Le confessioni religiose tra libertà di vivere nella realtà dell'ordinamento statale e potere di creare norme giuridiche all'interno dello Stato. Il caso della Chiesa di Scientology.

L'A. si pone nella prospettiva di delineare il possibile significato della compresenza delle due distinte previsioni, l’una nell’art. 8, l’altra nell’art. 19 della Costituzione, a garanzia del fenomeno associativo religioso. La ricerca è stata redatta, fra l’altro, in considerazione della circostanza che, ad una prima sommaria lettura della Carta Costituzionale, il lettore potrebbe essere indotto a pensare che il fenomeno religioso, ed in particolare quello che si svolge in forma associata, goda di una maggiore preferenza, rispetto a quello che si esprime in forma individuale, per essere più volte disciplinato in Costituzione. Problema, questo, il quale non sembra abbia sinora ricevuto adeguato rilievo dalla dottrina ecclesiasticista che si è meritevolmente impegnata sul tema. Si è posto al riguardo l’interrogativo che nasce dalla presenza di due distinte previsioni costituzionali a garanzia del fenomeno associativo religioso: la prima contenuta nell’art. 8 il quale - com’è noto - regola con novità di linguaggio la posizione dei culti diversi dalla religione cattolica, garantisce alle confessioni religiose l’eguale libertà davanti alla legge, il diritto di organizzarsi secondo i propri statuti ed il potere di concludere intese con gli organi dello Stato; la seconda nell’art. 19 che riconosce la libertà di professare liberamente la propria fede religiosa in qualsiasi forma “individuale o associata”. In ordine ai numerosi problemi che la previsione costituzionale dell’art. 8 solleva, si è riflettuto soprattutto sul dubbio se la fattispecie in essa contemplata sia sostanzialmente ripetitiva e si risolva in un inutile duplicato di quanto disposto dall’art. 19 per la parte che riguarda tale aspetto, oppure se, con ciascuna di tali disposizioni, il legislatore costituzionale abbia voluto conferire uno specifico rilievo a due distinte sfere dell’esperienza giuridica con caratteristiche proprie, per struttura e sistemi di garanzie. L’analisi intrapresa ha interessato anche la ricostruzione della definizione giuridica di confessione religiosa, nonché l’accertamento del carattere confessionale della Chiesa di Scientology alla luce delle sentenze della giurisprudenza costituzionale e di legittimità

Flat Low-Loss Silicon Gradient Index Lens for Millimeter and Submillimeter Wavelengths

We present the design, simulation, and planned fabrication process of a flat high resistivity silicon gradient index (GRIN) lens for millimeter and submillimeter wavelengths with very low absorption losses. The gradient index is created by sub wavelength holes whose size increases with the radius of the lens. The effective refractive index created by the subwavelength holes is constant over a very wide bandwidth, allowing the fabrication of achromatic lenses up to submillimeter wavelengths. The designed GRIN lens was successfully simulated and shows an expected efficiency better than that of a classic silicon plano-concave spherical lens with approximately the same thickness and focal length. Deep reactive ion etching (DRIE) and wafer-bonding of several patterned wafers will be used to realize our first GRIN lens prototype

The botanical drug PBI-05204, a supercritical CO2 extract of Nerium oleander, sensitizes alveolar and embryonal rhabdomyosarcoma to radiotherapy in vitro and in vivo

Treatment of rhabdomyosarcoma (RMS), the most common a soft tissue sarcoma in childhood, provides intensive multimodal therapy, with radiotherapy (RT) playing a critical role for local tumor control. However, since RMS efficiently activates mechanisms of resistance to therapies, despite improvements, the prognosis remains still largely unsatisfactory, mainly in RMS expressing chimeric oncoproteins PAX3/PAX7-FOXO1, and fusion-positive (FP)-RMS. Cardiac glycosides (CGs), plant-derived steroid-like compounds with a selective inhibitory activity of the Na+/K+-ATPase pump (NKA), have shown antitumor and radio-sensitizing properties. Herein, the therapeutic properties of PBI-05204, an extract from Nerium oleander containing the CG oleandrin already studied in phase I and II clinical trials for cancer patients, were investigated, in vitro and in vivo, against FN- and FP-RMS cancer models. PBI-05204 induced growth arrest in a concentration dependent manner, with FP-RMS being more sensitive than FN-RMS, by differently regulating cell cycle regulators and commonly upregulating cell cycle inhibitors p21Waf1/Cip1 and p27Cip1/Kip1. Furthermore, PBI-05204 concomitantly induced cell death on both RMS types and senescence in FN-RMS. Notably, PBI-05204 counteracted in vitro migration and invasion abilities and suppressed the formation of spheroids enriched in CD133+ cancer stem cells (CSCs). PBI-05204 sensitized both cell types to RT by improving the ability of RT to induce G2 growth arrest and counteracting the RT-induced activation of both Non‐Homologous End‐Joining and homologous recombination DSBs repair pathways. Finally, the antitumor and radio-sensitizing proprieties of PBI-05204 were confirmed in vivo. Notably, both in vitro and in vivo evidence confirmed the higher sensitivity to PBI-05204 of FP-RMS. Thus, PBI-05204 represents a valid radio-sensitizing agent for the treatment of RMS, including the intrinsically radio-resistant FP-RMS

Clinically relevant radioresistant rhabdomyosarcoma cell lines: Functional, molecular and immune-related characterization

Background: The probability of local tumor control after radiotherapy (RT) remains still miserably poor in pediatric rhabdomyosarcoma (RMS). Thus, understanding the molecular mechanisms responsible of tumor relapse is essential to identify personalized RT-based strategies. Contrary to what has been done so far, a correct characterization of cellular radioresistance should be performed comparing radioresistant and radiosensitive cells with the same isogenic background. Methods: Clinically relevant radioresistant (RR) embryonal (RD) and alveolar (RH30) RMS cell lines have been developed by irradiating them with clinical-like hypo-fractionated schedule. RMS-RR cells were compared to parental isogenic counterpart (RMS-PR) and studied following the radiobiological concept of the "6Rs", which stand for repair, redistribution, repopulation, reoxygenation, intrinsic radioresistance and radio-immuno-biology. Results: RMS-RR cell lines, characterized by a more aggressive and in vitro pro-metastatic phenotype, showed a higher ability to i) detoxify from reactive oxygen species; ii) repair DNA damage by differently activating non-homologous end joining and homologous recombination pathways; iii) counteract RT-induced G2/M cell cycle arrest by re-starting growth and repopulating after irradiation; iv) express cancer stem-like profile. Bioinformatic analyses, performed to assess the role of 41 cytokines after RT exposure and their network interactions, suggested TGF-β, MIF, CCL2, CXCL5, CXCL8 and CXCL12 as master regulators of cancer immune escape in RMS tumors. Conclusions: These results suggest that RMS could sustain intrinsic and acquire radioresistance by different mechanisms and indicate potential targets for future combined radiosensitizing strategies

Protein 4.1B Contributes to the Organization of Peripheral Myelinated Axons

Neurons are characterized by extremely long axons. This exceptional cell shape is likely to depend on multiple factors including interactions between the cytoskeleton and membrane proteins. In many cell types, members of the protein 4.1 family play an important role in tethering the cortical actin-spectrin cytoskeleton to the plasma membrane. Protein 4.1B is localized in myelinated axons, enriched in paranodal and juxtaparanodal regions, and also all along the internodes, but not at nodes of Ranvier where are localized the voltage-dependent sodium channels responsible for action potential propagation. To shed light on the role of protein 4.1B in the general organization of myelinated peripheral axons, we studied 4.1B knockout mice. These mice displayed a mildly impaired gait and motility. Whereas nodes were unaffected, the distribution of Caspr/paranodin, which anchors 4.1B to the membrane, was disorganized in paranodal regions and its levels were decreased. In juxtaparanodes, the enrichment of Caspr2, which also interacts with 4.1B, and of the associated TAG-1 and Kv1.1, was absent in mutant mice, whereas their levels were unaltered. Ultrastructural abnormalities were observed both at paranodes and juxtaparanodes. Axon calibers were slightly diminished in phrenic nerves and preterminal motor axons were dysmorphic in skeletal muscle. βII spectrin enrichment was decreased along the axolemma. Electrophysiological recordings at 3 post-natal weeks showed the occurrence of spontaneous and evoked repetitive activity indicating neuronal hyperexcitability, without change in conduction velocity. Thus, our results show that in myelinated axons 4.1B contributes to the stabilization of membrane proteins at paranodes, to the clustering of juxtaparanodal proteins, and to the regulation of the internodal axon caliber

The Persistent Challenge of Pneumocystis Growth Outside the Mammalian Lung: Past and Future Approaches

The pathogenic fungi in the genus, Pneumocystis, have eluded attempts to continuously grow them in anex vivocultivation system. New data from transcriptomic and genomic sequencing studies have identified a myriad of absent metabolic pathways, helping to define their host obligate nature. These nutrients, factors, and co-factors are acquired from their mammalian host and provide clues to further supplementation of existing media formulations. Likewise, a new appreciation of the pivotal role for the sexual cycle in the survival and dissemination of the infection suggests that Pneumocystis species are obligated to undergo mating and sexual reproduction in their life cycle with a questionable role for an asexual cycle. The lack of ascus formation in any previous cultivation attempts may explain the failure to identify a sustainable system. Many characteristics of these ascomycetes suggest a biotrophic existence within the lungs of the mammalian hosts. In the present review, previous attempts at growing these fungiex vivoare summarized. The significance of their life cycle is considered, and a list of potential supplements based on the genomic and transcriptomic studies is presented. State of the art technologies such as metabolomics, organoids, lung-on-a chip, and air lift cultures are discussed as potential growth systems.</jats:p

Blood coagulation factors in human embryonic-fetal development: preferential expression of the FVII/tissue factor pathway

The expression of a number of blood coagulation factors (F) (FX, FIX, FVIII, FVII, alpha-, beta-, gamma-fibrinogen chains, protein C, and antithrombin III [AT III]) was analyzed at RNA and protein level in 5- to 10-week-old human embryos and fetuses. FX, FIX, and FVII were also analyzed at protein level. Total and poly(A)+ RNA, extracted from embryonic-fetal (FL) and adult liver (AL), were analyzed by dot and Northern blot hybridization with specific cDNA probes. The results indicate that: (1) the size of the messenger RNAs of these factors is equivalent in FL and AL; (2) in the 5- to 10-week period, their abundance in FL increases from 30% to 50% of the adult level except for FIX (from 2% to 10%) and FX (always 100% of the adult value). Western blot analysis of FIX, FX, and FVII in 5- to 10-week soluble liver proteins and 6- to 8-week plasma showed a low level of FIX versus a higher concentration of both FVII and FX, when compared with corresponding adult values, ie, a liver protein level of 10% versus 100% and a plasma concentration level of 10% versus 40%. Although little is known so far on the activity and the functional role of the clotting factors in early human ontogenic development, these studies suggest an activation of FX via the FVII/tissue factor activity rather than the FIXa/FVIIIa phospholipid complex in human embryonic and early fetal life.</jats:p

Blood coagulation factors in human embryonic-fetal development: preferential expression of the FVII/tissue factor pathway

Abstract The expression of a number of blood coagulation factors (F) (FX, FIX, FVIII, FVII, alpha-, beta-, gamma-fibrinogen chains, protein C, and antithrombin III [AT III]) was analyzed at RNA and protein level in 5- to 10-week-old human embryos and fetuses. FX, FIX, and FVII were also analyzed at protein level. Total and poly(A)+ RNA, extracted from embryonic-fetal (FL) and adult liver (AL), were analyzed by dot and Northern blot hybridization with specific cDNA probes. The results indicate that: (1) the size of the messenger RNAs of these factors is equivalent in FL and AL; (2) in the 5- to 10-week period, their abundance in FL increases from 30% to 50% of the adult level except for FIX (from 2% to 10%) and FX (always 100% of the adult value). Western blot analysis of FIX, FX, and FVII in 5- to 10-week soluble liver proteins and 6- to 8-week plasma showed a low level of FIX versus a higher concentration of both FVII and FX, when compared with corresponding adult values, ie, a liver protein level of 10% versus 100% and a plasma concentration level of 10% versus 40%. Although little is known so far on the activity and the functional role of the clotting factors in early human ontogenic development, these studies suggest an activation of FX via the FVII/tissue factor activity rather than the FIXa/FVIIIa phospholipid complex in human embryonic and early fetal life.</jats:p