J. Craig WheelerThe Nature and Consequences of Cosmological Halo Formation: Dark Matter and the Dark Ages

First, I am deeply indebted to my wife, Younga, who had an uneasy summer season due to her guilt of having an aging graduate student as her hubby. At this right moment my writing this acknowledgment, she may be preparing warm breakfast for two children. I am guilty of depriving her of all the summer fun. Younga, I met you only seven years ago, but I should have met you much earlier. When you are away, I think about you. When you are near, I see you. You are my heart, my soul, my canvas, my wine, my potato chip, my sun. I appreciate my Parents-in-law for accepting me as Son-in-law, and supporting me. I wish to thank Father and Mother, who have raised and guided me on this hostile planet Earth. Hatred and poverty caused by its own inhabitants is the most difficult thing I can bear. Without them, I could not have survived it. Their life was a grand symphony. Now, here is my humble rose to you. My lovely kids! How pretty (and noisy) you are! Please grow healthy

Survival pattern in male breast cancer: distinct from female breast cancer

IntroductionMale breast cancer (MBC) is a rare condition, and recent research has underscored notable distinctions between MBC and breast cancer in women. This study aimed to assess and contrast the long-term survival outcomes and disease patterns of MBC patients with those of their female counterparts.MethodsWe analyzed data from 113,845 patients diagnosed with breast cancer who had undergone curative surgery from the Korean Breast Cancer Registry (KBCR) between January 1990 and August 2014 in Seoul, Korea. The five-year overall survival was analyzed according to clinicopathological characteristics.ResultsAmong 113,845 patients with breast cancer, 473 MBC cases were included. The median duration of follow-up was 72 months. The median age at diagnosis was 60 and 48 years for MBC and female breast cancer, respectively. Most male patients (92.6%) underwent total mastectomy, while 50.4% of female patients underwent breast-conserving surgery. Among MBC, 63.2% received chemotherapy, and 83.9% of hormone receptor-positive male patients received endocrine therapy. In survival analysis, MBC demonstrated distinct 5-year overall survival patterns compared with female breast cancer, according to age at diagnosis. In women with breast cancer, the younger age group (≤40 years) demonstrated worse 5-year overall survival than did the older age group (>40 years) (91.3% vs 92.7%, p <0.05). While in MBC, the younger age group (≤40 years) demonstrated better 5-year overall survival than did the older age group (>40 years) (97.4% vs 86.4%, p <0.05).DiscussionIn conclusion within this extensive cohort, we have revealed unique survival patterns in MBC that diverge from those observed in women with breast cancer. This study enhances our comprehension of MBC prognosis and can potentially shed light on unresolved questions, paving the way for future research in the realm of MBC

Preoperative serum HER2 extracellular domain levels in primary invasive breast cancer

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Abstract Background Despite the preclinical outcomes and biologic significance of the presence of the human epidermal growth factor receptor-2 (HER2) extracellular domain (ECD), there is little evidence supporting the measurement of ECD levels in any clinical setting. The aim of this study was to determine the prevalence of elevated serum HER2 ECD levels, the association between these levels and tissue HER2 overexpression, and the potential clinical prognostic value of HER2 ECD in primary invasive breast cancer. Methods Serum HER2 ECD levels were examined preoperatively in 2,862 consecutive stage I–III primary breast cancer patients between 2007 and 2009. Serum HER2 ECD levels were measured by chemiluminescence immunoassay (ADVIA Centaur), and the tissue HER2 status was assessed by immunohistochemistry and fluorescence in situ hybridization. The cutoff value for the serum level of HER2 ECD was set at 15.2 ng/ml. Results Among the 2,862 patients, 126 (4.4%) had elevated serum HER2 ECD levels, and HER2 was overexpressed in the tumor tissue of 692 patients (24.2%), with a concordance of 78.7%. Multivariate analysis revealed that elevated serum HER2 ECD was a significant independent prognostic factor for worse distant-metastasis-free survival [DMFS; hazard ratio (HR) = 2.50, 95% confidence interval (CI) = 1.5–4.3, P = 0.001] and breast-cancer-specific survival (BCSS; HR = 2.0, 95% CI = 1.1–3.8, P = 0.036), which were much stronger in patients with tissue HER2-positive tumors (DMFS: HR = 3.8, 95% CI = 2.0–7.0, P < 0.001; BCSS: HR = 2.6, 95% CI = 1.2-5.3, P = 0.012). Conclusions Given the prevalence of HER2 expression, its measurement as an independent prognostic factor can be clinically useful, particularly in patients with tissue HER2-positive tumors

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

Dioxinodehydroeckol Enhances the Differentiation of Osteoblasts by Regulating the Expression of Phospho-Smad1/5/8

Lack of bone formation-related health problems are a major problem for the aging population in the modern world. As a part of the ongoing trend of developing natural substances that attenuate osteoporotic bone loss conditions, dioxinodehydroeckol (DHE) from edible brown alga Ecklonia cava was tested for its effects on osteoblastogenic differentiation in MC3T3-E1 pre-osteoblasts. DHE was observed to successfully enhance osteoblast differentiation, as indicated by elevated cell proliferation, alkaline phosphatase activity, intracellular cell mineralization, along with raised levels of osteoblastogenesis indicators at the concentration of 20 μM. Results suggested a possible intervening of DHE on the bone morphogenetic protein (BMP) signaling pathway, according to elevated protein levels of BMP-2, collagen-I, and Smads. In addition, the presence of DHE was also able to raise the phosphorylated extracellular signal–regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) levels which are also activated by the BMP signaling pathway. In conclusion, DHE is suggested to be a potential bioactive compound against bone loss that could enhance osteoblastogenesis with a suggested BMP pathway interaction

Effect of Salicornia herbacea on Osteoblastogenesis and Adipogenesis in Vitro

Bone-related complications are among the highest concerning metabolic diseases in the modern world. Bone fragility and susceptibility to fracture increase with age and diseases like osteoporosis. Elevated adipogenesis in bone results in osteoporosis and loss of bone mass when coupled with lack of osteoblastogenesis. In this study the potential effect of Salicornia herbacea extract against osteoporotic conditions was evaluated. Adipogenesis inhibitory effect of S. herbacea has been evidenced by decreased lipid accumulation of differentiating cells and expression levels of crucial adipogenesis markers in 3T3-L1 pre-adipocytes. S. herbacea treatment reduced the lipid accumulation by 25% of the control. In addition, mRNA expression of peroxisome proliferator-activated receptor (PPAR)γ, CCAAT/enhancer-binding protein (C/EBP)α and sterol regulatory element binding protein (SREBP)1c were inhibited by the presence of S. herbacea. Bone formation enhancement effect of S. herbacea was also confirmed in MC3T3-E1 pre-osteoblasts. The presence of S. herbacea significantly elevated the alkaline phosphatase (ALP) activity by 120% at a concentration of 100 μg/mL in differentiating osteoblasts. S. herbacea also significantly increased the expression of osteoblastogenesis indicators, ALP, bone morphogenetic protein (BMP)-2, osteocalcin and collagen type I (collagen-I). In conclusion, S. herbacea possess potential to be utilized as a source of anti-osteoporotic agent that can inhibit adipogenesis while promoting osteoblastogenesis

Chitooligosaccharides attenuate UVB-induced damages in human dermal fibroblasts

As a continuation of our research on chitooligosaccharides (COS), this study focused on the protective effect of COS of various molecular weights (1–3, 3–5, and 5–10 kDa) on cellular damage caused by ultraviolet B (UVB)-induced oxidative stress in human dermal fibroblast cells. The results show that the protective effect of COS on UVB-stressed human fibroblasts was dependent on molecular weight. COS suppressed UVB irradiation-induced reactive oxygen species generation and DNA damage, accompanied by the downregulation of matrix metalloproteinase (MMP)-1 and MMP-13. In a comparative analysis, COS (3–5 kDa) exhibited the most potent protective effect on UVB-stressed fibroblasts. The presence of COS (3–5 kDa) attenuated UVB-induced collagenolytic MMP production and collagen degradation. The photoprotective activity of COS (3–5 kDa) was confirmed by transcriptional phosphorylation of mitogen-activated protein kinase-responsive signaling pathways

Phlorofucofuroeckol A from Edible Brown Alga Ecklonia Cava Enhances Osteoblastogenesis in Bone Marrow-Derived Human Mesenchymal Stem Cells

The deterioration of bone formation is a leading cause of age-related bone disorders. Lack of bone formation is induced by decreased osteoblastogenesis. In this study, osteoblastogenesis promoting effects of algal phlorotannin, phlorofucofuroeckol A (PFF-A), were evaluated. PFF-A was isolated from brown alga Ecklonia cava. The ability of PFF-A to enhance osteoblast differentiation was observed in murine pre-osteoblast cell line MC3T3-E1 and human bone marrow-derived mesenchymal stem cells (huBM-MSCs). Proliferation and alkaline phosphatase (ALP) activity of osteoblasts during differentiation was assayed following PFF-A treatment along extracellular mineralization. In addition, effect of PFF-A on osteoblast maturation pathways such as Runx2 and Smads was analyzed. Treatment of PFF-A was able to enhance the proliferation of differentiating osteoblasts. Also, ALP activity was observed to be increased. Osteoblasts showed increased extracellular mineralization, observed by Alizarin Red staining, following PFF-A treatment. In addition, expression levels of critical proteins in osteoblastogenesis such as ALP, bone morphogenetic protein-2 (BMP-2), osteocalcin and &beta;-catenin were stimulated after the introduction of PFF-A. In conclusion, PFF-A was suggested to be a potential natural product with osteoblastogenesis enhancing effects which can be utilized against bone-remodeling imbalances and osteoporosis-related complications

Anti-Inflammatory Effect of By-Products from Haliotis discus hannai in RAW 264.7 Cells

Several reports promoted the potential of shellfish due to their ability to act as antioxidant, anti-inflammatory, and antimicrobial agents. Pacific abalone, Haliotis discus hannai viscera is, reported to possess bioactivities such as antioxidative stress and anti-inflammatory. In this study, anti-inflammatory potential of mucus-secreting glands from shell-shucking waste of H. discus hannai was evaluated using RAW 264.7 mouse macrophage cell model. Results indicated that presence of H. discus hannai mucosubstance by-products (AM) significantly lowered the nitric oxide (NO) production along the expressional suppression of inflammatory mediators such as cytokines TNF-α, IL-1β, and IL-6 and enzymes iNOS and COX-2. Also, AM was shown to increase expression of anti-inflammatory response mediator HO-1. Presence of AM also scavenged the free radicals in vitro. In conclusion, by-products of H. discus hannai are suggested to possess notable anti-inflammatory potential which promotes the possibility of utilization as functional food ingredient