Improvement in functional motor scores in patients with non-ambulatory spinal muscle atrophy during Nusinersen treatment in South Korea: a single center study.

We analyzed the changes in various motor function scores over a four-year period in patients with non-ambulatory spinal muscular atrophy (SMA) during Nusinersen treatment. Patients underwent Hammersmith Infant Neurological Examination (HINE) or Hammersmith Functional Motor Scale Expanded (HFMSE) before treatment, and approximately every 4 months thereafter. Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) or Children's Hospital of Philadelphia - Adult Test of Neuromuscular Disorders (CHOP ATEND), Revised Upper Limb Module (RULM), and Motor Function Measure (MFM) were performed based on baseline functional status. Narrative interviews were conducted to explore post-treatment physical improvement regarding activities of daily living (ADLs) and fatigue after ADLs. Based on HFMSE results, 9 patients achieved minimum clinically important differences. Average rates of change (slopes) with corresponding 95% confidence intervals for all assessment tools were in a positive direction. CHOP-INTEND showed the most prominent improvement in children and adolescents followed by HFMSE. Improvements in CHOP-ATEND were most noticeable in adults. Improvements were accompanied by changes in ADLs as observed in the narrative interviews. It is necessary to consider various functional aspects to determine the effectiveness of Nusinersen therapy. The objective assessment of the therapeutic effect of Nusinersen in non-ambulatory SMA requires consideration of functional aspects and the related ADLs.

Tumors overcome the action of the wasting factor ImpL2 by locally elevating Wnt/Wingless.

Tumors often secrete wasting factors associated with atrophy and the degeneration of host tissues. If tumors were to be affected by the wasting factors, mechanisms allowing tumors to evade the adverse effects of the wasting factors must exist, and impairing such mechanisms may attenuate tumors. We use Drosophila midgut tumor models to show that tumors up-regulate Wingless (Wg) to oppose the growth-impeding effects caused by the wasting factor, ImpL2 (insulin-like growth factor binding protein [IGFBP]-related protein). Growth of Yorkie (Yki)-induced tumors is dependent on Wg while either elimination of ImpL2 or elevation of insulin/insulin-like growth factor signaling in tumors revokes this dependency. Notably, Wg augmentation could be a general mechanism for supporting the growth of tumors with elevated ImpL2 and exploited to attenuate muscle degeneration during wasting. Our study elucidates the mechanism by which tumors negate the action of ImpL2 to uphold their growth during cachexia-like wasting and implies that targeting the Wnt/Wg pathway might be an efficient treatment strategy for cancers with elevated IGFBPs.

Concomitant expression patterns of CDX2 and SATB2 as prognostic factors in stage III colorectal cancers.

CDX2 and SATB2 are often used as biomarkers for identification of colorectal origin in primary or metastatic adenocarcinomas. Loss of CDX2 or SATB2 expression has been associated with poor prognosis in patients with colorectal cancer (CRC). However, little is known regarding clinicopathological features, including prognosis, of CRCs with concomitant loss of CDX2 and SATB2. A total of 431 stage III CRCs were analyzed for their expression status in CDX2 and SATB2 using tissue microarray-based immunohistochemistry and expression status was correlated with clinicopathological variables, molecular alterations, and survival. CDX2-negative (CDX2-) CRCs and SATB2-negative (SATB2-) CRCs were found in 8.1 % and 17.2 % of CRCs, respectively, whereas both CDX2-negative and SATB2-negative (CDX2-/SATB2-) CRCs comprised 3.2 % of the CRCs. On survival analysis, neither CDX2-/SATB2+ nor CDX2+/SABT2- CRCs but CDX2-/SATB2- CRCs were associated with poor prognosis. CDX2-/SATB2- CRCs showed significant associations with tumor subsite of right colon, poor differentiation, decreased expression of CK20, aberrant expression of CK7, CIMP-high, MSI-high, and BRAF mutation. In summary, our results suggest that concomitant loss of CDX2 and SATB2 is a prognostic biomarker but isolated loss of CDX2 or SATB2 is not a prognostic biomarker for stage III CRCs.

Cholesterol sulfate inhibits osteoclast differentiation and survival by regulating the AMPK-Sirt1-NF-κB pathway.

Cholesterol sulfate (CS) is an activator of retinoic acid-related orphan receptor α (RORα). CS treatment or RORα overexpression attenuates osteoclastogenesis in a collagen-induced arthritis mouse model. However, the mechanism by which CS and RORα regulate osteoclast differentiation remains largely unknown. Thus, we aimed to investigate the role of CS and RORα in osteoclastogenesis and their underlying mechanism. CS inhibited osteoclast differentiation, but RORα deficiency did not affect osteoclast differentiation and CS-mediated inhibition of osteoclastogenesis. CS enhanced adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and sirtuin1 (Sirt1) activity, leading to nuclear factor-κB (NF-κB) inhibition by decreasing acetylation at Lys310 of p65. The NF-κB inhibition was restored by AMPK inhibitor, but the effects of CS on AMPK and NF-κB were not altered by RORα deficiency. CS also induced osteoclast apoptosis, which may be due to sustained AMPK activation and consequent NF-κB inhibition, and the effects of CS were significantly reversed by interleukin-1ß treatment. Collectively, these results indicate that CS inhibits osteoclast differentiation and survival by suppressing NF-κB via the AMPK-Sirt1 axis in a RORα-independent manner. Furthermore, CS protects against bone destruction in lipopolysaccharide- and ovariectomy-mediated bone loss mouse models, suggesting that CS is a useful therapeutic candidate for treating inflammation-induced bone diseases and postmenopausal osteoporosis.

Wear and tear of the intestinal visceral musculature by intrinsic and extrinsic factors.

BACKGROUND: The gut visceral musculature plays essential roles in not only moving substances through the lumen but also maintaining the function and physiology of the gut. Although the development of the visceral musculature has been studied in multiple model organisms, how it degenerates is poorly understood. RESULTS: Here, we employ the Drosophila midgut as a model to demonstrate that the visceral musculature is disrupted by intrinsic and extrinsic factors, such as aging, feeding, chemical-induced tissue damage, and oncogenic transformation in the epithelium. Notably, we define four prominent visceral musculature disruption phenotypes, which we refer as "sprout," "discontinuity," "furcation," and "crossover" of the longitudinal muscle. Given that the occurrence of these phenotypes is increased during aging and under various stresses, we propose that these phenotypes can be used as quantitative readouts of deterioration of the visceral musculature. Intriguingly, administration of a tissue-damaging chemical dextran sulfate sodium (DSS) induced similar visceral musculature disruption phenotypes in zebrafish larvae, indicating that ingestion of a tissue-damaging chemical can disrupt the visceral musculature in a vertebrate as well. CONCLUSIONS: Our study provides insights into the deterioration of the gut visceral musculature and lays a groundwork for investigating the underlying mechanisms in Drosophila as well as other animals.

Dynein light chain LC8 alleviates nonalcoholic steatohepatitis by inhibiting NF-κB signaling and reducing oxidative stress.

Nonalcoholic steatohepatitis (NASH) is a liver disease characterized by fat accumulation and chronic inflammation in the liver. Dynein light chain of 8 kDa (LC8) was identified previously as an inhibitor of nuclear factor kappa B (NF-κB), a key regulator of inflammation, however, its role in NASH remains unknown. In this study, we investigated whether LC8 can alleviate NASH using a mouse model of methionine and choline-deficient (MCD) diet-induced NASH and examined the underlying mechanism. LC8 transgenic (Tg) mice showed lower hepatic steatosis and less progression of NASH, including hepatic inflammation and fibrosis, compared to wild-type (WT) mice after consuming an MCD diet. The hepatic expression of lipogenic genes was lower, while that of lipolytic genes was greater in LC8 Tg mice than WT mice, which might be associated with resistance of LC8 Tg mice to hepatic steatosis. Consumption of an MCD diet caused oxidative stress, IκBα phosphorylation, and subsequent p65 liberation from IκBα and nuclear translocation, resulting in induction of proinflammatory cytokines and chemokines. However, these effects of MCD diet were reduced by LC8 overexpression. Collectively, these results suggest that LC8 alleviates MCD diet-induced NASH by inhibiting NF-κB through binding to IκBα to interfere with IκBα phosphorylation and by reducing oxidative stress via scavenging reactive oxygen species. Thus, boosting intracellular LC8 could be a potential therapeutic strategy for patients with NASH.

Combinatory statuses of tumor stromal percentage and tumor infiltrating lymphocytes as prognostic factors in stage III colorectal cancers.

BACKGROUND AND AIM: Tumor stroma and tumor-infiltrating lymphocytes (TILs) are major constituents of the tumor microenvironment, although they have different effects on the prognosis of patients with colorectal cancer (CRC). Combinatory statuses of tumor-stromal percentage (TSP) and TILs are expected to provide more powerful prognostic information but have never been studied in CRCs. METHODS: Stage III CRCs from patients (n = 487) treated with adjuvant chemotherapy were assessed for their TSP and CD3-TIL or CD8-TIL densities using computer-aided methodology. With cut-off values set at median values for intraepithelial TIL (iTIL) and stromal TIL (sTIL) densities, CRCs were sorted into low and high iTIL or sTIL groups. CRCs were classified into five quintile (Q1-Q5) groups according to their TSP and divided into high TSP (Q5) and low TSP (Q1-4) groups. RESULTS: The combination of CD8 iTIL density and TSP was found to be an independent prognostic parameter in multivariate survival analysis in terms of cancer-specific survival and recurrence-free survival. CRCs with low CD8 iTIL density and high TSP showed the worst survival. The combinatory status showed more prognostic power than CD8 iTIL density or TSP alone. Multivariate survival analysis in an independent cohort of stage III CRC validated the prognostic power of the combinatory statuses. CONCLUSIONS: The findings suggest that the combinatory status might serve as a prognostic parameter in stage III CRCs. Further research in a large-scale cohort of patients with stage III CRC is needed to validate the prognostic power of the combinatory status.

The role of translationally controlled tumor protein in proliferation of Drosophila intestinal stem cells.

Translationally controlled tumor protein (TCTP) is a highly conserved protein functioning in multiple cellular processes, ranging from growth to immune responses. To explore the role of TCTP in tissue maintenance and regeneration, we employed the adult Drosophila midgut, where multiple signaling pathways interact to precisely regulate stem cell division for tissue homeostasis. Tctp levels were significantly increased in stem cells and enteroblasts upon tissue damage or activation of the Hippo pathway that promotes regeneration of intestinal epithelium. Stem cells with reduced Tctp levels failed to proliferate during normal tissue homeostasis and regeneration. Mechanistically, Tctp forms a complex with multiple proteins involved in translation and genetically interacts with ribosomal subunits. In addition, Tctp increases both Akt1 protein abundance and phosphorylation in vivo. Altogether, Tctp regulates stem cell proliferation by interacting with key growth regulatory signaling pathways and the translation process in vivo.

Flunarizine inhibits osteoclastogenesis by regulating calcium signaling and promotes osteogenesis.

Many bone diseases such as osteoporosis and periodontitis are caused by hyperactivation of osteoclasts. Calcium (Ca2+ ) signals are crucial for osteoclast differentiation and function. Thus, the blockade of Ca2+ signaling may be a strategy for regulating osteoclast activity and has clinical implications. Flunarizine (FN) is a Ca2+ channel antagonist that has been used for reducing migraines. However, the role of FN in osteoclast differentiation and function remains unknown. Here, we investigated whether FN regulates osteoclastogenesis and elucidated the molecular mechanism. FN inhibited osteoclast differentiation along with decreased expression of nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), and attenuated osteoclast maturation and bone resorption. FN inhibition of osteoclast differentiation was restored by ectopic expression of constitutively active NFATc1. FN reduced calcium oscillations and its inhibition of osteoclast differentiation and resorption function was reversed by ionomycin, an ionophore that binds Ca2+ . FN also inhibited Ca2+ /calmodulin-dependent protein kinase IV (CaMKIV) and calcineurin leading to a decrease in the cAMP-responsive element-binding protein-dependent cFos and peroxisome proliferator-activated receptor-γ coactivator 1ß expression, and NFATc1 nuclear translocation. These results indicate that FN inhibits osteoclastogenesis via regulating CaMKIV and calcineurin as a Ca2+ channel blocker. In addition, FN-induced apoptosis in osteoclasts and promoted osteogenesis. Furthermore, FN protected lipopolysaccharide- and ovariectomy-induced bone destruction in mouse models, suggesting that it has therapeutic potential for treating inflammatory bone diseases and postmenopausal osteoporosis.

Cinchonine inhibits osteoclast differentiation by regulating TAK1 and AKT, and promotes osteogenesis.

Cinchonine (CN) has been known to exert antimalarial, antiplatelet, and antiobesity effects. It was also recently reported to inhibit transforming growth factor ß-activated kinase 1 (TAK1) and protein kinase B (AKT) through binding to tumor necrosis factor receptor-associated factor 6 (TRAF6). However, its role in bone metabolism remains largely unknown. Here, we showed that CN inhibits osteoclast differentiation with decreased expression of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), a key determinant of osteoclastogenesis. Immunoblot and quantitative real-time polymerase chain reaction analysis as well as the reporter assay revealed that CN inhibits nuclear factor-κB and activator protein-1 by regulating TAK1. CN also attenuated the activation of AKT, cyclic AMP response element-binding protein, and peroxisome proliferator-activated receptor-γ coactivator 1ß (PGC1ß), an essential regulator of mitochondrial biogenesis. Collectively, these results suggested that CN may inhibit TRAF6-mediated TAK1 and AKT activation, which leads to downregulation of NFATc1 and PGC1ß resulting in the suppression of osteoclast differentiation. Interestingly, CN not only inhibited the maturation and resorption function of differentiated osteoclasts but also promoted osteoblast differentiation. Furthermore, CN protected lipopolysaccharide- and ovariectomy-induced bone destruction in mouse models, suggesting its therapeutic potential for treating inflammation-induced bone diseases and postmenopausal osteoporosis.

Exosomal miRNA profiling from H5N1 avian influenza virus-infected chickens.

Exosomes are membrane vesicles containing proteins, lipids, DNA, mRNA, and micro RNA (miRNA). Exosomal miRNA from donor cells can regulate the gene expression of recipient cells. Here, Ri chickens were divided into resistant (Mx/A; BF2/B21) and susceptible (Mx/G; BF2/B13) trait by genotyping of Mx and BF2 genes. Then, Ri chickens were infected with H5N1, a highly pathogenic avian influenza virus (HPAIV). Exosomes were purified from blood serum of resistant chickens for small RNA sequencing. Sequencing data were analysed using FastQCv0.11.7, Cutadapt 1.16, miRBase v21, non-coding RNA database, RNAcentral 10.0, and miRDeep2. Differentially expressed miRNAs were determined using statistical methods, including fold-change, exactTest using edgeR, and hierarchical clustering. Target genes were predicted using miRDB. Gene ontology analysis was performed using gProfiler. Twenty miRNAs showed significantly different expression patterns between resistant control and infected chickens. Nine miRNAs were up-regulated and 11 miRNAs were down-regulated in the infected chickens compared with that in the control chickens. In target gene analysis, various immune-related genes, such as cytokines, chemokines, and signalling molecules, were detected. In particular, mitogen-activated protein kinase (MAPK) pathway molecules were highly controlled by differentially expressed miRNAs. The result of qRT-PCR for miRNAs was identical with sequencing data and miRNA expression level was higher in resistant than susceptible chickens. This study will help to better understand the host immune response, particularly exosomal miRNA expression against HPAIV H5N1 and could help to determine biomarkers for disease resistance.

Utility of Apical Lung Assessment on Computed Tomography Angiography as a COVID-19 Screen in Acute Stroke.

BACKGROUND AND PURPOSE: Evaluation of the lung apices using computed tomography angiography of the head and neck during acute ischemic stroke (AIS) can provide the first objective opportunity to screen for coronavirus disease 2019 (COVID-19). METHODS: We performed an analysis assessing the utility of apical lung exam on computed tomography angiography for COVID-19-specific lung findings in 57 patients presenting with AIS. We measured the diagnostic accuracy of apical lung assessment alone and in combination with patient-reported symptoms and incorporate both to propose a COVID-19 era AIS algorithm. RESULTS: Apical lung assessment when used in isolation, yielded a sensitivity of 0.67, specificity of 0.93, positive predictive value of 0.19, negative predictive value of 0.99, and accuracy of 0.92 for the diagnosis of COVID-19, in patients presenting to the hospital for AIS. When combined with self-reported clinical symptoms of cough or shortness of breath, sensitivity of apical lung assessment improved to 0.83. CONCLUSIONS: Apical lung assessment on computed tomography angiography is an accurate screening tool for COVID-19 and can serve as part of a combined screening approach in AIS.

Skullcapflavone II inhibits osteoclastogenesis by regulating reactive oxygen species and attenuates the survival and resorption function of osteoclasts by modulating integrin signaling.

Many bone diseases, such as osteoporosis and rheumatoid arthritis, are attributed to an increase in osteoclast number or activity; therefore, control of osteoclasts has significant clinical implications. This study shows how skullcapflavone II (SFII), a flavonoid with anti-inflammatory activity, regulates osteoclast differentiation, survival, and function. SFII inhibited osteoclastogenesis with decreased activation of MAPKs, Src, and cAMP response element-binding protein (CREB), which have been known to be redox sensitive. SFII decreased reactive oxygen species by scavenging them or activating nuclear factor-erythroid 2-related factor 2 (Nrf2), and its effects were partially reversed by hydrogen peroxide cotreatment or Nrf2 deficiency. In addition, SFII attenuated survival, migration, and bone resorption, with a decrease in the expression of integrin ß3, Src, and p130 Crk-associated substrate, and the activation of RhoA and Rac1 in differentiated osteoclasts. Furthermore, SFII inhibited osteoclast formation and bone loss in an inflammation- or ovariectomy-induced osteolytic mouse model. These findings suggest that SFII inhibits osteoclastogenesis through redox regulation of MAPKs, Src, and CREB and attenuates the survival and resorption function by modulating the integrin pathway in osteoclasts. SFII has therapeutic potential in the treatment and prevention of bone diseases caused by excessive osteoclast activity.-Lee, J., Son, H. S., Lee, H. I., Lee, G.-R., Jo, Y.-J., Hong, S.-E., Kim, N., Kwon, M., Kim, N. Y., Kim, H. J., Lee, Y. J., Seo, E. K., Jeong, W. Skullcapflavone II inhibits osteoclastogenesis by regulating reactive oxygen species and attenuates the survival and resorption function of osteoclasts by modulating integrin signaling.

Dehydrocostus lactone suppresses osteoclast differentiation by regulating NFATc1 and inhibits osteoclast activation through modulating migration and lysosome function.

Excessive osteoclast activity can lead to an imbalance between the synthesis and breakdown of bone, with pathologic consequences that include osteoporosis and periodontitis. Thus, controlling osteoclast differentiation and function has significant therapeutic implications. In this study, we investigated the effects of dehydrocostus lactone (DL) on osteoclast differentiation and activation and elucidated the possible mechanisms underlying these processes. DL suppressed osteoclast differentiation by reducing the expression of the nuclear factor of activated T-cells, cytoplasmic 1. When used to challenge differentiated osteoclasts, DL also effectively inhibited their enlargement and resorption activity, and biochemical approaches revealed that DL attenuates osteoclast activation by inhibiting the migration and lysosome biogenesis and secretion via the down-regulation of integrin ß3, PKC-ß, and autophagy related 5 expression. Furthermore, DL prevented bone destruction in inflammation- and ovariectomy-induced osteolytic mouse models. These results indicate that DL has therapeutic potential to treat bone diseases caused by excessive or hyperactive osteoclasts.-Lee, H. I., Lee, J., Hwang, D., Lee, G.-R., Kim, N., Kwon, M., Lee, H., Piao, D., Kim, H. J., Kim, N. Y., Kim, H. S., Seo, E. K., Kang, D., Jeong, W. Dehydrocostus lactone suppresses osteoclast differentiation by regulating NFATc1 and inhibits osteoclast activation through modulating migration and lysosome function.

MicroRNA gga-miR-200a-3p modulates immune response via MAPK signaling pathway in chicken afflicted with necrotic enteritis.

MicroRNAs (miRNAs) are small non-coding RNAs that contribute to host immune response as post-transcriptional regulation. The current study investigated the biological role of the chicken (Gallus gallus) microRNA-200a-3p (gga-miR-200a-3p), using 2 necrotic enteritis (NE) afflicted genetically disparate chicken lines, 6.3 and 7.2, as well as the mechanisms underlying the fundamental signaling pathways in chicken. The expression of gga-miR-200a-3p in the intestinal mucosal layer of NE-induced chickens, was found to be upregulated during NE infection in the disease-susceptible chicken line 7.2. To validate the target genes, we performed an overexpression analysis of gga-miR-200a-3p using chemically synthesized oligonucleotides identical to gga-miR-200a-3p, reporter gene analysis including luciferase reporter assay, and a dual fluorescence reporter assay in cultured HD11 chicken macrophage cell lines. Gga-miR-200a-3p was observed to be a direct transcriptional repressor of ZAK, MAP2K4, and TGFß2 that are involved in mitogen-activated protein kinase (MAPK) pathway by targeting the 3'-UTR of their transcripts. Besides, gga-miR-200a-3p may indirectly affect the expression of protein kinases including p38 and ERK1/2 at both transcriptional and translational levels, suggesting that this miRNA may function as an important regulator of the MAPK signaling pathway. Proinflammatory cytokines consisting of IL-1ß, IFN-γ, IL-12p40, IL-17A, and LITAF belonging to Th1 and Th17-type cytokines, were upregulated upon gga-miR-200a-3p overexpression. These findings have enhanced our knowledge of the immune function of gga-miR-200a-3p mediating the chicken immune response via regulation of the MAPK signaling pathway and indicate that this miRNA may serve as an important biomarker of diseases in domestic animals.

Coordinate control of terminal dendrite patterning and dynamics by the membrane protein Raw.

The directional flow of information in neurons depends on compartmentalization: dendrites receive inputs whereas axons transmit them. Axons and dendrites likewise contain structurally and functionally distinct subcompartments. Axon/dendrite compartmentalization can be attributed to neuronal polarization, but the developmental origin of subcompartments in axons and dendrites is less well understood. To identify the developmental bases for compartment-specific patterning in dendrites, we screened for mutations that affect discrete dendritic domains in Drosophila sensory neurons. From this screen, we identified mutations that affected distinct aspects of terminal dendrite development with little or no effect on major dendrite patterning. Mutation of one gene, raw, affected multiple aspects of terminal dendrite patterning, suggesting that Raw might coordinate multiple signaling pathways to shape terminal dendrite growth. Consistent with this notion, Raw localizes to branch-points and promotes dendrite stabilization together with the Tricornered (Trc) kinase via effects on cell adhesion. Raw independently influences terminal dendrite elongation through a mechanism that involves modulation of the cytoskeleton, and this pathway is likely to involve the RNA-binding protein Argonaute 1 (AGO1), as raw and AGO1 genetically interact to promote terminal dendrite growth but not adhesion. Thus, Raw defines a potential point of convergence in distinct pathways shaping terminal dendrite patterning.

The Trajectories of the Number of Pain Sites and Their Associated Factors in Older Adults: Results from the Korean Longitudinal Study of Ageing.

BACKGROUND: The aging of the population will result in an increase in demand for pain management. Pain adversely affects physical and mental functioning in older adults and accounts for a considerable proportion of all medical expenses. OBJECTIVES: This study was performed to investigate the patterns of changes in the trajectories of the number of pain sites in older adults and the factors that affect these patterns according to gender. METHODS: Data were extracted for subjects that participated in the Korean Longitudinal Study of Ageing from 2006 to 2014. The study population consisted of 2,839 individuals (1,190 men and 1,649 women) ≥60 years old. A group-based trajectory model was used to determine the optimal number of subgroups and the trajectories of the number of pain sites according to gender. A multinomial regression analysis was conducted to identify factors that affect the probability of inclusion in each trajectory group. RESULTS: The trajectories of the number of pain sites were consistent in both genders. Almost all women had one or more pain symptom, and a greater number of pain sites than men. Older age, longest-duration occupation requiring manual labor, lack of physical activity, depressive symptoms, and poor self-rated health were associated with a greater number of pain sites in both genders. A lower level of education, married status, and experience of injury were associated with the number of pain sites in men but not in women, while household income and chronic diseases were associated with the number of pain sites only in women. CONCLUSIONS: The pain status at the early stage is predictive of future pain. In this study, we identified gender differences in the trends of the number of pain sites and associated factors. Further comprehensive studies on pain intensity and duration are required.

Regulation of dendrite growth and maintenance by exocytosis.

Dendrites lengthen by several orders of magnitude during neuronal development, but how membrane is allocated in dendrites to facilitate this growth remains unclear. Here, we report that Ras opposite (Rop), the Drosophila ortholog of the key exocytosis regulator Munc18-1 (also known as STXBP1), is an essential factor mediating dendrite growth. Neurons with depleted Rop function exhibit reduced terminal dendrite outgrowth followed by primary dendrite degeneration, suggestive of differential requirements for exocytosis in the growth and maintenance of different dendritic compartments. Rop promotes dendrite growth together with the exocyst, an octameric protein complex involved in tethering vesicles to the plasma membrane, with Rop-exocyst complexes and exocytosis predominating in primary dendrites over terminal dendrites. By contrast, membrane-associated proteins readily diffuse from primary dendrites into terminals, but not in the reverse direction, suggesting that diffusion, rather than targeted exocytosis, supplies membranous material for terminal dendritic growth, revealing key differences in the distribution of materials to these expanding dendritic compartments.

Gender differences in the trajectories and the risk factors of depressive symptoms in later life.

BACKGROUND: The present study investigated changes in the trajectories of depressive symptoms in the elderly and attempted to identify risk factors that influence these changes according to gender. METHODS: All data were obtained from a subsample of subjects who participated in the Korean Longitudinal Study of Ageing between 2006 and 2012; 3,667 individuals (1,566 men and 2,101 women) aged 60 years and older were included in the present study. A group-based trajectory model was employed to determine the appropriate number of groups and to observe changes in depressive symptoms according to research year. Following the trajectory analysis, a multinomial regression analysis was performed to examine depressive symptom-related risk factors that influenced membership in the different trajectory groups. RESULTS: Significant gender differences were found in the trajectories of depressive symptoms among four groups (normal, mild depressed, worsening, and depressed) in men and five groups (normal, mild depressed, worsening, improving, and depressed) in women. Among the trajectory groups, physical health status such as chronic diseases, self-rated health (SRH), and somatic pain showed statistically significant differences in both genders. In addition, employment in men and social participation in women were associated with the trajectories. CONCLUSIONS: The present study suggested that maintaining one's physical health status played an important role in preventing depressive symptoms and that employment in men and social participation in women were preventative against the development of depressive symptoms.

cDNA cloning and molecular characterization of a defensin-like antimicrobial peptide from larvae of Protaetia brevitarsis seulensis (Kolbe).

We identified new defensin-like cDNA (called Psdefensin) by searching data set of high-throughput RNA sequencing (RNA-seq) expression profiling of immunized larva of white-spotted flower chafers, Protaetia brevitarsis seulensis. The length of the analyzed new defensin-like sequences were 240 base pair (bp) and encoded the deduced polypeptide of 79 amino acid residues with signal peptides (amino acids 1-20), pro-peptide region (amino acids 21-36), and mature peptide region (amino acids 37-79). The Psdefensin transcript levels were slightly up-regulated at 4 h post-infection and were highly expressed at 8 h post-infection compared to control larvae injected with sterile water. In addition, the Psdefensin did have antimicrobial activity against both Gram-negative bacteria, E. coli and Gram-positive bacteria, B. subtilis suggesting potentially pharmacologic agent.