Design, synthesis and evaluation the bioactivities of novel 1,3-dimethyl-6-amino-1H-indazole derivatives as anticancer agents.

Indoleamine 2,3-dioxygenase (IDO1) is a heme-containing enzyme mainly responsible for the metabolism of tryptophan to kynurenine. To date, the IDO1 inhibitors have been developed intensively for the re-activation of the anticancer immune response. In this report, we designed, and synthesized novel 1,3-dimethyl-6-amino indazole derivatives as IDO1 inhibitors based on the structure of IDO1 active site.

Age-Related Regional Network Covariance of Magnetic Resonance Imaging Gray Matter in the Rat.

Healthy human aging has been associated with brain atrophy in prefrontal and selective temporal regions, but reductions in other brain areas have been observed. We previously found regional covariance patterns of gray matter with magnetic resonance imaging (MRI) in healthy humans and rhesus macaques, using multivariate network Scaled Subprofile Model (SSM) analysis and voxel-based morphometry (VBM), supporting aging effects including in prefrontal and temporal cortices. This approach has yet to be applied to neuroimaging in rodent models of aging.

A novel p.A191D matrilin-3 variant in a Vietnamese family with multiple epiphyseal dysplasia: a case report.

Background: Multiple epiphyseal dysplasia (MED) is a common skeletal dysplasia that is characterized by variable degrees of epiphyseal abnormality primarily involving the hip and knee joints. Mutations in a gene encoding matrilin-3 (MATN3) have been reported as disease causing of autosomal dominant MED. The current study identified a novel c.

Gradual hypertension induction in middle-aged Cyp1a1-Ren2 transgenic rats produces significant impairments in spatial learning.

Hypertension is a major health concern in the developed world, and its prevalence increases with advancing age. The impact of hypertension on the function of the renal and cardiovascular systems is well studied; however, its influence on the brain regions important for cognition has garnered less attention. We utilized the Cyp1a1-Ren2 xenobiotic-inducible transgenic rat model to mimic both the age of onset and rate of induction of hypertension observed in humans.

Transcription of the immediate-early gene Arc in CA1 of the hippocampus reveals activity differences along the proximodistal axis that are attenuated by advanced age.

The CA1 region of the hippocampus receives distinct patterns of afferent input to distal (near subiculum) and proximal (near CA2) zones. Specifically, distal CA1 receives a direct projection from cells in the lateral entorhinal cortex that are sensitive to objects, whereas proximal CA1 is innervated by cells in the medial entorhinal cortex that are responsive to space. This suggests that neurons in different areas along the proximodistal axis of CA1 of the hippocampus will be functionally distinct.

Reduced gamma frequency in the medial frontal cortex of aged rats during behavior and rest: implications for age-related behavioral slowing.

Age-related cognitive and behavioral slowing may be caused by changes in the speed of neural signaling or by changes in the number of signaling steps necessary to achieve a given function. In the mammalian cortex, neural communication is organized by a 30-100 Hz "gamma" oscillation. There is a putative link between the gamma frequency and the speed of processing in a neural network: the dynamics of pyramidal neuron membrane time constants suggest that synaptic integration is framed by the gamma cycle, and pharmacological slowing of gamma also slows reaction times on behavioral tasks.

Activation patterns in superficial layers of neocortex change between experiences independent of behavior, environment, or the hippocampus.

Previous work suggests that activation patterns of neurons in superficial layers of the neocortex are more sensitive to spatial context than activation patterns in deep cortical layers. A possible source of this laminar difference is the distribution of contextual information to the superficial cortical layers carried by hippocampal efferents that travel through the entorhinal cortex and subiculum. To evaluate the role that the hippocampus plays in determining context sensitivity in superficial cortical layers, behavior-induced expression of the immediate early gene Arc was examined in hippocampus-lesioned and control rats after exposing them to 2 distinct contexts.

Experience-dependent firing rate remapping generates directional selectivity in hippocampal place cells.

When rodents engage in irregular foraging in an open-field environment, hippocampal principal cells exhibit place-specific firing that is statistically independent of the direction of traverse through the place field. When the path is restricted to a track, however, in-field rates differ substantially in opposite directions. Frequently, the representations of the track in the two directions are essentially orthogonal.

Dorsal hippocampus, CA3, and CA1 lesions disrupt temporal sequence completion.

An experiment was designed to evaluate effects of dorsal hippocampus, dorsal CA3a,b, dorsal CA1, and control lesions on performance of a temporal sequence task. Rats were trained on a sequential learning task involving six spatial locations on a radial 8-arm maze. After initial training followed by surgery, it was found that all lesioned animals were able to remember the sequence.

Sequences of clustered epitopes in Gag and Nef potentially presented by predominant class I human leukocyte antigen (HLA) alleles A and B expressed by human immunodeficiency virus type 1 (HIV-1)-infected patients in Vietnam.

The aim of this study was to define pluriepitopic regions in Gag and Nef possibly relevant in the perspective of a vaccine design in a vietnamese population. The protein sequences derived from gag and nef genes and phenotyping of the class I human leukocyte antigens (HLA) A and B alleles were established for 28 human immunodeficiency virus type 1 (HIV-1)-infected patients from Ho Chi Minh City, Vietnam. The protein sequences display polymorphism mutations as compared with a B reference strain (HXB2).

Different attenuated phenotypes of GM2 gangliosidosis variant B in Japanese patients with HEXA mutations at codon 499, and five novel mutations responsible for infantile acute form.

Eight mutations of the alpha subunit of beta-hexosaminidase A gene ( HEXA) were identified in eight patients with GM2 gangliosidosis variant B. They were five missense mutations, two splice-site mutations, and one two-base deletion. Five of them, R252L (CGT-->CTT), N295S (AAT-->AAC), W420C (TGG-->TGT), IVS 13, +2A-->C, and del 265-266AC (exon 2), were novel mutations responsible for infantile acute form of GM2 gangliosidosis.