In order to explore new antifungal agrochemicals, we reported the synthesis of two series
5a-f
,
6
and
7a-f
,
8
of benzothiazole-appended bis-triazole derivative-based structural isomers using a ...molecular hybridization approach. The synthesized compounds were tested for fungal growth inhibition against the plant pathogen
Rhizoctonia solani
. All the synthesized compounds showed excellent antifungal activity in their minimum concentrations (10-0.62 μM). Among all the synthetics, compounds
5b
(ED
50
: 2.33 μM),
5f
(ED
50
: 0.96 μM), and
7f
(ED
50
: 1.48 μM) exerted a superior inhibitory effect in comparison to the commercially available fungicide, hexaconazole (ED
50
: 2.44 μM). The binding interactions of the active compounds
5f
,
7f
,
6
, and
8
within the active site of the sterol 14α-demethylase enzyme were studied with the help of molecular docking studies. The studies revealed that these hybrid pharmacophores could be used as an important intermediate to demonstrate new structural isomer-based fungicides.
Two novel series (
5a-f
,
6
and
7a-f
,
8
) of benzothiazole-appended bis-triazole derivative-based fungicides were prepared and their antifungal activity evaluated against plant pathogen
Rhizoctonia solani
. It was found that compound
5f
is the most potent fungicide.
The pituitary function is regulated by a complex system involving the hypothalamus and biological networks within the pituitary. Although the hormones secreted from the pituitary have been well ...studied, comprehensive analyses of the pituitary proteome are limited. Pituitary proteomics is a field of postgenomic research that is crucial to understand human health and pituitary diseases. In this context, we report here a systematic proteomic profiling of human anterior pituitary gland (adenohypophysis) using high-resolution Fourier transform mass spectrometry. A total of 2164 proteins were identified in this study, of which 105 proteins were identified for the first time compared with high-throughput proteomic-based studies from human pituitary glands. In addition, we identified 480 proteins with secretory potential and 187 N-terminally acetylated proteins. These are the first region-specific data that could serve as a vital resource for further investigations on the physiological role of the human anterior pituitary glands and the proteins secreted by them. We anticipate that the identification of previously unknown proteins in the present study will accelerate biomedical research to decipher their role in functioning of the human anterior pituitary gland and associated human diseases.
Examination of brain structural and functional abnormalities in amnestic mild cognitive impairment (aMCI) has the potential to enhance our understanding of the initial pathophysiological changes in ...dementia. We examined gray matter volumes and white matter microstructural integrity, as well as resting state functional connectivity (rsFC) in patients with aMCI (N = 48) in comparison to elderly cognitively healthy comparison subjects (N = 48). Brain volumetric comparisons were carried out using voxel-based morphometric analysis of T1-weighted images using the FMRIB Software Library. White matter microstructural integrity was examined using whole-brain tract-based spatial statistics analysis of fractional anisotropy maps generated from diffusion tensor imaging data. Finally, rsFC differences between the samples were examined by Multivariate Exploratory Linear Optimised Decomposition into Independent Components of the resting state functional magnetic resonance imaging time series, followed by between-group comparisons of selected networks using dual regression analysis. Patients with aMCI showed significant gray matter volumetric reductions in bilateral parahippocampal gyri as well as multiple other brain regions including frontal, temporal, and parietal cortices. Additionally, reduced rsFC in the anterior subdivision of the default mode network (DMN) and increased rsFC in the executive network were noted in the absence of demonstrable impairment of white matter microstructural integrity. We conclude that the demonstrable neuroimaging findings in aMCI include significant gray matter volumetric reductions in the fronto-temporo-parietal structures as well as resting state functional connectivity disturbances in DMN and executive network. These findings differentiate aMCI from healthy aging and could constitute the earliest demonstrable neuroimaging findings of incipient dementia.
Multi-domain cognitive impairment (CI) has been frequently described in patients with essential tremor (ET). However, the exact neuroanatomical basis for this impairment is uncertain. This study aims ...to ascertain the role of the hippocampal formation in cognitive impairment in ET. Forty patients with ET and 40 age, gender and education matched healthy controls (HC) were enrolled. Cognition was assessed using a structured neuropsychological battery and patients were categorized as ET with CI (ETCI) and ET without CI (ETNCI). Automatic segmentation of hippocampal subfields was performed using FreeSurfer 6.0. The obtained volumes were correlated with scores of neuropsychological tests. Significant atrophy of the left subiculum, CA4, granule-cell layer of dentate gyrus, right molecular layer, and hypertrophy of bilateral parasubiculum, right hippocampus-amygdala-transition-area, bilateral hippocampal tail (HT) and widening of right hippocampal fissure was observed in ET. Trends toward atrophy of right subiculum, and widening of left HF was also observed. Comparison of HC and ETCI revealed atrophy of right subiculum, hypertrophy of bilateral parasubiculum, HT, and widening of left HF. ETCI showed a trend toward widening of right HF. ETNCI had isolated left parasubicular hypertrophy and in comparison, to ETNCI the ETCI subgroup had atrophy of bilateral fimbria. Significant correlations were observed between the volumes of HT, HF, fimbria and scores of tests for executive function, working and verbal memory. Patients with ET have significant volumetric abnormalities of several hippocampal subfields and these abnormalities may be important contributors for some forms of cognitive impairment observed in ET.
Objective
Multiple system atrophy (MSA) is a neurodegenerative disorder with progressive motor and autonomic dysfunction. There is a paucity of information on the early neurostructural changes in ...MSA, especially its subtypes, MSA-P (patients with predominant parkinsonism) and MSA-C (patients with predominant cerebellar signs). This study investigates the abnormalities of grey matter (GM) and white matter (WM) in early MSA and its subtypes using multi-modal voxel-based analysis.
Materials and methods
Twenty-six patients with MSA with duration of symptoms ≤ 2.5 years (mean duration: 1.6 ±0.9 years) were assessed clinically and with 3T MRI. Voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) were performed to identify the structural changes in MSA and its subtypes. The GM changes and diffusion parameters of WM tracts were correlated with the clinical scores. The results were compared with MRI of 25 age- and gender-matched healthy controls.
Results
The early structural changes in MSA included GM loss of the cerebellum and subcallosal gyrus with widespread involvement of supratentorial and infratentorial WM fibres. In MSA-C, GM loss was limited to the cerebellum with WM changes predominantly affecting the infratentorial WM and association tracts. In contrast, MSA-P did not demonstrate any GM loss and the WM involvement was mainly supratentorial. There was no significant correlation between structural changes and clinical severity score.
Conclusion
In early MSA, WM microstructure was more affected than GM. These changes were greater in MSA-C than in MSA-P, suggesting variable deterioration in the subtypes of MSA.
Key Points
• Structural changes in early multiple system atrophy were evaluated using multi-modal neuroimaging.
• White matter was more affected than grey matter in early MSA.
• Clinical variables did not correlate with early structural changes.
Abstract Background Neuropsychological evaluation with advanced neuroimaging may be a useful tool to determine the anatomical substrates that play crucial role in freezing of gait (FOG) in patients ...with Parkinson's Disease (PD). Objectives To compare the cognitive profile and gray matter (GM) changes (using Voxel Based Morphometry – VBM) between patients with PD with and without FOG (FOG+ve and FOG−ve). Methods Seventeen FOG+ve (M:F = 11:6) and 21 FOG−ve (M:F = 11:10) were evaluated clinically and with a structured neuropsychological battery. All patients underwent 3 T MRI. In order to determine areas of GM atrophy, T1W volumetric MRI data of the two groups were compared using VBM and Statistical Parametric Mapping 8. Results The mean age of FOG+ve and FOG−ve patients were 56.9 ± 6.6 and 47.4 ± 9.1 years respectively. There was no significant difference in the duration (6.0 ± 4.9 vs 5.2 ± 3.5 years, p < 0.05) and stage of PD (Hoehn & Yahr stage: 1.96 ± 0.53 vs 1.78 ± 0.37) between the two groups. Compared to the FOG−ve group, the FOG+ve group had (i) significant impairment in memory, attention, executive and visuospatial functions on neuropsychological tests, and (ii) significant GM atrophy in the right cerebellum (pyramis, declive), left cerebrum (Brodmann area (BA) 21 and 22) and right cerebrum (BA 10 and 6) on VBM analysis. Conclusions The FOG+ve group showed widespread involvement of cognition localizing to frontal, temporal (especially left) and parietal areas. VBM analysis showed significant GM atrophy in FOG+ve group in left temporal, right frontal areas (coinciding with that observed in neuropsychological tests) and significant involvement of right cerebellum.
This paper reports a new addition to the national bumblebee fauna of the Indian Himalayas. The newly recorded species viz., Bombus cryptarum (Fabricius, 1775) (Hymenoptera, Apidae) is fully described ...from the Gurez Valley (Jammu and Kashmir) and Panamik (Ladakh) in the Western Himalayan range. Males of the B. cryptarum have thoracic dorsum and T2 lemon yellow without black hairs. Gonostylus with the anterior apical process with long hairs and penis valve greatly broadened and flared outwards. With the addition of a new record, the Indian Himalayan region is now represented by 57 species of bumblebees. The species diagnosis, current distributional range, and host plants of this species are also provided.
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•The mPEG-b-PCL copolymer and CTAB as steric stabilizer was used to develop APMs.•The design of APMs were optimized by BBD using DoE software.•The optimized APMs were characterized ...using various techniques.•The dissolution of Gly in APMs was increased by 1.95-folds while sustained the release of VA by 1.2-folds.•The oral bioavailability of Gly and VA was increased by 868 % and 87 % respectively.
The co-formulation of glyburide (Gly) and vanillic acid (VA) as such in the form of nanomedicine has never been explored to treat metabolic diseases including type 2 diabetes mellitus. Both the drugs possess dissolution rate-limited oral bioavailability leading to poor therapeutic efficacy. Hence, co-loading these drugs into a nanocarrier could overcome their poor oral bioavailability related challenges. Owing to this objective, both drugs were co-loaded in amphiphilic polymeric micelles (APMs) and evaluated for their biopharmaceutical outcomes. The APMs were prepared using mPEG-b-PCL/CTAB as a copolymer-surfactant system via the liquid antisolvent precipitation (LAP) method. The design of these APMs were optimized using Box Behnken Design by taking various process/formulation based variables to achieve the desired micellar traits. The release of both the drugs from the optimized co-loaded APMs was compared in different media and displayed a remarkable sustained release profile owing to their hydrophobic interactions with the PCL core. The in vitro cytotoxicity study of co-loaded APMs on Caco-2 cells revealed 70 % cell viability in a concentration-dependent manner. The preventive effects of Gly and VA co-loaded in APMs on glucose uptake was studied in insulin-responsive human HepG2 cells treated with high glucose. The co-loading of both the drugs in optimized APMs exhibited synergistic glucose-lowering activity (p < 0.001) than raw drugs with low cytotoxicity on HepG2 cells within the test concentration. This could be attributed to an increase in the relative oral bioavailability of both the drugs in APMs i.e., 868 % for Gly and 87 % for VA respectively.
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