Amyloid β-protein oligomers upregulate the β-secretase, BACE1, through a post-translational mechanism involving its altered subcellular distribution in neurons

Quantification of fluorescence intensities in axons and dendrites. After double immunofluorescent staining of primary neurons with anti-BACE1 (green) and anti-MAP2 (red) antibodies, specimens were examined under a LSM780 microscope. BACE1 fluorescence intensities along MAP2-positive dendrites (red line) and MAP2-negative axons (blue line) were quantified as described in Methods. Scale bar = 10 μm. (PDF 66 kb

Cooking Vessels, Volumes, and Venues: Evidence from LM IIIC Kavousi Vronda and Karphi

Glowacki, K.T., and L.P. Day. “Cooking Vessels, Volumes, and Venues: Evidence from LM IIIC Kavousi Vronda and Karphi.” Abstract of paper read at Διατροφικές συνήθειες και πρακτικές στην Κρήτη διαχρονικά [Dietary Habits and Practices in Crete over Time], Museum of Cretan Ethnology, Voroi, Crete, Greece, September 9–10, 2017.Our understanding of diet and culinary practices at the Late Minoan IIIC settlement sites of Kavousi Vronda and Karphi is based upon several different types of physical evidence that have been recovered through excavation. These include the botanical and faunal remains of plants and animals available to and consumed by the inhabitants; ceramic vessels used for the cooking and consumption of food and drink; built and fixed cooking installations, such as hearths and ovens; and the architectural spaces within the settlements where food preparation and consumption most likely took place. Each type of evidence is, by itself, incomplete and dependent upon differential preservation resulting from site formation processes specific to each archaeological context. Taken together, however, they allow us to gain important insights into key aspects of food cultivation, provisioning, processing, preparation, and convivial practices on Crete in the 12th and 11th centuries BC. In this paper, we will compare and contrast the evidence for food preparation and dining at each site, paying special attention to the forms and sizes of ceramic vessels used for cooking and consumption

PNA–NLS conjugates as single-molecular activators of target sites in double-stranded DNA for site-selective scission

Artificial DNA cutters have been developed by us in our previous studies by combining two strands of pseudo-complementary peptide nucleic acid (pcPNA) with Ce(IV)–EDTA-promoted hydrolysis. The pcPNAs have two modified nucleobases (2,6-diaminopurine and 2-thiouracil) instead of conventional A and T, and can invade double-stranded DNA to activate the target site for the scission. This system has been applied to site-selective scissions of plasmid, λ-phage, E. coli genomic DNA, and human genomic DNA. Here, we have reported a still simpler and more convenient DNA cutter obtained by conjugating peptide nucleic acid (PNA) with a nuclear localization signal (NLS) peptide. This new DNA cutter requires only one PNA strand (instead of two) bearing conventional (non-pseudo-complementary) nucleobases. This PNA–NLS conjugate effectively activated the target site in double-stranded DNA and induced site-selective scission by Ce(IV)–EDTA. The complex formation between the conjugate and DNA was concretely evidenced by spectroscopic results based on time-resolved fluorescence. The target scission site of this new system was straightforwardly determined by the Watson–Crick base pairing rule, and mismatched sequences were clearly discriminated. Importantly, even highly GC-rich regions, which are difficult to be targeted by a previous strategy using pcPNA, were successfully targeted. All these features of the present DNA cutter make it promising for various future applications

Inward or Outward Costophrenic Angles: A Simple Sign on Chest X-ray for the Screening of Metabolic Syndrome

Prevention of cardiovascular diseases is a top-priority issue in Japan. To this end, we have developed a new screening method for metabolic syndrome (MetS) using chest X-ray. We recruited 200 patients who visited our outpatient cardiology clinic from March 2014 to August 2014. Patients with severe lung disease, acute coronary syndrome, and end-stage renal failure were excluded. We collected data on each patient\u27s medical history, laboratory results, waist circumference (WC), body weight, and height. Additionally, we measured two parameters from the chest X-ray: (A) width at the level of right dome of diaphragm and (B) width between the costophrenic (CP) angles. We classified the CP angles as either inward (A≥B) or outward (A<B). Increased WC was defined as ≥85cm in males and ≥90cm in females. Patients with outward CP angles had a significantly larger WC compared to those with inward CP angles (92.3±8.9 vs. 80.5±7.8cm, P<0.001). In particular, the percentage of male patients with increased WC (≥ 85cm) was significantly higher in patients with outward CP angles than in those with inward CP angles (89.2% vs. 41.3%, P<0.001). Body weight and BMI were both significantly higher in patients with outward CP angles than in those with inward CP angles in both gender groups. When laboratory data and risk factors were compared, patients with outward CP angles and those with positive WC criteria consistently tended toward high morbidity from hypertension, dyslipidemia, and diabetes. The inward/outward CP identified candidates for MetS, especially in the male subjects. Chest X-ray could become a useful screening tool for the detection of increased WC and coronary risk factors

Protection against Amyloid-&beta; Oligomer Neurotoxicity by Small Molecules with Antioxidative Properties: Potential for the Prevention of Alzheimer&rsquo;s Disease Dementia

Soluble oligomeric assemblies of amyloid &beta;-protein (A&beta;), called A&beta; oligomers (A&beta;Os), have been recognized as primary pathogenetic factors in the molecular pathology of Alzheimer&rsquo;s disease (AD). A&beta;Os exert neurotoxicity and synaptotoxicity and play a critical role in the pathological progression of AD by aggravating oxidative and synaptic disturbances and tau abnormalities. As such, they are important therapeutic targets. From a therapeutic standpoint, it is not only important to clear A&beta;Os or prevent their formation, it is also beneficial to reduce their neurotoxicity. In this regard, recent studies have reported that small molecules, most with antioxidative properties, show promise as therapeutic agents for reducing the neurotoxicity of A&beta;Os. In this mini-review, we briefly review the significance of A&beta;Os and oxidative stress in AD and summarize studies on small molecules with A&beta;O-neurotoxicity-reducing effects. We also discuss mechanisms underlying the effects of these compounds against A&beta;O neurotoxicity as well as their potential as drug candidates for the prevention and treatment of AD