Search

[This corrects the article DOI: 10.1371/journal.pone.0239224.].

Does knowing when mental arithmetic judgments are right--and when they are wrong--lead to more accurate judgments over time? We hypothesize that the successful detection of errors (and avoidance of false alarms) may contribute to the development of mental arithmetic performance. Insight into error detection abilities can be gained by examining the "calibration" of mental arithmetic judgments-that is, the alignment between confidence in judgments and the accuracy of those judgments. Calibration may be viewed as a measure of metacognitive monitoring ability. We conducted a developmental longitudinal investigation of the relationship between the calibration of children's mental arithmetic judgments and their performance on a mental arithmetic task. Annually between Grades 5 and 8, children completed a problem verification task in which they rapidly judged the accuracy of arithmetic expressions (e.g., 25 + 50 = 75) and rated their confidence in each judgment. Results showed that calibration was strongly related to concurrent mental arithmetic performance, that calibration continued to develop even as mental arithmetic accuracy approached ceiling, that poor calibration distinguished children with mathematics learning disability from both low and typically achieving children, and that better calibration in Grade 5 predicted larger gains in mental arithmetic accuracy between Grades 5 and 8. We propose that good calibration supports the implementation of cognitive control, leading to long-term improvement in mental arithmetic accuracy. Because mental arithmetic "fluency" is critical for higher-level mathematics competence, calibration of confidence in mental arithmetic judgments may represent a novel and important developmental predictor of future mathematics performance.

A growing body of evidence links the analysis of the KIR genotype and the presence of their HLA-B and -C ligands to a wide repertoire of human diseases. We noticed that, using a panel of 184 Caucasoid donors, a limited number of HLA alleles were incorrectly supratyped by previously described pyrosequence-based assays. Here we describe a simple implementation of the reported methods that corrects all the discrepancies found with HLA-B and -C molecular typing and allows establishing a quick and high-throughput method for the determination of HLA-Bw4 I 80 , Bw4T 80 , Bw6 and HLA-C1 or -C2 supratype. [ABSTRACT FROM AUTHOR]

The Approximate Number System (ANS) is a primitive mental system of nonverbal representations that supports an intuitive sense of number in human adults, children, infants, and other animal species. The numerical approximations produced by the ANS are characteristically imprecise and, in humans, this precision gradually improves from infancy to adulthood. Throughout development, wide ranging individual differences in ANS precision are evident within age groups. These individual differences have been linked to formal mathematics outcomes, based on concurrent, retrospective, or short-term longitudinal correlations observed during the school age years. However, it remains unknown whether this approximate number sense actually serves as a foundation for these school mathematics abilities. Here we show that ANS precision measured at preschool, prior to formal instruction in mathematics, selectively predicts performance on school mathematics at 6 years of age. In contrast, ANS precision does not predict non-numerical cognitive abilities. To our knowledge, these results provide the first evidence for early ANS precision, measured before the onset of formal education, predicting later mathematical abilities.

Cystic fibrosis is a multisystem disease with extremely variable onset, symptoms and course. One of the onset modality but also a complication of the disease is the pseudo-Bartter syndrome, characterized by hyponatremia, hypochloremic dehydration and metabolic alkalosis in absence of any renal disease. This syndrome occurs more frequently in the first year of life and has a peak in the summer. In this article, we describe two cases of cystic fibrosis associated with pseudo-Bartter syndrome in childhood. Excluding every possible cause of metabolic alkalosis associated with hyponatremia was crucial for our diagnostic pathway, and the experience gained with the first case helped a lot with the second one., (Copyright by Società Italiana di Nefrologia SIN, Rome,Italy.)

Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended genome-wide association meta-analysis of a well-characterized cohort of 3255 COVID-19 patients with respiratory failure and 12 488 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.31 to a ~0.9-Mb inversion polymorphism that creates two highly differentiated haplotypes and characterized the potential effects of the inversion in detail. Our data, together with the 5th release of summary statistics from the COVID-19 Host Genetics Initiative including non-Caucasian individuals, also identified a new locus at 19q13.33, including NAPSA, a gene which is expressed primarily in alveolar cells responsible for gas exchange in the lung., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The dynamics of a nuclear open quantum system could be revealed in the correlations between the breakup fragments of halo nuclei. The breakup mechanism of a proton halo nuclear system is of particular interest as the Coulomb polarization may play an important role, which, however, remains an open question. Here we use a highly efficient silicon detector array and measure the correlations between the breakup fragments of 8 B incident on 120 Sn at near-barrier energies. The energy and angular correlations can be explained by a fully quantum mechanical method based on the state-of-the-art continuum discretized coupled channel calculations. The results indicate that, compared to the neutron halo nucleus 6 He, 8 B presents distinctive reaction dynamics: the dominance of the elastic breakup. This breakup occurs mainly via the short-lived continuum states, almost exhausts the 7 Be yield, indicating the effect of Coulomb polarization on the proton halo state. The correlation information reveals that the prompt breakup mechanism dominates, occurring predominantly on the outgoing trajectory. We also show that, as a large environment, the continuum of 8 B breakup may not significantly influence elastic scattering and complete fusion., (© 2022. The Author(s).)

Surface expression of human leukocyte antigen (HLA)-class I molecules is critical for modulating T/natural killer lymphocytes' effector functions. Among HLA molecules, HLA-C, the most recently evolved form of class I antigens, is subjected to both transcriptional and multiple post-transcriptional regulation mechanisms affecting its cell surface expression. Among the latter a region placed in the 3' untranslated region of HLA-C transcript contains the single nucleotide polymorphism (SNP) rs67384697 "G-ins/del" that has been found to be strictly associated with surface levels of HLA-C allomorphs because of the effect on the binding site of a microRNA (Hsa-miR-148a). Higher expression of HLA-C has been proved to influence HIV-1 infection via a better control of viremia and a slower disease progression. More importantly, the analysis of SNP rs67384697 "G-ins/del" combined with the evaluation of the HLA-Bw4/-Bw6 C1/C2 supratype, as well as the killer immunoglobulin-like receptor genetic asset, has proved to be pivotal in defining the status of Elite Controllers in the Caucasian population. Here we describe a new reliable and fast method of allele-specific real-time PCR to monitor the integrity/disruption of the binding site of the microRNA Hsa-miR-148a in a high-throughput format that can be easily applied to studies involving large cohorts of individuals., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: B cell receptor Immunoglobulin (BcR IG) repertoire of Chronic Lymphocytic Leukemia (CLL) is characterized by the expression of quasi-identical BcR IG. These are observed in approximately 30% of patients, defined as stereotyped receptors and subdivided into subsets based on specific VH CDR3 aa motifs and phylogenetically related IGHV genes. Although relevant to CLL ontogeny, the distribution of CLL-biased stereotyped immunoglobulin rearrangements (CBS-IG) in normal B cells has not been so far specifically addressed using modern sequencing technologies. Here, we have investigated the presence of CBS-IG in splenic B cell subpopulations (s-BCS) and in CD5 + and CD5 - B cells from the spleen and peripheral blood (PB)., Methods: Fractionation of splenic B cells into 9 different B cell subsets and that of spleen and PB into CD5 + and CD5 - cells were carried out by FACS sorting. cDNA sequences of BcR IG gene rearrangements were obtained by NGS. Identification of amino acidic motifs typical of CLL stereotyped subsets was carried out on IGHV1-carrying gene sequences and statistical evaluation has been subsequently performed to assess stereotypes distribution., Results: CBS-IG represented the 0.26% average of IGHV1 genes expressing sequences, were detected in all of the BCS investigated. CBS-IG were more abundant in splenic and circulating CD5 + B (0.57%) cells compared to CD5 - B cells (0.17%). In all instances, most CBS IG did not exhibit somatic hypermutation similar to CLL stereotyped receptors. However, compared to CLL, they exhibited a different CLL subset distribution and a broader utilization of the genes of the IGHV1 family., Conclusions: CBS-IG receptors appear to represent a part of the "public" BcR repertoire in normal B cells. This repertoire is observed in all BCS excluding the hypothesis that CLL stereotyped BcR accumulate in a specific B cell subset, potentially capable of originating a leukemic clone. The different relative representation of CBS-IG in normal B cell subgroups suggests the requirement for additional selective processes before a full transformation into CLL is achieved.

The 'Immunogenetics of Aging' project is a component introduced in the 14th International HLA and Immunogenetics Workshop (IHIW) and developed further within subsequent workshops. The aim was to determine the relevance of immunogenetic markers, focusing on HLA, cytokine genes, and some innate immunity genes, for successful aging and an increased capacity to reach the extreme limits of life-span. Within the 17th IHIW we applied Next Generation Sequencing methods to refine further HLA associations at allele level in longevity, and to extend our knowledge to additional loci such as HLA-DQA1, HLA-DPB1 and HLA-DPA1. Analysis of relatively small number of healthy elderly and young controls from four populations showed that some HLA class I and class II alleles were significantly positively associated with healthy aging. Additionally we observed statistically significant differences in HLA allele distribution when the analysis was performed separately in elderly females and males compared to sex-matched young controls. Haplotypes, probably associated with better control of viral and malignant diseases were increased in the elderly sample. These preliminary NGS data could confirm our hypotheses that survival and longevity might be associated with selection of HLA alleles and haplotypes conferring disease resistance or susceptibility. Therefore HLA alleles and haplotypes could be informative immunogenetic markers for successful ageing., (Copyright © 2019 American Society for Histocompatibility and Immunogenetics. All rights reserved.)

Hepatocellular adenoma is a benign neoplasm that accounts for 2-4% of pediatric liver tumors. The inflammatory variant of the adenoma can be expressed at the clinical level only with the evidence of persistent elevation of the inflammatory indices, since the hepatic mass is itself silent unless there are complications. The main complications relate to the bleeding risk, the chronic inflammatory state and the low risk of malignant evolution. The predictive marker of hemorrhagic complication is the size and in particular if the diameter is greater than 5 cm surgical treatment is recommended. We describe the case of a 9-year-old girl with a hepatocellular adenoma in the telangiectatic inflammatory variant, with a clinical presentation of loss of appetite and high inflammatory indices.

The 17th International HLA and Immunogenetics Workshop (IHIW) organizers conducted a Pilot Study (PS) in which 13 laboratories (15 groups) participated to assess the performance of the various sequencing library preparation protocols, NGS platforms and software in use prior to the workshop. The organizers sent 50 cell lines to each of the 15 groups, scored the 15 independently generated sets of NGS HLA genotyping data, and generated "consensus" HLA genotypes for each of the 50 cell lines. Proficiency Testing (PT) was subsequently organized using four sets of 24 cell lines, selected from 48 of 50 PS cell lines, to validate the quality of NGS HLA typing data from the 34 participating IHIW laboratories. Completion of the PT program with a minimum score of 95% concordance at the HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 loci satisfied the requirements to submit NGS HLA typing data for the 17th IHIW projects. Together, these PS and PT efforts constituted the 17th IHIW Quality Control project. Overall PT concordance rates for HLA-A, HLA-B, HLA-C, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DRB1, HLA-DRB3, HLA-DRB4 and HLA-DRB5 were 98.1%, 97.0% and 98.1%, 99.0%, 98.6%, 98.8%, 97.6%, 96.0%, 99.1%, 90.0% and 91.7%, respectively. Across all loci, the majority of the discordance was due to allele dropout. The high cost of NGS HLA genotyping per experiment likely prevented the retyping of initially failed HLA loci. Despite the high HLA genotype concordance rates of the software, there remains room for improvement in the assembly of more accurate consensus DNA sequences by NGS HLA genotyping software., (Copyright © 2019 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Most active cancer immunotherapies able to induce a long-lasting protection against tumours are based on the activation of tumour-specific cytotoxic T lymphocytes (CTLs). Cell death by hyperthermia induces apoptosis followed by secondary necrosis, with the production of factors named "danger associated molecular pattern" (DAMP) molecules (DAMPs), that activate dendritic cells (DCs) to perform antigen uptake, processing and presentation, followed by CTLs cross priming. In many published studies, hyperthermia treatment of tumour cells is performed at 42-45 °C; these temperatures mainly promote cell surface expression of DAMPs. Treatment at 56 °C of tumour cells was shown to induce DAMPs secretion rather than their cell surface expression, improving DC activation and CTL cross priming in vitro. Thus we tested the relevance of this finding in vivo on the generation of a tumour-specific memory immune response, in the TRAMP-C2 mouse prostate carcinoma transplantable model. TRAMP-C2 tumour cells treated at 56 °C were able not only to activate DCs in vitro but also to trigger a tumour-specific CTL-dependent immune response in vivo. Prophylactic vaccination with 56 °C-treated TRAMP-C2 tumour cells alone provided protection against TRAMP-C2 tumour growth in vivo, whilst in the therapeutic regimen, control of tumour growth was achieved combining immunization with adjuvant chemotherapy., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

HLA-C*02:10:03 identified in a Venezuelan patient and characterized using next generation sequencing., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We discuss the most popular static and dynamic models of household behavior. Our main objective is to explain which aspects of household decisions different models can account for. Using this insight, we describe testable implications, identification results, and estimation findings obtained in the literature. Particular attention is given to the ability of different models to answer various types of policy questions.

Several studies described an association between killer-cell immunoglobulin-like receptor (KIR)/HLA gene combinations and clinical outcomes in various diseases. In particular, an important combined role for KIR3DS1 and HLA-B Bw4-I80 in controlling viral infections and a higher protection against leukemic relapses in donor equipped with activating KIRs in haplo-HSCT has been described. Here, we show that KIR3DS1 mediates positive signals upon recognition of HLA-B*51 (Bw4-I80) surface molecules on target cells and that this activation occurs only in Bw4-I80 neg individuals, including those carrying particular KIR/HLA combination settings. In addition, killing of HLA-B*51 transfected target cells mediated by KIR3DS1 + /NKG2A + natural killer (NK) cell clones from Bw4-I80 neg donors could be partially inhibited by antibody-mediated masking of KIR3DS1. Interestingly, KIR3DS1-mediated recognition of HLA-B*51 could be better appreciated under experimental conditions in which the function of NKG2D was reduced by mAb-mediated blocking. This experimental approach may mimic the compromised function of NKG2D occurring in certain viral infections. We also show that, in KIR3DS1 + /NKG2A + NK cell clones derived from an HLA-B Bw4-T80 donor carrying 2 KIR3DS1 gene copy numbers, the positive signal generated by the engagement of KIR3DS1 by HLA-B*51 resulted in a more efficient killing of HLA-B*51-transfected target cells. Moreover, in these clones, a direct correlation between KIR3DS1 and NKG2D surface density was detected, while the expression of NKp46 was inversely correlated with that of KIR3DS1. Finally, we analyzed KIR3DS1 + /NKG2A + NK cell clones from a HLA-B Bw4 neg donor carrying cytoplasmic KIR3DL1. Although these clones expressed lower levels of surface KIR3DS1, they displayed responses comparable to those of NK cell clones derived from HLA-B Bw4 neg donors that expressed surface KIR3DL1. Altogether these data suggest that, in particular KIR/HLA combinations, KIR3DS1 may play a role in the process of human NK cell education.

Gamma-ray spectroscopy measurements at MHz counting rates have been carried out, for the first time, with a compact spectrometer based on a LaBr 3 scintillator and silicon photomultipliers. The instrument, which is also insensitive to magnetic fields, has been developed in view of the upgrade of the gamma-ray camera diagnostic for α particle measurements in deuterium-tritium plasmas of the Joint European Torus. Spectra were measured up to 2.9 MHz with a projected energy resolution of 3%-4% in the 3-5 MeV range, of interest for fast ion physics studies in fusion plasmas. The results reported here pave the way to first time measurements of the confined α particle profile in high power plasmas of the next deuterium-tritium campaign at the Joint European Torus.

Objective: The prevalence of coeliac disease (CD) in Vietnam is unknown. To fill this void, we assessed the prevalence of serological markers of CD autoimmunity in a population of children in Hanoi., Setting: The outpatient blood drawing laboratory of the largest paediatric hospital in North Vietnam was used for the study, which was part of an international project of collaboration between Italy and Vietnam., Participants: Children having blood drawn for any reason were included. Exclusion criteria were age younger than 2 years, acquired or congenital immune deficiency and inadequate sample. A total of 1961 children (96%) were enrolled (838 females, 1123 males, median age 5.3 years)., Outcomes: Primary outcome was the prevalence of positive autoimmunity to both IgA antitransglutaminase antibodies (anti-tTG) assessed with an ELISA test and antiendomysial antibodies (EMA). Secondary outcome was the prevalence of CD predisposing human leucocyte antigens (HLA) (HLA DQ2/8) in the positive children and in a random group of samples negative for IgA anti-tTG., Results: The IgA anti-tTG test was positive in 21/1961 (1%; 95% CI 0.61% to 1.53%); however, EMA antibodies were negative in all. HLA DQ2/8 was present in 7/21 (33%; 95% CI 14.5% to 56.9%) of the anti-tTG-positive children and in 72/275 (26%; 95% CI 21% to 32%) of those who were negative., Conclusions: Coeliac autoimmunity is rare in Vietnam, although prevalence of HLA DQ2/8 is similar to that of other countries. We hypothesise that the scarce exposure to gluten could be responsible for these findings., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

A growing body of evidence links the analysis of the KIR genotype and the presence of their HLA-B and -C ligands to a wide repertoire of human diseases. We noticed that, using a panel of 184 Caucasoid donors, a limited number of HLA alleles were incorrectly supratyped by previously described pyrosequence-based assays. Here we describe a simple implementation of the reported methods that corrects all the discrepancies found with HLA-B and -C molecular typing and allows establishing a quick and high-throughput method for the determination of HLA-Bw4 I(80), Bw4T(80), Bw6 and HLA-C1 or -C2 supratype., (Copyright © 2015 Elsevier B.V. All rights reserved.)

In the Sp6 mouse plasmacytoma model, a whole-cell vaccination with Sp6 cells expressing de novo B7-1 (Sp6/B7) induced anatomically localized and cytotoxic T cell (CTL)-mediated protection against wild-type (WT) Sp6. Both WT Sp6 and Sp6/B7 showed down-regulated expression of MHC H-2 L(d). Increase of H-2 L(d) expression by cDNA transfection (Sp6/B7/L(d)) raised tumour immune protection and shifted most CTL responses towards H-2 L(d)-restricted antigenic epitopes. The tumour-protective responses were not specific for the H-2 L(d)-restricted immunodominant AH1 epitope of the gp70 common mouse tumour antigen, although WT Sp6 and transfectants were able to present it to specific T cells in vitro. Gp70 transcripts, absent in secondary lymphoid organs of naive mice, were detected in immunized mice as well as in splenocytes from naive mice incubated in vitro with supernatants of CTL-lysed Sp6 cell cultures, containing damage-associated molecular patterns (DAMPs). It has been shown that Toll-like receptor triggering induces gp70 expression. Damage-associated molecular patterns are released by CTL-mediated killing of Sp6/B7-Sp6/B7/L(d) cells migrated to draining lymph nodes during immunization and may activate gp70 expression and presentation in most resident antigen-presenting cells. The same could also apply for Mus musculus endogenous ecotropic murine leukaemia virus 1 particles present in Sp6-cytosol, discharged by dying cells and superinfecting antigen-presenting cells. The outcome of such a massive gp70 cross-presentation would probably be tolerogenic for the high-affinity AH1-gp70-specific CTL clones. In this scenario, autologous whole-tumour-cell vaccines rescue tumour-specific immunoprotection by amplification of subdominant tumour antigen responses when those against the immune dominant antigens are lost., (© 2015 The Authors. Immunology Published by John Wiley & Sons Ltd.)

We report on experiments in which the Texas Petawatt laser irradiated a mixture of deuterium or deuterated methane clusters and helium-3 gas, generating three types of nuclear fusion reactions: D(d,^{3}He)n, D(d,t)p, and ^{3}He(d,p)^{4}He. We measured the yields of fusion neutrons and protons from these reactions and found them to agree with yields based on a simple cylindrical plasma model using known cross sections and measured plasma parameters. Within our measurement errors, the fusion products were isotropically distributed. Plasma temperatures, important for the cross sections, were determined by two independent methods: (1) deuterium ion time of flight and (2) utilizing the ratio of neutron yield to proton yield from D(d,^{3}He)n and ^{3}He(d,p)^{4}He reactions, respectively. This experiment produced the highest ion temperature ever achieved with laser-irradiated deuterium clusters.

The plasma astrophysical S factor for the 3He(d,p)4He fusion reaction was measured for the first time at temperatures of few keV, using the interaction of intense ultrafast laser pulses with molecular deuterium clusters mixed with 3He atoms. Different proportions of D2 and 3He or CD4 and 3He were mixed in the gas target in order to allow the measurement of the cross section for the 3He(d,p)4He reaction. The yield of 14.7 MeV protons from the 3He(d,p)4He reaction was measured in order to extract the astrophysical S factor at low energies. Our result is in agreement with other S factor parametrizations found in the literature.

Two different methods have been employed to determine the plasma temperature in a laser-cluster fusion experiment on the Texas Petawatt laser. In the first, the temperature was derived from time-of-flight data of deuterium ions ejected from exploding D(2) or CD(4) clusters. In the second, the temperature was measured from the ratio of the rates of two different nuclear fusion reactions occurring in the plasma at the same time: D(d,(3)He)n and (3)He(d,p)(4)He. The temperatures determined by these two methods agree well, which indicates that (i) the ion energy distribution is not significantly distorted when ions travel in the disassembling plasma; (ii) the kinetic energy of deuterium ions, especially the "hottest part" responsible for nuclear fusion, is well described by a near-Maxwellian distribution.

We propose the use of the latent change and latent acceleration frameworks for modeling nonlinear growth in structural equation models. Moving to these frameworks allows for the direct identification of rates of change and acceleration in latent growth curves-information available indirectly through traditional growth curve models when change patterns are nonlinear with respect to time. To illustrate this approach, exponential growth models in the three frameworks are fit to longitudinal response time data from the Math Skills Development Project ( Mazzocco & Meyers, 2002 , 2003 ). We highlight the additional information gained from fitting growth curves in these frameworks as well as limitations and extensions of these approaches.

Quantum-mechanical shell effects are expected to strongly enhance nuclear binding on an "island of stability" of superheavy elements. The predicted center at proton number Z = 114, 120, or 126 and neutron number N = 184 has been substantiated by the recent synthesis of new elements up to Z = 118. However, the location of the center and the extension of the island of stability remain vague. High-precision mass spectrometry allows the direct measurement of nuclear binding energies and thus the determination of the strength of shell effects. Here, we present such measurements for nobelium and lawrencium isotopes, which also pin down the deformed shell gap at N = 152.

Embryo-fetal infections have been reported to cause recurrent spontaneous abortions (RSAs) at a rate lower than 4%. The possible mechanisms include production of toxic metabolic byproducts, fetal or placental infection, chronic endometrial infection, and chorio-amnionitis. Viruses appear to be the most frequently involved pathogens, since some of them can produce chronic or recurrent maternal infection. In particular, cytomegalovirus during pregnancy can reach the placenta by viremia, following both primary and recurrent infection, or by ascending route from the cervix, mostly following reactivation. Another herpesvirus, herpes simplex virus type 2, less frequently type 1, causes recurrent infections of the genital tract, which can involve the feto-placental unit. Parvoviruses have also been implicated in the development of repeated fetal loss. Among bacterial infections, Chlamydia trachomatis, Ureaplasma urealyticum,and Mycoplasma hominis have been mostly associated with occurrence of RSA. An increased risk of abortion among women with bacterial vaginosis (BV) during early pregnancy was also shown, but questions arise about the role of chronic BV in its occurrence. Although a definitive relationship between recurrently active infections and RSA is still lacking, mostly due to difficulties in demonstrating the pathogenic role of each individual isolated pathogen, diagnosis and therapy of RSA-related infections should be attempted. The diagnosis of infectious agents as a possible cause of RSA might lead to a therapeutic approach with antiviral drugs and antibiotics or using immunoglobulins, which can display both anti-infective neutralizing and immunomodulating properties.

Bone marrow mesenchymal stromal cells (BM-MSCs) may survive and proliferate in the presence of cycling neoplastic cells. Exogenously administered MSCs are actively incorporated in the tumor as stromal fibroblasts, thus competing with the local mesenchymal cell precursors. For this reason, MSCs have been suggested as a suitable carrier for gene therapy strategies, as they can be genetically engineered with genes encoding for biologically active molecules that can inhibit tumor cell proliferation and enhance the antitumor immune response. We used BM-MSCs engineered with the murine interferon-alpha (IFN-α) gene (BM-MSCs/IFN-α) to assess in a mouse plasmacytoma model the efficacy of this approach toward neoplastic plasma cells. We found that IFN-α can be efficiently produced and delivered inside the tumor microenvironment. Subcutaneous multiple administration of BM-MSCs/IFN-α significantly hampered the tumor growth in vivo and prolonged the overall survival of mice. The antitumor effect was associated with enhanced apoptosis of tumor cells, reduction in microvessel density, and ischemic necrosis. By contrast, intravenous administration of BM-MSCs/IFN-α did not significantly modify the survival of mice, mainly as a consequence of an excessive entrapment of injected cells in the pulmonary vessels. In conclusion, BM-MSCs/IFN-α are effective in inhibiting neoplastic plasma cell growth; however, systemic administration of engineered MSCs needs to be improved to make this approach potentially suitable for the treatment of multiple myeloma.

The masses of ten proton-rich nuclides, including the N=Z+1 nuclides ⁸⁵Mo and ⁸⁷Tc, were measured with the Penning trap mass spectrometer SHIPTRAP. Compared to the Atomic Mass Evaluation 2003 a systematic shift of the mass surface by up to 1.6 MeV is observed causing significant abundance changes of the ashes of astrophysical x-ray bursts. Surprisingly low α separation energies for neutron-deficient Mo and Tc are found, making the formation of a ZrNb cycle in the rp process possible. Such a cycle would impose an upper temperature limit for the synthesis of elements beyond Nb in the rp process.

De novo expression of B7-1 impaired tumorigenicity of TRAMP-C2 mouse prostate adenocarcinoma (TRAMP-C2/B7), but it did not elicit a protective response against TRAMP-C2 parental tumor, unless after in vitro treatment with IFN-gamma. TRAMP-C2 cells secrete TGF-beta and show low MHC-I expression. Treatment with IFN-gamma increased MHC-I expression by induction of some APM components and antagonizing the immunosuppressant activity of TGF-beta. Thus, immunization with TRAMP-C2/B7 conferred protection against TRAMP-C2-derived tumors in function of the IFN-gamma-mediated fine-tuned modulation of either APM expression or TGF-beta signaling. To explore possible clinical translation, we delivered IFN-gamma to TRAMP-C2 tumor site by means of genetically engineered MSCs secreting IFN-gamma., ((c) 2010 Elsevier Ltd. All rights reserved.)

The mass of an atom incorporates all its constituents and their interactions. The difference between the mass of an atom and the sum of its building blocks (the binding energy) is a manifestation of Einstein's famous relation E = mc(2). The binding energy determines the energy available for nuclear reactions and decays (and thus the creation of elements by stellar nucleosynthesis), and holds the key to the fundamental question of how heavy the elements can be. Superheavy elements have been observed in challenging production experiments, but our present knowledge of the binding energy of these nuclides is based only on the detection of their decay products. The reconstruction from extended decay chains introduces uncertainties that render the interpretation difficult. Here we report direct mass measurements of trans-uranium nuclides. Located at the farthest tip of the actinide species on the proton number-neutron number diagram, these nuclides represent the gateway to the predicted island of stability. In particular, we have determined the mass values of (252-254)No (atomic number 102) with the Penning trap mass spectrometer SHIPTRAP. The uncertainties are of the order of 10 keV/c(2) (representing a relative precision of 0.05 p.p.m.), despite minute production rates of less than one atom per second. Our experiments advance direct mass measurements by ten atomic numbers with no loss in accuracy, and provide reliable anchor points en route to the island of stability.

We report on the first measurement of the beta+ and orbital electron-capture decay rates of 140Pr nuclei with the simplest electron configurations: bare nuclei, hydrogenlike, and heliumlike ions. The measured electron-capture decay constant of hydrogenlike 140Pr58+ ions is about 50% larger than that of heliumlike 140Pr57+ ions. Moreover, 140Pr ions with one bound electron decay faster than neutral 140Pr0+ atoms with 59 electrons. To explain this peculiar observation one has to take into account the conservation of the total angular momentum, since only particular spin orientations of the nucleus and of the captured electron can contribute to the allowed decay.

Background: Serological testing for primary maternal cytomegalovirus (CMV) infection during pregnancy is not routine, but ultrasound studies are routine. Therefore, we evaluated placental thickening in women with primary CMV infection during pregnancy., Methods: The study included 92 women with primary CMV infection during pregnancy and 73 CMV-seropositive pregnant women without primary CMV infection. Neonatal CMV transmission was determined by CMV culture of urine samples. Thirty-two women were treated with CMV hyperimmune globulin to either prevent or treat intrauterine CMV infection. Maximal placental thickness was measured by longitudinal (nonoblique) scanning with the ultrasound beam perpendicular to the chorial dish. Programmed placental ultrasound evaluations were performed from 16 to 36 weeks of gestation., Results: At each measurement between 16 and 36 weeks of gestation, women with primary CMV infection who had a fetus or newborn with CMV disease had placentas that were significantly thicker than those of women with primary CMV infection who did not have a diseased fetus or newborn (P<.0001); the latter group, in turn, had placentas that were significantly thicker than those of seropositive control subjects (P<.0001). For both women with and women without diseased fetuses or newborns, receipt of hyperimmune globulin after primary CMV infection was associated with statistically significant reductions in placental thickness (P<.001). Placental vertical thickness values, which are predictive of primary maternal infection, were observed at each measurement from 16 to 36 weeks of gestation, and cutoff values ranged from 22 mm to 35 mm, with the best sensitivity and specificity at 28 and 32 weeks of gestation., Conclusions: Primary maternal CMV infection and fetal or neonatal disease are associated with sonographically thickened placentas, which respond to administration of hyperimmune globulin. These observations suggest that many of the manifestations of fetal and neonatal disease are caused by placental insufficiency.

We report the 1.6 Angstrom resolution crystal structure of SH3BGRL3, a member of a new mammalian protein family of unknown function. The observed "thioredoxin fold" of SH3BGRL3 matches the tertiary structure of glutaredoxins, even in the N-terminal region where the sequence similarity between the two protein families is negligible. In particular, SH3BGRL3 displays structural modifications at the N-terminal Cys-x-x-Cys loop, responsible for glutathione binding and catalysis in glutaredoxins. The loop hosts a six residue insertion, yielding an extra N-terminal-capped helical turn, first observed here for the thioredoxin fold. This, together with deletion of both Cys residues, results in a substantial reshaping of the neighboring cleft, where glutathione is hosted in glutaredoxins. While not active in redox reaction and glutathione binding, SH3BGRL3 may act as an endogenous modulator of glutaredoxin activities by competing, with its fully conserved thioredoxin fold, for binding to yet unknown target proteins.

We report on an infant with multi-system disease including liver fibrosis, right microphthalmia with cataract, interstitial pneumonitis, and hyperechoic lesions in the basal ganglia and in the periventricular and thalamic regions. Prenatal ascites with hepatomegaly concomitantly with detection of cytomegalovirus (CMV) DNA in the amniotic fluid, following recurrent maternal CMV infection, had been shown. Although CMV culture and DNA detection were negative in the urine, the infant was given foscarnet because CMV infection was demonstrated in the liver by DNA detection and immunohistochemical staining. Favorable clinical outcome and absence of CMV in the liver were subsequently shown. Our case suggests that congenital CMV disease following maternal recurrence may not be associated with disseminated infection but only with intracellular infection. The diagnosis should therefore be based on CMV detection in the involved organs. Moreover, this is the first report on the possible efficacy and safety of foscarnet for therapy of immunocompetent infants with congenital CMV disease.

Uterine anomalies implicated in female subfertility, implantation failure and miscarriages can often be detected often by two-dimensional transvaginal (2D TV) ultrasound scanning. When used as a screening test TV ultrasound has provided sensitivity rates of up to 100% about uterine anomalies. Improved depiction has been achieved with the development of hysterosalpingosonography (HSSG). The anechoic interface provided by the saline solution allows the examiner to determine whether an abnormality is intracavitary, endometrial, or submucosal. The aim of this study was to evaluate the role of 2D TV contrast sonography and 3D TV ultrasound in the diagnosis of congenital uterine anomalies in comparison with their appearance of hysterosalpingosonography findings.

Cytomegalovirus (CMV) is the leading infectious cause of prenatal neurological damage, which is particularly severe when primary maternal infection occurs during the first 16 weeks of gestation, at the time of organ development and neuronal migration. Vascular involvement has been suggested to be among the possible pathogenic mechanisms of virus-induced pathology, in addition to direct viral effects. We report on a fetus with cerebral CMV infection, which had intraventricular haemorrhage, together with oligohydramnios and hyperechogenic bowel, following maternal primary CMV infection., (Copyright 2002 John Wiley & Sons, Ltd.)

The SH3 binding glutamic acid-rich (SH3BGR) gene was cloned in an effort to identify genes located to human chromosome 21, within the congenital heart disease region, and expressed in the developing heart. After the identification of SH3BGR, two human homologous genes, SH3BGRL and SH3BGRL3, were identified and mapped to chromosome Xq13.3 and 1p34.3-35, respectively. SH3BGRL and SH3BGRL3 code for small proteins similar to the N-terminal region of the SH3BGR protein. SH3BGRL3 protein shows a significant similarity to Glutaredoxin 1 of Escherichia coli, and all the three proteins are predicted to belong to Thioredoxin-like protein Superfamily. Here we describe the identification and characterization of an additional human homologue of SH3BGR, named SH3BGRL2. The SH3BGRL2 gene maps to chromosome 6q13-15 and its messenger RNA has a large 3' untranslated region containing several AUUUA repeats. SH3BGRL2 codes for a protein of 107 amino acids, which, like SH3BGRL and SH3BGRL3 proteins, is highly homologous to the N-terminal region of the SH3BGR protein and appears to be related to Glutaredoxins and to PKC-interacting cousin of thioredoxin homology domain. We propose that the identification of SH3BGRL2 establishes a novel family of human genes, coding for highly conserved small proteins belonging to Thioredoxin-like protein Superfamily.

Glutaredoxins (GRXs) are ubiquitous GSH-dependent oxidoreductases, which catalyze the reduction of protein-glutathionyl-mixed disulfides and are considered to play an important role in the enzymatic regulation of redox-sensitive proteins. In this paper, we describe the identification and characterization of a new human homologue of the SH3BGR gene, named SH3BGRL3 (SH3 domain binding glutamic acid-rich protein like 3). SH3BGRL3 is widely expressed and codes for a highly conserved small protein, which shows a significant similarity to Glutaredoxin 1 (GRX1) of Escherichia coli and is predicted to belong to the Thioredoxin Superfamily. However, the SH3BGRL3 protein lacks both the conserved cysteine residues, which characterize the enzymatic active site of GRX. This structural feature raises the possibility that SH3BGRL3 could function as an endogenous modulator of GRX biological activity. EGFP-SH3BGRL3 fusion protein expressed in COS-7 cells localizes both to the nucleus and to the cytoplasm. The SH3BGRL3 gene was mapped to chromosome 1p34.3-35., (Copyright 2001 Academic Press.)