Research has documented that most of retail and institutional investors exhibit a strong preference for stocks issued by nearby listed firms (i.e. Local Home Bias). This phenomenon shapes corporate ...market value and the cost of funding. In this paper, we investigate whether the Local Home Bias is enhanced in family firms as a consequence of their symbiotic connection with the local community. Using a dataset of 2,951 Italian firm-year observations (1,481 are family firms) over the period 1999–2011, we find that Local Home Bias is not a widespread phenomenon and mainly occurs in founding family firms where the founder serves as CEO. The Local Home Bias is absent in non-family firms or in family firms where the owner has acquired control through a market transaction. Overall, results suggest that locally committed family firms trigger investor preference for local stocks and, in doing so, exploit the dedicated local clientele which shrinks the cost of funding. Ultimately, we argue the social contributions of family firms to the local community could even have opportunistic traits and a non-trivial economic effect.
The largest crystalline unit representing the mid-crust in the Himalayan belt is the Greater Himalayan Sequence (GHS) which stretches all over the 2400km of length of the belt. The GHS, recognized ...since the first geological explorations of the Himalayas, has been considered for a long time as a coherent tectonic unit, exhumed by the contemporaneous shearing along the Main Central Thrust and the South Tibetan Detachment System in the time span ~25–17Ma. A multidisciplinary approach, integrating geological mapping, structural analysis, petrology and geochronology allowed to better constrain on its internal architecture characterized by several levels of tectonic-metamorphic discontinuities on the regional scale with a top-to-the-S/SW sense of shear and active since ~40Ma. The GHS is consequently divided in three main tectonic units exhumed progressively from the upper part to the lower one by ductile shear zones, later involving the Lesser Himalayan Sequence.
Above the Main Central Thrust a cryptic tectono-metamorphic discontinuity (Higher Himalayan Discontinuity; HHD) has been recognized and mapped in Central-Eastern Himalaya. The mapping of the HHD has been allowed by the use of a multidisciplinary approach involving structural analysis, geochronology and petrology. A new map of Western Nepal is presented.
In this framework the popular models of exhumation of the GHS mainly based on the contemporaneous activity of the two bounding shear zones (Main Central Thrust and the South Tibetan Detachment) and considering the GHS as a coherent tectonic unit, should be reconsidered. An in-sequence shearing tectonic model, from the deeper to the upper structural levels, further affected by out-of-sequence-thrusts, is more appropriate to explain the deformation, metamorphism and exhumation of the mid-crust in the Himalayan belt.
Geological mapping of the Himalayan belt is very far away to be exhaustively completed. Anyway during the last 20, and particularly during the last few years, it has been notably improved due to a new multidisciplinary approach.
PARP inhibitors (PARPi) have changed the treatment paradigm of high-grade serous ovarian cancer (HG-SOC). However, the impact of this class of inhibitors in HG-SOC patients with a high rate of TP53 ...mutations is limited, highlighting the need to develop combinatorial therapeutic strategies to improve responses to PARPi. Here, we unveil how the endothelin-1/ET-1 receptor (ET-1/ET-1R) axis, which is overexpressed in human HG-SOC and associated with poor prognosis, instructs HG-SOC/tumor microenvironment (TME) communication via key pro-malignant factors and restricts the DNA damage response induced by the PARPi olaparib. Mechanistically, the ET-1 axis promotes the p53/YAP/hypoxia inducible factor-1α (HIF-1α) transcription hub connecting HG-SOC cells, endothelial cells and activated fibroblasts, hence fueling persistent DNA damage signal escape. The ET-1R antagonist macitentan, which dismantles the ET-1R-mediated p53/YAP/HIF-1α network, interferes with HG-SOC/stroma interactions that blunt PARPi efficacy. Pharmacological ET-1R inhibition by macitentan in orthotopic HG-SOC patient-derived xenografts synergizes with olaparib to suppress metastatic progression, enhancing PARPi survival benefit. These findings reveal ET-1R as a mechanistic determinant in the regulation of HG-SOC/TME crosstalk and DNA damage response, indicating the use of macitentan in combinatorial treatments with PARPi as a promising and emerging therapy.
The enrichment of lysosomes is a useful way to study their structure and function. These dynamic vesicles can be enriched from cell cultures in a variety of ways including immunoprecipitation and ...fluorescence-activated organelle sorting. These methods are extremely precise but often require the transfection and expression of an affinity or fluorophore-tagged lysosomal membrane protein. A simpler approach uses differential density of subcellular organelles, which are characteristic to a particular type of organelle. Separation of organelles along a density-gradient enables fractionation to enrich for specific organelles (such as lysosomes) in their native state. This protocol outlines an optimized method for enriching lysosomes from HeLa cells with a continuous density-gradient that contains Percoll. Gentle cell lysis and extraction conditions yield dense-fractions that are enriched with functional and intact lysosomes, which can be assayed in downstream analyses. This method is quick (conducted in less than 2 h after harvesting cells), and can be easily scaled and optimized for other cell types.
Candida species are an uncommon cause of infective endocarditis (IE). Given the rarity of this infection, the epidemiology, prognosis, and optimal therapy of Candida IE are poorly defined. We ...conducted a prospective, observational study at 18 medical centers in Italy, including all consecutive patients with a definite diagnosis of IE admitted from January 2004 through December 2007.A Candida species was the causative organism in 8 cases of prosthetic valve endocarditis (PVE), 5 cases of native valve endocarditis (NVE), 1 case of pacemaker endocarditis, and 1 case of left ventricular patch infection. Candida species accounted for 1.8% of total cases, and for 3.4% of PVE cases. Most patients (86.6%) had a health care-associated infection. PVE associated with a health care contact occurred after a median of 225 days from valve implantation. Ten patients (66.6%) were treated with caspofungin alone or in combination with other antifungal drugs. The overall mortality rate was 46.6%. Mortality was higher in patients with PVE (5 of 8 cases, 62.5%) than in patients with NVE (2 of 5 patients, 40%). A better outcome was observed in patients treated with a combined medical and surgical therapy.Candida IE should be classified as an emerging infectious disease, usually involving patients with intravascular prosthetic devices, and associated with substantial related morbidity and mortality. Candida PVE usually is a late-onset disease, which becomes clinically evident even several months after an initial episode of transient candidemia.
5′- and 3′-untranslated regions (UTRs) are important regulators of gene expression and play key roles in disease progression and susceptibility. The 5′-UTR of the fragile X mental retardation 1 ...(FMR1) gene contains a CGG repeat element that is expanded (>200 CGG repeats; full mutation) and methylated in fragile X syndrome (FXS), the most common form of inherited intellectual disability (ID) and known cause of autism. Significant phenotypic involvement has also emerged in some individuals with the premutation (55-200 CGG repeats), including fragile X-associated premature ovarian insufficiency (FXPOI) in females, and the neurodegenerative disorder, fragile X-associated tremor/ataxia syndrome (FXTAS), in older adult carriers. Here, we show that FMR1 mRNA in human and mouse brain is expressed as a combination of multiple isoforms that use alternative transcriptional start sites and different polyadenylation sites. Furthermore, we have identified a novel human transcription start site used in brain but not in lymphoblastoid cells, and have detected FMR1 isoforms generated through the use of both canonical and non-canonical polyadenylation signals. Importantly, in both human and mouse, a specific regulation of the UTRs is observed in brain of FMR1 premutation alleles, suggesting that the transcript variants may play a role in premutation-related pathologies.
In recent decades, constraining the timing of shear activity has been one of the main topics of research about the tectono-metamorphic evolution of orogenic belts. We present a review of a combined ...structural and geochronological approach to two major ductile regional shear zones, in two collisional orogens: the first one affecting the Variscan basement in northern Sardinia (Italy) and the External Crystalline Massifs of the Alps (East Variscan Shear Zone; EVSZ), and the second one deforming the medium- to high-grade rocks of the metamorphic core of the Himalaya (High Himalayan Discontinuity). High-resolution, texturally and chemically controlled monazite geochronology applied in separated shear zones of the Variscan belt allowed recognizing a similar timing of activity ranging between c. 340–330 and 300 Ma. This approach led to a better understanding of the evolution of the EVSZ, supporting a model where several branches were active according to a growth by linkage model. Following a similar approach, in situ U-Th-Pb analysis of monazite constrained the timing of top-to-the-S/SW shearing of a regional-scale High Himalayan Discontinuity in the Himalayan belt to between c. 28 Ma and 17 Ma. Earlier exhumation of the hanging wall was triggered by shear zone activity, whereas at the same time, the footwall was still experiencing burial with increasing P-T conditions. The timing of shearing of this shear zone fits with an in-sequence shearing tectonic model for the exhumation of the Himalayan mid-crust.
Context. QSO B1420+326 is a blazar classified as a flat-spectrum radio quasar (FSRQ). At the beginning of the year 2020, it was found to be in an enhanced flux state and an extensive multiwavelength ...campaign allowed us to trace the evolution of the flare. Aims. We search for very high-energy (VHE) gamma-ray emission from QSO B1420+326 during this flaring state. We aim to characterize and model the broadband emission of the source over different phases of the flare. Methods. The source was observed with a number of instruments in radio, near-infrared, optical (including polarimetry and spectroscopy), ultraviolet, X-ray, and gamma-ray bands. We use dedicated optical spectroscopy results to estimate the accretion disk and the dust torus luminosity. We performed spectral energy distribution modeling in the framework of combined synchrotron-self-Compton and external Compton scenario in which the electron energy distribution is partially determined from acceleration and cooling processes. Results. During the enhanced state, the flux of both SED components of QSO B1420+326 drastically increased and the peaks were shifted to higher energies. Follow-up observations with the MAGIC telescopes led to the detection of VHE gamma-ray emission from this source, making it one of only a handful of FSRQs known in this energy range. Modeling allows us to constrain the evolution of the magnetic field and electron energy distribution in the emission region. The gamma-ray flare was accompanied by a rotation of the optical polarization vector during a low -polarization state. Also, a new superluminal radio knot contemporaneously appeared in the radio image of the jet. The optical spectroscopy shows a prominent FeII bump with flux evolving together with the continuum emission and a MgII line with varying equivalent width.
Nutria (or coypu, Myocastor coypus), is a semi-aquatic rodent that is native to South America and has been introduced almost all over the world since the end of the 19th century. In Europe, this ...rodent is considered an invasive species. In this report, we analyzed nutria fecal samples in a small coastal wetland of Central Italy, using different techniques (fresh smear, direct immunofluorescence, Baermann technique, flotation, ethyl acetate sedimentation) to obtain an arrangement of eukaryote endoparasites (Protozoa and Helminths) and compare them with data available in the literature for both Italy and worldwide. We recorded five taxa, with a dominant occurrence (>70%) of nematodes of the genus Strongyloides. Moreover, we reported for the first time in nutria a bronchopulmonary strongyle nematode (Muellerius vel. Angiostrongylus) and, for the first time in Italy, protozoans of the genus Cryptosporidium. Since nutria co-occurs with humans and domestic animals in the study area, we highlighted possible sanitary and management implications.
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