Deoxyribonucleic acid flow cytometry was performed on aspirated prostatic cells from 198 patients who had benign cytological or histological findings. Unsatisfactory acellular histograms were ...obtained from 10.6 per cent of the cases. Three-fourths of the satisfactory samples (more than 5,000 cells after subtracting debris) showed the expected single peak deoxyribonucleic acid diploid to near diploid histograms. Unexpectedly, the remaining samples were deoxyribonucleic acid aneuploid, most having 2 peridiploid peaks (deoxyribonucleic acid index 0.82 to 1.31). Usually, proliferation was low with less than 20 per cent hyperdiploid cells and with 2.5 +/- 1.5 per cent G2 cells. In 10 per cent of the single peak histograms there was evidence of inflammation, identified as an increase in hyperdiploid cells without an increased percentage of G2 cells but with a tail of high channel values. The aforementioned histogram features were considered to be benign findings. Seven per cent of the samples had deoxyribonucleic acid histograms suggestive of prostate cancer. Of these samples 7 had diploid or peridiploid aneuploid histograms with high proliferation (more than 20 per cent hyperdiploid cells with 8.5 +/- 3.8 per cent G2 cells), while 5 had histograms with deoxyribonucleic acid aneuploidy other than peridiploidy.
Pregabalin has shown clinical efficacy for treatment of neuropathic pain syndromes, partial seizures, and anxiety disorders. Five studies in healthy volunteers are performed to investigate single‐ ...and multiple‐dose pharmacokinetics of pregabalin. Pregabalin is rapidly absorbed following oral administration, with peak plasma concentrations occurring between 0.7 and 1.3 hours. Pregabalin oral bioavailability is approximately 90% and is independent of dose and frequency of administration. Food reduces the rate of pregabalin absorption, resulting in lower and delayed maximum plasma concentrations, yet the extent of drug absorption is unaffected, suggesting that pregabalin may be administered without regard to meals. Pregabalin elimination half‐life is approximately 6 hours and steady state is achieved within 1 to 2 days of repeated administration. Corrected for oral bioavailability, pregabalin plasma clearance is essentially equivalent to renal clearance, indicating that pregabalin undergoes negligible nonrenal elimination. Pregabalin demonstrates desirable, predictable pharmacokinetic properties that suggest ease of use. Because pregabalin is eliminated renally, renal function affects its pharmacokinetics.
SOX2 is a member of SOX (SRY-related high mobility group box) family of transcription factors.
In this study, we examined the expression of SOX2 in murine and human prostatic specimens by ...immunohistochemistry.
We found that SOX2 was expressed in murine prostates during budding morphogenesis and in neuroendocrine (NE) prostate cancer (PCa) murine models. Expression of SOX2 was also examined in human prostatic tissue. We found that SOX2 was expressed in 26 of the 30 BPH specimens. In these BPH samples, expression of SOX2 was limited to basal epithelial cells. In contrast, 24 of the 25 primary PCa specimens were negative for SOX2. The only positive primary PCa was the prostatic NE tumor, which also showed co-expression of synaptophysin. Additionally, the expression of SOX2 was detected in all prostatic NE tumor xenograft lines. Furthermore, we have examined the expression of SOX2 on a set of tissue microarrays consisting of metastatic PCa tissues. Expression of SOX2 was detected in at least one metastatic site in 15 of the 24 patients with metastatic castration-resistant PCa; and the expression of SOX2 was correlated with synaptophysin.
SOX2 was expressed in developing prostates, basal cells of BPH, as well as prostatic NE tumors.
Gene content evolution in the arthropods Thomas, Gregg W C; Dohmen, Elias; Hughes, Daniel S T ...
Genome Biology,
01/2020, Letnik:
21, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Arthropods comprise the largest and most diverse phylum on Earth and play vital roles in nearly every ecosystem. Their diversity stems in part from variations on a conserved body plan, resulting from ...and recorded in adaptive changes in the genome. Dissection of the genomic record of sequence change enables broad questions regarding genome evolution to be addressed, even across hyper-diverse taxa within arthropods.
Using 76 whole genome sequences representing 21 orders spanning more than 500 million years of arthropod evolution, we document changes in gene and protein domain content and provide temporal and phylogenetic context for interpreting these innovations. We identify many novel gene families that arose early in the evolution of arthropods and during the diversification of insects into modern orders. We reveal unexpected variation in patterns of DNA methylation across arthropods and examples of gene family and protein domain evolution coincident with the appearance of notable phenotypic and physiological adaptations such as flight, metamorphosis, sociality, and chemoperception.
These analyses demonstrate how large-scale comparative genomics can provide broad new insights into the genotype to phenotype map and generate testable hypotheses about the evolution of animal diversity.
Deoxyribonucleic acid flow cytometry of bladder washings has proved to be a valuable procedure for the diagnosis and followup of patients with transitional cell carcinoma. However, for this procedure ...to gain maximal acceptance, it should be possible to use voided urine specimens instead of bladder washings. To evaluate this possibility we compared histogram findings for 114 bladder washings and 122 concomitantly obtained urine samples (voided and catheterized) from 89 consecutive patients who had active or a history of transitional cell carcinoma. Unsatisfactory histograms were obtained in 4 per cent of the urine samples and in 2.6 per cent of the bladder washing samples. The satisfactory rate for voided or catheterized urine samples was the same. We conclude that in this patient population satisfactory deoxyribonucleic acid histograms can be obtained from samples of voided urine.
Objective
The objective of this study was to describe clinical features, 18F‐fluorodeoxyglucose (FDG)‐positron emission tomography (PET) metabolism and digital pathology in patients with logopenic ...progressive aphasia (LPA) and pathologic diagnosis of diffuse Lewy body disease (DLBD) and compare to patients with LPA with other pathologies, as well as patients with classical features of probable dementia with Lewy bodies (pDLB).
Methods
This is a clinicopathologic case‐control study of 45 patients, including 20 prospectively recruited patients with LPA among whom 6 were diagnosed with LPA‐DLBD. We analyzed clinical features and compared FDG‐PET metabolism in LPA‐DLBD to an independent group of patients with clinical pDLB and regional α‐synuclein burden on digital pathology to a second independent group of autopsied patients with DLBD pathology and antemortem pDLB (DLB‐DLBD).
Results
All patients with LPA‐DLBD were men. Neurological, speech, and neuropsychological characteristics were similar across LPA‐DLBD, LPA‐Alzheimer's disease (LPA‐AD), and LPA‐frontotemporal lobar degeneration (LPA‐FTLD). Genetic screening of AD, DLBD, and FTLD linked genes were negative with the exception of APOE ε4 allele present in 83% of LPA‐DLBD patients. Seventy‐five percent of the patients with LPA‐DLBD showed a parietal‐dominant pattern of hy pometabolism; LPA‐FTLD – temporal‐dominant pattern, whereas LPA‐AD showed heterogeneous patterns of hypometabolism. LPA‐DLBD had more asymmetrical hypometabolism affecting frontal lobes, with relatively spared occipital lobe in the nondominantly affected hemisphere, compared to pDLB. LPA‐DLBD had minimal atrophy on gross brain examination, higher cortical Lewy body counts, and higher α‐synuclein burden in the middle frontal and inferior parietal cortices compared to DLB‐DLBD.
Interpretation
Whereas AD is the most frequent underlying pathology of LPA, DLBD can also be present and may contribute to the LPA phenotype possibly due to α‐synuclein‐associated functional impairment of the dominant parietal lobe. ANN NEUROL 2021;89:520–533
Shrub volume is used to calculate numerous, essential ecological indicators in rangeland ecosystems such as biomass, fuel loading, wildlife habitat, site productivity, and ecosystem structure. Field ...techniques for biomass estimation, including destructive sampling, ocular estimates, and allometric techniques, use shrub height and canopy widths to estimate volume and translate it to biomass with species‐specific allometric equations. These techniques are time‐consuming and pose challenges, including removal of plant material and training of observers. We compared canopy volume estimates from field‐based measurements with drone‐collected canopy volume estimates for seven dominant shrub species within mountain big sagebrush (Artemisia tridentata subsp. vaseyana) plant communities in southern Idaho, USA. Canopy height and two perpendicular width measurements were taken from 103 shrubs of varying sizes, and volume was estimated using a traditional allometric equation. Overlapping aerial images captured with a DJI Mavic 2 Professional drone were used to create a 3D representation of the study area using structure‐from‐motion photogrammetry. Each shrub was extracted from the point cloud, and volume was estimated using allometric and volumetric methods. The volumetric method, which involved converting point clouds to raster canopy height models with 2.5‐ and 5‐cm grid cells, outperformed the allometric method (R2 > 0.7) and was more reproducible and robust to user‐related variability. Drone‐estimated volume best‐matched field‐estimated volume (R2 > 0.9) for three larger species: A. tridentata subsp. tridentata, A. tridentata subsp. vaseyana, and Purshia tridentata. The volume of smaller shrubs (canopy widths <1 m) was slightly overestimated from drone‐based models. We argue that drone‐based models provide a suitable alternative to field methods, while having the added benefit of being less time‐consuming, with fewer limitations, and more easily scaled to larger study areas than traditional field techniques. Finally, we demonstrate a proof of concept for automating canopy volume estimates using point‐cloud‐based automatic shrub detection algorithms. These findings demonstrate that drone‐collected images can be used to assess shrub canopy volume for at least five upland sagebrush steppe shrub species and support the integration of drone data collection into rangeland vegetation monitoring.
Epithelial to mesenchymal transition (EMT) is implicated in the progression of primary tumours towards metastasis and is likely caused by a pathological activation of transcription factors regulating ...EMT in embryonic development. To analyse EMT-causing pathways in tumourigenesis, we identified transcriptional targets of the E-cadherin repressor ZEB1 in invasive human cancer cells. We show that ZEB1 repressed multiple key determinants of epithelial differentiation and cell-cell adhesion, including the cell polarity genes Crumbs3, HUGL2 and Pals1-associated tight junction protein. ZEB1 associated with their endogenous promoters in vivo, and strongly repressed promotor activities in reporter assays. ZEB1 downregulation in undifferentiated cancer cells by RNA interference was sufficient to upregulate expression of these cell polarity genes on the RNA and protein level, to re-establish epithelial features and to impair cell motility in vitro. In human colorectal cancer, ZEB1 expression was limited to the tumour-host interface and was accompanied by loss of intercellular adhesion and tumour cell invasion. In invasive ductal and lobular breast cancer, upregulation of ZEB1 was stringently coupled to cancer cell dedifferentiation. Our data show that ZEB1 represents a key player in pathologic EMTs associated with tumour progression.
Two mutations in the DJ‐1 gene on chromosome1p36 have been identified recently to cause early‐onset, autosomal recessive Parkinson’s disease. As no information is available regarding the distribution ...of DJ‐1 protein in the human brain, in this study we used a monoclonal antibody for DJ‐1 to map its distribution in frontal cortex and substantia nigra, regions invariably involved in Parkinson’s disease. Western blotting of human frontal cortex showed DJ‐1 to be an abundant protein in control, idiopathic Parkinson’s disease, cases with clinical and pathological phenotypes of Parkinson’s disease with R98Q polymorphism for DJ‐1, and in progressive supranuclear palsy (PSP) brains. We also showed that DJ‐1 immunoreactivity (IR) was particularly prominent in astrocytes and astrocytic processes in both control and Parkinson’s disease frontal cortex, whereas neurons showed light or no DJ‐1 IR. Only occasional Lewy bodies (LBs), the pathological hallmarks of Parkinson’s disease, showed faint DJ‐1 IR, localized to the outer halo. In preclinical studies we showed that DJ‐1 is expressed in primary hippocampal and astrocyte cultures of mouse brain. By 2D gel analysis we also showed multiple pI isoforms for DJ‐1 ranging between 5.5–6.6 in both control and Parkinson’s disease brains, whilst exposure of M17 cells to the oxidizing agent paraquat was manifested as a shift in pI of endogenous DJ‐1 towards more acidic isoforms. We conclude that DJ‐1 is not an essential component of LBs and Lewy neurites, is expressed mainly by astrocytes in human brain tissue and is sensitive to oxidative stress conditions. These results are consistent with the hypothesis that neuronal–glial interactions are important in the pathophysiology of Parkinson’s disease.
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