Blood genetic markers in Sri Lankan populations--reappraisal of the legend of Prince Vijaya

Serum protein (haptoglobin types; transferrin and group-specific component subtypes); haemoglobin and red cell enzymes (acid phosphatase, esterase D, glyoxalase I, 6-phosphogluconate dehydrogenase, adenylate kinase, and phosphoglucomutase (locus 1) (subtypes) were studied in the Sinhalese, Tamils, and Muslims of Sri Lanka. The allelic frequencies of all the polymorphic systems were similar in these populations without any significant differences. A close look at the present results and earlier investigations on 13 polymorphic loci controlled by 37 alleles did not reveal any genetic characteristics in the present-day Sinhalese population that are distinct from those in the Tamils of Sri Lanka. As such, genetic evidence linking the legendary origin of the Sinhalese population to East India (Prince Vijaya) is lacking.     

An operator-induced conformational change in the C-terminal domain of the lambda repressor.

4,4'-bis(1-anilino-8-naphthalenesulfonic acid (Bis-ANS), an environment-sensitive fluorescent probe for hydrophobic region of proteins, binds specifically to the C-terminal domain of lambda repressor. The binding is characterized by positive cooperativity, the magnitude of which is dependent on protein concentration in the concentration range where dimeric repressor aggregates to a tetramer. In this range, positive cooperativity becomes more pronounced at higher protein concentrations. This suggests a preferential binding of Bis-ANS to the dimeric form of the repressor. Binding of single operator OR1 to the N-terminal domain of the repressor causes enhancement of fluorescence of the C-terminal domain bound Bis-ANS. The binding of single operator OR1 also leads to quenching of fluorescence of tryptophan residues, all of which are located in the hinge or the C-terminal domain. Thus two different fluorescent probes indicate an operator-induced conformational change which affects the C-terminal domain. The significance of this conformational change with respect to the function of lambda repressor has been discussed.     

Genetic study of five populations of Bihar, India.

Four-hundred fifty-nine people, including 106 Santals, 43 Bhuiyas, 107 Sakaldipi Brahmins, 108 Chamars, and 95 Ansari Muslims, of the Giridhi district of Bihar have been tested for transferrin, group-specific component, phosphoglucomutase subtypes, and glyoxalase-I, 6-phosphogluconate dehydrogenase, and adenylate kinase types. Genetic distance estimates by both dendrogram and principal component methods for these 5 populations and the Oraons on the basis of 19 alleles at 6 polymorphic loci indicate 2 major clusters: Brahmins and Muslims, the latter of which is composed of two subclusters (Santals and Bhuiyas, and Oraons and Chamars). The Santal and Bhuiya tribes both speak Mundari, whereas the Oraons speak a Dravidian language. The Chamars, although low-caste Hindus, seem to have a non-Europoid origin, as do the Oraons.     

Detection of rabies virus in different tissues of experimentally infected mice at preclinical and postclinical stages of the disease.

Rabies fixed virus (CVS) was passaged 10 times in mice by intramuscular (im) route followed by experimental inoculation of the titrated virus in 4 groups of mice with the dose of 0.1 ml of 1000 mouse (LD50 0.03 ml) using intracerebral (ic), intravenous (iv), intramuscular (im), intraocular (io), and intranasal (in) routes respectively. No marked variation in clinical signs due to variation of routes could be detected. Involvement of brain with io route could be detected even in preclinical stage. Although the virus could be detected in the postclinical stage in all the tissues under study (brain, skin, salivary gland and corneal impression), with io and ic routes spread of the virus was observed in comparatively higher concentrations.     

Recovery of injured Campylobacter jejuni cells after animal passage.

Sixteen freeze-thaw-injured nonculturable stocks of Campylobacter jejuni were passed through rat gut, and seven were reisolated. These reisolated strains were converted to toxin producers, as they were before preservation, following consecutive passages through rat gut. This observation indicated the existence of an injured, viable, but nonresuscitated form of C. jejuni which can be resuscitated to a culturable and fully virulent form by passaging the organism through a susceptible host.     

Osmolytes modulate polyglutamine aggregation in a sequence dependent manner

Osmolytes stabilize protein structure and suppress protein aggregation. The mechanism of how osmolytes impact polyglutamine (polyQ) aggregation implicated in Huntington's disease was studied. By using a reverse‐phase chromatography assay, we show that methylamines‐trimethylamine N‐oxide and betaine are generic in enhancing polyQ aggregation, while a disaccharide trehalose and an amino acid citrulline moderately retard polyQ aggregation in a sequence specific manner. Despite the altered kinetics, the fundamental nucleation mechanism of polyQ aggregation and the nature of end stage aggregates remains unaffected. These results highlight the importance of using osmolytes as modulatory agents of polyQ aggregation.     

Photoluminescence intensity ratio of Eu‐conjugated lactates—A simple optical imaging technique for biomarker analysis for critical diseases

Instant measurement of elevated biomarkers such as lactic acid offers the most promising approaches for early treatment and prevention of many critical diseases including cardiac arrest, stroke, septic shock, trauma, liver dysfunction, as well as for monitoring lactic acid level during intense exercise. In the present study, a unique dependence of visible photoluminescence of Eu³⁺ ions resulting from ⁵D₀ to ⁷F_{J(J = 0,1,2,3,4)} transitions, which can be exploited for rapid detection of biomarkers, both in vitro and ex vivo, has been reported. It is observed that the integrated intensity ratio of photoluminescence signals dominating at 591 and 616 nm originating from ⁵D₀ to ⁷F₂ and ⁵D₀ to ⁷F₁ transitions in Eu³⁺ ions can be used as a biosensing and bioimaging tool for detection of biomarkers released at disease states. The Eu³⁺ integrated photoluminescence intensity ratio approach reported herein for optical detection of lactates in blood serum, plasma and confocal imaging of brain tissues has very high potential for exploitation of this technique in both in vitro monitoring and in vivo bioimaging applications for the detection of biomarkers in various diseases states.      

Dynamics of the active site loops in catalyzing aminoacylation reaction in seryl and histidyl tRNA synthetases

Aminoacylation reaction is the first step of protein biosynthesis. The catalytic reorganization at the active site of aminoacyl tRNA synthetases (aaRSs) is driven by the loop motions. There remain lacunae of understanding concerning the catalytic loop dynamics in aaRSs. We analyzed the functional loop dynamics in seryl tRNA synthetase from Methanopyrus kandleri (^mkSerRS) and histidyl tRNA synthetases from Thermus thermophilus (^ttHisRS), respectively, using molecular dynamics. Results confirm that the motif 2 loop and other active site loops are flexible spots within the catalytic domain. Catalytic residues of the loops form a network of interaction with the substrates to form a reactive state. The loops undergo transitions between closed state and open state and the relaxation of the constituent residues occurs in femtosecond to nanosecond time scale. Order parameters are higher for constituent catalytic residues which form a specific network of interaction with the substrates to form a reactive state compared to the Gly residues within the loop. The development of interaction is supported from mutation studies where the catalytic domain with mutated loop exhibits unfavorable binding energy with the substrates. During the open-close motion of the loops, the catalytic residues make relaxation by ultrafast librational motion as well as fast diffusive motion and subsequently relax rather slowly via slower diffusive motion. The Gly residues act as a hinge to facilitate the loop closing and opening by their faster relaxation behavior. The role of bound water is analyzed by comparing implicit solvent-based and explicit solvent-based simulations. Loops fail to form catalytically competent geometry in absence of water. The present result, for the first time reveals the nature of the active site loop dynamics in aaRS and their influence on catalysis.     

Neurofascin Knock Down in the Basolateral Amygdala Mediates Resilience of Memory and Plasticity in the Dorsal Dentate Gyrus Under Stress

Activation of the amygdala is one of the hallmarks of acute stress reactions and a central element of the negative impact of stress on hippocampus-dependent memory and cognition. Stress-induced psychopathologies, such as posttraumatic stress disorder, exhibit a sustained hyperactivity of the amygdala, triggered at least in part by deficits in GABAergic inhibition that lead to shifts in amygdalo-hippocampal interaction. Here, we have utilized lentiviral knock down of neurofascin to reduce GABAergic inhibition specifically at the axon initial segment (AIS) of principal neurons within the basolateral amygdala (BLA) of rats. Metaplastic effects of such a BLA modulation on hippocampal synaptic function were assessed using BLA priming prior to the induction of long-term potentiation (LTP) on dentate gyrus synapses in anesthetized rats in vivo. The knock down of neurofascin in the BLA prevented a priming-induced impairment on LTP maintenance in the dentate gyrus. At the behavioral level, a similar effect was observable, with neurofascin knock down preventing the detrimental impact of acute traumatic stress on hippocampus-dependent spatial memory retrieval in a water maze task. These findings suggest that reducing GABAergic inhibition specifically at the AIS synapses of the BLA alters amygdalo-hippocampal interactions such that it attenuates the adverse impact of acute stress exposure on cognition-related hippocampal functions.     

Promotion of shoot regeneration of <Emphasis Type="Italic">Swertia chirata</Emphasis> by biosynthesized silver nanoparticles and their involvement in ethylene interceptions and activation of antioxidant activity

A complete protocol for the in vitro induction of Eclipta alba tetraploids has been optimized to enhance the wedelolactone content, an anti-cancerous compound. The effects of different concentrations of colchicine (0, 0.01, 0.05, 0.1, 0.2 and 0.3%; w/v) along with treatment durations (12, 24, 36 and 48 h) were investigated on shoot tip (ST) and nodal segment (NS). The treated explants were then incubated on Murashige and Skoog (MS) medium having 1.5 mg L^?1 N⁶-benzylaminopurine and 0.5 mg L^?1 α-napthalene acetic acid for shoot regeneration and afterward root was induced on 1.0 mg L^?1 indole-3-acetic acid enriched ½MS medium. The tetraploids of E. alba were proficiently induced by the treatment of 0.1% colchicine for 24 h. The highest tetraploid induction efficiency was obtained from ST (30.56%) in comparison to the NS (22.22%). Analysis by spectrophotometry and flow cytometry showed that colchicine treated plants contained higher quantity of DNA than diploid plants. Cytological studies demonstrated doubled the chromosome number in tetraploids (2n?=?4x?=?44) than diploids (2n?=?2x?=?22). The ploidy level enhancement lead to alteration of other traits, like increased plant height, stem diameter, leaf size, stomatal size and chlorophyll content. As determined through high performance thin-layer chromatography, the ultimate achievement of this technique is the higher accumulation of wedelolactone in tetraploid plants (300.32 µg g^?1 dry weight) in evaluation to in vitro diploid (131.31 µg g^?1 dry weight) and in vivo diploid mother plants (93.26 µg g^?1 dry weight), thus improving the pharmaceutical value of E. alba.