In kinetoplastid protozoa, import of cytosolic tRNAs into mitochondria occurs through tRNAs interacting with membrane-bound proteins, the identities of which are unknown. The inner membrane RNA import complex of Leishmania tropica contains multiple proteins and is active for import in vitro . RIC1, the largest subunit of this complex, is structurally homologous to the conserved α subunit of F1 ATP synthase. The RIC1 gene complemented an atpA mutation in Escherichia coli . Antisense-mediated knockdown of RIC1/F1α in Leishmania resulted in depletion of several mitochondrial tRNAs belonging to distinct subsets (types I and II) that interact cooperatively or antagonistically within the import complex. The knockdown-induced defect in import of type I tRNAs was rectified in a reconstituted system by purified RIC1/F1α alone, but recovery of type II tRNA import additionally required a type I tRNA. RIC1/F1α formed stable complexes with type I, but not type II, tRNAs through the cooperation of its nucleotide binding and C-terminal domains. Thus, RIC1/F1α is a type I tRNA import receptor. As expected of a bifunctional protein, RIC1/F1α is shared by both the import complex and by respiratory complex V. Alternative use of ancient respiratory proteins may have been an important step in the evolution of tRNA import.
Many maternally inherited and incurable neuromyopathies are caused by mutations in mitochondrial (mt) transfer RNA (tRNA) genes. Kinetoplastid protozoa, including Leishmania, have evolved specialized systems for importing nucleus-encoded tRNAs into mitochondria. We found that the Leishmania RNA import complex (RIC) could enter human cells by a caveolin-1-dependent pathway, where it induced import of endogenous cytosolic tRNAs, including tRNA(Lys), and restored mitochondrial function in a cybrid harboring a mutant mt tRNA(Lys) (MT-TK) gene. The use of protein complexes to modulate mitochondrial function may help in the management of such genetic disorders.
The workability of beyond Born-Oppenheimer theory to construct diabatic potential energy surfaces (PESs) of a charge transfer atom-diatom collision process has been explored by performing scattering calculations to extract accurate integral cross sections (ICSs) and rate constants for comparison with most recent experimental quantities. We calculate non-adiabatic coupling terms among the lowest three singlet states of H system (1A, 2A, and 3A) using MRCI level of calculation and solve the adiabatic-diabatic transformation equation to formulate the diabatic Hamiltonian matrix of the same process [S. Mukherjee et al., J. Chem. Phys. 141, 204306 (2014)] for the entire region of nuclear configuration space. The nonadiabatic effects in the D + H reaction has been studied by implementing the coupled 3D time-dependent wave packet formalism in hyperspherical coordinates [S. Adhikari and A. J. C. Varandas, Comput. Phys. Commun. 184, 270 (2013)] with zero and non-zero total angular momentum (J) on such newly constructed accurate (ab initio) diabatic PESs of H. We have depicted the convergence profiles of reaction probabilities for the reactive non-charge transfer, non-reactive charge transfer, and reactive charge transfer processes for different collisional energies with respect to the helicity (K) and total angular momentum (J) quantum numbers. Finally, total and state-to-state ICSs are calculated as a function of collision energy for the initial rovibrational state (v = 0, j = 0) of the H molecule, and consequently, those quantities are compared with previous theoretical and experimental results.
Feathers account for 5–7% of the total weight of chicken have become one of the major pollutants due to their recalcitrant nature. Feather which is constituted of 90% keratin can be a good source of peptides, amino acids, and minerals for use as organic fertilizer. Traditional feather degradation methods consume large amount of energy and reduces the overall quality of the proteins. However, degradation of keratin by keratinolytic bacteria may represent as an alternative for the development of cheap, cost effective, eco‐friendly, and easily available nitrogen (N) and minerals rich source as potential organic fertilizers. Keratinase enzymes from bacteria are serine‐type proteases showing optimal activity at pH 6 to 9 and 30 to 50 °C. Mechanism of degradation includes, sulfitolysis, proteolysis, followed by deamination. Keratinolytic bacteria showing antagonism against important plant pathogens may act as biocontrol agent. Feather hydrolyzate can also be employed as nitrogenous fertilizers for plant growth. Tryptophan release from the feather degradation can act as precursor for plant phytohormone, indole‐3‐acetic acid (IAA). Solubilization of inorganic phosphate (P) by keratinolytic bacteria may further elevate the growth of plant. Application of hydrolyzate increases the water holding capacity, N, carbon (C) and mineral content of the soil. It elevates protein, amino acids, and chlorophyll content of plant. Feather hydrolyzate enhances seed germination and growth of plant. Soil application further increases the population of beneficial bacteria. The use of keratinolytic bacteria having antagonistic and plant growth promoting activities, and feather hydrolyzate can emerge as sustainable and alternative tools to promote and improve organic farming, agro‐ecosystem, environment, human health, and soil biological activities.
We calculate the adiabatic Potential Energy Surfaces (PESs) and the Non-Adiabatic Coupling Terms (NACTs) for the three lowest singlet states of H3 (+) in hyperspherical coordinates as functions of hyperangles (θ and ϕ) for a grid of fixed values of hyperradius (1.5 ⩽ ρ ⩽ 20 bohrs) using the MRCI level of methodology employing ab initio quantum chemistry package (MOLPRO). The NACT between the ground and the first excited state translates along the seams on the θ - ϕ space, i.e., there are six Conical Intersections (CIs) at each θ (60° ⩽ θ ⩽ 90°) within the domain, 0 ⩽ ϕ ⩽ 2π. While transforming the adiabatic PESs to the diabatic ones, such surfaces show up six crossings along those seams. Our beyond Born-Oppenheimer approach could incorporate the effect of NACTs accurately and construct single-valued, continuous, smooth, and symmetric diabatic PESs. Since the location of CIs and the spatial amplitudes of NACTs are most prominent around ρ = 10 bohrs, generally only those results are depicted.
We present the molecular symmetry (MS) adapted treatment of nonadiabatic coupling terms (NACTs) for the excited electronic states (2(2)E' and 1(2)A1') of Na3 cluster, where the adiabatic potential energy surfaces (PESs) and the NACTs are calculated at the MRCI level by using an ab initio quantum chemistry package (MOLPRO). The signs of the NACTs at each point of the configuration space (CS) are determined by employing appropriate irreducible representations (IREPs) arising due to MS group, and such terms are incorporated into the adiabatic to diabatic transformation (ADT) equations to obtain the ADT angles. Since those sign corrected NACTs and the corresponding ADT angles demonstrate the validity of curl condition for the existence of three-state (2(2)E' and 1(2)A1') sub-Hilbert space, it becomes possible to construct the continuous, single-valued, symmetric, and smooth 3 × 3 diabatic Hamiltonian matrix. Finally, nuclear dynamics has been carried out on such diabatic surfaces to explore whether our MS-based treatment of diabatization can reproduce the pattern of the experimental spectrum for system B of Na3 cluster.
The mechanism of active transport of transfer RNA (tRNA) across membranes is largely unknown. Factors mediating the import of tRNA into the kinetoplast mitochondrion of the protozoon Leishmania tropica are organized into a multiprotein RNA import complex (RIC) at the inner membrane. Here, we present the complete characterization of the identities and functions of the subunits of this complex. The complex contains three mitochondrion-and eight nuclear-encoded subunits; six of the latter are necessary and sufficient for import. Antisense-mediated knockdown of essential subunits resulted in the depletion of mitochondrial tRNAs and inhibition of organellar translation. Functional complexes were reconstituted with recombinant subunits expressed in Escherichia coli. Several essential RIC subunits are identical to specific subunits of respiratory complexes. These findings provide new information on the evolution of tRNA import and the foundation for detailed structural and mechanistic studies.
Polymer-based nanosystems have been extensively explored either as therapeutic agents or bioimaging probes in the cancer diagnosis. However, very few systems are successful in combining both therapy and imaging. Herein, a new class of norbornene based copolymer, Nor-Dox-Cob-Btn is proposed as potential theranostics agent for tumor diagonosis. The copolymer (Nor-Dox-Cob-Btn) with doxorubicin, cobalt carbonyl complex, and biotin as pendent functionalized group is synthesized, using ring opening metathesis polymerization (ROMP). The cell viability, drug release, NMR relaxation, NMR 1-D image and Epi fluorescence microscopy studies on Nor-Dox-Cob-Btn nanocarrier are thoroughly studied. The effect of nanocarrier on transverse relaxation (T 2 ) of water molecule and NMR 1-D image suggest that the nanocarrier has the potential application in magnetic resonance imaging agent. The T 2 -weighted MRI agent, along with biotin receptor assisted pH responsive doxorubicin release from Nor-Dox-Cob-Btn, prompts us to envision this newly developed polymer for future application in theranostics. ■ INTRODUCTIONDoxorubicin is a well-known frontline anticancer drug, however due to cardiotoxic effect of doxorubicin, it is always necessary to protect this drug from other healthy cells and tissues inside body. 1 There are several different models available to guide this drug more precisely into the tumor cells, for example, polymer, nanoparticle, liposome. 3 However, polymer based delivery vehicle emerged as a superior over all other existing systems due to its pharmacokinetics and biodistribution profiles via the enhanced permeability as well as retention (EPR) effect. 4 These systems also help to maintain the therapeutic concentration over long periods of time. 2−4 There are mainly two approaches to deliver drugs site-specifically to the tumor cells, namely, covalent and non covalent approaches. 5,8 Drugs encapsulated inside the polymeric aggregates can be placed inside the body for using it localized delivery following the burst mechanism. 3,5,6,8 On contrast, in stimuli responsive covalently attached drug (e.g., pH sensitive, light sensitive, etc.) to the polymeric system gives the sustained release of drug to the tumor cells over long period. 11 There are several reports available in literature based on the pH sensitivity linker, for example hydrazone, ester, and amide, in which hydrazone linker is the most commonly used for the sustained release. 11 The medical application of polymeric nanocarrier has enormous potential to improve the therapeutic efficacy, particularly in cancer therapy. The attachment of folate or biotin functionality to the same polymeric prodrug makes the system more site-specific via receptor mediated drug delivery. 5,7,9 This also improves the survival rates of healthy tissues and cells. The attachment of magnetic particles helps the drug-carrier system further, as this magnetic particle can be utilized as MR imaging agent. 11 Magnetic as well as drug containing polymersomes have a great potential for both ...
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