Tubulin isotypes contribute opposing properties to balance anaphase spindle morphogenesis.

Faithful chromosome segregation requires proper function of the mitotic spindle, which is built from, and depends on, the coordinated regulation of many microtubules and the activities of molecular motors and MAPs. In addition, microtubules themselves are assembled from multiple variants, or isotypes of α- and β-tubulin, yet whether they mediate the activities of motors and MAPs required for proper spindle function remains poorly understood. Here, we use budding yeast to reveal that α-tubulin isotypes regulate opposing outward- and inward-directed forces in the spindle midzone that facilitate optimal spindle elongation and length control.

A stable microtubule bundle formed through an orchestrated multistep process controls quiescence exit.

Cells fine-tune microtubule assembly in both space and time to give rise to distinct edifices with specific cellular functions. In proliferating cells, microtubules are highly dynamics, and proliferation cessation often leads to their stabilization. One of the most stable microtubule structures identified to date is the nuclear bundle assembled in quiescent yeast.

The memory ameliorating effects of novel N-benzyl pyridine-2-one derivatives on scopolamine-induced cognitive deficits in mice.

Background: Alzheimer's disease (AD), the most common form of progressive dementia in the elderly, is a chronic neurological disorder that decreases cognitive ability. Although the underlying cause of AD is yet unknown, oxidative stress and brain acetylcholine shortage are the key pathogenic causes.

Results: The current study shows that these derivatives have the potential to improve memory in mice by inhibiting scopolamine-induced acetylcholinesterase activity, oxidative and nitrosative stress, and improving locomotor activity and muscle grip strength in the rota rod test.

Comparison of online, offline, and hybrid hypotheses of motor sequence learning using a quantitative model that incorporate reactive inhibition.

Two hypotheses have been advanced for when motor sequence learning occurs: offline between bouts of practice or online concurrently with practice. A third possibility is that learning occurs both online and offline. A complication for differentiating between those hypotheses is a process known as reactive inhibition, whereby performance worsens over consecutively executed sequences, but dissipates during breaks.

Novel Substituted Pyrimidine Derivatives as Potential Anti-Alzheimer's Agents: Synthesis, Biological, and Molecular Docking Studies.

The most frequent type of age-related dementia is Alzheimer's disease. To discover novel therapeutic agents for Alzheimer's disease, a series of substituted pyrimidine derivatives were synthesized and evaluated for anti-Alzheimer's activity. All the synthesized compounds were validated by HNMR, CNMR, and HRMS to assess the structural conformance of the newly synthesized compounds.

Investigation, scaffold hopping of novel donepezil-based compounds as anti-Alzhiemer's agents: synthesis, in-silico and pharmacological evaluations.

Alzheimer's disease (AD) is a multifaceted neurodegenerative condition. The pathogenesis of AD is highly intricate and the disease is apparent in the aged population ~ 50-70 years old. Even after > 100 years of research, the root origin of AD and its pathogenesis is unclear, complex and multifaceted.

Tubulin CFEOM mutations both inhibit or activate kinesin motor activity.

Kinesin-mediated transport along microtubules is critical for axon development and health. Mutations in the kinesin Kif21a, or the microtubule subunit β-tubulin, inhibit axon growth and/or maintenance resulting in the eye-movement disorder congenital fibrosis of the extraocular muscles (CFEOM). While most examined CFEOM-causing β-tubulin mutations inhibit kinesin-microtubule interactions, Kif21a mutations activate the motor protein.

Using Taxol-sensitized budding yeast to investigate the effect of microtubule stabilization on anaphase onset.

The microtubule (MT)-stabilizing drug Taxol (paclitaxel) is a commonly used tool to investigate MT dynamics and MT-dependent processes. Here, we present a protocol for using Taxol-sensitized budding yeast to investigate the effect of microtubule stabilization on anaphase onset. We describe steps for establishing a log phase culture, synchronizing cells in G1, arresting in metaphase, and releasing cells into Taxol.

Neuroprotective effects of novel pyrrolidine-2-one derivatives on scopolamine-induced cognitive impairment in mice: Behavioral and biochemical analysis.

Alzheimer's disease (AD) is a long-term neurodegenerative condition that impairs cognitive abilities. In brain acetylcholine deficit and oxidative stress may be considered the key pathogenic causes for AD, even though the basic etiology is still unknown. The effects of some novel pyrrolidine-2-one derivatives on the learning and memory deficits caused by scopolamine in mice were examined in the current study.

The importance of microtubule-dependent tension in accurate chromosome segregation.

Accurate chromosome segregation is vital for cell and organismal viability. The mitotic spindle, a bipolar macromolecular machine composed largely of dynamic microtubules, is responsible for chromosome segregation during each cell replication cycle. Prior to anaphase, a bipolar metaphase spindle must be formed in which each pair of chromatids is attached to microtubules from opposite spindle poles.

Identification and characterization of probiotics isolated from indigenous chicken (Gallus domesticus) of Nepal.

Background: Excessive and irrational use of antibiotics as growth promoters in poultry has been one of key factors contributing to increased emergence of antibiotics resistant bacteria. Several alternatives for antibiotic growth promoters are being sought, and the search for effective probiotics to be used as feed additives is amongst the promising ones. Our study aimed to isolate and test potential probiotics bacteria from cloacal swabs of various indigenous chicken (Gallus domesticus) breeds from rural outskirts of the Kathmandu valley (Nepal).

Pulmonary function in cured pulmonary tuberculosis cases.

Background: In clinical practice it has been observed that several patients of cured pulmonary tuberculosis (PTB) suffer with lung dysfunction and these problems are less documented routinely. Prevalence of these abnormalities remains unknown. Aim of this study is to estimate the lung function abnormality and exercise capacity including diffusion capacity of lung for carbon monoxide (DLCO) in cured PTB cases.

Dissipation of reactive inhibition is sufficient to explain post-rest improvements in motor sequence learning.

The prevailing hypothesis for observed post-rest motor reaction time improvements is offline consolidation. In the present study, we present evidence for an alternate account involving the accrual and dissipation of reactive inhibition. Four groups of participants (N = 159) performed a finger-tapping task involving either massed (30 s per trial) or spaced (10 s per trial) training, and with one of two break intervals between each trial: 10 s or 30 s.

The role of anhedonia in predicting risk-taking behavior in university students.

There is a growing interest in understanding symptoms of psychological distress, such as anhedonia, not just as related to individual psychological disorders, but transdiagnostically. This broader focus allows for the investigation of the effects of symptoms across disorders, or in non-clinical samples. Previous work has linked anhedonia and risk-taking behavior in clinical samples, though the exploration of this relationship in healthy adolescents and early adults is still a relatively new area of research.

A Recent Appraisal of Small-Organic Molecules as Anti-Alzheimer's Agents.

Background: Alzheimer's disease (AD) is an irreversible, progressive and very complex brain disorder. There is still uncertainty about the etiology of AD; however, a few hallmarks like an aggregation of tau proteins, amyloid-β plaques, oxidative stress, low level of choline in the brain etc., play significant roles.

The adverse effects of solid biomass fuel exposure on lung functions in non-smoking female population.

Background: Though, smoking is the leading cause of chronic obstructive pulmonary disease worldwide, the household air pollution due to use of solid biomass fuel is considered as a major risk factor for the development of obstructive lung disease. The aim of the study was to assess the effect of solid biomass fuel exposure on lung functions in non-smoking female population.

Methods: A hospital based, descriptive cross sectional study was carried out among 140 non-smoking female patients aged 40 or more and who had been exposed to solid biomass fuel.

Design, synthesis, extra-precision docking, and molecular dynamics simulation studies of pyrrolidin-2-one derivatives as potential acetylcholinesterase inhibitors.

Inhibition of acetylcholinesterase (AChE) has been widely explored to develop novel molecules for management of Alzheimer's disease. In past research finding reported molecule 3-(4-(4-fluorobenzoyl)piperidin-1-yl)-1-(4-methoxybenzyl)pyrrolidin-2-one displayed a spectrum of anti-Alzheimer's properties herein, we report a library of 18 novel molecules that were rationally designed and synthesized employing known literature to mimic and explore the novel chemical space around the lead compound and donepezil. All the compounds were docked in extra-precision mode with AChE (PDB ID 4EY7) using the Glide module.

Microtubules in Microorganisms: How Tubulin Isotypes Contribute to Diverse Cytoskeletal Functions.

The cellular functions of the microtubule (MT) cytoskeleton range from relatively simple to amazingly complex. Assembled from tubulin, a heterodimeric protein with α- and β-tubulin subunits, microtubules are long, hollow cylindrical filaments with inherent polarity. They are intrinsically dynamic polymers that utilize GTP binding by tubulin, and subsequent hydrolysis, to drive spontaneous assembly and disassembly.

Tubulin isotypes - functional insights from model organisms.

The microtubule cytoskeleton is assembled from the α- and β-tubulin subunits of the canonical tubulin heterodimer, which polymerizes into microtubules, and a small number of other family members, such as γ-tubulin, with specialized functions. Overall, microtubule function involves the collective action of multiple α- and β-tubulin isotypes. However, despite 40 years of awareness that most eukaryotes harbor multiple tubulin isotypes, their role in the microtubule cytoskeleton has remained relatively unclear.

Severe publication bias contributes to illusory sleep consolidation in the motor sequence learning literature.

We explored the possibility of publication bias in the sleep and explicit motor sequence learning literature by applying precision effect test (PET) and precision effect test with standard errors (PEESE) weighted regression analyses to the 88 effect sizes from a recent comprehensive literature review (Pan & Rickard, 2015). Basic PET analysis indicated pronounced publication bias; that is, the effect sizes were strongly predicted by their standard error. When variables that have previously been shown to both moderate the sleep gain effect and substantially reduce unaccounted for effect size heterogeneity were included in that analysis, evidence for publication bias remained strong.

Tubulin isotypes optimize distinct spindle positioning mechanisms during yeast mitosis.

Microtubules are dynamic cytoskeleton filaments that are essential for a wide range of cellular processes. They are polymerized from tubulin, a heterodimer of α- and β-subunits. Most eukaryotic organisms express multiple isotypes of α- and β-tubulin, yet their functional relevance in any organism remains largely obscure.

Prior episodic learning and the efficacy of retrieval practice.

In three experiments we investigated how the level of study-based, episodic knowledge influences the efficacy of subsequent retrieval practice (testing) as a learning event. Possibilities are that the efficacy of a test, relative to a restudy control, decreases, increases, or is independent of the degree of prior study-based learning. The degree of study-based learning was manipulated by varying the number of item repetitions in the initial study phase between one and eight.

Novel Benzylated (Pyrrolidin-2-one)/(Imidazolidin-2-one) Derivatives as Potential Anti-Alzheimer's Agents: Synthesis and Pharmacological Investigations.

A series of -benzylated (pyrrolidin-2-one)/(imidazolidin-2-one) derivatives were synthesized and evaluated for anti-Alzheimer's activity. The analogs were designed and synthesized on the basis of lead compound donepezil, which is currently prescribed as a major drug for the management of mild to severe Alzheimer's disease. Considering the structure activity relationship (SAR) of the lead compound, we first replaced the 5,6-dimethoxy-1-indanone moiety with -benzylated (pyrrolidin-2-one)/(imidazolidin-2-one) () without depriving the key functionality interactions like carbonyl and dimethoxyphenyl and second substituted the spacer linkage () in donepezil.

Relationships between intrinsic functional connectivity, cognitive control, and reading achievement across development.

There are vast individual differences in reading achievement between students. Besides structural and functional variability in domain-specific brain regions, these differences may partially be explained by the organization of domain-general functional brain networks. In the current study we used resting-state functional MRI data from the Philadelphia Neurodevelopmental Cohort (PNC; N = 553; ages 8-22) to examine the relation between performance on a well-validated reading assessment task, the Wide Range Achievement Word Reading Test (WRAT-Reading) and patterns of functional connectivity.

State-Dependent Functional Dysconnectivity in Youth With Psychosis Spectrum Symptoms.

Psychosis spectrum disorders are conceptualized as neurodevelopmental disorders accompanied by disruption of large-scale functional brain networks. Dynamic functional dysconnectivity has been described in patients with schizophrenia and in help-seeking individuals at clinical high risk for psychosis. Less is known, about developmental aspects of dynamic functional network connectivity (dFNC) associated with psychotic symptoms (PS) in the general population.