Influence of APOE and RNF219 on Behavioral and Cognitive Features of Female Patients Affected by Mild Cognitive Impairment or Alzheimer's Disease.

The risk for Alzheimer's disease (AD) is associated with the presence of the ?4 allele of Apolipoprotein E (APOE) gene and, recently, with a novel genetic variant of the RNF219 gene. This study aimed at evaluating interactions between APOE-?4 and RNF219/G variants in the modulation of behavioral and cognitive features of two cohorts of patients suffering from mild cognitive impairment (MCI) or AD. We enrolled a total of 173 female MCI or AD patients (83 MCI; 90 AD). Subjects were screened with a comprehensive set of neuropsychological evaluations and genotyped for the APOE and RNF219 polymorphic variants. Analysis of covariance was performed to assess the main and interaction effects of APOE and RNF219 genotypes on the cognitive and behavioral scores. The analysis revealed that the simultaneous presence of APOE-?4 and RNF219/G variants results in significant effects on specific neuropsychiatric scores in MCI and AD patients. In MCI patients, RNF219 and APOE variants worked together to impact the levels of anxiety negatively. Similarly, in AD patients, the RNF219 variants were found to be associated with increased anxiety levels. Our data indicate a novel synergistic activity APOE and RNF219 in the modulation of behavioral traits of female MCI and AD patients

Development and distribution of the non-indigenous Pacific oyster (Crassostrea gigas) in the Dutch Wadden Sea

Pacific oysters (Crassostrea gigas) were first observed in the Dutch Wadden Sea near Texel in 1983. The population increased slowly in the beginning but grew exponentially from the mid-1990s onwards, although now some stabilisation seems to be occurring. They occur on a variety of substrates such as mussel beds (Mytilus edulis), shell banks, dikes and poles. After initial settlement spat may fall on older individuals and congregate to dense clumps and subsequently form reefs. Individual Pacific oysters grow 3–4 cm long in their first year and 2–3 cm in their second year. Many mussel beds (Mytilus edulis) are slowly taken over by Pacific oysters, but there are also several reports of mussel spat settling on Pacific oyster reefs. This might in the end result in combined reefs. Successful Pacific oyster spat fall seems to be related to high summer temperatures, but also after mild summers much spat can be found on old (Pacific oyster) shells. Predation is of limited importance. Mortality factors are unknown, but every now and then unexplained mass mortality occurs. The gradual spread of the Pacific oyster in the Dutch Wadden Sea is documented in the first instance based on historical and anecdotal information. At the start of the more in-depth investigation in 2002, Pacific oysters of all size classes were already present near Texel. Near Ameland the development could be followed from the first observed settlement. On dense reefs each square metre may contain more than 500 adult Pacific oysters, weighing more than 100 kg per m² fresh weigh

Proteomic and ionomic profiling reveals significant alterations of protein expression and calcium homeostasis in cystic fibrosis cells

Cystic fibrosis (CF) is an autosomal recessive disorder associated with mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene and defective chloride transport across the epithelial cell membranes. Abnormal epithelial ion transport is the primary cause of persistent airway infections and chronic inflammation in CF patients. In order to gain further insight into the mechanisms of epithelial dysfunctions linked to CFTR mutations, we performed and integrated proteomic and ionomic analysis of human bronchial epithelial IB3-1 cells and compared them with a CFTR-complemented isogenic cell line (C38). Aside from changes that were consistent with known effects related to CFTR mutations, such as differences in glycolytic and gluconeogenic pathways and unfolded protein responses, differential proteomics highlighted significant alteration of protein expression and, in particular, of the 14-3-3 signalling pathway that is known to be involved in cellular calcium (Ca) homeostasis. Of note, restoring chloride efflux by acting on Ca cellular homeostasis has been shown to be a promising therapeutic intervention for CF. Ionomic analysis showed significant changes in the IB3-1 element profile compared with C38 cells and in particular we observed an increase of intracellular Ca that significantly correlates with intracellular zinc (Zn) levels, suggesting a synergistic role of Ca and Zn influx. This finding is particularly intriguing because Zn has been reported to be effective in CF treatment increasing Ca influx. Taken together, our proteomic and ionomic data reveal that CFTR mutation sets in motion endogenous mechanisms counteracting impaired chloride transport mainly acting on epithelial ion transport and increasing intracellular Ca, suggesting potential links between protein expression and this response

Kajian Perbedaan Konsentrasi Larutan Garam Pada Perendaman Rgh Dan Vaksin Terhadap Kelulushidupan Dan Pertumbuhan Benih Ikan Lele Sangkuriang (Clarias Gariepinus)

Berdasarkan data KKP (2013), pencapaian produksi ikan lele pada tahun 2013 mampu melampaui target. Ikan lele merupakan ikan yang mudah dibudidayakan, sehingga banyak dilakukan penelitian agar didapatkan benih lele dengan pertumbuhan dan kelulushidupan yang lebih baik, serta tahan terhadap serangan penyakit. Penelitian ini bertujuan untuk mengetahui pengaruh konsentrasi larutan garam yang berbeda dan konsentrasi yang terbaik pada perendaman rGH dan vaksin terhadap kelulushidupan dan pertumbuhan benih lele sangkuriang. Penelitian ini dilaksanakan pada tanggal 13 November 2014 – 15 Februari 2015 di Satuan Kerja Pembenihan dan Budidaya Ikan Air Tawar (SATKER PBIAT), Siwarak, Ungaran, Semarang. Ikan uji yang digunakan adalah benih lele sangkuriang umur 12 hari. Metode yang digunakan adalah eksperimental dengan rancangan acak lengkap (RAL) 4 perlakuan dan 3 ulangan, yaitu: (A) perlakuan tanpa larutan garam, (B) konsentrasi 0,5%, (C) konsentrasi 1,0% dan (D) konsentrasi 1,5%. Pemeliharaan ikan dilakukan selama 42 hari. Variabel data yang diamati meliputi kelulushidupan, SGR, panjang mutlak, FCR, EPP dan kelulushidupan setelah uji tantang. Analisa data dengan menggunakan anova untuk mengetahui pengaruh perlakuan yang berbeda nyata, apabila hasil yang didapatkan berbeda nyata, maka dilanjutkan dengan uji duncan untuk mengetahui perlakuan yang terbaik. Hasil penelitian menunjukkan perlakuan terbaik adalah perlakuan C, dengan nilai kelulushidupan (87,00±1,00%), SGR (7,79±0,03%), nilai panjang mutlak (6,75±0,15cm), nilai FCR (0,71±0,01) dan nilai EPP (140,28±1,25%), sedangkan untuk kelulushidupan setelah uji tantang didapatkan hasil yang tidak berbeda nyata, dimana: A (93,33±5,77%), B (96,67±5,77%), C (96,67±5,77%) dan D (96,67±5,77%). Kesimpulan dari penelitian ini ialah pemberian konsentrasi larutan garam yang berbeda berpengaruh sangat nyata terhadap kelulushidupan, SGR, panjang mutlak, FCR dan EPP, namun tidak berpengaruh nyata terhadap kelulushidupan setelah uji tantang. Konsentrasi larutan garam terbaik pada penelitian ini adalah 1,0%. Based on data from KKP (2013), the achievement of the production of catfish in 2013 was able of exceeding the target. Catfish is a fish that easily cultivated, so a lot of research done to get catfish\u27s seed with better survival and growth, and it can resistant to attack of deseases. This research was aimed to find out the effect of different salt solution concentrations and the best concentration from immersion of rGH and vaccine for survival rate and growth of sangkuriang catfish\u27s seed. This research was conducted on November 13th, 2014 – February 15th, 2015 at Satuan Kerja Pembenihan dan Budidaya Ikan Air Tawar (SATKER PBIAT), Siwarak, Ungaran, Semarang. The fish that used for this research is sangkuriang catfish\u27s seed aged 12 days. Completely randomized design (CRD) was used in this research with four treatments and three replication, which treatments are: (A) without salt solution concentration, (B) Using concentration 0.5%, (C) Concentration 1.0% and (D) Concentration 1.5%. The Fishes are maintained for 42 days. Observational variable are survival rate, SGR, absolute length, FCR, EPP and survival rate after challenge test. Data analysis using anova to know the effect of treatment is significantly different, if the result is significantly different, then continue with duncan test to know the best treatment. The best result is treatment C, with survival rate (87.00±1.00%), SGR (7.79±0.03%), absolute length (6.75±0.15cm), FCR (0.71±0.01), EPP (140.28±1.25%), and for survival rate after challenge test are not significantly different, where: treatment A (93.33±5.77%), B (96.67±5.77%), C (96.67±5.77%) and D (96.67±5.77%). The conclusion of this research is giving of salt solution with different concentration take significantly effect for survival rate, SGR, absolute length, FCR and EPP, but did not take significantly effect for survival rate after challenge test. The best salt solution concentration is 1.0%

p63 isoforms regulate metabolism of cancer stem cells

p63 is an important regulator of epithelial development expressed in different variants containing (TA) or lacking (\u394N) the N-terminal transactivation domain. The different isoforms regulate stem-cell renewal and differentiation as well as cell senescence. Several studies indicate that p63 isoforms also play a role in cancer development; however, very little is known about the role played by p63 in regulating the cancer stem phenotype. Here we investigate the cellular signals regulated by TAp63 and \u394Np63 in a model of epithelial cancer stem cells. To this end, we used colon cancer stem cells, overexpressing either TAp63 or \u394Np63 isoforms, to carry out a proteomic study by chemical-labeling approach coupled to network analysis. Our results indicate that p63 is implicated in a wide range of biological processes, including metabolism. This was further investigated by a targeted strategy at both protein and metabolite levels. The overall data show that TAp63 overexpressing cells are more glycolytic-active than \u394Np63 cells, indicating that the two isoforms may regulate the key steps of glycolysis in an opposite manner. The mass-spectrometry proteomics data of the study have been deposited to the ProteomeXchange Consortium (http://proteomecentral. proteomexchange.org) via the PRIDE partner repository with data set identifiers PXD000769 and PXD000768

Age-dependent modifications of AMPA receptor subunit expression levels and related cognitive effects in 3xTg-AD mice

GluA1, GluA2, GluA3, and GluA4 are the constitutive subunits of amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), the major mediators of fast excitatory transmission in the mammalian central nervous system. Most AMPARs are Ca2+-impermeable because of the presence of the GluA2 subunit. GluA2 mRNA undergoes an editing process that results in a Q-R substitution, a key factor in the regulation of AMPAR Ca2+-permeability. AMPARs lacking GluA2 or containing the unedited subunit are permeable to Ca2+and Zn2+. The phenomenon physiologically modulates synaptic plasticity while, in pathologic conditions, leads to increased vulnerability to excitotoxic neuronal death. Given the importance of these subunits, we have therefore evaluated possible associations between changes in expression levels of AMPAR subunits and development of cognitive deficits in 3xTg-AD mice, a widely investigated transgenic mouse model of Alzheimer's disease (AD). With quantitative real-time PCR analysis, we assayed hippocampal mRNA expression levels of GluA1-4 subunits occurring in young [3 months of age (m.o.a.)] and old (12 m.o.a) Tg-AD mice and made comparisons with levels found in age-matched wild type (WT) mice. Efficiency of GluA2 RNA editing was also analyzed. All animals were cognitively tested for learning short- and long-term spatial memory with the Morris Water Maze (MWM) navigation task. 3xTg-AD mice showed age-dependent decreases of mRNA levels for all the AMPAR subunits, with the exception of GluA2. Editing remained fully efficient with aging in 3xTg-AD and WT mice. A one-to-one correlation analysis between MWM performances and GluA1-4 mRNA expression profiles showed negative correlations between GluA2 levels and MWM performances in young 3xTg-AD mice. On the contrary, positive correlations between GluA2 mRNA and MWM performances were found in young WT mice. Our data suggest that increases of AMPARs that contain GluA1, GluA3, and GluA4 subunits may help in maintaining cognition in pre-symptomatic 3xTg-AD mice.© 2014 Cantanelli, Sperduti, Ciavardelli, Stuppia, Gatta and Sensi

Correction: Zinc is required to ensure the expression of flagella and the ability to form biofilms in Salmonella enterica sv Typhimurium

: Correction for 'Zinc is required to ensure the expression of flagella and the ability to form biofilms in Salmonella enterica sv Typhimurium' by Serena Ammendola et al., Metallomics, 2016, DOI: 10.1039/c6mt00108d

Ceramic-on-metal coupling in THA: long term clinical and radiographic outcomes using two different short stems

Background: Hip prosthetic replacement surgery is the gold standard for patients affected by symptomatic osteoarthritis. The ceramic-on-metal hybrid hard-on-hard bearing was initially launched on the market with the purpose of reducing adhesive and corrosion wear, loss of metal debris and ions and risk of fracture and squeaking. However, this bearing was withdrawn from the market, in the apprehension of local and systemic toxicity. The aim of this study is to evaluate the reliability and safety of ceramic-on-metal bearing at long term follow-up. Methods: From 2 cohorts of patients suffering of hip osteoarthritis who underwent total hip arthroplasty using ceramic-on-metal bearing with two different short stems, 19 of the GROUP A and 25 of the GROUP B were suitable for this study. All patients were compared clinically using the Harris Hip Score (HHS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), visual analogue scale (VAS), 12-item Short Form Health Survey (SF12P/M), and radiographically. Blood samples were collected in order to evaluate chromium and cobalt ions level. The two groups were compared in terms of metal ions blood levels, and finally all the implanted prostheses were compared with a healthy control group. Results: All the implanted stems were well-positioned and osseointegrated at a mean follow-up of 114 months. Improvements were observed for all clinical scores comparing preoperative and postoperative values in both groups. Radiographic evaluation showed a good ability to restore proper articular geometry. Chromium and cobalt ion analysis revealed values below the safety threshold except for 1 case in GROUP A (cup malposition) and 2 cases in GROUP B (6.1%). No revision occurred. Conclusions: Ceramic-on-metal bearing is safe and reliable at long term follow-up in association to short stems arthroplasty, if the implant is correctly positioned. Chromium and cobalt metal ions blood levels evaluation should be performed annually

Nrf2-dependent persistent oxidative stress results in stress-induced vulnerability to depression.

Stressful life events produce a state of vulnerability to depression in some individuals. The mechanisms that contribute to vulnerability to depression remain poorly understood. A rat model of intense stress (social defeat (SD), first hit) produced vulnerability to depression in 40% of animals. Only vulnerable animals developed a depression-like phenotype after a second stressful hit (chronic mild stress). We found that this vulnerability to depression resulted from a persistent state of oxidative stress, which was reversed by treatment with antioxidants. This persistent state of oxidative stress was due to low brain-derived neurotrophic factor (BDNF) levels, which characterized the vulnerable animals. We found that BDNF constitutively controlled the nuclear translocation of the master redox-sensitive transcription factor Nrf2, which activates antioxidant defenses. Low BDNF levels in vulnerable animals prevented Nrf2 translocation and consequently prevented the activation of detoxifying/antioxidant enzymes, ultimately resulting in the generation of sustained oxidative stress. Activating Nrf2 translocation restored redox homeostasis and reversed vulnerability to depression. This mechanism was confirmed in Nrf2-null mice. The mice displayed high levels of oxidative stress and were inherently vulnerable to depression, but this phenotype was reversed by treatment with antioxidants. Our data reveal a novel role for BDNF in controlling redox homeostasis and provide a mechanistic explanation for post-stress vulnerability to depression while suggesting ways to reverse it. Because numerous enzymatic reactions produce reactive oxygen species that must then be cleared, the finding that BDNF controls endogenous redox homeostasis opens new avenues for investigation

The role of autophagy in the cross-talk between epithelial-mesenchymal transitioned tumor cells and cancer stem-like cells

Epithelial-mesenchymal transition (EMT) and cancer stem-like cells (CSC) are becoming highly relevant targets in anticancer drug discovery. A large body of evidence suggests that epithelial-mesenchymal transitioned tumor cells (EMT tumor cells) and CSCs have similar functions. There is also an overlap regarding the stimuli that can induce the generation of EMT tumor cells and CSCs. Moreover, direct evidence has been brought that EMT can give rise to CSCs. It is unclear however, whether EMT tumor cells should be considered CSCs or if they have to undergo further changes. In this article we summarize available evidence suggesting that, indeed, additional programs must be engaged and we propose that macroautophagy (hereafter, autophagy) represents a key trait distinguishing CSCs from EMT tumor cells. Thus, CSCs have often been reported to be in an autophagic state and blockade of autophagy inhibits CSCs. On the other hand, there is ample evidence showing that EMT and autophagy are distinct events. CSCs, however, represent, by themselves, a heterogeneous population. Thus, CSCs have been distinguished in predominantly noncycling and cycling CSCs, the latter representing CSCs that self-renew and replenish the pool of differentiated tumor cells. We now suggest that the non-cycling CSC subpopulation is in an autophagic state. We propose also two models to explain the relationship between EMT tumor cells and these two major CSC subpopulations: a branching model in which EMT tumor cells can give rise to cycling or non-cycling CSCs, respectively, and a hierarchical model in which EMT tumor cells are first induced to become autophagic CSCs and, subsequently, cycling CSCs. Finally, we address the therapeutic consequences of these insights