ABSTRACT
To promote optimal phosphorus (P) recovery from municipal wastewater and sewage sludge with viable legal instruments, it is imperative to understand the regional and national consequences of different legal requirements for recycling. In this study we develop a scenario-based analysis to assess the environmental and economic impact of different national P recovery strategies in the context of a detailed representation of the existing Austrian wastewater infrastructure. This assessment combines material flow analysis, life cycle assessment and life cycle costing and includes the indicators P recycling rate, P utilization degree, heavy metal removal rate, share of heavy metals' content in wastewater redirected to agricultural soils, global warming potential, cumulated energy demand, terrestrial acidification potential, volume of freight transport and annual costs. The following main conclusions can be drawn. P recovery from ash shows the highest potential regarding the utilization of P from wastewater. A high P utilization from wastewater should rely on recovery technologies that decontaminate products, otherwise pollutant loads to agricultural soils might increase. P recovery to the extent of 60-85 % of P in WWTPs influent can be achieved by savings/costs of -0.8 to +4.7 EUR inhabitant-1 yr-1 in addition to current cost of the wastewater treatment/sludge disposal system. Key factors to be considered for costs are the choice of recovery process, revenues from products, and the use of existing incineration infrastructure. P recovery can lead to the reduction of greenhouse gas emissions in Austria if nitrous oxide emissions from sludge incineration are limited and efficient heat utilization strategies are implemented. There is a trade-off in terms of environmental and economic costs in choosing a more centralized or decentralized mono-incineration strategy.
Subject(s)
Phosphorus , Recycling , Sewage , Austria , Wastewater/chemistry , Waste Disposal, Fluid/methods , Metals, HeavyABSTRACT
Decreased nicotinamide adenine dinucleotide (NAD+) levels contribute to various pathologies such as ageing, diabetes, heart failure and ischemia-reperfusion injury (IRI). Nicotinamide riboside (NR) has emerged as a promising therapeutic NAD+ precursor due to efficient NAD+ elevation and was recently shown to be the only agent able to reduce cardiac IRI in models employing clinically relevant anesthesia. However, through which metabolic pathway(s) NR mediates IRI protection remains unknown. Furthermore, the influence of insulin, a known modulator of cardioprotective efficacy, on the protective effects of NR has not been investigated. Here, we used the isolated mouse heart allowing cardiac metabolic control to investigate: (1) whether NR can protect the isolated heart against IRI, (2) the metabolic pathways underlying NR-mediated protection, and (3) whether insulin abrogates NR protection. NR protection against cardiac IRI and effects on metabolic pathways employing metabolomics for determination of changes in metabolic intermediates, and 13C-glucose fluxomics for determination of metabolic pathway activities (glycolysis, pentose phosphate pathway (PPP) and mitochondrial/tricarboxylic acid cycle (TCA cycle) activities), were examined in isolated C57BL/6N mouse hearts perfused with either (a) glucose + fatty acids (FA) ("mild glycolysis group"), (b) lactate + pyruvate + FA ("no glycolysis group"), or (c) glucose + FA + insulin ("high glycolysis group"). NR increased cardiac NAD+ in all three metabolic groups. In glucose + FA perfused hearts, NR reduced IR injury, increased glycolytic intermediate phosphoenolpyruvate (PEP), TCA intermediate succinate and PPP intermediates ribose-5P (R5P) / sedoheptulose-7P (S7P), and was associated with activated glycolysis, without changes in TCA cycle or PPP activities. In the "no glycolysis" hearts, NR protection was lost, whereas NR still increased S7P. In the insulin hearts, glycolysis was largely accelerated, and NR protection abrogated. NR still increased PPP intermediates, with now high 13C-labeling of S7P, but NR was unable to increase metabolic pathway activities, including glycolysis. Protection by NR against IRI is only present in hearts with low glycolysis, and is associated with activation of glycolysis. When activation of glycolysis was prevented, through either examining "no glycolysis" hearts or "high glycolysis" hearts, NR protection was abolished. The data suggest that NR's acute cardioprotective effects are mediated through glycolysis activation and are lost in the presence of insulin because of already elevated glycolysis.
Subject(s)
Glycolysis , Insulin , Mice, Inbred C57BL , Myocardial Reperfusion Injury , Niacinamide , Pyridinium Compounds , Animals , Pyridinium Compounds/pharmacology , Glycolysis/drug effects , Insulin/metabolism , Myocardial Reperfusion Injury/metabolism , Myocardial Reperfusion Injury/prevention & control , Niacinamide/pharmacology , Niacinamide/analogs & derivatives , Male , Myocardium/metabolism , Mice , Isolated Heart Preparation , Metabolomics , NAD/metabolism , Disease Models, Animal , Citric Acid Cycle/drug effectsABSTRACT
We use photoemission electron microscopy to measure the ferroelastic twin wall angles at the surface of CaTiO_{3} (001) and deduce the strain ordering. We analyze the angular dependence of the photoelectron emission from different domain surfaces, each with its own characteristic tilt angle in the factory rooflike topography. By considering the surface topography as a field perturbation, the offset in the photoemission threshold can be directly related to the tilt angles. With knowledge of the symmetry allowed twin walls we quantify the twin angles between 179.1° to 180.8°.
ABSTRACT
High-order harmonic generation (HHG) provides scalable sources of coherent extreme ultraviolet radiation with pulse duration down to the attosecond time scale. Efficient HHG requires the constructive interplay between microscopic and macroscopic effects in the generation volume, which can be achieved over a large range of experimental parameters from the driving field properties to those of the generating medium. Here, we present a systematic study of the harmonic yield as a function of gas pressure and medium length. Two regimes for optimum yield are identified, supporting the predictions of a recently proposed analytical model. Our observations are independent on the focusing geometry and, to a large extent, on the pulse duration and laser intensity, providing a versatile approach to HHG optimization.
ABSTRACT
A two-dimensional imaging spin-filter for photo-emission electron microscopy is described. The spin-filter is capable of imaging the electron spin polarization of either real space or momentum space electron distributions. As a scattering target either Au/Ir(001) comes into use, where spin sensitivity results from using spin-orbit scattering or Fe(001)-p(1×1)O that exploits exchange interaction. Both scattering targets were characterized with respect to their working points and Sherman function in a separate setup. Spin-polarization images of secondary electrons from the magnetic domains of a poly-crystalline iron sample are shown using both scattering targets. Images with a spin-filter using Au/Ir(001) show more than 104 discrete detection channels which increases the effective two-dimensional figure-of-merit (FoM) of this spin-filter by four orders of magnitude compared to single-channel spin detectors. Using the exchange scattering target two spin-components have been imaged for the first time. A method to detect all three spin-components is also outlined.
ABSTRACT
Resident cardiac macrophages (rcMACs) are among the most abundant immune cells in the heart. Plasticity and activation are hallmarks of rcMACs in response to changes in the microenvironment, which is essential for in vitro experimentation. The in vivo investigation is confounded by the infiltration of other cells hindering direct studies of rcMACs. As a tool to investigate rcMACs, we applied the ex vivo model of living myocardial slices (LMS). LMS are ultrathin ex vivo multicellular cardiac preparations in which the circulatory network is interrupted. The absence of infiltration in this model enables the investigation of the rcMACs response to immunomodulatory and mechanical stimulations. Such conditions were generated by applying interferon-gamma (IFN-γ) or interleukine-4 (IL-4) and altering the preload of cultured LMS, respectively. The immunomodulatory stimulation of the LMS induced alterations of the gene expression pattern without affecting tissue contractility. Following 24 h culture, low input RNA sequencing of rcMACs isolated from LMS was used for gene ontology analysis. Reducing the tissue stretch (unloading) of LMS altered the gene ontology clusters of isolated rcMACs with intermediate semantic similarity to IFN-γ triggered reaction. Through the overlap of genes affected by IFN-γ and unloading, we identified Allograft inflammatory factor 1 (AIF-1) as a potential marker gene for inflammation of rcMACs as significantly altered in whole immunomodulated LMS. MicroRNAs associated with the transcriptomic changes of rcMACs in unloaded LMS were identified in silico. Here, we demonstrate the approach of LMS to understand load-triggered cardiac inflammation and, thus, identify potential translationally important therapeutic targets.
Subject(s)
Heart , Myocardium , Humans , Macrophages , Interferon-gamma , InflammationABSTRACT
BACKGROUND AND PURPOSE: Photon-counting detector CT is a new technology with a limiting spatial resolution of ≤150 µm. In vivo comparisons between photon-counting detector CT and conventional energy-integrating detector CT are needed to determine the clinical impact of photon counting-detector CT in temporal bone imaging. MATERIALS AND METHODS: Prospectively recruited patients underwent temporal bone CT examinations on an investigational photon-counting detector CT system after clinically indicated temporal bone energy-integrating detector CT. Photon-counting detector CT images were obtained at an average 31% lower dose compared with those obtained on the energy-integrating detector CT scanner. Reconstructed images were evaluated in axial, coronal, and Pöschl planes using the smallest available section thickness on each system (0.4 mm on energy-integrating detector CT; 0.2 mm on photon-counting detector CT). Two blinded neuroradiologists compared images side-by-side and scored them using a 5-point Likert scale. A post hoc reassignment of readers' scores was performed so that the scores reflected photon-counting detector CT performance relative to energy-integrating detector CT. RESULTS: Thirteen patients were enrolled, resulting in 26 image sets (left and right sides). The average patient age was 63.6 [SD, 13.4] years; 7 were women. Images from the photon-counting detector CT scanner were significantly preferred by the readers in all reconstructed planes (P < .001). Photon-counting detector CT was rated superior for the evaluation of all individual anatomic structures, with the oval window (4.79) and incudostapedial joint (4.75) receiving the highest scores on a Likert scale of 1-5. CONCLUSIONS: Temporal bone CT images obtained on a photon-counting detector CT scanner were rated as having superior spatial resolution and better critical structure visualization than those obtained on a conventional energy-integrating detector scanner, even with a substantial dose reduction.
Subject(s)
Photons , Tomography, X-Ray Computed , Female , Humans , Middle Aged , Phantoms, Imaging , Radiation Dosage , Temporal Bone/diagnostic imaging , Tomography, X-Ray Computed/methodsABSTRACT
BACKGROUND: Hypophosphatasia (HPP) is a genetic disorder caused by one or more mutations in the alkaline phosphatase (ALP) gene, responsible for encoding tissue-specific ALP and for the mineralization process. OBJECTIVE: Identification of the prevalence of HPP in rheumatology patients. MATERIAL AND METHODS: Medical records of all adult rheumatology patients with pathologically low total ALP levels (<35â¯U/L) treated in the Department of Rheumatology at the Clinic of Internal Medicine III, University Hospital Bonn between January 2017 and June 2019, were retrospectively examined for clinical signs as well as for results of genetic tests for HPP. RESULTS: In 60 out of 2289 patients (2.62%) pathologically low ALP levels were detected. Of these 30 (1.31%) were found to have persistently low ALP levels. Genetic testing for ALP gene mutations was performed in 19 of these 30 patients and 7 of the 19 patients (36.84%) had HPP signs (insufficiency fractures, or bad dental status since childhood), all with pathologic ALP mutations. Of these patients 3 (15.78%) each had a history of insufficiency fracture with normal bone densitometry. Overall, 13 out of the 19 patients (68.42%) had mutations in the ALP gene. Interestingly, no association with chondrocalcinosis was detected in any of the patients. CONCLUSION: The HPP seems to be an underdiagnosed disease with a higher proportion of affected rheumatology patients. Therefore, future studies should aim to develop a diagnostic protocol in the clinical practice.
Subject(s)
Hypophosphatasia , Rheumatic Diseases , Adult , Alkaline Phosphatase/genetics , Humans , Hypophosphatasia/diagnosis , Hypophosphatasia/epidemiology , Hypophosphatasia/genetics , Mutation , Prevalence , Retrospective Studies , Rheumatic Diseases/complicationsABSTRACT
The use of medicinal zinc oxide (ZnO) in post-weaning diets must be phased out in the European Union by 2022, resulting in urgent needs for alternative strategies to prevent diarrhea in pigs. The objective of this study was to test the effect of four different dietary protein strategies with different amino acid profiles on diarrhea frequency and pig performance as alternative diet plans when medicinal ZnO was will be excluded from the diet. A total of 6â¯800 Duroc x (Danish Landrace x Yorkshire) pigs, weaned around 28â¯days of age, were randomly assigned by sex and size to six dietary treatments. The treatments were; standard CP levels (191, 184, 184â¯g/kg CP) and allocated 2â¯500â¯ppm ZnO in phase 1 (PCâ¯=â¯positive control), standard CP levels (191, 184, 184â¯g/kg CP) and no added ZnO in phase 1 (NCâ¯=â¯negative control), CP levels of 166, 184, 184â¯g/kg (LSSâ¯=â¯low-standard-standard), CP levels of 166, 162, 192â¯g/kg (LLHâ¯=â¯low-low-high), CP levels of 140, 193, 192â¯g/kg (VHHâ¯=â¯very low-high-high), and lastly 140, 174, 192â¯g/kg CP levels (VMHâ¯=â¯very low-medium-high). The pigs entered the trial at ~7â¯kg BW and exited at ~30â¯kg BW. As expected, the PC treatment resulted in 42% fewer diarrhea pen treatments in the total trial period compared to the NC group (Pâ¯<â¯0.05), whereas both PC and LLH had fewer diarrhea treatment days per pig compared to NC pigs (Pâ¯<â¯0.05). Additionally, at the point of treatment, the NC pens had 33% fecal floor samples positive for pathogens, compared to 80% samples positive for pathogens in the PC pens. This suggests that ZnO has a particular positive effect on non-infectious diarrhea without bacterial involvement. A reduction in dietary CP levels in phase 1 led to a reduced average daily gain (ADG) in LLH and VMH pigs and a poorer feed conversion ratio (FCR) in VHH pigs during the overall study period compared to the NC pigs (Pâ¯<â¯0.05). Conclusively, a diet with low CP levels from weaning to about 15â¯kg BW had a reducing effect on diarrhea, but decreased ADG without affecting the FCR.
Subject(s)
Zinc Oxide , Animal Feed/analysis , Animals , Diarrhea/drug therapy , Diarrhea/prevention & control , Diarrhea/veterinary , Diet/veterinary , Diet, Protein-Restricted/veterinary , Dietary Supplements , Swine , WeaningABSTRACT
OBJECTIVES: The aim of a pilot study was to clarify the question of whether mouth opening restrictions in patients with PTSD by means of splint therapy (st) show long-term therapeutic effects in the case of functional disorders. MATERIAL AND METHODS: In 31 of 36 inpatients (soldiers, average age 37.1 ± 7.3 years, 26.7 ± 2.1 teeth) with confirmed posttraumatic stress disorder, chronic pain intensity > 6 (visual analogue scale 0 to 10), the mouth opening was determined, and the functional status (RDC-TMD) was recorded. All participants received a splint that was worn at night. A control of the therapeutic effect of the splint occurred after 6 weeks, 3, 6, and 12 months. RESULTS: The mouth opening initially had an average of 30.9 ± 6.5 mm (median 31 mm). The pain intensity (PI) was reported to be on average VAS 8.3 ± 0.9, the chronic degree of pain according to von Korff was 3.9 ± 03. Six weeks after the st (n = 31), the average mouth opening was 49.5 ± 6.3 mm (median 51.5). PI was given as VAS 2.3 ± 1.1 on average. After 3, 6, and 12 months, 24, 15, and 14 subjects could be interviewed regarding PI. Based on the last examination date of all subjects, the average PI was given as 1.1 ± 0.9 (median 1). CONCLUSION: The presented data show that the therapeutic short-term results achieved by means of a splint remain valid on the long term despite continued PTSD. CLINICAL RELEVANCE: The presented study shows that patients will benefit in the long term from a splint and remain symptom-free, even if this mental illness persists.
Subject(s)
Occlusal Splints , Stress Disorders, Post-Traumatic/therapy , Adult , Humans , Military Personnel , Pilot Projects , Treatment OutcomeABSTRACT
BACKGROUND: The noble gas helium induces cardio- and neuroprotection by pre- and post-conditioning. We investigated the effects of helium pre- and post-conditioning on the brain and heart in a rat resuscitation model. METHODS: After approval by the Animal Care Committee, 96 Wistar rats underwent cardiac arrest for 6 min induced by ventricular fibrillation. Animals received 70% helium and 30% oxygen for 5 min before cardiac arrest and for 30 min after restoration of spontaneous circulation (ROSC). Control animals received 70% nitrogen and 30% oxygen. Hearts and brains were excised after 2, 4 h or 7 days. Neurological degeneration was evaluated using TUNEL and Nissl staining in the hippocampal CA-1 sector. Cognitive function after 7 days was detected with the tape removal test. Molecular targets were measured by infrared western blot. Data are shown as median [Interquartile range]. RESULTS: Helium treatment resulted in significantly less apoptosis (TUNEL positive cells/100 pixel 73.5 [60.3-78.6] vs.78.2 [70.4-92.9] P = 0.023). Changes in Caveolin-3 expression in the membrane fraction and Hexokinase-II in the mitochondrial fraction were observed in the heart. Caveolin-1 expression of treated animals significantly differed from control animals in the membrane fraction of the heart and brain after ROSC. CONCLUSION: Treatment with helium reduced apoptosis in our resuscitation model. Differential expression levels of Caveolin-1, Caveolin-3 and Hexokinase II in the heart were found after helium pre- and post-conditioning. No beneficial effects were seen on neurofunctional outcome.
Subject(s)
Brain/drug effects , Heart Arrest/physiopathology , Heart/drug effects , Helium/pharmacology , Animals , Apoptosis/drug effects , Blood Circulation , Brain/physiopathology , Cardiopulmonary Resuscitation , Caveolin 1/analysis , Caveolin 3/analysis , Heart/physiopathology , Male , Neuroprotective Agents/pharmacology , Rats , Rats, WistarABSTRACT
BACKGROUND: Obesity induces significant changes in lipid mediators, however, the extent to which these changes persist after weight loss has not been investigated. SUBJECTS/METHODS: We fed C57BL6 mice a high-fat diet to generate obesity and then switched the diet to a lower-fat diet to induce weight loss. We performed a comprehensive metabolic profiling of lipid mediators including oxylipins, endocannabinoids, sphingosines and ceramides in key metabolic tissues (including adipose, liver, muscle and hypothalamus) and plasma. RESULTS: We found that changes induced by obesity were largely reversible in most metabolic tissues but the adipose tissue retained a persistent obese metabolic signature. Prostaglandin signaling was perturbed in the obese state and lasting increases in PGD2, and downstream metabolites 15-deoxy PGJ2 and delta-12-PGJ2 were observed after weight loss. Furthermore expression of the enzyme responsible for PGD2 synthesis (hematopoietic prostaglandin D synthase, HPGDS) was increased in obese adipose tissues and remained high after weight loss. We found that inhibition of HPGDS over the course of 5 days resulted in decreased food intake in mice. Increased HPGDS expression was also observed in human adipose tissues obtained from obese compared with lean individuals. We then measured circulating levels of PGD2 in obese patients before and after weight loss and found that while elevated relative to lean subjects, levels of this metabolite did not decrease after significant weight loss. CONCLUSIONS: These results suggest that lasting changes in lipid mediators induced by obesity, still present after weight loss, may play a role in the biological drive to regain weight.
Subject(s)
Lipid Metabolism/physiology , Metabolome/physiology , Obesity/metabolism , Weight Loss/physiology , Adipocytes , Animals , Body Weight/physiology , Cells, Cultured , Diet, Fat-Restricted , Diet, High-Fat , Eating/physiology , Humans , Male , Mice , Mice, Inbred C57BL , Organ Specificity/physiologyABSTRACT
Epinephelus adscensionis sampled from Ascension Island, South Atlantic Ocean, exhibits distinct life-history traits, including larger maximum size and size at sexual maturity than previous studies have demonstrated for this species in other locations. Otolith analysis yielded a maximum estimated age of 25 years, with calculated von Bertalanffy growth parameters of: L∞ = 55·14, K = 0·19, t0 = -0·88. Monthly gonad staging and analysis of gonad-somatic index (IG ) provide evidence for spawning from July to November with an IG peak in August (austral winter), during which time somatic growth is also suppressed. Observed patterns of sexual development were supportive of protogyny, although further work is needed to confirm this. Mean size at sexual maturity for females was 28·9 cm total length (LT ; 95% C.I. 27·1-30·7 cm) and no females were found >12 years and 48·0 cm LT , whereas all confirmed males sampled were mature, >35·1 cm LT with an age range from 3 to 18 years. The modelled size at which 50% of individuals were male was 41·8 cm (95% C.I. 40·4-43·2 cm). As far as is known, this study represents the first comprehensive investigation into the growth and reproduction of E. adscensionis at its type locality of Ascension Island and suggests that the population may be affected less by fisheries than elsewhere in its range. Nevertheless, improved regulation of the recreational fishery and sustained monitoring of abundance, length frequencies and life-history parameters are needed to inform long-term management measures, which could include the creation of marine reserves, size or temporal catch limits and stricter export controls.
Subject(s)
Bass/physiology , Sexual Development , Animals , Atlantic Ocean , Bass/anatomy & histology , Bass/growth & development , Body Size , Female , Fisheries , Gonads/anatomy & histology , Gonads/growth & development , Islands , Male , Otolithic Membrane/anatomy & histology , Reproduction , SeasonsABSTRACT
Enterotoxigenic E. coli (ETEC) are a major cause of diarrhoea in weaned pigs. The objective of this study was to evaluate the agreement at pen level among three different diagnostic approaches for the detection of ETEC in groups of nursery pigs with diarrhoea. The diagnostic approaches used were: bacterial culturing of faecal samples from three pigs (per pen) with clinical diarrhoea and subsequent testing for virulence genes in E. coli isolates; bacterial culturing of pen floor samples and subsequent testing for virulence genes in E. coli isolates; qPCR testing of pen floor samples in order to determine the quantity of F18 and F4 genes. The study was carried out in three Danish pig herds and included 31 pens with a pen-level diarrhoea prevalence of > 25%, as well as samples from 93 diarrhoeic nursery pigs from these pens. All E. coli isolates were analysed by PCR and classified as ETEC when genes for one or more adhesin factors and one or more enterotoxins were detected. RESULTS: A total of 208 E. coli colonies from pig samples and 172 E. coli colonies from pen floor samples were isolated. Haemolytic activity was detected on blood agar plates in 111 (29.2%) of the 380 colonies that were isolated. The only adhesin factor detected in this study was F18. When comparing bacterial culture or qPCR testing of pen floor samples with detection of ETEC-positive diarrhoeic pigs by culture, agreement was found in 26 (83.9%, Kappa = 0.665) and 23 (74.2%, Kappa = 0.488) of the pens, respectively. Agreement was observed between the detection of ETEC by bacterial culture and qPCR in the same pen floor sample in 26 (83.9%, Kappa = 0.679) pens. CONCLUSION: We observed an acceptable agreement for the detection of ETEC-positive diarrhoeic nursery pigs in pen samples for both bacterial culture of pen floor samples and qPCR. This study showed that both bacterial culture and qPCR testing of pen floor samples can be used as a diagnostic approach for detecting groups of ETEC-positive diarrhoeic nursery pigs.
Subject(s)
Enterotoxigenic Escherichia coli/isolation & purification , Escherichia coli Infections/veterinary , Feces/microbiology , Polymerase Chain Reaction/veterinary , Swine Diseases/diagnosis , Animals , Diarrhea , Escherichia coli , Escherichia coli Infections/diagnosis , Floors and Floorcoverings , SwineABSTRACT
AIM: To determine the CO2 permeability (PCO2 ) of plasma membranes of cardiomyocytes. These cells were chosen because heart possesses the highest rate of O2 consumption/CO2 production in the body. METHODS: Cardiomyocytes were isolated from rat hearts using the Langendorff technique. Cardiomyocyte suspensions exhibited a vitality of 2-14% and were studied by the previously described mass spectrometric 18 O-exchange technique deriving PCO2 . We showed by mass spectrometry and by carbonic anhydrase (CA) staining that non-vital cardiomyocytes are free of CA and thus do not contribute to the mass spectrometric signal, which is determined exclusively by the fully functional vital cardiomyocytes. RESULTS: Lysed cardiomyocytes yielded an intracellular CA activity for vital cells of 5070; that is, the rate of CO2 hydration inside the cell is accelerated 5071-fold. Using this number, analyses of the mass spectrometric recordings from cardiomyocyte suspensions yield a PCO2 of 0.10 cm s-1 (SD ± 0.06, n = 15) at 37 °C. CONCLUSION: In comparison with the PCO2 of other cells, this value is quite high and about identical to that of the human red cell membrane. As no major protein CO2 channels such as aquaporins 1 and 4 are present in rat cardiac sarcolemma, the high PCO2 of this membrane is likely due to its low cholesterol content of about 0.2 (mol cholesterol)·(mol total membrane lipids)-1 . Previous work predicted a PCO2 of ≥0.1 cm s-1 from this level of cholesterol. We conclude that the low cholesterol establishes a PCO2 high enough to render the membrane resistance to CO2 diffusion almost negligible, even under conditions of maximal O2 consumption of the heart.
Subject(s)
Carbon Dioxide/metabolism , Carbonic Anhydrases/metabolism , Cell Membrane/physiology , Myocytes, Cardiac/metabolism , Animals , Bicarbonates/metabolism , Carbonic Anhydrases/genetics , Cell Membrane Permeability , Cells, Cultured , Cholesterol/pharmacology , Gene Expression Regulation, Enzymologic , Mass Spectrometry , Oxygen Consumption , Permeability , RatsABSTRACT
The electronic band structures of hexagonal ZnO and cubic ZnS, ZnSe, and ZnTe compounds are determined within hybrid-density-functional theory and quasiparticle calculations. It is found that the band-edge energies calculated on the [Formula: see text] (Zn chalcogenides) or GW (ZnO) level of theory agree well with experiment, while fully self-consistent QSGW calculations are required for the correct description of the Zn 3d bands. The quasiparticle band structures are used to calculate the linear response and second-harmonic-generation (SHG) spectra of the Zn-VI compounds. Excitonic effects in the optical absorption are accounted for within the Bethe-Salpeter approach. The calculated spectra are discussed in the context of previous experimental data and present SHG measurements for ZnO.
ABSTRACT
OBJECTIVES: The distribution of pathology in neurodegenerative disease can be predicted by the organizational characteristics of white matter in healthy brains. However, we have very little evidence for the impact these pathological changes have on brain function. Understanding any such link between structure and function is critical for understanding how underlying brain pathology influences the progressive behavioral changes associated with neurodegeneration. Here, we demonstrate such a link between structure and function in individuals with premanifest Huntington's. METHODS: Using diffusion tractography and resting state functional magnetic resonance imaging to characterize white matter organization and functional connectivity, we investigate whether characteristic patterns of white matter organization in the healthy human brain shape the changes in functional coupling between brain regions in premanifest Huntington's disease. RESULTS: We find changes in functional connectivity in premanifest Huntington's disease that link directly to underlying patterns of white matter organization in healthy brains. Specifically, brain areas with strong structural connectivity show decreases in functional connectivity in premanifest Huntington's disease relative to controls, while regions with weak structural connectivity show increases in functional connectivity. Furthermore, we identify a pattern of dissociation in the strongest functional connections between anterior and posterior brain regions such that anterior functional connectivity increases in strength in premanifest Huntington's disease, while posterior functional connectivity decreases. INTERPRETATION: Our findings demonstrate that organizational principles of white matter underlie changes in functional connectivity in premanifest Huntington's disease. Furthermore, we demonstrate functional antero-posterior dissociation that is in keeping with the caudo-rostral gradient of striatal pathology in HD.
ABSTRACT
Recent research efforts have progressively shifted towards preventative psychiatry and prognostic identification of individuals before disease onset. We describe the development of a serum biomarker test for the identification of individuals at risk of developing schizophrenia based on multiplex immunoassay profiling analysis of 957 serum samples. First, we conducted a meta-analysis of five independent cohorts of 127 first-onset drug-naive schizophrenia patients and 204 controls. Using least absolute shrinkage and selection operator regression, we identified an optimal panel of 26 biomarkers that best discriminated patients and controls. Next, we successfully validated this biomarker panel using two independent validation cohorts of 93 patients and 88 controls, which yielded an area under the curve (AUC) of 0.97 (0.95-1.00) for schizophrenia detection. Finally, we tested its predictive performance for identifying patients before onset of psychosis using two cohorts of 445 pre-onset or at-risk individuals. The predictive performance achieved by the panel was excellent for identifying USA military personnel (AUC: 0.90 (0.86-0.95)) and help-seeking prodromal individuals (AUC: 0.82 (0.71-0.93)) who developed schizophrenia up to 2 years after baseline sampling. The performance increased further using the latter cohort following the incorporation of CAARMS (Comprehensive Assessment of At-Risk Mental State) positive subscale symptom scores into the model (AUC: 0.90 (0.82-0.98)). The current findings may represent the first successful step towards a test that could address the clinical need for early intervention in psychiatry. Further developments of a combined molecular/symptom-based test will aid clinicians in the identification of vulnerable patients early in the disease process, allowing more effective therapeutic intervention before overt disease onset.