Biological and computational studies provide insights into Caesalphinia digyna Rottler stems

Caesalpinia digyna (Rottl.) (Family: Fabaceae) is an essential medicinal plant for it's conventional uses against a kind of human disorders. This research aims to investigate the antidiarrheal, antibacterial and antifungal properties of the methanol extract of the stems extracts of the C. digyna (MECD). The in vivo antidiarrheal activity of the stem extracts were evaluated by using castor oil-induced diarrhea, castor oil-induced enteropooling and charcoal induced intestinal transit in mice model. Besides, in vitro antimicrobial potentiality of MECD was investigated by the disc diffusion method. In silico activity of the isolated compounds were performed by Schrödinger-Maestro (Version 11.1) software. In addition, The ADME/T analysis and PASS prediction were implemented by using pass online tools. In the antidiarrheal investigation, the MECD exhibited a notable inhibition rate in all test approaches which were statistically significant (p < 0.05, p < 0.1, p < 0.01). MECD 400 mg/kg showed the maximum antidiarrheal potency in all the test methods. In vitro antimicrobial analysis unveiled that, MECD revealed higher potentiality against almost all pathogens and indicates dose-dependent activity against almost all the bacteria and fungi. In the case of in silico evaluation of anti-diarrheal, anti-bacterial and anti-fungal activity, all three isolated compounds met the pre-conditions of Lipinski's five rules for drug discovery. Pass predicted study also employed for all compounds. However, The chemical constituents of the C. digyna can be a potent source of anti-diarrheal, anti-bacterial and anti-fungal medicine and further modification and simulation studies are required to establish the effectiveness of bioactive compounds.     

Dynamic Alterations to α-Actinin Accompanying Sarcomere Disassembly and Reassembly during Cardiomyocyte Mitosis

Although mammals are thought to lose their capacity to regenerate heart muscle shortly after birth, embryonic and neonatal cardiomyocytes in mammals are hyperplastic. During proliferation these cells need to selectively disassemble their myofibrils for successful cytokinesis. The mechanism of sarcomere disassembly is, however, not understood. To study this, we performed a series of immunofluorescence studies of multiple sarcomeric proteins in proliferating neonatal rat ventricular myocytes and correlated these observations with biochemical changes at different cell cycle stages. During myocyte mitosis, α-actinin and titin were disassembled as early as prometaphase. α-actinin (representing the sarcomeric Z-disk) disassembly precedes that of titin (M-line), suggesting that titin disassembly occurs secondary to the collapse of the Z-disk. Sarcomere disassembly was concurrent with the dissolution of the nuclear envelope. Inhibitors of several intracellular proteases could not block the disassembly of α-actinin or titin. There was a dramatic increase in both cytosolic (soluble) and sarcomeric α-actinin during mitosis, and cytosolic α-actinin exhibited decreased phosphorylation compared to sarcomeric α-actinin. Inhibition of cyclin-dependent kinase 1 (CDK1) induced the quick reassembly of the sarcomere. Sarcomere dis- and re-assembly in cardiomyocyte mitosis is CDK1-dependent and features dynamic differential post-translational modifications of sarcomeric and cytosolic α-actinin.     

Persistent degenerative changes in thymic organ function revealed by an inducible model of organ regrowth

The thymus is the most rapidly aging tissue in the body, with progressive atrophy beginning as early as birth and not later than adolescence. Latent regenerative potential exists in the atrophic thymus, because certain stimuli can induce quantitative regrowth, but qualitative function of T lymphocytes produced by the regenerated organ has not been fully assessed. Using a genome-wide computational approach, we show that accelerated thymic aging is primarily a function of stromal cells, and that while overall cellularity of the thymus can be restored, many other aspects of thymic function cannot. Medullary islet complexity and tissue-restricted antigen expression decrease with age, representing potential mechanisms for age-related increases in autoimmune disease, but neither of these is restored by induced regrowth, suggesting that new T cells produced by the regrown thymus will probably include more autoreactive cells. Global analysis of stromal gene expression profiles implicates widespread changes in Wnt signaling as the most significant hallmark of degeneration, changes that once again persist even at peak regrowth. Consistent with the permanent nature of age-related molecular changes in stromal cells, induced thymic regrowth is not durable, with the regrown organ returning to an atrophic state within 2 weeks of reaching peak size. Our findings indicate that while quantitative regrowth of the thymus is achievable, the changes associated with aging persist, including potential negative implications for autoimmunity.     

Two new myrmecophilous species of the genus Scutacarus (Acari: Prostigmata: Scutacaridae) with world keys to related species groups

In a survey on heterostigmatic mites (Acari: Prostigmata: Heterostigmata) associated with insects including ants in northwestern Iran, two new species of myrmecophilous mites of the genus Scutacarus (Acari: Scutacaridae) were found. They are S. shajariani sp. nov. phoretic on Tetramorium sp. (Hymenoptera: Formicidae) and S. ebermanni sp. nov. phoretic on Messor sp. The mentioned new species belong to groups of species with reduced setae e and h₂, and no setae 4b, respectively. These two new species are described and illustrated, and world keys are provided for respective species groups.     

Insight into the interaction of antitubercular and anticancer compound clofazimine with human serum albumin: spectroscopy and molecular modelling

The binding of clofazimine to human serum albumin (HSA) was investigated by applying optical spectroscopy and molecular docking methods. Fluorescence quenching data revealed that clofazimine binds to protein with binding constant in the order of 10⁴ M^?1, and with the increase in temperature, Stern–Volmer quenching constants gradually decreased indicating quenching mode to be static. The UV–visible spectra showed increase in absorbance upon interaction of HSA with clofazimine which further reveals formation of the drug–albumin complex. Thermodynamic parameters obtained from fluorescence data indicate that the process is exothermic and spontaneous. Forster distance (R_o) obtained from fluorescence resonance energy transfer is found to be 2.05 nm. Clofazimine impelled rise in α-helical structure in HSA as observed from far-UV CD spectra while there are minor alterations in tertiary structure of the protein. Clofazimine interacts strongly with HSA inducing secondary structure in the protein and slight alterations in protein topology as suggested by dynamic light scattering results. Moreover, docking results indicate that clofazimine binds to hydrophobic pocket near to the drug site II in HSA.     

Effect of geographical location and stochastic weather variation on life cycle assessment of biodiesel production from camelina in the northwestern USA

Purpose

The effect of regional factors on life cycle assessment (LCA) of camelina seed production and camelina methyl ester production was assessed in this study. While general conclusions from LCA studies point to lower environmental impacts of biofuels, it has been shown in many studies that the environmental impacts are dependent on location, production practices, and even local weather variations.

Methods

A cradle-to-farm gate and well-to-pump approaches were used to conduct the LCA. To demonstrate the impact of agro-climatic and management factors (weather condition, soil characteristics, and management practices) on the overall emissions for four different regions including Corvallis, OR, Pendleton, OR, Pullman, WA, and Sheridan, WY, field emissions were simulated using the DeNitrification-DeComposition (DNDC) model. openLCA v.1.4.2 software was used to quantify the environmental impacts of camelina seed and camelina methyl ester production.

Results and discussion

The results showed that greenhouse gas (GHG) emissions during camelina production in different regions vary between 49.39 and 472.51 kg CO₂-eq./ha due to differences in agro-climatic and weather variations. The GHG emissions for 1 kg of camelina produced in Corvallis, Pendleton, Pullman, and Sheridan were 0.76 ± 11, 0.55 ± 10, 0.47 ± 18, and 1.26 ± 6 % kg CO₂-eq., respectively. The GHG emissions for 1000 MJ of camelina biodiesel using camelina produced in Corvallis, Pendleton, Pullman, and Sheridan were 53.60 ± 5, 48.87 ± 5, 44.33 ± 7, and 78.88 ± 4 % kg CO₂-eq., respectively. Other impact categories such as acidification and ecotoxicity for 1000 MJ of camelina biodiesel varied across the regions by 43 and 103 %, respectively.

Conclusions

It can be concluded that process-based crop models such as DNDC in conjunction with Monte Carlo analysis are helpful tools to quantitatively estimate the influence of regional factors on field emissions which consequently can provide information about the expected variability in LCA results.

     

Bioconversion of Hydrocortisone by Cyanobacterium Fischerella ambigua PTCC 1635

Summary The bioconversion of hydrocortisone by a locally isolated strain of cyanobacterium Fischerella ambigua PTCC 1635 was investigated. Fischerella ambigua had not been previously examined for this potential. The fermentation led to production of 11β,17α, 20β, 21-tetrahydroxypregn-4-en-3-one and 11β-hydroxyandrost-4-en-3,17-dione. The metabolites were isolated and purified by chromatographic methods and identified using instrumental analyses.     

Analysis of mosquito bloodmeals using RFLP markers

An important variable in the amplification of arthropod vector-borne diseases is the degree of contact between human hosts and mosquito vectors. To analyze this interaction, a DNA based method was developed to differentiate human bloodmeals from other sources in the mosquito Anopheles stephensi (Diptera: Culicidae) Liston. A portion of the host mitochondrial DNA cytochrome B genes were PCR amplified and classified to the species level based on their restriction fragment length polymorphism (RFLP). The cytochrome B sequences showed sufficient interspecific polymorphism to distinguish between human, cow, sheep, chicken, and guinea pig hosts. XhoI could distinguish human from other vertebrates whereas TaqI alone could separate the others. The importance of these results in epidemiological studies of malaria and other vector borne diseases is discussed.