516 research outputs found
Profiles in Parole Release and Revocation Idaho
Idaho has had a parole release authority since 1899. Idaho's sentencing framework requires judges to impose a minimum length of incarceration in each felony case; judges may also impose a subsequent indeterminate term of incarceration, during which an inmate may be eligible for parole. Idaho law also imposes mandatory minimum sentences for some crimes. Idaho does not have a sentencing commission or sentencing guidelines
Profiles in Parole Release and Revocation Iowa
Iowa does not have a sentencing commission or sentencing guidelines. It is an indeterminate sentencing state that has, over time, adopted mandatory minimum penalties for certain crimes. Its Board of Parole was established in 1907, and has operated continuously since
Mne1 Is a Novel Component of the Mitochondrial Splicing Apparatus Responsible for Processing of a \u3ci\u3eCOX1\u3c/i\u3e Group I Intron in Yeast
Saccharomyces cerevisiae cells lacking Mne1 are deficient in
intron splicing in the gene encoding the Cox1 subunit of cytochrome
oxidase but contain wild-type levels of the bc1 complex.
Thus, Mne1 has no role in splicing of COB introns or expression
of the COB gene. Northern experiments suggest that splicing of
the COX1 aI5β intron is dependent on Mne1 in addition to the
previously known Mrs1, Mss116, Pet54, and Suv3 factors. Processing
of the aI5_ intron is similarly impaired in mne1∆ and
mrs1∆ cells and overexpression of Mrs1 partially restores the
respiratory function of mne1∆ cells. Mrs1 is known to function
in the initial transesterification reaction of splicing. Mne1 is a
mitochondrial matrix protein loosely associated with the inner
membrane and is found in a high mass ribonucleoprotein complex
specifically associated with the COX1 mRNA even within
an intronless strain. Mne1 does not appear to have a secondary
function in COX1 processing or translation, because disruption
of MNE1 in cells containing intronless mtDNA does not lead to
a respiratory growth defect. Thus, the primary defect in mne1∆
cells is splicing of the aI5β intron in COX1
Zinc-enriched fertilisers as a potential public health intervention in Africa
Background
In this review, we examine the potential of Zn-enriched fertilisers to alleviate human dietary Zn deficiency. The focus is on ten African countries where dietary Zn supply is low and where fertiliser subsidies are routinely deployed on cereal crops.
Scope
Dietary Zn supply and deficiency prevalence were quantified from food supply and composition data. Typical effects of soil (granular) and foliar Zn applications on Zn concentrations in maize (Zea mays L.), rice (Oryza sativa L.) and wheat (Triticum aestivum L.) grains were based on a systematic literature review. Reductions in disease burdens attributable to Zn deficiency and cost-effectiveness were estimated using a disability-adjusted life years (DALYs) approach.
Conclusions
Baseline Zn supply in 2009 ranged from 7.1 (Zambia) to 11.9 (Mali) mg capita−1 day−1; prevalence of Zn deficiency ranged from 24 (Nigeria) to 66 % (Zambia). In reviewed studies, soil Zn application led to an increase in median Zn concentration in maize, rice and wheat grains of 23, 7 and 19 %; foliar application led to increases of 30, 25 and 63 %. Enriching granular fertilisers within current subsidy schemes would be most effective in Malawi, reducing DALYs lost due to Zn deficiency by 10 %. The cost per DALY saved ranged from US 46 to 347 via foliar fertilisers. Foliar applications are likely to be more cost effective than soil applications due to fixation of Zn in the soil but may be more difficult to deploy. Zinc fertilisation is likely to be less cost-effective than breeding in the longer term although other micronutrients such as selenium could be incorporated
Valuing increased zinc (Zn) fertiliser-use in Pakistan
Use of zinc (Zn) fertilisers may be cost-effective in increasing crop yields and in alleviating dietary Zn deficiency. However, Zn fertilisers are underutilised in many countries despite the widespread occurrence of Zn-deficient soils. Here, increased Zn fertiliser-use scenarios were simulated for wheat production in Punjab and Sindh Provinces, Pakistan. Inputs and outputs were valued in terms of both potential yield gains as well as health gains in the population.
Methods
The current dietary Zn deficiency risk of 23.9 % in Pakistan was based on food supply and wheat grain surveys. “Disability-adjusted life years (DALYs) lost” are a common metric of disease burden; an estimated 245,000 DALYs y−1 are lost in Punjab and Sindh due to Zn deficiency. Baseline Zn fertiliser-use of 7.3 kt y−1 ZnSO4.H2O was obtained from published and industry sources. The wheat area currently receiving Zn fertilisers, and grain yield responses of 8 and 14 % in Punjab and Sindh, respectively, were based on a recent survey of >2500 farmers. Increased grain Zn concentrations under Zn fertilisation were estimated from literature data and converted to improved Zn intake in humans and ultimately a reduction in DALYs lost
Heavily and fully modified RNAs guide efficient SpyCas9-mediated genome editing
RNA-based drugs depend on chemical modifications to increase potency and to decrease immunogenicity in vivo. Chemical modification will likely improve the guide RNAs involved in CRISPR-Cas9-based therapeutics as well. Cas9 orthologs are RNA-guided microbial effectors that cleave DNA. Here, we explore chemical modifications at all positions of the crRNA guide and tracrRNA cofactor. We identify several heavily modified versions of crRNA and tracrRNA that are more potent than their unmodified counterparts. In addition, we describe fully chemically modified crRNAs and tracrRNAs (containing no 2\u27-OH groups) that are functional in human cells. These designs will contribute to Cas9-based therapeutics since heavily modified RNAs tend to be more stable in vivo (thus increasing potency). We anticipate that our designs will improve the use of Cas9 via RNP and mRNA delivery for in vivo and ex vivo purposes
Heavily and Fully Modified RNAs Guide Efficient SpyCas9-Mediated Genome Editing [preprint]
RNA-based drugs depend on chemical modifications to increase potency and nuclease stability, and to decrease immunogenicity in vivo. Chemical modification will likely improve the guide RNAs involved in CRISPR-Cas9-based therapeutics as well. Cas9 orthologs are RNA-guided microbial effectors that cleave DNA. No studies have yet explored chemical modification at all positions of the crRNA guide and tracrRNA cofactor. Here, we have identified several heavily-modified versions of crRNA and tracrRNA that are more potent than their unmodified counterparts. In addition, we describe fully chemically modified crRNAs and tracrRNAs (containing no 2\u27-OH groups) that are functional in human cells. These designs demonstrate a significant breakthrough for Cas9-based therapeutics since heavily modified RNAs tend to be more stable in vivo (thus increasing potency). We anticipate that our designs will improve the use of Cas9 via RNP and mRNA delivery for in vivo and ex vivo purposes
Contrasting genetic association of IL2RA with SLE and ANCA-associated vasculitis.
BACKGROUND: Autoimmune diseases are complex and have genetic and environmental susceptibility factors. The objective was to test the genetic association of systemic lupus erythematosus (SLE) and anti-neutrophil cytoplasmic antibody (ANCA) - associated systemic vasculitis (AAV) with SNPs in the IL2RA region and to correlate genotype with serum levels of IL-2RA. METHODS: Using a cohort of over 700 AAV patients, two SLE case-control studies and an SLE trio collection (totalling over 1000 SLE patients), and a TaqMan genotyping approach, we tested 3 SNPs in the IL2RA locus, rs11594656, rs2104286 & rs41295061, each with a prior association with autoimmune disease; rs11594656 and rs41295061 with type 1 diabetes (T1D) and rs2104286 with multiple sclerosis (MS) and T1D. RESULTS: We show that SLE is associated with rs11594656 (P = 3.87 x 10-7) and there is some evidence of association of rs41295061 with AAV (P = 0.0122), which both have prior association with T1D. rs2104286, an MS and T1D - associated SNP in the IL2RA locus, is not associated with either SLE or AAV. CONCLUSION: We have confirmed a previous suggestion that the IL2RA locus is associated with SLE and showed some evidence of association with AAV. Soluble IL-2RA concentrations correlate with rs11594656 genotype in quiescent disease in both AAV and SLE. Differential association of autoimmune diseases and SNPs within the IL2RA locus suggests that the IL2RA pathway may prove to play differing, as yet undefined, roles in each disease
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