The identification and optimisation of novel and selective diamide neuropeptide Y Y2 receptor antagonists

A novel small molecule NPY Y2 antagonist (3) identified from high throughput screening is described. A subsequent SAR study and optimisation programme based around this molecule is also described, leading to the identification of potent and soluble pyridyl analogue 36.     

Clustering of Socioeconomic,Behavioural, and Neonatal Risk Factors for Infant Health in Pregnant Smokers

Background

Tobacco smoking is a major cause of morbidity and mortality, including during pregnancy. Although effective ways of promoting smoking cessation during pregnancy exist, the impact of these interventions has not been studied at a national level. We estimated the prevalence of smoking throughout pregnancy in the Netherlands and quantified associations of maternal smoking throughout pregnancy with socioeconomic, behavioural, and neonatal risk factors for infant health and development.

Methodology/Principal Findings

Data of five national surveys, containing records of 14,553 Dutch mothers and their offspring were analyzed. From 2001 to 2007, the overall rate of smoking throughout pregnancy fell by 42% (from 13.2% to 7.6%) mainly as a result of a decrease among highly educated women. In the lowest-educated group, the overall rate of smoking throughout pregnancy was six times as high as in the highest-educated group (18.7% versus 3.2%). Prenatal tobacco smoke exposure was associated with increased risk of extremely preterm (≤28 completed weeks) (OR 7.25; 95% CI 3.40 to 15.38) and small-for-gestational age (SGA) infants (OR 3.08; 95% CI 2.66 to 3.57). Smoking-attributable risk percents in the population (based on adjusted risk ratios) were estimated at 29% for extremely preterm births and at 17% for SGA outcomes. Infants of smokers were more likely to experience significant alcohol exposure in utero (OR 2.08; 95%CI 1.25 to 3.45) and formula feeding in early life (OR 1.91; 95% CI 1.69 to 2.16).

Conclusions

The rates of maternal smoking throughout pregnancy decreased significantly in the Netherlands from 2001 to 2007. If pregnant women were to cease tobacco use completely, an estimated 29% of extremely preterm births and 17% of SGA infants may be avoided annually.     

Neonatal tooth with Riga-Fide disease affecting breastfeeding: a case report

Background

Neonatal teeth erupt during the neonatal period and natal teeth are the presence of teeth since birth. While rare, natal teeth and neonatal teeth can have a significant impact on breastfeeding. Neonatal teeth are less common, and although its exact etiology is still unknown, it can cause difficulties in breastfeeding to the mother and may eventually lead to discontinuation of breastfeeding. Other associated possible complications include tooth aspiration and sublingual ulceration. This paper was aimed to discuss the clinical features, complications, and management of neonatal tooth, in addition to its impact on breastfeeding and role in sublingual ulcer formation.

Case presentation

We present a baby girl who had a neonatal tooth with sublingual ulceration (Riga-Fede disease), which resulted in a difficulty to breastfeed for the baby and nipple pain to the mother. Following the extraction of the baby’s tooth, she immediately continued breastfeeding, and her tongue ulcer healed well.

Conclusion

Extraction of the neonatal tooth promoted rapid healing of oral ulcers and the reestablishment of breastfeeding.

     

Production of biomass and flavonoid of Gynura procumbens (Lour.) Merr shoots culture in temporary immersion system

Gynura procumbens (Lour.) Merris one of medicinal plant which was carried out used as antioxidant, anticancer, anti-inflammatory, hepatoprotective, and antimicrobial. Many strategies were used to increase the production of biomass and valuable compounds. This study was to investigate the variation effect of growth regulators and immersion frequency on production of biomass and flavonoid contained of G. procumbens shoots culture in temporary immersion bioreactor. Stem nodes were used as an explants and induction of shoots were done in solid MS medium supplemented with many kinds of growth regulator. The best treatments were used to produce biomass and flavonoid compounds in temporary immersion bioreactor; there are combination of IAA 2?mg/L and BA 4, 6, 8?mg/L and immersion frequency (5 min each 3?h; 15?min each 12?h). Results showed that the growths of G. procumbens shoots in solid MS medium were influenced by supplementation of growth regulators. MS medium supplemented with single cytokinine (6 mg/L kinetin) and combination of auxin (IAA) and cytokinine (BA) caused increasing of shoots growth. Production of biomass of G. procumbens in temporary immersion bioreactor was achieved in long immersion interval (12?h) and highest flavonoid production was obtained in combination treatment of immersion frequency 15?min each 12?h and MS medium supplemented with IAA 2?mg/L, BA 8?mg/L.     

ROCK‐dependent phosphorylation of NUP62 regulates p63 nuclear transport and squamous cell carcinoma proliferation

p63, more specifically its ΔNp63α isoform, plays essential roles in squamous cell carcinomas (SCCs), yet the mechanisms controlling its nuclear transport remain unknown. Nucleoporins (NUPs) are a family of proteins building nuclear pore complexes (NPC) and mediating nuclear transport across the nuclear envelope. Recent evidence suggests a cell type‐specific function for certain NUPs; however, the significance of NUPs in SCC biology remains unknown. In this study, we show that nucleoporin 62 (NUP62) is highly expressed in stratified squamous epithelia and is further elevated in SCCs. Depletion of NUP62 inhibits proliferation and augments differentiation of SCC cells. The impaired ability to maintain the undifferentiated status is associated with defects in ΔNp63α nuclear transport. We further find that differentiation‐inducible Rho kinase reduces the interaction between NUP62 and ΔNp63α by phosphorylation of phenylalanine–glycine regions of NUP62, attenuating ΔNp63α nuclear import. Our results characterize NUP62 as a gatekeeper for ΔNp63α and uncover its role in the control of cell fate through regulation of ΔNp63α nuclear transport in SCC.     

Demonstration of antigenic similarities and variations in excretory/secretory antigens of Toxoplasma gondii.

C57BL/6 mice were orally infected with different doses of cysts of ME49 strain of Toxoplasma gondii to produce groups of acutely and chronically infected mice. Sera were obtained at different periods post-infection. SDS-PAGE was ran with excretory/secretory antigens of ME49 and RH strains of T. gondii, followed by Western blot analyses using the above sera and anti- IgA, IgM, IgG as conjugates. The SDS-PAGE profiles of the two antigens were similar. However the antigenic bands showed variations in all blots, most evidently in IgA blots of chronic sera. IgG blots showed greatest similarities in reactive bands. In IgM blots, more common bands were shown in chronic sera than in acute sera. Variations and similarities in prominence of some bands and time of their appearance were also noted, especially in IgM and IgG blots of chronic sera. Thus antigenic variations and similarities are present in excretory/secretory products of different strains of T. gondii.     

Low Fetal Weight is Directly Caused by Sequestration of Parasites and Indirectly by IL-17 and IL-10 Imbalance in the Placenta of Pregnant Mice with Malaria

The sequestration of infected erythrocytes in the placenta can activate the syncytiotrophoblast to release cytokines that affect the micro-environment and influence the delivery of nutrients and oxygen to fetus. The high level of IL-10 has been reported in the intervillous space and could prevent the pathological effects. There is still no data of Th17 involvement in the pathogenesis of placental malaria. This study was conducted to reveal the influence of placental IL-17 and IL-10 levels on fetal weights in malaria placenta. Seventeen pregnant BALB/C mice were divided into control (8 pregnant mice) and treatment group (9 pregnant mice infected by Plasmodium berghei). Placental specimens stained with hematoxylin and eosin were examined to determine the level of cytoadherence by counting the infected erythrocytes in the intervillous space of placenta. Levels of IL-17 and IL-10 in the placenta were measured using ELISA. All fetuses were weighed by analytical balance. Statistical analysis using Structural Equation Modeling showed that cytoadherence caused an increased level of placental IL-17 and a decreased level of placental IL-10. Cytoadherence also caused low fetal weight. The increased level of placental IL-17 caused low fetal weight, and interestingly low fetal weight was caused by a decrease of placental IL-10. It can be concluded that low fetal weight in placental malaria is directly caused by sequestration of the parasites and indirectly by the local imbalance of IL-17 and IL-10 levels.     

Inventing Engineered Organoids for end-stage liver failure patients

Journal of Molecular Histology - End-stage liver disease (ESLD) is a term used clinically in reference to a group of liver diseases with liver transplantation as the choice of treatment. Due to the...     

Triplex PCR using new primers for the detection of Toxoplasma gondii

Molecular methods are used increasingly for the detection of Toxoplasma gondii infection. This study developed a rapid, sensitive, and specific conventional triplex PCR for the detection of the B1 gene and ITS1 region of T. gondii using newly designed primers and an internal control based on the Vibrio cholerae HemM gene. The annealing temperature and concentrations of the primers, MgCl(2), and dNTPs were optimized. Two sets of primers (set 1 and 2) were tested, which contained different segments of the T. gondii B1 gene, 529 repeat region and ITS1 region. A series of sensitivity tests were performed using parasite DNA, whole parasites, and spiked human body fluids. Specificity tests were performed using DNA from common protozoa and bacteria. The newly developed assay based on set 2 primers was found to be specific and sensitive. The test was capable of detecting as little as 10 pg T. gondii DNA, 10(4) tachyzoites in spiked body fluids, and T. gondii DNA in the organ tissues of experimentally infected mice. The assay developed in this study will be useful for the laboratory detection of T. gondii infection.     

Production of reactive oxygen species in Arabidopsis thaliana cell suspension cultures in response to an elicitor from Fusarium oxysporum: implications for basal resistance

The present understanding of ROS generation in the defence responseof Arabidopsis thaliana is reviewed. Evidence suggests thatthe apoplastic oxidative burst generated during basal resistanceis peroxidase-dependent. The ROS generated during this basalresistance may serve to activate NADPH oxidase during the R-gene-mediatedhypersensitive response. The processes involved in the productionof reactive oxygen species in A. thaliana cell suspension culturesin response to an elicitor from Fusarium oxysporum are investigatedin the present work. This system appears analogous to the productionof ROS during the basal resistance response in French bean,which is peroxidase-dependent. A panel of modulators effectivein other pathogen elicitor and plant cell systems has been usedto investigate the Arabidopsis signalling pathways and the plantcell responses involved. Thus as in other systems, an earlycalcium influx into the cytosolic compartment, a rapid effluxof K⁺ and Cl^–, and extracellular alkalinization of elicitedcell cultures has been found. However the alkalinization isnot sufficient to stimulate the apoplastic oxidative burst byitself, unlike in French bean, although vectorial ion fluxesare needed. A secretory component which is sensitive to monensinand N-ethylmaleimide and insensitive to brefeldin A may alsobe necessary for the release and provision of substrates forperoxidase-dependent generation of H₂O₂. Key words: Arabidopsis thaliana, calcium, elicitation, hydrogen peroxide, oxidative burst, secretion