Prospektywne, trwające 6 miesięcy badanie poświęcone ocenie skuteczności i bezpieczeństwa stosowania walproinianu o przedłużonym uwalnianiu oraz jakości życia chorych na padaczkę stosujących ten lek

Celem tego prospektywnego, wieloośrodkowego badania, przeprowadzonego metodą otwartej próby, była ocena skuteczności i bezpieczeństwa stosowania walproinianu o przedłużonym uwalnianiu(ER, extender-release) oraz jego wpływu na jakość życia u chorych na padaczkę. Do badania włączono osoby z potwierdzonym rozpoznaniem padaczki. Uczestnikom przez 6 miesięcy podawano walproinian ER jako pierwszy lek w monoterapii lub w połączeniu z dotychczas stosowanym lekiem. Ocenę skuteczności i bezpieczeństwa leczenia przeprowadzono po 1 (V1), 3 (V3) i 6 miesiącach (V6) od rozpoczęcia badania. Do oceny jakości życia przed terapią i po 6 miesiącach leczenia użyto kwestionariusza QOLIE-31. W analizie uwzględniono 958 chorych na padaczkę. Wyjściowa częstość napadów padaczkowych wynosiła 8,56 na miesiąc. Średnia dawka podtrzymująca walproinianu ER wynosiła 750 mg na dobę. Liczba napadów padaczkowych w miesiącu, oszacowana podczas ostatniej wizyty, zmniejszyła się o 88,3% w stosunku do wartości wyjściowych. Nastąpiła poprawa jakości życia w zakresie następujących kategorii: &#8222;obawa przed napadami&#8221; (p = 0,000), &#8222;ogólna jakość życia&#8221; (p = 0,000), &#8222;funkcjonowanie społeczne&#8221; (p < 0,01) i &#8222;pytanie 31.&#8221; (ocena ogólnego stanu zdrowia) (p = 0,000). Odnotowano pogorszenie w zakresie aktywności życiowej (p = 0,000). We wczesnej fazie leczenia najczęstszymi działaniami niepożądanymi były suchość w jamie ustnej, zawroty głowy i jadłowstręt. Po 6 miesiącach pacjenci najczęściej skarżyli się na zwiększenie masy ciała, łysienie plackowate i drżenie. Wyniki badania dowodzą, że stosowanie walproinianu ER w monoterapii lub w terapii skojarzonej przez 6 miesięcy wiąże się z istotnie większym procentowym ograniczeniem częstości wszystkich rodzajów napadów w stosunku do wartości wyjściowych i z istotnie większym odsetkiem odpowiedzi na leczenie oraz odsetkiem chorych bez napadów. Ponadto terapia była dobrze tolerowana przez chorych i powodowała poprawę jakości życia. Polski Przegląd Neurologiczny 2010; 6 (4): 212&#8211;21

Transcriptome profile of halofuginone resistant and sensitive strains of Eimeria tenella

The antiparasitic drug halofuginone is important for controlling apicomplexan parasites. However, the occurrence of halofuginone resistance is a major obstacle for it to the treatment of apicomplexan parasites. Current studies have identified the molecular marker and drug resistance mechanisms of halofuginone in Plasmodium falciparum. In this study, we tried to use transcriptomic data to explore resistance mechanisms of halofuginone in apicomplexan parasites of the genus Eimeria (Apicomplexa: Eimeriidae). After halofuginone treatment of E. tenella parasites, transcriptome analysis was performed using samples derived from both resistant and sensitive strains. In the sensitive group, DEGs associated with enzymes were significantly downregulated, whereas the DNA damaging process was upregulated after halofuginone treatment, revealing the mechanism of halofuginone-induced parasite death. In addition, 1,325 differentially expressed genes (DEGs) were detected between halofuginone resistant and sensitive strains, and the DEGs related to translation were significantly downregulated after halofuginone induction. Overall, our results provide a gene expression profile for further studies on the mechanism of halofuginone resistance in E. tenella

Novel loci and pathways significantly associated with longevity

Only two genome-wide significant loci associated with longevity have been identified so far, probably because of insufficient sample sizes of centenarians, whose genomes may harbor genetic variants associated with health and longevity. Here we report a genome-wide association study (GWAS) of Han Chinese with a sample size 2.7 times the largest previously published GWAS on centenarians. We identified 11 independent loci associated with longevity replicated in Southern-Northern regions of China, including two novel loci (rs2069837-IL6; rs2440012-ANKRD20A9P) with genome-wide significance and the rest with suggestive significance (P < 3.65 × 10(−5)). Eight independent SNPs overlapped across Han Chinese, European and U.S. populations, and APOE and 5q33.3 were replicated as longevity loci. Integrated analysis indicates four pathways (starch, sucrose and xenobiotic metabolism; immune response and inflammation; MAPK; calcium signaling) highly associated with longevity (P ≤ 0.006) in Han Chinese. The association with longevity of three of these four pathways (MAPK; immunity; calcium signaling) is supported by findings in other human cohorts. Our novel finding on the association of starch, sucrose and xenobiotic metabolism pathway with longevity is consistent with the previous results from Drosophilia. This study suggests protective mechanisms including immunity and nutrient metabolism and their interactions with environmental stress play key roles in human longevity

Cell transcriptomic atlas of the non-human primate Macaca fascicularis.

Studying tissue composition and function in non-human primates (NHPs) is crucial to understand the nature of our own species. Here we present a large-scale cell transcriptomic atlas that encompasses over 1 million cells from 45 tissues of the adult NHP Macaca fascicularis. This dataset provides a vast annotated resource to study a species phylogenetically close to humans. To demonstrate the utility of the atlas, we have reconstructed the cell-cell interaction networks that drive Wnt signalling across the body, mapped the distribution of receptors and co-receptors for viruses causing human infectious diseases, and intersected our data with human genetic disease orthologues to establish potential clinical associations. Our M. fascicularis cell atlas constitutes an essential reference for future studies in humans and NHPs.We thank W. Liu and L. Xu from the Huazhen Laboratory Animal Breeding Centre for helping in the collection of monkey tissues, D. Zhu and H. Li from the Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory) for technical help, G. Guo and H. Sun from Zhejiang University for providing HCL and MCA gene expression data matrices, G. Dong and C. Liu from BGI Research, and X. Zhang, P. Li and C. Qi from the Guangzhou Institutes of Biomedicine and Health for experimental advice or providing reagents. This work was supported by the Shenzhen Basic Research Project for Excellent Young Scholars (RCYX20200714114644191), Shenzhen Key Laboratory of Single-Cell Omics (ZDSYS20190902093613831), Shenzhen Bay Laboratory (SZBL2019062801012) and Guangdong Provincial Key Laboratory of Genome Read and Write (2017B030301011). In addition, L.L. was supported by the National Natural Science Foundation of China (31900466), Y. Hou was supported by the Natural Science Foundation of Guangdong Province (2018A030313379) and M.A.E. was supported by a Changbai Mountain Scholar award (419020201252), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16030502), a Chinese Academy of Sciences–Japan Society for the Promotion of Science joint research project (GJHZ2093), the National Natural Science Foundation of China (92068106, U20A2015) and the Guangdong Basic and Applied Basic Research Foundation (2021B1515120075). M.L. was supported by the National Key Research and Development Program of China (2021YFC2600200).S

The Euscaphis japonica genome and the evolution of malvids

Malvids is one of the largest clades of rosids, includes 58 families and exhibits remarkable morphological and ecological diversity. Here, we report a high-quality chromosome-level genome assembly for Euscaphis japonica, an early-diverging species within malvids. Genome-based phylogenetic analysis suggests that the unstable phylogenetic position of E. japonica may result from incomplete lineage sorting and hybridization event during the diversification of the ancestral population of malvids. Euscaphis japonica experienced two polyploidization events: the ancient whole genome triplication event shared with most eudicots (commonly known as the c event) and a more recent whole genome duplication event, unique to E. japonica. By resequencing 101 samples from 11 populations, we speculate that the temperature has led to the differentiation of the evergreen and deciduous of E. japonica and the completely different population histories of these two groups. In total, 1012 candidate positively selected genes in the evergreen were detected, some of which are involved in flower and fruit development. We found that reddening and dehiscence of the E. japonica pericarp and long fruit-hanging time promoted the reproduction of E. japonica populations, and revealed the expression patterns of genes related to fruit reddening, dehiscence and abscission. The key genes involved in pentacyclic triterpene synthesis in E. japonica were identified, and different expression patterns of these genes may contribute to pentacyclic triterpene diversification. Our work sheds light on the evolution of E. japonica and malvids, particularly on the diversification of E. japonica and the genetic basis for their fruit dehiscence and abscission.DATA AVAILABILITY STATEMENT : All sequences described in this manuscript have been submitted to the National Genomics Data Center (NGDC). The raw whole-genome data of E. japonica have been deposited in BioProject/GSA (https://bigd.big.ac.cn/gsa.) under the accession codes PRJCA005268/CRA004271, and the assembly and annotation data have been deposited at BioProject/GWH (https://bigd.big.ac.cn/gwh) under the accession codes PRJCA005268/GWHBCHS00000000. The raw transcriptomes data of E. japonica have been deposited in BioProject/GSA (https://bigd.big.ac.cn/gsa.) under the accession codes PRJCA005298/CRA004272.SUPPLEMENTARY MATERIAL 1: Supplementary Note 1. Chromosome number assessment. Supplementary Note 2. Whole-genome duplication identification and dating. Supplementary Note 3. Observation of E. japonica seed dispersal. Supplementary Note 4. Determination of pentacyclic triterpene substances. Figure S1. Cytogenetic analysis of E. japonica. Figure S2. Genome size and heterozygosity of E. japonica estimation using 17 k-mer distribution. Figure S3. Interchromosomal of Hi-C chromosome contact map of E. japonica genome. Figure S4. Gene structure prediction results of E. japonica and other species. Figure S5. Venn diagram shows gene families of malvids. Figure S6. Phylogenetic tree constructed by chloroplast genomes from 17 species. Figure S7. Concatenated- and ASTRAL-based phylogenetic trees. Figure S8. Ks distribution in E. japonica. Figure S9. Distributions of synonymous substitutions per synonymous site (Ks) of one-to-one orthologs identified between E. japonica and P. trichocarpa and V. vinifera. Figure S10. Population structure plot. Figure S11. Fixation index (FST) heat map among E. japonica populations. Figure S12. Phylogenetic analysis of MADS-box genes from O. sativa, A. thaliana, E. japonica, and T. cacao. Figure S13. Observation the fruit development. Figure S14. Animal seed dispersal. Figure S15. Anthocyanin biosynthesis in E. japonica fruits. Figure S16. Carotenoid accumulation and the chlorophyll degradation in E. japonica fruits. Figure S17. Expression profile of fruit dehiscence-related genes. Figure S18. Phylogenetic tree of DELLA genes obtained from six malvids species. Figure S19. Phylogenetic tree of CAD genes obtained from seven malvids species. Figure S20. Expression pattern of fruit abscission-related genes. Figure S21. Structure of pentacyclic triterpene compounds separated from Euscaphis. Figure S22. Phylogenetic tree of HMGR gene in plants. Figure S23. Phylogenetic tree of P450s gene family obtained from A. thaliana and E. japonica.SUPPLEMENTARY MATERIAL 2: Table S1. Assembled statistics of E. japonica genome. Table S2. Evaluation of E. japonica genome assembly. Table S3. Chromosome length of E. japonica. Table S4. Prediction of gene structures of the E. japonica genome. Table S5. Statistics on the function annotation of the E. japonica genome. Table S6. Non-coding RNA annotation results of E. japonica genome. Table S7. BUSCO assessment of the E. japonica annotated genome. Table S8. Statistic of repeat sequence in E. japonica genome. Table S9. Gene-clustering statistics for 17 species. Table S10. KEGG enrichment result of unique genes families of E. japonica. Table S11. Gene Ontology (GO) and KEGG enrichment result of significant shared by malvids species gene families. Table S12. Gene Ontology (GO) and KEGG enrichment result of significant expansion of E. japonica gene families. Table S13. Gene Ontology (GO) enrichment result of significant contraction of E. japonica gene families. Table S14. Statistical sampling population information. Table S15. Statistics population resequencing information. Table S16. Statistical nucleotide polymorphisms in the populations. Table S17. Candidate positive selection genes (PSGs) in the evergreen population. Table S18. Candidate positive selection genes (PSGs) in the deciduous population. Table S19. Gene Ontology (GO) enrichment result of significant PSGs in the evergreen population. Table S20. List of MADS-box genes identified in E. japonica. Table S21. Genes involved in anthocyanin biosynthesis, carotenoid biosynthesis, and chlorophyll degradation. Table S22. Identification fruit dehiscence-related genes in E. japonica. Table S23. Genes related to lignin synthesis that are highly expressed during pericarp dehiscence. Table S24. Gene expression levels (FPKMs) of fruit abscission-related genes in pericarp. Table S25. Triterpene compounds separated from Euscaphis. Table S26. Number of putative pentacyclic triterpene-related genes in the malvids species. Table S27. Identified pentacyclic triterpene synthesis-related genes in E. japonica genome. Table S28. Statistical simple sequence repeat.Fund for Excellent Doctoral Dissertation of Fujian Agriculture and Forestry University, China; Fujian Provincial Department of Science E. japonica Evolution and Selection of Ornamental Medicinal Resources, China; the Project of Forestry Peak Discipline at Fujian Agriculture and Forestry University, China; the Collection, Development and Utilization of Eascaphis konlshli Germplasm Resources; the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program and from Ghent University.https://onlinelibrary.wiley.com/journal/1365313xam2022BiochemistryGeneticsMicrobiology and Plant Patholog

Measuring thermoelectric transport properties of materials

In this review we discuss considerations regarding the common techniques used for measuring thermoelectric transport properties necessary for calculating the thermoelectric figure of merit, zT. Advice for improving the data quality in Seebeck coefficient, electrical resistivity, and thermal conductivity (from flash diffusivity and heat capacity) measurements are given together with methods for identifying possible erroneous data. Measurement of the Hall coefficient and calculation of the charge carrier concentration and mobility is also included due to its importance for understanding materials. It is not intended to be a complete record or comparison of all the different techniques employed in thermoelectrics. Rather, by providing an overview of common techniques and their inherent difficulties it is an aid to new researchers or students in the field. The focus is mainly on high temperature measurements but low temperature techniques are also briefly discussed