Lattice-like structures known as perineuronal nets (PNNs) are key components of the extracellular matrix (ECM). Once fully crystallized by adulthood, they are largely stable throughout life. Contrary ...to previous reports that PNNs inhibit processes involving plasticity, here we report that the dynamic regulation of PNN expression in the adult auditory cortex is vital for fear learning and consolidation in response to pure tones. Specifically, after first confirming the necessity of auditory cortical activity for fear learning and consolidation, we observed that mRNA levels of key proteoglycan components of PNNs were enhanced 4 hr after fear conditioning but were no longer different from the control groups 24 hr later. A similar pattern of regulation was observed in numbers of cells surrounded by PNNs and area occupied by them in the auditory cortex. Finally, the removal of auditory cortex PNNs resulted in a deficit in fear learning and consolidation.
•Auditory cortex activity after auditory fear conditioning is necessary for learning•Removal of PNNs from the auditory cortex of adult mice decreases fear learning•Regrowth of PNNs restores the ability to learn new memories•Temporal regulation of PNNs occurs in response to fear learning
Banerjee et al., 2017 show that key components of the extracellular matrix, perineuronal nets (PNNs) in the auditory cortex of adult mice, are necessary for consolidation of fear learning in response to Pavlovian fear conditioning.
Post-traumatic stress disorder (PTSD) is a highly debilitating stress and anxiety-related disorder that occurs in response to specific trauma or abuse. Genetic risk factors may account for up to ...30–40% of the heritability of PTSD. Understanding the gene pathways that are associated with PTSD, and how those genes interact with the fear and stress circuitry to mediate risk and resilience for PTSD will enable the development of targeted therapies to prevent the occurrence of or decrease the severity of this complex multi-gene disorder. This review will summarize recent research on genetic approaches to understanding PTSD risk and resilience in human populations, including candidate genes and their epigenetic modifications, genome-wide association studies and neural imaging genetics approaches. Despite challenges faced within this field of study such as inconsistent results and replications, genetic approaches still offer exciting opportunities for the identification and development of novel therapeutic targets and therapies in the future.
Assessment of voltage unbalance von Jouanne, A.; Banerjee, B.
IEEE transactions on power delivery,
10/2001, Volume:
16, Issue:
4
Journal Article
Peer reviewed
This paper endeavors to present a comprehensive summary of the causes and effects of voltage unbalance and to discuss related standards, definitions and mitigation techniques. Several causes of ...voltage unbalance on the power system and in industrial facilities are presented as well as the resulting adverse effects on the system and on equipment such as induction motors and power electronic converters and drives. Standards addressing voltage unbalance are discussed and clarified, and several mitigation techniques are suggested to correct voltage unbalance problems. This paper makes apparent the importance of identifying potential unbalance problems for the benefit of both the utility and customer.
UCP1 and PRDM16 genes, primarily involved in browning of adipose tissue that can affect lipid metabolism are also associated with diabetes risk. Therefore, we planned to study the adipose tissue ...expression of UCP1 and PRDM 16 genes in subjects with glucose intolerance to find out its association with postprandial triglyceride (PPTg) measures and T2DM.
A total of 30 subjects were recruited in three groups i.e., NGT, prediabetes and T2DM (NDDM + known T2DM) who were matched for age, sex and BMI. An 8-hour standardized fat challenge test was performed to study lipemic responses. UCP1 and PRDM16 genes quantification in adipose tissue was performed by real-time PCR followed by SDS PAGE.
UCP1 gene expression in SAT was significantly lower in T2DM and prediabetes as compared to NGT group while PRDM16 gene expression was significantly lower in T2DM group as compared to NGT group. UCP1 gene expression correlated with PPTg measures as well as with glycaemic measures while PRDM16 gene expression correlated with glycaemic measures only.
This study found downregulation of PRDM16 and UCP1 gene expression in SAT in subjects with glucose intolerance. The association of UCP1 gene expression with PPTg dysmetabolism may contribute to greater predisposition to T2DM.
Stress is known to precipitate neuropsychiatric diseases, and depending upon its nature and intensity it can also influence the functioning of the immune system. Melatonin (N-acetyl-5-methoxy ...tryptamine) a pineal gland hormone and potent antioxidant is known to protect against many diseases. Effect of melatonin in stress-induced neuro-immunomodulation is not well elucidated. Therefore in the present study, the protective effects of melatonin were evaluated in restraint stress (RS)-induced behavioral and immunological changes in rats. RS for 1 h significantly reduces (i) percentage of open-arm entries and (ii) percentage of time spent on open-arm in elevated plus maze (EPM) test parameters (p < 0.01) and significant increase in MDA levels in brain homogenate when compared to non-RS control groups (p < 0.05). In immunological studies, both humoral and cell-mediated immune responses to antigen were significantly suppressed by RS for 1 h for 5 consecutive days, as evidenced by significant reduction in (i) anti-SRBC antibody titre, (ii) PFC counts, (iii) percentage change in paw volume, and (iv) Th
1
(IFN-γ) and Th
2
(IL-4) cytokine levels (p < 0.001 in all parameters). These RS-induced immunological changes were associated with significantly increased lipid peroxidation (MDA) levels in serum and significantly decreased activity of (i) SOD, (ii) CAT, and (iii) GSH levels in RS (X5)-exposed group (p < 0.02). Pretreatment with melatonin (10, 50, and 100 mg/kg) significantly reversed these RS-induced changes in EPM test parameters and humoral and cell-mediated immunological parameters, as well as oxidative stress markers in a dose-dependent manner by differential degrees (p < 0.001). Results are strongly suggestive of the involvement of free radicals during stress-induced neurobehavioral and immunological changes. These changes were significantly restored by melatonin pretreatment. We can conclude that melatonin may have a protective role during such stress-induced neuro-immunomodulation.
A simple, facile, and convenient practical method for one‐pot synthesis of pharmaceutically interesting diverse kind of pyran annulated heterocycles such as 4H‐pyrano3,2‐ccoumarins, ...4H‐pyrano3,2‐c‐α‐pyrones, 5,6,7,8‐tetrahydro‐5‐oxo‐4H‐chromenes and benzoh‐4H‐chromenes in the presence of ammonium or sodium formate as catalyst via three‐component condensation reaction of aromatic aldehydes, malononitrile, and C−H activated acidic compounds in aqueous ethanol has been developed mostly at room temperature. The salient features of the present method are mild reaction conditions, good to excellent yields, high atom economy, environmentally benign, easy isolation of products, no column chromatographic separation and reusability of reaction media.
Highlights ► We highlight new therapies for fear and anxiety from the connectome to epigenome. ► Optogenetic approaches will potentially be useful to treat fear and anxiety. ► Drugs that modify the ...epigenetic landscape hold therapeutic promise. ► Lifestyle interventions (e.g. diet, exercise, meditation) should be considered. ► Combinatorial approaches hold the most promise to alleviate fear and anxiety.
Abstract
We present the results of extensive modelling of the spectral energy distributions (SEDs) of the closest blazar (z = 0.031) Markarian 421 (Mrk 421) during a giant outburst in 2010 February. ...The source underwent rapid flux variations in both X-rays and very high energy (VHE) gamma rays as it evolved from a low-flux state on 2010 February 13–15 to a high-flux state on 2010 February 17. During this period, the source exhibited significant spectral hardening from X-rays to VHE gamma rays while exhibiting a ‘harder when brighter’ behaviour in these energy bands. We reproduce the broad-band SED using a time-dependent multizone leptonic jet model with radiation feedback. We find that an injection of the leptonic particle population with a single power-law energy distribution at shock fronts followed by energy losses in an inhomogeneous emission region is suitable for explaining the evolution of Mrk 421 from low- to high-flux state in 2010 February. The spectral states are successfully reproduced by a combination of a few key physical parameters, such as the maximum and minimum cut-offs and power-law slope of the electron injection energies, magnetic field strength, and bulk Lorentz factor of the emission region. The simulated light curves and spectral evolution of Mrk 421 during this period imply an almost linear correlation between X-ray flux at 1–10 keV energies and VHE gamma-ray flux above 200 GeV, as has been previously exhibited by this source. Through this study, a general trend that has emerged for the role of physical parameters is that, as the flare evolves from a low- to a high-flux state, higher bulk kinetic energy is injected into the system with a harder particle population and a lower magnetic field strength.
ABSTRACT
The evolution of the spectral energy distribution during flares constrains models of particle acceleration in blazar jets. The archetypical blazar BL Lacertae provided a unique opportunity ...to study spectral variations during an extended strong flaring episode from 2020 to 2021. During its brightest γ-ray state, the observed flux (0.1–300 GeV) reached up to $2.15\, \times \, 10^{-5}\, \rm {ph\, cm^{-2}\, s^{-1}}$, with sub-hour-scale variability. The synchrotron hump extended into the X-ray regime showing a minute-scale flare with an associated peak shift of inverse-Compton hump in γ-rays. In shock acceleration models, a high Doppler factor value >100 is required to explain the observed rapid variability, change of state, and γ-ray peak shift. Assuming particle acceleration in minijets produced by magnetic reconnection during flares, on the other hand, alleviates the constraint on required bulk Doppler factor. In such jet-in-jet models, observed spectral shift to higher energies (towards TeV regime) and simultaneous rapid variability arises from the accidental alignment of a magnetic plasmoid with the direction of the line of sight. We infer a magnetic field of ∼0.6 G in a reconnection region located at the edge of broad-line region (∼0.02 pc). The scenario is further supported by lognormal flux distribution arising from merging of plasmoids in reconnection region.
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