Background: Scientific evidence for the optimal number, timing, and size of meals is lacking. Objective: We investigated the relation between meal frequency and timing and changes in body mass index ...(BMI) in the Adventist Health Study 2 (AHS-2), a relatively healthy North American cohort. Methods: The analysis used data from 50,660 adult members aged ≥30 y of Seventh-day Adventist churches in the United States and Canada (mean ± SD follow-up: 7.42 ± 1.23 y). The number of meals per day, length of overnight fast, consumption of breakfast, and timing of the largest meal were exposure variables. The primary outcome was change in BMI per year. Linear regression analyses (stratified on baseline BMI) were adjusted for important demographic and lifestyle factors. Results: Subjects who ate 1 or 2 meals/d had a reduction in BMI per year (in kg · m−2 · y−1) (−0.035; 95% CI: −0.065, −0.004 and −0.029; 95% CI: −0.041, −0.017, respectively) compared with those who ate 3 meals/d. On the other hand, eating >3 meals/d (snacking) was associated with a relative increase in BMI (P < 0.001). Correspondingly, the BMI of subjects who had a long overnight fast (≥18 h) decreased compared with those who had a medium overnight fast (12-17 h) (P < 0.001). Breakfast eaters (−0.029; 95% CI: −0.047, −0.012; P < 0.001) experienced a decreased BMI compared with breakfast skippers. Relative to subjects who ate their largest meal at dinner, those who consumed breakfast as the largest meal experienced a significant decrease in BMI (−0.038; 95% CI: −0.048, −0.028), and those who consumed a big lunch experienced a smaller but still significant decrease in BMI than did those who ate their largest meal at dinner. Conclusions: Our results suggest that in relatively healthy adults, eating less frequently, no snacking, consuming breakfast, and eating the largest meal in the morning may be effective methods for preventing long-term weight gain. Eating breakfast and lunch 5-6 h apart and making the overnight fast last 18-19 h may be a useful practical strategy.
Selenoprotein P (Sepp1) contains most of the selenium in blood plasma, and it is utilized by the kidney, brain, and testis as a selenium source for selenoprotein synthesis. We recently demonstrated ...that apolipoprotein E receptor-2 (ApoER2) is required for Sepp1 uptake by the testis and that deletion of ApoER2 reduces testis and brain, but not kidney, selenium levels. This study examined the kidney Sepp1 uptake pathway. Immunolocalization experiments demonstrated that Sepp1 passed into the glomerular filtrate and was specifically taken up by proximal tubule epithelial cells. Neither the C terminus selenocysteine-rich domain of Sepp1 nor ApoER2 was required for Sepp1 uptake by proximal tubules. Tissue ligand binding assays using cryosections of Sepp1-/- kidneys revealed that the proximal tubule epithelium contained Sepp1-binding sites that were blocked by the receptor-associated protein, RAP, an inhibitor of lipoprotein receptor-ligand interactions. Ligand blotting assays of kidney membrane preparations fractionated by SDS-PAGE revealed that Sepp1 binds megalin, a lipoprotein receptor localized to the proximal tubule epithelium. Immunolocalization analyses confirmed the in vivo co-localization of Sepp1 and megalin in wild type kidneys and demonstrated the absence of proximal tubule Sepp1 uptake in megalin null mice. These results demonstrate that kidney selenium homeostasis is mediated by a megalin-dependent Sepp1 uptake pathway in the proximal tubule.
Selenoprotein P (Sepp1) is taken up by receptor‐mediated endocytosis for its selenium. The other extracellular selenoprotein, glutathione peroxidase‐3 (Gpx3), has not been shown to transport ...selenium. Mice with genetic alterations of Sepp1, the Sepp1 receptors apolipoprotein E receptor‐2 (apoER2) and megalin, and Gpx3 were used to investigate maternalfetal selenium transfer. Immunocytochemistry (ICC) showed receptor‐independent uptake of Sepp1 and Gpx3 in the same vesicles of d‐13 visceral yolk sac cells, suggesting uptake by pinocytosis. ICC also showed apoER2‐mediated uptake of maternal Sepp1 in the d‐18 placenta. Thus, two selenoprotein‐dependent maternalfetal selenium transfer mechanisms were identified. Selenium was quantified in d‐18 fetuses with the mechanisms disrupted. Maternal Sepp1 deletion, which lowers maternal whole‐body selenium, decreased fetal selenium under selenium‐adequate conditions but deletion of fetal apoER2 did not. Fetal apoER2 deletion did decrease fetal selenium, by 51%, under selenium‐deficient conditions, verifying function of the placental Sepp1‐apoER2 mechanism. Maternal Gpx3 deletion decreased fetal selenium, by 13%, but only under selenium‐deficient conditions. These findings indicate that the selenoprotein uptake mechanisms ensure selenium transfer to the fetus under selenium‐deficient conditions. The failure of their disruptions (apoER2 deletion, Gpx3 deletion) to affect fetal selenium under selenium‐adequate conditions indicates the existence of an additional maternal‐fetal selenium transfer mechanism.—Burk, R. F., Olson, G. E., Hill, K. E., Winfrey, V. P., Motley, A. K., and Kurokawa, S., Maternal‐fetal transfer of selenium in the mouse. FASEB J. 27, 3249–3256 (2013). www.fasebj.org
Glutathione peroxidase-3 (Gpx3), also known as plasma or extracellular glutathione peroxidase, is a selenoprotein secreted primarily by kidney proximal convoluted tubule cells. In this study ...Gpx3(-/-) mice have been produced and immunocytochemical techniques have been developed to investigate Gpx3 metabolism. Gpx3(-/-) mice maintained the same whole-body content and urinary excretion of selenium as did Gpx3(+/+) mice. They tolerated selenium deficiency without observable ill effects. The simultaneous knockout of Gpx3 and selenoprotein P revealed that these two selenoproteins account for >97% of plasma selenium. Immunocytochemistry experiments demonstrated that Gpx3 binds selectively, both in vivo and in vitro, to basement membranes of renal cortical proximal and distal convoluted tubules. Based on calculations using selenium content, the kidney pool of Gpx3 is over twice as large as the plasma pool. These data indicate that Gpx3 does not serve in the regulation of selenium metabolism. The specific binding of a large pool of Gpx3 to basement membranes in the kidney cortex strongly suggests a need for glutathione peroxidase activity in the cortical peritubular space.
Selenium is a micronutrient that is essential for the production of normal spermatozoa. The selenium-rich plasma protein selenoprotein P (Sepp1) is required for maintenance of testis selenium and for ...fertility of the male mouse. Sepp1 trafficking in the seminiferous epithelium was studied using conventional methods and mice with gene deletions. Immunocytochemistry demonstrated that Sepp1 is present in vesicle-like structures in the basal region of Sertoli cells, suggesting that the protein is taken up intact. Sepp1 affinity chromatography of a testicular extract followed by mass spectrometry-based identification of bound proteins identified apolipoprotein E receptor 2 (ApoER2) as a candidate testis Sepp1 receptor. In situ hybridization analysis identified Sertoli cells as the only cell type in the seminiferous epithelium with detectable ApoER2 expression. Testis selenium levels in apoER2-/- males were sharply reduced from those in apoER2+/+ males and were comparable with the depressed levels found in Sepp1-/- males. However, liver selenium levels were unchanged by deletion of apoER2. Immunocytochemistry did not detect Sepp1 in the Sertoli cells of apoER2-/- males, consistent with a defect in the receptor-mediated Sepp1 uptake pathway. Phase contrast microscopy revealed identical sperm defects in apoER2-/- and Sepp1-/- mice. Co-immunoprecipitation analysis demonstrated an interaction of testis ApoER2 with Sepp1. These data demonstrate that Sertoli cell ApoER2 is a Sepp1 receptor and a component of the selenium delivery pathway to spermatogenic cells.
Selenoprotein P (SEPP1), an extracellular glycoprotein of unknown function, is a unique member of the selenoprotein family
that, depending on species, contains 10â17 selenocysteines in its primary ...structure; in contrast, all other family members
contain a single selenocysteine residue. The SEPP1-null ( Sepp1 â/â ) male but not the female mice are infertile, but the cellular basis of this male phenotype has not been defined. In this
study, we demonstrate that mature spermatozoa of Sepp1 â/â males display a specific set of flagellar structural defects that develop temporally during spermiogenesis and after testicular
maturation in the epididymis. The flagellar defects include a development of a truncated mitochondrial sheath, an extrusion
of a specific set of axonemal microtubules and outer dense fibers from the principal piece, and ultimately a hairpin-like
bend formation at the midpiece-principal piece junction. The sperm defects found in Sepp1 â/â males appear to be the same as those observed in wild-type ( Sepp1 +/+ ) males fed a low selenium diet. Supplementation of dietary selenium levels for Sepp1 â/â males neither reverses the development of sperm defects nor restores fertility. These data demonstrate that SEPP1 is required
for development of functional spermatozoa and indicate that it is an essential component of the selenium delivery pathway
for developing germ cells.
Abstract
This manuscript demonstrates that infertility of selenoprotein P-null mice results from a defective sperm phenotype
Selenoprotein P (Sepp1) is a plasma and extracellular protein that is rich in selenium. Deletion of Sepp1 results in sharp decreases of selenium levels in the brain and testis with dysfunction of ...those organs. Deletion of Sepp1 also causes increased urinary selenium excretion, leading to moderate depletion of whole-body selenium. The lipoprotein receptor apolipoprotein E receptor-2 (apoER2) binds Sepp1 and facilitates its uptake by Sertoli cells, thus providing selenium for spermatogenesis. Experiments were performed to assess the effect of apoER2 on the concentration and function of selenium in the brain and on whole-body selenium. ApoER2-/- and apoER2+/+ male mice were fed a semipurified diet with selenite added as the source of selenium. ApoER2-/- mice had depressed brain and testis selenium, but normal levels in liver, kidney, muscle, and the whole body. Feeding a selenium-deficient diet to apoER2-/- mice led to neurological dysfunction and death, with some of the characteristics exhibited by Sepp1-/- mice fed the same diet. Thus, although it does not affect whole-body selenium, apoER2 is necessary for maintenance of brain selenium and for prevention of neurological dysfunction and death under conditions of selenium deficiency, suggesting an interaction of apoER2 with Sepp1 in the brain.
Glutathione peroxidase-3 (Gpx3), the extracellular glutathione peroxidase synthesized largely in the kidney, binds to basement membranes of renal cortical epithelial cells. The present study assessed ...extrarenal expression of Gpx3 using RT-PCR and presence of Gpx3 protein using immunocytochemistry. Gpx3 expression was higher in kidney and epididymis than in other tissues. Gpx3 bound to basement membranes of epithelial cells in the gastrointestinal tract, the efferent ducts connecting the seminiferous tubules with the epididymis, the bronchi, and type II pneumocytes. It was not detected on the basement membrane of type I pneumocytes. Gpx3 was also present in the lumen of the epididymis. Transplantation of Gpx3(+/+) kidneys into Gpx3(-/-) mice led to Gpx3 binding to the same basement membranes to which it bound in Gpx3(+/+) mice but not to its presence in the epididymal lumen. These results show that Gpx3 from the blood binds to basement membranes of specific epithelial cells and indicate that the cells modify their basement membranes to cause the binding. They further indicate that at least two Gpx3 compartments exist in the organism. In one compartment, kidney supplies Gpx3 through the blood to specific basement membranes in a number of tissues. In the other compartment, the epididymis provides Gpx3 to its own lumen. Tissues other than kidney and epididymis express Gpx3 at lower levels and may supply Gpx3 to other compartments.
Selenoprotein P (Sepp1) has two domains with respect to selenium content: the N-terminal, selenium-poor domain and the C-terminal, selenium-rich domain. To assess domain function, mice with deletion ...of the C-terminal domain have been produced and compared with Sepp1–/– and Sepp1+/+ mice. All mice studied were males fed a semipurified diet with defined selenium content. The Sepp1 protein in the plasma of mice with the C-terminal domain deleted was determined by mass spectrometry to terminate after serine 239 and thus was designated Sepp1Δ240–361. Plasma Sepp1 and selenium concentrations as well as glutathione peroxidase activity were determined in the three types of mice. Glutathione peroxidase and Sepp1Δ240–361 accounted for over 90% of the selenium in the plasma of Sepp1Δ240–361 mice. Calculations using results from Sepp1+/+ mice revealed that Sepp1, with a potential for containing 10 selenocysteine residues, contained an average of 5 selenium atoms per molecule, indicating that shortened and/or selenium-depleted forms of the protein were present in these wild-type mice. Sepp1Δ240–361 mice had low brain and testis selenium concentrations that were similar to those in Sepp1–/– mice but they better maintained their whole body selenium. Sepp1Δ240–361 mice had depressed fertility, even when they were fed a high selenium diet, and their spermatozoa were defective and morphologically indistinguishable from those of selenium-deficient mice. Neurological dysfunction and death occurred when Sepp1Δ240–361 mice were fed selenium-deficient diet. These phenotypes were similar to those of Sepp1–/– mice but had later onset or were less severe. The results of this study demonstrate that the C terminus of Sepp1 is critical for the maintenance of selenium in brain and testis but not for the maintenance of whole body selenium.
COVID-19 presented a range of challenges to the delivery of school psychology services in countries around the world. The current study aimed to investigate the practices of school psychologists from ...the United States of America, Australia, Germany, Canada, and the United Kingdom, including changes to practice and exploration of the factors that supported the delivery of school psychology services during the pandemic. Quantitative and qualitative data were collected from 1,030 school psychologists and analyzed using a mixed methods, multiple case study design. Differing impacts of the pandemic on the working hours of school psychologists were reported across countries. Participants in all countries reported a shift to online working, with an increased focus on consultation and intervention and a reduction in psychoeducational assessments. School psychologists from all nations emphazised the importance of self-care strategies, social connections and physical activity and the role of support via supervision or professional networks. Access to appropriate technology and responsive workplace policies and procedures were also identified as important. Results have implications for the internationalization of the school psychology profession and can inform international school psychology planning in response to future crises.
PDF
