ForestTreeDB: a database dedicated to the mining of tree transcriptomes

ForestTreeDB is intended as a resource that centralizes large-scale expressed sequence tag (EST) sequencing results from several tree species (). It currently encompasses 344 878 quality sequences from 68 libraries, from diverse organs of conifer and hybrid poplar trees. It utilizes the Nimbus data model to provide a hosting system for multiple projects, and uses object-relational mapping APIs in Java and Perl for data accesses within an Oracle database designed to be scalable, maintainable and extendable. Transcriptome builds or unigene sets occupy the focal point of the system. Several of the five current species-specific unigenes were used to design microarrays and SNP resources. The ForestTreeDB web application provides the means for multiple combination database queries. It presents the user with a list of discrete queries to retrieve and download large EST datasets or sequences from precompiled unigene assemblies. Functional annotation assignment is not trivial in conifers which are distantly related to angiosperm model plants. Optimal annotations are achieved through database queries that integrate results from several procedures based open-source tools. ForestTreeDB aims to facilitate sequence mining of coherent annotations in multiple species to support comparative genomic approaches. We plan to continuously enrich ForestTreeDB with other resources through collaborations with other genomic projects

Anatomy and Three-Dimensional Reconstructions of the Brain of the White Whale (Delphinapterus leucas) From Magnetic Resonance Images

Magnetic resonance imaging offers a means of observing the internal structure of the brain where traditional procedures of embedding, sectioning, staining, mounting, and microscopic examination of thousands of sections are not practical. Furthermore, internal structures can be analyzed in their precise quantitative spatial interrelationships, which is difficult to accomplish after the spatial distortions often accompanying histological processing. For these reasons, magnetic resonance imaging makes specimens that were traditionally difficult to analyze, more accessible. In the present study, images of the brain of a white whale (Beluga) Delphinapterus leucas were scanned in the coronal plane at 119 antero-posterior levels. Fromthese scans, a computer-generated three-dimensional model was constructed using the programs VoxelViewand VoxelMath (Vital Images, Inc.). This model, wherein details of internal and external morphology are represented in three-dimensional space, was then resectioned in orthogonal planes to produce corresponding series of “virtual” sections in the horizontal and sagittal planes. Sections in all three planes display the sizes and positions of such structures as the corpus callosum, internal capsule, cerebral peduncles, cerebral ventricles, certain thalamic nuclear groups, caudate nucleus, ventral striatum, pontine nuclei, cerebellar cortex and white matter, and all cerebral cortical sulci and gyri

Using atomic interference to probe atom-surface interaction

We show that atomic interference in the reflection from two suitably polarized evanescent waves is sensitive to retardation effects in the atom-surface interaction for specific experimental parameters. We study the limit of short and long atomic de Broglie wavelength. The former case is analyzed in the semiclassical approximation (Landau-Zener model). The latter represents a quantum regime and is analyzed by solving numerically the associated coupled Schroedinger equations. We consider a specific experimental scheme and show the results for rubidium (short wavelength) and the much lighter meta-stable helium atom (long wavelength). The merits of each case are then discussed.Comment: 11 pages, including 6 figures, submitted to Phys. Rev. A, RevTeX sourc

Common clonal origin of chronic myelomonocytic leukemia and B-cell acute lymphoblastic leukemia in a patient with a germline CHEK2 variant

Hematological malignancies are broadly divided into myeloid and lymphoid neoplasms, reflecting the two major cellular lineages of the hematopoietic system. It is generally rare for hematological malignancies to spontaneously progress with a switch from myeloid to lymphoid lineage. We describe the exceptional case of a patient who sequentially developed myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), and B-cell acute lymphoblastic leukemia (B-ALL), as well as our investigation into the underlying pathogenesis. Using whole-exome sequencing (WES) performed on sorted CMML and B-ALL cell fractions, we identified both common and unique potential driver mutations, suggesting a branching clonal evolution giving rise to both diseases. Interestingly, we also identified a germline variant in the cancer susceptibility gene CHEK2 We validated that this variant (c.475T > C; p.Y159H), located in the forkhead-associated (FHA) domain, impairs its capacity to bind BRCA1 in cellulo. This unique case provides novel insight into the genetics of complex hematological diseases and highlights the possibility that such patients may carry inherited predispositions

Nivolumab combined with brentuximab vedotin for R/R primary mediastinal large B-cell lymphoma: A 3-year follow-up

Patients with relapsed/refractory primary mediastinal large B-cell lymphoma (R/R PMBL) have poor responses to salvage therapy. Nivolumab and brentuximab vedotin (BV) showed promising early efficacy in patients with R/R PMBL in the phase 1/2 open-label, multicenter CheckMate 436 study; we report safety and efficacy findings from the 3-year follow-up. Patients who were eligible were aged ≥15 years with R/R PMBL previously treated with either high-dose chemotherapy plus autologous hematopoietic cell transplantation (HCT) or ≥2 prior multiagent chemotherapies, and had Eastern Cooperative Oncology Group performance status scores of 0 to 1 and CD30 expression of ≥1%. Patients were treated with nivolumab 240 mg and BV 1.8 mg/kg once every 3 weeks until disease progression or unacceptable toxicity. Primary end point was objective response rate (ORR); secondary end points included complete response rate, duration of response, progression-free survival (PFS), and overall survival (OS). Safety was monitored throughout. At final database lock (30 March 2022), 29 patients had received nivolumab plus BV; median follow-up was 39.6 months. Investigator-assessed ORR was 73.3%; median time to response was 1.3 months (range, 1.1-4.8). Median PFS was 26.0 months; median OS was not reached. PFS and OS rates at 24 months were 55.5% (95% confidence interval [CI], 32.0-73.8) and 75.5% (95% CI, 55.4-87.5), respectively. The most frequently occurring grade 3/4 treatment-related adverse event was neutropenia. Consolidative HCT was received by 12 patients, with a 100-day complete response rate of 100.0%. This 3-year follow-up showed long-term efficacy for nivolumab plus BV in R/R PMBL, with no new safety signals. This trial was registered at www.clinicaltrials.gov as #NCT02581631

Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed/Refractory Classic Hodgkin Lymphoma

Hodgkin, 9p24Purpose Hodgkin Reed-Sternberg cells harbor alterations in chromosome 9p24.1, leading to overexpression of programmed death-ligand 1 (PD-L1) and PD-L2. Pembrolizumab, a programmed death 1-blocking antibody, demonstrated a high overall response rate (ORR) in patients with relapsed or refractory classic Hodgkin lymphoma (rrHL) in phase I testing. Methods KEYNOTE-087 ( ClinicalTrials.gov identifier, NCT02453594) was a single-arm phase II study of pembrolizumab in three cohorts of patients with rrHL, defined on the basis of lymphoma progression after (1) autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV); (2) salvage chemotherapy and BV, and thus, ineligible for ASCT because of chemoresistant disease; and (3) ASCT, but without BV after transplantation. Patients received pembrolizumab 200 mg once every 3 weeks. Response was assessed every 12 weeks. The primary end points were ORR by central review and safety. Results A total of 210 patients were enrolled and treated (69 in cohort 1, 81 in cohort 2, and 60 in cohort 3). At the time of analysis, patients received a median of 13 treatment cycles. Per central review, the ORR was 69.0% (95% CI, 62.3% to 75.2%), and the complete response rate was 22.4% (95% CI, 16.9% to 28.6%). By cohort, ORRs were 73.9% for cohort 1, 64.2% for cohort 2, and 70.0% for cohort 3. Thirty-one patients had a response 65 6 months. The safety profile was largely consistent with previous pembrolizumab studies. Conclusion Pembrolizumab was associated with high response rates and an acceptable safety profile in patients with rrHL, offering a new treatment paradigm for this disease

A within-sibling pair analysis of lifestyle behaviours and BMI z-score in the multi-centre I.Family study

Background and aims: By investigating differences in lifestyle behaviours and BMI in sibling pairs, family-level confounding is minimized and causal inference is improved, compared to cross-sectional studies of unrelated children. Thus, we aimed to investigate within-sibling pair differences in different lifestyle behaviours and differences in BMI z-scores in children and adolesents. Methods and results: We examined three groups of sibling pairs 1) all same-sex sibling pairs with maximum 4 years age difference (n = 1209 pairs from 1072 families in 8 countries, mean age 10.7 years, standard deviation 2.4 years), 2) sibling pairs discordant for overweight (n = 262) and 3) twin pairs (n = 85). Usual dietary intake was estimated by 24-h recalls and time spent in light (LPA) and moderate-to-vigorous physical activity (MVPA) was measured by accelerometers. Screen time, sleep and dieting for weight loss were assessed by questionnaires. Within all 3 groups of sibling pairs, more time in MVPA was associated with lower BMI z-score. Higher energy intake was associated with higher BMI z-score within twin pairs and within all sibling pairs who were not currently dieting for weight loss. Regarding LPA, screen time or sleep duration, no or inconsistent associations were observed for the three groups of sibling pairs. Conclusions: MVPA and energy intake were associated with BMI differences within sibling and twin pairs growing up in the same home, thus independent of family-level confounding factors. Future studies should explore whether genetic variants regulating appetite or energy expenditure behaviours account for weight differences in sibling pairs. (C) 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.Peer reviewe

Population-level impact and herd effects following the introduction of human papillomavirus vaccination programmes: updated systematic review and meta-analysis

Background More than 10 years have elapsed since human papillomavirus (HPV) vaccination was implemented. We did a systematic review and meta-analysis of the population-level impact of vaccinating girls and women against human papillomavirus on HPV infections, anogenital wart diagnoses, and cervical intraepithelial neoplasia grade 2+ (CIN2+)to summarise the most recent evidence about the effectiveness of HPV vaccines in real-world settings and to quantify the impact of multiple age-cohort vaccination.Methods In this updated systematic review and meta-analysis, we used the same search strategy as in our previous paper. We searched MEDLINE and Embase for studies published between Feb 1, 2014, and Oct 11, 2018. Studies were eligible if they compared the frequency (prevalence or incidence) of at least one HPV-related endpoint (genital HPV infections, anogenital wart diagnoses, or histologically confirmed CIN2+) between pre-vaccination and post-vaccination periods among the general population and if they used the same population sources and recruitment methods before and after vaccination. Our primary assessment was the relative risk (RR) comparing the frequency (prevalence or incidence) of HPV-related endpoints between the pre-vaccination and post-vaccination periods. We stratified all analyses by sex, age, and years since introduction of HPV vaccination. We used random-effects models to estimate pooled relative risks.Findings We identified 1702 potentially eligible articles for this systematic review and meta-analysis, and included 65 articles in 14 high-income countries: 23 for HPV infection, 29 for anogenital warts, and 13 for CIN2+.After 5\u20138 years of vaccination, the prevalence of HPV 16 and 18 decreased significantly by 83% (RR 0\ub717, 95% CI 0\ub711\u20130\ub725) among girls aged 13\u201319 years, and decreased significantly by 66% (RR 0\ub734, 95% CI 0\ub723\u20130\ub749) among women aged 20\u201324 years. The prevalence of HPV 31, 33, and 45 decreased significantly by 54% (RR 0\ub746, 95% CI 0\ub733\u20130\ub766) among girls aged 13\u201319 years. Anogenital wart diagnoses decreased significantly by 67% (RR 0\ub733, 95% CI 0\ub724\u20130\ub746) among girls aged 15\u201319 years, decreased significantly by 54% (RR 0\ub746, 95% CI 0.36\u20130.60) among women aged 20\u201324 years, and decreased significantly by 31% (RR 0\ub769, 95% CI 0\ub753\u20130\ub789) among women aged 25\u201329 years. Among boys aged 15\u201319 years anogenital wart diagnoses decreased significantly by 48% (RR 0\ub752, 95% CI 0\ub737\u20130\ub775) and among men aged 20\u201324 years they decreased significantly by 32% (RR 0\ub768, 95% CI 0\ub747\u20130\ub798). After 5\u20139 years of vaccination, CIN2+ decreased significantly by 51% (RR 0\ub749, 95% CI 0\ub742\u20130\ub758) among screened girls aged 15\u201319 years and decreased significantly by 31% (RR 0\ub769, 95% CI 0\ub757\u20130\ub784) among women aged 20\u201324 years.Interpretation This updated systematic review and meta-analysis includes data from 60 million individuals and up to 8 years of post-vaccination follow-up. Our results show compelling evidence of the substantial impact of HPV vaccination programmes on HPV infections and CIN2+ among girls and women, and on anogenital warts diagnoses among girls, women, boys, and men. Additionally, programmes with multi-cohort vaccination and high vaccination coverage had a greater direct impact and herd effects

Edge effects on components of diversity and above-ground biomass in a tropical rainforest

Edge effects are among the most significant consequences of forest fragmentation. Therefore, understanding the impacts of edge creation on biodiversity is crucial for forest management and biological conservation. In this study, we used trait‐based and phylogenetic approaches to examine the effects of fragmentation on components of diversity and above‐ground biomass of rainforest tree communities in Madagascar in forest edge vs. interior habitats. Tree communities in forest edges showed lower phylogenetic diversity relative to those in interior habitats, suggesting that some clades may be more vulnerable to environmental filtering than others. Functional diversity was also significantly lower on the edge for productivity traits, but not for dispersal traits. Tree communities in the forest edge showed higher divergence of dispersal traits and lower divergence in productivity traits than expected, while functional diversity in interior forest did not differ from random expectations. This suggests that separate mechanisms affect productivity traits vs. dispersal traits in edge habitats. There was no significant difference in above‐ground biomass between edge and interior habitats, suggesting that edge effects have not yet negatively influenced the forest's potential for carbon storage. However, these changes may not have occurred yet, given the slow turnover of tree communities. Synthesis and applications. Our results highlight the role of edge effects in the erosion of functional and phylogenetic diversity of highly diverse tree communities. While above‐ground biomass did not appear to be affected by forest edge in our study, we suggest long‐term monitoring of forests for potential changes in ecosystem functioning. These findings also indicate the need to reduce edge creation and buffer existing edges for holistic biodiversity conservation

Telomeric expression sites are highly conserved in trypanosoma brucei

Subtelomeric regions are often under-represented in genome sequences of eukaryotes. One of the best known examples of the use of telomere proximity for adaptive purposes are the bloodstream expression sites (BESs) of the African trypanosome Trypanosoma brucei. To enhance our understanding of BES structure and function in host adaptation and immune evasion, the BES repertoire from the Lister 427 strain of T. brucei were independently tagged and sequenced. BESs are polymorphic in size and structure but reveal a surprisingly conserved architecture in the context of extensive recombination. Very small BESs do exist and many functioning BESs do not contain the full complement of expression site associated genes (ESAGs). The consequences of duplicated or missing ESAGs, including ESAG9, a newly named ESAG12, and additional variant surface glycoprotein genes (VSGs) were evaluated by functional assays after BESs were tagged with a drug-resistance gene. Phylogenetic analysis of constituent ESAG families suggests that BESs are sequence mosaics and that extensive recombination has shaped the evolution of the BES repertoire. This work opens important perspectives in understanding the molecular mechanisms of antigenic variation, a widely used strategy for immune evasion in pathogens, and telomere biology