A contiguous stretch of methionine residues mediates the energy-dependent internalization mechanism of a cell-penetrating peptide

Recently we characterized an unusual switch in the internalization mechanism of the monomeric and dimeric forms of the cell-penetrating peptide RDLWEMMMVSLACQY. Here, we observed both energy-dependent and energy-independent modes of peptide uptake by the target B-lymphocytes WI-L2-729HF2, suggesting that higher-order structure might modulate the action of this novel cell-penetrating peptide. In the present work, we propose a possible internalization mechanism for the dimeric peptide which involves an initial interaction with the cell membrane, followed by an energy-dependent internalization process which requires the contiguous Met(6-8) sequence.     

Renal angiomyolipoma and fever: assessment with isotopic renogram and 67Ga scintigraphy

A 26 year-old woman with tuberous sclerosis who came to the Emergency Department with high fever, bilious vomit, right hemiabdomen pain and syncope during 2 weeks. Laboratory analyses show hemoglobin 6.7 g/dl, creatinine 1.5 mg/dl and leukocytes 30,000. Abdominal CT is performed because of suspicion of active bleeding in right hemiabdomen, following rupture of right angiomyolipoma, treated by selective arterial embolization. She was referred to the Nuclear Medicine Department to perform a 67Gallium scintigraphy for the detection of infection, and static and dynamic renal scintigraphy for evaluation of the renal morphology and function.     

Plasma lipids as a risk factor in peripheral vascular disease

Plasma lipids were tested in 59 patients with symptomatic peripheral vascular disease (PVD) (confirmed by angiographic and, in many cases, operative examinations) and compared with the lipid balance in 47 nonarteriopathic subjects constituting the control group. Of all the elements considered, only the hypertriglyceridemia and the fall in the HDL cholesterol/total cholesterol ratio showed a statistically significant difference between the two groups. In particular, there was a significant difference between the two groups. In particular, there was a significant difference in the triglyceridemia present in the arteriopathic patients, as evidenced by the double check afforded by the frequency test (PVD: 25/59; control: 8/47; p less than 0.01) and the averages test (PVD: 201 +/- 131; control: 138 +/- 98; p less than 0.01).     

The Usher 1B protein, MYO7A, is required for normal localization and function of the visual retinoid cycle enzyme, RPE65

Mutations in the MYO7A gene cause a deaf-blindness disorder, known as Usher syndrome 1B. In the retina, the majority of MYO7A is in the retinal pigmented epithelium (RPE), where many of the reactions of the visual retinoid cycle take place. We have observed that the retinas of Myo7a-mutant mice are resistant to acute light damage. In exploring the basis of this resistance, we found that Myo7a-mutant mice have lower levels of RPE65, the RPE isomerase that has a key role in the retinoid cycle. We show for the first time that RPE65 normally undergoes a light-dependent translocation to become more concentrated in the central region of the RPE cells. This translocation requires MYO7A, so that, in Myo7a-mutant mice, RPE65 is partly mislocalized in the light. RPE65 is degraded more quickly in Myo7a-mutant mice, perhaps due to its mislocalization, providing a plausible explanation for its lower levels. Following a 50-60% photobleach, Myo7a-mutant retinas exhibited increased all-trans-retinyl ester levels during the initial stages of dark recovery, consistent with a deficiency in RPE65 activity. Lastly, MYO7A and RPE65 were co-immunoprecipitated from RPE cell lysate by antibodies against either of the proteins, and the two proteins were partly colocalized, suggesting a direct or indirect interaction. Together, the results support a role for MYO7A in the translocation of RPE65, illustrating the involvement of a molecular motor in the spatiotemporal organization of the retinoid cycle in vision.     

An ultrasound-based comparative study on carotid plaques in HIV-positive patients vs. atherosclerotic and arteritis patients: atherosclerotic or inflammatory lesions?

BACKGROUND: We have previously described two cases of HIV-1-positive patients undergoing surgery for stenosis of the internal carotid arteries. Histology revealed an extensive inflammatory infiltration of the vascular wall and no evidence of atheromasic plaque. This unexpected pattern of carotid damage prompted us to perform a more accurate investigation of the characteristics of carotid plaques in a group of HIV-positive patients. The results were compared with those obtained from young patients affected by atherosclerosis of the epi-aortic vessels and patients with arteritis. METHODS: The patients underwent ultrasonography of the epi-aortic vessels using one of the latest generation power color-Doppler with 7.5 MHz probes. RESULTS: The study population included 61 HIV-positive patients and 47 HIV-negative patients (37 atherosclerotic and 10 with arteritis). Compared with HIV-negative atherosclerotic patients, there were significantly higher proportions of HIV-positive patients with iso-hypoechogenic lesions (81.8 vs. 29%) that were homogeneous both in their parietal and endoluminal portions (96.7 vs. 21.6% and 88.5 vs. 54.0%, respectively), with a smooth or slightly irregular surface (99.0 vs. 56.7%) (P=0.001 for all differences). No statistically significant differences were seen between HIV-positive and arteritis patients. CONCLUSION: Our study evidenced that the ultrasonographic structure of the epi-aortic lesions in HIV-positive patients substantially differ from those of the plaques in atherosclerotic patients, although they share similar characteristics with patients affected by arteritis. Further investigations are warranted to better define the structure and the mechanism of onset of these lesions.     

Frontotemporal dementia and motor neurone disease: Overlapping clinic-pathological disorders

Advances in genetics and pathology have supported the idea of a continuum between frontotemporal dementia (FTD) and motor neurone disease (MND), which is strengthened by the discovery of the trans-activating responsive (Tar) sequence DNA binding protein (TDP-43) as a key component in the underlying pathology of FTD, FTD–MND and sporadic and familial MND patients. MND is a multisystem disorder associated with cognitive and behavioural changes which in some instances reaches the criteria for FTD, while a proportion of patients with FTD develop frank MND. We review the overlap between FTD and MND, emphasizing areas of controversy and uncertainty.