Human Synaptobrevin-like 1 Gene Basal Transcription Is Regulated through the Interaction of Selenocysteine tRNA Gene Transcription Activating Factor-Zinc Finger 143 Factors with Evolutionary Conserved Cis-elements

The synaptobrevin-like 1 (SYBL1) gene is ubiquitously expressed and codes for an unusual member of the v-SNAREs molecules implicated in cellular exocytosis. This X-linked gene has the peculiarity of also being present on the Y chromosome in a transcriptional inactive status. Moreover, although ubiquitous, the function of SYBL1 is prominent in specific tissues, such as brain. As a first insight into the molecular mechanisms controlling SYBL1 expression, in this report we describe the extent and role of SYBL1 upstream regions and characterize the binding of trans-acting factors. In vivo foot-printing experiments identify three protected regions. Band shift and transient reporter gene assays indicate a strong role of two of these evolutionary conserved regions in regulating SYBL1 transcription. Because one site is the classical CAAT box, we characterized the binding to the other site of the mammalian homologues of the selenocysteine tRNA gene transcription activating factor (Staf) family, zinc-finger transcription factors, and their role in regulating SYBL1 expression. The results reported here clarify that a Staf-zinc finger family factor, together with the CAAT factor, is the major nuclear protein bound to the SYBL1 promoter region and is responsible for its regulation in HeLa cells, thus identifying the basic control of SYBL1 transcription. In vivo binding of Staf proteins to the SYBL1 promoter is confirmed by chromatin immunoprecipitation assays. Our results identify a fourth mRNA promoter stimulated by a member of the Staf-zinc finger family, the function of which on mRNA polymerase II promoters is still very poorly understood

Highly radiogenic Sr-isotopic signature and trace element content of grape musts from northern Piedmont vineyards (Italy)

The analysis of trace metals and metalloids, and the Sr-isotopic systematics were applied to 16 must samples from vines growing in the Sesia Val Grande Supervolcano UNESCO Global Geopark in the northern Piedmont Region (Italy), a land worldwide famous for the production of quality Nebbiolo-based red wines. Twenty-four elements were measured in each sample with inductively coupled plasma-mass spectrometry (ICP-MS). The results indicate a wide variability in trace element concentration in musts from the different vineyards. In particular, Rb and Sr reach their maximum at 5110 and 694 \u3bcg L 121, respectively, reflecting the geological nature of the magmatic bedrocks. Fe, Cu, Pb and Ba concentrations reach 3118, 1200, 130 and 720 \u3bcg L 121, respectively, suggesting a source from iron oxide, Pb\u2013Zn and Ba ores associated to the volcanic activity. The 87Sr/86Sr ratio is in the range 0.711608\u20130.718160, showing a highly radiogenic signature which is uncommon in must/wine. This is consistent with the high 87Sr/86Sr isotopic ratio of the old rhyolitic bedrocks. Furthermore, the 87Sr/86Sr ratio in musts linearly correlates with the corresponding 87Rb/86Sr ratio, reflecting the Rb and 87Sr release from primary minerals during pedogenesis and matching the initial 87Sr/86Sr ratio of the parent bedrocks magmatic reservoir, thus assuming importance for authenticity assessment

Wearable Heart Rate Monitoring Device Communicating in 5G ISM Band for IoHT

Advances in wearable device technology pave the way for wireless health monitoring for medical and non-medical applications. In this work, we present a wearable heart rate monitoring platform communicating in the sub-6GHz 5G ISM band. The proposed device is composed of an Aluminium Nitride (AlN) piezoelectric sensor, a patch antenna, and a custom printed circuit board (PCB) for data acquisition and transmission. The experimental results show that the presented system can acquire heart rate together with diastolic and systolic duration, which are related to heart relaxation and contraction, respectively, from the posterior tibial artery. The overall system dimension is 20 mm by 40 mm, and the total weight is 20 g, making this device suitable for daily utilization. Furthermore, the system allows the simultaneous monitoring of multiple subjects, or a single patient from multiple body locations by using only one reader. The promising results demonstrate that the proposed system is applicable to the Internet of Healthcare Things (IoHT), and particularly Integrated Clinical Environment (ICE) applications

Co-treatment of tumor cells with hyaluronan plus doxorubicin affects endothelial cell behavior independently of VEGF expression

Hyaluronan, the main glycosaminoglycan of extracellular matrices, is concentrated in tissues with high cell proliferation and migration rates. In cancer, hyaluronan expression is altered and it becomes fragmented into low-molecular-weight forms, affecting mechanisms associated with cell proliferation, invasion, angiogenesis and multidrug resistance. Here, we analyzed the effect of low-molecular-weight hyaluronan on the response of T lymphoma, osteosarcoma, and mammary adenocarcinoma cell lines to the antineoplastic drug doxorubicin, and whether co-treatment with hyaluronan and doxorubicin modified the behavior of endothelial cells. Our aim was to associate the hyaluronan-doxorubicin response with angiogenic alterations in these tumors. After hyaluronan and doxorubicin co-treatment, hyaluronan altered drug accumulation and modulated the expression of ATP-binding cassette transporters in T-cell lymphoma cells. In contrast, no changes in drug accumulation were observed in cells from solid tumors, indicating that hyaluronan might not affect drug efflux. However, when we evaluated the effect on angiogenic mechanisms, the supernatant from tumor cells treated with doxorubicin exhibited a pro-angiogenic effect on endothelial cells. Hyaluronan-doxorubicin co-treatment increased migration and vessel formation in endothelial cells. This effect was independent of vascular endothelial growth factor but related to fibroblast growth factor-2 expression. Besides, we observed a pro-angiogenic effect on endothelial cells during hyaluronan and doxorubicin co-treatment in the in vivo murine model of T-cell lymphoma. Our results demonstrate for the first time that hyaluronan is a potential modulator of doxorubicin response by mechanisms that involve not only drug efflux but also angiogenic processes, providing an adverse tumor stroma during chemotherapy

Bioarchaeological and paleogenomic profiling of the unusual Neolithic burial from Grotta di Pietra Sant'Angelo (Calabria, Italy).

Acknowledgements: The authors would like to thank Dr. Leonardo Larocca, medical officer of San Lorenzo Bellizzi, who supervised the research on the modern inhabitants, and Dr. Andrea De Giovanni, who helped in the sampling processes. A special acknowledgement goes to the population of San Lorenzo Bellizzi, the mayor and the administration of the municipality, whose efforts and inseparable link to their roots made this study possible. This work is sustained by the MIUR-PRIN 20177PJ9XF grant to DL.The Neolithic burial of Grotta di Pietra Sant'Angelo (CS) represents a unique archaeological finding for the prehistory of Southern Italy. The unusual placement of the inhumation at a rather high altitude and far from inhabited areas, the lack of funerary equipment and the prone deposition of the body find limited similarities in coeval Italian sites. These elements have prompted wider questions on mortuary customs during the prehistory of Southern Italy. This atypical case requires an interdisciplinary approach aimed to build an integrated bioarchaeological profile of the individual. The paleopathological investigation of the skeletal remains revealed the presence of numerous markers that could be associated with craft activities, suggesting possible interpretations of the individual's lifestyle. CT analyses, carried out on the maxillary bones, showed the presence of a peculiar type of dental wear, but also a good density of the bone matrix. Biomolecular and micromorphological analyses of dental calculus highlight the presence of a rich Neolithic-like oral microbiome, the composition of which is consistent with the presence pathologies. Finally, paleogenomic data obtained from the individual were compared with ancient and modern Mediterranean populations, including unpublished high-resolution genome-wide data for 20 modern inhabitants of the nearby village of San Lorenzo Bellizzi, which provided interesting insights into the biodemographic landscape of the Neolithic in Southern Italy

Bioarchaeological and paleogenomic profiling of the unusual Neolithic burial from Grotta di Pietra Sant’Angelo (Calabria, Italy)

Abstract The Neolithic burial of Grotta di Pietra Sant’Angelo (CS) represents a unique archaeological finding for the prehistory of Southern Italy. The unusual placement of the inhumation at a rather high altitude and far from inhabited areas, the lack of funerary equipment and the prone deposition of the body find limited similarities in coeval Italian sites. These elements have prompted wider questions on mortuary customs during the prehistory of Southern Italy. This atypical case requires an interdisciplinary approach aimed to build an integrated bioarchaeological profile of the individual. The paleopathological investigation of the skeletal remains revealed the presence of numerous markers that could be associated with craft activities, suggesting possible interpretations of the individual’s lifestyle. CT analyses, carried out on the maxillary bones, showed the presence of a peculiar type of dental wear, but also a good density of the bone matrix. Biomolecular and micromorphological analyses of dental calculus highlight the presence of a rich Neolithic-like oral microbiome, the composition of which is consistent with the presence pathologies. Finally, paleogenomic data obtained from the individual were compared with ancient and modern Mediterranean populations, including unpublished high-resolution genome-wide data for 20 modern inhabitants of the nearby village of San Lorenzo Bellizzi, which provided interesting insights into the biodemographic landscape of the Neolithic in Southern Italy

An Attenuated Herpes Simplex Virus Type 1 (HSV1) Encoding the HIV-1 Tat Protein Protects Mice from a Deadly Mucosal HSV1 Challenge

Herpes simplex virus types 1 and 2 (HSV1 and HSV2) are common infectious agents in both industrialized and developing countries. They cause recurrent asymptomatic and/or symptomatic infections, and life-threatening diseases and death in newborns and immunocompromised patients. Current treatment for HSV relies on antiviral medications, which can halt the symptomatic diseases but cannot prevent the shedding that occurs in asymptomatic patients or, consequently, the spread of the viruses. Therefore, prevention rather than treatment of HSV infections has long been an area of intense research, but thus far effective anti-HSV vaccines still remain elusive. One of the key hurdles to overcome in anti-HSV vaccine development is the identification and effective use of strategies that promote the emergence of Th1-type immune responses against a wide range of epitopes involved in the control of viral replication. Since the HIV1 Tat protein has several immunomodulatory activities and increases CTL recognition of dominant and subdominant epitopes of heterologous antigens, we generated and assayed a recombinant attenuated replication-competent HSV1 vector containing the tat gene (HSV1-Tat). In this proof-of-concept study we show that immunization with this vector conferred protection in 100% of mice challenged intravaginally with a lethal dose of wild-type HSV1. We demonstrate that the presence of Tat within the recombinant virus increased and broadened Th1-like and CTL responses against HSV-derived T-cell epitopes and elicited in most immunized mice detectable IgG responses. In sharp contrast, a similarly attenuated HSV1 recombinant vector without Tat (HSV1-LacZ), induced low and different T cell responses, no measurable antibody responses and did not protect mice against the wild-type HSV1 challenge. These findings strongly suggest that recombinant HSV1 vectors expressing Tat merit further investigation for their potential to prevent and/or contain HSV1 infection and dissemination