The Latin Leaflet, Number 29

Polymer electrolytes represent the ultimate in terms of desirable properties of energy storage/conversion devices, as they can offer an all-solid-state construction, a wide variety of shapes and sizes, light-weight, low costs, high energy density and safety. Here we present our recent results concerning a novel strategy for preparing efficient polymer membranes which are successfully demonstrated as suitable electrolytes for several energy conversion and storage devices (i.e., Li- and Na-based batteries and DSSCs). Highly ionic conducting polymer electrolytes containing PEO-based functionalities and different components (e.g., Li/Na salts, RTILs, natural biosourced and cellulosic fillers) are successfully prepared via a rapid process and, directly or subsequently, cross-linked via UV irradiation (patent pending, PCT/IT2014/000008). All the prepared materials are thoroughly characterised in terms of their physical, chemical and morphological properties and tested for their electrochemical performances and durability. The UV-curing process on such materials led to the production of elastic and resistant amorphous macromolecular networks. Noticeably increased ionic conductivities are registered (10-3 S cm-1 at RT), along with very stable interfacial and storage stability and wide electrochemical stability windows. The different lab-scale solid-state devices show remarkable performances even at ambient temperature, at the level of those using liquid electrolytes, respect to which demonstrate much greater durability and safety. The obtained findings demonstrate a new, easy and low cost approach to fabricate and tailor-make polymer electrolytes with highly promising prospects for the next generation of advanced flexible energy production and storage devices

Lamination And Microstructuring Technology for a Bio-Cell Multiwell array

Microtechnology becomes a versatile tool for biological and biomedical applications. Microwells have been established long but remained non-intelligent up to now. Merging new fabrication techniques and handling concepts with microelectronics enables to realize intelligent microwells suitable for future improved cancer treatment. The described technology depicts the basis for the fabrication of a elecronically enhanced microwell. Thin aluminium sheets are structured by laser micro machining and laminated successively to obtain registration tolerances of the respective layers of 5..10\^A$\mu$m. The microwells lasermachined into the laminate are with 50..80\^A$\mu$m diameter, allowing to hold individual cells within the well. The individual process steps are described and results on the microstructuring are given.Comment: Submitted on behalf of EDA Publishing Association (http://irevues.inist.fr/EDA-Publishing

The Genetic Structure and History of Africans and African Americans.

Africa is the source of all modern humans, but characterization of genetic variation and of relationships among populations across the continent has been enigmatic. We studied 121 African populations, four African American populations, and 60 non-African populations for patterns of variation at 1327 nuclear microsatellite and insertion/deletion markers. We identified 14 ancestral population clusters in Africa that correlate with self-described ethnicity and shared cultural and/or linguistic properties. We observed high levels of mixed ancestry in most populations, reflecting historical migration events across the continent. Our data also provide evidence for shared ancestry among geographically diverse hunter-gatherer populations (Khoesan speakers and Pygmies). The ancestry of African Americans is predominantly from Niger-Kordofanian (approximately 71%), European (approximately 13%), and other African (approximately 8%) populations, although admixture levels varied considerably among individuals. This study helps tease apart the complex evolutionary history of Africans and African Americans, aiding both anthropological and genetic epidemiologic studies

MET increased gene copy number and primary resistance to gefitinib therapy in non-small-cell lung cancer patients

Background: MET amplification has been detected in ∼20% of non-small-cell lung cancer patients (NSCLC) with epidermal growth factor receptor (EGFR) mutations progressing after an initial response to tyrosine kinase inhibitor (TKI) therapy. Patients and methods: We analyzed MET gene copy number using FISH in two related NSCLC cell lines, one sensitive (HCC827) and one resistant (HCC827 GR6) to gefitinib therapy and in two different NSCLC patient populations: 24 never smokers or EGFR FISH-positive patients treated with gefitinib (ONCOBELL cohort) and 182 surgically resected NSCLC not exposed to anti-EGFR agents. Results: HCC827 GR6-resistant cell line displayed MET amplification, with a mean MET copy number >12, while sensitive HCC827 cell line had a mean MET copy number of 4. In the ONCOBELL cohort, no patient had gene amplification and MET gene copy number was not associated with outcome to gefitinib therapy. Among the surgically resected patients, MET was amplified in 12 cases (7.3%) and only four (2.4%) had a higher MET copy number than the resistant HCC827 GR6 cell line. Conclusions: MET gene amplification is a rare event in patients with advanced NSCLC. The development of anti-MET therapeutic strategies should be focused on patients with acquired EGFR-TKI resistanc

α‐Triazolylboronic Acids: A Novel Scaffold to Target FLT3 in AML

: The treatment of acute myeloid leukemia (AML) presents a challenge to current therapies because of the development of drug resistance. Genetic mutation of FMS-like tyrosine kinase-3 (FLT3) is a target of interest for AML treatment, but the use of FLT3-targeting agents on AML patients has so far resulted in poor overall clinical outcomes.1 The incorporation of the boronic group in a drug scaffold could enhance the bioavailability and pharmacokinetic profile of conventional anticancer chemotypes. Boronic acids represent an intriguing and unexplored class of compounds in the context of AML, and they are only scantly reported as inhibitors of protein kinases. We identified a-triazolylboronic acids as a novel chemotype for targeting FLT3 by screening a library of structurally heterogeneous in-house boronic acids. Selected compounds show low micromolar activities on enzymatic and cellular assays, selectivity against control cell lines and a recurring binding mode in in-silico studies. Furthermore, control analogues synthesized ad hoc and lacking the boronic acid are inactive, confirming that this group is essential for the activity of the series. All together, these results suggest α-triazolylboronic acids could be a promising novel chemotype for FLT3 inhibition, laying the ground for the design of further compounds

Intellectual Property, Open Science and Research Biobanks

In biomedical research and translational medicine, the ancient war between exclusivity (private control over information) and access to information is proposing again on a new battlefield: research biobanks. The latter are becoming increasingly important (one of the ten ideas changing the world, according to Time magazine) since they allow to collect, store and distribute in a secure and professional way a critical mass of human biological samples for research purposes. Tissues and related data are fundamental for the development of the biomedical research and the emerging field of translational medicine: they represent the “raw material” for every kind of biomedical study. For this reason, it is crucial to understand the boundaries of Intellectual Property (IP) in this prickly context. In fact, both data sharing and collaborative research have become an imperative in contemporary open science, whose development depends inextricably on: the opportunities to access and use data, the possibility of sharing practices between communities, the cross-checking of information and results and, chiefly, interactions with experts in different fields of knowledge. Data sharing allows both to spread the costs of analytical results that researchers cannot achieve working individually and, if properly managed, to avoid the duplication of research. These advantages are crucial: access to a common pool of pre-competitive data and the possibility to endorse follow-on research projects are fundamental for the progress of biomedicine. This is why the "open movement" is also spreading in the biobank's field. After an overview of the complex interactions among the different stakeholders involved in the process of information and data production, as well as of the main obstacles to the promotion of data sharing (i.e., the appropriability of biological samples and information, the privacy of participants, the lack of interoperability), we will firstly clarify some blurring in language, in particular concerning concepts often mixed up, such as “open source” and “open access”. The aim is to understand whether and to what extent we can apply these concepts to the biomedical field. Afterwards, adopting a comparative perspective, we will analyze the main features of the open models – in particular, the Open Research Data model – which have been proposed in literature for the promotion of data sharing in the field of research biobanks. After such an analysis, we will suggest some recommendations in order to rebalance the clash between exclusivity - the paradigm characterizing the evolution of intellectual property over the last three centuries - and the actual needs for access to knowledge. We argue that the key factor in this balance may come from the right interaction between IP, social norms and contracts. In particular, we need to combine the incentives and the reward mechanisms characterizing scientific communities with data sharing imperative

Optical Density Of Bone Repair After Implantation Of Homogenous Demineralized Dentin Matrix In Diabetic Rabbits

This research evaluated the bone repair process after implantation of homogenous demineralized dentin matrix (HDDM) in surgical defects in the parietal bone of rabbits with alloxan-induced diabetes, using a polytetrafluorethylene (PTFe) barrier for guided bone regeneration. Thirty-six rabbits were used and divided into four groups: control (C, n = 12), diabetic (D, n = 12, left parietal bone), diabetic with PTFe (DPTFe, same 12 rabbits, right parietal bone), and diabetic with PTFe associated to HDDM (D-PTFe+HDDM, n = 12). Bone defects were created in the parietal bone of the rabbits and the experimental treatments were performed, where applicable. The rabbits were sacrificed after 15, 30, 60 and 90 days. The bone defects were examined radiographically and by optical density (ANOVA and Tukey test, p < .05). The radiographic findings showed that the D-PTFe+HDDM group presented greater radiopacity and better trabecular bone arrangement when compared to that of the C, D and D-PTFe groups. The statistical analysis showed significant differences in the optical density of the newly formed bone among the studied groups. It was possible to conclude that HDDM was biocompatible in diabetic rabbits.223275280Abreu, P.P., Morosolli, A., Araújo, M.M., Carvalho, V.A.P., Gomes, M.F., Effects of autogenous demineralized dentin matrix on dental socket wound healing process in human (2004) Braz Oral Res, 18, p. 52. , SupplCarvalho, V.A.P., Tosello, D.O., Salgado, M.A.C., Gomes, M.F., Histomorphometric analysis of homogenous demineralized dentin matrix as osteopromotive material in rabbit mandibules (2004) Int J Oral Maxillofac Implants, 19 (5), pp. 679-686Gomes, M.F., Anjos, M.J.S., Nogueira, T.O., Catanzaro-Guimarães, S.A., Autogenous demineralized dentin matrix for tissue engineering applications: Radiographic and histomorphometric studies (2002) Int J Oral Maxillofac Implants, 17 (4), pp. 488-497Gomes, M.F., Silva, M.J.S., Nogueira, T.O., Catanzaro-Guimarães, S.A., Histologic evaluation of the osteoinductive property of autogenous demineralized dentin matrix on surgical bone defects in rabbit skulls using human amniotic membrane for guided bone regeneration (2001) Int J Oral Maxillofac Implants, 16 (4), pp. 563-571Guyton, A.C., Hall, J.E., (2006) Insulin, Glucagon, and Diabetes mellitus, pp. 827-840. , Guyton AC, Hall JE. Textbook of Medical Physiology. 11th ed, Elsevier;Fiorellini, J.P., Nevins, M.L., Norkin, A., Weber, H.P., Karimbux, N.Y., The effect of insulin therapy on osseointegration in a diabetic rat model (1999) Clin Oral Implants Res, 10 (5), pp. 362-368Lu, H., Kraut, D., Gerstenfeld, L.C., Graves, D.T., Diabetes interferes with the bone formation by affecting the expression of transcription factors that regulate osteoblast differentiation (2003) Endocrinology, 144 (1), pp. 346-352Nevins, M.L., Karimbux, N.Y., Weber, H.P., Giannobile, W.V., Fiorellini, J.P., Wound healing around endosseous implants in experimental diabetes (1998) Int J Oral Maxillofac Implants, 13 (5), pp. 620-629Claro, F.A., Lima, J.R., Salgado, M.A.C., Gomes, M.F., Porous Polyethylene for tissue engineering applications in diabetic rats treated with calcitonin: Histomorphometric analysis (2005) Int J Oral Maxillofac Implants, 20 (2), pp. 211-219Catanzaro-Guimarães, S.A., Catanzaro Guimarães, B.P., Garcia, R.B., Alle, N., Osteogenic potential of autogenic demineralized dentin implanted in bony defects in dogs (1986) Int J Oral Maxillofac Surg, 15 (2), pp. 160-169Bessho, K., Tagawa, T., Murata, M., Purification of rabbit bone morphogenetic protein derived from bone, dentin, and wound tissue after tooth extraction (1990) J Oral Maxillofac Surg, 48 (2), pp. 162-169Nakashima, M., Induction of dentine in amputated pulp of dogs by recombinant human bone morphogenetic proteins-2 and -4 with collagen matrix (1994) Arch Oral Biol, 39 (12), pp. 1085-1089Catanzaro-Guimarães SA. Possibility to reinforce bone repair with decalcified dentin matrix. In: Gesellschaft für orale Implantologie (ed.). Jahrbuch für Orale Implatologie. Berlin: Quintessenz1993. p. 33-

Subcutaneous Adipose Tissue Transcriptome Highlights Specific Expression Profiles in Severe Pediatric Obesity: A Pilot Study

The prevalence of pediatric obesity is rising rapidly worldwide, and "omic" approaches are helpful in investigating the molecular pathophysiology of obesity. This work aims to identify transcriptional differences in the subcutaneous adipose tissue (scAT) of children with overweight (OW), obesity (OB), or severe obesity (SV) compared with those of normal weight (NW). Periumbilical scAT biopsies were collected from 20 male children aged 1-12 years. The children were stratified into the following four groups according to their BMI z-scores: SV, OB, OW, and NW. scAT RNA-Seq analyses were performed, and a differential expression analysis was conducted using the DESeq2 R package. A pathways analysis was performed to gain biological insights into gene expression. Our data highlight the significant deregulation in both coding and non-coding transcripts in the SV group when compared with the NW, OW, and OB groups. A KEGG pathway analysis showed that coding transcripts were mainly involved in lipid metabolism. A GSEA analysis revealed the upregulation of lipid degradation and metabolism in SV vs. OB and SV vs. OW. Bioenergetic processes and the catabolism of branched-chain amino acids were upregulated in SV compared with OB, OW, and NW. In conclusion, we report for the first time that a significant transcriptional deregulation occurs in the periumbilical scAT of children with severe obesity compared with those of normal weight or those with overweight or mild obesity

Ethnic fragmentation and degree of urbanization strongly affect the discrimination power of Y-STR haplotypes in central Sahel

Y chromosome short tandem repeats (Y-STRs) are commonly used to identify male lineages for investigative and judicial purposes and could represent the only source of male-specific genetic information from unbalanced female-male mixtures. The Yfiler Plus multiplex, which includes twenty conventional and seven rapidly-mutating Y-STRs, represents the most discriminating patrilineal system commercially available to date. Over the past five years, this multiplex has been used to analyze several Eurasian populations, with a reported discrimination capacity (DC) approaching or corresponding to the highest possible value. However, despite the inclusion of rapidly mutating Y-STRs, extensive haplotype sharing was still reported for some African populations due to a number of different factors affecting the effective population size. In the present study, we analyzed 27 Y-STRs included in the Yfiler Plus multiplex and 82 Y-SNPs in central Sahel (northern Cameroon and western Chad), an African region characterized by a strong ethnic fragmentation and linguistic diversity. We evaluated the effects of population sub-structuring on genetic diversity by stratifying a sample composed of 431 males according to their ethnicity (44 different ethnic groups) and urbanization degree (four villages and four towns). Overall, we observed a low discrimination capacity (DC = 0.90), with 71 subjects (16.5 %) sharing 27 Y-STR haplotypes. Haplotype sharing was essentially limited to subjects with the same binary haplogroup, coming from the same location and belonging to the same ethnic group. Haplotype sharing was much higher in rural areas (average DC = 0.83) than urban settlements (average DC = 0.96) with a significant correlation between DC and census size (r = 0.89; p = 0.003). Notably, we found that genetic differentiation between villages from the same country (ΦST = 0.14) largely exceeded that found among countries (ΦST = 0.02). These findings have important implications for the choice of the appropriate reference population database to evaluate the statistical relevance of forensic Y-haplotype matches