scholarly journals Excretion and binding of tritium-labelled oestradiol in mice (Mus musculus): implications for the Bruce effect

Reproduction ◽  
2010 ◽  
Vol 139 (1) ◽  
pp. 255-263 ◽  
Author(s):  
Adam C Guzzo ◽  
Robert G Berger ◽  
Denys deCatanzaro
Keyword(s):  
Cerebral Cortex ◽  
Intranasal Administration ◽  
Male Mice ◽  
Olfactory Bulbs ◽  
Tissue Samples ◽  
Mouse Urine ◽  
Osmotic Pumps ◽  
Bruce Effect ◽  
Blastocyst Implantation ◽  
Pre Treatment

Male mouse urine contains 17β-oestradiol (E2) and other steroids. Given that males actively direct urine at proximate females and intrauterine implantation of blastocysts is vulnerable to minute amounts of exogenous oestrogens, males' capacity to disrupt early pregnancy could be mediated by steroids in their urine. When male mice were implanted with osmotic pumps containing tritium-labelled E2 (3H-E2) or injected i.p. with 3H-E2, radioactivity was reliably detected in their urine. Following intranasal administration of 3H-E2 to inseminated females, radioactivity was detected in diverse tissue samples, with there being significantly more in reproductive tissues than in brain tissues. When urine was taken from males injected with 3H-E2, and then intranasally administered to inseminated females, radioactivity was detected in the uterus, olfactory bulbs, and mesencephalon and diencephalon (MC+DC). When inseminated and ovariectomised females were perfused at the point of killing to remove blood from tissues, more radioactivity was detected in the uterus than in muscle, olfactory bulbs, MC+DC and cerebral cortex. Pre-treatment with unlabelled E2 significantly reduced the uptake of 3H-E2 in the uterus. Taken with evidence that males deliver their urine to the nasal area of females, these results indicate that male urinary E2 arrives in tissues, including the uterus, where it could lead to the disruption of blastocyst implantation.

Oligodendrocytes in Developing Hameter Cerebral Cortex

1976 ◽  
Vol 34 ◽  
pp. 126-127
Author(s):  
MB. Tank Buschmann
Keyword(s):  
Cerebral Cortex ◽  
Optic Nerve ◽  
Frontal Cortex ◽  
Osmium Tetroxide ◽  
Sodium Cacodylate Buffer ◽  
Sodium Cacodylate ◽  
Tissue Samples ◽  
Cacodylate Buffer ◽  
Layer V ◽  
Adult Hamster

Development of oligodendrocytes in rat corpus callosum was described as a sequential change in cytoplasmic density which progressed from light to medium to dark (1). In rat optic nerve, changes in cytoplasmic density were not observed, but significant changes in morphology occurred just prior to and during myelination (2). In our study, the ultrastructural development of oligodendrocytes was studied in newborn, 5-, 10-, 15-, 20-day and adult frontal cortex of the golden hamster (Mesocricetus auratus).Young and adult hamster brains were perfused with paraformaldehyde-glutaraldehyde in sodium cacodylate buffer at pH 7.3 according to the method of Peters (3). Tissue samples of layer V of the frontal cortex were post-fixed in 2% osmium tetroxide, dehydrated in acetone and embedded in Epon-Araldite resin.

Analytical and clinical validation of a novel amplicon-based NGS assay for the evaluation of circulating tumor DNA in metastatic colorectal cancer patients

2019 ◽  
Vol 57 (10) ◽  
pp. 1501-1510 ◽  
Author(s):  
Beili Wang ◽  
Shengchao Wu ◽  
Fei Huang ◽  
Minna Shen ◽  
Huiqin Jiang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Limit Of Detection ◽  
Clinical Performance ◽  
Circulating Tumor Dna ◽  
Concordance Rate ◽  
Tissue Samples ◽  
Percent Agreement ◽  
Pre Treatment ◽  
Tumor Dna

Abstract Background Evaluating the tumor RAS/BRAF status is important for treatment selection and prognosis assessment in metastatic colorectal cancer (mCRC) patients. Correction of artifacts from library preparation and sequencing is essential for accurately analyzing circulating tumor DNA (ctDNA) mutations. Here, we assessed the analytical and clinical performance of a novel amplicon-based next-generation sequencing (NGS) assay, Firefly™, which employs a concatemer-based error correction strategy. Methods Firefly assay targeting KRAS/NRAS/BRAF/PIK3CA was evaluated using cell-free DNA (cfDNA) reference standards and cfDNA samples from 184 mCRC patients. Plasma results were compared to the mutation status determined by ARMS-based PCR from matched tissue. Samples with a mutation abundance below the limit of detection (LOD) were retested again by droplet digital polymerase chain reaction (ddPCR) or NGS. Results The Firefly assay demonstrated superior sensitivity and specificity with a 98.89% detection rate at an allele frequency (AF) of 0.2% for 20 ng cfDNA. Generally, 40.76% and 48.37% of the patients were reported to be positive by NGS of plasma cfDNA and ARMS of FFPE tissue, respectively. The concordance rate between the two platforms was 80.11%. In the pre-treatment cohort, the concordance rate between plasma and tissue was 93.33%, based on the 17 common exons that Firefly™ and ARMS genotyped, and the positive percent agreement (PPA) and negative percent agreement (NPA) for KRAS/NRAS/BRAF/PIK3CA were 100% and 99.60%, respectively. Conclusions Total plasma cfDNA detected by Firefly offers a viable complement for mutation profiling in CRC patients, given the high agreement with matched tumor samples. Together, these data demonstrate that Firefly could be routinely applied for clinical applications in mCRC patients.

scholarly journals Neuronal Aquaporin 1 Inhibits Amyloidogenesis by Suppressing the Interaction Between Beta-Secretase and Amyloid Precursor Protein

2020 ◽  
Vol 76 (1) ◽  
pp. 23-31
Author(s):  
Jinsu Park ◽  
Meenu Madan ◽  
Srinivasulu Chigurupati ◽  
Seung Hyun Baek ◽  
Yoonsuk Cho ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Mouse Models ◽  
Cortical Neurons ◽  
Water Channel ◽  
Ectopic Expression ◽  
Amyloid Β ◽  
Human Neuroblastoma ◽  
Tissue Samples ◽  
Aquaporin 1 ◽  
Aβ Production

Abstract The accumulation of amyloid-β (Aβ) is a characteristic event in the pathogenesis of Alzheimer’s disease (AD). Aquaporin 1 (AQP1) is a membrane water channel protein belonging to the AQP family. AQP1 levels are elevated in the cerebral cortex during the early stages of AD, but the role of AQP1 in AD pathogenesis is unclear. We first determined the expression and distribution of AQP1 in brain tissue samples of AD patients and two AD mouse models (3xTg-AD and 5xFAD). AQP1 accumulation was observed in vulnerable neurons in the cerebral cortex of AD patients, and in neurons affected by the Aβ or tau pathology in the 3xTg-AD and 5xFAD mice. AQP1 levels increased in neurons as aging progressed in the AD mouse models. Stress stimuli increased AQP1 in primary cortical neurons. In response to cellular stress, AQP1 appeared to translocate to endocytic compartments of β- and γ-secretase activities. Ectopic expression of AQP1 in human neuroblastoma cells overexpressing amyloid precussir protein (APP) with the Swedish mutations reduced β-secretase (BACE1)-mediated cleavage of APP and reduced Aβ production without altering the nonamyloidogenic pathway. Conversely, knockdown of AQP1 enhanced BACE1 activity and Aβ production. Immunoprecipitation experiments showed that AQP1 decreased the association of BACE1 with APP. Analysis of a human database showed that the amount of Aβ decreases as the expression of AQP1 increases. These results suggest that the upregulation of AQP1 is an adaptive response of neurons to stress that reduces Aβ production by inhibiting the binding between BACE1 and APP.

A molybdenum - sulfur - cadmium interaction in sheep

1997 ◽  
Vol 48 (2) ◽  
pp. 147 ◽  
Author(s):  
G. M. Smith ◽  
C. L. White
Keyword(s):  
Control Diet ◽  
Dietary Treatment ◽  
Basal Diet ◽  
Dry Weight ◽  
Fresh Weight ◽  
Tissue Samples ◽  
Cd Accumulation ◽  
Treatment Groups ◽  
Pre Treatment ◽  
Treatment Concentration

We determined the effects of increased dietary concentrations of molybdenum and sulfur on the accumulation and tissue concentrations of cadmium in sheep, and compared them with effects on copper. Forty sheep, each weighing approximately 40 kg, were adjusted for 3 weeks to a basal diet of 80% wheaten chaff and 20% lupin seed containing (per kg dry weight) 0·016 mg Cd, 0·45 mg Mo, 3·4 mg Cu, and 1·9 g S. On Day 0 of treatment, 8 sheep were killed and the tissues analysed for trace minerals to provide a baseline value. The remaining sheep were divided into 4 dietary treatment groups: control (basal diet plus 4 mg Cd/kg), +Mo (control diet plus 15 mg Mo/kg), +S (control diet plus 4 g S/kg), +Mo+S (control diet+15 mg Mo+4 g S/kg). The treatment period lasted 80 days, after which sheep were killed for tissue samples. Sulfur alone reduced the accumulation of Cd in liver, kidney, and muscle by 60% compared with control sheep (P < 0·05). Molybdenum alone reduced Cd accumulation by 40% in liver and muscle (P < 0·05) and 30% in kidney (P = 0·09). When provided together (+Mo+S), the effect was equivalent to feeding with Mo alone, showing that Mo blocked the effect of S. Cadmium concentrations in whole kidneys for the 4 respective treatments were 6·40 ± 0· 7, 2·8 ± 0·3, 4·5 ± 0·8, and 5·0 ± 0·5 mg/kg fresh weight. The pre-treatment concentration was 0·7 ± 0·2 mg/kg. For Cu in blood and tissues, the effects of Mo and S treatment were consistent with the thiomolybdate hypothesis, and were quite different from those seen for Cd. Copper concentrations in whole kidney for the 4 treatments were 4·1 ± 0·1, 3·5 ± 0·2, 4·7 ± 0·3, and 22·4 ± 3·9 mg/kg fresh weight. The pre-treatment concentration was 4·1 ± 0·3 mg/kg. The results show that increased dietary levels of Mo and S reduce the accumulation of Cd in tissues, and the mechanisms of action differ from those involving Cu.

scholarly journals Sex-specific hippocampus-dependent cognitive deficits and increased neuronal autophagy in DEspR haploinsufficiency in mice

2008 ◽  
Vol 35 (3) ◽  
pp. 316-329 ◽  
Author(s):  
Victoria L. M. Herrera ◽  
Julius L. Decano ◽  
Pia Bagamasbad ◽  
Timothy Kufahl ◽  
Martin Steffen ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Cognitive Performance ◽  
Cognitive Deficits ◽  
Mammalian Target Of Rapamycin ◽  
Male Mice ◽  
Wild Type ◽  
Neuronal Homeostasis ◽  
Subcortical Regions ◽  
Neuronal Autophagy ◽  
Neuronal Vacuolation

Aside from abnormal angiogenesis, dual endothelin-1/VEGF signal peptide-activated receptor deficiency ( DEspR−/−) results in aberrant neuroepithelium and neural tube differentiation, thus elucidating DEspR's role in neurogenesis. With the emerging importance of neurogenesis in adulthood, we tested the hypothesis that nonembryonic-lethal DEspR haploinsufficiency ( DEspR+/−) perturbs neuronal homeostasis, thereby facilitating aging-associated neurodegeneration. Here we show that, in male mice only, DEspR-haploinsufficiency impaired hippocampus-dependent visuospatial and associative learning and induced noninflammatory spongiform changes, neuronal vacuolation, and loss in the hippocampus, cerebral cortex, and subcortical regions, consistent with autophagic cell death. In contrast, DEspR+/− females exhibited better cognitive performance than wild-type females and showed absence of neuropathological changes. Signaling pathway analysis revealed DEspR-mediated phosphorylation of activators of autophagy inhibitor mammalian target of rapamycin (mTOR) and dephosphorylation of known autophagy inducers. Altogether, the data demonstrate DEspR-mediated diametrical, sex-specific modulation of cognitive performance and autophagy, highlight cerebral neuronal vulnerability to autophagic dysregulation, and causally link DEspR haploinsufficiency with increased neuronal autophagy, spongiosis, and cognitive decline in mice.

scholarly journals Oestradiol transmission from males to females in the context of the Bruce and Vandenbergh effects in mice (Mus musculus)

Reproduction ◽  
2012 ◽  
Vol 143 (4) ◽  
pp. 539-548 ◽  
Author(s):  
Adam C Guzzo ◽  
Jihwan Jheon ◽  
Faizan Imtiaz ◽  
Denys deCatanzaro
Keyword(s):  
Mus Musculus ◽  
Reproductive Tract ◽  
Female Reproductive Tract ◽  
Male Mice ◽  
Reproductive Maturity ◽  
Reproductive Tissues ◽  
Uterine Growth ◽  
Blastocyst Implantation ◽  
Bladder Urine

Male mice actively direct their urine at nearby females, and this urine reliably contains unconjugated oestradiol (E2) and other steroids. Giving inseminated females minute doses of exogenous E2, either systemically or intranasally, can cause failure of blastocyst implantation. Giving juvenile females minute doses of exogenous E2 promotes measures of reproductive maturity such as uterine mass. Here we show that tritium-labelled E2 (3H-E2) can be traced from injection into novel male mice to tissues of cohabiting inseminated and juvenile females. We show the presence of 3H-E2 in male excretions, transmission to the circulation of females and arrival in the female reproductive tract. In males, 3H-E2 given systemically was readily found in reproductive tissues and was especially abundant in bladder urine. In females, 3H-E2 was found to enter the system via both nasal and percutaneous routes, and was measurable in the uterus and other tissues. As supraoptimal E2 levels can both interfere with blastocyst implantation in inseminated females and promote uterine growth in juvenile females, we suggest that absorption of male-excreted E2 can account for major aspects of the Bruce and Vandenbergh effects.

scholarly journals The influence of multiphytoadaptogen on leukocyte infiltration in mice hepatocarcinomas

2019 ◽  
Vol 18 (2) ◽  
pp. 60-65
Author(s):  
R. V. Karpova ◽  
E. V. Bocharov ◽  
O. A. Bocharova ◽  
I. V. Kazeev ◽  
V. G. Kucheryanu ◽  
...  
Keyword(s):  
Leukocyte Infiltration ◽  
Male Mice ◽  
Liquid Form ◽  
Liver Tumours ◽  
Tissue Samples ◽  
Experimental Animals ◽  
Tumour Formation ◽  
Hematoxylin And Eosin ◽  
Mice Liver ◽  
Therapeutic Administration

The aim of this study was the morphological investigation of the CBA mice liver tissue at different stages of ontogenesis as well as during liquid form multifitoadaptogen therapeutic administration.Materials and methods . The study objects are the liver samples of CBA male mice (subline CBA / LacY). Experimental animals received a 10 % solution of multifitoadaptogen from 6 months of age until natural death. Tissue samples were fixed in neutral buffered formalin and embedded in paraffin. Sections from paraffin blocks were stained with hematoxylin and eosin. The structure of the liver tumours was determined as well as the quantitаtive degree of leukocyte infiltration in the tumour tissue.Results . The tumours morphologically structured as moderately differentiated trabecular hepatocarcinomas (at 8 months of age) and low differentiated trabecular-acinar hepatocarcinomas (aged 22 months) were revealed in CBA male mice. Higher lever of leukocyte infiltration in hepatocarcinomas of experimental animals was determined.Conclusion . Leukocyte infiltration may be important for antitumour immune reaction as well as for reduction of the tumour formation incidence in high-cancer mice.

scholarly journals The effects of kumiss supplementation on body weight, food intake, nesfatin-1 and irisin levels in BALB/C mice

2020 ◽  
Vol 90 (6) ◽  
pp. 627-636
Author(s):  
Canan Gulmez ◽  
◽  
Onur Atakisi
Keyword(s):  
Weight Loss ◽  
Food Intake ◽  
Live Weight ◽  
Feed Consumption ◽  
Control Group ◽  
Male Mice ◽  
Tissue Samples ◽  
Bacterial Colony ◽  
Metabolic Functions ◽  
Significant Difference

The aim of this study was to investigate the plasma and tissue levels of nesfatin-1 and irisin hormones, which were discovered in recent years and are associated with endocrine and metabolic functions, in kumiss-supplemented mice. Sixteen BALB/C male mice were divided into two groups as control and kumiss groups. During the experiment, the kumiss was added to the drinking water of mice at a ratio of 1:1 to obtain a daily 2×108 cfu/mL bacterial colony, and was given once a day orally for 20 weeks. The weights and food intake of the animals were monitored during the experiment. The nesfatin-1 and irisin levels in plasma and tissue samples were determined using ELISA kits. Kumiss supplementation reduced the live weight for 2-12 weeks (P<0.05). However, no significant difference was observed after the 12th week. The feed consumption of the kumiss group was lower at the beginning and the 10th week, and at the end, compared to the control group (P<0.05). The plasma levels of nesfatin-1 and irisin (P<0.001) decreased while the liver levels increased (P<0.05 and P<0.001, respectively). The results indicate that plasma and liver levels of nesfatin-1 and irisin are regulated by diet and are effective in weight loss and food intake.

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