Flux creep in Bi2Sr2CaCu2O8(sub +x) single crystals

The results of a magnetic study on a Bi2Sr2CaCu2O(8+x) single crystal are reported. Low field susceptibility (dc and ac), magnetization cycles and time dependent measurements were performed. With increasing the temperature the irreversible regime of the magnetization cycles is rapidly restricted to low fields, showing that the critical current J(sub c) becomes strongly field dependent well below T(sub c). At 2.4 K the critical current in zero field, determined from the remanent magnetization by using the Bean formula for the critical state, is J(sub c) = 2 10(exp 5) A/sq cm. The temperature dependence of J(sub c) is satisfactorily described by the phenomenological law J(sub c) = J(sub c) (0) (1 - T/T(sub c) (sup n), with n = 8. The time decay of the zero field cooled magnetization and of the remanent magnetization was studied at different temperatures for different magnetic fields. The time decay was found to be logarithmic in both cases, at least at low temperatures. At T = 4.2 K for a field of 10 kOe applied parallel to the c axis, the average pinning energy, determined by using the flux creep model, is U(sub o) = 0.010 eV

Binge eating attitudes in community adolescent sample and relationships with interview-assessed attachment representations in girls: a multi-center study from North Italy

Purpose: To compare community girls at risk and not at risk for binge eating (BE) in attachment representations through a narrative interview and to test the predictive role of attachment pattern(s) on the risk of binge eating among community girls. Methods: From 772 community adolescents of both sexes (33% boys) screened through the Binge Eating Scale (BES), 112 girls between 14 and 18 years, 56 placed in a group at risk for binge eating (BEG), and 56 matched peers, not at risk (NBEG), were assessed in attachment representations through the Friends and Family Interview (FFI). Results: (1) Compared to NBEG, girls in the BEG showed more insecure-preoccupied classifications and scores, together with lower narrative coherence, mother\u2019s representation as a secure base/safe haven, reflective functioning, adaptive response, and more anger toward mother. (2) Both insecure-dismissing and preoccupied patterns predicted 15% more binge-eating symptoms in the whole sample of community girls. Conclusions: Insecure attachment representations are confirmed risk factors for more binge eating, affecting emotional regulation and leading to \u201cemotional eating\u201d, thus a dimensional assessment of attachment could be helpful for prevention and intervention. Implications and limits are discussed. Level of evidence: III. Evidence obtained from cohort or case\u2013control analytic studie

Placenta growth factor induces melanoma resistance to temozolomide through a mechanism that involves the activation of the transcription factor NF-κB

Placenta growth factor (PlGF) and its receptor vascular endothelial growth factor receptor-1 (VEGFR-1) are co-expressed in a large number of human melanoma cell lines. Moreover, a correlation between in vivo PlGF production and melanoma progression has been suggested. To investigate whether PlGF might have a role in protecting melanoma cells from the cytotoxic effects of the anticancer agent temozolomide (TMZ), which is used for the treatment of this malignancy, we stably transfected a doxycycline-inducible PlGF antisense mRNA into a human melanoma cell clone that secretes VEGF-A and PlGF and expresses receptors for both growth factors. Induction of PlGF antisense mRNA in the transfected cells (13443/ASP3 subclone) halved TMZ IC(50), and exogenous addition of PlGF to the culture medium 24 h before TMZ treatment, partially restored IC(50) values to that of control cells. The increased sensitivity of 13443/ASP3 cells upon PlGF antisense mRNA expression was not due to down-regulation of O6-methylguanine-DNA methyltransferase, a DNA repair protein that represents the main mechanism of resistance to TMZ. Since the activity of the transcription factor nuclear factor-κB (NF-κB) has been correlated to melanoma chemoresistance, we investigated whether NF-κB was involved in PlGF-induced melanoma cell resistance to TMZ. Induction of PlGF antisense mRNA in 13443/ASP3 cells halved the levels of active NF-κB and the specific inhibition of this transcription factor increased sensitivity of 13443/ASP3 cells to TMZ. In conclusion, our data strongly suggest that PlGF plays a role in melanoma cell resistance to TMZ through a pathway that involves NF-κB activation

\u201cWhat is more important than love?\u201d. Parental attachment and romantic relationship in Italian emerging adulthood

Previous researches suggest that individuals with different attachment styles practice different styles of love, but these do not consider the role of trust, communication, and closeness to the father and mother separately. The main aim of this study was to evaluate the relationship and the impact of parental attachment, through the analysis of the participants\u2019 self-reported account and 1. Department of Education, Cultural Heritage and Tourism, University of Macerata. Postbox: Piazzale Luigi Bertelli (Contrada Vallebona) 62100, Macerata, Italy 2. Psychology of Communication department, University of Macerata, Angelo Carrieri. 3. University of Pablo de Olavide, (ES), Health Plus Parish Priest Mifsud Str. Hamrun, Malta 4. Health Plus Parish Priest Mifsud Str. Hamrun, Malta Accepted Manuscript 4 romantic styles in Italians emerging adulthood by using a multidimensional approach (trust, communication, closeness to father and mother). The 296 participants (19\u201329 years; 50.7% males) rated items of information on a questionnaire, regarding their perspective of their attachment to their mother/father and attitude toward love. Using a variable-centred approach and a person-centred approach, the results suggest that the respondents differed in levels of parental attachment or love styles and that the present parental attachment has a positive impact on their romantic relationship. It is possible to estimate romantic relationships and prevent manic relationships based on the individual\u2019s current perceptions of their attachment to the father or mother. The role of parents and paternal attachment, are still fundamental in Italian young adults. The role of communication with the mother, in particular, is controversial and should be further investigated

Human exonuclease 1 role in response to UV irradiation

DNA damage checkpoints are surveillance mechanisms that monitor the integrity of the genome. Nucleotide excision repair (NER) is a DNA repair mechanism that cells use to remove UV-induced DNA lesions. Previous publication from our laboratory demonstrated that recognition and processing of UV-induced damage by NER is required for proper activation of checkpoint through interactions between NER proteins and checkpoint factors in yeast and human primary fibroblasts. From a two hybrid screening in yeast exonuclease 1 (Exo1) was identified as a 9-1-1 complex interactor. Exo1 is a 5\u2019-3\u2019 exonuclease and 5'-flap-endonuclease with many different roles in DNA metabolism such as meiotic and mitotic recombination, mismatch repair and telomere processing. Characterization of an exo1 yeast deleted strain has shown that this protein is involved in the early steps of UV-induced DNA damage checkpoint. In human cells EXO1 is present as two isoforms named hEXO1a and hEXO1b genetarated by alternative splicing. We are analyzing the role of EXO1 in checkpoint activation in response to UV-C damage in human cells: using siRNA against both a and b isoform of hEXO1 in G1 cells we were able to observe a defect in Chk1 and p53 phosphorylation induced by UV-C irradiation

NF-κB is activated in response to temozolomide in an AKT-dependent manner and confers protection against the growth suppressive effect of the drug.

BACKGROUND: Most DNA-damaging chemotherapeutic agents activate the transcription factor nuclear factor κB (NF-κB). However, NF-κB activation can either protect from or contribute to the growth suppressive effects of the agent. We previously showed that the DNA-methylating drug temozolomide (TMZ) activates AKT, a positive modulator of NF-κB, in a mismatch repair (MMR) system-dependent manner. Here we investigated whether NF-κB is activated by TMZ and whether AKT is involved in this molecular event. We also evaluated the functional consequence of inhibiting NF-κB on tumor cell response to TMZ. METHODS: AKT phosphorylation, NF-κB transcriptional activity, IκB-α degradation, NF-κB2/p52 generation, and RelA and NF-κB2/p52 nuclear translocation were investigated in TMZ-treated MMR-deficient (HCT116, 293TLα-) and/or MMR-proficient (HCT116/3-6, 293TLα+, M10) cells. AKT involvement in TMZ-induced activation of NF-κB was addressed in HCT116/3-6 and M10 cells transiently transfected with AKT1-targeting siRNA or using the isogenic MMR-proficient cell lines pUSE2 and KD12, expressing wild type or kinase-dead mutant AKT1. The effects of inhibiting NF-κB on sensitivity to TMZ were investigated in HCT116/3-6 and M10 cells using the NF-κB inhibitor NEMO-binding domain (NBD) peptide or an anti-RelA siRNA. RESULTS: TMZ enhanced NF-κB transcriptional activity, activated AKT, induced IκB-α degradation and RelA nuclear translocation in HCT116/3-6 and M10 but not in HCT116 cells. In M10 cells, TMZ promoted NF-κB2/p52 generation and nuclear translocation and enhanced the secretion of IL-8 and MCP-1. TMZ induced RelA nuclear translocation also in 293TLα+ but not in 293TLα- cells. AKT1 silencing inhibited TMZ-induced IκB-α degradation and NF-κB2/p52 generation. Up-regulation of NF-κB transcriptional activity and nuclear translocation of RelA and NF-κB2/p52 in response to TMZ were impaired in KD12 cells. RelA silencing in HCT116/3-6 and M10 cells increased TMZ-induced growth suppression. In M10 cells NBD peptide reduced basal NF-κB activity, abrogated TMZ-induced up-regulation of NF-κB activity and increased sensitivity to TMZ. In HCT116/3-6 cells, the combined treatment with NBD peptide and TMZ produced additive growth inhibitory effects. CONCLUSION: NF-κB is activated in response to TMZ in a MMR- and AKT-dependent manner and confers protection against drug-induced cell growth inhibition. Our findings suggest that a clinical benefit could be obtained by combining TMZ with NF-κB inhibitors

Haspin regulates Ras localization to promote Cdc24-driven mitotic depolarization

Cell polarization is of paramount importance for proliferation, differentiation, development, and it is altered during carcinogenesis. Polarization is a reversible process controlled by positive and negative feedback loops. How polarized factors are redistributed is not fully understood and is the focus of this work. In Saccharomyces cerevisiae, mutants defective in haspin kinase exhibit stably polarized landmarks and are sensitive to mitotic delays. Here, we report a new critical role for haspin in polarisome dispersion; failure to redistribute polarity factors, in turn, leads to nuclear segregation defects and cell lethality. We identified a mitotic role for GTP-Ras in regulating the local activation of the Cdc42 GTPase, resulting in its dispersal from the bud tip to a homogeneous distribution over the plasma membrane. GTP-Ras2 physically interacts with Cdc24 regulateing its mitotic distribution. Haspin is shown to promote a mitotic shift from a bud tip-favored to a homogenous PM fusion of Ras-containing vesicles. In absence of haspin, active Ras is not redistributed from the bud tip; Cdc24 remains hyperpolarized promoting the activity of Cdc42 at the bud tip, and the polarisome fails to disperse leading to erroneously positioned mitotic spindle, defective nuclear segregation, and cell death after mitotic delays. These findings describe new functions for key factors that modulate cell polarization and mitotic events, critical processes involved in development and tumorigenesis

Generation of three iPSC lines from fibroblasts of a patient with Aicardi Goutières Syndrome mutated in TREX1

Fibroblasts from a patient with Aicardi Gouti\ue8res Syndrome (AGS) carrying a compound heterozygous mutation in TREX1, were reprogrammed into induced pluripotent stem cells (iPSCs) to establish isogenic clonal stem cell lines: UNIBSi006-A, UNIBSi006-B, and UNIBSi006-C. Cells were transduced using the episomal Sendai viral vectors, containing human OCT4, SOX2, c-MYC and KLF4 transcription factors. The transgene-free iPSC lines showed normal karyotype, expressed pluripotent markers and displayed in vitro differentiation potential toward cells of the three embryonic germ layers

Left ventricular (LV) pacing in newborns and infants. Echo assessment of LV systolic function and synchrony at 5-year follow-up

Background: Small retrospective studies reported that left ventricular (LV) pacing is likely to preserve LV function in children with isolated congenital complete atrioventricular block (CCAVB). The aim of this study was to prospectively evaluate LV contractility and synchrony in a cohort of neonates/infants at pacemaker implantation and follow-up. Methods: Patients with CCAVB who underwent LV pacing were evaluated with electrocardiogram and echocardiogram in a single-center, prospective study. Data were collected at implantation, at 1-month and every year of follow-up, up to 5 years. LV ventricular dimensions (diameters and volumes), systolic function (ejection fraction [EF] and global longitudinal strain [GLS]), and synchrony were evaluated. Data are reported as median (25th-75th centiles). Results: Twenty consecutive patients with CCAVB underwent pacemaker implantation (12 single-chamber pacemaker [VVIR] and eight dual-chamber pacemaker [DDD]) with epicardial leads: 17 on the LV apex and three on the free wall. Age at implantation was 0.3 months (1 day-4.5 months). Patients showed good clinical status, normal LV dimensions, preserved systolic function, and synchrony at 60 (30-60) months follow-up. EF increased to normal values in patients with preimplantation EF <50%. Presence of antibodies and pacing mode (DDD vs VVIR) had no impact on the outcome. Conclusions: LV pacing preserved LV systolic function and synchrony in neonates and infants with CCAVB at 5-year follow-up. LV EF improved in patients with low preimplantation EF. Pacing mode or the presence of autoantibodies did not demonstrated an impact on LV contractility and synchrony