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Thioglycolic acid (TGA) capped CdSe quantum dots (QD) have been synthesized in aqueous solution using facile, one‐pot and soft chemical route at ambient condition. The excitonic absorption peak and band gap of the QD could be tuned from 435 nm to 472 nm and from 2.37 eV to 2.60 eV respectively. The morphology of these QD were dependent on the precursor's concentration during synthesis. These QD exhibited broad photoluminescence (PL) spectra with large Stokes shift. It was observed that in the synthesis of CdSe QD TGA played twin role of catalyzing and capping agent. Detailed reaction mechanism of synthesis studied using cyclic voltammetry confirms the role of thioglycolate anion in the synthesis of CdSe QD. Cytotoxicity effects of these QD were studied in both the normal and cancer cell, indicted that TGA capped CdSe QD are cytotoxic beyond 10 μg/ml concentration and leads to cell proliferation of cancer cells. [ABSTRACT FROM AUTHOR]

Background and Objectives Ferritin levels are often highly elevated at birth in neonates with alloimmune haemolytic disease of the fetus and newborn ( HDFN). Data on ferritin levels in these infants in the first 3 months of life are lacking. Objective of this study was to examine the course of iron status and incidence of iron deficiency and overload in neonates with alloimmune HDFN up to 3 months of age. Secondary objective was to analyse bilirubin levels, liver enzymes and red-blood-cell indices in the same time period and the association with intrauterine transfusion ( IUT). Materials and Methods Observational study of neonates with alloimmune HDFN admitted to our centre between November 2010 and March 2012. Data on iron status, bilirubin levels, liver enzymes and red-blood-cell indices up to 3 months of age were routinely collected and compared between neonates treated with and without IUT. Results Thirty-five infants with alloimmune HDFN were included. Iron overload occurred in 70% of neonates at birth and in 50% and 18% at the age of 1 and 3 months, respectively. No cases of iron deficiency at birth and only one case of iron deficiency at 3 months of age were found. No infants received iron therapy. Infants who received IUT had a significantly lower haemoglobin level and reticulocyte count and higher ferritin level at birth. Conclusion The vast majority of neonates with alloimmune HDFN have iron overload at birth. Incidence of iron overload gradually decreases within the first 3 months without iron supplementation. [ABSTRACT FROM AUTHOR]

The mycorrhizas of 12 species of Polygala ( Polygalaceae), including herbs, subshrubs and one shrub, collected from Germany, Mallorca ( Spain) and Malta, were investigated by morpho-anatomical and molecular methods. Aseptate hyphae, arbuscules and vesicles indicate an arbuscular mycorrhiza in all species examined. Hyphal spread in Polygala is predominantly, but not exclusively, intracellular and comprises three characteristic stages of colonization: (i) intracellular, linear hyphal growth in a cascading manner after penetration towards the penultimate parenchyma layer (layer 2), (ii) initially linear hyphal growth in the cells of layer 2 from where hyphal branches repeatedly penetrate the anatomically distinct innermost parenchyma layer (layer 1), forming arbuscule-like structures therein which are subject to degeneration, (iii) more branches from the linear hyphae in layer 2 develop, but coil and make contact to the layer outside layer 2 (layer 3) in which arbuscule-like structures similar to those in layer 1 form and degenerate. This general colonization pattern differs in details between the species, and critical comparisons, in particular between the woody P. myrtifolia, the herbaceous Polygala spp. and the mycoheterotrophic Epirixanthes spp. ( Polygalaceae) suggest an evolutionary shift of mycorrhizal features within the family towards an optimization of plant benefit through the fungus. Based on the molecular marker 18S rDNA mycorrhizal fungi detected in roots of Polygala spp. are largely restricted to five clades of Glomeraceae 1 ( Glomus Group A). This result rejects the hypothesis of a strict symbiotic specificity in Polygalaceae but may stimulate a discussion on functionally compatible groups of fungi. [ABSTRACT FROM AUTHOR]

Objective To evaluate the incidence and severity of and risk factors for thrombocytopenia at birth in neonates with red cell alloimmunization. Study design All neonates with haemolytic disease of the foetus/newborn (HDFN) due to red cell alloimmunization admitted to our centre between January 2000 and September 2010 were included in this retrospective study. We measured platelet counts at birth and determined the incidence of thrombocytopenia (platelet count < 150 × 109/l) and severe thrombocytopenia (platelet count < 50 × 109/l). Risk factors for thrombocytopenia at birth were evaluated. Results Thrombocytopenia was present in 26% (94/362) of included neonates with HDFN at birth. Severe thrombocytopenia was found in 6% (20/362) of neonates. Three risk factors were found to be independently associated with thrombocytopenia at birth: treatment with intrauterine red cell transfusion (IUT) (OR 3·32, 95% CI 1·67-6·60, P = 0·001), small for gestational age (SGA) below the 10th percentile (OR 3·32, 95% CI 1·25-8·80, P = 0·016) and lower gestational age at birth (OR 1·22/week, 95% CI 1·02-1·44, P = 0·025). Conclusions Thrombocytopenia at birth occurs in 26% of neonates with HDFN due to red cell alloimmunization and is independently associated with IUT treatment, SGA and lower gestational age at birth. [ABSTRACT FROM AUTHOR]

To evaluate neonatal outcome in Kell haemolytic disease compared to Rh D haemolytic disease. Retrospective study of all (near)-term neonates with Kell ( n = 34) and Rh D haemolytic disease ( n = 157) admitted to our centre between January 2000 and December 2008. We recorded the need for exchange transfusion and top-up transfusions up to 3 months of age. Neonates in the Kell group required less days of phototherapy than neonates in the Rh D group [2·4 vs. 4·1 days, respectively ( P < 0·01)]. The percentage of neonates requiring an exchange transfusion was lower in the Kell group than in the Rh D group [6% (2/34) and 62% (98/157), respectively ( P < 0·01)]. The percentage of neonates in the Kell group and Rh D group requiring a top-up transfusion was 62% (21/34) and 72% (113/157), respectively ( P = 0·20). The median number of top-up transfusions per neonate in the Kell group and Rh D group was 1 [interquartile range (IQR) 0-2] and 2(IQR 0-2), respectively ( P = 0·07). Neonates with Kell haemolytic disease require less phototherapy and less exchange transfusions compared to neonates with Rh D haemolytic disease, but an equal number of top-up transfusions. [ABSTRACT FROM AUTHOR]

Objective To study the effect of a restrictive guideline for exchange transfusion (ET) on the number of top-up transfusions in neonates with Rh hemolytic disease. Study Design Retrospective study of all (near)-term neonates with Rh hemolytic disease admitted to our center between 2000 and 2008. In December 2005, policy changed from using liberal ET criteria to more restrictive ET criteria. We recorded the number of ETs and the number of top-up transfusions in the group of neonates before (group I, n = 156) and after (group II, n = 27) the guideline change. Results The percentage of neonates requiring an ET decreased from 66% (103/156) in group I to 26% (7/27) in group II ( P < 0·01). The percentage of neonates receiving a top-up transfusion increased from 68% (105/154) in group I to 81% (22/27) in group II ( P = 0·25). The median number of top-up transfusions increased from 1 (interquartile range 0–2) in group I to 2 (interquartile range 1–3) in group II ( P = 0·01). Conclusion In this study, restrictive ET criteria in neonates with Rh hemolytic disease lead to a reduction of the rate of ET but an increase in the number of top-up transfusions for neonatal anemia. [ABSTRACT FROM AUTHOR]

Highly metastatic melanoma is resistant to existing therapies. A unique micronutrient mixture (NM) containing ascorbic acid, amino acids, green tea extract has been shown to exhibit anticancer activity in vivo and in vitro in a number of cancer cell lines including human and murine melanoma cells lines. In this study we examined the effect of dietary NM supplementation on hepatic metastasis of intrasplenic injection of B16FO melanoma cells in athymic nude mice. Athymic nude mice (n = 10), 10-12 weeks of age, received 106 B16FO melanoma cells by injection into the spleen and divided into two groups. The Control group of mice received Purina mouse chow and the NM group received the regular diet supplemented with NM 0.5%. After two weeks, animals were sacrificed and spleens, livers, kidneys and lungs were excised from all animals, examined, weighed and processed for histology. The Control mice developed large black spleens and livers indicating growth in the spleen and metastasis to the liver. However, the mice supplemented with NM not only showed less tumor growth in the spleen as the Control mice, but also drastically reduced metastasis to the liver. In all groups, no metastasis to the kidneys and lungs was evident. In conclusion, these results suggest that NM has potential in suppression of tumor metastasis. [ABSTRACT FROM AUTHOR]

Influenza, a long-standing common infection, poses a serious health problem causing significant morbidity and mortality, and imposing substantial economic costs. To date there are no effective antiviral therapies. A unique nutrient mixture (NM), containing lysine, proline, ascorbic acid, green tea extract, N-acetyl cysteine and selenium among other micro nutrients, has been shown to exert a wide range of biochemical and pharmacological effects, among them anti-carcinogenic and anti-atherogenic activity both in vitro and in vivo. In a previous study, NM was found to significantly inhibit influenza virus A associated neuraminidase enzyme as well as production of NP antigen in a dose-dependent manner. Influenza virus A not only infects pulmonary areas, but also manifests in extrapulmonary areas, which require basement membrane disruption by matrix metalloproteinases capable of degrading collagen type IV. This prompted us to study the effect of NM on cellular invasive parameters of virus-infected and non-infected MDCK and Vero cells. NM inhibited extracellular invasive parameters such as MMP-2 and MMP-9 secretion and Matrigel invasion. Results indicated that the relatively non-toxic nutrient mixture tested in this investigation has potential in influenza treatment by not only decreasing viral multiplication in infected cells but also by blocking the enzymatic degradation of the extracellular matrix. [ABSTRACT FROM AUTHOR]

Influenza, one of the oldest and most common infections, poses a serious health problem causing significant morbidity and mortality, and imposing substantial economic costs. The efficacy of current drugs is limited and improved therapies are needed. A unique nutrient mixture (NM), containing ascorbic acid, green tea extract, lysine, proline, N-acetyl cysteine, selenium among other micronutrients, has been shown to exert anti-carcinogenic and anti-atherogenic activity both in vitro and in vivo. Many of the constituents of NM have been shown to have an inhibitory effect on replication of influenza virus and HIV. This prompted us to study the effect of NM on influenza A virus multiplication in infected cells and neuraminidase activity (NA) in virus particles. Addition of NM to Vero or MDCK cells post infection resulted in dose-dependent inhibition of viral nucleoprotein (NP) production in infected cells. NM-mediated inhibition of viral NP was selective and not due to cytotoxicity towards host cells. This antiviral effect was enhanced by pretreatment of virus with the nutrient mixture. Individual components of NM, namely ascorbic acid and green tea extract, also blocked viral NP production, conferring enhanced inhibition when tested in combination. Incubation of cell-free virus with NM resulted in dose-dependent inhibition of associated NA enzyme activity. In conclusion, the nutrient mixture exerts an antiviral effect against influenza A virus by lowering viral protein production in infected cells and diminishing viral enzymatic activity in cell-free particles. [ABSTRACT FROM AUTHOR]

A comparative study of grazing behaviour, herbage intake and milk production of three strains of Holstein-Friesian dairy cow was conducted using three grass-based feeding systems over two years. The three strains of Holstein-Friesian cows were: high production North American (HP), high durability North American (HD) and New Zealand (NZ). The three grass-based feeding systems were: high grass allowance (MP), high concentrate (HC) and high stocking rate (HS). In each year seventy-two pluriparous cows, divided equally between strains of Holstein-Friesian and feeding systems were used. Strain of Holstein-Friesian cow and feeding system had significant effects on grazing behaviour, dry matter (DM) intake and milk production. The NZ strain had the longest grazing time while the HD strain had the shortest. The grazing time of cows in the HC system was shorter than those in both the HS and MP systems. There was a significant strain of Holstein-Friesian cow by feeding system interaction for DM intake of grass herbage and milk production. The NZ strain had the highest substitution rate with the HP strain having the lowest. Hence, response in milk production to concentrate was much greater with the HP than the NZ strain. Reduction in milk yield as a consequence of a higher stocking rate (MP vs. HS system) was, however, greater for the HP and HD strains compared with the NZ strain. The results suggest that differences in grazing behaviour are important in influencing DM intake and milk production. [ABSTRACT FROM AUTHOR]

The objective of this study was to compare the biological and economic efficiency of a seasonal pasture-based spring calving system of milk production on a high-rainfall, heavy-clay soil [Kilmaley (KMY)] to that on a lower-rainfall free-draining soil [Moorepark (MPN)] in Ireland. The physical performance data were obtained from a 3-year study (1998–2000) carried out at both sites. Analysis of the system of milk production at the two sites was undertaken using the Moorepark Dairy System Model. Herbage dry-matter production was greater at the MPN site with a greater proportion being produced between 1 September and 1 May. On average, over the 3 years, the system of milk production at the MPN site had a higher stocking rate (2·34 vs. 1·89 cows ha−1), higher milk production per cow (6421 vs. 5781 kg per cow), longer grazing season (250 vs. 149 d) and a higher proportion of the diet of the herd from grazed grass (0·70 vs. 0·40) than at KMY. Economic analysis showed that, in a 468 100 kg European Union milk quota scenario, the profitability at the MPN site was €28 417 greater than at the KMY site. At similar milk production per cow it was €19 138 greater. Monte Carlo simulation showed that the MPN site was stochastically dominant over the KMY site. Sensitivity analyses showed that farm profit was most sensitive to changes in milk price. The results also indicated that milk production in the future may not be sustainable economically on high-rainfall, heavy-clay soils in Ireland. [ABSTRACT FROM AUTHOR]

Background: Microglia are the resident immune cells in the brain where they play essential roles in the development and maintenance of physiological functions of this organ. Aberrant activation of microglia is speculated to be involved in the pathogenesis of a variety of neurological disorders, including alcohol use disorders. Repeated binge ethanol (EtOH) consumption can have a profound impact on the function and integrity of the brain resulting in changes in behaviors such as withdrawal and reward. However, the microglial molecular and cellular pathways associated with EtOH binge consumption remain poorly understood., Method: In this study, adult C57BL/6J male and female mice were subjected daily to a gelatin-based drinking-in-the-dark voluntary EtOH consumption paradigm (3 h/d for 4 months) to characterize EtOH consumption and withdrawal-associated and anxiety-like behaviors. Brain microglia were isolated at the end and analyzed for protein expression profile changes using unbiased mass spectrometry-based proteomic analysis., Results: Both male and female mice consistently consumed binge quantities of EtOH daily, resulting in blood EtOH levels > 80 mg/dl measured at the end of the 3-hour daily consumption period. Although female mice consumed a significantly greater amount of EtOH than male mice, EtOH withdrawal-associated anxiety-like behaviors measured by marble-burying, light-dark box, and elevated plus maze tests were predominantly observed in male mice. Proteomic analysis of microglia isolated from the brains of animals at the end of the 4-month binge EtOH consumption identified 117 and 37 proteins that were significantly up- or downregulated in EtOH-exposed male and female mice, respectively, compared to their pair-fed controls. Protein expression profile-based pathway analysis identified several cellular pathways that may underlie the sex-specific and EtOH withdrawal-associated behavioral abnormalities., Conclusion: Taken together, our findings revealed sex-specific changes in EtOH withdrawal-associated behaviors and signaling pathways in the mouse brain microglia and may help advance our understanding of the molecular, cellular, and behavioral changes related to human binge EtOH consumption., (© 2020 by the Research Society on Alcoholism.)

CCM3, originally described as PDCD10, regulates blood-brain barrier integrity and vascular maturation in vivo. CCM3 loss-of-function variants predispose to cerebral cavernous malformations (CCM). Using CRISPR/Cas9 genome editing, we here present a model which mimics complete CCM3 inactivation in cavernous endothelial cells (ECs) of heterozygous mutation carriers. Notably, we established a viral- and plasmid-free crRNA:tracrRNA:Cas9 ribonucleoprotein approach to introduce homozygous or compound heterozygous loss-of-function CCM3 variants into human ECs and studied the molecular and functional effects of long-term CCM3 inactivation. Induction of apoptosis, sprouting, migration, network and spheroid formation were significantly impaired upon prolonged CCM3 deficiency. Real-time deformability cytometry demonstrated that loss of CCM3 induces profound changes in cell morphology and mechanics: CCM3-deficient ECs have an increased cell area and elastic modulus. Small RNA profiling disclosed that CCM3 modulates the expression of miRNAs that are associated with endothelial ageing. In conclusion, the use of CRISPR/Cas9 genome editing provides new insight into the consequences of long-term CCM3 inactivation in human ECs and supports the hypothesis that clonal expansion of CCM3-deficient dysfunctional ECs contributes to CCM formation., (© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Grange syndrome is an autosomal recessive condition characterized by arterial occlusions and hypertension. Syndactyly, brachydactyly, bone fragility, heart defects, and learning disabilities have also been reported. Loss-of-function variants in YY1AP1 have only recently been associated with Grange syndrome. YY1AP1 encodes for the transcription coactivator yin yang 1-associated protein 1 which regulates smooth muscle cell proliferation and differentiation. We here report on three siblings with steno-occlusive arterial disorder and syndactyly in two of them. Whole exome sequencing including near-splice regions led to the identification of two intronic YY1AP1 variants which were predicted to interfere with normal splicing. Sanger sequencing demonstrated compound-heterozygosity in all affected siblings. RT-PCR analyses confirmed skipping of exon 6 on one allele and exonization of 22 bp in intron 6 on the other. This is the first report of biallelic YY1AP1 variants in noncoding regions and just the second family with multiple affected siblings. Therefore, our report further delineates the phenotypic spectrum of Grange syndrome., (© 2018 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals, Inc.)