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Beta‐secretase 1 (BACE1) is considered as the key enzyme in amyloid‐β formation. Previous works suggest that high BACE1 activity may be present in brain, cerebrospinal fluid and serum of patients with late‐onset Alzheimer's disease (LOAD) as well as mild cognitive impairment (MCI). Therefore, we evaluated whether serum BACE1 activity increases in MCI patients and is associated with the progression from MCI to dementia. BACE1 activity was measured in the serum of 259 MCI patients (162 amnestic—aMCI, 97 non‐amnestic—naMCI) and 204 healthy Controls. After a median follow‐up of 32 months (range: 10–153), 116 MCI progressed to dementia (87 aMCI and 29 naMCI). Serum BACE1 activity was higher in MCI compared with Controls (p < 0.001), and in aMCI with brain atrophy compared with naMCI without brain atrophy (p = 0.04). No difference in BACE1 activity emerged between converter and non‐converter MCI, and this was true for both aMCI and naMCI. However, among aMCI with better cognitive performance (n. 163, MMSE score ≥24/30) those converting to dementia had higher BACE1 activity compared to stable ones (p = 0.05). This was not associated with an increased risk to develop dementia (hazard ratio: 1.65; 95% confidence interval: 0.67–4.01). In conclusion, serum BACE1 activity significantly increased in MCI patients (both amnestic and non‐amnestic) compared with Controls. Moreover, higher serum BACE1 activity was observed only among aMCI with a better cognitive performance who progressed to dementia, suggesting that a dysregulation of this enzyme might be an early event primarily associated with neurodegeneration. [ABSTRACT FROM AUTHOR]

Understanding triggers and evolution of post‐depositional sediment intrusion is of major importance to decrease the risk associated with hazards to infrastructure and environment from events such as submarine landslides and fluid escape. Whereas deep‐sourced intrusions (>1 km) are widely documented, early burial examples are poorly recognized and have been described only in large deltas. Their formation had not yet been documented in deformed foredeeps. Here, we show an exceptionally well‐exposed, early burial mud diapir in the Northern Apennines fold and thrust belt. Disequilibrium compaction and tectonic basin tilt led to lateral pressure migration within shallow (<200 m) sediments. As a result, near‐lithostatic overpressure developed at the basin margin causing sediment intrusion and destabilization of the slope. This work shows that early burial mud diapirs can develop in deformed foredeeps with similar characteristics to their deep‐rooted counterparts, with important implications for hazard assessment in areas non‐traditionally prone to shallow overpressure buildup. Plain Language Summary: Unconsolidated mud can pierce the overlying sediments in a mechanism called mud diapirism. This process is associated with elevated pressure in the subsurface, which can be a relevant hazard for infrastructures and human society. The mud is most commonly sourced at great depth and shallow sourced mud diapirs, defined "early burial," were undocumented outside large river deltas. Here, we describe the first example of early burial mud diapirism in a different geological setting. The overpressure necessary for the mud diapir formation was generated by the lateral transfer of pressure along sedimentary strata. The lateral pressure transfer usually occurs in permeable sandstones, but we infer that here it occurred within low‐permeability sediments. This modality of lateral transfer has not been described before and has potential implications for predicting overpressure in areas not commonly affected by this phenomenon. Key Points: A shallow‐sourced, early‐burial mud diapir is documented in a deformed foredeep slopeRequired overpressure formed via lateral pressure transfer within shallow low‐permeable units, a modality previously undocumentedThe overpressure favored both slope instability and mud intrusion in a mutually related process [ABSTRACT FROM AUTHOR]

Photoprotective properties of Vitis vinifera L. leaves extract on UVA-induced damage in human endothelial cells (EA.hy926 cells) C and D, PBS control of 10 and 15 J/cm2 irradiation, respectively, kept in PBS for the same time of the irradiated samples; E and F, UVA 10 and 15 J/cm2 irradiation, respectively; G and H, VVWE 1 h pre-treatment and UVA 10 and 15 J/cm2 irradiated, respectively. Keywords: DNA damage; transmission electron microscopy; UVA; Vitisvinifera L. EN DNA damage transmission electron microscopy UVA Vitisvinifera L. 171 174 4 03/22/21 20210301 NES 210301 Dear Editor, Ultraviolet radiation of type A (UVA) represents more than 95% of the total UV radiation reaching the Earth's surface. [Extracted from the article]

Protein domains constitute regions of distinct structural properties and molecular functions that are retained when removed from the rest of the protein. However, due to the lack of tertiary structure, the identification of domains has been largely neglected for long (>50 residues) intrinsically disordered regions. Here we present a sequence‐based approach to assess and visualize domain organization in long intrinsically disordered regions based on compositional sequence biases. An online tool to find putative intrinsically disordered domains (IDDomainSpotter) in any protein sequence or sequence alignment using any particular sequence trait is available at http://www.bio.ku.dk/sbinlab/IDDomainSpotter. Using this tool, we have identified a putative domain enriched in hydrophilic and disorder‐promoting residues (Pro, Ser, and Thr) and depleted in positive charges (Arg and Lys) bordering the folded DNA‐binding domains of several transcription factors (p53, GCR, NAC46, MYB28, and MYB29). This domain, from two different MYB transcription factors, was characterized biophysically to determine its properties. Our analyses show the domain to be extended, dynamic and highly disordered. It connects the DNA‐binding domain to other disordered domains and is present and conserved in several transcription factors from different families and domains of life. This example illustrates the potential of IDDomainSpotter to predict, from sequence alone, putative domains of functional interest in otherwise uncharacterized disordered proteins. [ABSTRACT FROM AUTHOR]

Electron microscopy of macromolecular structures is an approach that is in increasing demand in the field of structural biology. The automation of image acquisition has greatly increased the potential throughput of electron microscopy. Here, the focus is on the possibilities in Scipion to implement flexible and robust image‐processing workflows that allow the electron‐microscope operator and the user to monitor the quality of image acquisition, assessing very simple acquisition measures or obtaining a first estimate of the initial volume, or the data resolution and heterogeneity, without any need for programming skills. These workflows can implement intelligent automatic decisions and they can warn the user of possible acquisition failures. These concepts are illustrated by analysis of the well known 2.2 Å resolution β‐galactosidase data set. [ABSTRACT FROM AUTHOR]

Electron microscopy is a valuable tool for elucidating the three-dimensional structures of macromolecular complexes. As the field matures and the number of solved structures increases, the existence of infrastructures that keep this information organized and accessible is crucial. At the same time, standards and clearly described conventions facilitate software maintenance, benefit interoperability with other packages and allow data interchange. This work describes three developments promoting integrative biology, standardization and workflow processing, namely PeppeR, the EMX initiative and Scipion. [ABSTRACT FROM AUTHOR]

Background: Data for time trends in the prevalence of occupational asthma (OA) and rhinitis (OR) are not known. Objective: To investigate the prevalence and incidence of OA and OR over time. Methods: We chose to review studies on the prevalence and incidence of OA and OR due to laboratory animals (LA) as a marker of changing OA and OR patterns over time and analysed 15 cross-sectional and 4 longitudinal studies published from 1980 to 2006. Results: The estimated prevalence of OA, defined as work-related chest symptoms (WRCS), declined from 8.2% in 1976 to 4.2% in 2001 ( P < 0.005). When defined by WRCS and positive skin prick test (SPT) to LA, the estimated prevalence of OA was 6.7% in 1977 and 2.9% in 1999 ( P < 0.02). The prevalence of OR, defined by WRNS or WRNS and SPT to LA, was not related to study date but was inversely associated with mean exposure duration. In four longitudinal studies no clear trend emerged over time. Conclusions: This review suggests a trend toward a progressive decline in the prevalence of occupational asthma due to laboratory animals, which may be due to the reduction of exposure since the early 1980s. A further reduction of exposure is needed to prevent the onset of occupational rhinitis. [ABSTRACT FROM AUTHOR]

Cigarette smoking is a known risk factor for many chronic illnesses such as coronary heart and chronic obstructive pulmonary diseases. Smoking is often described as a risk factor for occupational asthma even though its effect on the development of asthma is still under debate and the links between smoking and occupational asthma, occupational rhinitis or occupational sensitization are elusive, controversial and contradictory. This review describes these relationships in a wide range of occupations, from laboratory, farm, brewery and hospital workers, to bakers, printers, cleaners, fish processors and others as observed in cross-sectional, cohort, and case-control studies published over the past thirty-five years i.e. from 1970 to 2005. Surprisingly, the data show there is little to support the view that the risk of occupational asthma is increased in workers who are smokers. However, evidence emerges of an increased risk of occupational sensitization in smoking workers exposed to several high and low molecular weight agents. This in-depth review confirms the relationship between smoking and occupational asthma is complex and contradictory. It deserves more attention and further studies, which need to be conducted without being influenced by selection bias or by the justifiable prejudice against smoking. [ABSTRACT FROM AUTHOR]

Summary Background Larvae of insects and worms, used as live fish bait (LFB), are a common source of allergy in anglers and occupationally exposed workers, but the prevalence and predictors have not yet been investigated. Objective This study assessed the prevalence and associated factors of occupational allergy in workers exposed to LFB. Methods We assessed the prevalence of sensitization to LFB and work-related symptoms (WRS) in 76 workers occupationally exposed to it. All workers completed a case history questionnaire and underwent skin prick tests (SPT) for common aeroallergens and bluebottle (Calliphora vomitoria ), bee moth (Galleria mellonella ), mealworm (Tenebrio molitor ), and gusano rojo (Cilecomadia moorei ). Specific IgE were tested in 64 subjects. Two-thirds of the workers had a high level of LFB exposure. Results Sensitization to LFB was found in 24 workers (31.6%). Seven subjects (9.2%) reported WRS (asthma in 3, rhinoconjunctivitis in 5, and contact urticaria in 1), and 5 were positive for SPT and serum IgE to one or more LFB extracts. One was also exposed to LFB while fishing. Sensitization to LFB extracts and WRS were strongly associated (Odds Ratio = 6.6, P < 0.05). The 7 subjects with WRS had been exposed longer than asymptomatic subjects with positive skin tests to LFB (P < 0.05). No differences in sex, age, smoking habit, duration or level of exposure, and atopy were detected in symptomatic or in sensitized subjects, compared with normal workers. Conclusion Sensitization to LFB and WRS are relatively frequent in occupationally exposed workers. No associated factors of occupational allergy to LFB could be detected. [ABSTRACT FROM AUTHOR]

Background. The severity of occupational asthma (OA) at the time of diagnosis is not known. In this study we aimed to evaluate some features of the disease at the time of diagnosis, particularly looking at severity and treatment before diagnosis. Methods: Medical records of subjects (n = 197) who had received a diagnosis of OA in six specialized centres of Northern and Central Italy in the period 1992–97 were reviewed. The severity of the disease at the time of diagnosis was determined on the basis of symptoms, peak expiratory flow (PEF, percentage predicted), forced expiratory volume in one second (FEV1 , percentage predicted), and PEF variability, following the criteria of the National Institutes of Health and World Health Organizaton (NIH/WHO) guidelines on asthma. Medications used in the month before diagnosis were recorded. Results: The most common etiological agents were isocyanates (41.6%), flours (19.8%), woods (9.7%) and natural rubber latex (7.6%). The level of asthma severity (AS) was mild intermittent in 23.9% patients, mild persistent in 28.9%, moderate in 41.6%, and severe in 5.6%. Asthma severity was positively associated with current or previous smoking (P < 0.05), and was not related to atopy and current exposure. A relationship with bronchial reactivity to methacholine was shown in subjects at work. Treatment before diagnosis was consistent with the NIH/WHO guidelines in only 13.2% patients, whereas 75.6% were undertreated and 11.2% were overtreated. Conclusions: In this study we found that the majority of patients had mild asthma at the time of diagnosis and that cigarette smoking was associated with a greater severity. Moreover, the majority of patients were undertreated before etiological diagnosis. [ABSTRACT FROM AUTHOR]

Investigates the prevalence, etiology and determinants of occupational rhinitis. Methods for assessing prevalence; Objective methods for evaluating occupational rhinitis; High molecular weight compounds/allergens.

Electron microscopy is a powerful technique for imaging complex biological macromolecules in order to further the understanding of their functions. When combined with sufficiently careful sample preparation procedures that preserve the native structure of the macromolecules and with sophisticated image processing procedures, electron microscopy can lead to very informative estimates of the three-dimensional (3D) structures of the specimens under study. 3D reconstruction from electron microscopic data is achieving high goals and exceeding expectations unthinkable only a few years ago. However, there are still some areas where either not enough work has been invested or the work has not as yet been fruitful. We describe image processing approaches that shed further light on some of these difficult areas. © 2000 John Wiley & Sons, Inc. Int J Imaging Syst Technol, 11, 12–29, 2000 [ABSTRACT FROM AUTHOR]

A detailed structural analysis carried out on the volcanic products of the island of Pantelleria has shown that the large-scale setting is dominated by N-S trending normal faults and NW-SE right-lateral strike-slip faults, while mesostructural data show a more complex pattern which is characterized by four systems of discontinuity. The volcanological features show a marked difference between a north western sector characterized by products of a basaltic nature and a south central one in which evolved products connected with the presence of a magmatic chamber are present. The present-day stress field, as derived from structural analysis, is characterized by a maximum compression oriented NNW-SSE which allowed the activation of right-lateral strike-slip faults bordering the Pantelleria trough giving rise to a thinning of the underlyng crust. Inside this main dextral shear zone it is possible that the development of pull-apart basins bounded by N-S trending normal faults could generate further thinning of the already thinned out crust zone and give rise to the magmatic phenomena known to occur mostly along the N-S trending extension structures. Such a model would therefore help to understand the characters of the volcanism associated with a zone of continental collision as well as its distribution, which is not rigorously in accordance with a classical rifting process. [ABSTRACT FROM AUTHOR]

Chick embryos were treated on day 0 of incubation with two phenoxy herbicides, 2-methyl-4-chlorophenoxyacetic acid (MCPA) (0.4, 2 mg/egg) and 2,4-dichlorophenoxyacetic acid (2, 4-D) (1, 2, 4 mg/egg). Both herbicides seemed to exert toxic effects mainly on the liver of 19-day-old embryos. Specific histological analysis indicated biliary stasis. Ethoxycoumarin O-deethylase was depressed by MCPA but raised by 2, 4-D. Other hepatic monooxygenase activities were unaffected by the herbicides and no significant changes were found in cytochromes. The higher dose of MCPA increased NADPH-cytocrome P450 reductase. 2,4-D treatment increased by activity of glutathione-S-transferases in the hepatic post-microsomal fraction while MCPA increased them at the lower dose and significantly reduced them at the higher. The phenoxyacetic herbicides appear thus to have some effects on hepatic drug metabolizing enzymes of the chick embryo which cannot be easily interpreted. Biliary retention, produced in particular by MCPA, could be partly responsible for these effects. [ABSTRACT FROM AUTHOR]

The effect of a single oral dose of 400 mg fipexide on pituitary secretion was investigated in 10 elderly non-endocrine patients. Fipexide induced significant decrease (P less than 0.05) in serum prolactin (PRL) values at 90 and 120 min after drug administration, without affecting serum growth hormone (GH), gonadotropin (LH and FSH), thyrotropin (TSH) and cortisol values. Fipexide was unable to modify metoclopramide-induced PRL release in five of these patients. Our results show that this drug acts as a mild dopamine (DA) agonist, probably not directly affecting hypothalamic and/or pituitary DA receptors but indirectly via a reduced DA re-uptake at the pre-synaptic level. [ABSTRACT FROM AUTHOR]