Dynamique du peuplement et activités agro-pastorales durant l’âge du Bronze dans les massifs du haut Champsaur et de l’Argentiérois

Des programmes de recherche pluridisciplinaires sur l’occupation du sol et le pastoralisme de la Préhistoire au Moyen Âge dans le sud du massif alpin sont menés, depuis 1998, sur les massifs du Haut Champsaur, de Freissinières et de l’Argentièrois (Hautes-Alpes). Des dix phases d’occupation et d'activité agropastorale mises en évidence (prospections pédestres et fouilles), entre 1600 et 2700 m d’altitude, trois se distinguent: la fin du Néolithique, l’âge du Bronze et la période médiévale. Au travers des premières données archéologiques et environnementales, cet article présente, depuis le milieu du IIIe millénaire au début du Ier millénaire, les grandes caractéristiques de l’occupation du sol mais aussi l’originalité et l’importance de l’activité humaine dans cette zone alpine. La fin du Néolithique et l’âge du Bronze correspondent à une multiplication des gisements archéologiques marquant de façon évidente une rupture dans la gestion de l'espace montagnard. Les paysages sont largement façonnés par les activités humaines et l’entretien des terres cultivées, des prairies et des alpages, paraît continu. À la lumière des données de terrain, l’une des évolutions qui apparaît sur les sites d’altitude durant cette période concerne l’apparition de structures pastorales bâties entre 2 067 et 2 303 m d’altitude (datation 14C).

Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair.

Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ∼70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal effect of later ANM on breast cancer risk (∼6% increase in risk per year; P = 3 × 10(-14)), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms.

Genome-wide enrichment analysis between endometriosis and obesity-related traits reveals novel susceptibility loci.

Endometriosis is a chronic inflammatory condition in women that results in pelvic pain and subfertility, and has been associated with decreased body mass index (BMI). Genetic variants contributing to the heritable component have started to emerge from genome-wide association studies (GWAS), although the majority remain unknown. Unexpectedly, we observed an intergenic locus on 7p15.2 that was genome-wide significantly associated with both endometriosis and fat distribution (waist-to-hip ratio adjusted for BMI; WHRadjBMI) in an independent meta-GWAS of European ancestry individuals. This led us to investigate the potential overlap in genetic variants underlying the aetiology of endometriosis, WHRadjBMI and BMI using GWAS data. Our analyses demonstrated significant enrichment of common variants between fat distribution and endometriosis (P = 3.7 × 10(-3)), which was stronger when we restricted the investigation to more severe (Stage B) cases (P = 4.5 × 10(-4)). However, no genetic enrichment was observed between endometriosis and BMI (P = 0.79). In addition to 7p15.2, we identify four more variants with statistically significant evidence of involvement in both endometriosis and WHRadjBMI (in/near KIFAP3, CAB39L, WNT4, GRB14); two of these, KIFAP3 and CAB39L, are novel associations for both traits. KIFAP3, WNT4 and 7p15.2 are associated with the WNT signalling pathway; formal pathway analysis confirmed a statistically significant (P = 6.41 × 10(-4)) overrepresentation of shared associations in developmental processes/WNT signalling between the two traits. Our results demonstrate an example of potential biological pleiotropy that was hitherto unknown, and represent an opportunity for functional follow-up of loci and further cross-phenotype comparisons to assess how fat distribution and endometriosis pathogenesis research fields can inform each other.

Impact of a cis-associated gene expression SNP on chromosome 20q11.22 on bipolar disorder susceptibility, hippocampal structure and cognitive performance.

BackgroundBipolar disorder is a highly heritable polygenic disorder. Recent enrichment analyses suggest that there may be true risk variants for bipolar disorder in the expression quantitative trait loci (eQTL) in the brain.AimsWe sought to assess the impact of eQTL variants on bipolar disorder risk by combining data from both bipolar disorder genome-wide association studies (GWAS) and brain eQTL.MethodTo detect single nucleotide polymorphisms (SNPs) that influence expression levels of genes associated with bipolar disorder, we jointly analysed data from a bipolar disorder GWAS (7481 cases and 9250 controls) and a genome-wide brain (cortical) eQTL (193 healthy controls) using a Bayesian statistical method, with independent follow-up replications. The identified risk SNP was then further tested for association with hippocampal volume (n = 5775) and cognitive performance (n = 342) among healthy individuals.ResultsIntegrative analysis revealed a significant association between a brain eQTL rs6088662 on chromosome 20q11.22 and bipolar disorder (log Bayes factor = 5.48; bipolar disorder P = 5.85×10(-5)). Follow-up studies across multiple independent samples confirmed the association of the risk SNP (rs6088662) with gene expression and bipolar disorder susceptibility (P = 3.54×10(-8)). Further exploratory analysis revealed that rs6088662 is also associated with hippocampal volume and cognitive performance in healthy individuals.ConclusionsOur findings suggest that 20q11.22 is likely a risk region for bipolar disorder; they also highlight the informative value of integrating functional annotation of genetic variants for gene expression in advancing our understanding of the biological basis underlying complex disorders, such as bipolar disorder.

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.

Estudi de l'ensenyament-aprenentatge de la multiplicació de fraccions

Aquest treball és una investigació de com cal ensenyar la multiplicació de fraccions a l’Educació Primària. S’han recollit les dades a través d’entrevistes per conèixer com 6 mestres ensenyaven aquest coneixement matemàtic per comparar-ho amb el que diuen diferents autors com Van de Walle, Tipps, Tucker i Bruner. L’ensenyamentaprenentatge de la multiplicació de fraccions és un procés difícil i complex. Per adquirir aquest coneixement, els infants necessiten tenir experiències amb diferents situacions que es plantegi el producte de fraccions i deduir ells mateixos estratègies i algorismes propis per resoldre-les. Si se’ls dóna directament l’algorisme tradicional sense comprensió, tindran dificultats per identificar si el resultat és coherent o no.

Oeil et environnement

Résumé L'oeil est exposé à de multiples facteurs environnementaux qui influent sur le développement visuel, le confort et la santé visuelle. Une exposition excessive à la lumière solaire peut causer des pathologies de la surface oculaire et de la rétine, mais une exposition insuffisante à la lumière du jour pourrait être incriminée dans l'apparition ou la progression de la myopie. Les lumières artificielles, LED en particulier, comportent un risque accru de phototoxicité rétinienne. L'augmentation importante de la prévalence des allergies oculaires pourrait être liée à la multiplication des polluants environnementaux, comme la fumée de tabac, les dérivés de combustion de carburants ou les phtalates. Enfin, certains compléments alimentaires peuvent jouer un rôle protecteur dans certains types d'atteintes oculaire, rétinienne en particulier. Abstract The eyes are exposed to multiple environmental factors, which affect visual development, comfort, and visual health. While overexposure to sunlight can cause ocular surface and retinal pathologies, insufficient exposure to daylight could significantly contribute to myopia progression. New artificial lights, namely LED, have a higher risk of retinal phototoxicity, and could alter ocular circadian rhythm. The significant increase of prevalence of ocular allergies could be caused by the proliferation of environmental polluting substances, like tobacco smoke, fuel combustion by-products, or phtalates, which are found in many types of plastics. Finally, some dietary supplements could play a protective role in certain types of ocular pathologies, namely retinal pathologies.

Promoter DNA Hypermethylation and Gene Repression in Undifferentiated Arabidopsis Cells

Maintaining and acquiring the pluripotent cell state in plants is critical to tissue regeneration and vegetative multiplication. Histone-based epigenetic mechanisms are important for regulating this undifferentiated state. Here we report the use of genetic and pharmacological experimental approaches to show that Arabidopsis cell suspensions and calluses specifically repress some genes as a result of promoter DNA hypermethylation. We found that promoters of the MAPK12, GSTU10 and BXL1 genes become hypermethylated in callus cells and that hypermethylation also affects the TTG1, GSTF5, SUVH8, fimbrin and CCD7 genes in cell suspensions. Promoter hypermethylation in undifferentiated cells was associated with histone hypoacetylation and primarily occurred at CpG sites. Accordingly, we found that the process specifically depends on MET1 and DRM2 methyltransferases, as demonstrated with DNA methyltransferase mutants. Our results suggest that promoter DNA methylation may be another important epigenetic mechanism for the establishment and/or maintenance of the undifferentiated state in plant cells.

Knapsack sets for cryptography

The basic goal of this study is to extend old and propose new ways to generate knapsack sets suitable for use in public key cryptography. The knapsack problem and its cryptographic use are reviewed in the introductory chapter. Terminology is based on common cryptographic vocabulary. For example, solving the knapsack problem (which is here a subset sum problem) is termed decipherment. Chapter 1 also reviews the most famous knapsack cryptosystem, the Merkle Hellman system. It is based on a superincreasing knapsack and uses modular multiplication as a trapdoor transformation. The insecurity caused by these two properties exemplifies the two general categories of attacks against knapsack systems. These categories provide the motivation for Chapters 2 and 4. Chapter 2 discusses the density of a knapsack and the dangers of having a low density. Chapter 3 interrupts for a while the more abstract treatment by showing examples of small injective knapsacks and extrapolating conjectures on some characteristics of knapsacks of larger size, especially their density and number. The most common trapdoor technique, modular multiplication, is likely to cause insecurity, but as argued in Chapter 4, it is difficult to find any other simple trapdoor techniques. This discussion also provides a basis for the introduction of various categories of non injectivity in Chapter 5. Besides general ideas of non injectivity of knapsack systems, Chapter 5 introduces and evaluates several ways to construct such systems, most notably the "exceptional blocks" in superincreasing knapsacks and the usage of "too small" a modulus in the modular multiplication as a trapdoor technique. The author believes that non injectivity is the most promising direction for development of knapsack cryptosystema. Chapter 6 modifies two well known knapsack schemes, the Merkle Hellman multiplicative trapdoor knapsack and the Graham Shamir knapsack. The main interest is in aspects other than non injectivity, although that is also exploited. In the end of the chapter, constructions proposed by Desmedt et. al. are presented to serve as a comparison for the developments of the subsequent three chapters. Chapter 7 provides a general framework for the iterative construction of injective knapsacks from smaller knapsacks, together with a simple example, the "three elements" system. In Chapters 8 and 9 the general framework is put into practice in two different ways. Modularly injective small knapsacks are used in Chapter 9 to construct a large knapsack, which is called the congruential knapsack. The addends of a subset sum can be found by decrementing the sum iteratively by using each of the small knapsacks and their moduli in turn. The construction is also generalized to the non injective case, which can lead to especially good results in the density, without complicating the deciphering process too much. Chapter 9 presents three related ways to realize the general framework of Chapter 7. The main idea is to join iteratively small knapsacks, each element of which would satisfy the superincreasing condition. As a whole, none of these systems need become superincreasing, though the development of density is not better than that. The new knapsack systems are injective but they can be deciphered with the same searching method as the non injective knapsacks with the "exceptional blocks" in Chapter 5. The final Chapter 10 first reviews the Chor Rivest knapsack system, which has withstood all cryptanalytic attacks. A couple of modifications to the use of this system are presented in order to further increase the security or make the construction easier. The latter goal is attempted by reducing the size of the Chor Rivest knapsack embedded in the modified system. '

Predictors and consequences of adherence to the treatment of pediatric patients with attention-deficit/hyperactivity disorder in Central Europe and East Asia.

PURPOSE: To assess baseline predictors and consequences of medication non-adherence in the treatment of pediatric patients with attention-deficit/hyperactivity disorder (ADHD) from Central Europe and East Asia. PATIENTS AND METHODS: Data for this post-hoc analysis were taken from a 1-year prospective, observational study that included a total of 1,068 newly-diagnosed pediatric patients with ADHD symptoms from Central Europe and East Asia. Medication adherence during the week prior to each visit was assessed by treating physicians using a 5-point Likert scale, and then dichotomized into either adherent or non-adherent. Clinical severity was measured by the Clinical Global Impressions-ADHD-Severity (CGI-ADHD) scale and the Child Symptom Inventory-4 (CSI-4) Checklist. Health-Related Quality of Life (HRQoL) was measured using the Child Health and Illness Profile-Child Edition (CHIP-CE). Regression analyses were used to assess baseline predictors of overall adherence during follow-up, and the impact of time-varying adherence on subsequent outcomes: response (defined as a decrease of at least 1 point in CGI), changes in CGI-ADHD, CSI-4, and the five dimensions of CHIP-CE. RESULTS: Of the 860 patients analyzed, 64.5% (71.6% in Central Europe and 55.5% in East Asia) were rated as adherent and 35.5% as non-adherent during follow-up. Being from East Asia was found to be a strong predictor of non-adherence. In East Asia, a family history of ADHD and parental emotional distress were associated with non-adherence, while having no other children living at home was associated with non-adherence in Central Europe as well as in the overall sample. Non-adherence was associated with poorer response and less improvement on CGI-ADHD and CSI-4, but not on CHIP-CE. CONCLUSION: Non-adherence to medication is common in the treatment of ADHD, particularly in East Asia. Non-adherence was associated with poorer response and less improvement in clinical severity. A limitation of this study is that medication adherence was assessed by the treating clinician using a single item question.

Predictors of remission in the treatment of major depressive disorder: real-world evidence from a 6-month prospective observational study

BACKGROUND: This study examined potential predictors of remission among patients treated for major depressive disorder (MDD) in a naturalistic clinical setting, mostly in the Middle East, East Asia, and Mexico. METHODS: Data for this post hoc analysis were taken from a 6-month prospective, noninterventional, observational study that involved 1,549 MDD patients without sexual dysfunction at baseline in 12 countries worldwide. Depression severity was measured using the Clinical Global Impression of Severity and the 16-item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16). Depression-related pain was measured using the pain-related items of the Somatic Symptom Inventory. Remission was defined as a QIDS-SR16 score ≤5. Generalized estimating equation regression models were used to examine baseline factors associated with remission during follow-up. RESULTS: Being from East Asia (odds ratio [OR] 0.48 versus Mexico; P<0.001), a higher level of depression severity at baseline (OR 0.77, P=0.003, for Clinical Global Impression of Severity; OR 0.92, P<0.001, for QIDS-SR16), more previous MDD episodes (OR 0.92, P=0.007), previous treatments/therapies for depression (OR 0.78, P=0.030), and having any significant psychiatric and medical comorbidity at baseline (OR 0.60, P<0.001) were negatively associated with remission, whereas being male (OR 1.29, P=0.026) and treatment with duloxetine (OR 2.38 versus selective serotonin reuptake inhibitors, P<0.001) were positively associated with remission. However, the association between Somatic Symptom Inventory pain scores and remission no longer appeared to be significant in this multiple regression (P=0.580), (P=0.008 in descriptive statistics), although it remained significant in a subgroup of patients treated with selective serotonin reuptake inhibitors (OR 0.97, P=0.023), but not in those treated with duloxetine (P=0.182). CONCLUSION: These findings are largely consistent with previous reports from the USA and Europe. They also highlight the potential mediating role of treatment with duloxetine on the negative relationship between depression-related pain and outcomes of depression.

Katsauksia kirkon ja yhteiskunnan suhteisiin

Kirjallisuusarvostelu

In vitro antimicrobial activity of aqueous extracts from Lentinula edodes isolates against Colletotrichum sublineolum and Xanthomonas axonopodis pv. Passiflorae

The aim of this study was to evaluate the antimicrobial activity of aqueous extracts from fruiting bodies of different isolates of Lentinula edodeson the pathogens Colletotrichum sublineolum, the causal agent of anthracnose in sorghum, and Xanthomonas axonopodispv. passiflorae, the causal agent of bacterial spot in passion fruit. Results showed that the aqueous extracts from isolates LE JAB-K and LE 95/01 significantly reduced C. sublineolumspore germination,while the isolate LE 96/22 was the only one to inhibit the pathogen mycelial growth. However, all L. edodesisolates showed inhibitory effect on C. sublineolumappressorium formation. Regarding X. axonopodispv. passiflorae, the aqueous extracts from all L. edodesisolates significantly reduced the in vitromultiplication of the bacterium. However, antimicrobial activity was lost when the extracts were autoclaved, demonstrating their thermolabile property. The aqueous extract from isolate LE 96/22 was also partially purified by anion exchange chromatography and fraction V exhibited high inhibitory activity on the in vitromycelial growth of C. sublineolum, while the multiplication of X. axonopodispv. passifloraewas inhibited by fractions IV, V and VII. Thus, L. edodesisolates were shown to produce compounds exhibiting antifungal and antibacterial activities against phytopathogens, which are mainly concentrated in fraction V.

Perspectives interculturelles et interlinguistiques sur le discours académique – Crosscultural and Crosslinguistic Perspectives on Academic Discourse. Volume 1

The Department of French Studies of the University of Turku (Finland) organized an International Bilingual Conference on Crosscultural and Crosslinguistic Perspectives on Academic Discourse from 2022 May 2005. The event hosted specialists on Academic Discourse from Belgium, Finland, France, Germany, Italy, Norway, Spain, and the USA. This book is the first volume in our series of publications on Academic Discourse (AD hereafter). The following pages are composed of selected papers from the conference and focus on different aspects and analytical frameworks of Academic Discourse. One of the motivations behind organizing the conference was to examine and expand research on AD in different languages. Another one was to question to what extent academic genres are culturebound and language specific or primarily field or domain specific. The research carried out on AD has been mainly concerned with the use of English in different academic settings for a long time now – mainly written contexts – and at the expense of other languages. Alternatively the academic genre conventions of English and English speaking world have served as a basis for comparison with other languages and cultures. We consider this first volume to be a strong contribution to the spreading out of researches based on other languages than English in AD, namely Finnish, French, Italian, Norwegian and Romanian in this book. All the following articles have a strong link with the French language: either French is constitutive of the AD corpora under examination or the article was written in French. The structure of the book suggests and provides evidence that the concept of AD is understood and tackled to varying degrees by different scholars. Our first volume opens up the discussion on what AD is and backs dissemination, overlapping and expansion of current research questions and methodologies. The book is divided into three parts and contains four articles in English and six articles in French. The papers in part one and part two cover what we call the prototypical genre of written AD, i.e. the research article. Part one follows up on issues linked to the 13 Research Article (RA hereafter). Kjersti Fløttum asks wether a typical RA exists and concentrates on authors’ voices in RA (self and other dimensions), whereas Didriksen and Gjesdal’s article focuses on individual variation of the author’s voice in RA. The last article in this section is by Nadine Rentel and deals with evaluation in the writing of RA. Part two concentrates on the teaching and learning of AD within foreign language learning, another more or less canonical genre of AD. Two aspects of writing are covered in the first two articles: foreign students’ representations on rhetorical traditions (Hidden) and a contrastive assessment of written exercices in French and Finnish in Higher Education (Suzanne). The last contribution in this section on AD moves away from traditional written forms and looks at how argumentation is constructed in students’ oral presentations (Dervin and Fauveau). The last part of the book continues the extension by featuring four articles written in French exploring institutional and scientific discourses. Institutional discourses under scrutiny include the European Bologna Process (Galatanu) and Romanian reform texts (Moilanen). As for scientific discourses, the next paper in this section deconstructs an ideological discourse on the didactics of French as a foreign language (Pescheux). Finally, the last paper in part three reflects on varied forms of AD at university (Defays). We hope that this book will add some fuel to continue discussing diverse forms of and approches to AD – in different languages and voices! No need to say that with the current upsurge in academic mobility, reflecting on crosscultural and crosslinguistic AD has just but started.

MICROPROPAGATION AND ACCLIMATIZATION OF Aegiphila verticillata Vell.: AN ENDANGERED WOODY SPECIES

The objective of this work was to establish an efficient protocol for in vitro multiplication and rooting, as well as ex vitroacclimatization of Aegiphila verticillata, a woody species found in Brazilian rocky fields. Aseptic cultures were established by seeds and two multiplication analyses were performed. In the first, we employed 6-benzylaminopurine (BAP – 0, 2.5, 5 and 7.5 μM) + α-naphthalene acetic acid (NAA – 0, 0.2, 0.4 and 0.6 μM) and, in the second, were studied adenine sulfate, kinetin and thidiazuron (0, 5, 7.5, 10 and 12.5 μM). After 90 days, we assessed the quantitative and qualitative shoot propagation. There were more than 90% seed germination and low contamination (2%). In multiplication phase, the culture medium that promoted the best quantitative and qualitative culture development was supplemented with 7.5 μM BAP + 0.4 μM NAA. In the rooting assay, were used NAA, indole-3-acetic acid (IAA) and indole-3-butyric acid (IBA) (0, 0.1, 0.2, 0.3 or 0.4 μM). After 90 days, the root number and rooting quality were evaluated. In this analysis, differences were not found between the control and the other treatments. Rooted plantlets were acclimatized in styrofoam trays for 30 days, after which they were transferred to pots in the greenhouse. Only 3% of the plants subjected to initial acclimatization died and 70% of the plants transferred to the field conditions survived and showed normal development. The results founded in this work are the first involving in vitro propagation and ex vitroacclimatization of Aegiphila verticillata and provide a continuous supply of this medicinal native species, endangered due anthropogenic activities.