Identification of residues in ABCG2 affecting protein trafficking and drug transport,using co-evolutionary analysis of ABCG sequences

ABCG2 is an ABC (ATP-binding cassette) transporter with a physiological role in urate transport in the kidney and is also implicated in multi-drug efflux from a number of organs in the body. The trafficking of the protein and the mechanism by which it recognizes and transports diverse drugs are important areas of research. In the current study, we have made a series of single amino acid mutations in ABCG2 on the basis of sequence analysis. Mutant isoforms were characterized for cell surface expression and function. One mutant (I573A) showed disrupted glycosylation and reduced trafficking kinetics. In contrast with many ABC transporter folding mutations which appear to be ‘rescued’ by chemical chaperones or low temperature incubation, the I573A mutation was not enriched at the cell surface by either treatment, with the majority of the protein being retained in the endoplasmic reticulum (ER). Two other mutations (P485A and M549A) showed distinct effects on transport of ABCG2 substrates reinforcing the role of TM helix 3 in drug recognition and transport and indicating the presence of intracellular coupling regions in ABCG2.     

β-Adrenoceptor antagonists reinitiate meiotic maturation in Clarias batrachus oocytes

Effects of β-adrenoceptor antagonists propranolol and alprenolol in the oocyte maturation of the catfish (Clarias batrachus) were investigated under in vitro. Cyclic AMP (cAMP) levels were also measured in the control, propranolol and phosphodiesterase (PDE) inhibitor treated oocytes. When full-grown folliculated oocytes were cultured in vitro in the presence of different concentrations of propranolol or alprenolol, both the substances induced germinal vesicle breakdown (GVBD) in a dose-dependent manner. The maturational effect of alprenolol at the concentration of 1.0 mM was similar to that of the 1.5 mM dose of propranolol inducing more than 88% GVBD. In the time course study, when the oocytes were treated with 1.5 mM propranolol or with 1.0 mM alprenolol for various times, both the antagonists induced more than 80% GVBD after 4 h of incubations and this induction gradually increased with the increased duration of treatments. On the other hand, 1.5 mM propranolol treatment caused a significant decrease in oocyte cAMP which was maintained upto the duration of the study (36 h). When the oocytes were first stimulated by 1.5 mM propranolol or 1.0 mM alprenolol for 4 h and then treated with various doses of cAMP or PDE inhibitors (IBMX and theophylline), all these substances effectively blocked β-adrenoceptor antagonist-induced GVBD. Both these PDE inhibitors promoted the accumulation of cAMP in the oocytes. These results provide the first example of an existence of a cAMP-mediated mechanism of action of β-adrenoceptor antagonists in the induction of oocyte maturation in fish.     

Testis-specific fascin component FSCN3 is dispensable for mouse spermatogenesis and fertility

Molecular Biology Reports - Fascins belong to a family of actin-bundling proteins that are involved in a wide range of biological functions. FSCN3, a newly identified testis-specific actin-bundling...     

N-terminal HrpE from Xanthomonas oryzae pv. oryzae mediates the regulation of growth and photosynthesis in rice

Plant Growth Regulation - Harpin proteins, produced by gram-negative bacteria, can enhance the plant growth. The growth enhancing potential of the harpins are beneficial and may be associated with...     

Alcohol inhibition of formalin induced depletion of neurosecretory material in the teleost Clarias batrachus (L).

In the normal C. batrachus a fair amount of stainable neurosecretory material (NSM) is always present in all the component parts of the hypothalamo-neurohypophysial (HN) complex. When formalin was injected intraperitoneally 70 to 90% of the NSM was depleted from the HN complex. When ethyl alcohol was administered immediately after formalin treatment, the depletion of NSM was inhibited, and their staining intensity could be compared with those of untreated controls.     

Reconstructing feedback representations in the ventral visual pathway with a generative adversarial autoencoder

While vision evokes a dense network of feedforward and feedback neural processes in the brain, visual processes are primarily modeled with feedforward hierarchical neural networks, leaving the computational role of feedback processes poorly understood. Here, we developed a generative autoencoder neural network model and adversarially trained it on a categorically diverse data set of images. We hypothesized that the feedback processes in the ventral visual pathway can be represented by reconstruction of the visual information performed by the generative model. We compared representational similarity of the activity patterns in the proposed model with temporal (magnetoencephalography) and spatial (functional magnetic resonance imaging) visual brain responses. The proposed generative model identified two segregated neural dynamics in the visual brain. A temporal hierarchy of processes transforming low level visual information into high level semantics in the feedforward sweep, and a temporally later dynamics of inverse processes reconstructing low level visual information from a high level latent representation in the feedback sweep. Our results append to previous studies on neural feedback processes by presenting a new insight into the algorithmic function and the information carried by the feedback processes in the ventral visual pathway.     

The electromyographic DC potential as a correlate of muscular activity

The present experiment was undertaken to demonstrate the effect of muscular force as well as duration of muscular work on the electromyographic (EMG) DC potential. Thirty subjects had to lift different weights by flexing the right forearm within a defined and constant setting for 20 s. The experimental variables were weight (0.5, 1, 2, and 3 kg) and time. The EMG was recorded from the belly of the right biceps brachii muscle in a quasi-unipolar manner and split into an integrated ac channel (IEMG) and a dc channel (DC-EMG). The average IEMG showed a ramp-like shape. Analysis showed a positive relationship for weight (p less than 0.0001) and time (p less than 0.0001) with the IEMG. The average shape of the DC-EMG showed a negative initiation potential, a monotonically increasing negative potential during contraction (contraction potential), a positively peaking off potential and a slow return to baseline (after potential). Analyses of variance demonstrated a significant (p less than 0.001) relationship of weight to the magnitude of the initiation and the termination potential. Regression analyses displayed an inverse relationship of time to the termination (p less than 0.01) and to the resolution potential (p less than 0.001). The DC-EMG showed higher peaks (initiation and termination potential) for heavier weights. For the termination and after potential less positive deflections were found with increasing time (fatigue). A control condition (isometric contraction) indicated that the initiation, contraction, and termination potential of the DC-EMG may also be related to aspects of the movement. Results suggest that the DC-EMG is a more complex measure of muscular activity than the IEMG.