Immunohistochemical markers of prognosis in adult granulosa cell tumors of the ovary - a review.

BACKGROUND: Granulosa cell tumors (GCT) are rare malignant ovarian tumors. The two subtypes, adult and juvenile granulosa cell tumors, differ in clinical and molecular characteristics. GCT are low-malignant tumors and are generally associated with favorable prognosis. However, relapses are common even years and decades after diagnosis. Prognostic and predictive factors are difficult to assess in this rare tumor entity. The purpose of this review is to provide a comprehensive overview of the current state of knowledge on prognostic markers of GCT to identify patients with a high risk of recurrence. METHODS: Systematic research for adult ovarian granulosa cell tumors and prognosis revealed n = 409 English full text results from 1965 to 2021. Of these articles, n = 35 were considered for this review after title and abstract screening and topic-specific matching. A specific search for pathologic markers with prognostic relevance for GCT identified n = 19 articles that were added to this review. RESULTS: FOXL2 mutation and FOXL2 mRNA were inverse and immunohistochemical (IHC) expression of CD56, GATA-4 and SMAD3 was associated with reduced prognosis. IHC analysis of estrogen receptor, Anti-Mullerian hormone (AMH) and inhibin was not associated with prognosis for GCT. Analyses of mitotic rate, Ki-67, p53, ß-catenin and HER2 revealed inconsistent results.

Phase-adaptive brain stimulation of striatal D1 medium spiny neurons in dopamine-depleted mice.

Brain rhythms are strongly linked with behavior, and abnormal rhythms can signify pathophysiology. For instance, the basal ganglia exhibit a wide range of low-frequency oscillations during movement, but pathological "beta" rhythms at ~ 20 Hz have been observed in Parkinson's disease (PD) and in PD animal models. All brain rhythms have a frequency, which describes how often they oscillate, and a phase, which describes the precise time that peaks and troughs of brain rhythms occur. Although frequency has been extensively studied, the relevance of phase is unknown, in part because it is difficult to causally manipulate the instantaneous phase of ongoing brain rhythms. Here, we developed a phase-adaptive, real-time, closed-loop algorithm to deliver optogenetic stimulation at a specific phase with millisecond latency. We combined this Phase-Adaptive Brain STimulation (PABST) approach with cell-type-specific optogenetic methods to stimulate basal ganglia networks in dopamine-depleted mice that model motor aspects of human PD. We focused on striatal medium spiny neurons expressing D1-type dopamine receptors because these neurons can facilitate movement. We report three main results. First, we found that our approach delivered PABST within system latencies of 13 ms. Second, we report that closed-loop stimulation powerfully influenced the spike-field coherence of local brain rhythms within the dorsal striatum. Finally, we found that both 4 Hz PABST and 20 Hz PABST improved movement speed, but we found differences between phase only with 4 Hz PABST. These data provide causal evidence that phase is relevant for brain stimulation, which will allow for more precise, targeted, and individualized brain stimulation. Our findings are applicable to a broad range of preclinical brain stimulation approaches and could also inform circuit-specific neuromodulation treatments for human brain disease.

Structural Effects of Cellulose on Hydrolysis and Carbonization Behavior during Hydrothermal Treatment.

This study aims to investigate how the morphology of cellulose influences the hydrolysis and carbonization during hydrothermal treatment at temperatures between 180 and 240 °C. The morphology of cellulose, especially different crystallinities and degrees of polymerization, is represented by microcrystalline cellulose and α-cellulose. Kinetic analysis is considered a tool to allow the determination of the mechanisms of the two types of cellulose during the hydrothermal process. A kinetic model, in which cellulose is assumed to be hydrolyzed to a limited extent, is proposed. Five scenarios are used as models for pyrolysis of nonhydrolyzed cellulose that forms primary char, along with reaction pathways of hydrolyzable cellulose and its derivatives that latterly form secondary char. The morphologies of solid products are in good agreement with the results of the proposed model.

Hydrothermal carbonization of biogas digestate: Effect of digestate origin and process conditions.

Hydrothermal carbonization (HTC) solids were produced in a 250-ml batch reactor from three different digestates at varying temperatures (170, 190, 210, 230, and 250 °C) and 2 and 5 h reaction time. Three potential feedstocks of biogas plants were tested: organic household waste, cow manure, and energy crops. The proximate composition, elemental composition, heating values, and thermal stability of the HTC solids were characterized. The dry ash-free basis yields and carbon recovery of HTC solids decreased with increasing HTC temperature and time. The HTC solids from energy crop digestate had the highest yields (dry ash-free basis) except at the temperature of 250 °C. Increased HTC severity was found to have a positive effect on the dry basis carbon content and leads to a higher heating values (HHV) of cow manure digestate HTC solids. The preferred reaction condition for organic household waste digestate and energy crop digestate HTC solids was found to be 210 °C for 5 h, because of the highest HHV (dry basis) and the overall combustion performance was reached. Enhancing HTC temperature increased the peak intensity of functional groups of cow manure digestate HTC solids. Scanning electron microscopy imaging showed the fibrous structure of the plants from the digestates was mostly deconstructed at 250 °C-5 h. Experimental results indicated that both digestate origin and HTC condition influenced the properties of the HTC solids.

Influence of the pH Value on the Hydrothermal Degradation of Fructose.

The hydrothermal treatment of sugars features a promising technology for the production of fine and platform chemicals from renewable resources. In this work the hydrothermal decomposition of fructose was studied in a buffered medium at a pH range between 2.2 and 8.0. It is demonstrated that at lower pH values mainly 5-hydroxymethylfurfural (HMF), levulinic acid and humin are generated, while lactic acid and acetic acid are produced at higher pH values. The work shows that the use of moderate acidic conditions may have advantages for the hydrothermal HMF production over the use of strongly acidic conditions, as especially the degradation into levulinic acid is suppressed. Besides, this study deals with a rather complex reaction network, hence limitations and need for adaption of the kinetic model are discussed.

Scopolamine and Medial Frontal Stimulus-Processing during Interval Timing.

Neurodegenerative diseases such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), and Alzheimer's disease (AD) involve loss of cholinergic neurons in the basal forebrain. Here, we investigate how cholinergic dysfunction impacts the frontal cortex during interval timing, a process that can be impaired in PD and AD patients. Interval timing requires participants to estimate an interval of several seconds by making a motor response, and depends on the medial frontal cortex (MFC), which is richly innervated by basal forebrain cholinergic projections. Past work has shown that scopolamine, a muscarinic cholinergic receptor antagonist, reliably impairs interval timing. We tested the hypothesis that scopolamine would attenuate time-related ramping, a key form of temporal processing in the MFC. We recorded neuronal ensembles from eight mice during performance of a 12-s fixed-interval timing task, which was impaired by the administration of scopolamine. Consistent with past work, scopolamine impaired timing. To our surprise, we found that time-related ramping was unchanged, but stimulus-related activity was enhanced in the MFC. Principal component analyses revealed no consistent changes in time-related ramping components, but did reveal changes in higher components. Taken together, these data indicate that scopolamine changes stimulus processing rather than temporal processing in the MFC. These data could help understand how cholinergic dysfunction affects cortical circuits in diseases such as PD, DLB, and AD.

Conductive Carbon Materials from the Hydrothermal Carbonization of Vineyard Residues for the Application in Electrochemical Double-Layer Capacitors (EDLCs) and Direct Carbon Fuel Cells (DCFCs).

This study investigates the production of bio-based carbon materials for energy storage and conversion devices based on two different vineyard residues (pruning, pomace) and cellulose as a model biomass. Three different char categories were produced via pyrolysis at 900 °C for 2 h (biochars, BC), hydrothermal carbonization (HTC) (at 220, 240 or 260 °C) with different reaction times (60, 120 or 300 min) (hydrochars, HC), or HTC plus pyrolysis (pyrolyzed hydrochars, PHC). Physicochemical, structural, and electrical properties of the chars were assessed by elemental and proximate analysis, gas adsorption surface analysis with N2 and CO2, compression ratio, bulk density, and electrical conductivity (EC) measurements. Thermogravimetric analysis allowed conclusions to be made about the thermochemical conversion processes. Taking into consideration the required material properties for the application in electrochemical double-layer capacitors (EDLC) or in a direct carbon fuel cell (DCFC), the suitability of the obtained materials for each application is discussed. Promising materials with surface areas up to 711 m2 g-1 and presence of microporosity have been produced. It is shown that HTC plus pyrolysis from cellulose and pruning leads to better properties regarding aromatic carbon structures, carbon content (>90 wt.%), EC (up to 179 S m-1), and porosity compared to one-step treatments, resulting in suitable materials for an EDLC application. The one-step pyrolysis process and the resulting chars with lower carbon contents and low EC values between 51 and 56 S m-1 are preferred for DCFC applications. To conclude, biomass potentials can be exploited by producing tailored biomass-derived carbon materials via different carbonization processes for a wide range of applications in the field of energy storage and conversion.

Contrast-Enhanced µCT for Visualizing and Evaluating Murine Intestinal Inflammation.

Rationale: To develop a simple and fast protocol for the assessment of acute and chronic experimental intestinal inflammation using contrast-enhanced µCT. Methods: For the imaging studies, an acute 2% and 3% dextran sodium sulfate (n = 15, female, 8-12 weeks) and a chronic adoptive transfer colitis model (n = 10, female, 8-9 weeks) were established over 9 days or 6 weeks, respectively. Throughout the experiments, longitudinal measurement of murine intestinal wall thickness and time dependent perfusion was performed on a small animal µCT system (90 kV, 160 µA, FOV: 60 mm, scan time: 17 s, image size: 512x512, layer thickness: 118 µm) between 0.5 and 30 min after intravenous bolus injection of an iodine contrast agent. Weight development, small animal endoscopy, and histological ex vivo analysis were compared to contrast-enhanced µCT imaging findings. Results: Murine intestinal wall thickness was significantly increased in inflamed colons of acute colitis at day 9 in comparison to pre-inflamed state. Perfusion analysis revealed a late contrast enhancement in acute inflamed colons and the renal medulla at day 9 compared to control mice. An increasing intestinal wall thickness was monitored 3, 5 and 6 weeks after on-set of chronic colitis in comparison to controls. A good correlation with endoscopic (r = 0.75, p < 0.0001) and histologic degree of inflammation (r = 0.83, p = 0.04) was found. Conclusion: Contrast-enhanced µCT is a simple and fast method to assess acute intestinal inflammation and to monitor disease progression in experimental models of chronic colitis. According to our findings, one single contrast-enhanced µCT-scan is a valid non-invasive modality to quantify the degree of inflammation in the entire digestive tract in murine inflammatory models.

Ca2+ transport in mitochondria from yeast expressing recombinant aequorin.

We have expressed aequorin in mitochondria of the yeast Saccharomyces cerevisiae and characterized the resulting strain with respect to mitochondrial Ca(2+) transport in vivo and in vitro. When intact cells are suspended in water containing 1.4 mM ethanol and 14 mM CaCl(2), the matrix free Ca(2+) concentration is 200 nM, similar to the values expected in cytoplasm. Addition of ionophore ETH 129 allows an active accumulation of Ca(2+) and promptly increases the value to 1.2 microM. Elevated Ca(2+) concentrations are maintained for periods of 6 min or longer under these conditions. Isolated yeast mitochondria oxidizing ethanol also accumulate Ca(2+) when ETH 129 is present, but the cation is not retained depending on the medium conditions. This finding confirms the presence of a Ca(2+) release mechanism that requires free fatty acids as previously described [P.C. Bradshaw et al. (2001) J. Biol. Chem. 276, 40502-40509]. When a respiratory substrate is not present, Ca(2+) enters and leaves yeast mitochondria slowly, at a specific activity near 0.2 nmol/min/mg protein. Transport under these conditions equilibrates the internal and external concentrations of Ca(2+) and is not affected by ruthenium red, uncouplers, or ionophores that perturb transmembrane gradients of charge and pH. This activity displays sigmoid kinetics and a K(1/2) value for Ca(2+) that is near to 900 nM, in the absence of ethanol or when it is present. It is furthermore shown that the activity coefficient of Ca(2+) in yeast mitochondria is a function of the matrix Ca(2+) content and is substantially larger than that in mammalian mitochondria. Characteristics of the aequorin-expressing strain appear suitable for its use in expression-based methods directed at cloning Ca(2+) transporters from mammalian mitochondria and for further examining the interrelationships between mitochondrial and cytoplasmic Ca(2+) in yeast.