Expression of the insulin-like growth factor-II/mannose-6-phosphate receptor in multiple human tissues during fetal life and early infancy

The insulin like growth factor-II/mannose-6-phosphate (IGF-II/M6P) receptor has been detected in many cells and tissues. In the rat, there is a dramatic developmental regulation of IGF-II/M6P receptor expression, the receptor being high in fetal and neonatal tissues and declining thereafter. We have systematically studied the expression of the human IGF-II/M6P receptor protein in tissues from 10 human fetuses and infants (age 23 weeks gestation to 24 months postnatal). We have asked 1) whether there is differential expression among different organs, and 2) whether or not the human IGF-II/M6P receptor is developmentally regulated from 23 weeks gestation to 24 months postnatal. Protein was extracted from human tissues using a buffer containing 2% sodium dodecyl sulfate and 2% Triton X-100. Aliquots of the protein extracts were analyzed by sodium dodecyl sulfate- polyacrylamide gel electrophoresis and immunoblotting using an anti-IGF- II/M6P receptor antiserum (no. 66416) and 125I-protein A or an immunoperoxidase stain. IGF-II/M6P receptor immunoreactivity was detected in all tissues studied with the highest amount of receptor being expressed in heart, thymus, and kidney and the lowest receptor content being measured in brain and muscle. The receptor content in ovary, testis, lung, and spleen was intermediate. The apparent molecular weight of the IGF-II/M6P receptor (220,000 kilos without reduction of disulfide bonds) varied among the different tissues: in brain the receptor was of lower molecular weight than in other organs. Immunoquantitation experiments employing 125I-protein A and protein extracts from human kidney at different ages revealed a small, albeit not significant, difference of the receptor content between fetal and postnatal tissues: as in other species, larger amounts of receptor seemed to be present in fetal than in postnatal organs. In addition, no significant difference of the receptor content between human fetal liver and early postnatal liver was measured employing 125I-protein A- immunoquantitation in three fetal and five postnatal liver tissue samples. The distribution of IGF-binding protein (IGEBP) species, another abundant and major class of IGF binding principles, was also measured in human fetal and early postnatal lung, liver, kidney, muscle, and brain using Western ligand blotting with 125I-IGF-II: as with IGF-II/M6P receptor immunoreactivity there was differential expression of the different classes of IGFBPs in the various organs

Application of a picosecond soft x-ray source to time-resolved plasma dynamics

We demonstrate the application of an ultrashort x-ray source as an external probe to measure plasma dynamics. The plasma is generated by a 100-fs Ti:sapphire laser focused onto thin metallic films. Time-resolved spectroscopy of the gold x-ray probe transmission through a perturbed 1000 Å aluminum film reveals redshifts of the LL-shell photoabsorption edge. We show that the dynamic behavior of this shift is consistent with the relaxation of the aluminum following the compression generated by a shock wave traveling through the film. An analytic plasma model, with comparison to a numerical hydrodynamics model, indicates compression up to 1.4 times solid density. © 1997 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69766/2/APPLAB-70-3-312-1.pd

Maternal stress, child behavior and the promotive role of older siblings

Abstract Background: In the first years of their lives, children develop the cognitive, social and emotional skills that will provide the foundations for their lifelong health and achievements. To increase their life prospects and reduce the long-term effects of early aversive conditions, it is therefore crucial to understand the risk factors that negatively affect child development and the factors that are instead beneficial. In this study, we tested (i) the effects of different social and environmental stressors on maternal stress levels, (ii) the dynamic relationship between maternal stress and child behavior problems during development, and (iii) the potential promotive (i.e. main) or protective (i.e. buffering) effect of siblings on child behavior problems during development.Methods: We used longitudinal data from 373 mother–child pairs (188 daughters, 185 sons) from pregnancy until 10 years of age. We assessed maternal stress and child behavior problems (internalizing and externalizing) with vali-dated questionnaires, and then used linear mixed models, generalized linear mixed models and longitudinal cross-lagged models to analyze the data.Results: Our results showed that higher maternal stress levels were predicted by socio-environmental stressors (i.e. the lack of sufficient social areas in the neighborhood). Moreover, prenatal maternal stress reliably predicted the occurrence of behavior problems during childhood. Finally, the presence of older siblings had a promotive function, by reducing the likelihood that children developed externalizing problems.Conclusions: Overall, our results confirm the negative effects that maternal stress during pregnancy may have on the offspring, and suggest an important main effect of older siblings in promoting a positive child development

A new human adipocyte model with PTEN haploinsufficiency

Few human cell strains are suitable and readily available as in vitro adipocyte models. We used resected lipoma tissue from a patient with germline phosphatase and tensin homolog (PTEN) haploinsufficiency to establish a preadipocyte cell strain termed LipPD1 and aimed to characterize cellular functions and signalling pathway alterations in comparison to the established adipocyte model Simpson-Golabi-Behmel-Syndrome (SGBS) and to primary stromal-vascular fraction cells. We found that both cellular life span and the capacity for adipocyte differentiation as well as adipocyte-specific functions were preserved in LipPD1 and comparable to SGBS adipocytes. Basal and growth factor-stimulated activation of the PI3 K/AKT signalling pathway was increased in LipPD1 preadipocytes, corresponding to reduced PTEN levels in comparison to SGBS cells. Altogether, LipPD1 cells are a novel primary cell model with a defined genetic lesion suitable for the study of adipocyte biology. © 2020, © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group

Einstein-Podolsky-Rosen-Bohm experiment and Bell inequality violation using Type 2 parametric down conversion

We report a new two-photon polarization correlation experiment for realizing the Einstein-Podolsky-Rosen-Bohm (EPRB) state and for testing Bell-type inequalities. We use the pair of orthogonally-polarized light quanta generated in Type 2 parametric down conversion. Using 1 nm interference filters in front of our detectors, we observe from the output of a 0.5mm beta - BaB2O4 (BBO) crystal the EPRB correlations in coincidence counts, and measure an associated Bell inequality violation of 22 standard deviations. The quantum state of the photon pair is a polarization analog of the spin-1/2 singlet state

Phospholipid Scramblase 4 (PLSCR4) Regulates Adipocyte Differentiation via PIP3-Mediated AKT Activation

Phospholipid scramblase 4 (PLSCR4) is a member of a conserved enzyme family with high relevance for the remodeling of phospholipid distribution in the plasma membrane and the regulation of cellular signaling. While PLSCR1 and -3 are involved in the regulation of adipose-tissue expansion, the role of PLSCR4 is so far unknown. PLSCR4 is significantly downregulated in an adipose-progenitor-cell model of deficiency for phosphatase and tensin homolog (PTEN). PTEN acts as a tumor suppressor and antagonist of the growth and survival signaling phosphoinositide 3-kinase (PI3K)/AKT cascade by dephosphorylating phosphatidylinositol-3,4,5-trisphosphate (PIP3). Patients with PTEN germline deletion frequently develop lipomas. The underlying mechanism for this aberrant adipose-tissue growth is incompletely understood. PLSCR4 is most highly expressed in human adipose tissue, compared with other phospholipid scramblases, suggesting a specific role of PLSCR4 in adipose-tissue biology. In cell and mouse models of lipid accumulation, we found PLSCR4 to be downregulated. We observed increased adipogenesis in PLSCR4-knockdown adipose progenitor cells, while PLSCR4 overexpression attenuated lipid accumulation. PLSCR4 knockdown was associated with increased PIP3 levels and the activation of AKT. Our results indicated that PLSCR4 is a regulator of PI3K/AKT signaling and adipogenesis and may play a role in PTEN-associated adipose-tissue overgrowth and lipoma formation

Prevention of acute malnutrition: distribution of special nutritious foods and cash, and addressing underlying causes--what to recommend when, where, for whom, and how

Acute malnutrition is associated with increased morbidity and mortality risk. When episodes are prolonged or frequent, acute malnutrition is also associated with poor growth and development, which contributes to stunting Nutrition-specific and nutrition-sensitive strategies to prevent undernutrition during the first 1,000 days from conception to 24 months of age can reduce the risks of wasting, stunting, and micronutrient deficiencies. Under circumstances that exacerbate the underlying causes of undernutrition and increase the incidence of wasting, such as food insecurity related to lean seasons or emergencies, or increased incidence of illness, such as diarrhea or measles, additional efforts are required to prevent and treat wasting. Special nutritious foods directly meet the increased nutrient requirements of children at risk for wasting; assistance to vulnerable households, in the form of cash or food, enables households to better meet the food, health, and other needs of household members and may increase resilience; water, sanitation, and hygiene (WASH) and health interventions help prevent and address illness and hence reduce wasting risk. The contributions of specific interventions to reducing the incidence of wasting are difficult to assess under emergency conditions, due to ethical constraints and to the fact that multiple strategies are implemented at the same time. However, pragmatic studies under real-life circumstances, using different designs, e.g., including a group receiving "best possible" treatment, can provide evidence about what works, to what extent, at what cost, and under which circumstances. Programs should address the most important causes in given contexts, be feasible to implement at scale, and assess implementation, coverage, and outcomes