Effectiveness of entomopathogenic nematodes in the control of Cydia pomonella larvae in Northern Italy

Since 2006, a large scale research on the effectiveness of entomopathogenic nematodes (EPN) in the control of codling moth (CM), Cydia pomonella, overwintering larvae has been performed on about 35 ha of pear orchards per year in Emilia-Romagna, Northern Italy. Steinernema carpocapsae and Steinernema feltiae activity was checked after spray applications of EPNs to the trunk and branches. In 2006, the treatment was applied either in spring or in autumn at different doses, before CM pupation; in 2007 the EPN treatment was applied only in autumn at 1.5 x 109 I.J. ha –1. Every year it was distributed by means of a conventional mist blower. The larval mortality was assessed directly on sentinel larvae in card boards on the trunks and indirectly on the eggs laid by the females of the first CM generation in spring. Moreover, each year, a trial was performed applying only S. carpocapsae on sentinel larvae with the aim of testing this nematode at suitable temperatures but at different water volumes. The CM sentinel larvae were effectively parasitized after autumnal EPN application. Moreover, the egg assessment demonstrated a good decrease in CM population in spring 2007, when EPNs had been applied at the best weather conditions (t° 12-14 °C and rain) in the previous autumn

Restraining and unleashing chromatin remodelers - structural information guides chromatin plasticity.

Chromatin remodeling enzymes are large molecular machines that guard the genome by reorganizing chromatin structure. They can reposition, space and evict nucleosomes and thus control gene expression, DNA replication and repair. Recent cryo-electron microscopy (cryo-EM) analyses have captured snapshots of various chromatin remodelers as they interact with nucleosomes. In this review, we summarize and discuss the advances made in our understanding of the regulation of chromatin remodelers, the mode of DNA translocation, as well as the influence of associated protein domains and remodeler subunits on the specific functions of chromatin remodeling complexes. The emerging structural information will help our understanding of disease mechanisms and guide our knowledge toward innovative therapeutic interventions. Copyright © 2020 Elsevier Ltd. All rights reserved

PARG: A Macrodomain in Disguise

Our understanding of poly-ADP-ribosylation as a posttranslational modification was limited by the lack of structural information on poly-ADP-ribose (PAR) hydrolysing enzymes. A recent study in Nature (Slade et al., 2011) reports the structure of PAR glycohydrolase (PARG), revealing unexpected similarity to the ubiquitous ADP-ribose-binding macrodomains

Mutations of penicillin acylase residue B71 extend substrate specificity by decreasing steric constraints for substrate binding

Two mutant forms of penicillin acylase from Escherichia coli strains, selected using directed evolution for the ability to use glutaryl-L-leucine for growth [Forney, Wong and Ferber (1989) Appl. Environ. Microbiol. 55, 2550-2555], are changed within one codon, replacing the B-chain residue Phe(B71) with either Cys or Leu. Increases of up to a factor of ten in k(cat)/K-m values for substrates possessing a phenylacetyl leaving group are consistent with a decrease in K-s. Values of k(cat/)K(m) for glutaryl-L-leucine are increased at least 100-fold. A decrease in k(cat)/K-m for the CySB71 mutant with increased pH is consistent with binding of the uncharged glutaryl group. The mutant proteins are more resistant to urea denaturation monitored by protein fluorescence, to inactivation in the presence of substrate either in the presence of urea or at high pH, and to heat inactivation. The crystal structure of the Leu(B71) mutant protein, solved to 2 X resolution, shows a flip of the side chain of Phe(B256) into the periphery of the catalytic centre, associated with loss of the pi-stacking interactions between Phe(B256) and Phe(B71). Molecular modelling demonstrates that glutaryl-L-leucine may bind with the uncharged glutaryl group in the S-1 subsite of either the wild-type or the Leu(B71) mutant but with greater potential freedom of rotation of the substrate leucine moiety in the complex with the mutant protein. This implies a smaller decrease in the conformational entropy of the substrate on binding to the mutant proteins and consequently greater catalytic activity

Local IGF-1 isoform protects cardiomyocytes from hypertrophic and oxidative stresses via SirT1 activity

Oxidative and hypertrophic stresses contribute to the pathogenesis of heart failure. Insulin-like growth factor-1 (IGF-1) is a peptide hormone with a complex post-transcriptional regulation, generating distinct isoforms. Locally acting IGF-1 isoform (mIGF-1) helps the heart to recover from toxic injury and from infarct. In the murine heart, moderate overexpression of the NAD+-dependent deacetylase SirT1 was reported to mitigate oxidative stress. SirT1 is known to promote lifespan extension and to protect from metabolic challenges. Circulating IGF-1 and SirT1 play antagonizing biological roles and share molecular targets in the heart, in turn affecting cardiomyocyte physiology. However, how different IGF-1 isoforms may impact SirT1 and affect cardiomyocyte function is unknown. Here we show that locally acting mIGF-1 increases SirT1 expression/activity, whereas circulating IGF-1 isoform does not affect it, in cultured HL-1 and neonatal cardiomyocytes. mIGF-1-induced SirT1 activity exerts protection against angiotensin II (Ang II)-triggered hypertrophy and against paraquat (PQ) and Ang II-induced oxidative stress. Conversely, circulating IGF-1 triggered itself oxidative stress and cardiomyocyte hypertrophy. Interestingly, potent cardio-protective genes (adiponectin, UCP-1 and MT-2) were increased specifically in mIGF-1-overexpressing cardiomyocytes, in a SirT1-dependent fashion. Thus, mIGF-1 protects cardiomyocytes from oxidative and hypertrophic stresses via SirT1 activity, and may represent a promising cardiac therapeutic

Sequencing of folding events in Go-like proteins

We have studied folding mechanisms of three small globular proteins: crambin (CRN), chymotrypsin inhibitor 2 (CI2) and the fyn Src Homology 3 domain (SH3) which are modelled by a Go-like Hamiltonian with the Lennard-Jones interactions. It is shown that folding is dominated by a well-defined sequencing of events as determined by establishment of particular contacts. The order of events depends primarily on the geometry of the native state. Variations in temperature, coupling strengths and viscosity affect the sequencing scenarios to a rather small extent. The sequencing is strongly correlated with the distance of the contacting aminoacids along the sequence. Thus $\alpha$-helices get established first. Crambin is found to behave like a single-route folder, whereas in CI2 and SH3 the folding trajectories are more diversified. The folding scenarios for CI2 and SH3 are consistent with experimental studies of their transition states.Comment: REVTeX, 12 pages, 11 EPS figures, J. Chem. Phys (in press

Impact of response evaluation for resectable esophageal adenocarcinoma – A retrospective cohort study

AbstractIntroduction: The standard treatment concept in patients with locally advanced adenocarcinoma of the esophagogastric junction is neoadjuvant chemotherapy, followed by tumor resection in curative intent. Response evaluation of neoadjuvant chemotherapy using histopathological tumor regression grade (TRG) has been shown to be a prognostic factor in patients with esophageal cancer. Methods: We assessed the impact of the various methods of response control and their value in correlation to established prognostic factors in a cohort of patients with adenocarcinoma at the gastroesophageal junction treated by neoadjuvant chemotherapy. Results: After neoadjuvant chemotherapy, in 56 consecutive patients with locally advanced (T2/3/4 and/or N0/N1) esophageal adenocarcinoma an oncologic tumor resection for curative intent was performed. Median follow-up was 44 months. Histopathological tumor stages were stage 0 in 10.7%, stage I in 17.9%, stage II in 21.4%, stage III in 41.1% and stage IV 8.9%. The 3-year overall survival (OS) rate was 30.3%. In univariate analysis, ypN-status, histopathological tumor stage and tumor regression grade correlated significantly with overall survival (p = 0.022, p = 0.001, p = 0.035 respectively). Clinical response evaluation could not predict response and overall survival (p = 0.556, p = 0.254 respectively). Conclusion: After preoperative chemotherapy, outcomes of esophageal carcinoma are best predicted utilizing pathological tumor stage and histologic tumor regression. Clinical response assessments were not useful for guidance of treatment

Cerebral Localized Marginal Zone Lymphoma Presenting as Hypothalamic-Pituitary Region Disorder

Introduction: Marginal zone B-cell lymphoma is a rare disease which can be considerably difficult to recognize and diagnose when signs of systemic involvement are absent. Case Presentation: We report the case of a 57-year-old woman with initial olfactory disturbance, followed by psychosis, diabetes insipidus and hypothalamic eating disorder as an uncommon clinical presentation of marginal zone B-cell lymphoma. Conclusion: Marginal zone B-cell lymphoma should be considered as a potential differential diagnosis in patients with hypothalamic disturbances