168 research outputs found
Identification of furfural resistant strains of Saccharomyces cerevisiae and Saccharomyces paradoxus from a collection of environmental and industrial isolates
Background Fermentation of bioethanol using lignocellulosic biomass as a raw material provides a sustainable alternative to current biofuel production methods by utilising waste food streams as raw material. Before lignocellulose can be fermented it requires physical, chemical and enzymatic treatment in order to release monosaccharides, a process that causes the chemical transformation of glucose and xylose into the cyclic aldehydes furfural and hydroxyfurfural. These furan compounds are potent inhibitors of Saccharomyces fermentation, and consequently furfural tolerant strains of Saccharomyces are required for lignocellulosic fermentation. Results This study investigated yeast tolerance to furfural and hydroxyfurfural using a collection of 71 environmental and industrial isolates of the bakerâs yeast Saccharomyces cerevisiae and its closest relative Saccharomyces paradoxus. The Saccharomyces strains were initially screened for growth on media containing 100 mM glucose and 1.5 mg ml-1 furfural. Five strains were identified that showed a significant tolerance to growth in the presence of furfural and these were then screened for growth and ethanol production in the presence of increasing amounts (0.1-4 mg ml-1) of furfural. Conclusions Of the five furfural tolerant strains S. cerevisiae NCYC 3451 displayed the greatest furfural resistance, and was able to grow in the presence of up to 3.0 mg ml-1 furfural. Furthermore, ethanol production in this strain did not appear to be inhibited by furfural, with the highest ethanol yield observed at 3.0 mg ml-1 furfural. Although furfural resistance was not found to be a trait specific to any one particular lineage or population, three of the strains were isolated from environments where they might be continually exposed to low levels of furfural through the on-going natural degradation of lignocelluloses, and would therefore develop elevated levels of resistance to these furan compounds. Thus these strains represent good candidates for future studies of genetic variation relevant to understanding and manipulating furfural resistance and in the development of tolerant ethanologenic yeast strains for use in bioethanol production from lignocellulose processing
Sturgeon in the SacramentoâSan Joaquin Watershed: New Insights to Support Conservation and Management
The goal of a day-long symposium on March 3, 2015, Sturgeon in the SacramentoâSan Joaquin Watershed: New Insights to Support Conservation and Management, was to present new information about the physiology, behavior, and ecology of the green (Acipenser medirostris) and white sturgeon (Acipenser transmontanus) to help guide enhanced management and conservation efforts within the SacramentoâSan Joaquin watershed. This symposium identified current unknowns and highlighted new electronic tracking technologies and physiological techniques to address these knowledge gaps. A number of presentations, each reviewing ongoing research on the two species, was followed by a round-table discussion, in which each of the participants was asked to share recommendations for future research on sturgeon in the watershed. This article presents an in-depth review of the scientific information presented at the symposium with a summary of recommendations for future research
Risk factors for hospital morbidity and mortality after the Norwood procedure: A report from the Pediatric Heart Network Single Ventricle Reconstruction trial
ObjectivesWe sought to identify risk factors for mortality and morbidity during the Norwood hospitalization in newborn infants with hypoplastic left heart syndrome and other single right ventricle anomalies enrolled in the Single Ventricle Reconstruction trial.MethodsPotential predictors for outcome included patient- and procedure-related variables and center volume and surgeon volume. Outcome variables occurring during the Norwood procedure and before hospital discharge or stage II procedure included mortality, end-organ complications, length of ventilation, and hospital length of stay. Univariate and multivariable Cox regression analyses were performed with bootstrapping to estimate reliability for mortality.ResultsAnalysis included 549 subjects prospectively enrolled from 15 centers; 30-day and hospital mortality were 11.5% (63/549) and 16.0% (88/549), respectively. Independent risk factors for both 30-day and hospital mortality included lower birth weight, genetic abnormality, extracorporeal membrane oxygenation (ECMO) and open sternum on the day of the Norwood procedure. In addition, longer duration of deep hypothermic circulatory arrest was a risk factor for 30-day mortality. Shunt type at the end of the Norwood procedure was not a significant risk factor for 30-day or hospital mortality. Independent risk factors for postoperative renal failure (n = 46), sepsis (n = 93), increased length of ventilation, and hospital length of stay among survivors included genetic abnormality, lower center/surgeon volume, open sternum, and post-Norwood operations.ConclusionsInnate patient factors, ECMO, open sternum, and lower center/surgeon volume are important risk factors for postoperative mortality and/or morbidity during the Norwood hospitalization
Diffusion of a Peer-Led Suicide Preventive Intervention Through School-Based Student Peer and Adult Networks
Background: Peer-led interventions have been applied to prevent various health behavior problems and may be an important complement to individual-level suicide prevention approaches. Sources of Strength trains student âpeer leadersâ in secondary schools to conduct prevention activities that encourage other students to build healthy social bonds and strengthen help-seeking norms. Prior work examining diffusion of peer-led programs has focused on youths' closeness to peer leaders but minimally on other factors such as connections to adults and suicidal behavior.Methods: We examined implementation and dissemination of Sources of Strength in 20 schools. Over 1 year 533 students were trained as peer leaders and 3,730 9thâ12th graders completed baseline surveys assessing friendships and adults at school, and suicidal thoughts/behaviors; and end-of-year surveys reporting intervention exposure: viewed poster/video, attended presentation, direct peer communication, and activity participation. Chi-square tests compared exposure rates by student and network characteristics. Multi-level logistic regression models tested predictors of exposure across individual and school-level characteristics.Results: Exposure to the intervention varied greatly by school and by individual student characteristics and network position. Training more peer leaders increased school-wide exposure for all modalities except presentation (Bs 0.06â0.10, p's < 0.05). In multivariate models, exposure was consistently higher for students closer to peer leaders in the friendship network (ORs 1.13â1.54, p's < 0.05) and students who named more trusted adults (ORs 1.08â1.16, p's < 0.001); and lower for males (ORs 0.56â0.83, p's < 0.05). In multivariate models, training more students as peer leaders predicted exposure to poster-video and direct peer communication in larger schools (OR = 3.34 and 2.87, respectively). Network characteristics influenced exposure similarly for students with suicidal thoughts and behaviors.Discussion: Our findings confirm prior work showing the importance of personal affiliations to peer leaders and natural networks as a medium for diffusion of peer-led prevention efforts. We build on that work by showing independent effects of closeness to adults at school and number of peer leaders trained. There is a need to strategically select peer leaders to maximize closeness to students school-wide, particularly in larger schools. Additional work is required for Sources of Strength to devise messaging strategies to engage males and students isolated from adults at school
Systematic Error in Seed Plant Phylogenomics
Resolving the closest relatives of Gnetales has been an enigmatic problem in seed plant phylogeny. The problem is known to be difficult because of the extent of divergence between this diverse group of gymnosperms and their closest phylogenetic relatives. Here, we investigate the evolutionary properties of conifer chloroplast DNA sequences. To improve taxon sampling of Cupressophyta (non-Pinaceae conifers), we report sequences from three new chloroplast (cp) genomes of Southern Hemisphere conifers. We have applied a site pattern sorting criterion to study compositional heterogeneity, heterotachy, and the fit of conifer chloroplast genome sequences to a general time reversible + G substitution model. We show that non-time reversible properties of aligned sequence positions in the chloroplast genomes of Gnetales mislead phylogenetic reconstruction of these seed plants. When 2,250 of the most varied sites in our concatenated alignment are excluded, phylogenetic analyses favor a close evolutionary relationship between the Gnetales and Pinaceaeâthe Gnepine hypothesis. Our analytical protocol provides a useful approach for evaluating the robustness of phylogenomic inferences. Our findings highlight the importance of goodness of fit between substitution model and data for understanding seed plant phylogeny
Crystal structure of human XLF/Cernunnos reveals unexpected differences from XRCC4 with implications for NHEJ
The recently characterised 299-residue human XLF/Cernunnos protein plays a crucial role in DNA repair by non-homologous end joining (NHEJ) and interacts with the XRCC4âDNA Ligase IV complex. Here, we report the crystal structure of the XLF (1â233) homodimer at 2.3 Ă
resolution, confirming the predicted structural similarity to XRCC4. The XLF coiled-coil, however, is shorter than that of XRCC4 and undergoes an unexpected reverse in direction giving rise to a short distorted four helical bundle and a C-terminal helical structure wedged between the coiled-coil and head domain. The existence of a dimer as the major species is confirmed by size-exclusion chromatography, analytical ultracentrifugation, small-angle X-ray scattering and other biophysical methods. We show that the XLF structure is not easily compatible with a proposed XRCC4:XLF heterodimer. However, we demonstrate interactions between dimers of XLF and XRCC4 by surface plasmon resonance and analyse these in terms of surface properties, amino-acid conservation and mutations in immunodeficient patients. Our data are most consistent with head-to-head interactions in a 2:2:1 XRCC4:XLF:Ligase IV complex
Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe
Finishing the euchromatic sequence of the human genome
The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers âŒ99% of the euchromatic genome and is accurate to an error rate of âŒ1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead
Human Subjects Protection and Technology in Prevention Science: Selected Opportunities and Challenges
Internet-connected devices are changing the way people live, work, and relate to one another. For prevention scientists, technological advances create opportunities to promote the welfare of human subjects and society. The challenge is to obtain the benefits while minimizing risks. In this article, we use the guiding principles for ethical human subjects research and proposed changes to the Common Rule regulations, as a basis for discussing selected opportunities and challenges that new technologies present for prevention science. The benefits of conducting research with new populations, and at new levels of integration into participantsâ daily lives, are presented along with five challenges along with technological and other solutions to strengthen the protections that we provide: (1) achieving adequate informed consent with procedures that are acceptable to participants in a digital age; (2) balancing opportunities for rapid development and broad reach, with gaining adequate understanding of population needs; (3) integrating data collection and intervention into participantsâ lives while minimizing intrusiveness and fatigue; (4) setting appropriate expectations for responding to safety and suicide concerns; and (5) safeguarding newly available streams of sensitive data. Our goal is to promote collaboration between prevention scientists, institutional review boards, and community members to safely and ethically harness advancing technologies to strengthen impact of prevention science
- âŠ