to recognize emotions from vocal stimuli, we also conclude that this auditory emotion recognition task is suitable for a wide age range of children, providing a novel, empirical way to investigate children's affect recognition skills. [ABSTRACT FROM AUTHOR]

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Abstract: The COP9 signalosome (CSN) complex is critical for mammalian cell proliferation and survival, but it is not known how the CSN affects the cell cycle. In this study, MEFs lacking CSN5/Jab1 were generated using a CRE-flox system. MEFs ceased to proliferate upon elimination of CSN5/Jab1. Rescue experiments indicated that the JAMM domain of CSN5/Jab1 was essential. CSN5/Jab1-elimination enhanced the neddylation of cullins 1 and 4 and altered the expression of many factors including cyclin E and p53. CSN5/Jab1-elimination inhibited progression of the cell cycle at multiple points, seemed to initiate p53-independent senescence and increased the ploidy of cells. Thus, CSN5/Jab1 controls different events of the cell cycle, preventing senescence and endocycle as well as the proper progression of the somatic cell cycle. Structured summary: MINT-8046253: Csn1 (uniprotkb:Q99LD4) physically interacts (MI:0914) with Csn5 (uniprotkb:O35864), Csn8 (uniprotkb:Q8VBV7), Csn3 (uniprotkb:O88543), Csn7b (uniprotkb:Q8BV13) and Csn6 (uniprotkb:O88545) by anti bait coimmunoprecipitation (MI:0006) [ABSTRACT FROM AUTHOR]

Dyslipidemia is a potential unfavorable prognostic factor in neuroendocrine tumors (NETs); conversely, statins proved to have antiproliferative effects in NET cell lines and could be a helpful therapeutic strategy for these patients. The main objective of this observational cohort retrospective study is to explore the associations between dyslipidemia and NET progression and evaluate the potential influence of statins in this context. 393 patients with histologically confirmed gastroenteropancreatic or bronchopulmonary NETs from six Italian centres didicated to NET diagnosis and therapy were included. The cohort included 123 patients with dyslipidemia, 81 of which were taking statins. Clinicopathological data, including patient demographics, tumor characteristics, and treatment details as well as the prevalence, timing of dyslipidemia and hypolipemic therapy were collected. The main outcome measure used is progression‐free survival (PFS). Among the 393 patients, 123 (31.3%) had dyslipidemia. Statins were used by 81 (65.8%) dyslipidemic patients, mostly atorvastatin. Median PFS was 87 months overall, 124 months in non‐dyslipidemic patients, and 72 months in dyslipidemic patients (p = .268). Dyslipidemic patients on statins had a significantly better median PFS (108 months) than those not on statins (26 months; p = .024). Recurrence‐free survival (RFS) was also evaluated, but no significant differences were found. In conclusion, while PFS was lower in dyslipidemic patients compared to non‐dyslipidemic patients, the difference was not statistically significant. Statin therapy was associated with improved PFS among dyslipidemic patients, suggesting a potential antiproliferative effect of statins in NETs. These findings warrant further investigation to substantiate the role of statins in the management of NETs. [ABSTRACT FROM AUTHOR]

Shows how analytic first and second derivatives of the log-likelihood can be employed for estimation purposes. Information on the Generalized Autoregressive Conditional Heteroscedastic process (GARCH); Computational benefit of using the analytic derivatives; Comparison of various gradient algorithms that are used for the maximization of the GARCH Gaussian likelihood.

Presents an alternative estimator model for full information estimation method. Use of asymptotic covariance matrix to estimate coefficients; Simultaneous equations model containing stochastic equations; Rate of standard errors computed from outer products.

Thiopurine prodrugs are antiviral chemicals used in medical therapy whose mechanisms of action are associated with inhibition of purine biosynthesis. In terms of plant chemotherapy, previous research of 6-mercaptopurine (MP) administration in tobacco tissue culture infected by Tobacco mosaic virus (TMV) showed no inhibition of virus activity. Currently, not enough data exist to confirm thiopurine drug ineffectiveness against viruses in the plant kingdom. This paper presents a screening of MP, 6-methylmercaptopurine riboside (MMPR), 6-thioguanine (6-TG) and 1-amino-6-mercaptopurine (1A-MP) against TMV and Cucumber mosaic virus (CMV) in in vitro tobacco explants and against Grapevine leafroll-associated virus 3 (GLRaV 3) in in vitro grapevine explants. ELISA and RT-PCR were used to evaluate antiviral activity. Higher toxicity levels of MP derivatives, compared to MP, were noted in tobacco and grapevine explants. 1A-MP or 6-TG treatment resulted CMV and GLRaV 3 virus-eradicated explants as obtained with Inosine 5′-monophosphate dehydrogenase inhibitors, whereas TMV was not eradicated by any of the studied drugs. [ABSTRACT FROM AUTHOR]