A unique origin for Sicilian (δβ)∘-thalassemia in 33 unrelated families and its rapid diagnostic characterization by PCR analysis

Direct sequencing and restriction enzyme digestion of the polymerase chain reaction (PCR) product encompassing the breakpoint were used to characterize the Sicilian ()-thalassemia deletion in 33 unrelated Italian subjects. All cases showed the same sequencing features at the breakpoint region, suggesting a unique origin for this deletion in Italy. We also describe a one-step PCR assay for the rapid screening of homozygotes and carriers of Sicilian ()-thalassemia by the simultaneous use of three specific oligonucleotides. This procedure could have an impact on genetic counseling of couples at risk for this type of thalassemia, and with respect to compound heterozygotes bearing a Sicilian chromosome.     

Structural properties of Gerstmann-Straussler-Scheinker disease amyloid protein

Prion protein (PrP) amyloid formation is a central feature of genetic and acquired forms of prion disease such as Gerstmann-Str?ussler-Scheinker disease (GSS) and variant Creutzfeldt-Jakob disease. The major component of GSS amyloid is a PrP fragment spanning residues approximately 82-146. To investigate the determinants of the physicochemical properties of this fragment, we synthesized PrP-(82-146) and variants thereof, including entirely and partially scrambled peptides. PrP-(82-146) readily formed aggregates that were partially resistant to protease digestion. Peptide assemblies consisted of 9.8-nm-diameter fibrils having a parallel cross-beta-structure. Second derivative of infrared spectra indicated that PrP-(82-146) aggregates are primarily composed of beta-sheet (54%) and turn (24%) which is consistent with their amyloid-like properties. The peptide induced a remarkable increase in plasma membrane microviscosity of primary neurons. Modification of the amino acid sequence 106-126 caused a striking increase in aggregation rate, with formation of large amount of protease-resistant amorphous material and relatively few amyloid fibrils. Alteration of the 127-146 region had even more profound effects, with the inability to generate amyloid fibrils. These data indicate that the intrinsic properties of PrP-(82-146) are dependent upon the integrity of the C-terminal region and account for the massive deposition of PrP amyloid in GSS.     

Vertebrate Tracksites in the Middle Jurassic-Upper Cretaceous of South Tunisia

Four vertebrate tracksites from the Middle Jurassic and Upper Cretaceous in the Tataouine basin of southern Tunisia are described. Approximately 130 tridactyl footprints distributed over an area of 200 square meters, preserved on Callovian beds exposed at the Beni Ghedir site, represent the oldest evidence of a dinosaur fauna in Tunisia. In addition, three tracksites—Chenini, Ksar Ayaat, and Jebel Boulouha—have been discovered in the Cretaceous beds of the upper Continental Intercalaire, previously considered as a strictly marine depositional sequence. In addition to dinosaur tracks, the Chenini tracksite (late Albian) includes poorly preserved crocodilian tracks, and footprints assigned to a pleurodiran turtle have been recovered at the Ksar Ayaat locality (early Cenomanian). The Jebel Boulouha tracksite is dominated by well-preserved tridactyl tracks referred to small-sized theropods. Depositional settings of each tracksite have been defined on stratigraphic and sedimentologic data, and tracks were ascribed to different ichnocoenoses in relation to their paleoenvironments. This new and differentiated track record gives important information on how the fossil vertebrate fauna changed in southern Tunisia during mid-Jurassic to mid-Cretaceous times. These data provide a unique and useful census of tetrapod associations along the southern margin of the peri-Mediterranean area.     

Induction of robust diabetes resistance and prevention of recurrent type 1 diabetes following islet transplantation by gene therapy

We have previously shown that the development of type 1 diabetes (T1D) can be prevented in nonobese diabetic (NOD) mice by reconstitution with autologous hemopoietic stem cells retrovirally transduced with viruses encoding MHC class II I-A beta-chain molecules associated with protection from the disease. In this study we examined whether a blockade of the programmed death-1 (PD-1)-programmed death ligand-1 (PD-L1) pathway, a major pathway known to control diabetes occurrence, could precipitate T1D in young NOD mice following reconstitution with autologous bone marrow retrovirally transduced with viruses encoding protective MHC class II I-A beta-chain molecules. In addition, we examined whether the expression of protective MHC class II alleles in hemopoietic cells could be used to prevent the recurrence of diabetes in mice with pre-existing disease following islet transplantation. Protection from the occurrence of T1D diabetes in young NOD mice by the expression of protective MHC class II I-A beta-chain molecules in bone marrow-derived hemopoietic cells was resistant to induction by PD-1-PD-L1 blockade. Moreover, reconstitution of NOD mice with pre-existing T1D autologous hemopoietic stem cells transduced with viruses encoding protective MHC class II I-A beta-chains allowed for the successful transplantation of syngeneic islets, resulting in the long-term reversal of T1D. Reversal of diabetes was resistant to induction by PD-1-PDL-1 blockade and depletion of CD25(+) T cells. These data suggest that expression of protective MHC class II alleles in bone marrow-derived cells establishes robust self-tolerance to islet autoantigens and is sufficient to prevent the recurrence of autoimmune diabetes following islet transplantation.     

Polyphasic classification of Alternaria isolated from hazelnut and walnut fruit in Europe

Brown apical necrosis of English walnut and grey necrosis of hazelnut are destructive fruit diseases caused by a complex of opportunistic fungi including several small-spored catenulate Alternaria taxa. Thirty Alternaria isolates recovered from walnut and hazelnut fruit that were pathogenic on their respective host were compared along with type or representative isolates of A. alternata, A. tenuissima, A. arborescens, and A. infectoria using morphological and molecular criteria. Morphological examination using standardized procedures separated the walnut and hazelnut isolates into three morphological groups: the A. alternata group, the A. tenuissima group, and the A. arborescens group based upon common characteristics of the conidium and the sporulation apparatus. To evaluate genetic relationships among these groups, AFLP markers, inter simple sequence repeat (ISSR) markers, and histone gene sequence data were compared. Based upon AFLP data, the A. alternata and A. tenuissima groups comprised a single lineage, and the A. arborescens group comprised a separate lineage. ISSR data supported the grouping by AFLP data except for three isolates of the A. alternata group that clustered with the A. arborescens group. Base substitution of the H4 gene supported the discrimination of the A. arborescens group from the A. alternata and A. tenuissima groups. Tests of hypotheses based upon groupings derived from the various data sets supported the discrimination of the A. arborescens group but did not support the discrimination of the A. alternata group from the A. tenuissima group.     

Empathy in Cooperative Versus Non-cooperative Situations: The Contribution of Self-Report Measures and Autonomic Responses

Shared representations, emotion comprehension, and emotion regulation constitute the basic macro components of social empathy. The present study integrated two different measures of empathic behavior in a social context: verbal self-report measures (empathic response, emotional involvement and emotional significance, and valence), and autonomic responses (facial expression-corrugator supercilii and zygomaticus major muscle-, SCR-skin conductance-, and HR-heart rate-). Participants (N?=?thirty-five) were presented with different interpersonal scene types (cooperation, non-cooperation, conflict, indifference). Different empathic sensitivity to these interpersonal situations was verified, since self-rating on empathy, emotional involvement and valence varied as a function of interpersonal context. Situation rated as more empathically significant were considered also as the most positive (cooperation) and negative (non cooperation and conflictual) and emotionally significant (high emotional significance of the scenes) in comparison with neutral scenes. Nevertheless, subjective empathic response and personal emotional involvement were found to be dissociated measures in non-cooperative condition. On the autonomic level, facial mimicry was linked to and coherent with the empathic response in cooperative, non-cooperative and conflictual conditions, whereas SCR and HR were increased only in response to cooperative and conflictual situation, rated as more involving by the subject. The convergence of these multidimensional measures was discussed: empirical evidences are far from able to warrant claims that processes of emotional contagion and simulation provide the sole, primary important way by which we come to know what others are feeling.     

Prevalence and genotype identification of human papillomavirus in women undergoing voluntary cervical cancer screening in Molise,Central Italy

We examined the prevalence of HR- and LR-HPV by Linear Array genotyping test in 299 women aged 18–63 years who consecutively visited Molise Region main hospitals for routine Pap smear between February and August 2008. Ninety women were positive for any HPV (30.1%), and 66 for any HR-HPV (22.1%). The most prevalent HR-HPV types were HPV 16 (22.2% of all women with HPV infection), HPV 53 (14.4%), and HPV 66 (14.4%). HPV infections increased from 15.8% in the 18–20 years group to 50.0% in the 21–23 years group and then decreased to 9.1% in those aged 50 years or more (p = 0.008). Multiple HPV infections were observed in 15.7% of the study sample (52.2% of all HPV positive). There is a significantly higher prevalence of multiple infections in 18–32 years group women (24.5%) compared with females aged 33 years or more (6.8%) (p < 0.005). Current smokers were at increased risk of HPV infection (44.2% of HPV infections compared with 23.5% in never smokers, and 25.3% of multiple HPV infections compared with 11.3%; p = 0.001). HR-HPV infections were higher in women never been pregnant (27.1% compared with 7.7%; p = 0.001). Oral contraceptive use was completely unrelated to infection. Among the 122 women who had both cytological examination and HPV results, multiple HR-HPV types were found in 36.8% of those with abnormal cervical findings, and in 13.6% of those with normal cervical findings (p = 0.05). The results of the present investigation provide further evidence for the notion that cervical HPV infection is more widespread than previously suggested.