Heteromer score—using internal standards to assess the quality of proteomic data

In the cell, the majority of proteins exist in complexes. Most of these complexes have a constant stoichiometry and thus can be used as internal standards. In this rapid communication, we show that it is possible to calculate a correlation coefficient that reflects the reproducibility of the analytical approach used. The abundance of one subunit in a heterodimer is plotted against the abundance of the other, and this is repeated for all subunits in all heteromers found in the data set. The correlation coefficient obtained (the “heteromer score”) is a new bioinformatic tool that is independent of the method used to collect the data, requires no special sample preparation and can be used retrospectively on old datasets. It can be used for quality control, to indicate when a change becomes significant or identify complexes whose stoichiometry has been perturbed during the experiment.     

Effects of genomic estimated breeding value and dietary energy to protein ratio on growth performance,carcass trait,and lipogenic gene expression in Hanwoo steer

“Genome-based precision feeding” is a concept that involves the application of customised diets to different genetic groups of cattle. We investigated the effects of the genomic estimated breeding value (gEBV) and dietary energy to protein ratio (DEP) on growth performance, carcass traits, and lipogenic gene expression in Hanwoo (Korean cattle) steers. Forty-four Hanwoo steers (BW = 636 kg, age = 26.9 months) were genotyped using the Illumina Bovine 50 K BeadChip. The gEBV was calculated using genomic best linear unbiased prediction. Animals were separated into high gEBV of marbling score or low-gMS groups based on the upper and lower 50% groupings of the reference population, respectively. Animals were assigned to one of four groups in a 2 × 2 factorial arrangement: high gMS/high DEP (0.084 MJ/g), high gMS/low DEP (0.079 MJ/g), low gMS/high DEP, and low gMS/low DEP. Steers were fed concentrate with a high or low DEP for 31 weeks. The BW tended to be higher (0.05 < P < 0.1) in the high-gMS groups compared to the low-gMS groups at 0, 4, 8, 12, and 20 weeks. The average daily gain (ADG) tended to be lower (P = 0.08) in the high-gMS group than in the low-gMS group. Final BW and measured carcass weight (CW) were positively correlated with the gEBV of carcass weight (gCW). The DEP did not affect ADG. Neither the gMS nor the DEP affected the MS and beef quality grade. The intramuscular fat (IMF) content in the longissimus thoracis (LT) tended to be higher (P = 0.08) in the high-gMS groups than in the low-gMS groups. The mRNA levels of lipogenic acetyl-CoA carboxylase and fatty acid binding protein 4 genes in the LT were higher (P < 0.05) in the high-gMS group than in the low-gMS group. Overall, the IMF content tended to be affected by the gMS, and the genetic potential (i.e., gMS) was associated with the functional activity of lipogenic gene expression. The gCW was associated with the measured BW and CW. The results demonstrated that the gMS and the gCW may be used as early prediction indexes for meat quality and growth potential of beef cattle.     

Bone Analysis Using Trabecular Bone Score and Dual-Energy X-Ray Absorptiometry-Based 3-Dimensional Modeling in Postmenopausal Women With Primary Hyperparathyroidism

ObjectivePredominance of bone loss in cortical sites with relative preservation of trabecular bone, even in postmenopausal women, has been described in primary hyperparathyroidism (PHPT). The aim of this study was to evaluate bone microarchitectural differences using dual-energy x-ray absorptiometry (DXA), trabecular bone score (TBS), and DXA-based 3-dimensional (3D) modeling (3D-DXA) between postmenopausal women diagnosed with PHPT (PM-PHPT) and healthy postmenopausal controls.MethodsThis retrospective study included 44 women with PM-PHPT (9 of whom had fractures) and 48 healthy women matched by age, body mass index, and years since menopause treated at Hospital Universitario Fundación Jiménez Díaz between 2008 and 2017. The bone mineral density (BMD) of the lumbar spine (LS), femoral neck, total hip (TH), and 1/3 radius was assessed using DXA, and trabecular volumetric BMD (vBMD), cortical vBMD, integral vBMD, cortical thickness, and cortical surface BMD at TH were assessed using a 3D-DXA software and TBS at LS.ResultsThe mean adjusted BMD values at LS, the femoral neck, and TH; TBS at LS; and TH 3D-DXA parameters (trabecular vBMD, integral vBMD, cortical thickness, and cortical surface BMD) were significantly reduced in women with PM-PHPT compared with those in the controls. However, differences in mean cortical vBMD were not statistically significant (P = .078). There were no significant differences in mean BMD, TBS, or the 3D-DXA parameters between patients with fractures and those without fractures. The 25-hydroxyvitamin D level appeared to be associated with TBS but not with DXA and 3D-DXA measurements.ConclusionPM-PHPT has significant involvement of the trabecular and cortical compartments of the bone, as determined by DXA, TBS, and 3D-DXA.     

Ideal Cardiovascular Health and Adipokine Levels: The Multi-Ethnic Study of Atherosclerosis

ObjectiveTo evaluate the association between ideal cardiovascular health (CVH) and adipokine levels. Adipokines are hormones implicated in obesity and its cardiometabolic consequences. The concept of ideal CVH was introduced to promote 7 key health factors and behaviors in the general population. Previous studies have found strong associations between obesity and ideal CVH. However, existing literature on the link between CVH and adipokines is scarce.MethodsWe studied 1842 Multi-Ethnic Study of Atherosclerosis participants free of cardiovascular disease who had 7 CVH metrics (smoking, body mass index, physical activity, diet, total cholesterol, blood pressure, and fasting blood glucose) measured at baseline and serum adipokine levels measured at a median of 2.4 years later. Each CVH metric was assigned a score of 0 (poor), 1 (intermediate), or 2 (ideal), and all scores were summed for a total CVH score (0-14). The total CVH scores of 0 to 8, 9 to 10, and 11 to 14 were considered inadequate, average, and optimal, respectively. We used multivariable linear regression models to assess the nonconcurrent associations between the CVH score and log-transformed adipokine levels.ResultsThe mean age was 62.1 ± 9.8 years; 50.2% of participants were men. After adjusting for sociodemographic factors, a 1-unit higher CVH score was significantly associated with 4% higher adiponectin and 15% and 1% lower leptin and resistin levels. Individuals with optimal CVH scores had 27% higher adiponectin and 56% lower leptin levels than those with inadequate CVH scores. Similar trends were observed for those with average versus inadequate CVH scores.ConclusionIn a multi-ethnic cohort free of cardiovascular disease at baseline, individuals with average and optimal CVH scores had a more favorable adipokine profile than those with inadequate CVH scores.     

Influence of age,body weight and body condition score before mating start date on the pubertal rate of maiden Holstein–Friesian heifers and implications for subsequent cow performance and profitability

The aim of this study was to assess the influence of age, body weight (BW) and body condition score (BCS) of maiden Holstein–Friesian heifers before mating start date (MSD) on the rate of puberty, subsequent production and longevity and their implications with regard to farm profitability. Data were available on 871 Holstein–Friesian heifers from 48 herds. BW was recorded electronically and BCS was recorded by a single operator on a scale of 1 to 5. Heifer age was calculated as the number of days from birth to the day of visit. All of the independent variables of interest were grouped into three or four categories. Three age categories (thirtiles), four BW categories (quartiles) and four BCS categories (⩽2.75, 3.00, 3.25 and ⩾3.50) were formed. Heifers with an identifiable corpus lutuem (CL) in the presence or absence of large follicles and peri-ovulatory signs and with a plasma progesterone (P4) concentration ⩾1 ng/ml were classified as pubertal. In addition, heifers without an identifiable CL in the presence or absence of large follicles and peri-ovulatory signs but with a P4 concentration ⩾1 ng/ml were also classified as pubertal. Age, BW and BCS at MSD were all found to be significantly associated with pubertal rate (P < 0.05). Age was shown to have no practical implications on subsequent cow performance. BW at MSD was favourably associated with subsequent calving date (P < 0.05), subsequent cow BW (P < 0.001) and potential (305 days) milk fat plus protein yield (P < 0.001). BCS at MSD was found to be favourably associated with milk fat plus protein yield potential (P < 0.05) and BCS (P < 0.001) during lactation. The economic analysis undertaken indicated that larger, well-grown heifers will be more profitable because of superior production potential, all else being equal. However, because of the finding of poorer reproductive efficiency in heifers grown to more than 343 kg at MSD, heifers at ∼330 kg at MSD are deemed optimal. This will correspond to mature cow BW of ∼550 kg.     

Thyroid-Associated Ophthalmopathy: Preliminary Study Using T2 Mapping to Characterize Intraorbital Optic Nerve Changes Before Dysthyroid Optic Neuropathy

ObjectiveTo evaluate the performance of T2 mapping in detecting intraorbital optic nerve (ON) changes in patients with thyroid-associated ophthalmopathy (TAO) before the onset of dysthyroid optic neuropathy (DON).MethodsThirty-five patients with TAO and without DON (21 active, 14 inactive) and 21 healthy controls (HCs) were enrolled. Magnetic resonance imaging-derived parameters of T2 relaxation time (T2RT) at the intraorbital ON, extraocular muscle (EOM), orbital fat, exophthalmos, summed thickness of EOMs, orbital fat thickness, and clinical variables were compared. Correlations between T2RT at the ON and other variables were assessed.ResultsPatients with TAO showed significantly higher T2RTs at the intraorbital ON than HCs (P < .001). Patients with active TAO had significantly higher T2RTs than those with inactive TAO and HCs (P < .001). Differences between patients with inactive TAO and HCs were insignificant (P > .05/3). T2RT at the intraorbital ON was positively correlated with clinical activity score, modified NOSPECS score, T2RT at EOM, exophthalmos, and summed thickness of EOMs in the TAO group (P ≤ .003) and negatively correlated with visual acuity (P = .033) and visual field indices (P = .030) in patients with active TAO. A T2RT cutoff of 82.9 ms for the intraorbital ON distinguished active TAO and healthy eyes optimally (area under the curve, 0.800; sensitivity, 85.7%; specificity, 64.3%).ConclusionT2RT detects disturbance in the intraorbital ON in patients with TAO, especially active TAO, before DON develops. T2 mapping has a potential for noninvasive evaluation of ON changes in patients with TAO.     

Crystal structure of thioredoxin 1 from Cryptococcus neoformans at 1.8 Å resolution shows unexpected plasticity of the loop preceding the catalytic site

An elevated prevalence of cryptococcal infection is a tendency in low-income countries and constitutes a global public health problem due to factors such as the limited efficacy of antifungal therapy and the AIDS/transplant immunocompromised patients. The fungus Cryptococcus neoformans, implicated in this burden, has had several genes validated as drug targets. Among them, the thioredoxin system is one of the major regulators of redox homeostasis and antioxidant defense acting on protein disulfide bonds. Thioredoxin 1 from C. neoformans (CnTrx1) was cloned and expressed in E. coli and the recombinant protein was purified and crystallized. Functional assay shows that CnTrx1 catalyzes the reduction of insulin disulfide bonds using dithiothreitol, while acting as a monomer in solution. The crystal structure of oxidized CnTrx1 at 1.80 Å resolution presents a dimer in the asymmetric unit with typical Trx-fold. Differences between the monomers in the asymmetric unit are found specially in the loop leading to the Cys-Gly-Pro-Cys active-site motif, being even larger when compared to those found between reduced and oxidized states of other thioredoxins. Although the thioredoxins have been isolated and characterized from many organisms, this new structural report provides important clues for understanding the binding and specificity of CnTrx1 to its targets.     

Structural basis for thermostability revealed through the identification and characterization of a highly thermostable phosphotriesterase-like lactonase from Geobacillus stearothermophilus

A new enzyme homologous to phosphotriesterase was identified from the bacterium Geobacillus stearothermophilus (GsP). This enzyme belongs to the amidohydrolase family and possesses the ability to hydrolyze both lactone and organophosphate (OP) compounds, making it a phosphotriesterase-like lactonase (PLL). GsP possesses higher OP-degrading activity than recently characterized PLLs, and it is extremely thermostable. GsP is active up to 100 °C with an energy of activation of 8.0 kcal/mol towards ethyl paraoxon, and it can withstand an incubation temperature of 60 °C for two days. In an attempt to understand the thermostability of PLLs, the X-ray structure of GsP was determined and compared to those of existing PLLs. Based upon a comparative analysis, a new thermal advantage score and plot was developed and reveals that a number of different factors contribute to the thermostability of PLLs.