Anak seni pertama dilantik Senator

KUALA LUMPUR 1 Mac Seniman Negara, Allahyarham Tan Sri. Dr. Jins Shamsuddin yang menghembuskan nafas terakhir pada pukul 5.45 petang hari ini merupakan anak seni pertama dalam negara yang dilantik sebagai Senator di Dewan Negara selama dua penggal

Y-nvestigation: applicazione per analisi geografica della variabilità del cromosoma Y

In questi ultimi anni è stato ampiamente dimostrato e riportato dalla letteratura scientifica che, per scopi medico-legali e antropologici, vi è molto spesso la necessità di utilizzare banche dati di DNA mitocondriale e del NRY(regione non ricombinante sul cromosoma Y) in grado di combinare le informazioni sul genoma con informazioni geografiche. La somma di queste due informazioni consente di individuare le regioni nel mondo dove la frequenza di marcatori, o combinazioni di marcatori identici a quelli cercati (ad esempio in una traccia biologica qualsiasi) è più alta, ovvero di attribuire una o più regioni più probabili come origini del soggetto o della traccia. In particolare i marcatori del cromosoma Y ereditati nella linea paterna consentono la ricostruzione della storia naturale sulla base delle mutazioni via via acquisite. (permettendo di ipotizzare anche il tracciato territoriale o geografico del cammino percorso dai nostri avi) L'identificazione di sotto-aplogruppi (che fanno riferimento alla variazione della regione non ricombinante del cromosoma Y), la definizione della loro distribuzione geografica e la quantificazione della loro variazione interna, possono dare importanti informazioni sui processi migratori antichi e recenti e su eventi demografici che, avendo lasciato tracce nella struttura genetica delle popolazioni moderne, ce ne raccontano la storia. L'applicazione web sviluppata, chiamata Y-nvestigation, permette, tramite la costruzione di apposite banche dati, di raccogliere informazioni di tipo biologico su tale cromosoma, combinare tali informazioni sul genoma con i relativi dati geografici, esplorare quindi la variazione genetica e la distribuzione geografica dei tipi di cromosomi Y tramite la visualizzazione di mappe principalmente dello spazio eurasiatico

Y-nvestigation: applicazione per analisi geografica della variabilità del cromosoma Y

In questi ultimi anni è stato ampiamente dimostrato e riportato dalla letteratura scientifica che, per scopi medico-legali e antropologici, vi è molto spesso la necessità di utilizzare banche dati di DNA mitocondriale e del NRY(regione non ricombinante sul cromosoma Y) in grado di combinare le informazioni sul genoma con informazioni geografiche. La somma di queste due informazioni consente di individuare le regioni nel mondo dove la frequenza di marcatori, o combinazioni di marcatori identici a quelli cercati (ad esempio in una traccia biologica qualsiasi) è più alta, ovvero di attribuire una o più regioni più probabili come origini del soggetto o della traccia. In particolare i marcatori del cromosoma Y ereditati con la linea paterna consentono la ricostruzione della storia naturale sulla base delle mutazioni via via acquisite. L'identificazione di sotto-aplogruppi (che fanno riferimento alla variazione della regione non ricombinante del cromosoma Y), la definizione della loro distribuzione geografica e la quantificazione della loro variazione interna, possono dare importanti informazioni sui processi migratori antichi e recenti e su eventi demografici che, avendo lasciato tracce nella struttura genetica delle popolazioni moderne, ce ne raccontano la storia. L'applicazione web sviluppata, chiamata Y-nvestigation, permette, tramite la costruzione di apposite banche dati, di raccogliere informazioni di tipo biologico su tale cromosoma, combinare tali informazioni sul genoma con i relativi dati geografici, esplorare quindi la variazione genetica e la distribuzione geografica dei tipi di cromosomi Y tramite la visualizzazione di mappe principalmente dello spazio eurasiatico

Agammaglobulinemia associated to nasal polyposis due to a hypomorphic RAG1 mutation in a 12 years old boy

Recombination-activating gene (RAG) 1 and 2 mutations in humans cause T(-) B(-) NK(+) SCID and Omenn syndrome, but milder phenotypes associated with residual protein activity have been recently described. We report a male patient with a diagnosis of common variable immunodeficiency (CVID) born from non-consanguineous parents, whose immunological phenotype was characterized by severe reduction of B cells and agammaglobulinemia for which several candidate genes were excluded by targeted Sanger sequencing. Next Generation Sequencing revealed two compound heterozygous mutations in the RAG1 gene: the previously described p.R624H, and the novel p.Y728H mutation, as well as the known polymorphism p.H249R. This case reinforces the notion of large phenotypic spectrum in RAG deficiency and opens questions on the management and follow-up of these patients

Human Immunodeficiency Virus (HIV)-Antibody Repertoire Estimates Reservoir Size and Time of Antiretroviral Therapy Initiation in Virally Suppressed Perinatally HIV-Infected Children

Abstract Background: Assays to estimate human immunodeficiency virus (HIV) reservoir size require large amounts of blood, which represents a drawback especially in pediatric settings. We investigated whether HIV-antibody repertoire could estimate the viral reservoir size. Moreover, we assessed the magnitude of HIV-antibody response as a predictor of time of antiretroviral therapy (ART) initiation. Methods: Human immunodeficiency virus-antibody responses to 10 different viral proteins were evaluated by HIV Western blot (WB) kit and a WB score was assigned to each patient. Patients were classified in 2 subgroups based on the timing of ART initiation (early treated [ET], 0-24 weeks and late treated [LT], >24 weeks). Human immunodeficiency virus-deoxyribonucleic acid (DNA) was quantified using real-time quantitative polymerase chain reaction on total peripheral blood mononuclear cells. Logistic regression and principal component analysis were built on these data to test the ability of WB score to predict the expected value of HIV-DNA and the timing of ART initiation. Results: Sixty-nine perinatally HIV-infected children were evaluated. Reduced HIV-specific antibody responses and lower size of HIV-DNA were observed in ET compared with LT patients (P < .001 and P = .02, respectively). We found that WB score correlates with HIV-DNA (P = .032) and timing of ART initiation (P < .001). Based on the logistic regression analysis, we found that WB score can predict the HIV-DNA size and the timing of ART initiation with an Akaike information criterion of -118.13 and -151.51, respectively. Conclusions: Western blot score can estimate HIV-DNA size and timing of ART initiation in long-term virally suppressed children. This rapid, inexpensive, and easily reproducible tool can provide useful information to identify potential candidates for HIV remission studies

First Case of Patient With Two Homozygous Mutations in MYD88 and CARD9 Genes Presenting With Pyogenic Bacterial Infections, Elevated IgE, and Persistent EBV Viremia

We described for the first time a female patient with the simultaneous presence of two homozygous mutations in MYD88 and CARD9 genes presenting with pyogenic bacterial infections, elevated IgE, and persistent EBV viremia. In addition to defective TLR/IL1R-signaling, we described novel functional alterations into the myeloid compartment. In particular, we demonstrated a defective production of reactive oxygen species exclusively in monocytes upon E. coli stimulation, the inability of immature mono-derived DCs (iDCs) to differentiate into mature DCs (mDCs) and the incapacity of mono-derived macrophages (MDMs) to resolve BCG infection in vitro. Our data do not provide any evidence for digenic inheritance in our patient, but rather for the association of two monogenic disorders. This case illustrates the importance of using next generation sequencing (NGS) to determine the most accurate and early diagnosis in atypical clinical and immunological phenotypes, and with particular concern in consanguineous families. Indeed, besides the increased susceptibility to recurrent invasive pyogenic bacterial infections due to MYD88 deficiency, the identification of CARD9 mutations underline the risk of developing invasive fungal infections emphasizing the careful monitoring for the occurrence of fungal infection and the opportunity of long-term antifungal prophylaxis. Highlights - Patient with atypical primary immunodeficiency - Clinical manifestations: pyogenic bacterial infections, high IgE level, and persistent EBV viremia - Next-generation sequencing reveals two homozygous mutations in MYD88 and CARD9 genes leading to complete absence of proteins - Monocytes/macrophages function and DC differentiation were severely compromised - NGS has a key role to determine the correct diagnosis in atypical primary immunodeficiency leading to reconsider the individualized treatment

First Case of Patient With Two Homozygous Mutations in MYD88 and CARD9 Genes Presenting With Pyogenic Bacterial Infections, Elevated IgE, and Persistent EBV Viremia

We described for the first time a female patient with the simultaneous presence of two homozygous mutations in MYD88 and CARD9 genes presenting with pyogenic bacterial infections, elevated IgE, and persistent EBV viremia. In addition to defective TLR/IL1R-signaling, we described novel functional alterations into the myeloid compartment. In particular, we demonstrated a defective production of reactive oxygen species exclusively in monocytes upon E. coli stimulation, the inability of immature mono-derived DCs (iDCs) to differentiate into mature DCs (mDCs) and the incapacity of mono-derived macrophages (MDMs) to resolve BCG infection in vitro. Our data do not provide any evidence for digenic inheritance in our patient, but rather for the association of two monogenic disorders. This case illustrates the importance of using next generation sequencing (NGS) to determine the most accurate and early diagnosis in atypical clinical and immunological phenotypes, and with particular concern in consanguineous families. Indeed, besides the increased susceptibility to recurrent invasive pyogenic bacterial infections due to MYD88 deficiency, the identification of CARD9 mutations underline the risk of developing invasive fungal infections emphasizing the careful monitoring for the occurrence of fungal infection and the opportunity of long-term antifungal prophylaxis