Localization of transversal cracks in sandwich beams and evaluation of their severity

An algorithm to assess transversal cracks in composite structures based on natural frequency changes due to damage is proposed. The damage assessment is performed in two steps; first the crack location is found, and afterwards an evaluation of its severity is performed. The technique is based on a mathematical relation that provides the exact solution for the frequency changes of bending vibration modes, considering two terms. The first term is related to the strain energy stored in the beam, while the second term considers the increase of flexibility due to damage. Thus, it is possible to separate the problems of localization and severity assessment, which makes the localization process independent of the beams cross-section shape and boundary conditions. In fact, the process consists of comparing vectors representing the measured frequency shifts with patterns constructed using the mode shape curvatures of the undamaged beam. Once the damage is localized, the evaluation of its severity is made taking into account the global rigidity reduction. The damage identification algorithm was validated by experiments performed on numerous sandwich panel specimens

Negative Correlation between Fetuin-A and Indices of Vascular Disease in Systemic Lupus Erythematosus Patients with and without Lupus Nephritis

Introduction: Fetuin-A, a systemic calcification inhibitor, has been negatively related to vascular calcification (VC) and cardiovascular mortality. In this study we investigated the association between fetuin-A levels and atherosclerotic vascular complications in systemic lupus erythematosus (SLE) patients with and without lupus nephritis (LN). Methods: We recruited 20 SLE patients without LN, 20 SLE patients with LN and 20 healthy controls. We determined serum creatinine, lipid profile, high sensitivity C-reactive protein (hsCRP), calcium, phosphate and fetuin-A levels, and calculated the calcification risk index (CRI) and SLE disease activity index (SLEDAI) for all subjects. Vascular disease burden was assessed by quantification of carotid artery intima-media-thickness (IMT) and the ankle-brachial index (ABI). Results: Fetuin-A levels were significantly lower in LN patients (0.47 ± 0.1 g/L) compared to SLE patients without LN (0.54 ± 0.1 g/L) and both were significantly lower than controls (0.78 ± 0.2 g/L). CRI was significantly higher in LN patients (89.1 ± 12.1 mg/L) compared to SLE patients without LN (67.2 ± 9.3 mg/L) and both were significantly higher than controls (34.2 ± 6.2 mg/L). Peripheral arterial disease (ABI < 0.9) was significantly more common in LN patients (55%) compared to SLE patients without LN (30%) as well as controls (0%). Fetuin-A levels showed significant negative correlations with serum creatinine, hsCRP, CRI, IMT and ABI in SLE patients with and without LN. Conclusion: Fetuin-A levels were decreased in SLE patients with and without LN and negatively correlated with vascular complications. This suggests a potentially important role for fetuin-A deficiency as marker of vascular disease in SLE patients with and without LN. Keywords: Atherosclerosis; Fetuin-A; Lupus nephritis; SLE; Vascular Calcification

Amphibian host-defense peptides with potential for Type 2 diabetes therapy - an updated review

Investigations conducted since 2018 have identified several host-defense peptides present in frog skin secretions whose properties suggest the possibility of their development into a new class of agent for Type 2 diabetes (T2D) therapy. Studies in vitro have described peptides that (a) stimulate insulin release from BRIN-BD11 clonal β-cells and isolated mouse islets, (b) display β-cell proliferative activity and protect against cytokine-mediated apoptosis and (c) stimulate production of the anti-inflammatory cytokine IL-10 and inhibit production of the pro-inflammatory cytokines TNF-α and IL-1β. Rhinophrynin-27, phylloseptin-3.2TR and temporin F are peptides with therapeutic potential. Studies in vivo carried out in db/db and high fat-fed mice have shown that twice-daily administration of [S4K]CPF-AM1 and [A14K]PGLa-AM1, analogs of peptides first isolated from the octoploid frog Xenopus amieti, over 28 days lowers circulating glucose and HbA1c concentrations, increases insulin sensitivity and improves glucose tolerance and lipid profile. Peptide treatment produced potentially beneficial changes in the expression of skeletal muscle genes involved in insulin signaling and islet genes involved in insulin secretion in these murine models of T2D. Lead compounds uncovered by the study of frog HDPs may provide a basis for the design of new types of agents that can be used, alone or in combination with existing therapies, for the treatment of T2D.

Effects of Sub-lethal Lead Nitrate and Copper Sulfate Concentrations on Hematological Parameters During Long-term Exposure in Nile tilapia (Oreochromis niloticus)

437-441Nile tilapia (Oreochromis niloticus) weighing 51.66 ± 2.42 g were exposed to 0%, 20%, 40%, and 60% of LC50 to either lead nitrate (Pb(NO3)2) or copper sulfate (CuSO4) for 30 days. The Pb(NO3)2 and CuSO4 concentrations employed in the treatments of this study were 8.8, 17.6, and 26.4 mg/L and 2.57, 5.14, and 7.71 mg/l, respectively, and multiple hematological variables were evaluated. The red blood cell (RBC) count for the control group was 2.41 ± 0.13 while those of the treatment groups exposed to 8.8, 17.6, and 26.4 mg/L of Pb(NO3)2 were 2.21 ± 0.10, 1.94 ± 0.16, and 1.36 ± 0.10 × 106/µl, respectively, at the end of the study. Similarly, the hemoglobin (Hb), hematocrit (Hct), mean cell hemoglobin (MCH), mean cell hemoglobin concentration (MCHC), and platelet (PLT( levels significantly decreased as the Pb(NO3)2 concentration increased (p 4, showed decrease in the levels of RBC, Hb, Hct, WBC, and PLT when the concentration of CuSO4 increased, while the MCHC, MCH, and MCV levels significantly increased

Global consortium for the classification of fungi and fungus-like taxa

The Global Consortium for the Classification of Fungi and fungus-like taxa is an international initiative of more than 550 mycologists to develop an electronic structure for the classification of these organisms. The members of the Consortium originate from 55 countries/regions worldwide, from a wide range of disciplines, and include senior, mid-career and early-career mycologists and plant pathologists. The Consortium will publish a biannual update of the Outline of Fungi and fungus-like taxa, to act as an international scheme for other scientists. Notes on all newly published taxa at or above the level of species will be prepared and published online on the Outline of Fungi website (https://www.outlineoffungi.org/), and these will be finally published in the biannual edition of the Outline of Fungi and fungus-like taxa. Comments on recent important taxonomic opinions on controversial topics will be included in the biannual outline. For example, ‘to promote a more stable taxonomy in Fusarium given the divergences over its generic delimitation’, or ‘are there too many genera in the Boletales?’ and even more importantly, ‘what should be done with the tremendously diverse ‘dark fungal taxa?’ There are undeniable differences in mycologists’ perceptions and opinions regarding species classification as well as the establishment of new species. Given the pluralistic nature of fungal taxonomy and its implications for species concepts and the nature of species, this consortium aims to provide a platform to better refine and stabilise fungal classification, taking into consideration views from different parties. In the future, a confidential voting system will be set up to gauge the opinions of all mycologists in the Consortium on important topics. The results of such surveys will be presented to the International Commission on the Taxonomy of Fungi (ICTF) and the Nomenclature Committee for Fungi (NCF) with opinions and percentages of votes for and against. Criticisms based on scientific evidence with regards to nomenclature, classifications, and taxonomic concepts will be welcomed, and any recommendations on specific taxonomic issues will also be encouraged; however, we will encourage professionally and ethically responsible criticisms of others’ work. This biannual ongoing project will provide an outlet for advances in various topics of fungal classification, nomenclature, and taxonomic concepts and lead to a community-agreed classification scheme for the fungi and fungus-like taxa. Interested parties should contact the lead author if they would like to be involved in future outlines

HUWE1 cooperates with RAS activation to control leukemia cell proliferation and human hematopoietic stem cells differentiation fate

Acute myeloid leukemia (AML) is a poor prognosis hematopoietic malignance characterized by abnormal proliferation and differentiation of hematopoietic stem cells (HSCs). Although advances in treatment have greatly improved survival rates in young patients, in the elderly population, ~70% of patients present poor prognosis. A pan-cancer analysis on the TCGA cohort showed that AML has the second higher HUWE1 expression in tumor samples among all cancer types. In addition, pathway enrichment analysis pointed to RAS signaling cascade as one of the most important pathways associated to HUWE1 expression in this particular AML cohort. In silico analysis for biological processes enrichment also revealed that HUWE1 expression is correlated with 13 genes involved in myeloid differentiation. Therefore, to understand the role of HUWE1 in human hematopoietic stem and progenitor cells (HSPC) we constitutively expressed KRASG12V oncogene concomitantly to HUWE1 knockdown in stromal co-cultures. The results showed that, in the context of KRASG12V, HUWE1 significantly reduces cell cumulative growth and changes myeloid differentiation profile of HSPCs. Overall, these observations suggest that HUWE1 might contribute to leukemic cell proliferation and impact myeloid differentiation of human HSCs, thus providing new venues for RAS-driven leukemia targeted therapy approach

Preparation and in vivo evaluation of insulin-loaded biodegradable nanoparticles prepared from diblock copolymers of PLGA and PEG

The aim of this study was to design a controlled release vehicle for insulin to preserve its stability and biological activity during fabrication and release. A modified, double emulsion, solvent evaporation, technique using homogenisation force optimised entrapment efficiency of insulin into biodegradable nanoparticles (NP) prepared from poly (dl-lactic-co-glycolic acid) (PLGA) and its PEGylated diblock copolymers. Formulation parameters (type of polymer and its concentration, stabiliser concentration and volume of internal aqueous phase) and physicochemical characteristics (size, zeta potential, encapsulation efficiency, in vitro release profiles and in vitro stability) were investigated. In vivo insulin sensitivity was tested by dietinduced type II diabetic mice. Bioactivity of insulin was studied using Swiss TO mice with streptozotocin-induced type I diabetic profile. Insulin-loaded NP were spherical and negatively charged with an average diameter of 200–400 nm. Insulin encapsulation efficiency increased significantly with increasing ratio of co-polymeric PEG. The internal aqueous phase volume had a significant impact on encapsulation efficiency, initial burst release and NP size. Optimised insulin NP formulated from 10% PEG-PLGA retained insulin integrity in vitro, insulin sensitivity in vivo and induced a sustained hypoglycaemic effect from 3 hours to 6 days in type I diabetic mice

Esculentin-2CHa-Related Peptides Modulate Islet Cell Function and Improve Glucose Tolerance in Mice with Diet-Induced Obesity and Insulin Resistance

The frog skin host-defense peptide esculentin-2CHa (GFSSIFRGVA10KFASKGLGK D20LAKLGVDLVA30CKISKQC) displays antimicrobial, antitumor, and immunomodulatory properties. This study investigated the antidiabetic actions of the peptide and selected analogues. Esculentin-2CHa stimulated insulin secretion from rat BRIN-BD11 clonal pancreatic β-cells at concentrations greater than 0.3 nM without cytotoxicity by a mechanism involving membrane depolarization and increase of intracellular Ca2+. Insulinotropic activity was attenuated by activation of KATP channels, inhibition of voltage-dependent Ca2+ channels and chelation of extracellular Ca2+. The [L21K], [L24K], [D20K, D27K] and [C31S,C37S] analogues were more potent but less effective than esculentin-2CHa whereas the [L28K] and [C31K] analogues were both more potent and produced a significantly (P < 0.001) greater maximum response. Acute administration of [L28K]esculentin-2CHa (75 nmol/kg body weight) to high fat fed mice with obesity and insulin resistance enhanced glucose tolerance and insulin secretion. Twice-daily administration of this dose of [L28K]esculentin- 2CHa for 28 days had no significant effect on body weight, food intake, indirect calorimetry or body composition. However, mice exhibited decreased non-fasting plasma glucose (P < 0.05), increased non-fasting plasma insulin (P < 0.05) as well as improved glucose tolerance and insulin secretion (P < 0.01) following both oral and intraperitoneal glucose loads. Impaired responses of isolated islets from high fat fed mice to established insulin secretagogues were restored by [L28K]esculentin-2CHa treatment. Peptide treatment was accompanied by significantly lower plasma and pancreatic glucagon levels and normalization of α-cell mass. Circulating triglyceride concentrations were decreased but plasma cholesterol and LDL concentrations were not significantly affected. The data encourage further investigation of the potential of esculentin-2CHa related peptides for treatment of patients with type 2 diabetes

Mutations in ASXL1 are associated with poor prognosis across the spectrum of malignant myeloid diseases

The ASXL1 gene is one of the most frequently mutated genes in malignant myeloid diseases. The ASXL1 protein belongs to protein complexes involved in the epigenetic regulation of gene expression. ASXL1 mutations are found in myeloproliferative neoplasms (MPN), myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML). They are generally associated with signs of aggressiveness and poor clinical outcome. Because of this, a systematic determination of ASXL1 mutational status in myeloid malignancies should help in prognosis assessment

In vitro and in vivo insulinotropic properties of the multifunctional frog skin peptide hymenochirin-1B: a structure–activity study

Hymenochirin-1b (Hym-1B; IKLSPETKDNLKKVLKGAIKGAIAVAKMV.NH2) is a cationic, α-helical amphibian host-defense peptide with antimicrobial, anticancer, and immunomodulatory properties. This study investigates the abilities of the peptide and nine analogues containing substitutions of Pro5, Glu6, and Asp9 by either l-lysine or d-lysine to stimulate insulin release in vitro using BRIN-BD11 clonal β cells or isolated mouse islets and in vivo using mice fed a high-fat diet to produce obesity and insulin resistance. Hym-1B produced a significant and concentration-dependent increase in the rate of insulin release from BRIN-BD11 cells without cytotoxicity at concentrations up to 1 µM with a threshold concentration of 1 nM. The threshold concentrations for the analogues were: [P5K], [E6K], [D9K], [P5K, E6K] and [E6K, D9k] 0.003 nM, [E6K, D9K] and [D9k] 0.01 nM, [P5K, D9K] 0.1 nM and [E6k] 0.3 nM. All peptides displayed cytotoxicity at concentrations ≥1 µM except the [P5K] and [D9k] analogues which were non-toxic at 3 µM. The potency and maximum rate of insulin release from mouse islets produced by the [P5K] peptide were significantly greater than produced by Hym-1B. Neither Hym-1B nor the [P5K] analogue at 1 µM concentration had an effect on membrane depolarization or intracellular Ca2+. The [P5K] analogue (1 µM) produced a significant increase in cAMP concentration in BRIN-BD11 cells and stimulated GLP-1 secretion from GLUTag cells. Down-regulation of the protein kinase A pathway by overnight incubation with forskolin completely abolished the insulin-releasing effects of [P5K]hym-1B. Intraperitoneal administration of the [P5K] and [D9k] analogues (75 nmol/kg body weight) to high-fat-fed mice with insulin resistance significantly enhanced glucose tolerance with a concomitant increase in insulin secretion. We conclude that [P5K]hym-1B and [D9k]hym-1B show potential for development into anti-diabetic agents