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In today's global market, the movement of raw materials and goods in the free global market can lead to unintended consequences. One significant concern is the potential presence of contaminants and carcinogens, particularly when products originate from regions with less strict regulations and enforcement. This issue is particularly pertinent in the natural raw materials utilized in the global building materials market, where contamination by asbestos minerals can occur. Therefore, the screening of natural raw materials for asbestos content is crucial to mitigate the risk of exposure to carcinogens for both workers and the general public. In this study, we examine a challenging case involving a smectite–kaolinite clay from Gomsiqe–Puka, Albania, possibly containing mineral fibres. Detection and quantification of asbestos in this material push the boundaries of current experimental methods. Using transmission electron microscopy (TEM), micro-Raman spectroscopy, and electron probe microanalysis (EPMA), we identified the presence of asbestos tremolite, along with a rare fibrous variety of diopside. EPMA data allowed the advancement of some speculations on the origin of the observed tremolites, showing that Al-rich tremolites are typical of oceanic settings and Al-poor tremolites are more similar to continental tremolites. We also investigated the impact of milling on the detection and quantification of mineral fibres, testing different milling times. This investigation is crucial as it can influence the classification of the raw material as asbestos-containing material or not. Our findings indicate that tremolite, cleavage fragments, and elongated particles break down into smaller World Health Organization (WHO) fibres with increasing milling times (1–5 min). However, prolonged milling (10 min) leads to overgrinding, resulting in a decrease in the number of counted WHO fibres with a length exceeding 5 µm.

Abstract The relationship between rifting and continental flood basalt eruptions is debated, and a control by mantle plume is commonly invoked for flood basalts production. In this work, we investigate the relationship between magmatism and rifting by studying the flood basalts erupted in Afar (4.5–0.6 Ma), known as the Stratoid and Gulf Series. We present new field observations and petrography, major and trace elements analyses and mineral chemistry of lavas collected during a regional campaign in Afar. The Series are characterized by E‐MORB magmatism and residual amphibole in the mantle source, consistent with the contribution of metasomatized sub‐continental lithospheric mantle during partial melting. Differences in garnet‐compatible elements indicate a shallower melting column for the oldest and youngest products (4.5–2.6 Ma Lower Stratoid Series; 1.1–0.6 Ma Gulf Series), and deeper for the products erupted at 2.6–1.1 Ma (Upper Stratoid Series). Incompatible element ratios (Th/Nb, Th/Zr) indicate a higher degree of partial melting for the Gulf with respect to the Upper Stratoid Series. Accordingly with independent geophysical and stratigraphic evidence, we explain our results with rift re‐localization: the Pliocene rift caused thinning of the lithosphere and the Lower Stratoid eruptions in Southern Afar, then the Pleistocene rift jumped to Central Afar under a less‐extended lithosphere, producing the Upper Stratoid and, subsequently, as stretching of the lithosphere localized, the Gulf Series formed. Our findings suggest that rift migration and localization can exert a fundamental control on the spatial variability and character of flood basalts without requiring variations on the activity of the mantle plume.

This data article includes the description and the geochemical and mineralogical dataset of 67 pyroclastic rock samples from the Upper Pumice (UP) explosive activity of Nisyros volcano (eastern South Aegean Active Volcanic Arc). A detailed field and petrographic description of the studied outcrops and samples are reported, including representative photomicrographs and SEM images, whole-rock major and trace elements compositions of 31 representative samples and Sr-Nd isotope ratios on 22 selected samples. Analytical methods and conditions used for data acquisition are also reported.The UP eruption produced a stratigraphic sequence constituted by a basal fallout deposit, gradually substituted by pyroclastic density current (PDC) deposits; these are overlaid by a lag-breccia unit, and the sequence is closed by a grey ash flow level. The juvenile is mainly constituted by white-yellow, moderately crystalline pumice with rhyolitic composition and homogenous Sr-Nd isotope values. Variable amounts of dense, grey, crystalline juvenile lapilli clasts (CRC, Crystal-Rich Clast), with rounded shape and less evolved composition (andesite to dacite) are also present in the deposit. These mafic CRCs are peculiar due to their large variability in textures (from distinctive diktytaxitic to strongly fragmented structure without a defined fabric) and in the geochemical and isotopic composition.The data acquired were fundamental to reconstruct the complex and peculiar history of ascent, storage and differentiation/assimilation processes of these mafic melts before their intrusion into the shallow, rhyolitic magma chamber, with important implication on the possible eruption trigger during the more recent explosive phase of activity at Nisyros volcano. Moreover, the geochemical and isotopic analyses provide new original data to the general knowledge of the Aegean volcanics.All the data reported in this paper are related to the research article Braschi et al. (2022)

Background: Evidence-Based Medicine is built on the premise that clinicians can be more confident when their decisions are grounded in high-quality evidence. Furthermore, evidence from studies involving patient-oriented outcomes is preferred when making decisions about tests or treatments. Ideally, the findings of relevant and valid trials should be stable over time, that is, unlikely to be reversed in subsequent research., Objective: To evaluate the stability of evidence from trials relevant to primary healthcare and to identify study characteristics associated with their reversal., Methods: We studied synopses of randomized controlled trials (RCTs) published from 2002 to 2005 as "Daily POEMs" (Patient Oriented Evidence that Matters). The initial evidence (E1) from these POEMs (2002-2005) was compared with the updated evidence (E2) on that same topic in a summary resource (DynaMed 2019). Two physician-raters independently categorized each POEM-RCT as (i) reversed when E1 ≠ E2, or as (ii) not reversed, when E1 = E2. For all "Evidence Reversals" (E1 ≠ E2), we assessed the direction of change in the evidence., Results: We evaluated 408 POEMs on RCTs. Of those, 35 (9%; 95% confidence interval [6-12]) were identified as reversed, 359 (88%) were identified as not reversed, and 14 (3%) were indeterminate. On average, this represents about 2 evidence reversals per annum for POEMs about RCTs., Conclusions: Over 12-17 years, 9% of RCTs summarized as POEMs are reversed. Information alerting services that apply strict criteria for relevance and validity of clinical information are likely to identify RCTs whose findings are stable over time., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To summarize 10 high-quality studies or guidelines from 2021 that have strong relevance to physicians in comprehensive family practice., Selecting the Evidence: Routine literature surveillance of abstracts in high-impact journals and EvidenceAlerts was completed by the PEER (Patients, Experience, Evidence, Research) team, a group of health care professionals with a research interest in evidence-based medicine and primary care. Abstracts were screened, selected, and ranked by the PEER team., Main Message: The articles from 2021 that are most likely to impact primary care practice discuss the following topics: empagliflozin for heart failure with preserved ejection fraction; semaglutide for weight loss; stopping antidepressants in primary care; inhaled budesonide for COVID-19; acetylsalicylic acid for preeclampsia prevention; quarter-dose blood pressure medications for hypertension; aggressive blood pressure control for elderly patients; kangaroo care for low-birth-weight infants; footwear for knee osteoarthritis; and delayed antibiotics for pediatric respiratory infections. Two "honourable mention" studies are also briefly reviewed., Conclusion: Research from 2021 produced several high-quality studies in cardiovascular care but also addressed a variety of conditions relevant to primary care including weight loss, depression, and COVID-19., (Copyright © 2022 the College of Family Physicians of Canada.)

Aim: To perform a cross-cultural adaptation and validation of the Neurogenic Bladder Symptom Score (NBSS) to Spanish in patients with neurogenic lower urinary tract dysfunction., Materials and Methods: The questionnaire was culturally adapted according to international guidelines. It was applied, twice in a range of 14-28 days. Psychometric properties were tested such as content validity, construct validity, internal consistency, and test-retest reliability., Results: A total of 82 patients between 18 and 78 years old (mean age of 43.9) participated in the study, and completed the first NBSS assessment; only 39 (32.19%) performed the test-retest study. The internal consistency was tested by Cronbach α with a result of 0.86 (95% CI, 0.81-0.90). The reliability was tested by interclass correlation coefficient with a result of 0.91 [0.87-0.95] (p < 0.0001). The construct validity was tested by Pearson correlation between NBSS and Qualiveen-SF, which showed a moderate correlation with a result of 0.57 (p < 0.0001). One-way analysis of variance with trend analysis demonstrated that patients who reported having a more severe problem with their bladder function had a higher NBSS total score (p < 0.001)., Conclusion: The results of this study demonstrated that the Spanish version of the NBSS has a good internal consistency and reliability, proving its applicability., (© 2021 Wiley Periodicals LLC.)

Objective: Early reports have suggested that coronavirus disease 2019 (COVID-19) can present with significant urinary frequency and nocturia, and that these symptoms correlate with markers of inflammation in the urine. We evaluated surrogate markers of chronic urinary symptoms to determine if they were more frequent after COVID-19 infection., Methods: Routinely collected data from the province of Ontario was used to conduct a matched, retrospective cohort study. We identified patients 66 years of age or older who had a positive COVID-19 test between February and May 2020 and survived at least 2 months after their diagnosis. We matched them to two similar patients who did not have a positive COVID-19 test during the same time period. We measured the frequency of urology consultation, cystoscopy, and new prescriptions for overactive bladder medications during a subsequent 3-month period. Proportional hazard models were adjusted for any baseline differences between the groups., Results: We matched 5617 patients with COVID-19 to 11,225 people who did not have COVID-19. The groups were similar, aside from a higher proportion of patients having hypertension and diabetes in the CoVID-19 cohort. There was no significantly increased hazard of new receipt of overactive bladder medication (hazards ratio [HR]: 1.04, p = 0.88), urology consultation (HR: 1.40, p = 0.10), or cystoscopy (HR: 1.14, p = 0.50) among patients who had COVID-19, compared to the matched cohort., Conclusion: Surrogate markers of potential bladder dysfunction were not significantly increased in the 2-5 months after COVID-19 infection., (© 2021 Wiley Periodicals LLC.)

Background: To support student well-being, a mindfulness curriculum in undergraduate medical education was launched at our university in 2014. We describe the program and report 3-year results., Methods: Medical students responded to online questionnaires on mindfulness (Freiburg Mindfulness Inventory), empathy (Jefferson Scale of Physician Empathy), resilience (Connor-Davidson Resilience Scale) and perceived stress (Perceived Stress Scale) and were surveyed for demographics, home practice, and subjective experience at curriculum launch and yearly for 3 years., Results: In respondents, high stress (19.2 (SD=6)) and low resilience (71.2 (SD=12.5)) scores were seen throughout training. Scores for mindfulness correlated positively with those for empathy (r=.217 p < 0.01) and resilience ( r = .539, p < 0.01), and negatively with stress scores ( r = -.380, p < 0.01). While overall scale scores did not statistically change after curriculum implementation, statistically significant increases were seen in mindfulness (12%, p = 0.008), empathy (5%, p = 0.045), and resilience scores (12%, p = 0.002) with a trend toward lower stress scores (8%, p =0.080) in respondents who felt they applied the curriculum principles. Two hours of reported home practice per week was associated with statistically significant changes (14% increased mindfulness scores p < 0.001; 6% increased empathy scores p < 0.001, 10% increased resilience scores p = 0.003; 11% decreased stress scores p = 0.008). Despite positive program evaluations for both mandatory and elective sessions, student attendance at elective sessions was low., Conclusion: A mindfulness curriculum integrated into formal undergraduate medical education is feasible. Benefits may be confined to those students who apply curriculum principles and practice regularly. Further study is needed.Résumé., Contexte: Pour soutenir le bien-être des étudiants, un cursus de méditation pleine conscience dans le cadre du programme de doctorat en médecine a été lancé à notre université en 2014. Nous décrivons le programme et communiquons les résultats après trois ans., Méthodes: Des étudiants en médecine ont répondu à des questionnaires en ligne sur la pleine conscience (inventaire de pleine conscience de Freiburg), l'empathie (Échelle de Jefferson sur l'empathie du médecin), la résilience (échelle de résilience de Connor-Davidson) et le stress perçu (échelle du stress perçu) et ont été interrogés pour les caractéristiques démographiques, la pratique de la méditation pleine conscience à domicile et l'expérience subjective au moment du lancement du cursus et, ensuite, annuellement pendant trois ans., Résultats: Chez les répondants, un degré de stress élevé (19,2 (ET=6)) et une faible résilience (71,2 (ET=12,5)) ont été observés tout au long de la formation. Il y avait une corrélation positive entre les la pleine conscience et l'empathie (r=0,17, p<0,01) et de la résilience (r=0,539, p<0,01), et négative avec le stress (r=-0,380, p<0,01). Alors que les résultats globaux ne changent pas statistiquement après la mise en œuvre du cursus, des augmentations statistiquement significatives ont été observées pour la pleine conscience (12%, p=0,008), l'empathie (5%, p=0,045) et la résilience (12%, p=0,002) avec une tendance vers des résultats inférieurs pour le stress (8%, p=0,080) chez les répondants qui estimaient avoir appliqué les principes du programme. On retrouvait des changements significatifs chez les répondants qui rapportaient avoir pratiqué deux heures par semaine à domicile (résultats accrus de 14% pour la pleine conscience (p<0,001), de 6% pour l'empathie (p<0,001) et de 10% pour la résilience (p= 0,003), et réduits de 11% pour le stress (p=0,008)). Malgré des évaluations de programme positives pour les sessions obligatoires et optionnelles, l'assiduité des étudiants aux sessions optionnelles était faible., Conclusion: Un cursus de méditation pleine conscience intégré dans des études formelles de doctorat en médecine est faisable. Les avantages peuvent être confinés aux étudiants qui appliquent les principes du programme et qui le pratiquent sur une base régulière. D'autres études sont requises., Competing Interests: Conflicts of interest: Dr. MacLean participates in numerous sponsored clinical trials in multiple sclerosis (Bayer, Biogen, Genzyme, Immune Tolerance Network, Novartis, Opexa, Roche, Sanofi-Aventis). Dr. MacLean also wrote and published the Apple iBook, “Mindfulness for Medical School, Residency and Beyond”, which is used as a course guide for our mindfulness curriculum described and referenced in this manuscript. It is available through Apple iBooks as a free download so that students etc. can access it freely. She receives no royalties from the iBook. Drs. MacLean, Gonsalves and Sanchez have received honorariums for delivering educational workshops on mindfulness at local and national venues. Dr. Diana Koszycki has received research grants from the Canadian Institute of Health Research, the Ontario Mental Health Foundation, and the Canadian Medical Association., (© 2020 MacLean, Braschi, Archibald, Sanchez-Campos, Jebanesan, Koszycki, Gonsalves ; licensee Synergies Partners.)

Introduction: Medical education should portray evidence-based medicine (EBM) and shared decision making (SDM) as central to patient care. However, misconceptions regarding EBM and SDM are common in clinical practice, and these biases might unintentionally be transmitted to medical trainees through a hidden curriculum. The current study explores how assumptions of EBM and SDM can be hidden in formal curriculum material such as PowerPoint slides., Methods: We conducted a qualitative content analysis using a purposive sample of 18 PowerPoints on the management of upper respiratory tract infections. We identified concepts pertaining to decision making using theory-driven codes taken from the fields of EBM and SDM. We then re-analyzed the coded text using a constructivist latent thematic approach to develop a rich description of conceptualizations of decision making in relation to EBM and SDM frameworks., Results: PowerPoint slides can relay a hidden curriculum, which can normalize: pathophysiological reasoning, unexplained variations in clinical care, the use of EBM mimics, defensive medicine, an unrealistic portrayal of benefits, and paternalism., Discussion: Addressing the hidden curriculum in formal curricular material should be explored as a novel strategy to foster a positive attitude towards EBM and SDM and to improve patient outcomes by encouraging the use of these skills.

Competing Interests: Competing interests: None declared.

In this paper we report an experimental study to assess the process of Sr-isotope uptake from the soil and its transfer to the grapevine and then to the wine made through micro-vinification. The experimental work has been carried out with a deep control of the boundary conditions (i.e., type of soil, geologic substratum, ground water supply, etc.) on 11 selected vine-plant sites over a period of four harvest years. Sr-isotopes have been determined on grape-bunches, grapevine sap, on the bioavailable fraction of the soil, on bulk soil, and on the rocks of the substratum. No significant Sr-isotope variability has been observed among micro-vinifications from different harvest years. A slight but significant Sr-isotope variability occurred among wines from rows embedded on different soil type. The Sr-isotope data on micro-vinifications well match those of grapevine sap and bioavailable fraction of soils, all of them falling well within the whole geological range of the bedrock, despite an evident decoupling between bioavailable fraction, whole soils and bedrocks does exist. This decoupling has been ascribed to differential geochemical behaviour of minerals in response to pedogenetic processes. The findings of our experiments indicate that the biological activity of the vine is not able to change the original 87 Sr/ 86 Sr composition up-taken from the bio-available fraction of the soil. Thus, the 87 Sr/ 86 Sr of the wine is an unadulterated feature of the terroir., (Copyright © 2018 Elsevier B.V. All rights reserved.)

An analytical protocol for high-precision, in situ microscale isotopic investigations is presented here, which combines the use of a high-performing mechanical microsampling device and high-precision TIMS measurements on micro-Sr samples, allowing for excellent results both in accuracy and precision. The present paper is a detailed methodological description of the whole analytical procedure from sampling to elemental purification and Sr-isotope measurements. The method offers the potential to attain isotope data at the microscale on a wide range of solid materials with the use of minimally invasive sampling. In addition, we present three significant case studies for geological and life sciences, as examples of the various applications of microscale 87 Sr/ 86 Sr isotope ratios, concerning (i) the pre-eruptive mechanisms triggering recent eruptions at Nisyros volcano (Greece), (ii) the dynamics involved with the initial magma ascent during Eyjafjallajökull volcano's (Iceland) 2010 eruption, which are usually related to the precursory signals of the eruption, and (iii) the environmental context of a MIS 3 cave bear, Ursus spelaeus . The studied cases show the robustness of the methods, which can be also be applied in other areas, such as cultural heritage, archaeology, petrology, and forensic sciences.

This data article describes the soils characterisation, bedrock geochemical composition and descriptive statistics of 87 Sr/ 86 Sr in wines, grape saps, labile fractions of soils (bio-available), whole soils, and bedrocks used to explore the Sr isotope conservation from rocks and soils to vine and wine. These data also describe the reproducibility of the isotopic composition of wine over four harvest years (2008-2011) on 11 selected experimental parcels (sampling point). The data reported in this paper are related to the research article (Braschi et al., 2018) [1].

Background: While journals and reporting guidelines recommend the presentation of confidence intervals, many authors adhere strictly to statistically significant testing. Our objective was to determine what proportions of not statistically significant (NSS) cardiovascular trials include potentially clinically meaningful effects in primary outcomes and if these are associated with authors' conclusions., Methods: Cardiovascular studies published in six high-impact journals between 1 January 2010 and 31 December 2014 were identified via PubMed. Two independent reviewers selected trials with major adverse cardiovascular events (stroke, myocardial infarction, or cardiovascular death) as primary outcomes and extracted data on trial characteristics, quality, and primary outcome. Potentially clinically meaningful effects were defined broadly as a relative risk point estimate ≤0.94 (based on the effects of ezetimibe) and/or a lower confidence interval ≤0.75 (based on the effects of statins)., Results: We identified 127 randomized trial comparisons from 3200 articles. The primary outcomes were statistically significant (SS) favoring treatment in 21% (27/127), NSS in 72% (92/127), and SS favoring control in 6% (8/127). In 61% of NSS trials (56/92), the point estimate and/or lower confidence interval included potentially meaningful effects. Both point estimate and confidence interval included potentially meaningful effects in 67% of trials (12/18) in which authors' concluded that treatment was superior, in 28% (16/58) with a neutral conclusion, and in 6% (1/16) in which authors' concluded that control was superior. In a sensitivity analysis, 26% of NSS trials would include potential meaningful effects with relative risk thresholds of point estimate ≤0.85 and/or a lower confidence interval ≤0.65., Conclusions: Point estimates and/or confidence intervals included potentially clinically meaningful effects in up to 61% of NSS cardiovascular trials. Authors' conclusions often reflect potentially meaningful results of NSS cardiovascular trials. Given the frequency of potentially clinical meaningful effects in NSS trials, authors should be encouraged to continue to look beyond significance testing to a broader interpretation of trial results.

Constraining the timescales of pre-eruptive magmatic processes in active volcanic systems is paramount to understand magma chamber dynamics and the triggers for volcanic eruptions. Temporal information of magmatic processes is locked within the chemical zoning profiles of crystals but can be accessed by means of elemental diffusion chronometry. Mineral compositional zoning testifies to the occurrence of substantial temperature differences within magma chambers, which often bias the estimated timescales in the case of multi-stage zoned minerals. Here we propose a new Non-Isothermal Diffusion Incremental Step model to take into account the non-isothermal nature of pre-eruptive processes, deconstructing the main core-rim diffusion profiles of multi-zoned crystals into different isothermal steps. The Non-Isothermal Diffusion Incremental Step model represents a significant improvement in the reconstruction of crystal lifetime histories. Unravelling stepwise timescales at contrasting temperatures provides a novel approach to constraining pre-eruptive magmatic processes and greatly increases our understanding of magma chamber dynamics.

(87)Sr/(86)Sr has been determined in wines, musts grape juices, soils and rocks from six selected vineyards of 'Cesanese' wine area. Cesanese is a monocultivar wine from a small region characterised by different geologic substrata, a key locality to test the influence of both substratum and winemaking procedure on the (87)Sr/(86)Sr of wines. Experimental work has been performed on wines from different vintage years to check possible seasonal variations. The data reveal that (87)Sr/(86)Sr does not change through time, to validate the selection of wineries performed, and in addition no isotopic variations are observed during winemaking. Indeed, no significant isotopic variations have been observed in musts and wines. These findings reinforce the hypothesis that the isotopic signature of wines is strongly related to the bioavailable fraction of the soil rather than to its bulk. The data corroborate the possibility that Sr-isotopes of high-quality wines can be used as a reliable tool for fingerprinting wine geographic provenance., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Introduction: The neurogenic urinary bladder has been known for at least 30 years now and the concepts behind it are continuously evolving, but there is actually not much work that has been done to accumulate solid clinical evidence in this field. We review the surgical and experimental techniques used in the management of this condition., Material and Methods: TO ACHIEVE OUR GOAL, WE PERFORMED INTERNET SEARCHES USING THE SAME SEARCH STRING: Urinary bladder, neurogenic. In each case, the search was limited to clinical trial, subjects were human and the language was English. After duplicate removal, we obtained a final number of 580 papers. Data was extracted from each paper into a database file and was analyzed separately for adult and pediatric populations., Results: A total of 70 full text papers were reviewed and analyzed according to the previously mentioned algorithm. The first prospective, randomized surgical trials were published less than 20 years ago, starting with 1994, and the number of papers published each year since then has remained in the range of 1-3. The oldest prospective clinical trial for this indication dates back to 1975. The total number of patients included in surgical trials is 3453, out of which 59% are males. The papers include a total of 369 children (21.2%), essentially looking at all the techniques that are also used in adults., Conclusions: There is still a lot of work to be done in order to obtain a significant level of evidence in the field of surgical procedures used in neurogenic bladder patients.

Introduction: The neurogenic urinary bladder is defined as a dysfunctional bladder associated with a known neurological injury. We review the data from good quality clinical trials looking at drug therapy for the neurogenic bladder., Materials and Methods: IN ORDER TO IDENTIFY AS MANY PROSPECTIVE TRIALS AS POSSIBLE, WE PERFORMED INTERNET SEARCHES, USING THE SAME SEARCH STRING: Urinary Bladder, neurogenic (MESH). In each case, the search was limited to clinical trial, prospective trial, subjects were human and the language was English. There was no year limit for our search. The next step was duplicate removal, which led to a final number of 580 papers. We defined clear inclusion criteria for the papers., Results: A total of 82 full text papers were reviewed and analyzed according to the previously mentioned algorithm. The oldest two prospective clinical trials date back to 1976, with an obvious increase in number of trials each year, reaching more than five trials per year after 2001, which demonstrates increased interest toward the subject. The total number of patients included in the trials is 3904, 888 of which are children. The male: female ratio is close to 1, although there were 9 studies where no information regarding the sex of the patients was available., Conclusions: Our analysis stresses the acute need for good quality trials looking at the drugs used for the management of the patients with neurogenic bladders, with adequate statistical power to support the data they present.

The radiogenic isotopic compositions of inorganic heavy elements such as Sr, Nd, and Pb of the food chain may constitute a reliable geographic fingerprint, their isotopic ratios being inherited by the geological substratum of the territory of production. The Sr isotope composition of geomaterials (i.e., rocks and soils) is largely variable, and it depends upon the age of the rocks and their nature (e.g., genesis, composition). In this study we developed a high-precision analytical procedure for determining Sr isotopes in wines at comparable uncertainty levels of geological data. With the aim of verifying the possibility of using Sr isotope in wine as a reliable tracer for geographic provenance, we performed Sr isotope analyses of 45 bottled wines from four different geographical localities of the Italian peninsula. Their Sr isotope composition has been compared with that of rocks from the substrata (i.e., rocks) of their vineyards. In addition wines from the same winemaker but different vintage years have been analyzed to verify the constancy with time of the (87)Sr/(86)Sr. Sr isotope compositions have been determined by solid source thermal ionization mass spectrometry following purification of Sr in a clean laboratory. (87)Sr/(86)Sr of the analyzed wines is correlated with the isotopic values of the geological substratum of the vineyards, showing little or no variation within the same vineyard and among different vintages. Large (87)Sr/(86)Sr variation is observed among wines from the different geographical areas, reinforcing the link with the geological substratum of the production territory. This makes Sr isotopes a robust geochemical tool for tracing the geographic authenticity and provenance of wine.

Mitochondrial respiration relies on electron transport, an essential yet dangerous process in that it leads to the generation of reactive oxygen species (ROS). ROS can be neutralized within the mitochondria through enzymatic activity, yet the mechanism for steady-state removal of oxidized mitochondrial protein complexes and lipids is not well understood. We have previously characterized vesicular profiles budding from the mitochondria that carry selected cargo. At least one population of these mitochondria-derived vesicles (MDVs) targets the peroxisomes; however, the fate of the majority of MDVs was unclear. Here, we demonstrate that MDVs carry selected cargo to the lysosomes. Using a combination of confocal and electron microscopy, we observe MDVs in steady state and demonstrate that they are stimulated as an early response to oxidative stress, the extent of which is determined by the respiratory status of the mitochondria. Delivery to the lysosomes does not require mitochondrial depolarization and is independent of ATG5 and LC3, suggesting that vesicle delivery complements mitophagy. Consistent with this, ultrastructural analysis of MDV formation revealed Tom20-positive structures within the vesicles of multivesicular bodies. These data characterize a novel vesicle transport route between the mitochondria and lysosomes, providing insights into the basic mechanisms of mitochondrial quality control., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

As endosymbionts, the mitochondria are unique among organelles. This review provides insights into mitochondrial behavior and introduces the idea of a unified collective, an interconnected reticulum reminiscent of the Borg, a fictional humanoid species from the Star Trek television series whereby decisions are made within their network (or "hive"), linked to signaling cascades that coordinate the cross-talk between mitochondrial and cellular processes ("subspace domain"). Similarly, mitochondrial dynamics are determined by two distinct processes, namely the local regulation of fission/fusion and the global control of their behavior through cellular signaling pathways. Indeed, decisions within the hive provide each mitochondrial unit with autonomous control of their own degradation, whereby mitochondrial fusion is inactivated and they become substrates for autophagy. Decisions within the subspace domain couple signaling pathways involved in the functional integration of mitochondria with complex cellular transitions, including developmental cues, mitosis, and apoptosis., (Copyright © 2010 WILEY Periodicals, Inc.)

Mitochondria-derived vesicles (MDVs) have been shown to transport cargo from the mitochondria to the peroxisomes. Mitochondria and peroxisomes share common functions in the oxidation of fatty acids and the reduction of damaging peroxides. Their biogenesis is also linked through both the activation of master transcription factors such as PGC-1alpha and the common use of fission machinery, including DRP1, Mff, and hFis1. We have previously shown that MDVs are formed independently of the known mitochondrial fission GTPase Drp1 and are enriched for a mitochondrial small ubiquitin-like modifier (SUMO) E3 ligase called MAPL (mitochondrial-anchored protein ligase). Here, we demonstrate that the retromer complex, a known component of vesicle transport from the endosome to the Golgi apparatus, regulates the transport of MAPL from mitochondria to peroxisomes. An unbiased screen shows that Vps35 and Vps26 are found in complex with MAPL, and confocal imaging reveals Vps35 recruitment to mitochondrial vesicles. Silencing of Vps35 or Vps26A leads to a significant reduction in the delivery of MAPL to peroxisomes, placing the retromer within a novel intracellular trafficking route and providing insight into the formation of MAPL-positive MDVs., (2010 Elsevier Ltd. All rights reserved.)

The modification of proteins by the small ubiquitin-like modifier (SUMO) is known to regulate an increasing array of cellular processes. SUMOylation of the mitochondrial fission GTPase dynamin-related protein 1 (DRP1) stimulates mitochondrial fission, suggesting that SUMOylation has an important function in mitochondrial dynamics. The conjugation of SUMO to its substrates requires a regulatory SUMO E3 ligase; however, so far, none has been functionally associated with the mitochondria. By using biochemical assays, overexpression and RNA interference experiments, we characterized the mitochondrial-anchored protein ligase (MAPL) as the first mitochondrial-anchored SUMO E3 ligase. Furthermore, we show that DRP1 is a substrate for MAPL, providing a direct link between MAPL and the fission machinery. Importantly, the large number of unidentified mitochondrial SUMO targets suggests a global role for SUMOylation in mitochondrial function, placing MAPL as a crucial component in the regulation of multiple conjugation events.

The mechanisms that ensure an equal inheritance of cellular organelles during mitosis are an important area of study in cell biology. For the mitochondria fragment during mitosis, however, the cellular links that signal these changes are largely unknown. We recently identified a SUMO protease, SenP5, that deSUMOylates a number of mitochondrial targets, including the dynamin-related fission GTPase, DRP1. In interphase, SenP5 resides primarily within the nucleoli, in addition to a cytosolic pool. Here we report the relocalization of SenP5 from the nucleoli to the mitochondrial surface at G2/M transition prior to nuclear envelope breakdown. The recruitment of SenP5 results in a significant loss in mitochondrial SUMOylation, and a concomitant increase in the labile pool of DRP1 that drives mitochondrial fragmentation. Importantly, silencing of SenP5 leads to an arrest in the cell cycle precisely at the time when the protease is translocated to the mitochondria. These data indicate that transition of SenP5 to the mitochondria plays an important role in mitochondrial fragmentation during mitosis. The altered intracellular localization of SenP5 represents the first example of the mitochondrial recruitment of a SUMO protease and provides new insights into the mechanisms of interorganellar communication during the cell cycle.

Mitochondria and peroxisomes share a number of common biochemical processes, including the beta oxidation of fatty acids and the scavenging of peroxides. Here, we identify a new outer-membrane mitochondria-anchored protein ligase (MAPL) containing a really interesting new gene (RING)-finger domain. Overexpression of MAPL leads to mitochondrial fragmentation, indicating a regulatory function controlling mitochondrial morphology. In addition, confocal- and electron-microscopy studies of MAPL-YFP led to the observation that MAPL is also incorporated within unique, DRP1-independent, 70-100 nm diameter mitochondria-derived vesicles (MDVs). Importantly, vesicles containing MAPL exclude another outer-membrane marker, TOM20, and vesicles containing TOM20 exclude MAPL, indicating that MDVs selectively incorporate their cargo. We further demonstrate that MAPL-containing vesicles fuse with a subset of peroxisomes, marking the first evidence for a direct relationship between these two functionally related organelles. In contrast, a distinct vesicle population labeled with TOM20 does not fuse with peroxisomes, indicating that the incorporation of specific cargo is a primary determinant of MDV fate. These data are the first to identify MAPL, describe and characterize MDVs, and define a new intracellular transport route between mitochondria and peroxisomes.