Biochar, the solid product of biomass pyrolysis, can be used as a soil amendment to stabilize metals in contaminated soils. The effects of biochar on the mobility of metals in soils are, however, ...poorly understood. To identify the predominant processes, we focused on (i) a possible kinetic limitation by transport in biochar particles, (ii) the evolution of biochar mineral phases and (iii) the effect of biochar on soil pH. Batch experiments were conducted to measure the sorption kinetics of copper (Cu), cadmium (Cd) and nickel (Ni) and the sorption‐desorption isotherms for lead (Pb), Cu, Cd, zinc (Zn) and Ni in a wood‐derived biochar. Sorption data were then compared with extraction test results using biochar with one acidic and one basic soil contaminated by Zn, Cd and Pb. Kinetic results showed that biochar particle sizes controlled metal sorption rate despite a similar specific surface area, which indicated a limitation by intra‐particle diffusion. Isotherms showed a partially reversible sorption to biochar following the order Pb > Cu > Cd ≥ Zn > Ni, which we explained primarily by the (co)precipitation of metals or their adsorption on specific biochar mineral phases. Effective metal immobilization was observed with biochar in both contaminated soils but could not be predicted from the sorption isotherms. This immobilization appeared to be governed by the soil pH increase, which induced a greater retention of metals on soil particles. Short‐term effects of biochar on contaminated soils may therefore be controlled by diffusion in biochar particles and by soil alkalinization processes.
Rotator cuff tears are a common cause of shoulder pain and can result in prolonged periods of pain, disability and absence from work. Rotator cuff repair surgery is increasingly used in an attempt to ...resolve symptoms but has failure rates of around 40%. There is a pressing need to improve the outcome of rotator cuff repairs. Patch augmentation increasingly being used within the NHS in an attempt to reduce repair failures. The aim of this survey was to determine current UK practice and opinion relating to the factors that influence choice of patch, current patient selection and willingness to assist with generation of improved evidence.
An online survey was sent to the surgeon members of the British Elbow and Shoulder Society (BESS). Questions covered respondent demographics, experience with patches, indications for patch augmentation and willingness to be involved in a randomised trial of patch augmented rotator cuff surgery.
The response rate was 105/550 (19%). 58% of respondents had used a patch to augment rotator cuff surgery. 70% of patch users had undertaken an augmented repair within the last 6 months. A wide surgical experience in augmentation was reported (ranging 1 to 200 implants used). However, most surgeons reported low volume usage, with a median of 5 rotator cuff augmentation procedures performed. At least 10 different products had been used. Most of the patches used were constructed from human decellularised dermis tissue, although porcine derived and synthetic based patches had also been used. Only 3-5% stated they would undertake an augmented repair for small tears across ages, whereas 28-40% and 19-59% would do so for large or massive tears respectively. When assessing patient suitability, patient age seemed relevant only for those with large and massive tears. Half of the surgeons reported an interest in taking part in a randomised controlled trial (RCT) evaluating the role of patch augmentation for rotator cuff surgery, with a further 22% of respondent's undecided.
A variety of patches have been used by surgeons to augment rotator cuff repair with a wide range of operator experience. There was substantial uncertainty about which patch to use and differing views on which patients were most suitable. There is a clear need for robust clinical evaluation and further research in this area.
In this article, we describe the Mid-Infrared Imager Module (MIRIM), which provides broadband imaging in the 5-27 μm wavelength range for the James Webb Space Telescope. The imager has a pixel scale ...and a total unobstructed view of 74″ × 113″. The remainder of its nominal 113″ × 113″ field is occupied by the coronagraphs and the low-resolution spectrometer. We present the instrument optical and mechanical design. We show that the test data, as measured during the test campaigns undertaken at CEA-Saclay, at the Rutherford Appleton Laboratory, and at the NASA Goddard Space Flight Center, indicate that the instrument complies with its design requirements and goals. We also discuss the operational requirements (multiple dithers and exposures) needed for optimal scientific utilization of the MIRIM.
Humans vary >100-fold in their sensitivity to the harmful effects of ultraviolet radiation. The main determinants of sensitivity are melanin pigmentation and less-well-characterized differences in ...skin inflammation and repair processes. Pigmentation has a high heritability, but susceptibility to cancers of the skin, a key marker of sun sensitivity, is less heritable. Despite a large number of murine coat-color mutations, only one gene in humans, the melanocortin 1 receptor (
MC1R), is known to account for substantial variation in skin and hair color and in skin cancer incidence.
MC1R encodes a 317–amino acid G-coupled receptor that controls the relative amounts of the two major melanin classes, eumelanin and pheomelanin. Most persons with red hair are homozygous for alleles of the
MC1R gene that show varying degrees of diminished function. More than 65 human
MC1R alleles with nonsynonymous changes have been identified, and current evidence suggests that many of them vary in their physiological activity, such that a graded series of responses can be achieved on the basis of (i) dosage effects (of one or two alleles) and (ii) individual differences in the pharmacological profile in response to ligand. Thus, a single locus, identified within a Mendelian framework, can contribute significantly to human pigmentary variation.
Schizophrenia (SCZ) is a highly heritable neuropsychiatric disorder of complex genetic etiology. Previous genome-wide surveys have revealed a greater burden of large, rare copy number variations ...(CNVs) in SCZ cases and identified multiple rare recurrent CNVs that increase risk of SCZ although with incomplete penetrance and pleiotropic effects. Identification of additional recurrent CNVs and biological pathways enriched for SCZ CNVs requires greater sample sizes. We conducted a genome-wide survey for CNVs associated with SCZ using a Swedish national sample (4719 cases and 5917 controls). High-confidence CNV calls were generated using genotyping array intensity data, and their effect on risk of SCZ was measured. Our data confirm increased burden of large, rare CNVs in SCZ cases as well as significant associations for recurrent 16p11.2 duplications, 22q11.2 deletions and 3q29 deletions. We report a novel association for 17q12 duplications (odds ratio=4.16, P=0.018), previously associated with autism and mental retardation but not SCZ. Intriguingly, gene set association analyses implicate biological pathways previously associated with SCZ through common variation and exome sequencing (calcium channel signaling and binding partners of the fragile X mental retardation protein). We found significantly increased burden of the largest CNVs (>500 kb) in genes present in the postsynaptic density, in genomic regions implicated via SCZ genome-wide association studies and in gene products localized to mitochondria and cytoplasm. Our findings suggest that multiple lines of genomic inquiry--genome-wide screens for CNVs, common variation and exonic variation--are converging on similar sets of pathways and/or genes.
Organ shortage is the major limitation to kidney transplantation in the developed world. Conversely, millions of patients in the developing world with end‐stage renal disease die because they cannot ...afford renal replacement therapy—even when willing living kidney donors exist. This juxtaposition between countries with funds but no available kidneys and those with available kidneys but no funds prompts us to propose an exchange program using each nation's unique assets. Our proposal leverages the cost savings achieved through earlier transplantation over dialysis to fund the cost of kidney exchange between developed‐world patient–donor pairs with immunological barriers and developing‐world patient–donor pairs with financial barriers. By making developed‐world health care available to impoverished patients in the developing world, we replace unethical transplant tourism with global kidney exchange—a modality equally benefitting rich and poor. We report the 1‐year experience of an initial Filipino pair, whose recipient was transplanted in the United states with an American donor's kidney at no cost to him. The Filipino donor donated to an American in the United States through a kidney exchange chain. Follow‐up care and medications in the Philippines were supported by funds from the United States. We show that the logistical obstacles in this approach, although considerable, are surmountable.
The authors propose a system of kidney exchange between developed‐world patient–donor pairs with immunological barriers and developing‐world patient–donor pairs with financial barriers in which the savings from transplantation over continued dialysis fund the cost of transplantation, donor and recipient follow‐up, and long‐term recipient immunosuppression for the developing‐world pair. See Wiseman and Gill's editorial on page 597.
Prime editing is a versatile genome-editing technique that shows great promise for the generation and repair of patient mutations. However, some genomic sites are difficult to edit and optimal design ...of prime-editing tools remains elusive. Here we present a fluorescent prime editing and enrichment reporter (fluoPEER), which can be tailored to any genomic target site. This system rapidly and faithfully ranks the efficiency of prime edit guide RNAs (pegRNAs) combined with any prime editor variant. We apply fluoPEER to instruct correction of pathogenic variants in patient cells and find that plasmid editing enriches for genomic editing up to 3-fold compared to conventional enrichment strategies. DNA repair and cell cycle-related genes are enriched in the transcriptome of edited cells. Stalling cells in the G1/S boundary increases prime editing efficiency up to 30%. Together, our results show that fluoPEER can be employed for rapid and efficient correction of patient cells, selection of gene-edited cells, and elucidation of cellular mechanisms needed for successful prime editing.
GENETICS OF HAIR AND SKIN COLOR Rees, Jonathan L
Annual review of genetics,
01/2003, Letnik:
37, Številka:
1
Journal Article
Recenzirano
Differences in skin and hair color are principally genetically determined
and are due to variation in the amount, type, and packaging of melanin polymers
produced by melanocytes secreted into ...keratinocytes. Pigmentary phenotype is
genetically complex and at a physiological level complicated. Genes determining
a number of rare Mendelian disorders of pigmentation such as albinism have been
identified, but only one gene, the melanocortin 1 receptor (
MCR1
), has
so far been identified to explain variation in the normal population such as
that leading to red hair, freckling, and sun-sensitivity. Genotype-phenotype
relations of the
MC1R
are reviewed, as well as methods to improve the
phenotypic assessment of human pigmentary status. It is argued that given
advances in model systems, increases in technical facility, and the lower cost
of genotype assessment, the lack of standardized phenotype assessment is now a
major limit on advance.
No consensus on the indications for surgical resection of colorectal liver metastases exists. This systematic review has been undertaken to assess the published evidence for its efficacy and safety ...and to identify prognostic factors. Studies were identified by computerised and hand searches of the literature, scanning references and contacting investigators. The outcome measures were overall survival, disease-free survival, postoperative morbidity and mortality, quality of life and cost effectiveness, and a qualitative summary of the trends across all studies was produced. Only 30 of 529 independent studies met all the eligibility criteria for the review, and data on 30-day mortality and morbidity only were included from a further nine studies. The best available evidence came from prospective case series, but only two studies reported outcomes for all patients undergoing surgery. The remainder reported outcomes for selected groups of patients: those undergoing hepatic resection or those undergoing curative resection. Postoperative mortality rates were generally low (median 2.8%). The majority of studies described only serious postoperative morbidity, the most common being bile leak and associated perihepatic abscess. Approximately 30% of patients remained alive 5 years after resection and around two-thirds of these are disease free. The quality of the majority of published papers was poor and ascertaining the benefits of surgical resection of colorectal hepatic metastases is difficult in the absence of randomised trials. However, it is clear that there is group of patients with liver metastases who may become long-term disease-free survivors following hepatic resection. Such survival is rare in apparently comparable patients who do not have surgical treatment. Further work is needed to more accurately define this group of patients and to determine whether the addition of adjuvant treatments results in improved survival.
European grassland‐based livestock production systems face the challenge of producing more meat and milk to meet increasing world demands and to achieve this using fewer resources. Legumes offer ...great potential for achieving these objectives. They have numerous features that can act together at different stages in the soil–plant–animal–atmosphere system, and these are most effective in mixed swards with a legume proportion of 30–50%. The resulting benefits include reduced dependence on fossil energy and industrial N‐fertilizer, lower quantities of harmful emissions to the environment (greenhouse gases and nitrate), lower production costs, higher productivity and increased protein self‐sufficiency. Some legume species offer opportunities for improving animal health with less medication, due to the presence of bioactive secondary metabolites. In addition, legumes may offer an adaptation option to rising atmospheric CO2 concentrations and climate change. Legumes generate these benefits at the level of the managed land‐area unit and also at the level of the final product unit. However, legumes suffer from some limitations, and suggestions are made for future research to exploit more fully the opportunities that legumes can offer. In conclusion, the development of legume‐based grassland–livestock systems undoubtedly constitutes one of the pillars for more sustainable and competitive ruminant production systems, and it can be expected that forage legumes will become more important in the future.
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