Showing papers by "Sapienza University of Rome published in 2005"

Nanostructured materials for advanced energy conversion and storage devices

Abstract: New materials hold the key to fundamental advances in energy conversion and storage, both of which are vital in order to meet the challenge of global warming and the finite nature of fossil fuels. Nanomaterials in particular offer unique properties or combinations of properties as electrodes and electrolytes in a range of energy devices. This review describes some recent developments in the discovery of nanoelectrolytes and nanoelectrodes for lithium batteries, fuel cells and supercapacitors. The advantages and disadvantages of the nanoscale in materials design for such devices are highlighted.

Cytoplasmic Nucleophosmin in Acute Myelogenous Leukemia with a Normal Karyotype

Abstract: Background Nucleophosmin (NPM), a nucleocytoplasmic shuttling protein with prominent nucleolar localization, regulates the ARF-p53 tumor-suppressor pathway. Translocations involving the NPM gene cause cytoplasmic dislocation of the NPM protein. Methods We used immunohistochemical methods to study the subcellular localization of NPM in bone marrow–biopsy specimens from 591 patients with primary acute myelogenous leukemia (AML). We then correlated the presence of cytoplasmic NPM with clinical and biologic features of the disease. Results Cytoplasmic NPM was detected in 208 (35.2 percent) of the 591 specimens from patients with primary AML but not in 135 secondary AML specimens or in 980 hematopoietic or extrahematopoietic neoplasms other than AML. It was associated with a wide spectrum of morphologic subtypes of the disease, a normal karyotype, and responsiveness to induction chemotherapy, but not with recurrent genetic abnormalities. There was a high frequency of FLT3 internal tandem duplications and absen...

Synthesis and functionalization of indoles through palladium-catalyzed reactions

Abstract: The substituted indole nucleus [indole is the acronym from indigo (the natural dye) and oleum (used for the isolation)] is a structural component of a vast number of biologically active natural and unnatural compounds. The synthesis and functionalization of indoles has been the object of research for over 100 years, and a variety of well-established classical methods are now available, to name a few of them, the Fisher indole synthesis, the Gassman synthesis of indoles from N-halo-anilines, the Madelung cyclization of N-acyl-o-toluidines, the Bischler indole synthesis, the Batcho-Leimgruber synthesis of indoles from o-nitrotoluenes and dimethylformamide acetals, and the reductive cyclization of o-nitrobenzyl ketones.1 In the last 40 years or so, however, palladiumcatalyzed reactions, generally tolerant of a wide range of functionalities and therefore applicable to complex molecules, have achieved an important place in the arsenal of the practicing organic chemist. Since the invention of an industrial process for the palladium-catalyzed production of acetaldehyde from ethylene in the presence of PdCl2 and CuCl2, an everincreasing number of organic transformations have been based on palladium catalysis. Almost every area of the organic synthesis has been deeply influenced by the profound potential of this versatile transition metal, modifying the way organic chemists design and realize synthetic processes.2,3 Because of its catalytic nature, palladium-catalyzed synthesis can provide access to fine chemicals, agrochemical and pharmaceutical intermediates, and active ingredients in fewer steps and with less waste than classical † In memory of Prof. Bianca Rosa Pietroni, a colleague and very close friend. * To whom correspondence should be addressed. Phone: + 39 (06) 4991-2785. Fax: + 30 (06) 4991-2780. E-mail: sandro.cacchi@ uniroma1.it. 2873 Chem. Rev. 2005, 105, 2873−2920

Musculoskeletal ultrasound including definitions for ultrasonographic pathology

Abstract: Ultrasound (US) has great potential as an outcome in rheumatoid arthritis trials for detecting bone erosions, synovitis, tendon disease, and enthesopathy. It has a number of distinct advantages over magnetic resonance imaging, including good patient tolerability and ability to scan multiple joints in a short period of time. However, there are scarce data regarding its validity, reproducibility, and responsiveness to change, making interpretation and comparison of studies difficult. In particular, there are limited data describing standardized scanning methodology and standardized definitions of US pathologies. This article presents the first report from the OMERACT ultrasound special interest group, which has compared US against the criteria of the OMERACT filter. Also proposed for the first time are consensus US definitions for common pathological lesions seen in patients with inflammatory arthritis.

Low-Dose Aspirin for the Prevention of Atherothrombosis

Abstract: This review considers the role of low-dose aspirin for the prevention of atherothrombosis, discussing the molecular mechanism of action of aspirin as well as clinical and epidemiologic studies of aspirin as an antiplatelet agent, with special emphasis on the benefits and risks in different patient populations.

Mechanisms of Antibacterial Action of Three Monoterpenes

Abstract: In the present paper, we report the antimicrobial efficacy of three monoterpenes [linalyl acetate, (+)menthol, and thymol] against the gram-positive bacterium Staphylococcus aureus and the gram-negative bacterium Escherichia coli. For a better understanding of their mechanisms of action, the capability of these three monoterpenes to damage biomembranes was evaluated by monitoring the release, following exposure to the compounds under study, of the water-soluble fluorescent marker carboxyfluorescein from unilamellar vesicles with different lipidic compositions (phosphatidylcholine, phosphatidylcholine/phosphatidylserine [9:1], phosphatidylcholine/stearylamine [9:1], and phosphatidylglycerol/cardiolipin [9:1]). Furthermore, the interaction of the terpenes tested with dimyristoylphosphatidylcholine multilamellar vesicles as model membranes was monitored by means of differential scanning calorimetry. Finally, the results were related to the relative lipophilicity and water solubility of the compounds examined. Taken together, our findings lead us to speculate that the antimicrobial effect of (+)menthol, thymol, and linalyl acetate may result, at least partially, from a perturbation of the lipid fraction of microorganism plasma membrane, resulting in alterations of membrane permeability and in leakage of intracellular materials. Besides being related to physicochemical characteristics of the drugs (such as lipophilicity and water solubility), this effect seems to be dependent on lipid composition and net surface charge of microbial membranes. Furthermore, the drugs might cross the cell membranes, penetrating into the interior of the cell and interacting with intracellular sites critical for antibacterial activity.

Peginterferon alfa-2b and ribavirin for 12 vs. 24 weeks in HCV genotype 2 or 3.

Abstract: background We hypothesized that in patients with hepatitis C virus (HCV) genotype 2 or 3 in whom HCV RNA is not detectable after 4 weeks of therapy, 12 weeks of treatment is as effective as 24 weeks. methods A total of 283 patients were randomly assigned to a standard 24-week regimen of peginterferon alfa-2b at a dose of 1.0 µg per kilogram weekly plus ribavirin at a dose of 1000 mg or 1200 mg daily, on the basis of body weight. Of these, 70 patients were assigned to the 24-week regimen (standard-duration group) and 213 patients to a variable regimen (variable-duration group) of 12 or 24 weeks, depending on whether tests for HCV RNA were negative or positive at week 4. The primary end point was HCV that was not detectable by polymerase-chain-reaction (PCR) assay 24 weeks after the completion of therapy. results In the standard-duration group, 45 (64 percent) patients had HCV that was not detectable by PCR assay at week 4, as compared with 133 (62 percent) in the variable-duration group (difference [the rate in the standard-duration group minus that in the variableduration group], 2 percent; 95 percent confidence interval, i11 to 15 percent). Fiftythree patients (76 percent) in the standard-duration group and 164 patients (77 percent) in the variable-duration group had a sustained virologic response (difference, i1 percent; 95 percent confidence interval, i13 to 10 percent). Fewer patients in the variableduration group receiving the 12-week regimen had adverse events and withdrew than in the group receiving the 24-week regimen (P=0.045). The rate of relapse (defined as HCV not detectable at the end of treatment but detectable at the end of follow-up) was 3.6 percent in the standard-duration group and 8.9 percent in the variable-duration group (P=0.16). Overall, the rate of sustained virologic response was 80 percent among patients with HCV genotype 2 and 66 percent among those with genotype 3 (P<0.001). conclusions A shorter course of therapy over 12 weeks with peginterferon alfa-2b and ribavirin is as effective as a 24-week course for patients with HCV genotype 2 or 3 who have a response to treatment at 4 weeks.

Some Contagion, Some Interdependence: More Pitfalls in Tests of Financial Contagion

Abstract: This paper builds on a standard factor model of stock market returns to reconsider recent empirical literature on contagion in financial markets based on bivariate correlation analysis. According to this literature, contagion is defined as a structural break in the linear transmission mechanism of financial shocks. Using our framework, we show that the result of 'no contagion, only interdependence' stressed by recent contributions is due to arbitrary and unrealistic restrictions on the variance of country-specific shocks. We focus on the international effects of the Hong Kong stock market crisis of October 1997 as a case study. For plausible values of the variance of country-specific shocks in Hong Kong, current tests cannot reject the null of interdependence for 16 countries out of a sample of 17. Our analysis strongly questions such conclusion, finding evidence of 'contagion' for at least five countries.

Single, rapid coastal settlement of Asia revealed by analysis of complete mitochondrial genomes.

Abstract: A recent dispersal of modern humans out of Africa is now widely accepted, but the routes taken across Eurasia are still disputed. We show that mitochondrial DNA variation in isolated “relict” populations in southeast Asia supports the view that there was only a single dispersal from Africa, most likely via a southern coastal route, through India and onward into southeast Asia and Australasia. There was an early offshoot, leading ultimately to the settlement of the Near East and Europe, but the main dispersal from India to Australia ∼65,000 years ago was rapid, most likely taking only a few thousand years.

Passive Immunization during Pregnancy for Congenital Cytomegalovirus Infection

Abstract: methods We studied pregnant women with a primary CMV infection. The therapy group comprised women whose amniotic fluid contained either CMV or CMV DNA and who were offered intravenous CMV hyperimmune globulin at a dose of 200 U per kilogram of maternal weight. A prevention group, consisting of women with a recent primary infection before 21 weeks’ gestation or who declined amniocentesis, was offered monthly hyperimmune globulin (100 U per kilogram intravenously). results In the therapy group, 31 women received hyperimmune globulin, only 1 (3 percent) of whom gave birth to an infant with CMV disease (symptomatic at birth and handicapped at two or more years of age), as compared with 7 of 14 women who did not receive hyperimmune globulin (50 percent). Thus, hyperimmune globulin therapy was associated with a significantly lower risk of congenital CMV disease (adjusted odds ratio, 0.02; 95 percent confidence interval, i ∞ to 0.15; P<0.001). In the prevention group, 37 women received hyperimmune globulin, 6 (16 percent) of whom had infants with congenital CMV infection, as compared with 19 of 47 women (40 percent) who did not receive hyperimmune globulin. Thus, hyperimmune globulin therapy was associated with a significantly lower risk of congenital CMV infection (adjusted odds ratio, 0.32; 95 percent confidence interval, 0.10 to 0.94; P=0.04). Hyperimmune globulin therapy significantly (P<0.001) increased CMV-specific IgG concentrations and avidity and decreased natural killer cells and HLA-DR+ cells and had no adverse effects. conclusions Treatment of pregnant women with CMV-specific hyperimmune globulin is safe, and the findings of this nonrandomized study suggest that it may be effective in the treatment and prevention of congenital CMV infection. A controlled trial of this agent may now be appropriate.

Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: a meta-analysis.

Abstract: Summary Objectives Ageing in men is associated with a gradual decline in serum testosterone levels and a concomitant loss of muscle mass, accumulation of central adiposity, impaired mobility and increased risk of bone fractures. Whether androgen treatment might be beneficial in these subjects is still under debate. We have carried out a systematic review of randomized controlled trials (RCTs) evaluating the effects of testosterone (T) administration to middle-aged and ageing men on body composition, muscle strength, bone density, markers of bone metabolism and serum lipid profile. Data source A comprehensive search of all published randomized clinical trials was performed using the MEDLINE, Cochrane Library, EMBASE and Current Contents databases. Review methods Guided by prespecified criteria, software-assisted data abstraction and quality assessed by two independent reviewers, 29 RCTs were found to be eligible. For each investigated variable, we reported the results of pooled estimates of testosterone treatment using the random effect model of meta-analysis. Heterogeneity, reproducibility and consistency of the findings across studies were explored using sensitivity and meta-regression analysis. Results Overall, 1083 subjects were evaluated, 625 randomized to T, 427 to placebo and 31 to observation (control group). Weighted mean age was 64·5 years (range 49·9–77·6) and mean serum testosterone was 10·9 nmol/l (range 7·8–19). Testosterone treatment produced: (i) a reduction of 1·6 kg (CI: 2·5–0·6) of total body fat, corresponding to −6·2% (CI: 9·2–3·3) variation of initial body fat, (ii) an increase in fat free mass of 1·6 kg (CI: 0·6–2·6), corresponding to +2·7% (CI: 1·1–4·4) increase over baseline and (iii) no change in body weight. The effects of T on muscle strength were heterogeneous, showing a tendency towards improvement only at the leg/knee extension and handgrip of the dominant arm (pooled effect size = 0·3 standard mean difference (SMD), CI: −0·0 to 0·6). Testosterone improved bone mineral density (BMD) at the lumbar spine by +3·7% (CI: 1·0–6·4%) compared to placebo, but not at the femoral neck, and produced a consistent reduction in bone resorption markers (pooled effect size = −0·6 SMD, CI: −1·0 to −0·2). Testosterone also reduced total cholesterol by 0·23 mmol/l (CI: −0·37 to −0·10), especially in men with lower baseline T concentrations, with no change in low density lipoprotein (LDL)-cholesterol. A significant reduction of high density lipoprotein (HDL)-cholesterol was found only in studies with higher mean T-values at baseline (−0·085 mmol/l, CI: −0·017 to −0·003). Sensitivity and meta-regression analysis revealed that the dose/type of T used, in particular the possibility of aromatization, explained the heterogeneity in findings observed on bone density and HDL-cholesterol among studies. Conclusion The present analysis provides an estimate of the average treatment effects of testosterone therapy in middle-aged men. Our findings are sufficiently strong to justify further interventional studies focused on alternative targets of androgenic treatment carrying more stringent clinical implications, in particular the cardiovascular, metabolic and neurological systems.

Diquark-antidiquark states with hidden or open charm and the nature of X(3872)

Abstract: Heavy-light diquarks can be the building blocks of a rich spectrum of states which can accommodate some of the newly observed charmoniumlike resonances not fitting a pure $c\overline{c}$ assignment. We examine this possibility for hidden and open charm diquark-antidiquark states deducing spectra from constituent quark masses and spin-spin interactions. Taking the $X(3872)$ as input we predict the existence of a ${2}^{++}$ state that can be associated to the $X(3940)$ observed by Belle and reexamine the state claimed by SELEX, $X(2632)$. The possible assignment of the previously discovered states ${D}_{s}(2317)$ and ${D}_{s}(2457)$ is discussed. We predict $X(3872)$ to be made of two components with a mass difference related to ${m}_{u}\ensuremath{-}{m}_{d}$ and discuss the production of $X(3872)$ and of its charged partner ${X}^{\ifmmode\pm\else\textpm\fi{}}$ in the weak decays of ${B}^{+,0}$.

Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis

Abstract: Although anecdotal reports suggest that cannabis may be used to alleviate symptoms of depression, the psychotropic effects and abuse liability of this drug prevent its therapeutic application. The active constituent of cannabis, delta9-tetrahydrocannabinol, acts by binding to brain CB1 cannabinoid receptors, but an alternative approach might be to develop agents that amplify the actions of endogenous cannabinoids by blocking their deactivation. Here, we show that URB597, a selective inhibitor of the enzyme fatty-acid amide hydrolase, which catalyzes the intracellular hydrolysis of the endocannabinoid anandamide, exerts potent antidepressant-like effects in the mouse tail-suspension test and the rat forced-swim test. Moreover, URB597 increases firing activity of serotonergic neurons in the dorsal raphe nucleus and noradrenergic neurons in the nucleus locus ceruleus. These actions are prevented by the CB1 antagonist rimonabant, are accompanied by increased brain anandamide levels, and are maintained upon repeated URB597 administration. Unlike direct CB1 agonists, URB597 does not exert rewarding effects in the conditioned place preference test or produce generalization to the discriminative effects of delta9-tetrahydrocannabinol in rats. The findings support a role for anandamide in mood regulation and point to fatty-acid amide hydrolase as a previously uncharacterized target for antidepressant drugs.

CT colonography reporting and data system: a consensus proposal.

Abstract: Computed tomographic (CT) colonography continues to evolve rapidly. Advances in scanning and display technologies, encouraging performance data, and increased utilization necessitate clarification and standardization of results reporting in CT colonography. There are several reasons for this. First and most important, standardized reporting can better assist patients and referring physicians in making management decisions on the basis of the results of CT colonography. The precedent of the mammography Breast Imaging Reporting and Data System, or BI-RADS, schema is a strong incentive to provide a similar structure for CT colonography. Second, as more examinations are performed, the likelihood increases that radiologists interpreting results of a CT colonography examination performed at one center will require comparison to examination results and reports generated at other sites. As has been seen with mammography, a common set of terms facilitates this kind of assessment (1). Third, as utilization of CT colonography increases, our colleagues in other medical specialties, the various third-party payers, and the general public will insist on larger-scale evaluations of examination performance, examination quality, patient outcome, and cost. Here again, a common approach to interpretation will assist us in meeting these demands. Finally, a common scheme for reporting facilitates structured reporting. The purpose of this communication is to facilitate clear and consistent communication of CT colonography results. The authors—an ad hoc group of investigators active in the area of CT colonography—have collaborated to develop a reporting scheme that is coupled to recommendations for follow-up. Our group, the Working Group on Virtual Colonoscopy, includes members of the American College of Radiology Colon Cancer Committee. On the basis of our collective experience and a review of the relevant literature, we present a practical guide to the interpretation of CT colonography results: the CT Colonography Reporting and Data System, or “C-RADS.” Future multidisciplinary collaboration and longitudinal data may lead to a refinement of the terms and concepts we present here; our effort is a starting point in which we attempt to address the needs of current practice. Adequate training and rigorous quality control of examination performance are essential elements for maximizing the potential of CT colonography; however, these related topics will not be discussed here. Instead, we will focus on the interpretation and follow-up of CT colonography results in three parts: first, a description of terms useful for reporting the size, morphologic features, and location of polyps and masses; second, a description of a classification scheme for colonic lesions and suggestions for follow-up; Published online 10.1148/radiol.2361041926 Radiology 2005; 236:3–9 1 From the Division of Abdominal Imaging and Intervention, Department of Radiology/ White 270, Massachusetts General Hospital, Boston, MA 02114 (M.E.Z.). The complete list of author affiliations is at the end of this article. Received November 12, 2004; accepted November 15. Address correspondence to M.E.Z. (e-mail: mzalis@partners.org).

Transcranial magnetic stimulation highlights the sensorimotor side of empathy for pain

Abstract: Pain is intimately linked with action systems that are involved in observational learning and imitation. Motor responses to one's own pain allow freezing or escape reactions and ultimately survival. Here we show that similar motor responses occur as a result of observation of painful events in others. We used transcranial magnetic stimulation to record changes in corticospinal motor representations of hand muscles of individuals observing needles penetrating hands or feet of a human model or noncorporeal objects. We found a reduction in amplitude of motor-evoked potentials that was specific to the muscle that subjects observed being pricked. This inhibition correlated with the observer's subjective rating of the sensory qualities of the pain attributed to the model and with sensory, but not emotional, state or trait empathy measures. The empathic inference about the sensory qualities of others' pain and their automatic embodiment in the observer's motor system may be crucial for the social learning of reactions to pain.

Levofloxacin to prevent bacterial infection in patients with cancer and neutropenia.

Abstract: Background The prophylactic use of fluoroquinolones in patients with cancer and neutropenia is controversial and is not a recommended intervention. Methods We randomly assigned 760 consecutive adult patients with cancer in whom chemotherapy-induced neutropenia (<1000 neutrophils per cubic millimeter) was expected to occur for more than seven days to receive either oral levofloxacin (500 mg daily) or placebo from the start of chemotherapy until the resolution of neutropenia. Patients were stratified according to their underlying disease (acute leukemia vs. solid tumor or lymphoma). Results An intention-to-treat analysis showed that fever was present for the duration of neutropenia in 65 percent of patients who received levofloxacin prophylaxis, as compared with 85 percent of those receiving placebo (243 of 375 vs. 308 of 363; relative risk, 0.76; absolute difference in risk, –20 percent; 95 percent confidence interval, –26 to –14 percent; P=0.001). The levofloxacin group had a lower rate of microbiological...

Physical discipline and children's adjustment: Cultural normativeness as a moderator

Abstract: Interviews were conducted with 336 mother-child dyads (children's ages ranged from 6 to 17 years; mothers' ages ranged from 20 to 59 years) in China, India, Italy, Kenya, the Philippines, and Thailand to examine whether normativeness of physical discipline moderates the link between mothers' use of physical discipline and children's adjustment. Multilevel regression analyses revealed that physical discipline was less strongly associated with adverse child outcomes in conditions of greater perceived normativeness, but physical discipline was also associated with more adverse outcomes regardless of its perceived normativeness. Countries with the lowest use of physical discipline showed the strongest association between mothers' use and children's behavior problems, but in all countries higher use of physical discipline was associated with more aggression and anxiety.

Parkinson-like syndrome induced by continuous MPTP infusion: Convergent roles of the ubiquitin-proteasome system and α-synuclein

Abstract: In animals, sporadic injections of the mitochondrial toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) selectively damage dopaminergic neurons but do not fully reproduce the features of human Parkinson's disease. We have now developed a mouse Parkinson's disease model that is based on continuous MPTP administration with an osmotic minipump and mimics many features of the human disease. Although both sporadic and continuous MPTP administration led to severe striatal dopamine depletion and nigral cell loss, we find that only continuous administration of MPTP produced progressive behavioral changes and triggered formation of nigral inclusions immunoreactive for ubiquitin and α-synuclein. Moreover, only continuous MPTP infusions caused long-lasting activation of glucose uptake and inhibition of the ubiquitin-proteasome system. In mice lacking α-synuclein, continuous MPTP delivery still induced metabolic activation, but induction of behavioral symptoms and neuronal cell death were almost completely alleviated. Furthermore, the inhibition of the ubiquitinproteasome system and the production of inclusion bodies were reduced. These data suggest that continuous low-level exposure of mice to MPTP causes a Parkinson-like syndrome in an α-synuclein-dependent manner.

Exploiting Sink Mobility for Maximizing Sensor Networks Lifetime

Abstract: This paper explores the idea of exploiting the mobility of data collection points (sinks) for the purpose of increasing the lifetime of a wireless sensor network with energy-constrained nodes. We give a novel linear programming formulation for the joint problems of determining the movement of the sink and the sojourn time at different points in the network that induce the maximum network lifetime. Differently from previous solutions, our objective function maximizes the overall network lifetime (here defined as the time till the first node "dies" because of energy depletion) rather than minimizing the energy consumption at the nodes. For wireless sensor networks with up to 256 nodes our model produces sink movement patterns and sojourn times leading to a network lifetime up to almost five times that obtained with a static sink. Simulation results are performed to determine the distribution of the residual energy at the nodes over time. These results confirm that energy consumption varies with the current sink location, being the nodes more drained those in the proximity of the sink. Furthermore, the proposed solution for computing the sink movement results in a fair balancing of the energy depletion among the network nodes.

A meta-analysis of cognitive deficits in adults with a diagnosis of schizophrenia.

Abstract: This review identified 1275 studies examining cognitive deficits in people with schizophrenia, published between 1990 and 2003. Data from 113 studies (4365 patients and 3429 controls) were combined in a meta-analysis carried out on the five cognitive domains of IQ, memory, language, executive function, and attention. Studies were excluded where they lacked a suitable control group or failed to present complete information. In all five cognitive domains, analysis indicated a consistent trend for patients to perform more poorly than healthy controls, with significant heterogeneity across studies. Sources of heterogeneity were analyzed and a need to ensure more appropriate composition of patient and control groups and to adopt a more refined and methodologically correct, hypothesis-driven approach was identified.

Mitochondrial import and enzymatic activity of PINK1 mutants associated to recessive parkinsonism

Abstract: Parkinson's disease (PD) is a progressive neurodegenerative illness associated with a selective loss of dopaminergic neurons in the nigrostriatal pathway of the brain. Despite the overall rarity of the familial forms of PD, the identification of single genes linked to the disease has yielded crucial insights into possible mechanisms of neurodegeneration. Recently, a putative mitochondrial kinase, PINK1, has been found mutated in an inherited form of parkinsonism. Here, we describe that PINK1 mutations confer different autophosphorylation activity, which is regulated by the C-terminal portion of the protein. We also demonstrate the mitochondrial localization of both wild-type and mutant PINK1 proteins unequivocally and prove that a short N-terminal part of PINK1 is sufficient for its mitochondrial targeting.