•Our vaccine candidate (6611 strain) reduced the infection in challenged mice.•Our vaccine candidate induced humoral and cellular immune response.•No false PPDb reactor was detected in the caudal ...fold tuberculin test.
Bovine paratuberculosis is one of the most important chronic infectious diseases in livestock. This disease is difficult to control because of its inefficient management (test and cull strategy and inadequate biosecurity). Thus, the development of an effective vaccine is essential. In this study, we evaluated a local virulent strain (6611) of Mycobacterium avium subsp. paratuberculosis as an inactivated vaccine in comparison with the Silirum vaccine in mouse model and cattle. Regarding the mice model, only the groups vaccinated with 6611 showed lower colony forming unit (CFU) counts with a lower lesion score in the liver in comparison to the control group at 6 and 12 weeks post-challenge (wpc). The immune response was predominantly humoral (IgG1), although both vaccinated groups presented a cellular response with IFNγ production as well, but the 6611 group had also significant production of IL-2, IL-6, IL-17a, TNF, and IL-10. In cattle, the 6611 vaccinated group was the only one that maintained significant antibody values at the end of the trial, with significant production of IgG2 and IFNγ. No PPDb reactor was detected in the vaccinated animals, according to the intradermal caudal fold tuberculin test. Our results indicate that the 6611 local strain protected mice from challenge with a virulent strain, by inducing a humoral and cellular immune response. In the bovine, the natural host, the evaluated vaccine also induced humoral and cellular immune responses, with higher levels of CD4 + CD25+ and CD8 + CD25+ T cells populations than the commercial vaccine. Despite the encouraging results obtained in this study, an experimental challenge trial in cattle is mandatory to evaluate the efficacy of our candidate vaccine in the main host.
Smith-Lemli-Opitz syndrome (SLOS) is a rare genetic neurodevelopmental disorder caused by the defect in the 7-dehydrocholesterol reductase. This defect leads to the deficiency of cholesterol ...biosynthesis with accumulation of 7-dehydrocholesterol. Inhibitory factor 1 (IF
) is a well-known mitochondrial protein. Recently, it has been discovered in the human serum where it is reported to be involved in the HDL-cholesterol intake. Here we report the IF
presence in the serum of two paediatric SLOS dizygotic twins treated with dietary cholesterol supplementation.
The patients showed a typical phenotype. They started dietary supplementation with cholesterol when 2 months old. The cholesterol intake was periodically titrated on the basis of weight increase and the twin 1 required a larger supplementation than the twin 2 during the follow-up. When 6.4-year-old, they underwent IF
assay that was 7-fold increased in twin 2 compared to twin 1 (93.0 pg/ml vs 13.0 pg/ml, respectively).
We report, for the first time, the presence of circulating IF
in the serum of SLOS patients, showing different levels among them. Our findings confirm that IF
could be a novel research target in cholesterol-related disorders and also in SLOS, and could contribute to the general debate on IF
as a new modulator of cholesterol levels.
Scaffold proteins are crucial regulators of signaling networks, and their abnormal expression may favor the development of tumors. Among the scaffold proteins, immunophilin covers a unique role as ...'protein-philin' (Greek 'philin' = friend) that interacts with proteins to guide their proper assembly. The growing list of human syndromes associated with the immunophilin defect underscores the biological relevance of these proteins that are largely opportunistically exploited by cancer cells to support and enable the tumor's intrinsic properties. Among the members of the immunophilin family, the
gene was the only one identified to have a splicing variant. Cancer cells impose unique demands on the splicing machinery, thus acquiring a particular susceptibility to splicing inhibitors. This review article aims to overview the current knowledge of the
gene functions in human cancer, illustrating how cancer cells exploit the scaffolding function of canonical FKBP51 to foster signaling networks that support their intrinsic tumor properties and the spliced FKBP51s to gain the capacity to evade the immune system.
Synthesis of Staphylococcus aureus type 5 capsular polysaccharide repeating unit using novel l-FucNAc and d-FucNAc synthons and immunochemical evaluation.
Staphylococcus aureus is a major cause of ...nosocomial infections. Glycoconjugates of type 5 and 8 capsular polysaccharides have been investigated for vaccine application. The proposed structure of type 5 polysaccharide is: →4-β-d-ManNAcA-(1→4)-α-l-FucNAc(3OAc)-(1→3)-β-d-FucNAc-(1→. The stereocontrolled insertion of these three glycosydic bonds is a real synthetic challenge. In the present paper we report the preparation of two novel versatile l- and d-fucosamine synthons from commercially available starting materials. In addition we applied the two building blocks to the synthesis of type 5 trisaccharide repeating unit. The immunochemical properties of the synthesized trisaccharide were assessed by competitive ELISA and by immunodot blot analysis using sera of mice immunized with type 5 polysaccharide conjugated to CRM197. The results suggest that although the type 5 S. aureus trisaccharide is recognized by specific anti polysaccharide antibodies in dot blot, structures longer than the trisaccharide may be needed in order to significantly compete with the native type 5 polymer in the binding with sera from mice immunized with S. aureus type 5 polysaccharide–CRM197 conjugate.
In diverse taxa, photoperiodic responses that cause seasonal physiological and behavioural shifts are controlled by genes, including the vertebrate Clock orthologues, that encode for circadian ...oscillator mechanisms. While the genetic network behind circadian rhythms is well described, relatively few reports exist of the phenological consequences of and selection on Clock genes in the wild. Here, we investigated variation in breeding phenology in relation to Clock genetic diversity in a long-distance migratory bird, the barn swallow (Hirundo rustica).
In a sample of 922 adult barn swallows from a single population breeding in Italy we found one very common (Q(7)) and three rare (Q(5), Q(6), Q(8)) length variants of a functionally significant polyglutamine repeat. Rare (2.9%) Q(7)/Q(8) heterozygous females, but not males, bred significantly later than common (91.5%) Q(7)/Q(7) females, consistent with the expectation that 'long' alleles cause late breeding, as observed in a resident population of another bird species. Because breeding date depends on arrival date from migration, present results suggest that the association between breeding date and Clock might be mediated by migration phenology. In addition, fecundity selection appears to be operating against Q(7)/Q(8) because late migrating/breeding swallows have fewer clutches per season, and late breeding has additional negative selection effects via reduced offspring longevity. Genotype frequencies varied marginally non-significantly with age, as Q(7)/Q(8) frequency showed a 4-fold reduction in old individuals. This result suggests negative viability selection against Q(7)/Q(8), possibly mediated by costs of late breeding.
This is the first study of migratory birds showing an association between breeding phenology and Clock genotype and suggesting that negative selection occurs on a phenologically deviant genotype. Low polymorphism at Clock may constrain microevolutionary phenological response to changing climate, and may thus contribute to the decline of barn swallow populations.
Chronic lymphocytic leukaemia (CLL) is associated with apoptosis resistance and defective control of cell growth. Our study describes for the first time a critical role in CLL for the KRAB-zinc ...finger protein ZNF224. High ZNF224 transcript levels were detected in CLL patients with respect to control cells. Moreover, ZNF224 expression was significantly lowered after conventional chemotherapy treatment in a subset of CLL patients. By in vitro experiments we confirmed that ZNF224 expression is suppressed by fludarabine and demonstrated that ZNF224 is involved in apoptosis resistance in CLL cells. Moreover, we showed that ZNF224 positively modulates cyclin D3 gene expression. Consistently, we observed that alteration of ZNF224 expression leads to defects in cell cycle control. All together, our results strongly suggest that in CLL cells high expression level of ZNF224 can lead to inappropriate cell growth and apoptosis resistance, thus contributing to CLL progression. Targeting ZNF224 could thus improve CLL response to therapy.
In recent years, many progresses have been pursued in the management of advanced pancreatic neuroendocrine tumor (pNET); most of them were prompted by increasing knowledge of biology of these ...neoplasms, including the identification of promising biological targets for therapy. PNETs belong to a group of rare neoplastic diseases. They originate from neuroendocrine system cells and are very heterogeneous regarding anatomic localization and aggressiveness. Recently, many efforts have been particularly focused on the identification of pathologic pathways and innovative drugs in order to treat patients with unresectable, metastatic disease, in progressive well-differentiated pNETs. Chemotherapy remains the mainstay of treatment of poorly-differentiated pNETs. The positive results obtained by sunitinib, a multi-targeted tyrosine kinase receptor inhibitor of vascular endothelial growth factor receptor (VEGFR) 1-3, platelet-derived growth factor receptor (PDGFR), c-kit, RET, colony stimulating factor-1 receptor (CSF-1R) and Fms-like tyrosine kinase 3 (FLT3), with direct antitumor and antiangiogenic effects, have highlighted the importance of tumor angiogenesis inhibition in controlling these tumors. Angiogenesis is a crucial process during tumor progression and plays a key role in development of metastasis. The role of angiogenesis in the malignant spread of pNET cells is finally supported by in vivo studies conducted on the RIP1-Tag2 mouse model. In this mini-review, we focus on the two pharmaceuticals that have given the most interesting results in clinical trials: bevacizumab and sunitinib. These drugs are changing the management of advanced pNETs.
Aim and objective
To test the psychometric properties of the nursing students' version of the 24‐item Caring Behaviours Inventory.
Background
Caring is at the heart of nursing and should also be a ...core value in nursing education. Caring can be manifested through measurable behaviours. The Caring Behaviors Inventory is a valid and reliable measure of nurses' caring behaviours in clinical settings. It has already been used among nursing students, but it needs more psychometric testing.
Design
Cross‐sectional validation study.
Method
The questionnaire was filled in by 300 undergraduate nursing students at two Italian universities in May 2016. Exploratory factor analysis was conducted using Mplus maximum likelihood with GEOMIN oblique rotation. A multifaceted approach was used to evaluate the model fit. The STROBE checklist for cross‐sectional studies was followed.
Results
Four dimensions were identified: “being with,” “doing with competence,” “responding to individual needs” and “providing effective care.” Adequate fit indices and high reliability of the factors were found. Correlations between factors were positive and significant.
Conclusion
This study makes it possible to use the same tool to compare the caring practices perceived by students, nurses and patients. Further studies with bigger samples could be stratified to investigate the associations between caring levels and student characteristics. The Caring Behaviors Inventory can be used to call attention to caring in nursing education, helping to make this concept less elusive.
Relevance to clinical practice
The effective self‐assessment of nursing students' caring behaviours offers opportunities for reflection on their caring practice. This could improve the caring level of their behaviours in clinical practice and help them to become caring nurses in the future.
The rise of antibiotic-resistant
, a leading nosocomial pathogen, prompts the need for alternative therapies. We have identified and characterized a novel depolymerase enzyme encoded by
phage KP36 ...(depoKP36), from the
family. To gain insights into the catalytic and structural features of depoKP36, we have recombinantly produced this protein of 93.4 kDa and showed that it is able to hydrolyze a crude exopolysaccharide of a
host. Using in vitro and in vivo assays, we found that depoKP36 was also effective against a native capsule of clinical
strains, representing the K63 type, and significantly inhibited
-induced mortality of
larvae in a time-dependent manner. DepoKP36 did not affect the antibiotic susceptibility of
strains. The activity of this enzyme was retained in a broad range of pH values (4.0-7.0) and temperatures (up to 45 °C). Consistently, the circular dichroism (CD) spectroscopy revealed a highly stability with melting transition temperature (T
) = 65 °C. In contrast to other phage tailspike proteins, this enzyme was susceptible to sodium dodecyl sulfate (SDS) denaturation and proteolytic cleavage. The structural studies in solution showed a trimeric arrangement with a high β-sheet content. Our findings identify depoKP36 as a suitable candidate for the development of new treatments for
infections.
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