The Spindle Assembly Checkpoint Lara-Gonzalez, Pablo; Westhorpe, Frederick G.; Taylor, Stephen S.
Current biology,
11/2012, Letnik:
22, Številka:
22
Journal Article
Recenzirano
Odprti dostop
During mitosis and meiosis, the spindle assembly checkpoint acts to maintain genome stability by delaying cell division until accurate chromosome segregation can be guaranteed. Accuracy requires that ...chromosomes become correctly attached to the microtubule spindle apparatus via their kinetochores. When not correctly attached to the spindle, kinetochores activate the spindle assembly checkpoint network, which in turn blocks cell cycle progression. Once all kinetochores become stably attached to the spindle, the checkpoint is inactivated, which alleviates the cell cycle block and thus allows chromosome segregation and cell division to proceed. Here we review recent progress in our understanding of how the checkpoint signal is generated, how it blocks cell cycle progression and how it is extinguished.
Tobacco products present a deadly combination of nicotine addiction and carcinogen exposure resulting in millions of cancer deaths per year worldwide. A plethora of smokeless tobacco products lead to ...unacceptable exposure to multiple carcinogens, including the tobacco-specific nitrosamine N'-nitrosonornicotine, a likely cause of the commonly occurring oral cavity cancers observed particularly in South-East Asian countries. Cigarettes continue to deliver a large number of carcinogens, including tobacco-specific nitrosamines, polycyclic aromatic hydrocarbons and volatile organic compounds. The multiple carcinogens in cigarette smoke are responsible for the complex mutations observed in critical cancer genes. The exposure of smokeless tobacco users and smokers to carcinogens and toxicants can now be monitored by urinary and DNA adduct biomarkers that may be able to identify those individuals at highest risk of cancer so that effective cancer prevention interventions can be initiated. Regulation of the levels of carcinogens, toxicants and nicotine in tobacco products and evidence-based tobacco control efforts are now recognized as established pathways to preventing tobacco related cancer.
Zoonoses originating from wildlife represent a significant threat to global health, security and economic growth, and combatting their emergence is a public health priority. However, our ...understanding of the mechanisms underlying their emergence remains rudimentary. Here we update a global database of emerging infectious disease (EID) events, create a novel measure of reporting effort, and fit boosted regression tree models to analyze the demographic, environmental and biological correlates of their occurrence. After accounting for reporting effort, we show that zoonotic EID risk is elevated in forested tropical regions experiencing land-use changes and where wildlife biodiversity (mammal species richness) is high. We present a new global hotspot map of spatial variation in our zoonotic EID risk index, and partial dependence plots illustrating relationships between events and predictors. Our results may help to improve surveillance and long-term EID monitoring programs, and design field experiments to test underlying mechanisms of zoonotic disease emergence.
Lignin-Based Thermoplastic Materials Wang, Chao; Kelley, Stephen S.; Venditti, Richard A.
ChemSusChem,
April 21, 2016, Letnik:
9, Številka:
8
Journal Article
Recenzirano
Lignin‐based thermoplastic materials have attracted increasing interest as sustainable, cost‐effective, and biodegradable alternatives for petroleum‐based thermoplastics. As an amorphous ...thermoplastic material, lignin has a relatively high glass‐transition temperature and also undergoes radical‐induced self‐condensation at high temperatures, which limits its thermal processability. Additionally, lignin‐based materials are usually brittle and exhibit poor mechanical properties. To improve the thermoplasticity and mechanical properties of technical lignin, polymers or plasticizers are usually integrated with lignin by blending or chemical modification. This Review attempts to cover the reported approaches towards the development of lignin‐based thermoplastic materials on the basis of published information. Approaches reviewed include plasticization, blending with miscible polymers, and chemical modifications by esterification, etherification, polymer grafting, and copolymerization. Those lignin‐based thermoplastic materials are expected to show applications as engineering plastics, polymeric foams, thermoplastic elastomers, and carbon‐fiber precursors.
Lignin for thermoplastics: Lignin‐based thermoplastic materials have attracted increasing interest as sustainable, cost effective, and biodegradable alternatives for petroleum‐based thermoplastics. This Review summarizes approaches towards the development of lignin‐based thermoplastic materials, including plasticization, blending with miscible polymers, and chemical modifications by esterification, etherification, polymer grafting, and copolymerization.
Background & objectives: Information on recent cancer statistics is important for planning, monitoring and evaluating cancer control activities. This article aims to provide an update on the cancer ...incidence estimates in India by sex, age groups and anatomical sites for the year 2022.
Methods: The National Cancer Registry Programme Report 2020, reported the cancer incidence from 28 Population-Based Cancer Registries (PBCRs) for the years 2012-2016. This was used as the basis to calculate cancer estimates in India. Information pertaining to the population at risk was extracted from the Census of India (2001 and 2011) for the estimation of age-sex stratified population. PBCRs were categorised into the respective State and regions of the country to understand the epidemiology of cancer. The age-specific incidence rate for each specific anatomical site of cancer was applied to the estimated population to derive the number of cancer cases in India for 2022.
Results: The estimated number of incident cases of cancer in India for the year 2022 was found to be 14,61,427 (crude rate:100.4 per 100,000). In India, one in nine people are likely to develop cancer in his/her lifetime. Lung and breast cancers were the leading sites of cancer in males and females, respectively. Among the childhood (0-14 yr) cancers, lymphoid leukaemia (boys: 29.2% and girls: 24.2%) was the leading site. The incidence of cancer cases is estimated to increase by 12.8 per cent in 2025 as compared to 2020.
Interpretation & conclusions: The cancer incidence is continuing to increase in India. The new estimates will be helpful in planning cancer prevention and control activities through the intervention of early detection, risk reduction and management.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The changing prevalence and patterns of tobacco use, the advent of novel nicotine delivery devices, and the development of new biomarkers prompted an update of the 2002 Society for Research on ...Nicotine and Tobacco (SRNT) report on whether and how to apply biomarker verification for tobacco use and abstinence.
The SRNT Treatment Research Network convened a group of investigators with expertise in tobacco biomarkers to update the recommendations of the 2002 SNRT Biochemical Verification Report.
Biochemical verification of tobacco use and abstinence increases scientific rigor and is recommended in clinical trials of smoking cessation, when feasible. Sources, appropriate biospecimens, cutpoints, time of detection windows and analytic methods for carbon monoxide, cotinine (including over the counter tests), total nicotine equivalents, minor tobacco alkaloids, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol are reviewed, as well as biochemical approaches to distinguishing cigarette smoking from use of electronic nicotine delivery devices (ENDS).
Recommendations are provided for whether and how to use biochemical verification of tobacco use and abstinence. Guidelines are provided on which biomarkers to use, which biospecimens to use, optimal cutpoints, time windows to detection, and methodology for biochemical verifications. Use of combinations of biomarkers is recommended for assessment of ENDS use.
Biochemical verification increases scientific rigor, but there are drawbacks that need to be assessed to determine whether the benefits of biochemical verification outweigh the costs, including the cost of the assays, the feasibility of sample collection, the ability to draw clear conclusions based on the duration of abstinence, and the variability of the assay within the study population. This paper provides updated recommendations from the 2002 SRNT report on whether and how to use biochemical markers in determining tobacco use and abstinence.
DNA sequence variation within human leukocyte antigen (HLA) genes mediate susceptibility to a wide range of human diseases. The complex genetic structure of the major histocompatibility complex (MHC) ...makes it difficult, however, to collect genotyping data in large cohorts. Long-range linkage disequilibrium between HLA loci and SNP markers across the major histocompatibility complex (MHC) region offers an alternative approach through imputation to interrogate HLA variation in existing GWAS data sets. Here we describe a computational strategy, SNP2HLA, to impute classical alleles and amino acid polymorphisms at class I (HLA-A, -B, -C) and class II (-DPA1, -DPB1, -DQA1, -DQB1, and -DRB1) loci. To characterize performance of SNP2HLA, we constructed two European ancestry reference panels, one based on data collected in HapMap-CEPH pedigrees (90 individuals) and another based on data collected by the Type 1 Diabetes Genetics Consortium (T1DGC, 5,225 individuals). We imputed HLA alleles in an independent data set from the British 1958 Birth Cohort (N = 918) with gold standard four-digit HLA types and SNPs genotyped using the Affymetrix GeneChip 500 K and Illumina Immunochip microarrays. We demonstrate that the sample size of the reference panel, rather than SNP density of the genotyping platform, is critical to achieve high imputation accuracy. Using the larger T1DGC reference panel, the average accuracy at four-digit resolution is 94.7% using the low-density Affymetrix GeneChip 500 K, and 96.7% using the high-density Illumina Immunochip. For amino acid polymorphisms within HLA genes, we achieve 98.6% and 99.3% accuracy using the Affymetrix GeneChip 500 K and Illumina Immunochip, respectively. Finally, we demonstrate how imputation and association testing at amino acid resolution can facilitate fine-mapping of primary MHC association signals, giving a specific example from type 1 diabetes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In this meta-analysis, we systematically reviewed research on digital games and learning for K–16 students. We synthesized comparisons of game versus nongame conditions (i.e., media comparisons) and ...comparisons of augmented games versus standard game designs (i.e., value-added comparisons). We used random-effects meta-regression models with robust variance estimates to summarize overall effects and explore potential moderator effects. Results from media comparisons indicated that digital games significantly enhanced student learning relative to nongame conditions (ḡ = 0.33, 95% confidence interval 0.19, 0.48, k = 57, n = 209). Results from value-added comparisons indicated significant learning benefits associated with augmented game designs (ḡ = 0.34, 95% confidence interval 0.17, 0.51, k = 20, n = 40). Moderator analyses demonstrated that effects varied across various game mechanics characteristics, visual and narrative characteristics, and research quality characteristics. Taken together, the results highlight the affordances of games for learning as well as the key role of design beyond medium.
The tobacco-specific
-nitrosamines 4-(
-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK) and
'-nitrosonornicotine (NNN) always occur together and exclusively in tobacco products or in environments ...contaminated by tobacco smoke. They have been classified as "carcinogenic to humans" by the International Agency for Research on Cancer. In 1998, we published a review of the biochemistry, biology and carcinogenicity of tobacco-specific nitrosamines. Over the past 20 years, considerable progress has been made in our understanding of the mechanisms of metabolism and DNA adduct formation by these two important carcinogens, along with progress on their carcinogenicity and mutagenicity. In this review, we aim to provide an update on the carcinogenicity and mechanisms of the metabolism and DNA interactions of NNK and NNN.
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