499 research outputs found
GeneBase 1.1: a tool to summarize data from NCBI gene datasets and its application to an update of human gene statistics
We release GeneBase 1.1, a local tool with a graphical interface useful for parsing, structuring and indexing data from the National Center for Biotechnology Information (NCBI) Gene data bank. Compared to its predecessor GeneBase (1.0), GeneBase 1.1 now allows dynamic calculation and summarization in terms of median, mean, standard deviation and total for many quantitative parameters associated with genes, gene transcripts and gene features (exons, introns, coding sequences, untranslated regions). GeneBase 1.1 thus offers the opportunity to perform analyses of the main gene structure parameters also following the search for any set of genes with the desired characteristics, allowing unique functionalities not provided by the NCBI Gene itself. In order to show the potential of our tool for local parsing, structuring and dynamic summarizing of publicly available databases for data retrieval, analysis and testing of biological hypotheses, we provide as a sample application a revised set of statistics for human nuclear genes, gene transcripts and gene features. In contrast with previous estimations strongly underestimating the length of human genes, a 'mean' human protein-coding gene is 67 kbp long, has eleven 309\u2009bp long exons and ten 6355\u2009bp long introns. Median, mean and extreme values are provided for many other features offering an updated reference source for human genome studies, data useful to set parameters for bioinformatic tools and interesting clues to the biomedical meaning of the gene features themselves.Database URL: http://apollo11.isto.unibo.it/software/
Laser surface texturing of alumina/zirconia composite ceramics for potential use in hip joint prosthesis
The use of metal shell to fix an acetabular cup to bone in hip joint prosthesis carries some limitations, including restrictions in prosthetic femur ball diameter and in patientâs range of motion. These drawbacks could be ideally overcome by using a monolithic ceramic acetabular cup, but the fixation of such an implant to host bone still remains a challenge. Since porous surfaces are known to promote more bone tissue interlocking compared to smooth materials, in this work the surfaces of sintered alumina/zirconia composite ceramics were treated by a pulsed laser radiation at 1064 nm with a pulse width in the nanosecond range, in order to impart controlled textural patterns. The influence of laser process parameters (e.g., energy per pulse, repetition rate, scanning speed, repetition number, angle of laser beam, and number of cycles) on the roughness and texture orientation was systematically investigated. The obtained surface topographies were inspected by optical and scanning electron microscopy, and the roughness was assessed by contact profilometry. Surface roughness could be modulated in the range of 3 to 30 ”m by varying the processing parameters, among which the number of cycles was shown to play a major role. The laser treatment was also successfully adapted and applied to ceramic acetabular cups with a curved profile, thus demonstrating the feasibility of the proposed approach to process real prosthetic componentsPostprint (published version
Effect of tyrosin kinase inhibitors on NK Cell and ILC3 development and function
Tyrosin kinase inhibitors (TKI) sharply improved the prognosis of Chronic Myeloid Leukemia (CML) and of Philadelphia+ Acute Lymphoblastic Leukemia (Ph+ALL) patients. However, TKI are not curative because of the development of resistance and lack of complete molecular remission in the majority of patients. Clinical evidences would support the notion that patient's immune system may play a key role in preventing relapses. In particular, increased proportions of terminally differentiated CD56+CD16+CD57+ NK cells have been reported to be associated with successful Imatinib therapy discontinuation or with a deep molecular response in Dasatinib-treated patients. In view of the potential role of NK cells in immune-response against CML, it is important to study whether any TKI have an effect on the NK cell development and identify possible molecular mechanism(s) by which continuous exposure to in vitro TKI may influence NK cell development and repertoire. To this end, CD34+ hematopoietic stem cells (HSC) were cultured in the absence or in the presence of Imatinib, Nilotinib, or Dasatinib. We show that all compounds exert an inhibitory effect on CD56+ cell recovery. In addition, Dasatinib sharply skewed the repertoire of CD56+ cell population, leading to an impaired recovery of CD56+CD117-CD16+CD94/NKG2A+EOMES+ mature cytotoxic NK cells, while the recovery of CD56+CD117+CD94/NKG2A ROR\u3b3t+ IL-22-producing ILC3 was not affected. This effect appears to involve the Dasatinib-mediated inhibition of Src kinases and, indirectly, of STAT5-signaling activation in CD34+ cells during first days of culture. Our studies, reveal a possible mechanism by which Dasatinib may interfere with the proliferation and maturation of fully competent NK cells, i.e., by targeting signaling pathways required for differentiation and survival of NK cells but not of ILC3
Effect of Tyrosin Kinase Inhibitors on NK Cell and ILC3 Development and Function
Tyrosin kinase inhibitors (TKI) sharply improved the prognosis of Chronic Myeloid Leukemia (CML) and of Philadelphia+ Acute Lymphoblastic Leukemia (Ph+ALL) patients. However, TKI are not curative because of the development of resistance and lack of complete molecular remission in the majority of patients. Clinical evidences would support the notion that patient's immune system may play a key role in preventing relapses. In particular, increased proportions of terminally differentiated CD56+CD16+CD57+ NK cells have been reported to be associated with successful Imatinib therapy discontinuation or with a deep molecular response in Dasatinib-treated patients. In view of the potential role of NK cells in immune-response against CML, it is important to study whether any TKI have an effect on the NK cell development and identify possible molecular mechanism(s) by which continuous exposure to in vitro TKI may influence NK cell development and repertoire. To this end, CD34+ hematopoietic stem cells (HSC) were cultured in the absence or in the presence of Imatinib, Nilotinib, or Dasatinib. We show that all compounds exert an inhibitory effect on CD56+ cell recovery. In addition, Dasatinib sharply skewed the repertoire of CD56+ cell population, leading to an impaired recovery of CD56+CD117âCD16+CD94/NKG2A+EOMES+ mature cytotoxic NK cells, while the recovery of CD56+CD117+CD94/NKG2AâRORÎłt+ IL-22-producing ILC3 was not affected. This effect appears to involve the Dasatinibâmediated inhibition of Src kinases and, indirectly, of STAT5-signaling activation in CD34+ cells during first days of culture. Our studies, reveal a possible mechanism by which Dasatinib may interfere with the proliferation and maturation of fully competent NK cells, i.e., by targeting signaling pathways required for differentiation and survival of NK cells but not of ILC3
Perspectives for the small historical centres at risk of abandonment. A pilot project for the Granfonte district in Leonforte (Italy)
[EN] The town of Leonforte, in Sicily, is currently characterised by two antithetical phenomena: the abandoment
of a significant part of the historic centre and an increasing urban sprawl in the peripheral areas. The
paper illustrates the ongoing research on the historic district of Granfonte and the pilot project for a small
block with two alternative scenarios: the restoration of the ruins and the recovery of residential use. The
two proposals can be conceived as two phases of the same project, and as alternatives to the demolitions
that nowadays seem to be the only answer to the daily challenge of living in this place.Vitale, M.; Circo, C.; Sanzaro, D.; SebĂ stian Franco, S.; Cacciatore, I.; Massimino, M. (2022). Perspectives for the small historical centres at risk of abandonment. A pilot project for the Granfonte district in Leonforte (Italy). Editorial Universitat PolitĂšcnica de ValĂšncia. 937-944. https://doi.org/10.4995/HERITAGE2022.2022.1452893794
Systematic reanalysis of partial trisomy 21 cases with or without Down syndrome suggests a small region on 21q22.13 as critical to the phenotype
A "Down Syndrome critical region" (DSCR) sufficient to induce the most constant phenotypes of Down syndrome (DS) had been identified by studying partial (segmental) trisomy 21 (PT21) as an interval of 0.6-8.3 Mb within human chromosome 21 (Hsa21), although its existence was later questioned. We propose an innovative, systematic reanalysis of all described PT21 cases (from 1973 to 2015). In particular, we built an integrated, comparative map from 125 cases with or without DS fulfilling stringent cytogenetic and clinical criteria. The map allowed to define or exclude as candidates for DS fine Hsa21 sequence intervals, also integrating duplication copy number variants (CNVs) data. A highly restricted DSCR (HR-DSCR) of only 34 kb on distal 21q22.13 has been identified as the minimal region whose duplication is shared by all DS subjects and is absent in all non-DS subjects. Also being spared by any duplication CNV in healthy subjects, HR-DSCR is proposed as a candidate for the typical DS features, the intellectual disability and some facial phenotypes. HR-DSCR contains no known gene and has relevant homology only to the chimpanzee genome. Searching for HR-DSCR functional loci might become a priority for understanding the fundamental genotype-phenotype relationships in DS
Human Innate Lymphoid Cells: Their Functional and Cellular Interactions in Decidua
Innate lymphoid cells (ILC) are developmentally related cell subsets that play a major role in innate defenses against pathogens, in lymphoid organogenesis and in tissue remodeling. The best characterized ILC are natural killer (NK) cells. They are detectable in decidua in the early phases of pregnancy. During the first trimester, NK cells represent up to 50% of decidua lymphocytes. Differently from peripheral blood (PB) NK cells, decidual NK (dNK) cells are poorly cytolytic, and, instead of IFNÎł, they release cytokines/chemokines that induce neo-angiogenesis, tissue remodeling, and placentation. dNK interact with resident myeloid cells and participate in the induction of regulatory T cells that play a pivotal role in maintaining an efficient fetalâmaternal tolerance. dNK cells may originate from CD34+ precursor cells present in situ and/or from immature NK cells already present in endometrial tissue and/or from PB NK cells migrated to decidua. In addition to NK cells, also ILC3 are present in human decidua during the first trimester. Decidual ILC3 include both natural cytotoxic receptor (NCR)+ and NCRâ cells, producing respectively IL-8/IL-22/GM-CSF and TNF/IL-17. NCR+ILC3 have been shown to establish physical and functional interactions with neutrophils that, in turn, produce factors that are crucial for pregnancy induction/maintenance and for promoting the early inflammatory phase, a fundamental process for a successful pregnancy. While NCR+ILC3 display a stable phenotype, most of NCRâILC3 may acquire phenotypic and functional features of NCR+ILC3. In conclusion, both NK cells and ILC3 are present in human decidua and may establish functional interactions with immune and myeloid cells playing an important role both in innate defenses and in tissue building/remodeling/placentation during the early pregnancy. It is conceivable that altered numbers or function of these cells may play a role in pregnancy failure
Biomimetic and mesoporous nano-hydroxyapatite for bone tissue application: a short review
In the last decades, many research groups have experimented the synthesis of hydroxyapatite (HA) for bone tissue application obtaining products with different shapes and dimensions. This review aims to summarise and critically analyse the most used methods to prepare physiologic-like nano-HA, in the form of plates or rods, similar to the HA present in the human bones. Moreover, mesoporous HA has gained increasing interest in the biomedical field due its pecualiar structural features, such as high surface area and accessible mesoporous volume, which is known to confer enhanced biological behaviour and the possibility to act as nanocarriers of functional agents for bone-related therapies. For this reason, more recent studies related to the synthesis of mesoporous HA, with physiological-like morphology, are also considered in this review. Since a wide class of surfactant molecules plays an essential role both in the shape and size control of HA crystals and in the formation of mesoporosity, a section devoted to the mechanisms of action of several surfactants is also provided
Surface Functionalisation of biomaterials with alkaline phosphatase
Two different glasses, one biocompatible but with a low bioactivity index (G1) and the other with an higher bioactivity index (G2), the ceramic version of the second glass and a titanium alloy (Ti6Al4V) have been functionalizated by anchoring alkaline phosphatase (ALP) on their surfaces. The enzyme has been chosen because it is involved in mineralization processes of hard tissues and is a model for more complex ones. ALP has been grafted on glasses and glass-ceramics surfaces both with and without samples silanization and on metallic surfaces with and without tresyl chloride activation. Samples have been analyzed at each step of the functionalization process in order to verify i
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