Meta-analyses have been carried out to quantify the effect of dietary vitamin E on α-tocopherol accumulation and on lipid oxidation in porcine
M. longissimus. Published results of 13 (vitamin E ...accumulation) and 10 (lipid oxidation) experiments respectively were used for the analyses. After a number of standardization procedures, a nonlinear relationship was found between the supplementary vitamin E and the accumulation of α-tocopherol in pork which approached a maximum value of 6.4
μg/g tissue. Pork lipid oxidation levels were described in terms of Thiobarbituric Acid Reacting Substances (TBARS) values. The statistical analysis revealed significant effect of vitamin E dose, muscle α-tocopherol concentration and supplementation time on TBARS, resulting in two prediction models for lipid oxidation.
Meta-analysis has proven to be a valuable tool for combining results from previous studies to quantify the effects of dietary vitamin E. Further studies, carried out with standardized experimental protocols would be beneficial for model validation and to increase the predictive power of the derived models.
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Technological meat quality is a significant economic factor in pork production, and numerous publications have shown that it is strongly influenced both by genetic status and by rearing and slaughter ...conditions. The quality of meat is often described by meat pH at different times postmortem, as well as by color and drip loss, whereas carcass quality is often characterized by lean percentage. A meta-analysis of findings relating to 3,530 pigs reported in 23 publications was carried out to assess the effects of the halothane gene, sex, breed, and slaughter weight of animals on 7 selected variables: pH at 45 min postmortem, ultimate pH, reflectance (L*-value), redness (a*-value), yellowness (b*-value), drip loss, and lean percentage. Two statistical methods were used in the meta-analysis: the method of effect size and the better known random effects model. The method of effect size was associated with Markov chain Monte Carlo techniques for implementing Bayesian hierarchical models to avoid the problems of limited data and publication bias. The results of our meta-analysis showed that the halothane genotype had a significant effect on all analyzed pork quality variables. Between-study variance was evaluated with the Cochran (1954) Q-test of heterogeneity. Meta-regression was used to explain this variance, with covariates such as breed, sex, slaughter weight, and fasting duration being integrated into different regression models. The halothane gene effect was associated with the breed effect only for the following variables: L*-value, b*-value, and drip loss. Slaughter weight contributed significantly only to the explanation of differences in ultimate pH between homozygous genotypes. In response to inconsistencies reported in the literature regarding the difference between the genotypes NN and Nn, results of the meta-analysis showed that the difference between these 2 genotypes was significant for all the analyzed variables except the a*-value.
Technological meat quality is a significant economic factor in pork production, and numerous publications have shown that it is strongly influenced both by genetic status and by rearing and slaughter ...conditions. The quality of meat is often described by meat pH at different times postmortem, as well as by color and drip loss, whereas carcass quality is often characterized by lean percentage. A meta-analysis of findings relating to 3,530 pigs reported in 23 publications was carried out to assess the effects of the halothane gene, sex, breed, and slaughter weight of animals on 7 selected variables: pH at 45 min postmortem, ultimate pH, reflectance (L*-value), redness (a*-value), yellowness (b*-value), drip loss, and lean percentage. Two statistical methods were used in the meta-analysis: the method of effect size and the better known random effects model. The method of effect size was associated with Markov chain Monte Carlo techniques for implementing Bayesian hierarchical models to avoid the problems of limited data and publication bias. The results of our meta-analysis showed that the halothane genotype had a significant effect on all analyzed pork quality variables. Between-study variance was evaluated with the Cochran (1954) Q-test of heterogeneity. Meta-regression was used to explain this variance, with covariates such as breed, sex, slaughter weight, and fasting duration being integrated into different regression models. The halothane gene effect was associated with the breed effect only for the following variables: L*-value, b*-value, and drip loss. Slaughter weight contributed significantly only to the explanation of differences in ultimate pH between homozygous genotypes. In response to inconsistencies reported in the literature regarding the difference between the genotypes NN and Nn, results of the meta-analysis showed that the difference between these 2 genotypes was significant for all the analyzed variables except the a*-value. PUBLICATION ABSTRACT
To determine the relation of neuritic plaques (NPs) and neurofibrillary tangles (NFTs) to the development and evolution of Alzheimer disease (AD).
An autopsy series of 102 patients with dementia and ...pathologically confirmed AD and 29 normal control subjects (NCs) was studied. AD cases were stratified according to their last Mini-Mental State Examination (MMSE) before death as mild, moderate, severe, or very severe. NPs and NFTs were enumerated in the midfrontal (MF), inferior parietal (IP), superior temporal (ST), hippocampal (Hip), or entorhinal cortices using thioflavin-S preparations.
Most (87%) of the NCs had allocortical NFTs, whereas only a minority (37%) displayed neocortical NPs, and even fewer (19%) showed Hip NPs. In contrast, none of the NCs exhibited neocortical NFTs, except one case with a single ST tangle. However, neocortical NFTs were not detected in even 10% of the patients with AD and, in particular, were absent in nearly 50% of those with mild disease at death. Thus, their sensitivity as a marker of AD was lower than that of NPs, which, conversely, were found in all patients with AD. Comparing NCs and patients with mild AD, significant differences were found for numbers of NPs only. Across the AD groups, in contrast, although NP and NFT density increased with dementia severity, significant differences consistently emerged for NFTs alone.
Deterioration in Alzheimer disease appears to be driven by neuritic plaques and neurofibrillary tangles at different stages of the disease. The significant increase in neuritic plaques, but not neurofibrillary tangles, in patients with even mild Alzheimer disease at death compared with normal control subjects suggests that only neuritic plaques are associated with the earliest symptoms of Alzheimer disease.
We apply airborne measurements across three seasons (summer, winter and spring 2017-2018) in a multi-inversion framework to quantify methane emissions from the US Corn Belt and Upper Midwest, a key ...agricultural and wetland source region. Combing our seasonal results with prior fall values we find that wetlands are the largest regional methane source (32 %, 20 16-23 Gg/d), while livestock (enteric/manure; 25 %, 15 14-17 Gg/d) are the largest anthropogenic source. Natural gas/petroleum, waste/landfills, and coal mines collectively make up the remainder. Optimized fluxes improve model agreement with independent datasets within and beyond the study timeframe. Inversions reveal coherent and seasonally dependent spatial errors in the WetCHARTs ensemble mean wetland emissions, with an underestimate for the Prairie Pothole region but an overestimate for Great Lakes coastal wetlands. Wetland extent and emission temperature dependence have the largest influence on prediction accuracy; better representation of coupled soil temperature-hydrology effects is therefore needed. Our optimized regional livestock emissions agree well with the Gridded EPA estimates during spring (to within 7 %) but are ∼25 % higher during summer and winter. Spatial analysis further shows good top-down and bottom-up agreement for beef facilities (with mainly enteric emissions) but larger (∼30 %) seasonal discrepancies for dairies and hog farms (with >40 % manure emissions). Findings thus support bottom-up enteric emission estimates but suggest errors for manure; we propose that the latter reflects inadequate treatment of management factors including field application. Overall, our results confirm the importance of intensive animal agriculture for regional methane emissions, implying substantial mitigation opportunities through improved management.
The rapid succession of discoveries of short-duration hard-spectrum gamma-ray bursts (GRBs) has led to unprecedented insights into the energetics of the explosion and nature of the progenitors. Yet ...short of the detection of a smoking gun, such as a burst of coincident gravitational radiation or a Li-Paczynski minisupernova, it is unlikely that a definitive claim can be made for the progenitors. As was the case with long-duration soft-spectrum GRBs, however, the expectation is that a systematic study of the hosts and locations of short GRBs could begin to yield fundamental clues as to their nature. We present an aggregate study of the host galaxies of short-duration hard-spectrum GRBs. In particular, we present the Gemini-North and Keck discovery spectra of the galaxies that hosted three short GRBs and a moderate-resolution (R - 6000) spectrum of a fourth host. We find that these short-hard GRBs originate in a variety of low-redshift (z < 1) environments that differ substantially from those of long-soft GRBs, both on individual galaxy scales and on galaxy-cluster scales. Specifically, three of the bursts are found to be associated with old and massive galaxies with no current (<0.1 M sub( )yr super(-1)) or recent star formation. Two of these galaxies are located within a cluster environment. These observations support an origin from the merger of compact stellar remnants, such as double neutron stars or a neutron star-black hole binary. The fourth event, in contrast, occurred within a dwarf galaxy with a star formation rate exceeding 0.3 M sub( )yr super(-1). Therefore, it appears that like supernovae of Type la, the progenitors of short-hard bursts are created in all galaxy types, suggesting a corresponding class with a wide distribution of delay times between formation and explosion.
Type 2 diabetes (T2D) is characterised by the loss of first-phase insulin secretion. We studied mice with β-cell selective loss of the glucagon receptor (Gcgrfl/fl X Ins-1Cre), to investigate the ...role of intra-islet glucagon receptor (GCGR) signalling on pan-islet Ca2+I activity and insulin secretion.
Metabolic profiling was conducted on Gcgrβ-cell−/− and littermate controls. Crossing with GCaMP6f (STOP flox) animals further allowed for β-cell specific expression of a fluorescent calcium indicator. These islets were functionally imaged in vitro and in vivo. Wild-type mice were transplanted with islets expressing GCaMP6f in β-cells into the anterior eye chamber and placed on a high fat diet. Part of the cohort received a glucagon analogue (GCG-analogue) for 40 days and the control group were fed to achieve weight matching. Calcium imaging was performed regularly during the development of hyperglycaemia and in response to GCG-analogue treatment.
Gcgrβ-cell−/− mice exhibited higher glucose levels following intraperitoneal glucose challenge (control 12.7 mmol/L ± 0.6 vs. Gcgrβ-cell−/− 15.4 mmol/L ± 0.0 at 15 min, p = 0.002); fasting glycaemia was not different to controls. In vitro, Gcgrβ-cell−/− islets showed profound loss of pan-islet Ca2+I waves in response to glucose which was only partially rescued in vivo. Diet induced obesity and hyperglycaemia also resulted in a loss of co-ordinated Ca2+I waves in transplanted islets. This was reversed with GCG-analogue treatment, independently of weight-loss (n = 8).
These data provide novel evidence for the role of intra-islet GCGR signalling in sustaining synchronised Ca2+I waves and support a possible therapeutic role for glucagonergic agents to restore the insulin secretory capacity lost in T2D.
•Beta-cell selective loss of the glucagon receptor (Gcgrβ-cell−/−) results in defective insulin secretion.•Gcgrβ-cell−/− islets display reduced ability for calcium waves to propagate and reduced beta-cell connectivity.•Long-term glucagon therapy reverts the loss of beta-cell calcium waves and dysglycaemia associated with diet induced obesity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To determine whether AD neurofibrillary pathology influences clinical diagnostic accuracy in dementia with Lewy bodies (DLB).
Pathologic diagnosis of DLB mandates Lewy bodies but also allows for AD ...pathology in the form of plaques and tangles. Because clinical diagnostic accuracy of DLB remains low, the authors questioned whether the severity of AD pathology in the form of tangles might affect the clinician's ability to correctly diagnose DLB in life.
Ninety-eight subjects with autopsy-proven DLB who had been evaluated annually at the University of California San Diego AD Research Center were identified. The clinical diagnosis used was the last diagnosis before death. Pathologic diagnosis of DLB was made according to Consensus guidelines, and Braak staging was used to assess the degree of neurofibrillary AD pathology. The clinical characteristics of subjects with DLB with low vs high Braak stages were compared and the clinical diagnostic accuracy for subjects stratified according to Braak stage was determined.
Only 27% of the subjects with DLB demonstrated both visual hallucinations and spontaneous extrapyramidal signs (EPS). The low Braak stage (0 to 2, n = 24) subjects had a higher frequency of visual hallucinations (65%) than did subjects with DLB with higher (3 to 6, n = 66) Braak stages (33%, p = 0.008), and showed a slightly greater but not significant degree of EPS. Although clinical diagnostic accuracy for DLB was relatively low (49%), it was higher for subjects with low (75%) compared to high (39%) Braak stages (p = 0.0039).
The degree of concomitant AD tangle pathology has an important influence on the clinical characteristics and, therefore, the clinical diagnostic accuracy of DLB.
N-methyl-D-aspartate (NMDA) glutamate receptors are regulators of fast neurotransmission and synaptic plasticity in the brain. Disruption of NMDA-mediated glutamate signaling has been linked to ...behavioral deficits displayed in psychiatric disorders such as schizophrenia. Recently, noncoding RNA molecules such as microRNAs (miRNAs) have emerged as critical regulators of neuronal functions. Here we show that pharmacological (dizocilpine) or genetic (NR1 hypomorphism) disruption of NMDA receptor signaling reduces levels of a brain-specific miRNA, miR-219, in the prefrontal cortex (PFC) of mice. Consistent with a role for miR-219 in NMDA receptor signaling, we identify calcium/calmodulin-dependent protein kinase II γ subunit (CaMKIIγ), a component of the NMDA receptor signaling cascade, as a target of miR-219. In vivo inhibition of miR-219 by specific antimiR in the murine brain significantly modulated behavioral responses associated with disrupted NMDA receptor transmission. Furthermore, pretreatment with the antipsychotic drugs haloperidol and clozapine prevented dizocilpine-induced effects on miR-219. Taken together, these data support an integral role for miR-219 in the expression of behavioral aberrations associated with NMDA receptor hypofunction.
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