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1.
Ch. Sultan J. M. Lobaccaro S. Lumbroso S. Missov Ch. Belon M. Bost R. Dumas 《Andrologie》1994,4(3):283-287
Klinfelter syndrome was first described in adult males with gynecomastia, azoospermia and hypergonadotropic hypogonadism. Children with the 47, XXY karyotype demonstrate few clinical findings so Klinefelter syndrome is rarely diagnosed until adult life. Besides children who have been diagnosed during prenatal genetic testing, in infancy a male with 47, XXY (or variants: 46, XY-47, XXY; 48, XXXY; 48, XXYY, 49, XXXXY) may be found while undergoing evaluation of micropenis, hypospadias, cryptorchidism or facial anomalies. The older child may present with learning disabilities, behavior disorders or tall stature. At the time of puberty, the clinical picture includes small testes, gynecomastia and an eunuchoid habitus. Early diagnosis of Klinefelter syndrome must be performed since it has been demonstrated that early treatment with androgens may ameliorate many aspects of the clinical symptoms and attenuate or prevent behavioral and psychiatric disorders associated with 47, XXY males. 相似文献
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damo Davi Digenes Siena Isabela Ichihara de Barros Camila Baldin Storti Carlos Alberto Oliveira de Biagi Júnior Larissa Anastacio da Costa Carvalho Silvya Stuchi Maria&#x;Engler Josane de Freitas Sousa Wilson Araújo Silva Jr 《Journal of cellular and molecular medicine》2022,26(3):671
Our previous work using a melanoma progression model composed of melanocytic cells (melanocytes, primary and metastatic melanoma samples) demonstrated various deregulated genes, including a few known lncRNAs. Further analysis was conducted to discover novel lncRNAs associated with melanoma, and candidates were prioritized for their potential association with invasiveness or other metastasis‐related processes. In this sense, we found the intergenic lncRNA U73166 (ENSG00000230454) and decided to explore its effects in melanoma. For that, we silenced the lncRNA U73166 expression using shRNAs in a melanoma cell line. Next, we experimentally investigated its functions and found that migration and invasion had significantly decreased in knockdown cells, indicating an essential association of lncRNA U73166 for cancer processes. Additionally, using naïve and vemurafenib‐resistant cell lines and data from a patient before and after resistance, we found that vemurafenib‐resistant samples had a higher expression of lncRNA U73166. Also, we retrieved data from the literature that indicates lncRNA U73166 may act as a mediator of RNA processing and cell invasion, probably inducing a more aggressive phenotype. Therefore, our results suggest a relevant role of lncRNA U73166 in metastasis development. We also pointed herein the lncRNA U73166 as a new possible biomarker or target to help overcome clinical vemurafenib resistance. 相似文献
3.
In this short report, the genome-wide homologous recombination events were re-evaluated for classical swine fever virus (CSFV) strain AF407339. We challenged a previous study which suggested only one recombination event in AF407339 based on 25 CSFV genomes. Through our re-analysis on the 25 genomes in the previous study and the 41 genomes used in the present study, we argued that there should be possibly at least two clear recombination events happening in AF407339 through genome-wide scanning. The reasons for identifying only one recombination event in the previous study might be due to the limited number of available CSFV genome sequences at that time and the limited usage of detection methods. In contrast, as identified by most detection methods using all available CSFV genome sequences, two major recombination events were found at the starting and ending zones of the genome AF407339, respectively. The first one has two parents AF333000 (minor) and AY554397 (major) with beginning and ending breakpoints located at 19 and 607 nt of the genome respectively. The second one has two parents AF531433 (minor) and GQ902941 (major) with beginning and ending breakpoints at 8397 and 11,078 nt of the genome respectively. Phylogenetic incongruence analysis using neighbor-joining algorithm with 1000 bootstrapping replicates further supported the existence of these two recombination events. In addition, we also identified additional 18 recombination events on the available CSFV strains. Some of them may be trivial and can be ignored. In conclusion, CSFV might have relatively high frequency of homologous recombination events. Genome-wide scanning of identifying recombination events should utilize multiple detection methods so as to reduce the risk of misidentification. 相似文献
4.
Derek M. Shore Gemma L. Baillie Dow H. Hurst Frank Navas III Herbert H. Seltzman Jahan P. Marcu Mary E. Abood Ruth A. Ross Patricia H. Reggio 《The Journal of biological chemistry》2014,289(9):5828-5845
The cannabinoid 1 (CB1) allosteric modulator, 5-chloro-3-ethyl-1H-indole-2-carboxylic acid [2-(4-piperidin-1-yl-phenyl)-ethyl]-amide) (ORG27569), has the paradoxical effect of increasing the equilibrium binding of [3H](−)-3-[2-hydroxyl-4-(1,1-dimethylheptyl)phenyl]-4-[3-hydroxylpropyl]cyclohexan-1-ol (CP55,940, an orthosteric agonist) while at the same time decreasing its efficacy (in G protein-mediated signaling). ORG27569 also decreases basal signaling, acting as an inverse agonist for the G protein-mediated signaling pathway. In ligand displacement assays, ORG27569 can displace the CB1 antagonist/inverse agonist, N-(piperidiny-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide(SR141716A). The goal of this work was to identify the binding site of ORG27569 at CB1. To this end, we used computation, synthesis, mutation, and functional studies to identify the ORG27569-binding site in the CB1 TMH3-6-7 region. This site is consistent with the results of K3.28192A, F3.36200A, W5.43279A, W6.48356A, and F3.25189A mutation studies, which revealed the ORG27569-binding site overlaps with our previously determined binding site of SR141716A but extends extracellularly. Additionally, we identified a key electrostatic interaction between the ORG27569 piperidine ring nitrogen and K3.28192 that is important for ORG27569 to act as an inverse agonist. At this allosteric site, ORG27569 promotes an intermediate conformation of the CB1 receptor, explaining ORG27569''s ability to increase equilibrium binding of CP55,940. This site also explains ORG27569''s ability to antagonize the efficacy of CP55,940 in three complementary ways. 1) ORG27569 sterically blocks movements of the second extracellular loop that have been linked to receptor activation. 2) ORG27569 sterically blocks a key electrostatic interaction between the third extracellular loop residue Lys-373 and D2.63176. 3) ORG27569 packs against TMH6, sterically hindering movements of this helix that have been shown to be important for receptor activation. 相似文献
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We analyzed the temporal and spatial diversity of the microbiota in a low-usage and a high-usage hospital tap. We identified a tap-specific colonization pattern, with potential human pathogens being overrepresented in the low-usage tap. We propose that founder effects and local adaptation caused the tap-specific colonization patterns. Our conclusion is that tap-specific colonization represents a potential challenge for water safety.Humans are exposed to and consume large amounts of tap water in their everyday life, with the tap water microbiota representing a potent reservoir for pathogens (8). Despite the potential impact, our knowledge about the ecological diversification processes of the tap water microbiota is limited (4, 11).The aim of the present work was to determine the temporal and spatial distribution patterns of the planktonic tap water microbiota. We compared the summer and winter microbiota from two hospital taps supplied from the same water source. We analyzed 16S rRNA gene clone libraries by using a novel alignment-independent approach for operational taxonomic unit (OTU) designation (6), while established OTU diversity and richness estimators were used for the ecological interpretations.Tap water samples (1 liter) from a high-usage kitchen and a low-usage toilet cold-water tap in Akershus University Hospital, Lørenskog, Norway, were collected in January and July 2006. The total DNA was isolated and the 16S rRNA gene PCR amplified and sequenced. Based on the sequences, we estimated the species richness and diversity, we calculated the distances between the communities, and trees were constructed to reflect the relatedness of the microbiota in the samples analyzed. Details about these analytical approaches are given in the materials and methods section in the supplemental material.Our initial analysis of species composition was done using the RDPII hierarchical classifier. We found that the majority of pathogen-related bacteria in our data set belonged to the class Gammaproteobacteria. The genera encompassed Legionella, Pseudomonas, and Vibrio (Table (Table1).1). We found a significant overrepresentation of pathogen-related bacteria in the toilet tap (P = 0.04), while there were no significant differences between summer and winter samples. Legionella showed the highest relative abundance for the pathogen-related bacteria. With respect to the total diversity, we found that Proteobacteria dominated the tap water microbiota (representing 86% of the taxa) (see Table S1 in the supplemental material). There was, however, a large portion (56%) of the taxa that could not be assigned to the genus level using this classifier.
Open in a separate windowaThe relatedness between the cloned sequences and potential pathogens was determined by BLAST searches of the NCBI database, carried out using default settings.To obtain a better resolution of the uncharacterized microbiota, we analyzed the data using a clustering approach that is not dependent on a predefined bacterial group (see the materials and methods section in the supplemental material for details). These analyses showed that there were three relatively tightly clustered groups in our data set (Fig. (Fig.1A).1A). The largest group (n = 590) was only distantly related to characterized betaproteobacteria within the order Rhodocyclales. We also identified another large betaproteocaterial group (n = 320) related to Polynucleobacter. Finally, a tight group (n = 145) related to the alphaproteobacterium Sphingomonas was identified.Open in a separate windowFIG. 1.Tap water microbiota diversity, determined by use of a principal component analysis coordinate system. (A) Each bacterium is classified by coordinates, with the following color code: brown squares, kitchen summer; red diamonds, toilet summer; green triangles, kitchen winter; and green circles, toilet winter. (B and C) Each square represents a 1 × 1 (B) or 5 × 5 (C) OTU. PC1, first principal component; PC2, second principal component.The tap-specific distributions of the bacterial groups were investigated using density distribution analyses. A dominant population related to Polynucleobacter was identified for the toilet summer samples, while for the winter samples there was a dominance of the Rhodocyclales-related bacteria. The kitchen summer samples revealed a dominance of Sphingomonas. The corresponding winter samples did not reveal distinct high-density bacterial populations (see Table S2 in the supplemental material).Hierarchical clustering for the 1 × 1 OTU density distribution confirmed the relatively low overlap for the microbiota in the samples analyzed (Fig. (Fig.2).2). We found that the microbiota clustered according to tap and not season.Open in a separate windowFIG. 2.Hierarchical clustering for the density distribution of the tap water microbiota. The density of 1 × 1 OTUs was used as a pseudospecies for hierarchical clustering. The tree for the Cord distance matrix is presented, while the distances calculated using the three distance matrices Cord, Brad Curtis, and Sneath Sokal, respectively, are shown for each branch.We have described the species diversity and richness of the microbiota in Table S3 in the supplemental material. For the low taxonomic level, these analyses showed that the diversity and species richness were greater for the winter samples than for the summer samples. Comparing the two taps, the diversity and richness were greater in the kitchen tap than in the toilet tap. In particular, the winter sample from the kitchen showed great richness and diversity. The high taxonomic level, however, did not reveal the same clear differences as did the low level, and the distributions were more even. Rarefaction analyses for the low taxonomic level confirmed the richness and diversity estimates (see Fig. S1 in the supplemental material).Our final analyses sought to fit the species rank distributions to common rank abundance curves. Generally, the rank abundance curves were best fitted to log series or truncated log normal distributions (see Table S4 in the supplemental material). The log series distribution could be fit to all of the samples except the kitchen summer samples at the low taxonomic level, while the truncated log normal distribution could not be fit to the kitchen samples at the high taxonomic level. Interestingly, however, the kitchen winter sample was best fit to a geometric curve at both the high and the low taxonomic level.Diversifying, adaptive biofilm barriers have been documented for tap water bacteria (7), and it is known that planktonic bacteria can interact with biofilms in an adaptive manner (3). On the other hand, tap usage leads to water flowthrough and replacement of the global with the local water population by stochastic founder effects (1).Therefore, we propose that parts of the local diversity observed can be explained by local adaptation (10) and parts by founder effects (9).Most prokaryote diversity measures assume log normal or log series OTU dominance density distributions (5). The kitchen winter sample, however, showed deviations from these patterns by being correlated to geometric distributions (in addition to the log series and truncated log normal distributions for the high taxonomic level). This sample also showed a much greater species richness than the other samples. A possible explanation is that the species richness of the tap water microbiota can be linked to usage and that the kitchen tap is driven toward a founder microbiota by high usage.Since our work indicates an overrepresentation of Legionella in the low-usage tap, it would be of high interest to determine whether the processes for local Legionella colonization can be related to tap usage. Understanding the ecological forces affecting Legionella and other pathogens are of great importance for human health. At the Akerhus University Hospital, this was exemplified by a Pseudomonas aeruginosa outbreak in an intensive care unit, where the outbreak could be traced back to a single tap (2). 相似文献
TABLE 1.
Cloned sequences related to human pathogensa| Sampling place | Sampling time | Pathogen | NCBI accession no. | Identity (%) |
|---|---|---|---|---|
| Toilet | Summer | Escherichia coli | EF418614 | 99 |
| Toilet | Summer | Escherichia sp. | EF074307 | 99 |
| Toilet | Summer | Legionella sp. | AY924155 | 95 |
| Toilet | Summer | Legionella sp. | AY924153 | 95 |
| Toilet | Summer | Legionella sp. | AY924153 | 96 |
| Toilet | Winter | Legionella sp. | AY924061 | 96 |
| Toilet | Winter | Legionella sp. | AY924158 | 97 |
| Toilet | Winter | Legionella sp. | AY924158 | 97 |
| Kitchen | Winter | Legionella sp. | AY923996 | 97 |
| Toilet | Summer | Pseudomonas fluorescens | EF413073 | 98 |
| Toilet | Summer | Pseudomonas fluorescens | EF413073 | 98 |
| Kitchen | Summer | Pseudomonas fluorescens | DQ207731 | 99 |
| Toilet | Winter | Vibrio sp. | DQ408388 | 98 |
| Toilet | Winter | Vibrio sp. | AB274760 | 98 |
| Kitchen | Winter | Vibrio sp. | DQ408388 | 98 |
| Kitchen | Winter | Vibrio lentus | AY292936 | 99 |
| Kitchen | Winter | Vibrio sp. | AM183765 | 97 |
| Toilet | Winter | Stenotrophomonas maltophilia | AY837730 | 99 |
| Kitchen | Winter | Stenotrophomonas maltophilia | DQ424870 | 98 |
| Toilet | Winter | Streptococcus suis | AF284578 | 98 |
| Toilet | Winter | Streptococcus suis | AF284578 | 98 |
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Lavanya Rishishwar Lee S. Katz Nitya V. Sharma Lori Rowe Michael Frace Jennifer Dolan Thomas Brian H. Harcourt Leonard W. Mayer I. King Jordan 《Journal of bacteriology》2012,194(20):5649-5656
Containment strategies for outbreaks of invasive Neisseria meningitidis disease are informed by serogroup assays that characterize the polysaccharide capsule. We sought to uncover the genomic basis of conflicting serogroup assay results for an isolate (M16917) from a patient with acute meningococcal disease. To this end, we characterized the complete genome sequence of the M16917 isolate and performed a variety of comparative sequence analyses against N. meningitidis reference genome sequences of known serogroups. Multilocus sequence typing and whole-genome sequence comparison revealed that M16917 is a member of the ST-11 sequence group, which is most often associated with serogroup C. However, sequence similarity comparisons and phylogenetic analysis showed that the serogroup diagnostic capsule polymerase gene (synD) of M16917 belongs to serogroup B. These results suggest that a capsule-switching event occurred based on homologous recombination at or around the capsule locus of M16917. Detailed analysis of this locus uncovered the locations of recombination breakpoints in the M16917 genome sequence, which led to the introduction of an ∼2-kb serogroup B sequence cassette into the serogroup C genomic background. Since there is no currently available vaccine for serogroup B strains of N. meningitidis, this kind capsule-switching event could have public health relevance as a vaccine escape mutant. 相似文献
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Bacterial regeneration of ammonium and phosphate as affected by the carbon:nitrogen:phosphorus ratio of organic substrates 总被引：10，自引：2，他引：8
Yasuhiko Tezuka 《Microbial ecology》1990,19(3):227-238
The effect of carbonnitrogenphosphorus (CNP) ratio of organic substrates on the regeneration of ammonium and phosphate was investigated by growing natural assemblages of freshwater bacteria in mineral media supplemented with the simple organic C, N, and P sources (glucose, asparagine, and sodium glycerophosphate, respectively) to give 25 different substrate CNP ratios. Both ammonium and phosphate were regenerated when CN and NP atomic ratios of organic substrates were 101 and 161, respectively. Only ammonium was regenerated when CN and NP ratios were 101 and 10–201, respectively. On the other hand, neither ammonium nor phosphate was regenerated when CN and NP ratios were 151 and 51, respectively. In no case was phosphate alone regenerated. As bacteria were able to alter widely the CNP ratio of their biomass, the growth yield of bacteria appeared primarily dependent on the substrate carbon concentration, irrespective of a wide variation in the substrate CNP ratio. 相似文献
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Integrin 5 1 and 2 1 are the major integrin receptors in human hepatocytes. However, in human hepatocellular carcinoma cells it was found that the expression of integrin 5 1 was decreased and another integrin 6 1 increased. In this study, the SMMC7721 human hepatocellular carcinoma cells cotransfected or singlely transfected with integrin 5 and/or 1 cDNAs were established, and designated 5 1.6-7721, 5.3-7721, and 1.6-7721 cell lines, respectively. Transfection with cDNAs of integrin 5 and 1 subunits resulted in the overexpression of each integrin and modified biological properties, including a slowed growth rate, changes in the cell cycle from 15.5% of control cells in the G2/M phase to 12.1%, 9.6% and 9.4% in 5.3-7721, 1.6-7721, 5 1.6-7721, respectively, and a decrease in the Cell Mitosis Index from 1.6 in controls to 0.96, 0.95, and 0.72, and 34%, 28% and 52% derived from colony forming ability, respectively. Tumorigenicity was also tested in nude mice with inoculation of cells subcutaneously. Tumor masses growing in nude mice following inoculation with 1.6-7721,and 5 1.6-7721 cells weighed only 52% or 31% those of control cells. These results indicated that deletion or low expression of integrin 5 1 may play an important role in the development of hepatocellular carcinoma. Therefore, induction of expression of the integrin 5 1 in malignant cells could be a potential means of treating hepatocellular carcinoma. 相似文献
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通过对近些年关于护理人员职业价值观研究的回顾与总结,对关键词“价值观”“工作价值观”“职业价值观”“护士职业价值观”“护士工作价值观”“护生价值观”“护生职业价值观”“护生工作价值观”“医学生职业价值观”“组织价值观”“道德价值观”进行网络检索。针对护理人员职业价值观内涵的总结与界定,形成构成护理人员职业价值观因素分析,提出研究护理人员职业价值观时代新意。 相似文献
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In a recent landmark paper, the Huntington''s disease (HD) iPSC Consortium reports on the establishment and characterization of a panel of iPSC lines from HD patients, and more importantly, the successful modeling of HD in vitro. In the same issue of Cell Stem Cell, An et al. reports on the successful targeted gene correction of HD in human iPSCs. Both advances are exciting, provide new resources for current and future HD research, and uncover new challenges to better understand and, most importantly, treat this devastating disease in the near future.Modeling human diseases using induced pluripotent stem cells (iPSCs) has created novel opportunities for both mechanistic studies as well as for the discovery of new disease therapies. Combined with advanced gene correction technology, human iPSCs hold great promise to provide patient-specific and mutation-free cells for potential cell replacement therapy. Huntington''s disease (HD) is an autosomal dominant neurodegenerative disorder, which causes motor dysfunction, psychiatric disturbances and cognitive impairment1. HD is caused by an expanded cystosine adenine guanine (CAG) tri-nucleotide repeat encoding polyglutamine in the first exon of the Huntingtin (HTT) gene. To date, there is no effective therapy for preventing the onset or slowdown of this disorder. Preliminary clinical trials using fetal neural grafts had shown long-lasting functional benefits in patients2. Though only effective in limited cases, these results suggest that cell-based therapy could be a potential treatment if a reliable and consistent cell source is available. For this purpose, an alternative cell source to overcome the logistical and biological hurdles of this disease had been actively explored in the past decade. With recent advancement in human iPSCs technology, HD patient-specific iPSCs coupled with an efficient directed cell differentiation protocol offers hope for an unlimited supply of autologous cells. Since HD is a monogenic disease, with a very well-established correlation between the number of CAG repeats and the age of disease onset, it provides an ideal target for iPSC-based gene correction that will allow for the production of disease-free cells for potential autologous cell therapy, and at the same time provide a much needed, valuable platform to further study the pathogenesis of the disease3,4.This is in fact what has been recently accomplished in two reports published in Cell Stem Cell5,6. The HD iPSC Consortium reports on the generation of HD patient-specific iPSC lines that showed CAG-repeat-expansion-associated phenotypes5. The study from An et al.6 reports on the successful targeted correction of expanded CAG repeat in HD patient iPSCs and the reversion of disease phenotypes.In the study reported from the HD iPSC Consortium, the authors generated 14 iPSC lines from HD patients and controls (listed in Open in a separate window
Open in a separate windowHD, Huntington''s Disease; iPSC, induced pluripotent stem cell; NPC, neural progenitor cell; O, Oct4; S, Sox2; K, Klf4; M, Myc; N, Nanog; L, Lin28.Meanwhile, using a homologous recombination-based gene targeting strategy, An et al.6 reported on the successful correction of the CAG-repeat-expanded HTT allele in HD patient iPSCs. These corrected iPSCs shared the same genetic background as the disease iPSCs, thereby serving as non-biased controls for their uncorrected counterparts. By comparing gene expression profiles of corrected iPSCs versus disease iPSCs, An et al. found that the alterations of cadherin, TGF-β, and caspase-related pathways in HD were rescued in the non-expanded iPSCs. The authors further demonstrated that gene correction in HD iPSCs reversed disease phenotypes such as susceptibility to cell death and altered mitochondrial bioenergetics in NSCs. More importantly, when transplanted into a mouse model of HD, the corrected HD iPSC-derived NSCs could survive and differentiate into GABAergic neurons and DARPP-32-positive neurons in vivo.Taken together, these two studies present very significant advances for iPSC-based disease modeling of HD and provide a potential donor source for cell replacement therapy. Though exciting indeed, several important challenges remain unsolved.First, complete recapitulation of neuropathology phenotypes in the iPSC-based models in vitro remains a challenge in the field. As a neurodegenerative disease, pathologic development of HD usually takes several decades and may be influenced by several external factors. In the HD iPSC-based model, the derivation method, clonal discrepancy as well as the culture conditions may affect the manifestation of phenotypes. Indeed, in previously reported HD iPSC lines, only slight increases in caspase and lysosomal activity were observed7,8,9. Although in both reports of HD iPSCs, significant phenotypes in electrophysiology, energy metabolism and cell death were recorded, other typical HD-associated phenotypes such as oligomeric mutant HTT aggregation, formation of nuclear inclusions and preferential striatal degeneration were not observed.Second, it is still an open question whether neural cells derived from gene-corrected iPSCs are fully functional, that is, whether they may restore physiological functions after cell replacement therapy. Ma et al.10 have recently reported on a protocol to differentiate striatal projection neurons from human embryonic stem cells with a high efficiency. After transplantation, these cells survived, reconnected striatal circuitry, and restored motor function in a striatal neurodegenerative mouse model. In spite of these encouraging first attempts, further improvements of the methodology for the directed cell differentiation in vitro and cell transplantation in vivo are still needed.Third, HTT protein is ubiquitously expressed and functional in different tissue. It has been hypothesized that HD may also develop in a non-autonomous manner11. The current studies mainly focused on the phenotypes of HD iPSC-derived neurons. However, supporting cells such as astrocytes might also play direct or indirect roles in HD progression. Indeed, a vacuolation phenotype has been observed in HD iPSC-derived astrocytes12. Therefore, it will be interesting to expand the HD iPSC platform into other cell types with the goal to extend and uncover the various ethiopathological factors involved in HD.Finally, human iPSC models of monogenic disorders in general possess great potential for the mechanistic study of the disease. However, as is the case with many neuropsychiatric disorders, HD establishment and progression is linked to different genetic and epigenetic factors, including environmental change-induced epigenetic modification, multiple mutations, and genetic alternation in non-coding regions. To this end, although the successful generation of HD iPSCs as well as targeted gene correction would greatly facilitate the study of HD, a comprehensive understanding of HD pathogenesis will need to be achieved before trying to translate the recent results into the clinic.In summary, despite all of these open questions, the recent studies have uncovered the unlimited potential of iPSCs for modeling HD in vitro. These studies will promote and enhance HD research in various areas, including elucidation of HD cellular pathogenesis, development of HD-specific biomarkers, screening for small therapeutic molecules, and manipulation of HD iPSCs for stem cell replacement therapy, which together may ultimately fulfill the promise of using iPSCs as a tool for regenerative medicine and drug discovery for HD in the near future. 相似文献
| Code | Number of iPSC line | CAG repeats | HD type | Age of sample procured | Reprogramming strategy | Phenotype detected cell type | Gene correction line available | Phenotype | References |
|---|---|---|---|---|---|---|---|---|---|
| HD 43 | 1 | 39/43 | Adult onset HD | 44 years | OSKM (lentivirus) | iPSCs | no | Increased Iysosomal activity | 7 |
| HD 44 | 4 | 42/44 | Adult onset HD | 59 years | 2 lines:OSKM (lentivirus) 2 lines: OSK (lentivirus) | iPSCs | no | Increased Iysosomal activity | 7 |
| HD 50 | 1 | 50 | Adult onset HD | unknown (father) | OSKM (retrovirus) | Astrocyte | no | Neural differentiation normal, Vacuolation in astrocyte | 12 |
| HD109-1 | 1 | 109 | Juvenile HD | unknown (daughter) | OSKM (retrovirus) | Astrocyte | no | Similar to HD 50, more vacuolation in astrocyte | 12 |
| HD 72 | 1 | 72 | Juvenile HD | 20 years | OSKM (retrovirus) | NPCs | yes | Elevated caspase activity; more vulnerable to cell death | 6,8,9 |
| HD 60 | 3 | 60 | Adult onset HD | 29 years | 2 lines:OSKMNL (lentivirus) 1 line: OSKM (episomal) | NPCs, neurons | no | Altered cell adhesion, energetics, and electrophysiology; Increased cell death in long time neural differentiation | 5 |
| HD109-2 | 1 | 109 | Juvenile HD | 9 years | OSKMNL (lentivirus) | NPCs, neurons | no | Similar to HD 60; higher risk to cell death in response to BDNF withdrawal | 5 |
| HD180 | 4 | 180 | Juvenile HD | 6 years | 3 lines:OSKMNL (lentivirus) 1 line: OSKM (episomal) | NPCs, neurons | no | Similar to HD 60 and 109; Increased vulnerable to stress and toxicity | 5 |
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Nidiane D. R. Prado Soraya S. Pereira Michele P. da Silva Michelle S. S. Morais Anderson M. Kayano Leandro S. Moreira-Dill Marcos B. Luiz Fernando B. Zanchi André L. Fuly Maribel E. F. Huacca Cleberson F. Fernandes Leonardo A. Calderon Juliana P. Zuliani Luiz H. Pereira da Silva Andreimar M. Soares Rodrigo G. Stabeli Carla F. C. Fernandes 《PloS one》2016,11(3)
Antivenoms, produced using animal hyperimmune plasma, remains the standard therapy for snakebites. Although effective against systemic damages, conventional antivenoms have limited efficacy against local tissue damage. Additionally, the hypersensitivity reactions, often elicited by antivenoms, the high costs for animal maintenance, the difficulty of producing homogeneous lots, and the instability of biological products instigate the search for innovative products for antivenom therapy. In this study, camelid antibody fragments (VHH) with specificity to Bothropstoxin I and II (BthTX-I and BthTX-II), two myotoxic phospholipases from Bothrops jararacussu venom, were selected from an immune VHH phage display library. After biopanning, 28 and 6 clones recognized BthTX-I and BthTX-II by ELISA, respectively. Complementarity determining regions (CDRs) and immunoglobulin frameworks (FRs) of 13 VHH-deduced amino acid sequences were identified, as well as the camelid hallmark amino acid substitutions in FR2. Three VHH clones (KF498607, KF498608, and KC329718) were capable of recognizing BthTX-I by Western blot and showed affinity constants in the nanomolar range against both toxins. VHHs inhibited the BthTX-II phospholipase A2 activity, and when tested for cross-reactivity, presented specificity to the Bothrops genus in ELISA. Furthermore, two clones (KC329718 and KF498607) neutralized the myotoxic effects induced by B. jararacussu venom, BthTX-I, BthTX-II, and by a myotoxin from Bothrops brazili venom (MTX-I) in mice. Molecular docking revealed that VHH CDRs are expected to bind the C-terminal of both toxins, essential for myotoxic activity, and to epitopes in the BthTX-II enzymatic cleft. Identified VHHs could be a biotechnological tool to improve the treatment for snake envenomation, an important and neglected world public health problem. 相似文献
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In Vivo Fitness Cost of the M184V Mutation in Multidrug-Resistant Human Immunodeficiency Virus Type 1 in the Absence of Lamivudine 总被引：1，自引：0，他引：1
Roger Paredes Manish Sagar Vincent C. Marconi Rebecca Hoh Jeffrey N. Martin Neil T. Parkin Christos J. Petropoulos Steven G. Deeks Daniel R. Kuritzkes 《Journal of virology》2009,83(4):2038-2043
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Senbagam Duraisamy Fazal Husain Senthilkumar Balakrishnan Aswathy Sathyan Prabhu Subramani Prahalathan Chidambaram Selvaraj Arokiyaraj Wahidah H. Al-Qahtani Jothiramalingam Rajabathar Anbarasu Kumarasamy 《Current issues in molecular biology》2022,44(2):731
Breast milk is the combination of bioactive compounds and microflora that promote newborn’s proper growth, gut flora, and immunity. Thus, it is always considered the perfect food for newborns. Amongst their bioactives, probiotic communities—especially lactic acid bacteria (LAB)—are characterized from breast milk over the first month of parturition. In this study, seven LAB were characterized phenotypically and genotypically as Levilactobacillus brevis BDUMBT08 (MT673657), L. gastricus BDUMBT09 (MT774596), L. paracasei BDUMBT10 (MT775430), L. brevis BDUMBT11 (MW785062), L. casei BDUMBT12 (MW785063), L. casei BDUMBT13 (MW785178), and Brevibacillus brevis M2403 (MK371781) from human breast milk. Their tolerance to lysozyme, acid, bile, gastric juice, pancreatic juice, and NaCl and potential for mucoadhesion, auto-aggregation, and co-aggregation with pathogens are of great prominence in forecasting their gut colonizing ability. They proved their safety aspects as they were negative for virulence determinants such as hemolysis and biofilm production. Antibiogram of LAB showed their sensitivity to more than 90% of the antibiotics tested. Amongst seven LAB, three isolates (L. brevis BDUMBT08 and BDUMBT11, and L. gatricus BDUMBT09) proved their bacteriocin producing propensity. Although the seven LAB isolates differed in their behavior, their substantial probiotic properties with safety could be taken as promising probiotics for further studies to prove their in vivo effects, such as health benefits, in humans. 相似文献
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Bryony N. Parsons Suzanne Humphrey Anne Marie Salisbury Julia Mikoleit Jay C. D. Hinton Melita A. Gordon Paul Wigley 《PLoS neglected tropical diseases》2013,7(10)
Salmonella enterica serovar Typhimurium Sequence Type (ST) 313 is a major cause of invasive non-Typhoidal salmonellosis in sub-Saharan Africa. No animal reservoir has been identified, and it has been suggested that ST313 is adapted to humans and transmission may occur via person-to-person spread. Here, we show that ST313 cause severe invasive infection in chickens as well as humans. Oral infection of chickens with ST313 isolates D23580 and Q456 resulted in rapid infection of spleen and liver with all birds infected at these sites by 3 days post-infection. In contrast, the well-defined ST19 S. Typhimurium isolates F98 and 4/74 were slower to cause invasive disease. Both ST19 and ST313 caused hepatosplenomegaly, and this was most pronounced in the ST313-infected animals. At 3 and 7 days post-infection, colonization of the gastrointestinal tract was lower in birds infected with the ST313 isolates compared with ST19. Histological examination and expression of CXCL chemokines in the ileum showed that both D23580 (ST313) and 4/74 (ST19) strains caused increased CXCL expression at 3 days post-infection, and this was significantly higher in the ileum of D23580 vs 4/74 infected birds. At 7 days post-infection, reduced chemokine expression occurred in the ileum of the D23580 but not 4/74-infected birds. Histological analysis showed that D23580 infection resulted in rapid inflammation and pathology including villous flattening and fusion at 3 days post-infection, and subsequent resolution by 7 days. In contrast, 4/74 induced less inflammation and pathology at 3 days post-infection. The data presented demonstrate that ST313 is capable of causing invasive disease in a non-human host. The rapid invasive nature of infection in the chicken, coupled with lower gastrointestinal colonization, supports the hypothesis that ST313 is a distinct pathovariant of S. Typhimurium that has evolved to become a systemic pathogen that can cause disease in several hosts. 相似文献