Dinosaur Tracks as Paleogeographic Constraints: New Scenarios for the Cretaceous Geography of the Periadriatic Region

A really unexpected finding of sauropod and theropod footprints in southern Latium raises to four the number of the trampled levels recognized in central and southern Italy. After the recent findings in Latest Jurassic and Early, mid and Late Cretaceous carbonate platform deposits of the Periadriatic region, dinosaur footprints seem to provide very important paleogeographic constraints for reconstructing the geodynamic history of the Mediterranean area. The presence of a varied ichnoassociation makes acceptance of the current paleogeographic models concerning the relative and absolute position of the Laziale-Abruzzese-Campano and of Apulian-Dinaric domains during the Late Cretaceous more and more problematic. Dinosaur footprints, combined with other paleontological data, demonstrate that these areas were never completely pulled apart by deep seaways, while frequent or continuous links between them, and to southern and northern mainlands, probably persisted. These data also allowed us to improve our understanding of the timing of the Mesozoic plate motion in this segment of the Western Tethys.     

Italian Dermestidae: notes on some species and?an?updated checklist (Coleoptera)

An up-to-date checklist of the Italian Dermestidae is provided. The presence of 95 species in Italy is confirmed, while further 5 species (Dermestes (Dermestes) vorax Motschulsky, 1860, Thorictuspilosus Peyron, 1857, T. wasmanni Reitter, 1895, Attagenus (Attagenus) simonis Reitter, 1881 and Globicornis (G.) breviclavis (Reitter, 1878)) and 1 subspecies (A. (A.) tigrinus pulcher Faldermann, 1835) are excluded from the Italian fauna.Attagenus (Attagenus) calabricus Reitter, 1881 and A. (A.) lobatus Rosenhauer, 1856 are for the first time recorded from Abruzzi and Tuscany respectively; A. (A.) silvaticus Zhantiev, 1976 is recorded for the first time from mainland Italy (Apulia); Anthrenus (Anthrenus) angustefasciatus Ganglbauer, 1904 is new to northern Italy (Friuli-Venezia Giulia), central Italy (Tuscany), Apulia and Basilicata; A. (A.) munroi Hinton, 1943 is new to central Italy (Elba Island); A. (A.) delicatus Kiesenwetter, 1851 is for the first time recorded from Apulia; Globicornis (Globicornis) fasciata (Fairmaire & Brisout de Barneville, 1859) is new to southern Italy (Basilicata); G. (Hadrotoma) sulcata (C.N.F. Brisout de Barneville, 1866) is for the first time recorded from central Italy (Abruzzi), Campania and Sicily, whileTrogoderma inclusum LeConte, 1854 is new to Apulia.Seven species (Dermestes (Dermestes) peruvianus Laporte de Castelnau, 1840, D. (Dermestinus) carnivorus Fabricius, 1775, D. (Dermestinus) hankae Háva, 1999, D. (Dermestinus) intermedius intermedius Kalík, 1951, D. (Dermestinus) szekessyi Kalík, 1950, Anthrenus (Anthrenops) coloratus Reitter, 1881 and Trogodermaangustum (Solier, 1849)) recently recorded from Italy (without further details) are discussed.The lectotype and a paralectotype are designated forAttagenus (A.) calabricus Reitter, 1881 from Calabria.Attagenus pellio (Linnaeus, 1758) var. pilosissimus Roubal, 1932 is removed from synonymy with A. (A.) pellio and recognized as a valid species (stat. prom.); it is known from Lombardy, Apulia and Calabria.     

Direct inhibition of hexokinase activity by metformin at least partially impairs glucose metabolism and tumor growth in experimental breast cancer

Emerging evidence suggests that metformin, a widely used anti-diabetic drug, may be useful in the prevention and treatment of different cancers. In the present study, we demonstrate that metformin directly inhibits the enzymatic function of hexokinase (HK) I and II in a cell line of triple-negative breast cancer (MDA-MB-231). The inhibition is selective for these isoforms, as documented by experiments with purified HK I and II as well as with cell lysates. Measurements of ¹⁸F-fluoro-deoxyglycose uptake document that it is dose- and time-dependent and powerful enough to virtually abolish glucose consumption despite unchanged availability of membrane glucose transporters. The profound energetic imbalance activates phosphorylation and is subsequently followed by cell death. More importantly, the “in vivo” relevance of this effect is confirmed by studies of orthotopic xenografts of MDA-MB-231 cells in athymic (nu/nu) mice. Administration of high drug doses after tumor development caused an evident tumor necrosis in a time as short as 48 h. On the other hand, 1 mo metformin treatment markedly reduced cancer glucose consumption and growth. Taken together, our results strongly suggest that HK inhibition contributes to metformin therapeutic and preventive potential in breast cancer.     

EV20, a Novel Anti-ErbB-3 Humanized Antibody,Promotes ErbB-3 Down-Regulation and Inhibits Tumor Growth In Vivo

ErbB-3 (HER-3) receptor is involved in tumor progression and resistance to therapy. Development of specific inhibitors impairing the activity of ErbB-3 is an attractive tool for cancer therapeutics. MP-RM-1, a murine monoclonal antibody targeting human ErbB-3, has shown anticancer activity in preclinical models. With the aim to provide novel candidates for clinical use, we have successfully generated a humanized version of MP-RM-1. The humanized antibody, named EV20, abrogates both ligand-dependent and ligand-independent receptor signaling of several tumor cell types, strongly promotes ErbB-3 down-regulation, and efficiently and rapidly internalizes into tumor cells. Furthermore, treatment with EV20 significantly inhibits growth of xenografts originating from prostatic, ovarian, and pancreatic cancers as well as melanoma in nude mice. In conclusion, we provide a novel candidate for ErbB-3-targeted cancer therapy.     

Prognostic factors and predictors of outcome in patients with COVID-19 and related pneumonia: a retrospective cohort study

The aim of the present study was to simultaneously assess several potential predictors of outcome (co-morbidity, previous and in-hospital treatment, radiologic Brixia score) in patients with COVID-19.This retrospective cohort study included 258 consecutive patients with confirmed COVID-19 admitted to a medical ward at Montichiari Hospital, Brescia, Italy from February 28th to April 30rd, 2020. Patients had SARS-CoV-2 related pneumonia with respiratory failure, and were treated with hydroxychloroquine and lopinavir plus ritonavir. In some patients, additional treatment with tocilizumab, dexamethasone and enoxaparin was adopted. Outcomes (death or recovery) were assessed at the end of the discharge period or at the end of the follow-up (August 2020).During hospitalization, 59 patients died, while 6 died after discharge. The following variables were demonstrated to be associated with a worse prognosis: Radiologic Brixia score higher than 8, presence at baseline of hypertension, diabetes, chronic obstructive pulmonary disease, heart disease, cancer, previous treatment with ACE-inhibitors or anti-platelet drugs. Anticoagulant treatment during hospital admission with enoxaparin at a dose higher than 4000 U once daily was associated with a better prognosis.In conclusion, our study demonstrates that some co-morbidities and cardiovascular risk factors may affect prognosis. The radiologic Brixia score may be a useful tool to stratify the risk of death at baseline. Anticoagulant treatment with enoxaparin might be associated to a clinical benefit in terms of survival in patients with COVID-19.     

Circulating miRNAs expression as potential biomarkers of mild traumatic brain injury

Molecular Biology Reports - TBI is the main cause of death and disability in individuals aged 1–45 in Western countries. One of the main challenges of TBI at present is the lack of specific...     

Machine learning techniques for protein function prediction

Proteins play important roles in living organisms, and their function is directly linked with their structure. Due to the growing gap between the number of proteins being discovered and their functional characterization (in particular as a result of experimental limitations), reliable prediction of protein function through computational means has become crucial. This paper reviews the machine learning techniques used in the literature, following their evolution from simple algorithms such as logistic regression to more advanced methods like support vector machines and modern deep neural networks. Hyperparameter optimization methods adopted to boost prediction performance are presented. In parallel, the metamorphosis in the features used by these algorithms from classical physicochemical properties and amino acid composition, up to text-derived features from biomedical literature and learned feature representations using autoencoders, together with feature selection and dimensionality reduction techniques, are also reviewed. The success stories in the application of these techniques to both general and specific protein function prediction are discussed.     

CARD14/CARMA2sh and TANK differentially regulate poly(I:C)–induced inflammatory reaction in keratinocytes

CARD14/CARMA2sh (CARMA2sh) is a scaffold protein whose mutations are associated with the onset of human genetic psoriasis and other inflammatory skin disorders. Here we show that the immunomodulatory adapter protein TRAF family member-associated NF-κB activator (TANK) forms a complex with CARMA2sh and MALT1 in a human keratinocytic cell line. We also show that CARMA2 and TANK are individually required to activate the nuclear factor κB (NF-κB) response following exposure to polyinosinic-polycytidylic (poly [I:C]), an agonist of toll-like receptor 3. Finally, we present data indicating that TANK is essential for activation of the TBK1/IRF3 pathway following poly (I:C) stimulation, whereas CARMA2sh functions as a repressor of it. More important, we report that two CARMA2sh mutants associated with psoriasis bind less efficiently to TANK and are therefore less effective in suppressing the TBK1/IRF3 pathway. Overall, our data indicate that TANK and CARMA2sh regulate TLR3 signaling in human keratinocytes, which could play a role in the pathophysiology of psoriasis.