Encapsulation of In Situ Nanoprecipitated Inorganic Materials in Confined Geometries Into a Polymer Shell Using Inverse Miniemulsion

Highly insoluble inorganic nanoparticles can be prepared in situ by precipitation inside of aqueous nanodroplets of cosonicated inverse miniemulsions containing salts, which are readily soluble in water. If the different salt droplets are fused, a hardly soluble salt is formed in the dispersed phase with a size considerably smaller than the size of the droplets. Subsequent encapsulation of the nanoparticles into a polymer shell is achieved by an interfacial polyaddition reaction between a polyol present in the aqueous phase and a (second) monomer (2,4‐toluene diisocyanate (TDI)) in the continuous phase. The materials are studied by transmission electron microscopy, X‐ray diffraction, dynamic light scattering (DLS), and TGA.     

Prosomatostatin-specific antigen in rat brain: localization by immunocytochemical staining with an antiserum to a synthetic sequence of preprosomatostatin.

Using an antiserum to a 15-amino acid synthetic peptide corresponding to amino acids 63-77 of rat preprosomatostatin (rat somatostatin cryptic peptide, RSCP), we have compared the distribution of immunoreactive RSCP (IR-RSCP) with that of immunoreactive somatostatin-14 in the rat brain. IR-RSCP was present in neuronal cell bodies, processes, and axon terminals in the hypothalamic tuberoinfundibular system as well as in diverse regions of the central nervous system in an identical distribution to immunoreactive somatostatin. These observations indicate that in neurons the somatostatin prohormone or the NH2-terminal extension peptide of somatostatin-28 (or both) is stored and transported intracellularly along with somatostatin 14. In addition, the presence of IR-RSCP in nerve terminals suggests that this material may be secreted as a hormone or neuromodulator and may serve as a biologic marker of somatostatin secretion.     

Selective hydroxylation of aryl iodides to produce phenols under mild conditions using a supported copper catalyst

Owing to the high activity and low-cost, copper-based catalysts are promising candidates for transforming aromatic halides to yield phenols. In this work, we report the selective hydroxylation of aromatic iodides to produce phenols using an atomically dispersed copper catalyst (Cu–ZnO–ZrO₂) under mild reaction conditions. The reactions were conducted without the use of additional organic ligands, and the protection of an inert atmosphere environment is not required. The catalyst can be easily prepared, scalable, and is very efficient for a wide range of substrates. The catalytic reactions can be carried out with only 1.24 mol% Cu loading, which shows great potential in mass production.

Atomically dispersed Cu catalyst was designed for highly efficient hydroxylation of aryl iodides under mild conditions.     

Biperiden and mepazine effectively inhibit MALT1 activity and tumor growth in pancreatic cancer

MALT1 is a key mediator of NF-κB signaling and a main driver of B-cell lymphomas. Remarkably, MALT1 is expressed in the majority of pancreatic ductal adenocarcinomas (PDACs) as well, but absent from normal exocrine pancreatic tissue. Following, MALT1 shows off to be a specific target in cancer cells of PDAC without affecting regular pancreatic cells. Therefore, we studied the impact of pharmacological MALT1 inhibition in pancreatic cancer and showed promising effects on tumor progression. Mepazine (Mep), a phenothiazine derivative, is a known potent MALT1 inhibitor. Newly, we described that biperiden (Bip) is a potent MALT1 inhibitor with even less pharmacological side effects. Thus, Bip is a promising drug leading to reduced proliferation and increased apoptosis in PDAC cells in vitro and in vivo. By compromising MALT1 activity, nuclear translocation of c-Rel is prevented. c-Rel is critical for NF-κB-dependent inhibition of apoptosis. Hence, off-label use of Bip or Mep represents a promising new therapeutic approach to PDAC treatment. Regularly, the Anticholinergicum Bip is used to treat neurological side effects of Phenothiazines, like extrapyramidal symptoms.     

Theoretical potential for endometrial cancer prevention through primary risk factor modification: Estimates from the EPIC cohort

Endometrial cancer (EC) incidence rates vary ~10-fold worldwide, in part due to variation in EC risk factor profiles. Using an EC risk model previously developed in the European EPIC cohort, we evaluated the prevention potential of modified EC risk factor patterns and whether differences in EC incidence between a European population and low-risk countries can be explained by differences in these patterns. Predicted EC incidence rates were estimated over 10 years of follow-up for the cohort before and after modifying risk factor profiles. Risk factors considered were: body mass index (BMI, kg/m²), use of postmenopausal hormone therapy (HT) and oral contraceptives (OC) (potentially modifiable); and, parity, ages at first birth, menarche and menopause (environmentally conditioned, but not readily modifiable). Modeled alterations in BMI (to all ≤23 kg/m²) and HT use (to all non-HT users) profiles resulted in a 30% reduction in predicted EC incidence rates; individually, longer duration of OC use (to all ≥10 years) resulted in a 42.5% reduction. Modeled changes in not readily modifiable exposures (i.e., those not contributing to prevention potential) resulted in ≤24.6% reduction in predicted EC incidence. Women in the lowest decile of a risk score based on the evaluated exposures had risk similar to a low risk countries; however, this was driven by relatively long use of OCs (median = 23 years). Our findings support avoidance of overweight BMI and of HT use as prevention strategies for EC in a European population; OC use must be considered in the context of benefits and risks.     

Cognitive interviewing to improve women's empowerment questions in surveys: Application to the health and nutrition and intrahousehold relationships modules for the project‐level Women's Empowerment in Agriculture Index

In 2015, the United Nations adopted the Sustainable Development Goals, which include fostering gender equality and women's empowerment and ending hunger and malnutrition. To monitor progress and evaluate programmes that aim to achieve these goals, survey instruments are needed that can accurately assess related indicators. The project‐level Women's Empowerment in Agriculture Index (pro‐WEAI) is being developed to address the need for an instrument that is sensitive to changes in empowerment over the duration of an intervention. The pro‐WEAI includes new modules with previously untested survey questions, including a health and nutrition module (focused on women's agency in this area) and an intrahousehold relationships module. This study uses cognitive interviewing to identify how new survey questions might be misinterpreted and to understand what experiences women are referencing when they respond to these questions. This was undertaken with the goal of informing revision to the modules. The study was conducted in Bangladesh with women from nuclear, extended, and migrant‐sending households and from two regions of the country to identify difficulties with interpretation and response formulation across these groups. Findings revealed that questions were generally understood, but participants occasionally responded to the wrong part of the question, did not understand key phrases, or were uncomfortable with questions. The findings also suggested ways to revise the modules and strengthen the pro‐WEAI. The revised pro‐WEAI health and nutrition and intrahousehold relationships modules will advance the ability to measure changes in these domains and their relationship with the health and nutritional status of women and their children.     

In vivo requirement of TGF-β/GDNF cooperativity in mouse development: focus on the neurotrophic hypothesis

Neurotrophic factors are well-recognized extracellular signaling molecules that regulate neuron development including neurite growth, survival and maturation of neuronal phenotypes in the central and peripheral nervous system. Previous studies have suggested that TGF-β plays a key role in the regulation of neuron survival and death and potentiates the neurotrophic activity of several neurotrophic factors, most strikingly of GDNF. To test the physiological relevance of this finding, TGF-β2/GDNF double mutant (d-ko) mice were generated. Double mutant mice die at birth like single mutants due to kidney agenesis (GDNF−/−) and congential cyanosis (TGF-β2−/−), respectively. To test for the in vivo relevance of TGF-β2/GDNF cooperativity to regulate neuron survival, mesencephalic dopaminergic neurons, lumbar motoneurons, as well as neurons of the lumbar dorsal root ganglion and the superior cervical ganglion were investigated. No loss of mesencephalic dopaminergic neurons was observed in double mutant mice at E18.5. A partial reduction in neuron numbers was observed in lumbar motoneurons, sensory and sympathetic neurons in GDNF single mutants, which was further reduced in TGF-β2/GDNF double mutant mice at E18.5. However, TGF-β2 single mutant mice showed no loss of neurons. These data point towards a cooperative role of TGF-β2 and GDNF with regard to promotion of survival within the peripheral motor and sensory systems investigated.     

Testicular morphology and antispermatogenic effects of 2,4-dichlorophenoxyacetic acid (2,4-D) in male West African Dwarf (WAD) goats

This study investigated the testicular morphology as well as the gonadal and extra-gonadal sperm reserves of West African Dwarf (WAD) goats exposed to graded levels of 2,4-dichlorophenoxyacetic acid (2,4-D). Twenty male WAD goats of five goats per group were used for this study. Goats in groups A, B and C received low [75?mg/kg body weight (BW)], medium (100?mg/kg BW) and high (125?mg/kg BW) dose levels of 2,4-D, respectively. The group D goats served as the control. On day?112, goats in the four groups were sacrificed and the testicular and epididymal sperm reserves were determined. Histopathologic changes in the testis of the 2,4-D-exposed and control goats were also assessed. The mean number of spermatozoa in the testes and the various segments of the epididymides decreased significantly (p?<?0.05) in all the treatment groups relative to the control. Combined testicular sperm reserve per millilitre for the treatment groups (group A—19.61?±?2.63?×?10⁸, group B—12.02?±?1.02?×?10⁸ and group C—9.95?±?0.97?×?10⁸) reduced significantly (p?<?0.05) relative to the mean value (23.52?±?4.43?×?10⁸) of the control—group D. The total epididymal sperm reserve per millilitre in the treatment groups (group A—24.25?±?4.19?×?10⁸, group B—17.18?±?2.57?×?10⁸ and group C—17.88?±?2.89?×?10⁸) was also found to be significantly (p?<?0.05) lower than the mean value (40.85?±?11.24?×?10⁸) for the control—group D. This reduction in the testicular and epididymal sperm counts of the 2,4-D-exposed WAD goats in this study suggest disruption in spermatogenic activity, which may lead to low productivity. Variable degrees of circulatory disturbances were observed in the testis sections of 2,4-D-exposed goats.