Bryophytes (Musci) unexpectedly rare or absent in the Azores.

Search for bryophytes in the Azores has until now resulted in a recording of about 430 species of mosses and hepatics. A few of these species are endemic to the Azores or to the Macaronesian island groups. The majority of the other species includes cosmopolitan or oceanic/suboceanic European species. This paper treats some mosses (Musci) which have not managed to get established in the Azorean bryovegetation. Some are just unexpectedly rare and frequently recorded as present in only one or two of the nine Azorean islands. All such species must overcome the gap between the Azorean islands and/or between the islands and the continents. This is quite possible, especially for richly diaspore-spreading species. However, I hypothesize that the principal hinder to the establishment of new bryophyte species, in the remote islands of the Azores, is the potent competition of already established bryo-communities on all sorts of substrates. Also, the influx of diaspores may not be large enough to secure an establishment there. The recent (last 50 yrs) influx of new species to the Azores has mainly been to sites within the low-altitude, profoundly maninfluenced landscape. There, competition from already established bryophyte species is much less potent than in the native plant communities in forest/shrub vegetation at altitudes above 500 m (cf. SJÖGREN 2003). Far-reaching changes of the composition of endemic Azorean bryo-communities within the remains of native Juniperus-Laurus-Erica forests are consequently not likely to take place within the near future. However, continued man-made changes within the Azorean high-altitude landscape, such as plantation of alien tree species, construction or improvement of roads and tracks, extension of areas of managed grasslands, plantation of invasive alien vascular plants may facilitate the influx of new bryophyte species, even there

De nouvelles sources pour l'histoire politique de la 'première chine populaire' (1949-1976)

Les changements politiques intervenus en Chine depuis 1976 ont entraîné un renouvellement de la politique officielle en matière historique qui a favorisé la publication de nouvelles sources sur l’histoire de la première Chine populaire. Pour l’essentiel, il s’agit de recueils documentaires, de biographies, de mémoires et de témoignages de toutes sortes, parmi lesquels les plus novateurs sont ceux des épouses et des enfants de dirigeants, et ceux plus récents de victimes des calamités. Bien que la plupart d’entre elles se situent à l’intérieur de la vulgate officielle, ces sources autorisent des progrès incontestables dans la connaissance de l’histoire du régime chinois, de la société formée par ses chefs et de certaines dissidences locales.The political changes in China since 1976 brought about a renewal of official policy in terms of history that has led to the publication of new sources on the history of the first People’s China. For the most part, they concern documentary collections, biographies, memoires and first-hand testimonies of all sorts, among which the most revealing are those from the leaders’ wives and children, and the more recent ones of the victims of calamities. Although most of them can be placed within the official Vulgate, these sources provide incontestable progress in the knowledge of the history of the Chinese regime, of the society formed by its leaders and of some of the local dissent

Study protocol for locoregional precision treatment of hepatocellular carcinoma with transarterial chemoembolisation (TACTida), a clinical study:idarubicin dose selection, tissue response and survival

INTRODUCTION: Hepatocellular carcinoma (HCC) is a common cause of cancer-related death, often detected in the intermediate stage. The standard of care for intermediate-stage HCC is transarterial chemoembolisation (TACE), where idarubicin (IDA) is a promising drug. Despite the fact that TACE has been used for several decades, treatment success is unpredictable. This clinical trial has been designed believing that further improvement might be achieved by increasing the understanding of interactions between local pharmacology, tumour targeting, HCC pathophysiology, metabolomics and molecular mechanisms of drug resistance. METHODS AND ANALYSIS: The study population of this single-centre clinical trial consists of adults with intermediate-stage HCC. Each tumour site will receive TACE with two different IDA doses, 10 and 15 mg, on separate occasions. Before and after each patient's first TACE blood samples, tissue and liquid biopsies, and positron emission tomography (PET)/MRI will be performed. Blood samples will be used for pharmacokinetics (PK) and liver function evaluation. Tissue biopsies will be used for histopathology analyses, and culturing of primary organoids of tumour and non-tumour tissue to measure cell viability, drug response, multiomics and gene expression. Multiomics analyses will also be performed on liquid biopsies. PET/MRI will be used to evaluate tumour viability and liver metabolism. The two doses of IDA will be compared regarding PK, antitumour effects and safety. Imaging, molecular biology and multiomics data will be used to identify HCC phenotypes and their relation to drug uptake and metabolism, treatment response and survival. ETHICS AND DISSEMINATION: Participants give informed consent. Personal data are deidentified. A patient will be withdrawn from the study if considered medically necessary, or if it is the wish of the patient. The study has been approved by the Swedish Ethical Review Authority (Dnr. 2021-01928) and by the Medical Product Agency, Uppsala, Sweden. TRIAL REGISTRATION NUMBER: EudraCT number: 2021-001257-31

The gut microbiota is a major regulator of androgen metabolism in intestinal contents

Androgens exert important effects both in androgen-responsive tissues and in the intestinal tract. To determine the impact of the gut microbiota (GM) on intestinal androgen metabolism, we measured unconjugated (free) and glucuronidated androgen levels in intestinal contents from the small intestine, with a low bacterial density, and from cecum and colon, with a high bacterial density. Using a specific, sensitive gas chromatography-tandem mass spectrometry method, we detected high levels of glucuronidated testosterone (T) and dihydrotestosterone (DHT) in small intestinal content of mice of both sexes, whereas in the distal intestine we observed remarkably high levels of free DHT, exceeding serum levels by >20-fold. Similarly, in young adult men high levels of unconjugated DHT, >70-fold higher than in serum, were detected in feces. In contrast to mice with a normal GM composition, germ-free mice had high levels of glucuronidated T and DHT, but very low free DHT levels, in the distal intestine. These findings demonstrate that the GM is involved in intestinal metabolism and deglucuronidation of DHT and T, resulting in extremely high free levels of the most potent androgen, DHT, in the colonic content of young and healthy mice and men

Early divergent strains of Yersinia pestis in Eurasia 5,000 years ago.

The bacteria Yersinia pestis is the etiological agent of plague and has caused human pandemics with millions of deaths in historic times. How and when it originated remains contentious. Here, we report the oldest direct evidence of Yersinia pestis identified by ancient DNA in human teeth from Asia and Europe dating from 2,800 to 5,000 years ago. By sequencing the genomes, we find that these ancient plague strains are basal to all known Yersinia pestis. We find the origins of the Yersinia pestis lineage to be at least two times older than previous estimates. We also identify a temporal sequence of genetic changes that lead to increased virulence and the emergence of the bubonic plague. Our results show that plague infection was endemic in the human populations of Eurasia at least 3,000 years before any historical recordings of pandemics

Tailored vs. Standardized Internet-Based Cognitive Behavior Therapy for Depression and Comorbid Symptoms: A Randomized Controlled Trial

Background and Aims:Major depression can be treated by means of cognitive behavior therapy, delivered via the Internet as guided self-help. Individually tailored guided self-help treatments have shown promising results in the treatment of anxiety disorders. This randomized controlled trial tested the efficacy of an Internet-based individually tailored guided selfhelp treatment which specifically targeted depression with comorbid symptoms. The treatment was compared both to standardized (non-tailored) Internet-based treatment and to an active control group in the form of a monitored online discussion group. Both guided self-help treatments were based on cognitive behavior therapy and lasted for 10 weeks. The discussion group consisted of weekly discussion themes related to depression and the treatment of depression. Methods:A total of 121 participants with diagnosed major depressive disorder and with a range of comorbid symptoms were randomized to three groups. The tailored treatment consisted of a prescribed set of modules targeting depression as well as comorbid problems. The standardized treatment was a previously tested guided self-help program for depression. Results:From pre-treatment to post-treatment, both treatment groups improved on measures of depression, anxiety and quality of life. The results were maintained at a 6-month follow-up. Subgroup analyses showed that the tailored treatment was more effective than the standardized treatment among participants with higher levels of depression at baseline and more comorbidity, both in terms of reduction of depressive symptoms and on recovery rates. In the subgroup with lower baseline scores of depression, few differences were seen between treatments and the discussion group. Conclusions:This study shows that tailored Internet-based treatment for depression is effective and that addressing comorbidity by tailoring may be one way of making guided self-help treatments more effective than standardized approaches in the treatment of more severe depression

The Human Melanoma Proteome Atlas—Complementing the melanoma transcriptome

The MM500 meta‐study aims to establish a knowledge basis of the tumor proteome to serve as a complement to genome and transcriptome studies. Somatic mutations and their effect on the transcriptome have been extensively characterized in melanoma. However, the effects of these genetic changes on the proteomic landscape and the impact on cellular processes in melanoma remain poorly understood. In this study, the quantitative mass‐spectrometry‐based proteomic analysis is interfaced with pathological tumor characterization, and associated with clinical data. The melanoma proteome landscape, obtained by the analysis of 505 well‐annotated melanoma tumor samples, is defined based on almost 16 000 proteins, including mutated proteoforms of driver genes. More than 50 million MS/MS spectra were analyzed, resulting in approximately 13,6 million peptide spectrum matches (PSMs). Altogether 13 176 protein‐coding genes, represented by 366 172 peptides, in addition to 52 000 phosphorylation sites, and 4 400 acetylation sites were successfully annotated. This data covers 65% and 74% of the predicted and identified human proteome, respectively. A high degree of correlation (Pearson, up to 0.54) with the melanoma transcriptome of the TCGA repository, with an overlap of 12 751 gene products, was found. Mapping of the expressed proteins with quantitation, spatiotemporal localization, mutations, splice isoforms, and PTM variants was proven not to be predicted by genome sequencing alone. The melanoma tumor molecular map was complemented by analysis of blood protein expression, including data on proteins regulated after immunotherapy. By adding these key proteomic pillars, the MM500 study expands the knowledge on melanoma disease