Host cell CRISPR genomics and modelling reveal shared metabolic vulnerabilities in the intracellular development of Plasmodium falciparum and related hemoparasites.

Parasitic diseases, particularly malaria (caused by Plasmodium falciparum) and theileriosis (caused by Theileria spp.), profoundly impact global health and the socioeconomic well-being of lower-income countries. Despite recent advances, identifying host metabolic proteins essential for these auxotrophic pathogens remains challenging.

Metformin mediates neuroprotection and attenuates hearing loss in experimental pneumococcal meningitis.

Background: Pneumococcal meningitis is associated with high risk of neurological sequelae such as cognitive impairment and hearing loss. These sequelae are due to parenchymal brain and inner ear damage primarily induced by the excessive inflammatory reaction in response to bacterial brain invasion. Metformin-a biguanide drug to treat diabetes mellitus type 2-was recently found to suppress neuroinflammation and induce neuroregeneration.

Combining Ceftriaxone with Doxycycline and Daptomycin Reduces Mortality, Neuroinflammation, Brain Damage, and Hearing Loss in Infant Rat Pneumococcal Meningitis.

Despite appropriate antibiotic therapy, pneumococcal meningitis (PM) is associated with a case fatality rate of up to 30% in high-income countries. Survivors often suffer from severe lifelong disabilities. An excessive inflammatory reaction drives the pathophysiology, leading to brain damage and neurologic sequelae.

Thermal vibrations in the metallic glass CuZr.

Neutrons with 14.7 and 34 meV energy were used to determine the elastic and inelastic part of the structure factor for the metallic glass CuZr at 250 K. Based on the temperature dependence of the elastic scattering between 150 K and RT, an average mean-square displacement [Formula: see text] [Formula: see text] at 250 K is obtained.

Clustered field evaporation of metallic glasses in atom probe tomography.

Field evaporation of metallic glasses is a stochastic process combined with spatially and temporally correlated events, which are referred to as clustered evaporation (CE). This phenomenon is investigated by studying the distance between consecutive detector hits. CE is found to be a strongly localized phenomenon (up to 3nm in range) which also depends on the type of evaporating ions.

Crystal-Like Rearrangements of Icosahedra in Simulated Copper-Zirconium Metallic Glasses and their Effect on Mechanical Properties.

Indications of the Cu2Zr Laves phase are observed in MD simulations of amorphous Cu64Zr36 upon isothermal holding just above the glass transition temperature. The structural evolution towards Cu2Zr is accompanied by an increase in the fraction of Cu-centered icosahedra, which demonstrates that a large icosahedral fraction does not just indicate structural relaxation. The crystal-like regions generate an increase in strength and Young's modulus, and a stronger localized shear band.

Dopaminergic mediation of long-term behavioral effects of in utero drug exposure.

The influence of external agents on the developing brain has led to the hypothesis that, during critical periods of rapid development, such agents may have long-lasting effects on brain function and behavior. The dopaminergic systems are particularly suitable for examining the hypothesis, since the neural tracts using dopamine have been widely studied; their influence on behavior is, to some extent, understood; the tracts begin development in mice and rats late in gestation; and there are a number of drugs known to have particular effects on these systems. Literature is reviewed that supports the hypothesis that drugs affecting dopamine metabolism, when administered during the early development of the dopaminergic tracts, produce persistent changes both in the metabolism of dopamine and in behavior mediated by neural systems which utilize dopamine as a transmitter.

Pregnancy increases reactivity of mice to phenobarbital.

Compared to nonpregnant controls, pregnant mice injected with phenobarbital had lower concentrations of the drug in the plasma but equivalent concentrations in the brain. In spite of the similar concentrations in the brain, the behavioral response to phenobarbital was greater for pregnant than nonpregnant mice. These results suggest that the concentration of phenobarbital in the plasma, which is commonly used as a basis for adjusting phenobarbital dosage during pregnancy, is not an appropriate indicator of the dynamics of the drug.

Brain concentrations of phenobarbital and behavioral activation or depression.

Brain concentrations of phenobarbital and its effects on locomotor activity and lever responding for food reinforcement were determined at several intervals following injections into C57BL/6J mice. Phenobarbital either elevated or depressed both types of behavior depending on dose and time after injection. Excitation was noted at times and doses when brain concentration was 9 micrograms-11.

Prenatal maternal phenobarbital increases reactivity and retards habituation of mature offspring to environmental stimuli.

Adult female offspring of C57BL/6J mice injected daily with phenobarbital for the last third of pregnancy were more active than control offspring during a 3-min test period in an open field arena, thus confirming previous reports of lasting effects of prenatal exposure to phenobarbital. These offspring habituated less rapidly than control offspring to the open field and were more reactive to sudden changes in environmental stimuli. The behavioral changes were not accompanied by body or brain weight deficits.

Effects of prenatal maternal injections of phenobarbital on brain neurotransmitters and behavior of young C57 mice.

Offspring of C57BL/6J mice injected daily with phenobarbital (20 or 40 mg/kg) for the last 6 or 7 days of pregnancy were compared with offspring of saline control mice on behavioral and neurochemical measures of brain function at 21 days of age. Activity in an open field arena was elevated in male offspring and reactivity to presentation of a tone-light stimulus was increased for female offspring of drug treated dams. Brain concentration of dopamine and norepinephrine was reduced and the uptake of dopamine, norepinephrine serotonin and gamma-aminobutyric acid into synaptosomal preparations of brain tissue was greater for treated offspring.

Ascorbate blocks amphetamine-induced turning behavior in rats with unilateral nigro-striatal lesions.

Unilateral nigro-striatal lesions were produced in rats using 6-hydroxydopamine. Intraperitoneal injections of amphetamine induced circling behavior in these rats due to release of striatal dopamine contralateral to the lesion. Intraperitoneal injections of 1 g/kg of ascorbic acid elevated brain ascorbate.

Effects of methadone on activity and on brain monoamines in two strains of mice.

Two strains of mice (C57BL/6J and DBA/2J) were used to determine the effects of single and multiple injections of methadone on open field activity and on brain monoamines. For the DBA strain, the initial injection of methadone produced an attenuation of locomotor activity. After 7 daily injections, activity increased to that of controls.

Neurochemical and behavioral effects of diet related perinatal folic acid restriction.

Some effects of restricting dietary folic acid during the perinatal period on tissue folate and S-adenosyl-L-methionine (SAM) concentrations and on behavior were examined in 35-day-old DBA/2J mice. In one study dams were started on diets containing no folate (FO), 1.1 mg of folic acid/kg diet (F1.

Phenobarbital during pregnancy alters operant behavior of offspring in C57BL/6J mice.

Offspring of C57BL/6J injected daily with phenobarbital for the last third of pregnancy responded less than control animals when maintained on various fixed ratio schedules of reinforcement. The response decrement became more pronounced as the schedule demands were increased and was noted in offspring of both sexes. The higest dose (80 mg/kg) was less effective than the 2 lower doses (20 mg and 40 mg/kg) in producing the decrement which may reflect a selection factor due to high neonatal mortality previously reported at this dose.

Effects of phenobarbital given to pregnant mice on behavior of mature offspring.

Mature offspring of C57BL/6J mice (Mus musculus) injected daily with phenobarbital (40 mg/kg) for the last third of pregnancy differed from saline and untreated control animals on 3 measures of behavior. Offspring of phenobarbital treated animals had higher locomotor scores than controls during an open field activity test at 75 days of age. Male offspring were also tested on a 1-trial passive avoidance task and treated animals were found to be deficient.

Some effects of prenatal exposure to d-amphetamine sulfate and phenobarbital on developmental neurochemistry and on behavior.

Amphetamine. Prenatal intraperitoneal injection of d-amphetamine sulfate (5 mg/kg) produces decreases in the levels of catecholamines in the brain the day of birth and increases on day 30. Open-field activity from days 12 to 31 was higher for the group of animals injected with amphetamine or saline if scores were totaled across all test days.