Circadian rhythm of airways caliber and its autonomic modulation

ABSTRACT

The autonomic nervous system (ANS) is one of the effector pathways for circadian variation of many physiological parameters. Autonomic tone and airways caliber have been reported to exhibit circadian variation in separate studies. A simultaneous investigation of heart rate variability (HRV) and airway caliber might ascertain how airway caliber is modulated by autonomic tone. This study was planned to identify the variations in airway caliber and autonomic function tone during a 24-hour span. A total of 56 healthy male subjects with almost similar daily routines were studied. Time domain, frequency domain and nonlinear analysis of R-R interval from 5 min electrocardiogram (ECG) was done seven times during the daytime wake span at 3-hour intervals starting at 05:00 h in the morning until 23:00 h in the night. Simultaneously peak expiratory flow rate (PEFR) was determined using a mini Wright’s peak flow meter. Rhythmometric analysis was done for PEFR and HRV parameters. Significant circadian variation in low frequency (LF) and high frequency (HF) variance was identified in this group of healthy subjects. The circadian rhythm of LF variance was characterized by a gradual increase and corresponding reciprocal change in HF variance from morning until night. The LF/HF ratio and SD2/SD1 ratio reflecting sympatho-vagal balance showed low to high values from morning to evening. The acrophase of the PEFR temporal pattern is similar to that of LF power and almost opposite in phase to that of HF power. PEFR is positively correlated with LF power. The circadian rhythm of airway caliber co-varies with cardiac autonomic tone. It appears that the temporal pattern of cardiac autonomic tone precedes in time that of airways caliber, thereby suggesting the latter operates under the modulatory effect of the 24-hour pattern in sympatho-vagal balance.     

Prime–Boost with Mycobacterium smegmatis Recombinant Vaccine Improves Protection in Mice Infected with Mycobacterium tuberculosis

The development of a new vaccine as a substitute for Bacillus Calmette–Guerin or to improve its efficacy is one of the many World Health Organization goals to control tuberculosis. Mycobacterial vectors have been used successfully in the development of vaccines against tuberculosis. To enhance the potential utility of Mycobacterium smegmatis as a vaccine, it was transformed with a recombinant plasmid containing the partial sequences of the genes Ag85c, MPT51, and HspX (CMX) from M. tuberculosis. The newly generated recombinant strain mc²-CMX was tested in a murine model of infection. The recombinant vaccine induced specific IgG1 or IgG2a responses to CMX. CD4⁺ and CD8⁺ T cells from the lungs and spleen responded ex vivo to CMX, producing IFN-γ, IL17, TNF-α, and IL2. The vaccine thus induced a significant immune response in mice. Mice vaccinated with mc²-CMX and challenged with M. tuberculosis showed better protection than mice immunized with wild-type M. smegmatis or BCG. To increase the safety and immunogenicity of the CMX antigens, we used a recombinant strain of M. smegmatis, IKE (immune killing evasion), to express CMX. The recombinant vaccine IKE-CMX induced a better protective response than mc²-CMX. The data presented here suggest that the expression of CMX antigens improves the immune response and the protection induced in mice when M. smegmatis is used as vaccine against tuberculosis.     

Genes involved in phosphatidylcholine biosynthesis correlate with nuclear factor-κB in biliary tract cancer patients: Evidence from 1H NMR and computational analyses

Gallbladder cancer (GBC) is an aggressive malignancy of gastrointestinal tract. Due to uncontrolled growth, GBC cells rapidly synthesize biomolecules including lipids. The lipids are integral component of cell membrane with a wide range of cellular functions. In this study, we measured the clinicopathological features in 40 cases of histologically confirmed GBC and 16 cases of chronic cholecystitis (CC). The female to male ratio in the GBC and CC groups were 3.44:1 and 2.2:1, respectively. The GBC patients exhibited well to poorly differentiated tumor. In the CC group, all patients showed cholecystitis with no evidence of dysplasia or malignancy. The majority of GBC and CC patients reported pain. Using ¹H NMR spectroscopy, we observed 4-folds increase in the level of choline containing phospholipids (CCPLs) in the gallbladder of GBC patients as compared to CC patients. Other lipid metabolites such as cholesterol ester, C18-cholesterol and saturated fatty acids were insignificantly changed between GBC and CC patients. Moreover, the level of CCPLs in the GBC patients with BMI <25 kg/m² was significantly higher as compared to CC patients. Further, a significant increase in the CCPLs level was observed in GBC female patients in comparison to CC patients. From the computational analyses, we observed that the genes involved in the biosynthesis of phosphatidylcholine (PtdCho) indirectly interact with the RELA, which encodes the NF-κB p65 subunit. The genes involved in the PtdCho biosynthesis were also correlated with the overall and disease-free survival of cholangiocarcinoma patients. The study opens new window for exploring the diagnostic and therapeutic potential of CCPLs in GBC patients.     

APC Inhibits Ligand-Independent Wnt Signaling by the Clathrin Endocytic Pathway

1. Download high-res image (220KB)
2. Download full-size image

     

Inter and intraspecific genetic diversity (RAPD) among three most frequent species of macrofungi (Ganoderma lucidum,Leucoagricus sp. and Lentinus sp.) of Tropical forest of Central India

In present study seven RAPD primers were used to access the diversity within and among twelve populations of three mushroom species Ganoderma lucidum, leucoagaricus sp. and Lentinus sp. Total of 111 bands were scored by 7 RAPD primers in 30 accessions of three mushroom species collected from different sampling sites of central India. Total 111 bands were generated using seven primers which were F-1, OPG-06, OPC-07, OPD-08, OPA-02, OPD-02, OPB-10. All 111 bands were polymorphic in nature (100%). Therefore, it revealed that the used primers had sufficient potency for population studies and 30 accessions had higher genetic differences among each other. In best of the knowledge, this is the first report, which accesses the genetic diversity between three mushroom species (Gd Ganoderma lucidum, Lg Leucoagaricus sp., Ls Lentinus). The polymorphic percentage ranged from 3.60 to 23% within twelve populations, while polymorphic percentage among group was 40.56, among population within groups was 41.12 and within population was 18.32. This indicated that the genetic diversity within the population was very low, but slightly higher in the populations of three species. Among three groups representing Gd., Lg and Ls, Among populations within groups shown highest percentage of variation (Pv?=?41.12) while within populations, the lowest percentage of variation (18.32) was observed. This result also support that the highest genetic variation was present among groups in comparison to among the population within a species and lowest genetic variation was observed within the population.     

Scavenging of hydroxyl,methoxy, and nitrogen dioxide free radicals by some methylated isoflavones

Free radicals can be scavenged from biological systems by genistein, daidzein, and their methyl derivatives through hydrogen atom transfer (HAT), single-electron transfer (SET), and sequential proton-loss electron-transfer (SPLET) mechanisms. Reactions between these derivatives and the free radicals OH^., OCH₃^., and NO₂^. via the HAT mechanism in the gas phase were studied using the transition state theory within the framework of DFT. Solvation of all the species and complexes involved in the HAT reactions in aqueous media was treated by performing single point energy calculations using the polarizable continuum model (PCM). The SET and SPLET mechanisms for the above reactions were also considered by applying the Marcus theory of electron transfer, and were found to be quite sensitive to geometry and solvation. Therefore, the geometries of all the species involved in the SET and SPLET mechanisms were fully optimized in aqueous media. The calculated barrier energies and rate constants of the HAT-based scavenging reactions showed that the OH group of the B ring in genistein, daidzein, and their methyl derivatives plays a major role in the scavenging of free radicals, and the role of this OH group in the HAT-based free-radical scavenging decreases in the following order: OH^.?>?OCH₃^. > NO₂^.. The SPLET mechanism was found to be an important mechanism in these free-radical scavenging reactions, whereas the SET mechanism was not important in this context.     

Leucas pachmarhiensis sp. nov. (Lamioideae; Lamiaceae) from central India

A new species, Leucas pachmarhiensis (Lamiaceae), is described and illustrated from the Pachmarhi Biosphere Reserve, Hoshangabad district, Madhya Pradesh, India with conservation status assessed as ‘Critically Endangered’. This novelity is endemic to central India and belongs to Leucas sect. Plagiostoma. It differs from other species of this section by its height up to 120 cm, and inflorescence positioned at multiple nodes. Detailed notes on its conservation status and ecology are provided.     

Capitalizing on multi-element interactions through balanced nutrition - A pathway to improve nitrogen use efficiency in China, India and North America

A viable option for increasing nitrogen (N) use efficiency and mitigation of negative impacts of N on the environment is to capitalize on multi-element interactions through implementation of nutrient management programs that provide balanced nutrition. Numerous studies have demonstrated the immediate efficacy of this approach in the developing regions like China and India as well as developed countries in North America. Based on 241 site-years of experiments in these countries, the first-year N recovery efficiency (RE) for the conventional or check treatments averaged 21% while the balanced treatments averaged 54% RE, for an average increase of 33% in RE due to balanced nutrition. Effective policies to promote adoption are most likely those that enable site-specific approaches to nutrient management decisions rather than sweeping, nation-wide incentives supporting one nutrient over another. Local farmers, advisers and officials need to be empowered with tools and information to help them define necessary changes in practices to create more balanced nutrient management.