Modeling Alzheimer\u27s Disease Using CRISPR/CAS9 Gene Editing and Induced Pluripotent Stem Cells Reveals Conserved Cellular Mechanisms

Alzheimer’s disease (AD) is the most common cause of dementia worldwide and a leading cause of death in the United States. Rare cases of autosomal dominant familial AD (fAD) result from genetic mutations in three key genes: amyloid precursor protein (APP), and two APP processing-related genes (presenilin-1 (PSEN1), and presenilin-2 (PSEN2)), supporting the theory that altered APP metabolism is a central cause of AD. However, which product of APP metabolism is causal remains a matter of investigation. A probable source of this lack of understanding stems from the poor disease model systems that have been utilized in the field for many years. Recently, advances in human induced pluripotent stem cell (iPSC) technology has enabled the study of uniquely human diseases, such as AD, in human tissue. However, the inability to precisely and efficiently genetically engineer human iPSCs has limited their use in effectively studying monogenic human diseases like fAD

Age and beauty are in the eye of the beholder

How “old” and “attractive” an individual appears has increasingly become an individual concern leading to the utilisation of various cosmetic surgical procedures aimed at enhancing appearance. Using eyetracking, in the present study we aimed to investigate how individuals perceive age and attractiveness of younger and older faces and what “bottom-up” facial cues are used in this process. One hundred and twenty eight digital images of neutral faces of ages ranging from 20 to 89 years were paired and presented to subjects who judged age and attractiveness levels while having their eye movements recorded. There was an effect of face attractiveness on age-rating accuracy, with attractive faces being rated younger than their true age. Similarly, stimulus age affected attractiveness ratings, with younger faces being perceived as more attractive. Judgments of age and attractiveness were tightly linked to fixations on the eye region, along with the nose and mouth. It is thus likely that cosmetic surgical procedures targeted at the eyes, nose, and mouth may be most efficacious at enhancing one's physical appearance

A Mutation in Amino Acid Permease AAP6 Reduces the Amino Acid Content of the Arabidopsis Sieve Elements but Leaves Aphid Herbivores Unaffected.

The aim of this study was to investigate the role of the amino acid permease gene AAP6 in regulating phloem amino acid composition and then to determine the effects of this altered diet on aphid performance. A genotype of Arabidopsis thaliana (L.) was produced in which the function of the amino acid permease gene AAP6 (At5g49630) was abolished. Plants homozygous for the insertionally inactivated AAP6 gene had a significantly larger mean rosette width than the wild type and a greater number of cauline leaves. Seeds from the aap6 mutant were also significantly larger than those from the wild-type plants. Sieve element (SE) sap was collected by aphid stylectomy and the amino acids derivatized, separated, and quantified using Capillary Electrophoresis with Laser Induced Fluorescence (CE-LIF). In spite of the large variation across samples, the total amino acid concentration of SE sap of the aap6 mutant plants was significantly lower than that of the wild-type plants. The concentrations of lysine, phenylalanine, leucine, and aspartic acid were all significantly lower in concentration in the aap6 mutant plants compared with wild-type plants. This is the first direct demonstration of a physiological role for an amino acid transporter in regulating SE composition in vivo. The amino acid availability in sieve element sap is thought to be the major limiting factor for aphid growth and reproduction. Despite the changes in their diet, the aphid Myzus persicae(Sulzer) displayed only small changes in feeding behaviour on mutant plants when measured using the Electronic Penetration Graph (EPG) technique. Salivation by the aphid into the SE (E1 phase) was increased on mutant plants but there was no significant effect on other feeding EPG behaviours, or in the rate of honeydew production. Consistent with the small effect on aphid feeding behaviour, there was only a small effect of reduced sieve element amino acid concentration on aphid reproduction. The data are discussed in relation to the regulation of phloem composition and the role of phloem amino acids in regulating aphid performance

Elektrophile Alkylierungen von Norbornen - Synthese 7-substituierter Norbornene

Die Lewis-Säure-katalysierte Addition SN1-reaktiver Alkylhalogenide 2 an Norbornen liefert syn-7-Alkyl-exo-2-halogennorbornane 3 neben geringen Mengen der anti-Isomeren 9. Bei der Behandlung von 3 mit Kalium-tert-butoxid erhält man die syn-7-substituierten Norbornene 4, die zu all-cis-1,2,3-trisubstituierten Cyclopentanen oxidiert werden können

Mechanochemically driven solid-state Diels-Alder reaction of graphite into graphene nanoplatelets

A mechanochemically driven solid-state Diels-Alder reaction is demonstrated via dry ball-milling graphite as the diene in the presence of maleic anhydride or maleimide as the dienophile. On the basis of various characterizations, the Diels-Alder adducts are edge-selectively functionalized and subsequently delaminated into graphene nanoplatelets.close7

Synthesis, Structure and Reactivity of Sulfur-Rich Cyclopentadienyl-Transition Metal Complexes: Sulfur Chemistry from an Organometallic Point of View

Metal-sulfur centers play an important role in the activity of metalloproteins in enzymatic catalysis and the activity of metal sulfides as heterogeneous catalysts. The systematic search for M[BOND]S model compounds led to the discovery of an interesting and novel structural chemistry, which stems from the numerous coordination possibilities of sulfur ligands. The intention of this review article is to present and outline new approaches to sulfur chemistry from the organometallic point of view. Reactive cyclopentadienyl-transition metal fragments incorporate elemental sulfur to give polynuclear sulfur-rich complexes, which can contain either mono-, di- or polysulfido ligands or several such ligands in combined form. The versatile structural chemistry of the complexes formed and their reactivity towards organic, inorganic and organometallic compounds are discussed, and examples of some simple and rational procedures for their synthesis starting from cyclopentadienylcarbonyl- and cyclopentadienylhydrido-complexes are outlined. Their reactivity is manifested in numerous metal- and ligandcentered reactions. Finally the, albeit far less extensive, complex chemistry of the other chalcogens (O, Se, Te) is also considered for comparison, thus providing a more detailed survey of particular aspects of this area of chemistry

Sigmatropic Rearrangement of Vinyl Aziridines: Expedient Synthesis of Cyclic Sulfoximines from Chiral Sulfinimines

A novel rearrangement of 2-vinyl aziridine 2-carboxylates to unusual chiral cyclic sulfoximines is described herein. The method allows the synthesis of substituted cyclic sulfoximines in high yields with complete stereocontrol, displaying a wide substrate scope under mild conditions. Further development of a one-pot process directly from sulfinimines shows the synthetic applicability of this protocol, providing access to complex chiral sulfoximines in only two steps from commercially available aldehydes. A mechanistic hypothesis and synthetic application in the formal synthesis of trachelanthamidine by transformation of a cyclic sulfoximine into a pyrroline is also disclosed