Objective
Alcohol dependence is more prevalent in men than in women. The evidence for how prenatal and adult androgens influence alcohol dependence is limited. We investigated the effects of prenatal ...and adult androgen activity on alcohol dependence. Moreover, we studied how the behaviours of pregnant women affect their children's prenatal androgen load.
Method
We quantified prenatal androgen markers (e.g., second‐to‐fourth finger length ratio 2D : 4D) and blood androgens in 200 early‐abstinent alcohol‐dependent in‐patients and 240 controls (2013–2015, including a 12‐month follow‐up). We also surveyed 134 women during pregnancy (2005–2007) and measured the 2D : 4D of their children (2013–2016).
Results
The prenatal androgen loads were higher in the male alcohol‐dependent patients compared to the controls (lower 2D : 4D, P = 0.004) and correlated positively with the patients’ liver transaminase activities (P < 0.001) and alcohol withdrawal severity (P = 0.019). Higher prenatal androgen loads and increasing androgen levels during withdrawal predicted earlier and more frequent 12‐month hospital readmission in alcohol‐dependent patients (P < 0.005). Moreover, stress levels (P = 0.002), alcohol (P = 0.010) and tobacco consumption (P = 0.017), and lifetime stressors (P = 0.019) of women during pregnancy related positively to their children's prenatal androgen loads (lower 2D : 4D).
Conclusion
Androgen activities in alcohol‐dependent patients and behaviours of pregnant women represent novel preventive and therapeutic targets of alcohol dependence.
Cell-penetrating peptides (CPPs) have been widely used to deliver nanomaterials and other types of macromolecules into mammalian cells for therapeutic and diagnostic use. Cationic CPPs that bind to ...heparan sulfate (HS) proteoglycans on the cell surface induce potent endocytosis; however, the role of other surface receptors in this process is unclear. We describe the convergence of an HS-dependent pathway with the C-end rule (CendR) mechanism that enables peptide ligation with neuropilin-1 (NRP1), a cell surface receptor known to be involved in angiogenesis and vascular permeability. NRP1 binds peptides carrying a positive residue at the carboxyl terminus, a feature that is compatible with cationic CPPs, either intact or after proteolytic processing. We used CPP and CendR peptides, as well as HS- and NRP1-binding motifs from semaphorins, to explore the commonalities and differences of the HS and NRP1 pathways. We show that the CendR-NRP1 interaction determines the ability of CPPs to induce vascular permeability. We also show at the ultrastructural level, using a novel cell entry synchronization method, that both the HS and NRP1 pathways can initiate a macropinocytosis-like process and visualize these CPP-cargo complexes going through various endosomal compartments. Our results provide new insights into how CPPs exploit multiple surface receptor pathways for intracellular delivery.
We characterize the distribution of surface-enhanced Raman spectroscopy (SERS) enhancement factors observed in individual hot spots of single Ag "nanocapsules", encapsulated Ag nanoparticle dimers ...formed via controlled nanoparticle linking, polymer encapsulation, and small molecule infusion. The enhancement factors are calculated for over 1000 individual nanocapsules by comparing Raman scattering intensities of 4-mercaptobenzoic acid (MBA) measured from single SERS hot spots to intensities measured from high-concentration solutions of MBA. Correlation spectroscopy measurements of the rotational diffusion identify nanocapsules with signals dominated by single hot spots via their strong polarization response. Averaging over the entire surface of the nanocapsules, the distribution of enhancement factors is found to range from 10(6) to 10(8), with a mean of 6 × 10(6). Averaging only over nanoparticle junctions (where most SERS signals are expected) increases this average value to 10(8), with a range from 2 × 10(7) to 2 × 10(9). This significant statistical sampling shows that very high SERS enhancement factors can be obtained on a consistent basis using nanoparticle linking.
We developed an air-liquid interphase culture procedure for mammalian oviduct epithelial cells leading to the formation of functional epithelial tissues, which generate oviduct fluid surrogates. ...These in vitro oviduct epithelia can be co-cultured with living zygotes and enable embryonic development up to the blastocyst stage without addition of embryo culture medium. The described strategy is broadly applicable to analyze early embryo-maternal interactions under standardized in vitro conditions.
Abstract
Quantum spin liquids are materials that feature quantum entangled spin correlations and avoid magnetic long-range order at
T
= 0 K. Particularly interesting are two-dimensional honeycomb ...spin lattices where a plethora of exotic quantum spin liquids have been predicted. Here, we experimentally study an effective
S
= 1/2 Heisenberg honeycomb lattice with competing nearest and next-nearest-neighbour interactions. We demonstrate that YbBr
3
avoids order down to at least
T
= 100 mK and features a dynamic spin–spin correlation function with broad continuum scattering typical of quantum spin liquids near a quantum critical point. The continuum in the spin spectrum is consistent with plaquette type fluctuations predicted by theory. Our study is the experimental demonstration that strong quantum fluctuations can exist on the honeycomb lattice even in the absence of Kitaev-type interactions, and opens a new perspective on quantum spin liquids.
Highlights • Learning a motor skill specifically induces Arc mRNA within primary motor cortex of rats. • The amount of Arc mRNA expression is positively correlated with learning success. • No changes ...in Arc mRNA expression were observed in other regions related to motor control. • Our findings suggest a link between M1 Arc expression and motor skill learning.
Hyperlipidemia (HL) is a condition associated with endothelial dysfunction and inflammatory disorders. Purinergic system ectoenzymes play an important role in modulating the inflammatory and immune ...response. This study investigated whether the preventive treatment with quercetin is able to prevent changes caused by hyperlipidemia in the purinergic system, through the activities of E-NTPDase and E-ADA in lymphocytes, and quantify the nucleotides and nucleoside, and the secretion of anti- and proinflammatory cytokines. Animals were divided into saline/control, saline/quercetin 5 mg/kg, saline/quercetin 25 mg/kg, saline/quercetin 50 mg/kg, saline/simvastatin (0.04 mg/kg), hyperlipidemia, hyperlipidemia/quercetin 5 mg/kg, hyperlipidemia/quercetin 25 mg/kg, hyperlipidemia/quercetin 50 mg/kg, and hyperlipidemia/simvastatin. Animals were pretreated with quercetin for 30 days and hyperlipidemia was subsequently induced by intraperitoneal administration of 500 mg/kg of poloxamer-407. Simvastatin was administered after the induction of hyperlipidemia. Lymphocytes were isolated and E-NTPDase and E-ADA activities were determined. Serum was separated for the cytokines and nucleotide/nucleoside quantification. E-NTPDase and E-ADA activities were increased in lymphocytes from hyperlipidemic rats and pretreatment with quercetin was able to prevent the increase in the activities of these enzymes caused by hyperlipidemia. Hyperlipidemic rats when receiving pretreatment with quercetin and treatment with simvastatin showed decreased levels of ATP and ADP when compared to the untreated hyperlipidemic group. The IFN-γ and IL-4 cytokines were increased in the hyperlipidemic group when compared with control group, and decreased when hyperlipidemic rats received the pretreatment with quercetin. However, pretreatment with quercetin was able to prevent the alterations caused by hyperlipidemia probably by regulating the inflammatory process. We can suggest that the quercetin is a promising compound to be used as an adjuvant in the treatment of hyperlipidemia.
Contents
Maturation of oocytes is a prerequisite for successful embryo development. The fertilization competence of in vivo derived oocytes is significantly higher than that of oocytes matured in ...vitro. Commonly evaluated morphological criteria for oocyte maturation do not reflect the complexity and quality of maturation processes. Oocytes and granulosa cells are communicating closely in a bidirectional way during follicular growth and maturation. Assessing the mRNA expression of specific genes in granulosa cells could be a non‐invasive way to evaluate the conditions of in vitro oocyte maturation. The objective of this study was to elucidate the influence of two different FSH additives on the in vitro maturation rate and gene expression of cumulus–oocytes complexes in domestic cat. Feline oocytes were matured in a medium, supplemented with LH and 0.02 IU/ml porcine FSH versus 0.02 IU or 1.06 IU/ml human FSH. Granulosa cells were separated from oocytes directly after 24 hr of maturation or after additional 12 hr of in vitro fertilization. Gene expression levels were analysed by quantitative PCR for aromatase, antimullerian hormone, follicle stimulating hormone receptor (FSHR), luteinizing hormone/choriogonadotropin receptor (LHCGR) and prostaglandin E synthase. Neither oocyte maturation rate nor gene expression levels differed after 24 or 36 hr in all three groups. However, variations were discovered in correlations of expression levels, for instance for FSHR and LHCG, indicating differences in the fine‐tuning of in vitro maturation processes under varying FSH supplementations. We suppose that correlation between gene expressions of selected genes suggests a superior maturation quality of feline oocytes.
Fracture healing in the elderly is associated with a declined healing potential caused by multiple factors including a delay of vascularization. Erythropoietin (EPO) has been demonstrated to improve ...vascularization and fracture healing in adult mice. We, therefore, hypothesized that EPO in aged mice also improves fracture healing. For this purpose, EPO was given daily in a femoral fracture model in aged mice and compared to vehicle-treated controls using radiological, biomechanical, histomorphometric and Western blot techniques.
Blood analyses revealed significantly higher concentrations of hemoglobin and a higher hematocrit in EPO-treated animals at 14 and 35 days after fracture. Micro-computed tomography (μCT) indicated that the fraction of bone volume/tissue volume within the callus did not differ between the two groups. However, μCT showed a 3-fold increased tissue mineral density (TMD) in the callus of EPO-treated animals compared to controls. The callus TMD of the EPO-treated animals was also 2-fold higher when compared to the TMD of the unfractured contralateral femur. Interestingly, biomechanical analyses revealed a reduced bending stiffness in femurs of EPO-treated animals at day 35. The histomorphometrically analyzed callus size and callus composition did not show significant differences between the study groups. However, Western blot analyses exhibited an increased expression of osteoprotegerin (OPG), but in particular of receptor activator of NF-κB ligand (RANKL) in the callus of the EPO-treated animals. Further histological analyses of the callus tissue showed that this was associated with an increased number of newly formed blood vessels and a higher number of tartrate-resistant acid phosphatase (TRAP)+ cells.
Conclusion: In fracture healing of aged mice EPO treatment increases callus TMD as well as OPG and RANKL expression, indicating an accelerated bone turnover when compared to controls. However, EPO does not improve fracture healing in aged mice. The process of fracture healing may be altered by EPO due to a deterioration of the microcirculation caused by the worsened rheological properties of the blood and due to an increased bone fragility caused by the accelerated bone turnover. Thus, EPO may not be used to improve fracture healing in the elderly.
•EPO treatment increased hemoglobin, hematocrit and vascularization in aged mice.•EPO treatment increased tissue mineral density and reduced bending stiffness.•EPO-treated animals presented more osteoclasts and an accelerated bone turnover.•In contrast to young mice EPO may not be used to improve bone healing in the elderly.
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