Hyperactive Strains Research Articles

Assessment of the phylogenetic analysis and antimicrobial, antiviral, and anticancer activities of marine endophytic Streptomyces species of the soft coral Sarcophyton convolutum.

In the present work, the extensive biological activities of marine endophytic Streptomyces strains isolated from marine soft coral Sarcophyton convolutum have been demonstrated. Within fifty-one Streptomyces isolates evaluated for their hydrolytic enzymes and enzyme inhibitors productivities, six isolates showed the hyperactivities. Pharmaceutical metabolites productivities evaluated include enzymes (alkaline protease, L-asparaginase, L-glutaminase, tyrosinase, and L-methioninase) and enzyme inhibitors (inhibitors of α-amylase, hyaluronidase, β-lactamase, α-glucosidase, and β-glucosidase). These isolates were identified based on their morphological, biochemical, and genetic characteristics as Streptomyces sp. MORSY 17, Streptomyces sp. MORSY 22, Streptomyces sp. MORSY 25, Streptomyces sp. MORSY 36, Streptomyces sp. MORSY 45, and Streptomyces sp. MORSY 50. Moreover, in further evaluation, these strains exhibited wide spectrum of antimicrobial (against bacteria and fungi), antiviral (against hepatitis C virus), antibiofilm against biofilm-forming bacteria (methicillin-resistant Staphylococcus aureus and multidrug-resistant Pseudomonas species), and anti-proliferative activities (against liver and colon carcinoma cell lines). The GC-MS analysis of the hyperactive strains MORSY 17 and MORSY 22 revealed the presence of different bioactive agents in the ethyl acetate extract of both strains.

Nicotinic cholinergic mechanisms causing elevated dopamine release and abnormal locomotor behavior

Firing rates of dopamine (DA) neurons in substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) control DA release in target structures such as striatum and prefrontal cortex. DA neuron firing in the soma and release probability at axon terminals are tightly regulated by cholinergic transmission and nicotinic acetylcholine receptors (nAChRs). To understand the role of α6* nAChRs in DA transmission, we studied several strains of mice expressing differing levels of mutant, hypersensitive (leucine 9' to serine [L9'S]) α6 subunits. α6 L9'S mice harboring six or more copies of the hypersensitive α6 gene exhibited spontaneous home-cage hyperactivity and novelty-induced locomotor activity, whereas mice with an equal number of WT and L9'S α6 genes had locomotor activity resembling that of control mice. α6-dependent, nicotine-stimulated locomotor activation was also more robust in high-copy α6 L9'S mice versus low-copy mice. In wheel-running experiments, results were also bi-modal; high-copy α6 L9'S animals exhibited blunted total wheel rotations during each day of a 9-day experiment, but low-copy α6 L9'S mice ran normally on the wheel. Reduced wheel running in hyperactive strains of α6 L9'S mice was attributable to a reduction in both overall running time and velocity. ACh and nicotine-stimulated DA release from striatal synaptosomes in α6 L9'S mice was well-correlated with behavioral phenotypes, supporting the hypothesis that augmented DA release mediates the altered behavior of α6 L9'S mice. This study highlights the precise control that the nicotinic cholinergic system exerts on DA transmission and provides further insights into the mechanisms and consequences of enhanced DA release.

Optimization of laccase production using response surface methodology coupled with differential evolution

In the present study, laccase production from a locally isolated hyperactive strain of Pleurotus sp. under solid state fermentation (SSF) was carried out and the interactions between different parameters of fermentation were studied using response surface methodology. The saddle shaped response surface plots depicting dual conditions for the enhanced production indicated the presence of isozymes with production optima at different conditions which was verified experimentally. Isoelectric focusing of the enzyme extract revealed that two isoforms were found with a widely varying pI of 3.8 and 9.3 emphasizing the capacity of the enzyme to be deployed at both acidic and alkaline conditions. Optimization of production conditions by coupling the regression equation with differential evolution technique yielded over 54,600IU/gds (3,412,500U/L) with a surfactant concentration of 0.016%, pH 7.99, particle size of 0.25cm, liquid to solid ratio of 4.99 and an incubation period of 8 days. In this study, the optimization process yielded highest titer value of laccase reported to date.

Physiology of amidase production by M. methylotrophus: Isolation of hyperactive strains using continuous culture

Physiology of amidase production by M. methylotrophus: Isolation of hyperactive strains using continuous culture

QTL analyses of spontaneous activity by using mouse strains from Mishima battery.

We reported previously that spontaneous activity in the home cage is highly variable among the Mishima battery of mouse strains. In that study, NJL and KJR were found to be hyperactive strains in contrast to BLG2, which showed one of the lowest activity levels. To unravel the genetic loci involved in this behavioral phenotype, we conducted QTL analyses on backcross populations of crosses between either NJL or KJR and BLG2 strains. In the backcross of NJL to BLG2, no single locus was associated with increased spontaneous activity. In the backcross of KJR to BLG2, linkage analysis showed that a locus on the most telomeric region of Chromosome (Chr) 3 was involved in the spontaneous activity, thus named Loco1. Further linkage analysis using selected progeny carrying the allele from KJR at the Loco1 locus suggested the presence of another locus, Loco2, on Chr 17. An analysis showed that Loco1 and Loco2 interacted epistatically.

Strain and sex differences in the locomotor response and behavioral sensitization to cocaine in hyperactive rats

Individual variability in the behavioral responsiveness to psychostimulant drugs is due, in part, to genetic factors. The present study investigated the effects of acute and repeated administrations of cocaine (0, 5, 10 or 20 mg/kg, i.p.) on locomotor activity in male and female rats from genetically distinct strains often used as a model of human childhood hyperactivity/attentional deficit disorder: Wistar Kyoto Hyperactive (WKHA) rats, Spontaneous Hypertensive rats (SHR) and their control Wistar Kyoto (WKY). The results, expressed as percent change in locomotor activity relative to respective control groups, showed that cocaine elicits a dose-dependent hyperactivity in all strains and revealed neither strain nor sex differences in acute sensitivity to moderate doses of the drug. Nevertheless, across repeated administrations, strain and sex differences appeared: WKHA rats displayed a moderate extent of sensitization to psychomotor stimulant effects of cocaine and female rats showed more robust sensitization than males, whatever the strain. These findings support the genotype-dependence in the development of behavioral sensitization to cocaine and confirm the robustness of the sexual dimorphism across different inbred rat strains. Interestingly, the present results demonstrate that sensitization to psychostimulant drugs occurs in genetically hyperactive strains as well as in their normoactive control strain.

Blood cell changes in spontaneously hypertensive rats are not all associated with the hypertensive phenotype

To search for cosegregation of a change in specific blood cells with either the hypertension or the hyperactivity phenotype in spontaneously hypertensive rats (SHR), Wistar-Kyoto (WKY) rats and two new inbred strains. Standard hematological procedures were used to examine erythrocytes, leukocytes and platelets in blood drawn from adult SHR, WKY rats and the two new inbred strains of rats. The hypertensive strains exhibited significant erythrocytosis, microcytosis, lymphocytosis and monocytosis relative to the normotensive strains. The hyperactive strains exhibited significant neutrophilia and increased platelet count relative to the non-hyperactive strains. Not all of the differences in blood cells described originally in SHR versus WKY rats were associated with the inheritance of hypertension. The changes in the lymphocytes and in the erythrocytes should be examined as possible factors in the pathophysiology of hypertension.

Interstrain aggression in hypertensive and/or hyperactive rats: SHR, WKY, WKHA, WKHT

Four inbred rat strains, all derived from Wistar-Kyoto (WKY) rats, express hypertension and hyperactivity in all combinations: SHRs have both traits, WKYs have neither, WKHAs are hyperactive/normotensive, and WKHTs are hypertensive/normoactive. Rats of the four strains were tested for aggression, at one time only, by pairing subjects of same sex, same age, but different strain, in a novel arena, i.e., on neutral ground, for three consecutive, 5-min observation periods. Total aggression scores were highest in females, highest in the first 5-min period, and lower at 7–9 months than at younger ages. Allogrooming was more frequently observed than other types of aggression, such as attacks, mounts, aggressive postures, and blocks. Allogrooming scores were significantly elevated in the hypertensive strains, especially WKHT, and very low in the hyperactive strains, especially WKHA. The other forms of aggression were significantly higher in females with hyperactivity. It was concluded that interstrain aggression, as seen in SHRs and WKYs, is differentially expressed by two new strains genetically derived from them. Furthermore, no one strain among these four expresses all components of the behavioral responses seen in this form of aggression.

Cardiovascular Responsiveness to Stress in Relation to Behavior and Hypertension

The spontaneously hypertensive rat (SHR) exhibits cardiovascular (CV) hyperreactivity to environmental stress and behavioral hyperactivity relative to the Wistar-Kyoto rat (WKY). The present study sought to determine whether hyperreactivity in the SHR is related to hypertension or to behavioral hyperactivity. By breeding SHR with WKY, followed by inbreeding, one of us (EDH) has developed two new strains in which the hypertensive trait seems to be separated from the hyperactivity trait: the Wistar-Kyoto Hypertensive (WK-HT) and the Wistar-Kyoto Hyperactive (WK-HA) strains. Conscious SHR, WKY, WK-HT, and WK-HA rats were instrumented with catheters and Doppler flow-velocity probes to record arterial pressure, heart rate (HR), and changes in regional vascular resistances, and subjected to air-jet stress and pharmacological interventions. The hyperactive strains (SHR and WK-HA) exhibited enhanced pressor-, renal-, and splanchnic responses to stress, and higher HRs under all conditions, even after ganglionic bl...

Two New Wistar-Kyoto Rat Strains in which Hypertension and Hyperactivity are Expressed Separately

Two inbred strains have been developed from a cross between SHR and WKY. WK-HTs are hypertensive but not hyperactive, and WK-HAs are hyperactive but normotensive. Together with SHR (that express both traits) and WKY (expressing neither trait) we used four strains to follow correlations of biological changes with the expression of hyperactivity or hypertension. We show that the well known sympathetic hyperreactivity of SHRs to acute stress is associated with the hyperactivity trait and not the hypertension among the four strains. Similarly, the well known ventricular hypertrophy in SHRs is more prominent among the hyperactive strains than the hypertensives. Examination of regional brain amine levels revealed an imbalance in forebrain serotonin transmission in the hyperactive strains, and no significant correlations with hypertension. On the other hand, neuropeptides in brainstem and spinal cord revealed a decrease, in hypertension, in neuropeptide Y and PNMT content of terminals of C1 fibers that innervate the spinal cord sympathetic outflow. Also, the two hypertensive strains showed increased TRH-and proctolin-like immunoreactivity in fibers that innervate the C1 cells in the rostral ventrolateral medulla. These findings illustrate the unique advantage provided by WK-HA and WK-HT strains as additional controls for SHRs in studying hypertension and hyperactivity.

Association between cardiovascular reactivity to stress and hypertension or behavior

The spontaneously hypertensive rat (SHR) exhibits increased cardiovascular reactivity (CVR) to environmental stress and behavioral hyperactivity relative to the Wistar-Kyoto rat (WKY). This study sought to determine whether enhanced CVR to stress in the SHR is related to hypertension or to behavioral hyperactivity. By breeding SHR with WKY, followed by inbreeding, E. D. Hendley has developed two strains in which the hypertensive trait seems to be separated from the hyperactivity trait: the Wistar-Kyoto hypertensive (WK-HT) and the Wistar-Kyoto hyperactive (WK-HA) strains. Male SHR, WKY, WK-HT, and WK-HA rats were implanted with intravascular catheters and Doppler flow-velocity probes to record arterial pressure, heart rate (HR), and changes in regional vascular resistances. Five days after surgery, the rats were subjected to air-jet stress and pharmacological interventions. The hyperactive strains (SHR and WK-HA) exhibited enhanced pressor, renal, and mesenteric responses to stress, and higher HRs under all conditions, even after autonomic blockade. Both hypertension and hyperactivity were associated with reduced baroreceptor sensitivity. These data indicate that CVR to stress is related to behavioral traits.

Physiology of Amidase Production by Methylophilus methylotrophus: Isolation of Hyperactive Strains Using Continuous Culture

The obligately methylotrophic bacterium Methylophilus methylotrophus hydrolyses aliphatic amides to ammonia and aliphatic acid using a cytoplasmic amidase. Physiological regulation of amidase activity was investigated by growing the organism under various conditions in batch, fed-batch and continuous culture. The results showed that synthesis of the enzyme was induced by various amides (acrylamide > acetamide) and repressed by ammonia. Growth of the wild-type organism in acetamide-limited continuous culture at very low dilution rate (D 0·025 h−1) led to the selection of a hyperactive strain (MM6), the subsequent growth of which under acrylamide limitation led to the selection of another strain (MM8) which showed even higher activity. The amidase activities of strains MM6 and MM8 were respectively approximately four and twelve times higher than that of the wild-type organism following growth under similar conditions, whereas the concentrations of the enzyme as determined by SDS-PAGE and scanning densitometry were approximately four times higher than the wild-type organism in both strains. The amidase in strain MM8 exhibited a K m for acrylamide that was approximately one-third lower than that of the wild-type organism or of strain MM6. It is concluded that the hyperactivity of strain MM6 was due predominantly to the production of more wild-type enzyme, whilst the hyperactivity of strain MM8 was due to the production of approximately the same amount of enzyme as strain MM6 (up to 25% of the total cell protein depending on the nature of the limiting amide) but with a substantially enhanced catalytic activity (K cat). These changes were apparently the result of spontaneous mutations that occurred in response to growth at extremely low amide concentrations, giving the novel strains a strong selective advantage under these conditions (possibly by enhancing the rate of diffusion of amide into the cell).

Behavioral and metabolic effects of sucrose-supplemented feeding in hyperactive rats.

Two hyperactive rat strains [spontaneously hypertensive rats (SHR) and SHR-Wistar-Kyoto cross (WK-HA)] and their nonhyperactive genetic control strain (Wistar-Kyoto) were fed ad libitum sucrose-supplemented rat chow, or chow alone in controls, to determine the effects of dietary sugar on behavior. The diets were given either overnight (acute sugar) or for 14-18 days (chronic sugar), and testing was carried out on the morning after each of the dietary schedules. The metabolic studies revealed significant strain, sex, and age differences in appetite for sucrose, caloric intake, postprandial plasma levels of glucose and insulin, and weight gain after sucrose feeding. The findings indicate that sugar feeding led to increased plasma glucose and insulin levels; however, total caloric intake was decreased, and less weight gain was observed than in chow-fed controls, particularly among the hyperactive strains. In behavioral tests, sugar feeding did not alter spontaneous activity levels in any of the strains after either acute or chronic diets. There were also no significant effects of sucrose consumption on spatial learning and memory in a plus-shaped maze as determined by use of a shock-avoidance paradigm. The only significant behavioral effects of sucrose observed were an impairment in habituation and distractibility among the WK-HA females, the most hyperactive group among these strains.