•Amla juice was spray dried into powder.•Effects of inlet temperature and maltodextrin level on amla powder were studied.•Inlet temperature significantly influenced TPC and DPPH activity of ...powder.•DPPH activity and TPC were significantly influenced by maltodextrin concentration.•Amla powder showed excellent WSI.
The effects of inlet temperatures of 125, 150, 175 and 200°C and maltodextrin levels at 3, 5, 7 and 9% on the physicochemical properties, total phenolic content (TPC) and 2,2-diphenyl picryl hydrazile (DPPH) scavenging activity of spray dried amla juice powder were studied. Moisture content and hygroscopicity of powder were significantly affected by inlet temperature and maltodextrin level. However, an increase in the level of maltodextrin did not significantly affect the bulk density and water solubility index (WSI). An increase in drying temperature and maltodextrin concentration decreased the free radical scavenging activity of the powder. Morphological study revealed that at higher inlet temperatures the spray dried powder had small sized particles that were densely packed. Spray dried amla juice powder made with 7% maltodextrin and processed at 175°C inlet temperature had less hygroscopicity, acceptable color and potent free radical scavenging activity.
Representatives from academia, industry, regulatory agencies, and patient groups convened in March 2019 with the primary goal of developing agreement on chronic HBV treatment endpoints to guide ...clinical trials aiming to ‘cure’ HBV. Agreement among the conference participants was reached on some key points. ‘Functional’ but not sterilising cure is achievable and should be defined as sustained HBsAg loss in addition to undetectable HBV DNA 6 months post-treatment. The primary endpoint of phase III trials should be functional cure; HBsAg loss in ≥30% of patients was suggested as an acceptable rate of response in these trials. Sustained virologic suppression (undetectable serum HBV DNA) without HBsAg loss 6 months after discontinuation of treatment would be an intermediate goal. Demonstrated validity for the prediction of sustained HBsAg loss was considered the most appropriate criterion for the approval of new HBV assays to determine efficacy endpoints. Clinical trials aimed at HBV functional cure should initially focus on patients with HBeAg-positive or negative chronic hepatitis, who are treatment-naïve or virally suppressed on nucleos(t)ide analogues. A hepatitis flare associated with an increase in bilirubin or international normalised ratio should prompt temporary or permanent cessation of an investigational treatment. New treatments must be as safe as existing nucleos(t)ide analogues. The primary endpoint for phase III trials for HDV coinfection should be undetectable serum HDV RNA 6 months after stopping treatment. On treatment HDV RNA suppression associated with normalisation of alanine aminotransferase is considered an intermediate goal. In conclusion, regarding HBV ‘functional cure’, the primary goal is sustained HBsAg loss with undetectable HBV DNA after completion of treatment and the intermediate goal is sustained undetectable HBV DNA without HBsAg loss after stopping treatment.
An increase in the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel conductance reduces input resistance, whereas the consequent increase in the inward h current depolarizes the ...membrane. This results in a delicate and unique conductance-current balance triggered by the expression of HCN channels. In this study, we employ experimentally constrained, morphologically realistic, conductance-based models of hippocampal neurons to explore certain aspects of this conductance-current balance. First, we found that the inclusion of an experimentally determined gradient in A-type K(+) conductance, but not in M-type K(+) conductance, tilts the HCN conductance-current balance heavily in favor of conductance, thereby exerting an overall restorative influence on neural excitability. Next, motivated by the well-established modulation of neuronal excitability by synaptically driven high-conductance states observed under in vivo conditions, we inserted thousands of excitatory and inhibitory synapses with different somatodendritic distributions. We measured the efficacy of HCN channels, independently and in conjunction with other channels, in altering resting membrane potential (RMP) and input resistance (Rin) when the neuron received randomized or rhythmic synaptic bombardments through variable numbers of synaptic inputs. We found that the impact of HCN channels on average RMP, Rin, firing frequency, and peak-to-peak voltage response was severely weakened under high-conductance states, with the impinging synaptic drive playing a dominant role in regulating these measurements. Our results suggest that the debate on the role of HCN channels in altering excitability should encompass physiological and pathophysiological neuronal states under in vivo conditions and the spatiotemporal interactions of HCN channels with other channels.
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•Resin and enzymatic hydrolysis combined with sonication is applied for the first time.•Sonication-assisted resin debittering results in a lowered level of bitterness.•Sonication ...markedly influenced the phytochemical properties of pomelo juice.•Sonication assisted enzymatic hydrolysis improved the flavor, chemical and phytochemical properties.•Significant improvement in enzymatic activities and degradation of naringin.
In the present study, sonication assisted debittering of pomelo fruit juice was carried out and the effect of sonication along with resin/enzyme on the chemical, phytochemical and volatile composition of juice was also investigated. The optimum conditions for sonication coupled debittering using resin were 50 kHz, 2 min, and 45 ℃ while 50 kHz, 60 min, and 60 ℃ were obtained for enzyme hydrolysis. Sonication treatment not only reduced the debittering time but also enhanced the adsorption and hydrolysis of naringin by 17% and 20% in resin and enzyme respectively. In addition, enzymatic activity was also improved and weakened C-O bonds in naringin. At the same time, sonication significantly affected the bioactive compounds of juice, chemical composition, and volatile compounds of juice. Flavor compounds including octanal, linalool, citral, and ethyl butyrate were enhanced by sonication-assisted enzymatic treated juice.
Degeneracy, the ability of multiple structural components to elicit the same characteristic functional properties, constitutes an elegant mechanism for achieving biological robustness. In this study, ...we sought electrophysiological signatures for the expression of ion‐channel degeneracy in the emergence of intrinsic properties of rat hippocampal granule cells. We measured the impact of four different ion‐channel subtypes—hyperpolarization‐activated cyclic‐nucleotide‐gated (HCN), barium‐sensitive inward rectifier potassium (Kir), tertiapin‐Q‐sensitive inward rectifier potassium, and persistent sodium (NaP) channels—on 21 functional measurements employing pharmacological agents, and report electrophysiological data on two characteristic signatures for the expression of ion‐channel degeneracy in granule cells. First, the blockade of a specific ion‐channel subtype altered several, but not all, functional measurements. Furthermore, any given functional measurement was altered by the blockade of many, but not all, ion‐channel subtypes. Second, the impact of blocking each ion‐channel subtype manifested neuron‐to‐neuron variability in the quantum of changes in the electrophysiological measurements. Specifically, we found that blocking HCN or Ba‐sensitive Kir channels enhanced action potential firing rate, but blockade of NaP channels reduced firing rate of granule cells. Subthreshold measures of granule cell intrinsic excitability (input resistance, temporal summation, and impedance amplitude) were enhanced by blockade of HCN or Ba‐sensitive Kir channels, but were not significantly altered by NaP channel blockade. We confirmed that the HCN and Ba‐sensitive Kir channels independently altered sub‐ and suprathreshold properties of granule cells through sequential application of pharmacological agents that blocked these channels. Finally, we found that none of the sub‐ or suprathreshold measurements of granule cells were significantly altered upon treatment with tertiapin‐Q. Together, the heterogeneous many‐to‐many mapping between ion channels and single‐neuron intrinsic properties emphasizes the need to account for ion‐channel degeneracy in cellular‐ and network‐scale physiology.
Bitterness and tartness are one of the crucial reasons for the poor commerciality of Pomelo fruits. The present study intends to optimize the process variables such as resin concentration (Amberlite ...IRA-400) (3–10 g), time exposure (10–60 s), and stirring speed (300–1000 rpm) for removal of naringin content and tartness using response surface methodology. All the independent variables have shown a significant effect on naringin content, titrable acidity, and vitamin C content of pomelo juice. The optimized process variables for debittering and deacidification were 3.27 g resin concentration, 60 s time and 1000 rpm stirring speed, and the naringin content and titrable acidity at these optimized conditions were 0.22 mg ml
−1
and 0.64% citric acid equivalent respectively. The treated juice under optimum conditions was analyzed for physicochemical properties where pH, clarity, and
L*
value of juice increased. In contrast, total soluble solids, vitamin C content, and
a*
value decreased slightly. The finding of present investigation will be helpful to improve the commercial acceptability of the sour variety of citrus fruit juice.
Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease. The progressive subtype of NAFLD or nonalcoholic steatohepatitits (NASH), may progress to cirrhosis ...and its complications. Unfortunately, accurate noninvasive modalities for diagnosing NASH and monitoring its progression are unavailable, necessitating a liver biopsy. Abdominal ultrasound (US) is widely used for screening asymptomatic patients with an incidental elevation of liver enzymes. However, US cannot detect small amounts of hepatic steatosis and cannot establish the diagnosis of NASH or stage of hepatic fibrosis. In this issue of AJG, a new radiologic scoring system has been reported to have excellent performance in diagnosing NAFLD and visceral obesity. However, the utility of this scoring system in establishing the diagnosis of NASH and hepatic fibrosis, has not been shown. Additionally, validity of this scoring system to other populations (i.e. obese) and in the setting of private practice must be proven. In summary, this study provides some valuable data regarding the utility of radiologic modalities in detecting hepatic steatosis and abdominal fat but still falls short in answering some important diagnostic and prognostic questions in NAFLD. The evolving field of diagnostic imaging for NAFLD holds promise. A combination of serum biomarkers and radiologic modalities may one day provide the best diagnostic approach for patients with NAFLD, and potentially replace the necessity for liver biopsy in most patients.
Plasticity in the brain is ubiquitous. How do neurons and networks encode new information and simultaneously maintain homeostasis in the face of such ubiquitous plasticity? Here, we unveil a form of ...neuronal plasticity in rat hippocampal granule cells, which is mediated by conjunctive changes in HCN, inward-rectifier potassium, and persistent sodium channels induced by theta-modulated burst firing, a behaviorally relevant activity pattern. Cooperation and competition among these simultaneous changes resulted in a unique physiological signature: sub-threshold excitability and temporal summation were reduced without significant changes in action potential firing, together indicating a concurrent enhancement of supra-threshold excitability. This form of intrinsic plasticity was dependent on calcium influx through L-type calcium channels and inositol trisphosphate receptors. These observations demonstrate that although brain plasticity is ubiquitous, strong systemic constraints govern simultaneous plasticity in multiple components—referred here as plasticity manifolds—thereby providing a cellular substrate for concomitant encoding and homeostasis in engram cells.
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•Theta-burst firing induces intrinsic plasticity in dentate gyrus granule cells•Changes in HCN, inward-rectifier K+, and persistent Na+ channels mediate plasticity•Ca2+ influx through L-type Ca2+ channels and InsP3 receptors governs plasticity•Intrinsic plasticity could drive encoding and homeostasis in engram cells
Biological sciences; Molecular physiology; Molecular neuroscience; Cellular neuroscience
Heterogeneities in biological neural circuits manifest in afferent connectivity as well as in local-circuit components such as neuronal excitability, neural structure and local synaptic strengths. ...The expression of adult neurogenesis in the dentate gyrus (DG) amplifies local-circuit heterogeneities and guides heterogeneities in afferent connectivity. How do neurons and their networks endowed with these distinct forms of heterogeneities respond to perturbations to individual ion channels, which are known to change under several physiological and pathophysiological conditions? We sequentially traversed the ion channels-neurons-network scales and assessed the impact of eliminating individual ion channels on conductance-based neuronal and network models endowed with disparate local-circuit and afferent heterogeneities. We found that many ion channels differentially contributed to specific neuronal or network measurements, and the elimination of any given ion channel altered several functional measurements. We then quantified the impact of ion-channel elimination on response decorrelation, a well-established metric to assess the ability of neurons in a network to convey complementary information, in DG networks endowed with different forms of heterogeneities. Notably, we found that networks constructed with structurally immature neurons exhibited functional robustness, manifesting as minimal changes in response decorrelation in the face of ion-channel elimination. Importantly, the average change in output correlation was dependent on the eliminated ion channel but invariant to input correlation. Our analyses suggest that neurogenesis-driven structural heterogeneities could assist the DG network in providing functional resilience to molecular perturbations.
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•Perturbations at one scale result in a cascading impact on physiology across scales.•Heterogeneous multi-scale models used to assess the impact of ion-channel deletion.•Mapping of structural components to functional outcomes is many-to-many.•Differential & variable impact of ion channel deletion on response decorrelation.•Neurogenesis-induced structural heterogeneity confers resilience to perturbations.
Therapeutic options for treatment of chronic hepatitis C have improved substantially since the approval of direct‐acting antiviral agents (DAAs). Several interferon (IFN)‐free or IFN‐ and ribavirin ...(RBV)‐free treatment regimens with shorter durations and improved efficacy and safety profiles are now available. The U.S. Food and Drug Administration (FDA) used several scientific approaches and regulatory mechanisms, such as (1) use of a “validated” surrogate (sustained virological response) for a primary endpoint, (2) shortening the time point for measuring the surrogate by 12 weeks, (3) use of historical controls when clinically appropriate, and (4) use of modeling when scientifically sound to extend treatment indications to subpopulations not fully evaluated in clinical trials, which had an impact on DAA development and subsequent approvals. This article intends to provide increased transparency about the FDA's scientific approaches and regulatory processes that supported drug development and marketing approval of DAAs for treatment of hepatitis C, a serious, life‐threatening infection. (Hepatology 2015;62:1298‐1303)
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