Using FASS-LTP in postmortem mice brain tissues to assess pathological synaptic function.

Background: Study of synaptic integrity using conventional electrophysiology is a gold standard for quantitative assessment of neurodegeneration. Fluorescence assisted single-synapse long-term potentiation (FASS-LTP) provides a high throughput method to assess the synaptic integrity of neurotransmission within and between different brain regions as a measure of pharmacological efficacy in translational models.

New Method: We adapted the existing method to our purpose by adding a step during the thawing of frozen samples, by an extra step of placing them on a rocker at room temperature for 30 minutes immediately following thawing with constant mixing on a shaker.

Electrical stimulation of the vagus nerve ameliorates inflammation and disease activity in a rat EAE model of multiple sclerosis.

Multiple sclerosis (MS) is a demyelinating central nervous system (CNS) disorder that is associated with functional impairment and accruing disability. There are multiple U.S.

A neonate with a spongy failing heart - What could it be?

A neonate born of third-degree consanguineous marriage presented on day 12 of life with congestive cardiac failure. A male sibling died at 3 months of age, cause of which was not known. He was treated with decongestive measures and multiple inotropes.

Interaction of eugenol-based anti-tuberculosis nanoemulsion with bovine serum albumin: A spectroscopic study including Rifampicin, Isoniazid, Pyrazinamide, and Ethambutol.

Tuberculosis (TB), a deadly infectious disease, is primarily caused by the bacterium . The misuse of antibiotics has led to the development of drug resistance, prompting researchers to explore new technologies to combat multidrug-resistant Tuberculosis (MDR TB). Phospholipid-based nanotherapeutics, such as nanoemulsions, are gaining traction as they enhance drug solubility, stability, and bioavailability.

Gene regulatory changes underlie developmental plasticity in respiration and aerobic performance in highland deer mice.

Phenotypic plasticity can play an important role in the ability of animals to tolerate environmental stress, but the nature and magnitude of plastic responses are often specific to the developmental timing of exposure. Here, we examine changes in gene expression in the diaphragm of highland deer mice (Peromyscus maniculatus) in response to hypoxia exposure at different stages of development. In highland deer mice, developmental plasticity in diaphragm function may mediate changes in several respiratory traits that influence aerobic metabolism and performance under hypoxia.

Phospholipase D1 Attenuation Therapeutics Promotes Resilience against Synaptotoxicity in 12-Month-Old 3xTg-AD Mouse Model of Progressive Neurodegeneration.

Abrogating synaptotoxicity in age-related neurodegenerative disorders is an extremely promising area of research with significant neurotherapeutic implications in tauopathies including Alzheimer's disease (AD). Our studies using human clinical samples and mouse models demonstrated that aberrantly elevated phospholipase D1 (PLD1) is associated with amyloid beta (Aβ) and tau-driven synaptic dysfunction and underlying memory deficits. While knocking out the lipolytic gene is not detrimental to survival across species, elevated expression is implicated in cancer, cardiovascular conditions and neuropathologies, leading to the successful development of well-tolerated mammalian PLD isoform-specific small molecule inhibitors.

ZnO/Graphene Composite from Solvent-Exfoliated Few-Layer Graphene Nanosheets for Photocatalytic Dye Degradation under Sunlight Irradiation.

ZnO/graphene nanocomposites were prepared using a facile approach. Graphene nanosheets were prepared by ultrasonication-based liquid phase exfoliation of graphite powder in a low boiling point organic solvent, 1,2-Dichloroethane, for the preparation of ZnO/graphene nanocomposites. Structural properties of the synthesized ZnO/graphene nanocomposites were studied through powder XRD and micro-Raman analysis.

Evolution and molecular basis of a novel allosteric property of crocodilian hemoglobin.

The extraordinary breath-hold diving capacity of crocodilians has been ascribed to a unique mode of allosterically regulating hemoglobin (Hb)-oxygenation in circulating red blood cells. We investigated the origin and mechanistic basis of this novel biochemical phenomenon by performing directed mutagenesis experiments on resurrected ancestral Hbs. Comparisons of Hb function between the common ancestor of archosaurs (the group that includes crocodilians and birds) and the last common ancestor of modern crocodilians revealed that regulation of Hb-O affinity via allosteric binding of bicarbonate ions represents a croc-specific innovation that evolved in combination with the loss of allosteric regulation by ATP binding.

Novel in vitro methods for simultaneous screening of two antagonistic bacteria against multiple fungal phytopathogens in a single agar plate.

Two novel and rapid in vitro agar plate methods for simultaneous screening of two bacterial isolates for antagonism against multiple fungal phytopathogens in a single agar plate are described. In the modified plus streak method (MPS), in a 10 cm diameter PDA agar plate, two different bacterial isolates were screened against four fungal pathogens. The second method used 20 cm diameter PDA agar plate surface and was termed as the parallel multiple streak (PMS) method.

Comparison of albumin adjusted ischemia-modified albumin and total antioxidant status in patients with locally advanced head and neck cancer: A pilot study.

Background: Among all types of cancers in India, head and neck cancer (HNC) accounts for 30%. Oxidative stress (OS) is one of the aetiologies for cancer. However, it is not evaluated for these patients scheduled for anticancer therapy.

Aβ/tau oligomer interplay at human synapses supports shifting therapeutic targets for Alzheimer's disease.

Background: Alzheimer's disease (AD) is characterized by progressive cognitive decline due to accumulating synaptic insults by toxic oligomers of amyloid beta (AβO) and tau (TauO). There is growing consensus that preventing these oligomers from interacting with synapses might be an effective approach to treat AD. However, recent clinical trial failures suggest low effectiveness of targeting Aβ in late-stage AD.

Genetic variation in haemoglobin is associated with evolved changes in breathing in high-altitude deer mice.

Physiological systems often have emergent properties but the effects of genetic variation on physiology are often unknown, which presents a major challenge to understanding the mechanisms of phenotypic evolution. We investigated whether genetic variants in haemoglobin (Hb) that contribute to high-altitude adaptation in deer mice (Peromyscus maniculatus) are associated with evolved changes in the control of breathing. We created F2 inter-population hybrids of highland and lowland deer mice to test for phenotypic associations of α- and β-globin variants on a mixed genetic background.

Changes in hemoglobin function and isoform expression during embryonic development in the American alligator, .

In the developing embryos of egg-laying vertebrates, O flux takes place across a fixed surface area of the eggshell and the chorioallantoic membrane. In the case of crocodilians, the developing embryo may experience a decrease in O flux when the nest becomes hypoxic, which may cause compensatory adjustments in blood O transport. However, whether the switch from embryonic to adult hemoglobin isoforms (isoHbs) plays some role in these adjustments is unknown.

New insights into the allosteric effects of CO2 and bicarbonate on crocodilian hemoglobin.

Crocodilians are unique among vertebrates in that their hemoglobin (Hb) O2 binding is allosterically regulated by bicarbonate, which forms in red blood cells upon hydration of CO2. Although known for decades, this remarkable mode of allosteric control has not yet been experimentally verified with direct evidence of bicarbonate binding to crocodilian Hb, probably because of confounding CO2-mediated effects. Here, we provide the first quantitative analysis of the separate allosteric effects of CO2 and bicarbonate on purified Hb of the spectacled caiman (Caiman crocodilus).

The adaptive benefit of evolved increases in hemoglobin-O affinity is contingent on tissue O diffusing capacity in high-altitude deer mice.

Background: Complex organismal traits are often the result of multiple interacting genes and sub-organismal phenotypes, but how these interactions shape the evolutionary trajectories of adaptive traits is poorly understood. We examined how functional interactions between cardiorespiratory traits contribute to adaptive increases in the capacity for aerobic thermogenesis (maximal O consumption, V̇Omax, during acute cold exposure) in high-altitude deer mice (Peromyscus maniculatus). We crossed highland and lowland deer mice to produce F inter-population hybrids, which expressed genetically based variation in hemoglobin (Hb) O affinity on a mixed genetic background.

Novel and rapid agar plate methods for in vitro assessment of bacterial biocontrol isolates' antagonism against multiple fungal phytopathogens.

Biological control of plant diseases with antagonistic bacteria is a promising alternative to conventional chemical control strategies. In vitro screening for inhibition of mycelial growth of phytopathogenic fungi by bacterial isolates is the first step in selecting putative bacterial biocontrol agents. Dual culture plate assay is the most common method involved in this first-line selection process.

Chronic Low Dose Neutron Exposure Results in Altered Neurotransmission Properties of the Hippocampus-Prefrontal Cortex Axis in Both Mice and Rats.

The proposed deep space exploration to the moon and later to Mars will result in astronauts receiving significant chronic exposures to space radiation (SR). SR exposure results in multiple neurocognitive impairments. Recently, our cross-species (mouse/rat) studies reported impaired associative memory formation in both species following a chronic 6-month low dose exposure to a mixed field of neutrons (1 mGy/day for a total dose pf 18 cGy).

Prognostic Value of Amplitude-Integrated Electroencephalography in Term Neonates With Encephalopathy.

Objective: To evaluate the prognostic value of amplitude-integrated EEG in term neonates with encephalopathy.

Methods: In this prospective observational study we enrolled 58 term neonates with encephalopathy from March, 2019 to March, 2020. Level of alertness was ascertained as per Volpe's classification and tone as per Amiel-Tison scale of tone assessment.

Functional Integrity of Synapses in the Central Nervous System of Cognitively Intact Individuals with High Alzheimer's Disease Neuropathology Is Associated with Absence of Synaptic Tau Oligomers.

Background: Certain individuals, here referred to as Non-Demented with Alzheimer Neuropathology (NDAN), do not show overt neurodegeneration (N-) and remain cognitively intact despite the presence of plaques (A+) and tangles (T+) that would normally be consistent with fully symptomatic Alzheimer's disease (AD).

Objective: The existence of NDAN (A + T+N-) subjects suggests that the human brain utilizes intrinsic mechanisms that can naturally evade cognitive decline normally associated with the symptomatic stages of AD (A + T+N+). Deciphering the underlying mechanisms would prove relevant to develop complementing therapeutics to prevent progression of AD-related cognitive decline.

Effect of NH2-terminal acetylation on the oxygenation properties of vertebrate haemoglobin.

In vertebrate haemoglobin (Hb), the NH2-terminal residues of the α- and β-chain subunits are thought to play an important role in the allosteric binding of protons (Bohr effect), CO2 (as carbamino derivatives), chloride ions, and organic phosphates. Accordingly, acetylation of the α- and/or β-chain NH2-termini may have significant effects on the oxygenation properties of Hb. Here we investigate the effect of NH2-terminal acetylation by using a newly developed expression plasmid system that enables us to compare recombinantly expressed Hbs that are structurally identical except for the presence or absence of NH2-terminal acetyl groups.

Anacardic acid induces IL-33 and promotes remyelination in CNS.

Given the known neuroreparative actions of IL-33 in experimental models of central nervous system (CNS) injury, we predicted that compounds which induce IL-33 are likely to promote remyelination. We found anacardic acid as a candidate molecule to serve as a therapeutic agent to promote remyelination. Addition of anacardic acid to cultured oligodendrocyte precursor cells (OPCs) rapidly increased expression of myelin genes and myelin proteins, suggesting a direct induction of genes involved in myelination by anacardic acid.