Tau, Glial Fibrillary Acidic Protein, and Neurofilament Light Chain as Brain Protein Biomarkers in Cerebrospinal Fluid and Blood for Diagnosis of Neurobiological Diseases.

Neurological damage is the pathological substrate of permanent disability in various neurodegenerative disorders. Early detection of this damage, including its identification and quantification, is critical to preventing the disease's progression in the brain. Tau, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL), as brain protein biomarkers, have the potential to improve diagnostic accuracy, disease monitoring, prognostic assessment, and treatment efficacy.

Celf4 controls mRNA translation underlying synaptic development in the prenatal mammalian neocortex.

Abnormalities in neocortical and synaptic development are linked to neurodevelopmental disorders. However, the molecular and cellular mechanisms governing initial synapse formation in the prenatal neocortex remain poorly understood. Using polysome profiling coupled with snRNAseq on human cortical samples at various fetal phases, we identify human mRNAs, including those encoding synaptic proteins, with finely controlled translation in distinct cell populations of developing frontal neocortices.

Breast Tissue Reconstruction Using Polycaprolactone Ball Scaffolds in a Partial Mastectomy Pig Model.

Background: Breast cancer patients suffer from lowered quality of life (QoL) after surgery. Breast conservancy surgery (BCS) such as partial mastectomy is being practiced and studied as an alternative to solve this problem. This study confirmed breast tissue reconstruction in a pig model by fabricating a 3-dimensional (3D) printed Polycaprolactone spherical scaffold (PCL ball) to fit the tissue resected after partial mastectomy.

Making sense of mRNA landscapes: Translation control in neurodevelopment.

Like all other parts of the central nervous system, the mammalian neocortex undergoes temporally ordered set of developmental events, including proliferation, differentiation, migration, cellular identity, synaptogenesis, connectivity formation, and plasticity changes. These neurodevelopmental mechanisms have been characterized by studies focused on transcriptional control. Recent findings, however, have shown that the spatiotemporal regulation of post-transcriptional steps like alternative splicing, mRNA traffic/localization, mRNA stability/decay, and finally repression/derepression of protein synthesis (mRNA translation) have become just as central to the neurodevelopment as transcriptional control.

Extrinsic Regulators of mRNA Translation in Developing Brain: Story of WNTs.

Extrinsic molecules such as morphogens can regulate timed mRNA translation events in developing neurons. In particular, Wingless-type MMTV integration site family, member 3 (Wnt3), was shown to regulate the translation of mRNA encoding a Forkhead transcription factor P2 in the neocortex. However, the Wnt receptor that possibly mediates these translation events remains unknown.

Translational derepression of Elavl4 isoforms at their alternative 5' UTRs determines neuronal development.

Neurodevelopment requires precise regulation of gene expression, including post-transcriptional regulatory events such as alternative splicing and mRNA translation. However, translational regulation of specific isoforms during neurodevelopment and the mechanisms behind it remain unknown. Using RNA-seq analysis of mouse neocortical polysomes, here we report translationally repressed and derepressed mRNA isoforms during neocortical neurogenesis whose orthologs include risk genes for neurodevelopmental disorders.

Longer lifespan in the Rpd3 and Loco signaling results from the reduced catabolism in young age with noncoding RNA.

Downregulation of Rpd3 (histone deacetylase) or Loco (regulator of G-protein signaling protein) extends lifespan with higher stress resistance. We found -downregulated long-lived flies genetically interact with -upregulated short-lived flies in stress resistance and lifespan. Gene expression profiles between those flies revealed that they regulate common target genes in metabolic enzymes and signaling pathways, showing an opposite expression pattern in their contrasting lifespans.

Appropriate Amount of Regular Exercise Is Associated with a Reduced Mortality Risk.

Purpose: This study aimed at investigating whether there is a continuous dose-response relationship between the amount of physical activity (PA) and longevity benefit.

Methods: We evaluated the records of 23,257,723 Koreans age ≥20 yr who had undergone one biennial medical evaluation by the National Health Insurance Corporation. Participants with ≥20 min of vigorous or ≥30 min of moderate PA or walking were stratified into four groups: 0 d·wk; 1-3 d·wk; 4 to 5 d·wk; and 6-7 d·wk.

Stress resistance and lifespan enhanced by downregulation of antimicrobial peptide genes in the Imd pathway.

Biological behaviors and longevity of ectothermic animals are remarkably influenced by ambient temperature. Development at 18°C significantly enhances the stress resistance of adult flies with more accumulation of nutrients (especially fat) in the body than development at 25°C. Gene expression analysis between the flies developed at 18°C and 25°C revealed that the Immune deficiency (Imd) pathway, including the downstream antimicrobial peptides (AMPs), is downregulated in the flies developed at 18°C.

Gender-specific relationship between alcohol consumption and injury in the South Korean adults: A nationwide cross-sectional study.

Alcohol-related injuries have been concerned worldwide. However, there have been no large cross-sectional epidemiologic studies. The aim of this study was to investigate the association between alcohol and the prevalence of injury according to gender in a representative sample of the South Korean population.

Socioeconomic Disparities in the Prevalence of Blepharoptosis in the South Korean Adult Population Based on a Nationwide Cross-Sectional Study.

Purpose: We investigated the association between socioeconomic status (SES) and the prevalence of blepharoptosis in a representative South Korean population.

Methods: This cross-sectional study was based on data obtained in the Korea National Health and Nutrition Examination Survey from 2010 to 2012. In total, 17,178 Korean adults (7,261 men and 9,917 women) aged 19 years or older were enrolled.

Structure-activity relationships of amide-phosphonate derivatives as inhibitors of the human soluble epoxide hydrolase.

Structure-activity relationships of amide-phosphonate derivatives as inhibitors of the human soluble epoxide hydrolase (sEH) were investigated. First, a series of alkyl or aryl groups were substituted on the carbon alpha to the phosphonate function in amide compounds to see whether substituted phosphonates can act as a secondary pharmacophore. A tert-butyl group (16) on the alpha carbon was found to yield most potent inhibition on the target enzyme.

Heart-specific Rpd3 downregulation enhances cardiac function and longevity.

Downregulation of Rpd3, a homologue of mammalian Histone Deacetylase 1 (HDAC1), extends lifespan in Drosophila melanogaster. Once revealed that long-lived fruit flies exhibit limited cardiac decline, we investigated whether Rpd3 downregulation would improve stress resistance and/or lifespan when targeted in the heart. Contested against three different stressors (oxidation, starvation and heat), heart-specific Rpd3 downregulation significantly enhanced stress resistance in flies.

miR-206 Mediates YAP-Induced Cardiac Hypertrophy and Survival.

Rationale: In Drosophila, the Hippo signaling pathway negatively regulates organ size by suppressing cell proliferation and survival through the inhibition of Yorkie, a transcriptional cofactor. Yes-associated protein (YAP), the mammalian homolog of Yorkie, promotes cardiomyocyte growth and survival in postnatal hearts. However, the underlying mechanism responsible for the beneficial effect of YAP in cardiomyocytes remains unclear.

Normal range albuminuria and metabolic syndrome in South Korea: the 2011-2012 Korean National Health and Nutrition Examination Survey.

Background: It is well-known that there is a close relationship between metabolic syndrome (MetS) and microalbuminuria. However, some recent studies have found that even normal range albuminuria was associated with MetS and cardiometabolic risk factors. The purpose of this study is to analyze the relationship between MetS and normal range albuminuria and to calculate the cutoff value for albuminuria that correlates with MetS in the representative fraction of Korean population.

Lateral growth of ZnO nanorod arrays in polyhedral structures for high on-current field-effect transistors.

Lateral growth of one-dimensional nanostructures is crucial for high performance field-effect transistors (FETs) which can drive a high on-current that is proportional to the number of nanorods (NRs) aligned between electrodes. Hence, it is strongly required to laterally and directly grow a large number of NRs between electrodes. For the first time, we propose a polyhedral-type FET (PH-FET) based on laterally-grown ZnO NRs, which includes circle, square and triangle configurations.

Loco signaling pathway in longevity.

Despite the various roles of regulator of G protein signaling (RGS) protein in the G protein signaling pathway that have been defined, the function of RGS has not been characterized in longevity signaling pathways. We found that reduced expression of Loco, a Drosophila RGS protein, resulted in a longer lifespan of flies with stronger resistance to stress, higher MnSOD activity and increased fat content. In contrast, overexpression of the loco gene shortened the fly lifespan significantly, lowered stress resistance and reduced fat content, also indicating that the RGS domain containing GTPase-activating protein (GAP) activity is related to the regulation of longevity.

Structure-activity relationships of cycloalkylamide derivatives as inhibitors of the soluble epoxide hydrolase.

Structure-activity relationships of cycloalkylamide compounds as inhibitors of human sEH were investigated. When the left side of amide function was modified by a variety of cycloalkanes, at least a C6 like cyclohexane was necessary to yield reasonable inhibition potency on the target enzyme. In compounds with a smaller cycloalkane or with a polar group on the left side of amide function, no inhibition was observed.

Regulation of longevity by regulator of G-protein signaling protein, Loco.

Regulator of G-protein signaling (RGS) proteins contribute to G-protein signaling pathways as activators or repressors with GTPase-activating protein (GAP) activity. To characterize whether regulation of RGS proteins influences longevity in several species, we measured stress responses and lifespan of RGS-overexpressing and RGS-lacking mutants. Reduced expression of Loco, a RGS protein of Drosophila melanogaster, resulted in a longer lifespan for both male and female flies, also exhibiting stronger resistance to three different stressors (starvation, oxidation, and heat) and higher manganese-containing superoxide dismutase (MnSOD) activity.

Enhancement of stress resistances and downregulation of Imd pathway by lower developmental temperature in Drosophila melanogaster.

Ambient temperature affects the lifespan of cold-blooded organisms such as Drosophila melanogaster. To better understand what influences the lifespan of an adult fruit fly, we tested whether developmental temperature could affect stress responses used as surrogate markers for the aging process. When 2-day-old adult flies developed at two representative temperatures (18°C and 25°C) were challenged with three stresses (starvation, oxidation, and heat), both male and female flies developed at 18°C exhibited stronger resistance to all three stresses compared to those developed at 25°C.

MSL cis-spreading from roX gene up-regulates the neighboring genes.

The male-specific lethal (MSL) complex in Drosophila melanogaster paints the male X chromosome in a manner that is both cis and trans to induce 2-fold hypertranscription of the X chromosome. To characterize the upregulation of gene expression by MSL cis-spreading, we measured the expressional change of neighboring genes by microarray when the genes were bound by MSL complexes that spread from an autosomal roX transgene. Genes within a 200kb region that includes roX transgenes were upregulated concurrently with MSL cis-spreading.

Regulation of inter- and intramolecular interaction of RNA, DNA, and proteins by MLE.

Drosophila maleless (MLE) is a member of helicase superfamily 2 and functions as a dosage compensation factor essential for the development of male flies. This function provides a good opportunity to investigate diverse biochemical activities associated with MLE in the context of a defined in vivo pathway, i.e.

Predicting consensus structures for RNA alignments via pseudo-energy minimization.

Thermodynamic processes with free energy parameters are often used in algorithms that solve the free energy minimization problem to predict secondary structures of single RNA sequences. While results from these algorithms are promising, an observation is that single sequence-based methods have moderate accuracy and more information is needed to improve on RNA secondary structure prediction, such as covariance scores obtained from multiple sequence alignments. We present in this paper a new approach to predicting the consensus secondary structure of a set of aligned RNA sequences via pseudo-energy minimization.