PIB is a non-specific imaging marker of amyloid-beta (Aβ) peptide-related cerebral amyloidosis

The in vivo imaging probe [11C]-PIB (Pittsburgh Compound B, N-methyl[11C]2-(4′-methylaminophenyl-6-hydroxybenzathiazole) is under evaluation as a key imaging tool in Alzheimer's disease (AD) and to date has been assumed to bind with high affinity and specificity to the amyloid structures associated with classical plaques (CPs), one of the pathological hallmarks of the disease. However, no studies have systematically investigated PIB binding to human neuropathological brain specimens at the tracer concentrations achieved during in vivo imaging scans. Using a combination of autoradiography and histochemical techniques, we demonstrate that PIB, in addition to binding CPs clearly delineates diffuse plaques and cerebrovascular amyloid angiopathy (CAA). The interaction of PIB with CAA was not fully displaceable and this may be linked to the apolipoprotein E-ε4 allele. PIB was also found to label neurofibrillary tangles, although the overall intensity of this binding was markedly lower than that associated with the amyloid-beta (Aβ) pathology. The data provide a molecular explanation for PIB's limited specificity in diagnosing and monitoring disease progression in AD and instead indicate that the ligand is primarily a non-specific marker of Aβ-peptide related cerebral amyloidosi

Crystal structures of the Gon7/Pcc1 and Bud32/Cgi121 complexes provide a model for the complete yeast KEOPS complex.

International audienceThe yeast KEOPS protein complex comprising Kae1, Bud32, Cgi121, Pcc1 and Gon7 is responsible for the essential tRNA threonylcarbamoyladenosine (t(6)A) modification. Deletion of genes coding for the KEOPS subunits also affects telomere elongation and transcriptional regulation. In the present work, the crystal structure of Bud32/Cgi121 in complex with ADP revealed that ADP is bound in the catalytic site of Bud32 in a canonical manner characteristic of Protein Kinase A (PKA) family proteins. We found that Gon7 forms a stable heterodimer with Pcc1 and report the crystal structure of the Pcc1-Gon7 heterodimer. Gon7 interacts with the same Pcc1 region engaged in the archaeal Pcc1 homodimer. We further show that yeast KEOPS, unlike its archaeal counterpart, exists as a heteropentamer in which Gon7, Pcc1, Kae1, Bud32 and Cgi121 also adopt a linear arrangement. We constructed a model of yeast KEOPS that provides structural insight into the role of Gon7. The model also revealed the presence of a highly positively charged crater surrounding the entrance of Kae1 that likely binds tRNA

Laparoscopic removal of mullerian duct remnants in boys

Abstract: Purpose: Mullerian duct remnants (MDRs) are present in a male pseudohermaphroditic form characterized by failure of the mullerian duct to regress due to insufficient production or peripheral action of mullerian inhibiting substance. The MDR can be asymptomatic but it often results in infections, stones and voiding troubles. Furthermore, it may develop into a neoplasm. Therefore, surgery is mandatory for large MDRs and symptomatic patients. Laparoscopic removal is described. Materials and Methods: Six males were treated from February 1998 to February 2003. Age at surgery was between 3 and 18 years (mean 8.6). All patients showed severe hypospadias and 2 had mixed gonadal dysgenesis with ambiguous genitalia. Three patients presented with urogenital infections and all had a large MDR. Laparoscopic procedures, which were preceded by cystoscopy, were performed using a 10 mm umbilical trocar for the camera and 3, 5 mm trocars for instruments placed in the suprapubic region and iliac fossa bilaterally. The remnants were ligated with endoscopic loops or an endoscopic GIA stapler and cut. Results: Mean operative time was 2 hours. We noted no complications. In 2 cases there was deferential ectopia and in another of mixed gonadal dysgenesis bilateral gonadectomy was performed because of the risk of degeneration. Feeding started on postoperative day I and the patients were discharged home on day 5. After a followup of 8 months to 4 years all boys were healthy. Conclusions: Multiple approaches are used in traditional surgery, often leading to complications. Laparoscopy improves the view, decreases surgical risk and operative time, avoids large scars and allows more rapid hospital discharge

Peran Pemerintah Desa dan Manajemen Penyelenggaraan PAUD Berkualitas di Kecamatan Kroya Indramayu

Pemerintah memiliki peran yang besar dalam memajukan pendidikan bagi masyarakatnya, pemerintah desa menjadi penyambung penyalur dana dari pemerintah pusat maka dari itu mempunyai peranan penting untuk menyelenggarakan PAUD di desa masing-masing. Dukungan yang diberikan dapat berupa tanah, bangunan dan tunjangan bagi pendidik serta tendik. Satuan PAUD di kecamatan Kroya sudah menyelenggarakan PAUD  berkualitas bagi peserta didiknya melalui kegiatan yang dibuat oleh masing-masing Lembaga dan disesuaikan dengan karakteristik orangtua. Tujuan dari penelitian untuk mengetahui peran pemerintah desa dan gambaran PAUD berkualitas di Kecamatan Kroya. Jenis Penelitiannya kualitatif, subyek penelitian kepala sekolah, pendidik serta orangtua. Teknik Pengumpulan data wawancara, observasi dan dokumentasi. Teknik analisis data menggunakan Teknik analisis deskriptif kualitatif dengan cara menganalisis data yang didapat kemudian diolah dan disajikan dengan narasi. Temuan penelitian ini adalah masing-masing satuan PAUD mendapat dukungan dari pemerintah desa setempat dan memiliki kegiatan yang berbeda untuk bertransformasi menjadi PAUD berkualitas

Fighting viral infections and virus-driven tumors with cytotoxic CD4+ T cells

CD4+ T cells have been and are still largely regarded as the orchestrators of immune responses, being able to differentiate into distinct T helper cell populations based on differentiation signals, transcription factor expression, cytokine secretion, and specific functions. Nonetheless, a growing body of evidence indicates that CD4+ T cells can also exert a direct effector activity, which depends on intrinsic cytotoxic properties acquired and carried out along with the evolution of several pathogenic infections. The relevant role of CD4+ T cell lytic features in the control of such infectious conditions also leads to their exploitation as a new immunotherapeutic approach. This review aims at summarizing currently available data about functional and therapeutic relevance of cytotoxic CD4+ T cells in the context of viral infections and virus-driven tumors

Multifunctional cytomegalovirus (CMV)-specific CD8(+) T cells are not restricted by telomere-related senescence in young or old adults

"This is the peer reviewed version of the following article:Riddell, N. E., Griffiths, S. J., Rivino, L., King, D. C. B., Teo, G. H., Henson, S. M., Cantisan, S., Solana, R., Kemeny, D. M., MacAry, P. A., Larbi, A. and Akbar, A. N. (2015), Multifunctional cytomegalovirus (CMV)-specific CD8+ T cells are not restricted by telomere-related senescence in young or old adults. Immunology, 144: 549–560 which has been published in final form at doi:10.1111/imm.12409. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.This study was supported by the BBRSC (ANA, NER andSMH) and MRC (SG)