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The Mecsek Mountains in SW Hungary represent an uplifted basement block of the Pannonian Basin. Their Neogene cover includes deposits both from the Middle Miocene Central Paratethys and from its Late Miocene (Pannonian) brackish‐water descendant, Lake Pannon. Along the mountain front, the Pannonian sands of the Pécsvárad sand pit contain a mixed vertebrate fossil assemblage, which gives insight into terrestrial and aquatic biota during various time intervals of the Miocene. The fossil‐bearing sands accumulated between 7.6–6.8 Ma, in a high‐energy littoral setting of Lake Pannon, as indicated by the mollusc remains. The verte brate fossil assemblage is relatively diverse compared to the number of finds. The most abundant group, aquatic mammals, encompasses a minimum of four odontocete species and a few mysticete taxa, which originally lived in the Para tethys during the Badenian and the Sarmatian. Rhinocerotid remains are reworked from sediments aged somewhere between the Karpatian and earliest Pannonian. The single shark tooth must be Badenian, and the scombrid fishes probably also date back to that age. Fossils of other fishes (sparids, latids and acipenserids), giant salamanders, turtles, crocodilians and cervids might originate from older Miocene deposits but can be coeval with the host sands as well. Tapirs and giraffids must have lived on the lakeshores of Lake Pannon, probably contemporaneously with sand deposition or not much earlier. The erosion, enrichment and mixing of the fauna is a result of the uplift and denudation of the Mecsek Mountains during Lake Pannon sedimentation, caused by neotectonic basin inversion. This example shows that in spite of the uncertainties in the dating of some fossils, mixed faunas can provide important data on the evolution history of an area.

Laskarev’s seminal contribution to the recognition and elucidation of the Paratethys Sea within geological discourse stands as one of the pivotal milestones in our understanding of Neogene European paleogeography. Although the Neogene marine deposits of central and southeastern Europe were known before him, he greatly facilitated discourse and communication about them by giving them a paleogeographical name. By officially introducing the term Paratethys and meticulously delineating its geographic extent and history, Laskarev unveiled profound insights into past climates, environments, and biotic evolution across Central and Eastern Europe. His work provided a solid foundation for subsequent investigations of the Paratethys region. Moreover, beyond its scientific intrigue, the Paratethys Sea holds considerable economic importance due to its rich geo logical endowment. This reservoir of resources includes hydrocarbon reserves, mineral deposits, and a burgeoning potential for geotourism. While substantial strides have been made in unraveling its mysteries, the Paratethys Sea still beckons further exploration, promising untapped realms of knowledge and economic opportunity.

Medium chain fatty acids are candidates of partial sulphur dioxide replacement in wine, as a solution to the growing consumer concerns about chemical additives. In botrytised sweet wine specialties, large amount of sulphur dioxide addition is one of the effective practices to stop alcoholic fermentation. Increasing medium chain fatty acid levels up to 80 mg l-1 was tested as a sole inhibitor on solid agar surface. S. bacillaris seemed to be the most sensitive, S. cerevsisiae and S. bayanus were more tolerant, while Z. bailii showed the highest tolerance. Then, increasing medium chain fatty acid levels up to 40 mg l-1 combined with 100 mg l-1 sulphur dioxide was introduced into a Tokaj Essence under refermentation. After 56 days, the highest dosage had pronounced effect on the yeast population, but the refermentation was not inhibited completely. Medium chain fatty acids have varying inhibitory effect on botrytised wine-related yeasts, moreover, it could be used effectively in media with high ethanol content, unlike Tokaj Essence. [ABSTRACT FROM AUTHOR]

Stratigraphic subdivision of the Upper Miocene deposits in the Pannonian Basin has been traditionally based on the endemic mollusc species of Lake Pannon. The cockle species Lymnocardium soproniense Vitális, apparently evolving through a sympatric speciation event in the sublittoral zone of Lake Pannon about 10.2-10.3 Ma, attained wide geographical distribution in the Pannonian basin and thus may serve as a good stratigraphic marker. Lymnocardium soproniense was one of the few large-sized cockles in Lake Pannon, most closely related to its ancestor, L. schedelianum (Fuchs), and to another descendant of the latter, L. variocostatum Vitális. According to the δ18O stable isotope record of its shells, the large size of L. soproniense was coupled with an extended life time of more than 10 years, probably reflecting a stable lake environment with increased resource availability and decreased predation. The species lived in quiet offshore conditions, below the storm wave base, where clay was deposited from suspension and the influence of currents was negligible. The base of the Lymnocardium soproniense Zone in the sublittoral deposits of Lake Pannon is defined by the first occurrence of the species, whereas the top of the zone is marked with the base of the overlying Congeria praerhomboidea Zone, defined by the FAD of C. praerhomboidea.

The Danube / Kisalföld Basin is the north-western sub-basin of the Pannonian Basin System. The lithostratigraphic subdivision of the several-km-thick Upper Miocene to Pliocene sedimentary succession related to Lake Pannon has been developed independently in Slovakia and Hungary. A study of the sedimentary formations across the entire basin led us to claim that these formations are identical or similar between the two basin parts to such an extent that their correlation is indeed a matter of nomenclature only. Nemčiňany corresponds to the Kálla Formation, representing locally derived coarse clastics along the basin margins (11- 9.5 Ma). The deep lacustrine sediments are collectively designated the Ivanka Formation in Slovakia, while in Hungary they are subdivided into Szák (fine-grained transgressive deposits above basement highs, 10.5 - 8.9 Ma), Endrőd (deep lacustrine marls, 11.6 -10 Ma), Szolnok (turbidites, 10.5 - 9.2 Ma) and Algyő Formations (fine-grained slope deposits, 10 - 9 Ma). The Beladice Formation represents shallow lacustrine deltaic deposits, fully corresponding to Újfalu (10.5 - 8.7 Ma). The overlying fluvial deposits are the Volkovce and Zagyva Formations (10 - 6 Ma). The synoptic description and characterization of these sediments offer a basin-wide insight into the development of the basin during the Late Miocene. The turbidite systems, the slope, the overlying deltaic and fluvial systems are all genetically related and are coeval at any time slice after the regression of Lake Pannon initiated about 10 Ma ago. All these formations get younger towards the S, SE as the progradation of the shelf-slope went on. The basin got filled up to lake level by 8.7 Ma, since then fluvial deposition dominated.

Although the rhinoceros remains have high biochronological significance, they are poorly known or scarcely documented in the uppermost Miocene deposits of Europe. Several specimens collected from the Upper Miocene (around 7.0 Ma, Turolian) deposits of Kávás (Pannonian Basin, Western Hungary), previously determined as Rhinoceros sp., are revised and described in this paper. The postcranial remains of these specimens belong to “Dihoplus” megarhinus (de Christol) on the basis of the morphological and morphometric characters of humerus, radii, metacarpal and metatarsal elements. An overview of rhinoceros remains from several uppermost Miocene localities and the revision of the rhinoceros material from the Pannonian Basin suggest that “D.” megarhinus spread during the latest Miocene from the Pannonian Basin towards Italy. The occurrences of this species in Western Hungary and Italy during the latest Miocene further imply that Rhinocerotini species were biogeographically segregated between Western, Southern and Central Europe.

The floor of Lake Pannon covering the Pannonian Basin in the Late Miocene had considerable relief, including both deep sub-basins, like the Drava Basin, and basement highs, like the Mecsek Mts, in close proximity. The several km thick lacustrine succession in the Drava Basin includes profundal marls, basin-center turbidites, overlain by shales of basin-margin slopes, coarsening-upward deltaic successions and alluvial deposits. Along the margin of the Mecsek Mts locally derived shoreface sands and deltaic deposits from further away have been mapped so far on the surface. Recent field studies at the transition between the two areas revealed a succession that does not fit into either of these environments. A series of sandstone a few meters thick occurs above laminated to bioturbated clayey siltstone. The sandstone show normal grading, plane lamination, flat erosional surfaces, soft-sediment deformations (load and water-escape structures) and sharp-based beds with small reverse faults and folds. These indicate rapid deposition from turbidity currents and their deformation as slumps on an inclined surface. These beds are far too thick and may reveal much larger volumes of mass wasting than is expected on the 20–30 m high delta slopes; however, regional seismic lines also exclude outcropping of deep-basin turbidites. We suggest that slopes with transitional size (less than 100 m high) may have developed on the flank of the Mecsek as a consequence of lake-level rise. Although these slopes were smaller than the usually several hundred meter high clinoforms in the deep basins, they could still provide large enough inertia for gravity flows. This interpretation is supported by the occurrence of sublittoral mollusc assemblages in the vicinity, indicating several tens of meters of water depth. Fossils suggest that sedimentation in this area started about 8 Ma ago.

An overview of Pál Müller's 40-year palaeontological career is presented, inclusive of all decapod crustacean genera and species he erected, as well as those named after him, plus a complete listing of all papers devoted to axiideans, gebiideans, anomurans and brachyurans (co-)authored by Pál between 1974 and 2012. [ABSTRACT FROM AUTHOR]

Understanding the underlying reasons for phenotypic plasticity and resulting morphological disparity is one of the key topics of evolutionary research. The phenotypic plasticity of extant and fossil melanopsids has been widely documented. Yet millennial-resolution, well-dated records from small aquatic habitats harboring endemics are scarce. The thermal spring-fed Lake Pețea is an ice age refugia harboring a unique endemic warm-water fauna. Subfossil melanopsids display incredible morphological variability from smooth to keeled, elongated to ribbed, shouldered forms. Numerous morphotypes have been considered as individual taxa with a fluent succession from the smooth elongated to the ribbed, shouldered types. This study presents an extensive morphometric analysis of subfossil melanopsids (ca. 3500 specimens) derived from stratified samples with an independent chronology. The aim was to separate morphotypes for investigations of temporal morphological disparity. Our results challenge the widely accepted hypothesis that proposes the evolution of shouldered, compressed, ribbed shells through a two-step process from smooth elongated spindle-shaped shells. Instead, it suggests that the subfossil shells belong to two distinct taxa present throughout the available stratigraphic data. The main components of shape variation, shape globularity, and shell coiling seem allometry-related. Ribs, striation, and keels appear randomly. High-spired spindle-shaped forms were considered to represent specimens of Microcolpia daudebartii hazayi. Bulkier low-spired and shouldered specimens represent phenotypes of Mi. parreyssii parreyssii. The collective and random distribution of morphotypes from the early stages of the lake's history also refutes the idea of a continuous transformation of the elongated forms into compressed, shouldered ones. Rather points to multiple events and environmental stimuli triggering development. Melanopsids appear in Late Glacial horizons, with Theodoxus prevostianus preferring temperatures above 23°C which may indicate the subordinate presence of hot water microhabitats in cooler waters., (© 2024 Wiley Periodicals LLC.)

Environmental operators perform their activities in accordance with the relevant legal provisions; however, this does not mean that they operate at their technological optima using the operational information available. The possible negative effects (odor, noise, etc.) of a sub-optimal operation can be felt first and foremost by those living in the immediate vicinity of the given object. It would be important to make effective use of these citizens feedback (quickly to revealing the root causes) thus minimize negative environmental impact of operations. The solution proposed in this paper is a portal called EnviroMind, which allows citizens feedback to be recorded in an easy, immediate, and structured way via a form and on the other hand, it provides a real-time graphical odor transmission model output in a dashboard to operators. Using this portal as a monitoring system the magnitude of the odor effect could be reduced and a smaller area around the industrial object could be affected. In a landfill monitoring pilot project where this monitoring system was used the decrease in the number of indicated odor observations was 85% and the decrease in maximal distance from landfill to odor detection positions was 45%. It is proposed to use EnviroMind monitoring system for all industrial objects which have a significant odor effect on the environment, because by using it we can make the odor effect visible to operators in real time, thus, the reaction time for solving the problem can be minimized. Implications : monitoring is available online to the surrounding community, the affected population, so that quick responses and interventions are available; in the knowledge of the current technological activity carried out on the site its expected odor effect in the area can be determined, whether a protected area can be reached and what odor concentration is expected; in every 15 minutes model results to accurately track expected odor emission values; possibility of intervention, stopping or modification of the technology steps. Experience and main achievements of portal operation in a landfill monitoring pilot project from recent 3 years: the decreasing number of odor perceptions (the decrease in the number of indicated observations was 85%) and the cessation of odor effects in certain areas (and the decrease in maximal distance from landfill to odor detection positions was 45%).

Cardiofaciocutaneous (CFC) syndrome [Online Mendelian Inheritance in Man (OMIM) #115150] is characterized by craniofacial dysmorphism, heart malformation, ectodermal abnormalities, neuromotor delay and intellectual disability. It is not a frequent disease, about 300 cases have been reported in the medical literature. We describe the case of a 34-year-old patient presenting with CFC syndrome phenotype, monitored since the age of 1 1∕2 years. Clinical findings included craniofacial dysmorphism, development delay, heart malformation and severe intellectual disability. The evolution was with progressive intellectual disability, hypogonadism, hypertrophic cardiomyopathy, wrinkled palms and soles. Molecular analysis showed a heterozygous variant in the B-Raf proto-oncogene, serine∕threonine kinase (BRAF) gene (7q34): NM_001354609.2:c.1502A>G, with pathogenic significance. We report this case, observed along a period of 33 years, for illustration of clinical evolutive particularities, and for difficulties in establishing the positive diagnosis.

Congenital cataracts are the prime cause for irreversible blindness in children. The global incidence of congenital cataract is 2.2-13.6 per 10,000 births, with the highest prevalence in Asia. Nearly half of the congenital cataracts are of familial nature, with a predominant autosomal dominant pattern of inheritance. Over 38 of the 45 mapped loci for isolated congenital or infantile cataracts have been associated with a mutation in a specific gene. The clinical and genetic heterogeneity of congenital cataracts makes the molecular diagnosis a bit of a complicated task. Hence, whole exome sequencing (WES) was utilized to concurrently screen all known cataract genes and to examine novel candidate factors for a disease-causing mutation in probands from 11 pedigrees affected with familial congenital cataracts. Analysis of the WES data for known cataract genes identified causative mutations in six pedigrees (55%) in PAX6, FYCO1 (two variants) , EPHA2 , P3H2, TDRD7 and an additional likely causative mutation in a novel gene NCOA6 , which represents the first dominant mutation in this gene. This study identifies a novel cataract gene not yet linked to human disease. NCOA6 is a transcriptional coactivator that interacts with nuclear hormone receptors to enhance their transcriptional activator function.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited., Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19., Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020., Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108)., Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%)., Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively., Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions., Trial Registration: ClinicalTrials.gov Identifier: NCT02735707.

When we discuss the genetics of tumors, we cannot fail to remember that in the second decade of the twentieth century, more precisely in 1914, Theodore Boveri defined for the first time the chromosomal bases of cancer. In the last 30 years, progresses in genetics have only confirmed Boveri's remarkable predictions made more than 80 years ago. Before the cloning of the retinoblastoma 1 (RB1) gene, the existence of a genetic component in most, if not all, solid childhood tumors were well known. The existence of familial tumor aggregations has been found much more frequently than researchers expected to find at random. Sometimes, the demonstration of this family predisposition was very difficult, because the survival of children diagnosed as having a certain tumor, up to an age at which reproduction and procreation is possible, was very rare. In recent years, advances in the diagnosis and treatment of these diseases have made it possible for these children to survive until the age when they were able to start their own families, including the ability to procreate. Four distinct groups of so-called cancer genes have been identified: oncogenes, which promote tumor cell proliferation; tumor suppressor genes, which inhibit this growth/proliferation; anti-mutational genes, with a role in deoxyribonucleic acid (DNA) stability; and micro-ribonucleic acid (miRNA) genes, with a role in the posttranscriptional process.

Background: Equisetum arvense L., commonly known as field horsetail is a perennial fern of which extracts are rich sources of phenolic compounds, flavonoids, and phenolic acids. Activation of SIRT1 that was shown to be involved in well-known signal pathways of diabetic cardiomyopathy has a protective effect against oxidative stress, inflammatory processes, and apoptosis that are the basis of diseases such as obesity, diabetes mellitus, or cardiovascular diseases. The aim of our study was to evaluate the antidiabetic and cardioprotective effects of horsetail extract in streptozotocin induced diabetic rats., Methods: Diabetes was induced by a single intraperitoneal injection of 45 mg/kg streptozotocin. In the control groups (healthy and diabetic), rats were administered with vehicle, whilst in the treated groups, animals were administered with 50, 100, or 200 mg/kg horsetail extract, respectively, for six weeks. Blood glucose levels, glucose tolerance, and insulin sensitivity were determined, and SIRT1 levels were measured from the cardiac muscle., Results: The horsetail extract showed moderate beneficial changes in blood glucose levels and exhibited a tendency to elevate SIRT1 levels in cardiomyocytes, furthermore a 100 mg/kg dose also improved insulin sensitivity., Conclusions: Altogether our results suggest that horsetail extract might have potential in ameliorating manifested cardiomyopathy acting on SIRT1., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Starmerella bacillaris (synonym Candida zemplinina ) is an important non-S accharomyces yeast in winemaking with valuable oenological properties, accompanying Saccharomyces species in sweet wine fermentation, and has been suggested also for application as combined starter culture in dry or sweet wines. In this study, the major metabolites and nitrogen utilization of these yeasts are evaluated in the musts with high or extremely high sugar concentration. The change in the metabolic footprint of Saccharomyces cerevisiae , Saccharomyces uvarum and Starmerella bacillaris strains was compared when they were present as pure cultures in chemically defined grape juice medium with 220 and 320 g/L of sugar, to represent a fully matured and an overripe grape. Surprisingly, the extreme sugar concentration did not result in a considerable change in the rate of sugar consumption; only a shift of the sugar consumption curves could be noticed for all species, especially for Starmerella bacillaris . At the extreme sugar concentration, Starmerella bacillaris showed excellent glycerol production, moderate nitrogen demand together with a noticeable proline utilisation. The change in the overall metabolite pattern of Starmerella bacillaris allowed clear discrimination from the change of the Saccharomyces species. In this experiment, the adequacy of this non- Saccharomyces yeast for co-fermentation in juices with high sugar concentration is highlighted. Moreover, the results suggest that Starmerella bacillaris has a more active adaptation mechanism to extremely high sugar concentration., Competing Interests: CONFLICT OF INTEREST: The authors declare no conflict of interest.

Optic nerve hypoplasia (ONH) is a congenital optic nerve abnormality caused by underdevelopment of retinal ganglion cells (RGCs). Despite being a rare disease, ONH is the most common optic disk anomaly in ophthalmological practice. So far, mutations in several genes have been identified as causative; however, many cases of ONH remain without a molecular explanation. The early transcription factor atonal basic-helix-loop-helix (bHLH) transcription factor 7 (ATOH7) is expressed in retinal progenitor cells and has a crucial role in RGC development. Previous studies have identified several mutations in the ATOH7 locus in cases of eye developmental diseases such as non-syndromic congenital retinal non-attachment and persistent hyperplasia of the primary vitreous. Here we present two siblings with a phenotype predominated by bilateral ONH, with additional features of foveal hypoplasia and distinct vascular abnormalities, where whole-exome sequencing identified two compound heterozygous missense mutations affecting a conserved amino acid residue within the bHLH domain of ATOH7 (NM_145178.3:c.175G>A; p.(Ala59Thr) and c.176C>T; p.(Ala59Val)). ATOH7 expression constructs with patient single nucleotide variants were cloned for functional characterization. Protein analyses revealed decreased protein amounts and significantly enhanced degradation in the presence of E47, a putative bHLH dimerization partner. Protein interaction assays revealed decreased heterodimerization and DNA-binding of ATOH7 variants, resulting in total loss of transcriptional activation of luciferase reporter gene expression. These findings strongly support pathogenicity of the two ATOH7 mutations, one of which is novel. Additionally, this report highlights the possible impact of altered ATOH7 dimerization on protein stability and function., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Tokaj wines (Hungaricum) are botrytized wines acknowledged for the unique organoleptic properties bestowed by botrytized grape berries during production. Excluding these berries during wine production or manipulating the sugar content of low-grade wines to imitate high-grade wines are some recent suspicious activities that threaten the wine quality. Advanced methods such as spectroscopy and sensor-based devices have been lauded for rapid, reliable, and cost-effective analysis, but there has been no report of their application to monitor grape must concentrate adulteration in botrytized wines. The study aimed to develop models to rapidly discriminate lower grade Tokaj wines, "Forditas I" and "Forditas II," that were artificially adulterated with grape must concentrate to match the sugar content of high-grade Tokaj wines using an electronic tongue (e-tongue) and two near infrared spectrometers (NIRS). Data were evaluated with the following chemometrics: principal component analysis (PCA), discriminant analysis (LDA), partial least square regression (PLSR), and aquaphotomics (a novel approach). There was a noticeable pattern of separation in PCA for all three instruments and 100% classification of adulterated and nonadulterated wines in LDA using the e-tongue. Aquagrams from the aquaphotomics approach showed important water absorption bands capable of being markers of Tokaj wine quality. PLSR models showed coefficient of determination (R 2 CV) of 0.98 (e-tongue), 0.97 (benchtop NIRS), 0.87 (handheld NIRS), and low root mean squared errors of cross-validation. All three instruments could discriminate, classify, and predict grape must concentrate adulteration in Tokaj with a high accuracy and low error. The methods can be applied for routine quality checks of botrytized wines. PRACTICAL APPLICATION: Tokaj wines (Hungaricum) are botrytized wines acknowledged for the unique organoleptic properties bestowed by botrytized grape berries during production. Excluding these berries during wine production or manipulating the sugar content of low-grade wines to imitate high-grade wines are some recent suspicious activities that threaten the wine quality. Using advanced instruments, the electronic tongue, benchtop near infrared spectroscopy, and a handheld near infrared spectroscopy, we could discriminate, classify, and predict grape must concentrate adulteration in Tokaj with a high accuracy and low error. The models in our study can be applied for routine quality checks of botrytized wines., (© 2019 The Authors. Journal of Food Science published by Wiley Periodicals, Inc. on behalf of Institute of Food Technologists.)

Purpose: To define the phenotype of C2orf71 associated retinopathy and to present novel mutations in this gene., Methods: A retrospective multicenter study of patients with retinopathy and identified C2orf71 mutations was performed. Ocular function (visual acuity, visual fields, electroretinogram [ERG] responses); retinal morphology (fundus, optical coherence tomography); and underlying mutations were analyzed., Results: Thirteen patients from 11 families, who were aged 7 to 63 years (mean: 32.1 years) at their first examination with presumed compound heterozygous (6/13 patients) or homozygous (7/13 patients) C2orf71 mutations were identified. Eight of the mutations were novel. Truncation mutations were responsible in all cases. Nyctalopia was observed in less than 50% of patients. Visual acuity ranged from 20/20 to light perception. Severe visual loss was associated with atrophic maculopathy. Full-field ERG responses showed severe progressive cone-rod or rod-cone dysfunction. Typical fundus changes were progressive symmetrical retinopathy with an early mild maculopathy and patchy circular midperipheral RPE atrophy. Normal retinal lamination was preserved despite early disruption of the ellipsoid zone and RPE irregularities. Outer retinal tubulations were associated with better-preserved visual acuity., Conclusions: On the basis of our multicenter analysis, C2orf71 might represent a more frequently mutated gene in autosomal recessive retinitis pigmentosa in some populations. The phenotype analysis over a wide age range showed a variable and progressive retinal degeneration with early onset maculopathy and a better visual potential before the age of 30 years.

Aims: To evaluate potential differences in the genetic profile of cases with 'definite', 'borderline', and 'possible' arrhythmogenic right ventricular cardiomyopathy (ARVC) phenotype by 2010 task force criteria using a custom genetic panel after whole-exome analysis., Methods and Results: We performed whole-exome sequencing in 14 cases with the clinical diagnosis ARVC using an 'Illumina HighSeq 2000' system. We presented our initial results focused on 96 known cardiomyopathy and channelopathy genes. According to the 2010 task force criteria, 7/14 cases (50%) were classified as 'definite' phenotype, 4/14 (29%) were 'borderline', and 3/14 (21%) were diagnosed with the 'possible' phenotype. Nine out of 14 patients (64%) were males, and all were Caucasians, with an average age at genetic diagnosis of 50 ± 15 years. Among the seven cases with the 'definite' phenotype, six (86%) had a putative desmosomal mutation, while none of the seven patients with a 'possible' or borderline task force classification phenotype hosted putative mutations in desmosomal genes. Four (57%) of them had rare variants in other dilated cardiomyopathy (DCM) genes., Conclusions: Most of the patients with 'definite' ARVC phenotype by task force 2010 host mutations in desmosomal genes. Weaker ARVC phenotypes host variants/mutations in other DCM genes and result in a disease spectrum, including DCM or phenocopies of ARVC., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Organic acid production under oxygen-limited conditions has been thoroughly studied in the Saccharomyces species, but practically never investigated in Candida zemplinina, which seems to be an acidogenic species under oxidative laboratory conditions. In this study, several strains of C. zemplinina were tested for organic acid metabolism, in comparison with Saccharomyces cerevisiae, Saccharomyces uvarum and Candida stellata, under fermentative conditions. Only C. stellata produced significantly higher acidity in simple minimal media (SM) with low sugar content and two different nitrogen sources (ammonia or glutamic acid) at low level. However, the acid profile differed largely between the Saccharomyces and Candida species and showed inverse types of N-dependence in some cases. Succinic acid production was strongly enhanced on glutamic acid in Saccharomyces species, but not in Candida species. 2-oxoglutarate production was strongly supported on ammonium nitrogen in Candida species, but remained low in Saccharomyces. Candida species, C. stellata in particular, produced more pyruvic acid regardless of N-sources. From the results, we concluded that the anaerobic organic acid metabolisms of C. zemplinina and C. stellata are different from each other and also from that of the Saccharomyces species. In the formation of succinic acid, the oxidative pathway from glutamic acid seems to play little or no role in C. zemplinina. The reductive branch of the TCA cycle, however, produces acidic intermediates (malic, fumaric, and succinic acid) in a level comparable with the production of the Saccharomyces species. An unidentified organic acid, which was produced on glutamic acid only by the Candida species, needs further investigation., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Wagner syndrome (WS) is an autosomal dominant vitreoretinopathy affecting various ocular features and is caused by mutations in the canonical splice sites of the VCAN gene, which encodes the large chondroitin sulfate proteoglycan, versican. We report the identification of novel splice acceptor and donor-site mutations (c.4004-1G>C and c.9265+2T>A) in two large WS families from France and the United Kingdom. To characterize their pathogenic mechanisms we performed qRT-PCR experiments on RNA from patient-derived tissues (venous blood and skin fibroblasts). We also analyzed RNA from the original Swiss family reported by Wagner (who has the previously reported c.9265+1G>A mutation). All three mutations resulted in a quantitative increase of transcript variants lacking exons 7 and/or 8. However, the magnitude of the increase varied between tissues and mutations. We discuss altered balance of VCAN splice variants in combination with reduction in glycosaminoglycan protein modifications as possible pathogenic mechanisms.

Due to the recent changes in yeast taxonomy, a novel wine-related species Candida zemplinina as well as a "reinstated" species Saccharomyces uvarum have been accepted in addition to Candida stellata, Saccharomyces bayanus and Saccharomyces cerevisiae, and the use of the different taxon names has been inconsistent in the literature of food microbiology. The aim of this work is to make an exact comparison of genetically identified strains of these species, under oenological conditions. Dynamics and some important products of alcoholic fermentation were investigated in laboratory fermentations. The results show that C. zemplinina and C. stellata are similar in their strong fructophilic character. C. stellata produces more glycerol and fare more ethanol, which is comparable with that produced by S. uvarum. Strains of the latter species differed from S. cerevisiae mainly in low acetic acid production and lower ethanol yield. Revision of the oenological traits of these yeasts provides new data for consideration in the control of fermentation, with special regard to botrytized sweet wines, where they are frequently found in mixed population., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Botrytized wines are natural sweet wines, produced from grapes that are affected by Botrytis cinerea under particular conditions. This rare and special form of fungal infection, called noble rot, includes complex enzymatic conversions and concurrent dehydration of the grape berry and results in a highly concentrated final product. The main characteristics of the noble rotted grapes involve high sugar, acid, glycerol and mineral contents, special polysaccharides, and particular aroma composition, which are thoroughly studied. The saprophytic microbiota of the grapes is also affected. Harvest and vinification of the noble rotted grapes are difficult, having special requirements. Microbiology and biochemistry of the alcoholic fermentation in these wines have been recently studied more deeply. Depending on the grape varieties as well as vinification and ageing technologies, botrytized wines show large diversity in style. Most of them are rich in polyphenols, possessing high antioxidant capacity. Biogenic amine and micotoxine contents of these wines are no public health concerns. This chapter presents the microbiological, biochemical, and technological aspects of noble rot and botrytized wines and discusses the recent findings on these fields., (Copyright © 2011 Elsevier Inc. All rights reserved.)

PURPOSE. Knowledge of genetic factors predisposing to age-related cataract is very limited. The aim of this study was to identify DNA sequences that either lead to or predispose for this disease. METHODS. The candidate gene SLC16A12, which encodes a solute carrier of the monocarboxylate transporter family, was sequenced in 484 patients with cataract (134 with juvenile cataract, 350 with age-related cataract) and 190 control subjects. Expression studies included luciferase reporter assay and RT-PCR experiments. RESULTS. One patient with age-related cataract showed a novel heterozygous mutation (c.-17A>G) in the 5'untranslated region (5'UTR). This mutation is in cis with the minor G-allele of the single nucleotide polymorphism (SNP) rs3740030 (c.-42T/G), also within the 5'UTR. Using a luciferase reporter assay system, a construct with the patient's haplotype caused a significant upregulation of luciferase activity. In comparison, the SNP G-allele alone promoted less activity, but that amount was still significantly higher than the amount of the common T-allele. Analysis of SLC16A12 transcripts in surrogate tissue demonstrated striking allele-specific differences causing 5'UTR heterogeneity with respect to sequence and quantity. These differences in gene expression were mirrored in an allele-specific predisposition to age-related cataract, as determined in a Swiss population (odds ratio approximately 2.2; confidence intervals, 1.23-4.3). CONCLUSIONS. The monocarboxylate transporter SLC16A12 may contribute to age-related cataract. Sequences within the 5'UTR modulate translational efficiency with pathogenic consequences.

We improved, evaluated, and used Sanger sequencing for quantification of single nucleotide polymorphism (SNP) variants in transcripts and gDNA samples. This improved assay resulted in highly reproducible relative allele frequencies (e.g., for a heterozygous gDNA 50.0+/-1.4%, and for a missense mutation-bearing transcript 46.9+/-3.7%) with a lower detection limit of 3-9%. It provided excellent accuracy and linear correlation between expected and observed relative allele frequencies. This sequencing assay, which can also be used for the quantification of copy number variations (CNVs), methylations, mosaicisms, and DNA pools, enabled us to analyze transcripts of the FBN1 gene in fibroblasts and blood samples of patients with suspected Marfan syndrome not only qualitatively but also quantitatively. We report a total of 18 novel and 19 known FBN1 sequence variants leading to a premature termination codon (PTC), 26 of which we analyzed by quantitative sequencing both at gDNA and cDNA levels. The relative amounts of PTC-containing FBN1 transcripts in fresh and PAXgene-stabilized blood samples were significantly higher (33.0+/-3.9% to 80.0+/-7.2%) than those detected in affected fibroblasts with inhibition of nonsense-mediated mRNA decay (NMD) (11.0+/-2.1% to 25.0+/-1.8%), whereas in fibroblasts without NMD inhibition no mutant alleles could be detected. These results provide evidence for incomplete NMD in leukocytes and have particular importance for RNA-based analyses not only in FBN1 but also in other genes.