Abstract The function of many bacterial processes depends on the formation of functional membrane microdomains (FMMs), which resemble the lipid rafts of eukaryotic cells. However, the mechanism and ...the biological function of these membrane microdomains remain unclear. Here, we show that FMMs in the pathogen methicillin-resistant Staphylococcus aureus (MRSA) are dedicated to confining and stabilizing proteins unfolded due to cellular stress. The FMM scaffold protein flotillin forms a clamp-shaped oligomer that holds unfolded proteins, stabilizing them and favoring their correct folding. This process does not impose a direct energy cost on the cell and is crucial to survival of ATP-depleted bacteria, and thus to pathogenesis. Consequently, FMM disassembling causes the accumulation of unfolded proteins, which compromise MRSA viability during infection and cause penicillin re-sensitization due to PBP2a unfolding. Thus, our results indicate that FMMs mediate ATP-independent stabilization of unfolded proteins, which is essential for bacterial viability during infection.
Pyrenean glaciers are the largest in southern Europe. Their survival is threatened by climate change, highlighting the significance of their study. This research presents an assessment of changes in ...the glacierized area and thickness of Pyrenean glaciers from 2011 to 2020, using high‐resolution optical satellite, airborne lidar and UAV images. The total glacierized area has shrunk by 23.2% and thickness has decreased on average by 6.3 m. These two variables show no correlation for individual glaciers. Although climatic conditions do not vary much among glaciers, their evolution was heterogeneous during the study period. The smaller glaciers (<10 ha) show a higher variability in their area decrease and thickness loss whereas the four largest glaciers (>10 ha) have a more homogeneous response. This can be attributed to the generally larger influence of local topography on the response of the smaller Pyrenean glaciers. There is no sign of slowdown in glacier shrinkage respect to previous decades.
Plain Language Summary
Pyrenean glaciers are the largest in southern Europe. Their survival is threatened by climate change, highlighting the significance and relevance of their study. This study presents an assessment of changes in the glacierized area and thickness of Pyrenean glaciers during 2011–2020 based on UAV, optical satellite imagery and lidar observations. In this period, their total area shrank by 23.2% and thickness decreased by 6.3 m on average. Although climatic conditions do not vary much among glaciers, their evolution was heterogeneous during the observed period. The smaller Pyrenean glaciers (area <10 ha) are highly controlled by local topography, whereas the largest glaciers are predominantly influenced by regional climate forcing. There is no sign of slowdown in shrinkage of Pyrenean glaciers respect to previous decades. This indicates the continuous decline of Pyrenean glaciers toward an ice‐free mountain range in the coming decades.
Key Points
The glacierized area shrank by 23.2% and thickness decreased on average by 6.3 m during the 2011–2020 period
There is no sign of slowdown in glacier shrinkage respect to previous decades
The smaller Pyrenean glaciers are influenced by local topography as they show highly contrasted evolution under the same climatic conditions
While marine sediments have been used to constrain a history of redox chemistry throughout the Precambrian, far fewer data have been generated from lakes. With major biological innovations thought to ...have occurred in Proterozoic lakes, understanding their chemistry is critical for understanding the evolution of eukaryotic life. We use sediment geochemistry to characterize the redox conditions of the Nonesuch Formation (~1.1 Ga) and a modern analogue for the Proterozoic: the Middle Island Sinkhole in Lake Huron (USA). Iron speciation, Mo contents, and Mo‐U covariation demonstrate oxic and anoxic—not euxinic—environments, with no clear indicators of enhanced biological productivity in the Nonesuch Formation. Moderate Mo enrichments observed in the Nonesuch Formation are not attributed to euxinia, but instead to an authigenic particulate shuttle. We suggest that the Fe and Mo sediment geochemistry of these lacustrine systems reflect only local water column and sediment burial conditions and not atmospheric oxygenation.
Plain Language Summary
Lakes are proposed to have been critical environments for the evolution of life during the Proterozoic (~2.5 to 0.5 billion years ago). However, relatively little is known about the chemistry of ancient lakes, including the availability of oxygen for biological productivity, and how local oxygen availability can be extrapolated to understand global oxygen availability. In addition, with no lakes remaining from the Proterozoic, the only way to study ancient lakes is to use the chemistry of the sediments left behind. This study uses the sediment chemistry of elements that are sensitive to oxygen to understand oxygen availability in a Proterozoic lake environment. These data were then compared to modern lake environments with known chemistry and oxygen levels in order to interpret the results better. We found that oxygen availability in the Proterozoic lake was variable, with no clear indicators of abundant biological productivity. We conclude that ancient lake sediments only constrain the chemistry of the local environment, with no major implications for global or even regional atmospheric oxygenation.
Key Points
Fe, Mo, and U sediment geochemistry of the Nonesuch Formation (~1.1 Ga; USA) indicate fluctuating oxic and anoxic redox chemistry
Mo and U covariation in the Nonesuch Formation and modern analogue sediments confirm euxinia is not necessary for moderate Mo burial
Comparison of Nonesuch Formation and modern analogue indicates that Proterozoic lakes are unlikely to constrain atmospheric oxygen
This work combines very detailed measurements from terrestrial laser scanner (TLS), ground-based interferometry radar (GB-SAR) and ground-penetrating radar (GPR) to diagnose current conditions and to ...analyse the recent evolution of the Monte Perdido Glacier in the Spanish Pyrenees from 2011 to 2017. Thus, this is currently one of the best monitored small glacier (<0.5 km2) worldwide. The evolution of the glacier surface was surveyed with a TLS evidencing an important decline of 6.1 ± 0.3 m on average, with ice losses mainly concentrated over 3 years (2012, 2015 and 2017). Ice loss is unevenly distributed throughout the study period, with 10–15 m thinning in some areas while unchanged areas in others. GB-SAR revealed that areas with higher ice losses are those that are currently with no or very low ice motion. In contrast, sectors located beneath the areas with less ice loss are those that still exhibit noticeable ice movement (average 2–4.5 cm d─1 in summer, and annual movement of 9.98 ma─1 from ablation stakes data). GPR informed that ice thickness was generally <30 m, though locally 30–50 m. Glacier thinning is still accelerating and will lead to extinction of the glacier over the next 50 years.
Spastic paraplegia (SPG) is a syndrome characterised by lower limb spasticity, occurring alone or in association with other neurological manifestations. Despite of the new molecular technologies, ...many patients remain yet undiagnosed.
The purpose of this study was to describe the clinical presentation and molecular characteristics of a cohort of 27 patients from 18 different families with SPG in the south of Spain.
We used a targeted next-generation sequencing (NGS) approach to study a proband from each family.
Variants in SPG11 gene were the most common cause of SPG in our area. We made a genetic diagnosis in 52% of cases, identified 3 novel variants and reclassified one uncertain variant in SPG11 gene as pathogenic variant. We identified a patient with two truncanting mutations in SPG11 gene and late onset disease and report another missense mutation outside of motor domain of KIF1A gene in a family with pure SPG.
Our study contributes to enhance the scientific knowledge of SPG. It is important to note the large group of cases (48%) that were not genetically diagnosed in our cohort. Therefore NGS approach is an efficient diagnostic tool, but it still large the number of non-diagnosed subjects, suggesting further genetic heterogeneity.
Introduction
Tianeptine is prescribed as an antidepresant in Europe. The prescription drug is produced as tianeptine sodium. However, it can also be found on the Internet as tianeptine sulfate sold ...as a nootropric. Misuse of tianeptine sodium has been documented, but there’s little scientific evidence of tianeptine sulfate use.
Objectives
Review the use of tianeptine sulfate without prescription.
Present a clinical report of tianeptine sulfate use.
Methods
PubMed review of tienptine use without prescription.
Clinical report of a patient using tianeptine sulfate adquiered on the Internet.
Results
Systematic review on PubMed using the search term “tianeptine abuse” conducted on 01/10/2022. A total of 71 articles were found from wich 33 mentioned the use of tianeptine use without prescription. A total of 23 case reports of tianeptine use without prescription were found. None of them made the difference between tiaenptine sodium or tianeptine sulfate. Only one article mentioned the use of tianeptine sulfate from an Internet search on Internet fora (Smith et al. Am J Drug Alcohol Abuse 2021 47(4), 455–466).
The case report of a 23 years old patient is presented. Diagnoses: ADHD (F98.8); Psychotic episodes four (F23) and two (F16.150) years ago; Major depressive disorder (F32.2). Use of psychedelics, cannabis, psychoestimulants and opioids meeting substance use disorder (SUD) criteria. The patient brought proof of the tianeptine sulfate bought on the Internet (image 1) for self-treatment of his depressive symptoms. Tianeptine sodium is prescribed. The patient then restarts opioid use with fear of a new opioid use disorder episode and an oxicodone prescription is maintained. The patient then interrupts the antipsychotic medication and suffers a psychotic relapse. After this psychotic episode a LAI treatment with paliperidone is started. Currently, the patient is recovered and maintains psychopathological stability and abstinence from other substances. Blod test result unaltered. Current treatment: lisdexamphetamine 70mg /day, tianeptina sodium 12.5mg/day; oxicodone 40mg/12h and paliperidone 150mg /28d.
Image:
Conclusions
Tianeptine sulfate is believed to present some diferences versus tianeptine sodium: it is sold only through the Internet without prescrption, the daily dose is 25mg per day versus 12.5mg every 8 hours and it might be more potent and long lasting. Those differences were confirmed by the patient after the prescription of tianeptine sodium.
Self-medication with psychoactive substances is one of the theories for substance use and might lead to a substance use disorder. This case shows how the prescription of a drug similar to the one used without presription might favour the therapeutical alliance and reduce the risk associated to the use of non-regulated substances.
Further research is needed to better understand the use of tianeptine sulfate.
Disclosure of Interest
None Declared
We report the architecture of testis transcriptomes of four closely related species of Calligrapha (Chrysomelidae) beetles, which diverged during the last 3 million years. Five cDNA libraries were ...sequenced using Illumina HiSeq technology, retrieving 102 884–176 514 assembled contigs, of which ~33–45% of these longer than 499 nt were functionally annotated. Annotation and sequence similarity comparisons of these libraries revealed high homogeneity in gene composition and the presence of several functional candidates related to reproduction or reproductive processes (0.72–1.08% of annotated sequences). Stringent sequence similarity analyses of these transcriptomes against empirically demonstrated male‐biased genes in Drosophila melanogaster and Tribolium castaneum allowed the identification of 77 homologues in Calligrapha, possible candidates of male‐biased expression. Some of these genes – including CG9313, Tektin‐A or tomboy40 – were confirmed as orthologs of these male‐biased genes using phylogenetic inference and available model insect data, increasing our confidence that they represent functional homologues too. Our transcriptomes are a valuable transcriptomic resource for the analysis of male‐biased genes in Calligrapha, which has the added interest of including several female‐only species. But it simultaneously represents a landmark for similar studies in Coleoptera, broadening the taxonomic diversity currently represented by the model species T. castaneum, and incipient genomic data in other herbivorous lineages, including weevils, longhorn beetles and leaf beetles.
To identify patients with adult-onset temporal lobe epilepsy (TLE) at risk of developing cognitive decline. Detecting which patients, aetiologies, or factors are most closely related with memory ...decline would allow us to identify patients that would eventually benefit from more specific treatment.
Single centre, retrospective analysis of a prospectively followed-up cohort study, including all patients with the diagnosis of adult-onset TLE during 2013, with a minimum follow-up of five years. Memory and cognitive decline were analysed at 5 years and at last follow-up.
Of 89 initially selected patients, 71 were included. After 5 years, 11/71 (15.5%) patients suffered cognitive decline, of which 1/71 (4%) developed dementia. At last follow-up (range 65–596 m) a total of 34/71 (47.8%) patients were diagnosed with cognitive decline, specifically either memory decline or dementia. Cognitive decline at 5 years was related to: 1. Age at onset: 62.65 years (SD 9.04) in the group with cognitive decline vs 50.33 y. (SD 13.02 in the group without cognitive decline; p=0.004); 2. Onset as status epilepticus (3/6 in patients with memory decline vs 8/65 in patients without cognitive decline; p=0.04); 3. Immune aetiology: 42% compared with unknown (10%) and structural (10%) aetiologies; p=0.036; 4. Hippocampal sclerosis on MRI: 5/11 patients with cognitive decline vs 9/51 patients without cognitive decline; p=0.035. Cognitive decline was not related to seizure frequency, sex, or age (p=0.78; p=0.40; p=0.95, respectively).
Older age at epilepsy onset, onset as status epilepticus, immune aetiology, and hippocampal sclerosis are risk factors for developing cognitive decline in patients with adult-onset temporal lobe epilepsy.
•Patients with temporal lobe epilepsy have a higher risk of developing cognitive decline or dementia compared to the general population.•Immune aetiology has a higher risk of developing cognitive or memory decline compared to those with other aetiologies.•Cognitive decline in immune epilepsy develops even in seizure-free patients.
One of the oldest laments in agrarian development has been over the ageing and loss of the farm population but, for the first time since the Second World War, a noticeable return to farming is now ...taking place across most of Europe. These farm entrants we classify as Continuers and Newcomers. Research shows that they have different characteristics. Newcomers are characterized by their profiles (female and higher education), the barriers they face (access to land, capital and markets) and by the business models that they adopt (pluriactive and multifunctional). This paper describes the main features of Newcomers as they form a new and dynamic group in European rural society and contribute strong social motivations and practices to farming. This change may be referred to as a shift from an agroindustrial to an agrosocial paradigm and, together with new social and environmental relations in food systems, forms a new rurality in Europe.
Una de les preocupacions més antigues del desenvolupament agrari ha estat l’envelliment i la pèrdua de la població agrària, però, per primera vegada des de la Segona Guerra Mundial, hi ha un retorn apreciable de la pagesia a bona part d’Europa. Les noves instal·lacions agràries han estat classificades com a pagesia tradicional i pagesia nouvinguda. La investigació mostra que tenen característiques diferents. La pagesia nouvinguda es caracteritza pels seus perfils (femení i educació superior), les barreres que enfronten (accés a la terra, al capital i al mercat) i els models de negoci que adopten (pluriactius i multifuncionals). Aquest article descriu les principals característiques de la pagesia nouvinguda, ja que forma un grup nou i dinàmic dins de la societat rural europea i contribueix amb fortes motivacions i pràctiques socials a la nova agricultura. Aquest canvi es pot entendre com un canvi d’un model agroindustrial a un nou paradigma agrosocial, que, conjuntament amb els moviments socials i ambientals dels nous sistemes alimentaris, formen una nova ruralitat a Europa.
Uno de los lamentos más antiguos del desarrollo agrario ha sido el envejecimiento y la pérdida de la población agrícola, pero, por primera vez desde la Segunda Guerra Mundial, hay un retorno apreciable a la agricultura en la mayor parte de Europa. Las nuevas instalaciones agrícolas han sido clasificadas como agricultores tradicionales y agricultores nuevos. Nuestra investigación muestra que tienen características diferentes. Los agricultores nuevos se caracterizan por sus perfiles (femeninos y educación superior), las barreras que enfrentan (acceso a la tierra, al capital y al mercado) y por los modelos de negocio que adoptan (pluriactivos y multifuncionales). Este artículo describe las principales características de los agricultores nuevos, ya que forman un nuevo y dinámico grupo de la sociedad rural europea y contribuyen con sus fuertes motivaciones y prácticas sociales a una nueva agricultura. Este cambio puede ser referido como un cambio de un modelo agroindustrial a un nuevo paradigma agrosocial, que, junto con los movimientos sociales y ambientales de los nuevos sistemas alimentarios, forman una nueva ruralidad en Europa.
Un des plus anciens freins au développement rural est le vieillissement et la perte de la population agricole, mais, pour la première fois depuis la Seconde Guerre mondiale, il existe un retour notable à l’agriculture dans la plupart des pays européens. Ces entrants agricoles ont été classés en continuateurs ou nouveaux venus. La recherche montre qu’ils ont des caractéristiques différentes. Les nouveaux venus sont caractérisés par leur profil (femmes et avec des études supérieures), par les obstacles qu’ils rencontrent (accès à la terre, au capital et au marché) et par modèles d’entreprise qu’ils construisent (pluriactifs et multifonctionnels). Ce document décrit les principales caractéristiques des nouveaux venus, qui forment un nouveau groupe dynamique dans la société rurale européenne et contribuent à l’agriculture via leur forte motivation et leurs pratiques sociales. Ce changement peut être considéré comme le passage d’un paradigme agro-industriel à un paradigme agro-social et, de concert avec les mouvements sociaux et environnementaux dans les systèmes alimentaires, il forme une nouvelle ruralité en Europe.
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