Characterization of iodothyronine sulfatase activities in human and rat liver and placenta

In conditions associated with high serum iodothyronine sulfate concentrations, e.g. during fetal development, desulfation of these conjugates may be important in the regulation of thyroid hormone homeostasis. However, little is known about which sulfatases are involved in this process. Therefore, we investigated the hydrolysis of iodothyronine sulfates by homogenates of V79 cells expressing the human arylsulfatases A (ARSA), B (ARSB), or C (ARSC; steroid sulfatase), as well as tissue fractions of human and rat liver and placenta. We found that only the microsomal fraction from liver and placenta hydrolyzed iodothyronine sulfates. Among the recombinant enzymes only the endoplasmic reticulum-associated ARSC showed activity toward iodothyronine sulfates; the soluble lysosomal ARSA and ARSB were inactive. Recombinant ARSC as well as human placenta microsomes hydrolyzed iodothyronine sulfates with a substrate preference for 3,3'-diiodothyronine sulfate (3,3'-T(2)S) approximately T(3) sulfate (T(3)S) >> rT(3)S approximately T(4)S, whereas human and rat liver microsomes showed a preference for 3,3'-T(2)S > T(3)S >> rT(3)S approximately T(4)S. ARSC and the tissue microsomal sulfatases were all characterized by high apparent K(m) values (>50 microM) for 3,3'-T(2)S and T(3)S. Iodothyronine sulfatase activity determined using 3,3'-T(2)S as a substrate was much higher in human liver microsomes than in human placenta microsomes, although ARSC is expressed at higher levels in human placenta than in human liver. The ratio of estrone sulfate to T(2)S hydrolysis in human liver microsomes (0.2) differed largely from that in ARSC homogenate (80) and human placenta microsomes (150). These results suggest that ARSC accounts for the relatively low iodothyronine sulfatase activity of human placenta, and that additional arylsulfatase(s) contributes to the high iodothyronine sulfatase activity in human liver. Further research is needed to identify these iodothyronine sulfatases, and to study the physiological importance of the reversible sulfation of iodothyronines in thyroid hormone metabolism

Characterization of human iodothyronine sulfotransferases

Sulfation is an important pathway of thyroid hormone metabolism that facilitates the degradation of the hormone by the type I iodothyronine deiodinase, but little is known about which human sulfotransferase isoenzymes are involved. We have investigated the sulfation of the prohormone T4, the active hormone T3, and the metabolites rT3 and 3,3'-diiodothyronine (3,3'-T2) by human liver and kidney cytosol as well as by recombinant human SULT1A1 and SULT1A3, previously known as phenol-preferring and monoamine-preferring phenol sulfotransferase, respectively. In all cases, the substrate preference was 3,3'-T2 >> rT3 > T3 > T4. The apparent Km values of 3,3'-T2 and T3 [at 50 micromol/L 3'-phosphoadenosine-5'-phosphosulfate (PAPS)] were 1.02 and 54.9 micromol/L for liver cytosol, 0.64 and 27.8 micromol/L for kidney cytosol, 0.14 and 29.1 micromol/L for SULT1A1, and 33 and 112 micromol/L for SULT1A3, respectively. The apparent Km of PAPS (at 0.1 micromol/L 3,3'-T2) was 6.0 micromol/L for liver cytosol, 9.0 micromol/L for kidney cytosol, 0.65 micromol/L for SULT1A1, and 2.7 micromol/L for SULT1A3. The sulfation of 3,3'-T2 was inhibited by the other iodothyronines in a concentration-dependent manner. The inhibition profiles of the 3,3'-T2 sulfotransferase activities of liver and kidney cytosol obtained by addition of 10 micromol/L of the various analogs were better correlated with the inhibition profile of SULT1A1 than with that of SULT1A3. These results indicate similar substrate specificities for iodothyronine sulfation by native human liver and kidney sulfotransferases and recombinant SULT1A1 and SULT1A3. Of the latter, SULT1A1 clearly shows the highest affinity for both iodothyronines and PAPS, but it remains to be established whether it is the prominent isoenzyme for sulfation of thyroid hormone in human liver and kidney

Breast feeding in Australia: A comparative study of Aboriginal and non Aboriginal women

The superiority of breast feeding over bottle feeding is universally acknowledged, and its crucial contribution to infant health is accepted by health authorities. Australia in recognition of the importance of breast feeding to infant health, aims to increase the prevalence of breast feeding. Breast feeding provides benefits for all children, however the health advantage that is gained by breast feeding in comparison to artificial feeding is more apparent among disadvantaged groups. Aboriginal Australians are identified as one such disadvantaged group. This study compares the available literature regarding the prevalence of breast feeding in Aboriginal and non Aboriginal women. It is apparent that breast feeding prevalence differs, between population groups within Australia. Aboriginal children are less likely to have been breast fed than non Aboriginal children. The comparison, indicates that there are deficiencies in the research regarding breast feeding prevalence in both population groups. Many factors affect a woman's decision to breast feed, and the duration of her breast feeding. These factors include, socioeconomic status, age, marital status, educational attainment, occupation and smoking status. These factors are clearly associated with breast feeding in non Aboriginal women. For Aboriginal women, the factors influencing breast feeding are more complex. It is recommended therefore, that it is essential for future research to examine the attitudinal and socialdeterminants of infant feeding practices in Aboriginal women. This is necessary, if educational or interventional strategies are to be effective for this population

Biometric conversion factors as a unifying platform for comparative assessment of invasive freshwater bivalves

Invasive bivalves continue to spread and negatively impact freshwater ecosystems worldwide. As different metrics for body size and biomass are frequently used within the literature to standardise bivalve-related ecological impacts (e.g. respiration and filtration rates), the lack of broadly applicable conversion equations currently hinders reliable comparison across bivalve populations. To facilitate improved comparative assessment among studies originating from disparate geographical locations, we report body size and biomass conversion equations for six invasive freshwater bivalves (or species complex members) worldwide: Corbicula fluminea, C. largillierti, Dreissena bugensis, D. polymorpha, Limnoperna fortunei and Sinanodonta woodiana, and tested the reliability (i.e. precision and accuracy) of these equations. Body size (length, width and height) and biomass metrics of living-weight (LW), wet-weight (WW), dry-weight (DW), dry shell-weight (SW), shell free dry-weight (SFDW) and ash-free dry-weight (AFDW) were collected from a total of 44 bivalve populations located in Asia, the Americas and Europe. Relationships between body size and individual biomass metrics, as well as proportional weight-to-weight conversion factors, were determined. For most species, although inherent variation existed between sampled populations, body size directional measurements were found to be good predictors of all biomass metrics (e.g. length to LW, WW, SW or DW: R2 = 0.82–0.96), with moderate to high accuracy for mean absolute error (MAE): ±9.14%–24.19%. Similarly, narrow 95% confidence limits and low MAE were observed for most proportional biomass relationships, indicating high reliability for the calculated conversion factors (e.g. LW to AFDW; CI range: 0.7–2.0, MAE: ±0.7%–2.0%). Synthesis and applications. Our derived biomass prediction equations can be used to rapidly estimate the biologically active biomass of the assessed species, based on simpler biomass or body size measurements for a wide range of situations globally. This allows for the calculation of approximate average indicators that, when combined with density data, can be used to estimate biomass per geographical unit-area and contribute to quantification of population-level effects. These general equations will support meta-analyses, and allow for comparative assessment of historic and contemporary data. Overall, these equations will enable conservation managers to better understand and predict ecological impacts of these bivalves. © 2021 The Authors. Journal of Applied Ecology published by John Wiley & Sons Ltd on behalf of British Ecological Societ

Muscle architecture and passive lengthening properties of the gastrocnemius medialis and Achilles tendon in children who idiopathically toe-walk

Children who idiopathically toe-walk (ITW) habitually operate at greater plantarflexion angles and thus, at shorter muscle-tendon unit (MTU) lengths than typically developing (TD) children. Therefore, it is often assumed that habitual use of the gastrocnemius muscle in this way will cause remodelling of the muscle-tendon architecture compared to TD children. However, the gastrocnemius muscle architecture of children who ITW has never been measured. It is essential that we gain a better understanding of these muscle-tendon properties, to ensure that appropriate clinical interventions can be provided for these children. Five children who ITW (age 8 ± 2 years) and 14 TD children (age 10 ± 2 years) participated in this study. Ultrasound was combined with isokinetic dynamometry and surface electromyography, to measure muscle architecture at common positions and passive lengthening properties of the gastrocnemius muscle and tendon across full range of motion. Regardless of which common condition groups were compared under, both the absolute and normalised to MTU muscle belly and fascicle lengths were always longer, and the Achilles tendon length was always shorter in children who ITW than TD children (p 0.05); however, passive joint stiffness was greater in children who ITW at maximum dorsiflexion (p = 0.001) and at a joint moment common to all participants (p = 0.029). Consequently, the findings of this pilot study indicate a remodelling of the relative MTU that does not support the concept that children who ITW commonly experience muscle shortening. Therefore, greater consideration of the muscle and tendon properties are required when prescribing clinical interventions that aim to lengthen the MTU, and treatments may be better targeted at the Achilles tendon in children who ITW

Pion contamination in the MICE muon beam

The international Muon Ionization Cooling Experiment (MICE) will perform a systematic investigation of ionization cooling with muon beams of momentum between 140 and 240\,MeV/c at the Rutherford Appleton Laboratory ISIS facility. The measurement of ionization cooling in MICE relies on the selection of a pure sample of muons that traverse the experiment. To make this selection, the MICE Muon Beam is designed to deliver a beam of muons with less than $\sim$1\% contamination. To make the final muon selection, MICE employs a particle-identification (PID) system upstream and downstream of the cooling cell. The PID system includes time-of-flight hodoscopes, threshold-Cherenkov counters and calorimetry. The upper limit for the pion contamination measured in this paper is $f_\pi < 1.4\%$ at 90\% C.L., including systematic uncertainties. Therefore, the MICE Muon Beam is able to meet the stringent pion-contamination requirements of the study of ionization cooling.Department of Energy and National Science Foundation (U.S.A.), the Instituto Nazionale di Fisica Nucleare (Italy), the Science and Technology Facilities Council (U.K.), the European Community under the European Commission Framework Programme 7 (AIDA project, grant agreement no. 262025, TIARA project, grant agreement no. 261905, and EuCARD), the Japan Society for the Promotion of Science and the Swiss National Science Foundation, in the framework of the SCOPES programme

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele