The TOR (target of rapamycin) kinase limits longevity by poorly understood mechanisms. Rapamycin suppresses the mammalian TORC1 complex, which regulates translation, and extends lifespan in diverse ...species, including mice. We show that rapamycin selectively blunts the pro-inflammatory phenotype of senescent cells. Cellular senescence suppresses cancer by preventing cell proliferation. However, as senescent cells accumulate with age, the senescence-associated secretory phenotype (SASP) can disrupt tissues and contribute to age-related pathologies, including cancer. MTOR inhibition suppressed the secretion of inflammatory cytokines by senescent cells. Rapamycin reduced IL6 and other cytokine mRNA levels, but selectively suppressed translation of the membrane-bound cytokine IL1A. Reduced IL1A diminished NF-κB transcriptional activity, which controls much of the SASP; exogenous IL1A restored IL6 secretion to rapamycin-treated cells. Importantly, rapamycin suppressed the ability of senescent fibroblasts to stimulate prostate tumour growth in mice. Thus, rapamycin might ameliorate age-related pathologies, including late-life cancer, by suppressing senescence-associated inflammation.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, UILJ, UKNU, UL, UM, UPUK
Development and deployment of commercial biorefineries based on conversion of lignocellulosic biomass into biofuels and bioproducts faces many challenges that must be addressed before they are ...commercially viable. One of the biggest challenges faced is the efficient and scalable valorization of lignin, one of the three major components of the plant cell wall. Lignin is the most abundant aromatic biopolymer on earth, and its presence hinders the extraction of cellulose and hemicellulose that is essential to biochemical conversion of lignocellulose to fuels and chemicals. There has been a significant amount of work over the past 20 years that has sought to develop innovative processes designed to extract and recycle lignin into valuable compounds and help reduce the overall costs of the biorefinery process. Due to the complex matrix of lignin, which is essential for plant survival, the development of a reliable and efficient lignin conversion technology has been difficult to achieve. One approach that has received significant interest relies on the use of enzymes, notably laccases, a class of multi‑copper green oxidative enzymes that catalyze bond breaking in lignin to produce smaller oligomers. In this review, we first assess the different innovations of lignin valorization using laccases within the context of a biorefinery process, and then assess the latest economical advances that these innovations offered. Finally, we review laccase characterization and optimization, as well as the prospects and bottlenecks of this class of enzymes within the industrial and biorefining sectors.
Green word cloud: Word cloud generated from the titles of the latest 100 review papers on laccase in PubMed. The size of the words is proportional to the number of times the word figures in the review titles. Blue pie chart: Proportion of journal editors publishing on laccase review of the latest 200 review researches in Pubmed. Pink graph: The number of review published about laccase figuring in PubMed since 1967. Display omitted
Transition to adult life can be a challenging time for disabled youth and their families. This article describes the collaborative creation of Transitions Theatre, a research-based reader’s theatre ...activity based on narrative interviews with eight disabled youth (aged 17–22) and seven parents. Analysis of these interviews generated two opposing yet interrelated themes. On one hand, youth and families felt lost in transition facing multiple gaps in healthcare, financial support, education, and opportunities for social participation after having “aged out” of the pediatric system. On the other hand, they started cripping “normal” adulthood to envision more inclusive futures wherein disabilities are understood as integral to society. These two themes were transformed into two reader’s theatre scripts, one featuring a youth, the other featuring a parent. Seven youth and four parents (six of them were original interview participants) then participated in a Transitions Theatre workshop to read the scripts together and discuss the authenticity and relatability of the scripts. Participant feedback suggested that the reader’s theatre method was effective in sharing findings with research participants and stimulating a critical dialogue on how to (re)imagine transition to adulthood. We discuss the importance of implementing inclusive design strategies to make reader’s theatre accessible to participants with diverse abilities and preferences.
Mobility of large woody debris (LWD) in low gradient channels is an important but often overlooked transport process. The majority of studies on LWD have focused on its role in geomorphic and ...ecologic river processes. When jams extend across the width of the channel, they have the potential to retain sediment and alter the channel profile. When jams obstruct only a portion of the channel, they can re-direct flow, altering patterns of scour and deposition. The boundary complexity created by LWD has a recognized role in riverine ecosystems which has led to programs of replacing LWD in-channel corridors where it was previously removed. Although LWD jams are common in rivers around the world, they have been studied most intensely in steep, forested channel reaches where they are often found to be stable channel features. It is not fully known how much of the information on LWD from steep forested channels will transfer to other channel types. Whereas it may be reasonable to assume that the ecological benefits of LWD are similar in low gradient channels, research has shown that a much higher rate of LWD transport occurs in low gradient channels, with jams mobilized on timescales of 10
0–10
2
years.
This study evaluates the distribution and mobility of LWD over 72
km of the San Antonio River, a low gradient channel in southeast Texas. LWD jam locations were identified for 2003 and 2007 using a combination of aerial photography and field mapping. Each jam was cataloged according to its location in the channel cross-section and the amount of channel area blocked. During the four-year period, all the LWD jams were mobilized, including those jams extending across the channel width. Although easily mobilized, 34 jams re-form in the same locations, creating 34 channel locations with persistent LWD jams. Data from the San Antonio River are applied to two models developed to predict LWD mobility and transport distances to assess the applicability of each model to a low gradient channel. The locations of stable (or recurring) LWD jams were matched to model results where predicted LWD transport distances were equal to measured LWD jam spacing. Model results showed good agreement with the mean and median spacing of LWD jams when given input parameters specific to the channel and wood species. The ability to predict where LWD jams will persist over time in a low gradient channel has application in watershed management. Persistent LWD jams can exert a greater influence on channel morphology and may require active management.
Genetic Control over the Resting Brain Glahn, D. C.; Winkler, A. M.; Kochunov, P. ...
Proceedings of the National Academy of Sciences - PNAS,
01/2010, Letnik:
107, Številka:
3
Journal Article, Web Resource
Recenzirano
Odprti dostop
The default-mode network, a coherent resting-state brain network, is thought to characterize basal neural activity. Aberrant defaultmode connectivity has been reported in a host of neurological and ...psychiatric illnesses and in persons at genetic risk for such illnesses. Whereas the neurophysiologic mechanisms that regulate defaultmode connectivity are unclear, there is growing evidence that genetic factors play a role. In this report, we estimate the importance of genetic effects on the default-mode network by examining covariation patterns in functional connectivity among 333 individuals from 29 randomly selected extended pedigrees. Heritability for default-mode functional connectivity was 0.424 ± 0.17 (P = 0.0046). Although neuroanatomic variation in this network was also heritable, the genetic factors that influence default-mode functional connectivity and gray-matter density seem to be distinct, suggesting that unique genes influence the structure and function of the network. In contrast, significant genetic correlations between regions within the network provide evidence that the same genetic factors contribute to variation in functional connectivity throughout the default mode. Specifically, the left parahippocampal region was genetically correlated with all other network regions. In addition, the posterior cingulate/precuneus region, medial prefrontal cortex, and right cerebellum seem to form a subnetwork. Default-mode functional connectivity is influenced by genetic factors that cannot be attributed to anatomic variation or a single region within the network. By establishing the heritability of default-mode functional connectivity, this experiment provides the obligatory evidence required before these measures can be considered as endophenotypes for psychiatric or neurological illnesses or to identify genes influencing intrinsic brain function.
Employment participation offers benefits including income, sense of accomplishment, social engagement, and meaningful contribution to society. Rates of competitive employment of youth with ...disabilities are amongst the lowest in society, despite having capacity and motivation to participate in the workplace. The marginalization of young workers with disability presents a lost opportunity for youth, potential employers, and social care systems. In order to engage young people with disabilities in employment, we present an integrated, community-based model for employment participation preparation.
The employment participation pathway model is based on best available evidence and 15 years of program delivery for youth with disabilities preparing to transition out of school and into employment in the Canadian context. It was conceptualized using the Knowledge to Action framework and presented for consideration in the current paper.
Starting early, taking a person-directed approach to planning, and considering the individual and our systems contribute to effective and comprehensive transition to employment.
The employment participation model provides evidence and examples for service providers to consider integrating into their repertoire and begin to construct similar pathways to equip their clients and families with skills, capacities, and knowledge as they journey towards workplace participation.
IMPLICATIONS FOR REHABILITATION
Employment for individuals with disabilities is lower than the national average, with rates being even lower for young people (ages 15-25) with disabilities.
Low workplace participation for individuals with disabilities is particularly troubling due to the myriad social and health benefits of engagement in employment.
Programs that start early (during high school) and provide ongoing, community-integrated support are reported to be most beneficial to the eventual job attainment and retention for young job seekers with disabilities.
The presented employment participation pathway model that was developed using the Knowledge to Action Framework integrates evidence and best practices to support service providers in facilitating progressive workplace participation for clients and families.
This study presents ecomorphological methods for reconstructing paleohabitats using three-dimensional geometric morphometric analyses of Cervidae (deer and relatives) post-cranial elements. Cervids ...are often the most abundant taxon in Eurasian Plio-Pleistocene sites, yet their post-cranial remains are rarely utilized in paleoecological reconstructions. Cervids are found in a wide variety of habitats, and thus their ecomorphology spans an appropriate range to serve as a proxy for paleohabitat. Four morphological features are examined in this study; the calcaneus as a whole (n = 122), the medial margin of the patellar surface of the femur (n = 133), the lateral margin of the tibial plateau (n = 136), and the plantar margin of the third phalanx (n = 62). These features were chosen because they represent various aspects of cervid locomotion important for power generation, stability, and substrate interaction. For each feature, canonical variates analyses with cross-validations were used to assess how well landmark configurations distinguish among specimens from different habitat types. Cross-validations returned correct reclassifications rates ranging from 38.9% to 66.3% in a four-habitat system, with resubstitution rates of 55.4% to 79.1% correct. Most habitat groups were found to be significantly different at p < 0.0001 using permutations tests. Variation in these ecomorphological adaptations are explored via visualizations depicting “open” and “closed” habitat types, and hypotheses are presented for cervid functional morphology.
► Methods for Cervidae ecomorphology using geometric morphometrics are established. ► Morphologies of the femur, tibia, calcaneus, and third phalanx are explored. ► Most habitat groups were found to be significantly different with permutation testing. ► Correct reclassifications ranged from 71.8% to 79.1% (resubstitution) and 42.1% to 66.3% (cross-validation). ► Visualizations of ecomorphological variation and models of cervid locomotion are provided.
Background There are no large studies documenting quality outcomes and complication rates of ERCP in community practice. The American Society for Gastrointestinal Endoscopy (ASGE)/American College of ...Gastroenterology Task Force on Quality proposed 5 questions regarding ERCP in community practice. The ASGE Committee on Outcomes Research recommended 8 ERCP-specific quality indicators be used to provide a better accounting of quality in ERCP. Objective To determine ERCP quality outcomes, including complications, in a community practice. Design Prospective study. Setting Eight community hospitals in the Minneapolis-St. Paul, Minnesota, area. Patients Every patient undergoing ERCP by Minnesota Gastroenterology PA from December 1, 2005, through July 31, 2006. Main Outcome Measurements ASGE-recommended quality indicators, especially 30-day complication rates. Results A total of 805 ERCP procedures were performed in 696 patients. Therapeutic ERCP accounted for 78.4%. The complication rate was 5.0% (5.7% of therapeutic and 2.3% of diagnostic procedures). Pancreatitis occurred in 3.2% of procedures (3.6% of therapeutic and 1.7% of diagnostic procedures). Infection (0.75%), hemorrhage (0.62%), and perforation (0.12%) only occurred after therapeutic ERCP. Cardiopulmonary complications occurred in 2 patients (0.25%). Precut sphincterotomy was performed in 26 cases (3.2%), and sphincter of Oddi manometry in 23 cases (2.9%). Success rates were 94.0% for biliary cannulation, 87.0% for stone extraction, and 90.2% for relieving biliary obstruction. A total of 530 patient satisfaction surveys were completed and revealed that the response to the question, “Would you have the procedure done again by this physician?” was the most sensitive indicator of patient satisfaction. Conclusions In this community practice, complication rates compare very favorably with those of academic centers. The technical success rates achieved or exceeded rates recommended by the ASGE/American College of Gastroenterology Task Force.
Aspergillus niger and other filamentous fungi are widely used in industry, but efficient genetic engineering of these hosts remains nascent. For example, while molecular genetic tools have been ...developed, including CRISPR/Cas9, facile genome engineering of A. niger remains challenging. To address these challenges, we have developed a simple Cas9-based gene targeting method that provides selectable, iterative, and ultimately marker-free generation of genomic deletions and insertions. This method leverages locus-specific "pop-out" recombination to suppress off-target integrations. We demonstrated the effectiveness of this method by targeting the phenotypic marker albA and validated it by targeting the glaA and mstC loci. After two selection steps, we observed 100% gene editing efficiency across all three loci. This method greatly reduces the effort required to engineer the A. niger genome and overcomes low Cas9 transformations efficiency by eliminating the need for extensive screening. This method represents a significant addition to the A. niger genome engineering toolbox and could be adapted for use in other organisms. It is expected that this method will impact several areas of industrial biotechnology, such as the development of new strains for the secretion of heterologous enzymes and the discovery and optimization of metabolic pathways.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Youth Facilitators (YFs) are peer service providers (SPs) with childhood-onset disabilities working in pediatric rehabilitation teams. This study explored the YF role focusing on what work YFs do, ...the perceived facilitators and challenges pertinent to the role integration process, and the evolution of the role over the study period.
A longitudinal, qualitative case study approach was used to gather data over a total period of 14 months through interviews, focus groups, workload logs, and observations. Data were analyzed using the method of thematic analysis.
Two YFs, 23 SPs and two managers participated in the study. YFs' work included independent consultation, resource provision, referral making, and program co-facilitation. Analysis produced two contrasting themes. When viewed as a representative of clients, YFs were considered bringing client perspectives to care, adding credibility to clinical services, and empowering clients and families through role modeling. However, when viewed as a professional SP, their expertise was questioned due to role unclarity, limited generalizability of lived experience, and organizational limitations.
Training tailored to local care contexts and organizational supports are needed to transform YFs' experiential knowledge into experiential expertise. We propose strategies for optimal integration of peer providers into clinical care teams.
Implications for rehabilitation
As peer service providers with lived experience of disabilities, Youth Facilitators (YFs) have the potential to benefit pediatric rehabilitation services by facilitating empowerment in clients and families as they navigate through life transitions.
The YF scope of practice and training should be adapted to fit with individual clinical teams and local care contexts to help YFs establish their experiential expertise in interdisciplinary teams.
Establishing YF's core competencies (e.g., advocacy, coaching, and boundary setting skills) can help transform their experiential knowledge into experiential expertise.
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