Ixora parviflora Protects against UVB-Induced Photoaging by Inhibiting the Expression of MMPs, MAP Kinases, and COX-2 and by Promoting Type I Procollagen Synthesis

Ixora parviflora with high polyphenol content exhibited antioxidant activity and reducing UVB-induced intracellular reactive oxygen species production. In this study, results of the photoaging screening experiments revealed that IPE at 1000 μg/mL reduced the activity of bacterial collagenase by 92.7 ± 4.2% and reduced the activity of elastase by 32.6 ± 1.4%. Therefore, we investigated the mechanisms by which IPE exerts its anti-photoaging activity. IPE at 1 μg/mL led to an increase in type I procollagen expression and increased total collagen synthesis in fibroblasts at 5 μg/mL. We found that IPE inhibited MMP-1, MMP-3, and MMP-9 expression at doses of 1, 5, and 10 μg/mL, respectively, in fibroblasts exposed to UV irradiation (40 mJ/cm2). Gelatin zymography assay showed that IPE at 50 μg/mL inhibited MMP-9 secretion/activity in cultured fibroblasts after UVB exposure. In addition, IPE inhibited the phosphorylation of p38, ERK, and JNK induced by UVB. Furthermore, IPE inhibited the UVB-induced expression of Smad7. In addition, IPE at 1 μg/mL inhibited NO production and COX-2 expression in UV-exposed fibroblasts. These findings show that IPE exhibits anti-inflammatory and anti-photoaging activities, indicating that IPE could be a potential anti-aging agent

Disruption of the Suprachiasmatic Nucleus in Fibroblast Growth Factor Signaling-Deficient Mice.

Fibroblast growth factor (Fgf) 8 is essential for the development of multiple brain regions. Previous studies from our laboratory showed that reduced Fgf8 signaling led to the developmental alterations of neuroendocrine nuclei that originated within the diencephalon, including the paraventricular (PVN) and supraoptic (SON) nuclei. To further understand the role of Fgf8 in the development of other hypothalamic nuclei, we examined if Fgf8 and its cognate receptor, Fgfr1, also impact the integrity of the suprachiasmatic nuclei (SCN). The SCN control an organism's circadian rhythm and contain vasoactive intestinal peptide (VIP)-producing neurons as the main input neurons. Mice hypomorphic for Fgf8, Fgfr1, or both were examined for their SCN volume and the number of VIP neurons on postnatal day (PN) 0; adult hypomorphic mice were further examined for SCN function by quantifying SCN neuronal activation using cFos as a marker. On PN0, mice homozygous for Fgf8 hypomorphy displayed the most severe reduction of the SCN volume and VIP neurons. Those heterozygous for Fgf8 hypomorphy alone or Fgf8 combined with Fgfr1 hypomorphy, called double heterozygotes (DH), showed normal SCN volume but significantly reduced VIP neurons, albeit less severely than the homozygotes. Adult wild type, heterozygous Fgf8 hypomorphs (F8 Het), and DH mice were also examined for SCN cFos activation at three time points: 1 h (morning), 6 h (afternoon), and 11 h (evening) after light onset. In F8 Het mice, a significant change in the pattern of cFos immunostaining that may reflect delayed morning SCN activation was observed. Overall, our studies provide evidence supporting that deficiencies in Fgf8 not only impact the structural integrity of the SCN but also the pattern of SCN activation in response to light

Prediction of Future Land Use and Land Cover (LULC) in Makassar City

Migration from rural area to urban area increases urban population. It increases and needs for settlements, leading to conversion of agricultural lands into settlement areas. Inconsistent land use compared with spatial planning causes change in land use. Spatial land use expansion can be monitored and predicted by modeling. NetLogo application is a software integrated with Agent-Based Modeling (ABM), which can be used to predict change of land use with various complex parameters. The present study used population growth as a parameter to predict change of land use of Makassar in 2050 based on 2017 land use classification map as the start of the prediction. The analysis result showed that the biggest change of land use happens to Settlement class which is 594.74 hectares and the smallest is Water Body class which is 8.76 hectares

Exploring Spirituality of Elders Relocating into Long-Term Care Facilities

Background: Spirituality is recognized as an important contributor to quality of life, particularly for older adults. Yet, limited research has been conducted to examine spirituality of older adults relocating to long-term care facilities (LTCFs). The intent of this mixed methods study was to cull data from a parent study to explore different aspects of spirituality among residents newly admitted to LTCFs. Method: Qualitative and quantitative data of six participants from a parent study including interviews and scores from the religious and existential well-being sections of the Spiritual Well Being Scale (SWBS) were analyzed and triangulated. Results: Descriptive analysis of the demographic data including age, gender, ethnicity, and spirituality scores was conducted. Emerging themes from the qualitative interviews included: hope/hopelessness for the future; sense of belonging in the LTCF; contentment/discontentment with life; and personal religious beliefs. These themes, in turn, were triangulated with and supported by the SWBS scores Conclusion: The findings have the potential of developing recommendations for spiritually-based interventions to facilitate successful relocation to LTCFs. Clinical implications for occupational therapy and future research are discussed

Ser-634 and Ser-636 of Kaposi’s Sarcoma-Associated Herpesvirus RTA are Involved in Transactivation and are Potential Cdk9 Phosphorylation Sites

The replication and transcription activator (RTA) of Kaposi’s sarcoma-associated herpesvirus (KSHV), K-RTA, is a lytic switch protein that moderates the reactivation process of KSHV latency. By mass spectrometric analysis of affinity purified K-RTA, we showed that Thr-513 or Thr-514 was the primary in vivo phosphorylation site. Thr-513 and Thr-514 are proximal to the nuclear localization signal (527KKRK530) and were previously hypothesized to be target sites of Ser/Thr kinase hKFC. However, substitutions of Thr with Ala at 513 and 514 had no effect on K-RTA subcellular localization or transactivation activity. By contrast, replacement of Ser with Ala at Ser-634 and Ser-636 located in a Ser/Pro-rich region of K-RTA, designated as S634A/S636A, produced a polypeptide with ∼10 kDa shorter in molecular weight and reduced transactivation in a luciferase reporter assay relative to the wild type. In contrast to prediction, the decrease in molecular weight was not due to lack of phosphorylation because the overall Ser and Thr phosphorylation state in K-RTA and S634A/S636A were similar, excluding that Ser-634 or Ser-636 motif served as docking sites for consecutive phosphorylation. Interestingly, S634A/S636A lost ∼30% immuno-reactivity to MPM2, an antibody specific to pSer/pThr-Pro motif, indicating that 634SPSP637 motif was in vivo phosphorylated. By in vitro kinase assay, we showed that K-RTA is a substrate of CDK9, a Pro-directed Ser/Thr kinase central to transcriptional regulation. Importantly, the capability of K-RTA in associating with endogenous CDK9 was reduced in S634A/S636A, which suggested that Ser-634 and Ser-636 may be involved in CDK9 recruitment. In agreement, S634A/S636A mutant exhibited ∼25% reduction in KSHV lytic cycle reactivation relative to that by the wild type K-RTA. Taken together, our data propose that Ser-634 and Ser-636 of K-RTA are phosphorylated by host transcriptional kinase CDK9 and such a process contributes to a full transcriptional potency of K-RTA

Targeted expression of a dominant-negative fibroblast growth factor (FGF) receptor in gonadotropin-releasing hormone (GnRH) neurons reduces FGF responsiveness and the size of GnRH neuronal population

Increasing evidence suggests that fibroblast growth factors (FGFs) are neurotrophic in GnRH neurons. However, the extent to which FGFs are involved in establishing a functional GnRH system in the whole organism has not been investigated. In this study, transgenic mice with the expression of a dominant-negative FGF receptor mutant (FGFRm) targeted to GnRH neurons were generated to examine the consequence of disrupted FGF signaling on the formation of the GnRH system. To first test the effectiveness of this strategy, GT1 cells, a GnRH neuronal cell line, were stably transfected with FGFRm. The transfected cells showed attenuated neurite outgrowth, diminished FGF-2 responsiveness in a cell survival assay, and blunted activation of the signaling pathway in response to FGF-2. Transgenic mice expressing FGFRm in a GnRH neuron-specific manner exhibited a 30% reduction in GnRH neuron number, but the anatomical distribution of GnRH neurons was unaltered. Although these mice were initially fertile, they displayed several reproductive defects, including delayed puberty, reduced litter size, and early reproductive senescence. Overall, our results are the first to show, at the level of the organism, that FGFs are one of the important components involved in the formation and maintenance of the GnRH system

Advanced age affects the outcome-predictive power of RIFLE classification in geriatric patients with acute kidney injury

The RIFLE (risk, injury, failure, loss, and end-stage) classification is widely used to gauge the severity of acute kidney injury, but its efficacy has not been formally tested in geriatric patients. To correct this we conducted a prospective observational study in a multicenter cohort of 3931 elderly patients (65 years of age or older) who developed acute kidney injury in accordance with the RIFLE creatinine criteria after major surgery. We studied the predictive power of the RIFLE classification for in-hospital mortality and investigated the potential interaction between age and RIFLE classification. In general, the survivors were significantly younger than the nonsurvivors and more likely to have hypertension. In patients 76 years of age and younger, RIFLE-R, -I, or -F classifications were significantly associated with increased hospital mortality in a stepwise manner. There was no significant difference, however, in hospital mortality in those over 76 years of age between patients with RIFLE-R and RIFLE-I, although RIFLE-F patients had significantly higher mortality than both groups. Thus, the less severe categorizations of acute kidney injury per RIFLE classification may not truly reflect the adverse impact on elderly patients

Effects of Growth Hormone Treatment on Height, Weight, and Obesity in Taiwanese Patients with Prader-Willi Syndrome

BackgroundInformation regarding the efficacy of growth hormone (GH) therapy in Asian Prader-Willi syndrome (PWS) patients is lacking. We report our experience with GH treatment in children with PWS in Taiwan.MethodsForty-six PWS patients (27 males, 19 females; age range, 1 year 4 months to 13 years 7 months) who received and/or who are currently receiving GH treatment (0.1 IU/kg/day subcutaneously) for a period from 1 year to 3 years were retro-spectively analyzed. We evaluated height, weight, body mass index (BMI) and Rohrer index, before and after GH treatment.ResultsAfter patients had received GH for 1, 2 and 3 years, a significant improvement in mean height standard deviation score (SDS) was noted from −1.24 to −0.31 (p <0.01), 0.00 (p <0.001) and −0.26 (p <0.001), respectively. Mean BMI SDS decreased significantly from 1.93 to 1.13 (p <0.05) after 1 year of treatment; however, no significant changes were observed afterward. Mean Rohrer index decreased significantly, from 224.2 to 186.6 (p <0.001), 178.9 (p <0.001) and 169.3 (p <0.001). No significant gender or genotype pattern differences were noted among the 4 parameters examined.ConclusionThis 3-year, retrospective study indicates that PWS patients benefit from GH therapy in height increase and improved body composition

RUNX2 mutations in Taiwanese patients with cleidocranial dysplasia

Cleidocranial dysplasia (CCD) is an autosomal dominant human skeletal disorder comprising hypoplastic clavicles, wide cranial sutures, supernumerary teeth, short stature, and other skeletal abnormalities. It is known that mutations in the human RUNX2 gene mapped at 6p21 are responsible for CCD. We analyzed the mutation patterns of the RUNX2 gene by direct sequencing in six Taiwanese index cases with typical CCD. One of the patients was a familial case and the others were sporadic cases. Sequencing identified four mutations. Three were caused by single nucleotide substitutions, which created a nonsense (p.R391X), two were missense mutations (p.R190W, p.R225Q), and the forth was a novel mutation (c.1119delC), a one-base deletion. Real time quantitative PCR adapted to determine copy numbers of the promoter, all exons and the 3’UTR region of the RUNX2 gene detected the deletion of a single allele in a sporadic case. The results extend the spectrum of RUNX2 mutations in CCD patients and indicate that complete deletions of the RUNX2 gene should be considered in those CCD patients lacking a point mutation detected by direct sequencing

Fak56 functions downstream of integrin alphaPS3betanu and suppresses MAPK activation in neuromuscular junction growth

Background: Focal adhesion kinase (FAK) functions in cell migration and signaling through activation of the mitogen-activated protein kinase (MAPK) signaling cascade. Neuronal function of FAK has been suggested to control axonal branching; however, the underlying mechanism in this process is not clear. Results: We have generated mutants for the Drosophila FAK gene, Fak56. Null Fak56 mutants display overgrowth of larval neuromuscular junctions (NMJs). Localization of phospho-FAK and rescue experiments suggest that Fak56 is required in presynapses to restrict NMJ growth. Genetic analyses imply that FAK mediates the signaling pathway of the integrin αPS3βν heterodimer and functions redundantly with Src. At NMJs, Fak56 downregulates ERK activity, as shown by diphospho-ERK accumulation in Fak56 mutants, and suppression of Fak56 mutant NMJ phenotypes by reducing ERK activity. Conclusion: We conclude that Fak56 is required to restrict NMJ growth during NMJ development. Fak56 mediates an extracellular signal through the integrin receptor. Unlike its conventional role in activating MAPK/ERK, Fak56 suppresses ERK activation in this process. These results suggest that Fak56 mediates a specific neuronal signaling pathway distinct from that in other cellular processes