Selective Deamidation and Enzymatic Methylation of Seminal Ribonuclease

Isoenzymatic forms alfa2, alfa-beta, and beta2 of bovine seminal ribonuclease are generated by the transformation of beta-type into alfa-type subunit through deamidation of a single amide group. The residue involved in this selective deamidation has been identified as Asn67 . Deamidation occurs by formation of a cyclic imide intermediate involving the Gly at position 68. Opening of the cyclic imide may occur on either side of the nitrogen, generating both the normal alfa-aspartyl and an isoaspartyl residue at position 67. The alfa-carboxyl of the isoaspartyl residue is effectively methylated by bovine brain protein carboxylmethyltransferase

Fertility preservation in ovarian tumours

A considerable number of patients with a cancer diagnosis are of childbearing age and have not satisfied their desire for a family. Despite ovarian cancer (OC) usually occurring in older patients, 3%–14% are diagnosed at a fertile age with the overall 5-year survival rate being 91.2% in women ≤44 years of age when it is found at 1A–B stage. In this scenario, testing the safety and the efficacy of fertility sparing strategies in OC patients is very important overall in terms of quality of life. Unfortunately, the lack of randomised trials to validate conservative approaches does not guarantee the safety of fertility preservation strategies. However, evidence-based data from descriptive series suggest that in selected cases, the preservation of the uterus and at least one part of the ovary does not lead to a high risk of relapse. This conservative surgery helps to maintain organ function, giving patients of childbearing age the possibility to preserve their fertility. We hereby analysed the main evidence from the international literature on this topic in order to highlight the selected criteria for conservative management of OC patients, including healthy BRCA mutations carriers

Analysis of fossil planktonic foraminifera: the sieve mesh effect

The choice of the sediment size fraction in the analysis of fossil planktonic foraminifera is of great importance in determining the composition of assemblages. In past studies several size fractions have been utilised. Imbrie and Kipp (1971) stated that “smaller fractions give rise to too many uncertainties in the identification of small specimens and require too long to process. Large mesh size yield undesiderable loss of small species, and small specimens of larger species”. The adoption of coarser sieve meshes has the effect to reduce the percentages of small sized (usually living in cold waters) species (Bé and Hutson, 1977). In a comparison between >63 μm and >150 μm size-fraction of planktonic foraminifera assemblages from NW Atlantic Ocean, Smart (2002), stated that because particular smaller species are either under-represented or even absent from the larger (>150 μm) size-fraction, the smaller (>63 μm) size-fraction must be included in studies of planktonic foraminifera. Di Donato et al. (2008) highlighted in the >150 μm size fraction of a core from the Tyrrhenian Sea, a great loss of the small-sized species Turborotalita quinqueloba in glacial samples, where this species is very abundant. This caused an increase in warm water species such as Globigerinoides ruber, apparently reaching typical Holocene values in some full glacial levels. From the above mentioned statements, it is clear that treatment changes can strongly influence the results of palaeoclimatic reconstructions based on planktonic foraminiferal assemblages. As stated by Aitchison (1986, 1992) scale invariance and subcompositional coherence are fundamental properties of the compositional data analysis (CODA). The main goal of this paper is to verify if the variable relationships pointing out from CODA of foraminiferal assemblages are or not influenced by the size fraction and, more in general, to test the robustness of CODA respect to treatment changes related to different preparation techniques for the analysis of planktonic foraminifera

Quantitative analysis of late gadolinium enhancement in hypertrophic cardiomyopathy

Background: Cardiovascular Magnetic resonance (CMR) with the late gadolinium enhancement (LGE) technique allows the detection of myocardial fibrosis in Hypertrophic cardiomyopathy (HCM). The aim of this study was to compare different methods of automatic quantification of LGE in HCM patients. Methods: Forty HCM patients (mean age 48 y, 30 males) and 20 normal subjects (mean age 38 y, 16 males) underwent CMR, and we compared 3 methods of quantification of LGE: 1) in the SD2 method a region of interest (ROI) was placed within the normal myocardium and enhanced myocardium was considered as having signal intensity>2 SD above the mean of ROI; 2) in the SD6 method enhanced myocardium was defined with a cut-off of 6 SD above mean of ROI; 3) in the RC method a ROI was placed in the background of image, a Rayleigh curve was created using the SD of that ROI and used as ideal curve of distribution of signal intensity of a perfectly nulled myocardium. The maximal signal intensity found in the Rayleigh curve was used as cut-off for enhanced myocardium. Parametric images depicting non enhanced and enhanced myocardium was created using each method. Three investigators assigned a score to each method by the comparison of the original LGE image to the respective parametric map generated. Results: Patients with HCM had lower concordance between the measured curve of distribution of signal intensity and the Rayleigh curve than controls (63.7 ± 12.3 % vs 92.2 ± 2.3%, p < 0.0001)

ROS in cancer therapy: the bright side of the moon.

Reactive oxygen species (ROS) constitute a group of highly reactive molecules that have evolved as regulators of important signaling pathways. It is now well accepted that moderate levels of ROS are required for several cellular functions, including gene expression. The production of ROS is elevated in tumor cells as a consequence of increased metabolic rate, gene mutation and relative hypoxia, and excess ROS are quenched by increased antioxidant enzymatic and nonenzymatic pathways in the same cells. Moderate increases of ROS contribute to several pathologic conditions, among which are tumor promotion and progression, as they are involved in different signaling pathways and induce DNA mutation. However, ROS are also able to trigger programmed cell death (PCD). Our review will emphasize the molecular mechanisms useful for the development of therapeutic strategies that are based on modulating ROS levels to treat cancer. Specifically, we will report on the growing data that highlight the role of ROS generated by different metabolic pathways as Trojan horses to eliminate cancer cells

Immunotherapy in endometrial cancer: new scenarios on the horizon

This extensive review summarizes clinical evidence on immunotherapy and targeted therapy currently available for endometrial cancer (EC) and reports the results of the clinical trials and ongoing studies. The research was carried out collecting preclinical and clinical findings using keywords such as immune environment, tumor infiltrating lymphocytes, programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) expression, immune checkpoint inhibitors, anti-PD-1/PD-L1 antibodies and others’ on PubMed. Finally, we looked for the ongoing immunotherapy trials on ClinicalTrials.gov. EC is the fourth most common malignancy in women in developed countries. Despite medical and surgical treatments, survival has not improved in the last decade and death rates have increased for uterine cancer in women. Therefore, identification of clinically significant prognostic risk factors and formulation of new rational therapeutic regimens have great significance for enhancing the survival rate and improving the outcome in patients with advanced or metastatic disease. The identification of genetic alterations, including somatic mutations and microsatellite instability, and the definition of intracellular signaling pathways alterations that have a major role in in tumorigenesis is leading to the development of new therapeutic options for immunotherapy and targeted therapy

Biomass valorization: Sustainable methods for the production of hemicellulolytic catalysts from thermoanaerobacterium thermostercoris strain buff

Processing and selection of fruits and vegetables generate high quantities of wastes that represent an economic and environmental issue for the agroindustry sector. According to the so-called “biorefinery” approach, this biomass can be exploited for the recovery of value-added molecules. In this study, the residues of industrial processing of tomato (Lycopersicon esculentum variety “Hybrid Rome”), fennel (Foeniculum vulgare), potato (Solanum tuberosum) and carrot (Daucus carota) were used as sole carbon sources to support cheap and sustainable microbial growth as well as the production of secondary metabolites (hydrogen and ethanol) by Thermoanaerobacterium thermostercoris strain BUFF, a thermophilic anaerobic microorganism isolated from buffalo-dung compost. Moreover, the use of hemicellulolytic enzymes of T. thermostercoris was assayed in the bioconversion reaction of the polymer fraction extracted from the rhizome of giant reed (Arundo donax) and of the leaves and stems of cardoon (Cynara cardunculus), dedicated non-food crops employed in energy supply

Evidence of oxidative stress in young and aged DJ-1-deficient mice

AbstractLoss of DJ-1 function contributes to pathogenesis in Parkinson’s disease. Here, we investigate the impact of aging and DJ-1 deficiency in transgenic mice. Ventral midbrain from young DJ-1-deficient mice revealed no change in 4-hydroxy-2-nonenal (4-HNE), but HSP60, HSP40 and striatal dopamine turnover were significantly elevated compared to wildtype. In aged mice, the chaperone response observed in wildtype animals was absent from DJ-1-deficient transgenics, and nigral 4-HNE immunoreactivity was enhanced. These changes were concomitant with increased striatal dopamine levels and uptake. Thus, increased oxidants and diminished protein quality control may contribute to nigral oxidative damage with aging in the model

Parageobacillus thermantarcticus, an Antarctic Cell Factory: From Crop Residue Valorization by Green Chemistry to Astrobiology Studies

Knowledge of Antarctic habitat biodiversity, both marine and terrestrial, has increased considerably in recent years, causing considerable development in the studies of life science related to Antarctica. In the Austral summer 1986–1987, a new thermophilic bacterium, Parageobacillus thermantarcticus strain M1 was isolated from geothermal soil of the crater of Mount Melbourne (74°22′ S, 164°40′ E) during the Italian Antarctic Expedition. In addition to the biotechnological potential due to the production of exopolysaccharides and thermostable enzymes, successful studies have demonstrated its use in the green chemistry for the transformation and valorization of residual biomass and its employment as a suitable microbial model for astrobiology studies. The recent acquisition of its genome sequence opens up new opportunities for the use of this versatile bacterium in still unexplored biotechnology sectors