1,724,175 research outputs found
When more is not worse: genetic subtypes of obesity challenge conventional risk paradigms
No full textEmerging evidence challenges the view of obesity as a uniform metabolic risk. Spotlighting the recent Nature Medicine study by Chami et al., this piece discusses how "uncoupling" adiposity from its cardiometabolic consequences reveals biologically distinct subtypes of obesity. Integrating imaging and multi-omics offers a promising path toward personalized obesity management and deeper mechanistic insight
Investigating the Effects of Hot Isostatic Pressing on Additively Manufactured parts
Get PDFL'abstract è presente nell'allegato / the abstract is in the attachmen
The unirationality of the Hurwitz schemes H_10,8 and H_13,7
No full textWe show that the Hurwitz scheme Hg; d parametrizing d-sheeted simply branched covers of the projective line by smooth curves of genus g, up to isomorphism, is unirational for ðg; dÞ 1⁄4 ð10; 8Þ and ð13; 7Þ. The unirationality is settled by using liaison constructions in P1 P2 and P6 respectively, and through the explicit computation of single examples over a finite field
Brain tumours in infancy : a clinicopathological study
No full textTo investigate the clinicopathological features of brain tumours occurring in the first year of life, the records of the Department of Histopathology at the Adelaide Children's Hospital were examined for cases where the initial diagnosis of intracranial neoplasm had been made in infancy. Surgical material was available for review from 1972 to 1993 and autopsy cases were reviewed for an additional 12 years from 1962 to 1993. Twenty-four infants with intracranial neoplasms were diagnosed ranging in age from 5 days to 1 year (average = 7 months). There were 23 surgical cases and 1 autopsy case. The male to female ratio was 17:7. Fifty-eight percent of the tumours were located in the supratentorial region. Although the incidence is relatively low, this study demonstrates that a wide range of brain tumours, which differ significantly in both clinical presentation and location from those found in the older child, do occur during the first year of life. The location of the primary tumour may be affected by associated congenital malformations, and metastatic malignancy, although rare, may occur. Antenatal ultrasound examination may be useful in identifying congenital intracranial tumours.S Hanieh, A Hanieh, A.J Bourne and R.W Byar
DR1 As22 Open Data Sharing Project Hanieh Aslani
No full textThis study delves into the factors that either foster or inhibit data sharing behavior among a sample of 173 innovation management researchers
Parte A: Divide et impera: tramite uno screening in silico che targhetta l'omodimerizzazione del fattore di processività di HCMV, ppUL44, sono state identificate piccole molecole inibenti la replicazione virale. ParteB: Identificazione del proteoma nucleare di tutti i virus umani tramite un'analisi completa della localizzazione nucleare classica.
Get PDFHuman cytomegalovirus (HCMV) è un agente patogeno principale di molte malattie in persone immunosoppresse, inclusi pazienti affetti da AIDS e sottoposti a trapianto, e nascituri congenitamente infetti. Le terapie ed i farmaci antivirali utilizzati per il trattamento dell’infezioni da HCMV presentano una serie di limitazioni, tra cui la bassa biodisponibilità, tossicità, e l’insorgenza di ceppi virali farmaco resistenti, rendendo cruciale la necessità di identificare nuovi target terapeutici efficaci. Studi sulle interazioni tra proteine virali (PPI) si sono rivelati alleati importanti per lo sviluppo di nuovi farmaci antivirali, in quanto questi ultimi possono inibire il ciclo vitale del virus interferendo con le attività delle proteine virali. La dimerizzazione del fattore di processività della DNA polimerasi, ppUL44, di HCMV è essenziale per il ciclo vitale del virus infatti necessaria per la replicazione del DNA virale mediata da oriLyt e può essere quindi considerata come un potenziale target terapeutico. Pertanto, in precedenza, tramite uno screening in silico sono state identificate 18 piccole molecole (Small Molecules, SMs) potenzialmente capaci di interferire con la omodimerizazzione di ppUL44. Saggi antivirali delle 18 SMs sul virus ricombinante . In questo lavoro sono riuscita a caratterizzare l’effetto di questi composti sulla viabilità e crescita cellulare, e quindi cominciare un’analisi preliminare del loro meccanismo di azione. Tutte hanno compromesso la replicazione dei virus reporter AD169 di HCMV ed una sua controparte resistente al GCV in maniera simile. Tra le 4 SMs scelte, B3, ha mostrato il Selectivity Index (SI) più alto e quindi l’unico composto ad essere ulteriormente analizzato. Siamo riusciti a dimostrare che B3 efficientemente inibisce lo strain virale AD169 di HCMV in saggi di Plaque Reduction (PRA). Come misurato tramite qPCR, B3 ha specificatamente inibito la sintesi del DNA virale a partire da 72 ore post infezione, come anche l’espressiIl nostro Gruppo di ricerca ha precedentemente identificato il proteoma nucleare di tutti i virus infettanti l’essere umano, distinguendo tra proteine virali che traslocano all’interno del nucleo della cellula infetta in modo IMPα/β1 dipendente o meno, combinando analisi bioinformatiche estese anche alla caratterizzazione funzionale delle sequenze di localizzazione nucleare (NLS) virali. Questo studio presenta l’opportunità senza precedenti di comparare la diversa interazione tra virus differenti con l’apparato di trasporto al nucleo della cellula infetta, con importanti implicazioni sullo sviluppo di nuovi target terapeutici antivirali a largo spettro. Una profonda analisi funzionale sui classici NLS (cNLS) putative identificati ci ha portato alla scoperta di più di 500 proteine codificanti cNLS. Siamo riusciti anche a fare una prima caratterizzazione del processo di import nucleare delle proteine Large T antigen (LTA) dei Polyomavirus (HPyV) e delle cNLS coinvolte. Nonostante i LT di 14 HPyV presentavano cNLS funzionali, queste erano molto diverse tra di loro sia in termini di struttura che di attività. Le attività delle cNLS hanno riflesso I livelli di accumulo nucleare delle proteine full-length, con l’attività più bassa associata alla cNLS di HPyV7. Nonostante molti HPyV codificano per una o più cNLS monopartite, 4 di esse presentavano cNLS bipartita. Chiaramente queste differenze strutturali influenzano affinità verso l’apparato IMPα/β1 dipendente ed il tropismo del virus. Inoltre, 2 tra le 26 cNLS con il punteggio di cNLS mapper più alto identificate con i nostri studi, sono altamente conservate e presentano vari ortologhi di due proteine, A19 e N2, della famiglia dei Poxivirdae. Entrambe le proteine localizzano nel nucleo della cellula ospite, in un pathway attivo IMPα/β1 dipendente, e la loro traslocazione nucleare viene inibita in presenza di mutazioni sito-specifico.Human cytomegalovirus (HCMV) is a leading cause of severe diseases in immunocompromised individuals, including AIDS patients and transplant recipients, and in congenitally infected newborns. The utility of available drugs is limited by poor bioavailability, toxicity, and emergence of resistant strains. Therefore, it is crucial to identify new targets for therapeutic intervention. Among the latter, viral protein–protein interactions are becoming increasingly attractive. Since dimerization of HCMV DNA polymerase processivity factor ppUL44 plays an essential role in the viral life cycle, being required for oriLyt-dependent DNA replication, it can be considered a potential therapeutic target. We therefore previously performed an in silico screening and selected 18 small molecules (SMs) potentially interfering with ppUL44 homodimerization. Antiviral assays using recombinant HCMV TB4-UL83-YFP in the presence of the selected SMs led to the identification of four active compounds. In this work I have characterized the effect of such compounds on cell viability and growth and began a preliminary analysis of their mode of action. All of them impaired replication of an AD169-GFP reporter virus and its ganciclovir-resistant counterpart to a similar extend. Among the 4 selected SMs compound B3 exhibited the highest selectivity index (SI) and was further investigated. We could show that it also efficiently inhibited HCMV AD169 strain in plaque reduction assays (PRAs). As assessed by qPCR by Western blotting experiments, B3 specifically reduced viral DNA synthesis starting from 72 h post infection, consistent with the inhibition of viral gene expression starting from 48 h post infection by Western blotting experiments. Therefore, our data suggest that inhibition of ppUL44 dimerization could represent a new class of HCMV inhibitors, complementary to those targeting the DNA polymerase catalytic subunit or the viral terminase complex.
Our research group previously defined the nuclear proteome of all human viruses, discriminating between viral proteins translocated in an IMPα/β1 dependent or independent process by combining bioinformatics analysis with extensive functional characterization of viral cNLSs. This study represents an unprecedented opportunity to compare how viruses differently interact with the host cell nuclear transport machinery, with important implications for the development of broad-range host targeted antivirals. In depth functional validation of identified putative classical nuclear localization signals (cNLSs) led to the discovery of more than 500 novel viral cNLS. We also report the first characterization of the nuclear import process of Human Polyomaviruses (HPyVs) Large T antigens (LT) as well as of the cNLS involved. Although LT from all 14 HPyVs bear a functional cNLS, the latter are extremely heterogenous, both in terms of activity and structural organization. Importantly, cNLS activity mirrored the levels of nuclear accumulation of full-length proteins, with lowest activity associated to HPyV7. Surprisingly, while most HPyVs bear one or more monopartite cNLS, four of them bear a bipartite cNLS. Clearly, such structural differences suggest an important role in conferring binding abilities to specific IMPα isoforms with potential implication for viral tropism determination. Furthermore, among the 26 top ranked cNLS based on cNLS mapper score, two extremely well conserved cNLS in orthologues of Vaccinia Virus proteins A19 and N2 were identified. Both proteins localized in the cell nucleus via energy and IMPα/β-dependent process, and their nuclear import could be abolished by site specific mutagenesis of the cNLSs, thus A19 and N2 mutant derivatives failed to localize in the nucleus
Rutidermatidae BRADY & NORMAN 1896
No full textFAMILY RUTIDERMATIDAE BRADY & NORMAN, 1896 Undescribed genera and species of Rutidermatidae.Published as part of Brandão, Simone N., Saeedi, Hanieh & Brandt, Angelika, 2022, Macroecology of Southern Ocean benthic Ostracoda (Crustacea) from the continental margin and abyss, pp. 226-255 in Zoological Journal of the Linnean Society 194 on page 237, DOI: 10.1093/zoolinnean/zlab078, http://zenodo.org/record/579981
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