Determination of C-terminal group of aspergillopeptidase Af

Résumé Nos observations concernent la détermination de groupes C-terminaux d'aspergillopeptidase Af extraite de la culture d'Aspergillus fumigatus. Nous avons utilisé la technique de l'hydrazinolyse et avec la chromatographie alternante et démontré que la leucine constitue un aminoacide C-terminal.     

The mechanical and biochemical effects of pentoxifylline on the perfused rat heart

Summary Perfusion of the isolated rat heart at constant heart rate and coronary flow with the inhibitor of cyclic nucleotide phosphodiesterase, pentoxifylline (10^–4 moles/l), produced no significant effect on the maximum rate and the peak of contraction, but increased the maximum rate of relaxation. cAMP level and cAMP-dependent protein kinase activity were increased in the absence of changes in cGMP. The results were identical in hearts of reserpinized rats.This work was supported by grants from the Consejo Nacional de Investigaciones Cientificas y Técnicas and the Comisión de Investigaciones Científicas. Buenos Aires, Argentina.We thank Hoechst Laboratories for the partial support and Mrs Alicia R. Ramirez and María Prinzo for the excellent technical assistance.     

实时声学数字信号处理实验研究

针对声回波对消、语音去混响及语音盲信号分离等声学信号处理应用领域中，自适应算法的有效性、实时可行性的研究与测试，作者研究并构建出基于浮点DSP及虚拟仪器LabVIEW的实时声学信号处理实验平台（EP），该EP既能同时测量多路房间冲激响应（RIR）及两两RIR间的差异（DRIR）信息，并用于相关算法的离线研究，又能借助DSP可编程的灵活性及LabVIEW方便的图形用户界面对相关的自适应算法进行实时实验研究。     

Isozymes of cathepsin B1 in developing human placenta

Summary Cathepsin B1 was purified from human placentas of different gestational ages and analyzed by isoelectric focusing on polyacrylamide gel. The enzyme was shown to consist of 3 or 4 isozymes with pI values between 5.1 and 5.7.     

Effect of substitution of glycine by D- or L-alanine on the activity of the C-terminal hexapeptide analogue of substance P on isolated guinea-pig ileum

Summary Two new C-terminal hexapeptide analogues of substance P having D- or L-alanine in position 9 were synthetized. Their contracting activities on isolated guinea-pig ileum were considerably lower than that of 7–11.     

Defective ristocetin and bovine factor VIII-induced platelet aggregation in normal rats

Riassunto Le piastrine di 3 diversi ceppi di ratti, contrariamente alle piastrine umane e di cavia, non sono aggregate (sia in vitro che in vivo) nè dalla ristocetine nè dal fattore von Willebrand bovino, porcino o umano, quest'ultimo reso aggregante previo trattamento enzimatico. Tale insensibilità, di cui si è potuta escludere l'origine plasmatica, potrebbe derivare dall'assenza, sulle piastrine di ratto, di un recettore per il fattore von Willebrand (acido sialico?); potrebbe essere cosi spiegata anche la mancata risposta delle piastrine alla ristocetina. Questi risultati suggeriscono che le piastrine di ratto possono essere un utile modello sperimentale per lo studio della sindrome di Bernard-Soulier nell'uomo.

---

---

This work was supported by Contract No. 73-00400-04 of the C.N.R., Roma, Italy. The skilful technical assistance of MissAnnalisa Cavenaghi is appreciated.     

Identification of cells initiating human melanomas

Tumour-initiating cells capable of self-renewal and differentiation, which are responsible for tumour growth, have been identified in human haematological malignancies and solid cancers. If such minority populations are associated with tumour progression in human patients, specific targeting of tumour-initiating cells could be a strategy to eradicate cancers currently resistant to systemic therapy. Here we identify a subpopulation enriched for human malignant-melanoma-initiating cells (MMIC) defined by expression of the chemoresistance mediator ABCB5 (refs 7, 8) and show that specific targeting of this tumorigenic minority population inhibits tumour growth. ABCB5+ tumour cells detected in human melanoma patients show a primitive molecular phenotype and correlate with clinical melanoma progression. In serial human-to-mouse xenotransplantation experiments, ABCB5+ melanoma cells possess greater tumorigenic capacity than ABCB5- bulk populations and re-establish clinical tumour heterogeneity. In vivo genetic lineage tracking demonstrates a specific capacity of ABCB5+ subpopulations for self-renewal and differentiation, because ABCB5+ cancer cells generate both ABCB5+ and ABCB5- progeny, whereas ABCB5- tumour populations give rise, at lower rates, exclusively to ABCB5- cells. In an initial proof-of-principle analysis, designed to test the hypothesis that MMIC are also required for growth of established tumours, systemic administration of a monoclonal antibody directed at ABCB5, shown to be capable of inducing antibody-dependent cell-mediated cytotoxicity in ABCB5+ MMIC, exerted tumour-inhibitory effects. Identification of tumour-initiating cells with enhanced abundance in more advanced disease but susceptibility to specific targeting through a defining chemoresistance determinant has important implications for cancer therapy.     

Autophagy fights disease through cellular self-digestion

Autophagy, or cellular self-digestion, is a cellular pathway involved in protein and organelle degradation, with an astonishing number of connections to human disease and physiology. For example, autophagic dysfunction is associated with cancer, neurodegeneration, microbial infection and ageing. Paradoxically, although autophagy is primarily a protective process for the cell, it can also play a role in cell death. Understanding autophagy may ultimately allow scientists and clinicians to harness this process for the purpose of improving human health.