Helena’s Many Daughters: More Mitogenome Diversity behind the Most Common West Eurasian mtDNA Control Region Haplotype in an Extended Italian Population Sample

The high number of matching haplotypes of the most common mitochondrial (mt)DNA lineages are considered to be the greatest limitation for forensic applications. This study investigates the potential to solve this constraint by massively parallel sequencing a large number of mitogenomes that share the most common West Eurasian mtDNA control region (CR) haplotype motif (263G 315.1C 16519C). We augmented a pilot study on 29 to a total of 216 Italian mitogenomes that represents the largest set of the most common CR haplotype compiled from a single country. The extended population sample confirmed and extended the huge coding region diversity behind the most common CR motif. Complete mitogenome sequencing allowed for the detection of 163 distinct haplotypes, raising the power of discrimination from 0 (CR) to 99.6% (mitogenome). The mtDNAs were clustered into 61 named clades of haplogroup H and did not reveal phylogeographic trends within Italy. Rapid individualization approaches for investigative purposes are limited to the most frequent H clades of the dataset, viz. H1, H3, and H7.     

Ag/ZnO nanomaterials as high performance sensors for flammable and toxic gases

Ag/ZnO nanocomposites supported on polycrystalline Al2O3 were synthesized by an unprecedented approach combining plasma enhanced chemical vapor deposition (PE-CVD) of ZnO matrices and the subsequent deposition of Ag nanoparticles (NPs) by radio frequency (RF) sputtering. The system structure, composition and morphology were investigated by glancing incidence x-ray diffraction (GIXRD), secondary ion mass spectrometry (SIMS), field emission scanning electron microscopy (FE-SEM) and energy dispersive x-ray spectroscopy (EDXS). A tailored dispersion and distribution of silver particles could be obtained under mild conditions by the sole variation of the sputtering time. Gas sensing properties toward flammable and toxic gases, both reducing (CH3CH2OH, CH3COCH3) and oxidizing (O3), were investigated in the temperature range 100-400?°C. Beside the high sensitivity, the developed sensors exhibited a response proportional to Ag content, thanks to catalytic and electronic effects promoted by silver NPs. In addition, discrimination between oxidizing and reducing analytes was enabled by a suitable choice of the adopted working temperature.     

Experimental Investigations on Condensation in the Framework of ENhanced COndensers in Microgravity (ENCOM-2) Project

We report preliminary results on experimental investigations on condensation in the framework of the European Space Agency funded programme Enhanced Condensers in Microgravity (ENCOM-2) which aims at better understanding underlying phenomena during condensation. The first experiment is a study on condensation of HFE on external curvilinear surface of 15 mm height during reduced gravity experiments. It is found that the local minimum of the film thickness exists at the conjugation area of condensed film and the meniscus at the bottom of the fin; this leads to the local maximum of the heat transfer coefficient, which we also found moves towards the fin tip. The second experiment is a study of falling films hydrodynamics inside a vertical long pipe. In particular, characteristics of wavy falling films produced employing intermittent liquid feed are examined in order to assess wave effects on film condensation. Preliminary results suggest that intermittent feed simply divides the film in two autonomous regions with the wave feature of each one depending only on its flow rate. The processing of registered film thickness data can lead to the estimation of the transverse velocity profile in the film, which is mainly responsible for heat transfer during condensation. The third experiment looks at in-tube convective condensation at low mass fluxes (typical of Loop Heat Pipes and Capillary Pumped Loops) of n-pentane inside a 0.56 mm diameter channel. The results show that the mean heat transfer in the annular zone when it is elongated may be less than the mean heat transfer when it is shorter, due to the interface deformation involved by surface tension effect. When the length of this annular zone reaches a critical value, the interface becomes unstable, and a liquid bridge forms, involving the release of a bubble. The heat transfer due to the phase-change in this isolated bubble zone appears to be very small compared to the sensible heat transfer: the bubbles evolve and collapse in a highly subcooled liquid. The last experiment concerns in-tube condensation of R134a inside a square channel of 1.23 mm hydraulic diameter at mass fluxes of 135 kg m^?2 s^?1 and 390 kg m^?2 s^?1 for three different configurations: horizontal, vertical downflow and vertical upflow. For the calculated heat transfer coefficient it is found that gravity has no effect on condensation in downflow configurations at 390 kg m^?2 s^?1 and in upflow conditions at both values of mass velocity. The effect of gravity on the condensation heat transfer coefficient becomes noteworthy in downflow at mass velocity G = 135 kg m^?2 s^?1 and vapour quality lower than 0.6.     

Turning Seashell Waste into Electrically Conductive Particles

Biomaterials such as seashells are intriguing due to their remarkable properties, including their hierarchical structure from the nanometer to the micro- or even macroscopic scale. Transferring this nanostructure to generate nanostructured polymers can improve their electrical conductivity. Here, we present the synthesis of polypyrrole using waste seashell powder as a template to prepare a polypyrrole/CaCO₃ composite material. Various synthesis parameters were optimized to produce a composite material with an electrical conductivity of 2.1 × 10⁻⁴ ± 3.2 × 10⁻⁵ S/cm. This work presents the transformation of waste seashells into sustainable, electronically conductive materials and their application as an antistatic agent in polymers. The requirements of an antistatic material were met for a safety shoe sole.     

Old and Promising Markers Related to Autophagy in Traumatic Brain Injury

Traumatic brain injury (TBI) is one of the first causes of death and disability in the world. Because of the lack of macroscopical or histologic evidence of the damage, the forensic diagnosis of TBI could be particularly difficult. Considering that the activation of autophagy in the brain after a TBI is well documented in literature, the aim of this review is to find all autophagy immunohistological protein markers that are modified after TBI to propose a method to diagnose this eventuality in the brain of trauma victims. A systematic literature review on PubMed following PRISMA 2020 guidelines has enabled the identification of 241 articles. In all, 21 of these were enrolled to identify 24 markers that could be divided into two groups. The first consisted of well-known markers that could be considered for a first diagnosis of TBI. The second consisted of new markers recently proposed in the literature that could be used in combination with the markers of the first group to define the elapsed time between trauma and death. However, the use of these markers has to be validated in the future in human tissue by further studies, and the influence of other diseases affecting the victims before death should be explored.     

CRISPR/Cas9-Induced Inactivation of the Autism-Risk Gene setd5 Leads to Social Impairments in Zebrafish

Haploinsufficiency of the SETD5 gene, encoding a SET domain-containing histone methyltransferase, has been identified as a cause of intellectual disability and Autism Spectrum Disorder (ASD). Recently, the zebrafish has emerged as a valuable model to study neurodevelopmental disorders because of its genetic tractability, robust behavioral traits and amenability to high-throughput drug screening. To model human SETD5 haploinsufficiency, we generated zebrafish setd5 mutants using the CRISPR/Cas9 technology and characterized their morphological, behavioral and molecular phenotypes. According to our observation that setd5 is expressed in adult zebrafish brain, including those areas controlling social behavior, we found that setd5 heterozygous mutants exhibit defective aggregation and coordination abilities required for shoaling interactions, as well as indifference to social stimuli. Interestingly, impairment in social interest is rescued by risperidone, an antipsychotic drug used to treat behavioral traits in ASD individuals. The molecular analysis underscored the downregulation of genes encoding proteins involved in the synaptic structure and function in the adult brain, thus suggesting that brain hypo-connectivity could be responsible for the social impairments of setd5 mutant fishes. The zebrafish setd5 mutants display ASD-like features and are a promising setd5 haploinsufficiency model for drug screening aimed at reversing the behavioral phenotypes.     

Improving the Laboratory Diagnosis of M-like Variants Related to Alpha1-Antitrypsin Deficiency

Alpha1-antitrypsin (AAT) is a serine protease inhibitor that is encoded by the highly polymorphic SERPINA1 gene. Mutations in this gene can lead to AAT deficiency (AATD), which is associated with an increased risk of lung and/or liver disease. On the basis of electrophoretic migration, AAT variants are named with capital letters; M (medium) signifies the normal protein. Among pathological variants, the M-like ones represent a heterogeneous group of rare allelic variants that exhibit the same electrophoretic pattern as the M wild-type protein, which makes them difficult to detect with routine methods. In order to avoid their misdiagnosis, the present study defines and validates effective methods for the detection of two pathogenic M-like variants, M_wurzburg and M_whitstable. Comparison of protein phenotypes using isoelectric focusing of samples that presented the M_wurzburg variant, as revealed by exons 5 sequencing, identified a particular electrophoretic pattern amenable to the M_wurzburg protein. The specific phenotyping pattern was retrospectively validated, thus enabling the detection of 16 patients with M_wurzburg variant among the subjects already tested but not sequenced according to our diagnostic algorithm. The M_whitstable allele was detected by intron 4 sequencing of SERPINA1 gene. M_wurzburg and M_whitstable are often misdiagnosed and the introduction of diagnostic improvements can help the clinical management, especially in patients with established lung disease without any other reported risk factors.     

Circulating Biomarkers of Endothelial Dysfunction and Inflammation in Predicting Clinical Outcomes in Diabetic Patients with Critical Limb Ischemia

Critical limb ischemia (CLI) is a severe manifestation of peripheral artery disease characterized by ischemic pain, which is frequently associated with diabetes and non-healing lesions to inferior limbs. The clinical management of diabetic patients with CLI typically includes percutaneous transluminal angioplasty (PTA) to restore limb circulation and surgical treatment of diabetic foot ulcers (DFU). However, even after successful treatment, CLI patients are prone to post-procedure complications, which may lead to unplanned revascularization or foot surgery. Unfortunately, the factors predicting adverse events in treated CLI patients are only partially known. This study aimed to identify potential biomarkers that predict the disease course in diabetic patients with CLI. For this purpose, we measured the circulating levels of a panel of 23 molecules related to inflammation, endothelial dysfunction, platelet activation, and thrombophilia in 92 patients with CLI and DFU requiring PTA and foot surgery. We investigated whether these putative biomarkers were associated with the following clinical endpoints: (1) healing of the treated DFUs; (2) need for new revascularization of the limb; (3) appearance of new lesions or relapses after successful healing. We found that sICAM-1 and endothelin-1 are inversely associated with DFU healing and that PAI-1 and endothelin-1 are associated with the need for new revascularization. Moreover, we found that the levels of thrombomodulin and sCD40L are associated with new lesions or recurrence, and we show that the levels of these biomarkers could be used in a decision tree to assign patients to clusters with different risks of developing new lesions or recurrences.     

Anti-Inflammatory Effects of GLP-1R Activation in the Retina

Glucagon-like peptide-1 (GLP-1) is an incretin hormone, mainly produced by enteroendocrine L cells, which participates in the regulation of glucose homeostasis, and in reduction in body weight by promoting satiety. Actions of GLP-1 are mediated by activation of its receptor GLP-1R, which is widely expressed in several tissues including the retina. The effects of GLP-1R activation are useful in the management of type 2 diabetes mellitus (T2DM). In addition, the activation of GLP-1R has anti-inflammatory effects in several organs, suggesting that it may be also useful in the treatment of inflammatory diseases. Inflammation is a common element in the pathogenesis of several ocular diseases, and the protective effects of treatment with GLP-1 emerged also in retinal diseases. In this review we highlight the anti-inflammatory effects of GLP-1R activation in the retina. Firstly, we summarized the pathogenic role of inflammation in ocular diseases. Then, we described the pleiotropic effects of GLP-1R activation on the cellular components of the retina which are mainly involved in the pathogenesis of inflammatory retinal diseases: the retinal ganglion cells, retinal pigment epithelial cells and endothelial cells.