Functional single nucleotide polymorphisms in dopaminergic receptors D2 predict clinical response to Cariprazine

Cariprazine (CAR) is an antipsychotic drug for the treatment of schizophrenia (SCZ) and bipolar disorder (BD), and it acts as a partial agonist on the dopamine receptors (DR), D2, and D3. Although many single nucleotide polymorphisms (SNPs) in genes coding for these receptors are known to influence response to antipsychotics, to date, no study on CAR pharmacogenetics exists. In this pilot study, we investigated the relationship between SNPs in DRD2 (rs1800497 and rs6277) and DRD3 (rs6280), and response to CAR treatment, evaluated by the psychometric Brief Psychiatric Rating Scale (BPRS), in a cohort of Caucasian patients. We found a significant association between DRD2 rs1800497 and rs6277 and response to CAR treatment. When genotypes were combined into an arbitrary score, the receiver operating characteristic curve analysis showed that using a cut-off value of -2.5 the response to CAR treatment could be predicted with a positive likelihood ratio of 8.0. Our study report, for the first time, a correlation between SNPs in DRD2 and response to CAR treatment. After confirmation in a larger cohort of patients, our results could open the way for the identification of new tools for the provision of response to CAR treatment

Isometries, submetries and distance coordinates on Finsler manifolds

This paper considers fundamental issues related to Finslerian iso- metries, submetries, distance and geodesics. It is shown that at each point of a Finsler manifold there is a distance coordinate system. Us- ing distance coordinates, a simple proof is given for the Finslerian version of the Myers-Steenrod theorem and for the differentiability of Finslerian submetries

Cortical β-amyloid burden, neuropsychiatric symptoms, and cognitive status: the Mayo Clinic Study of Aging

Abstract Neuropsychiatric symptoms (NPS) are a risk factor for cognitive impairment and are associated with cortical β-amyloid (Aβ) deposition. We conducted a cross-sectional study derived from the ongoing population-based Mayo Clinic Study of Aging to examine the frequency of NPS among cognitively unimpaired (CU) and mild cognitive impairment (MCI) participants who either have normal (A−) or abnormal (A+) Aβ deposition. We also investigated whether combined presence of MCI and amyloid positivity (MCI/A+) is associated with greater odds of having NPS as compared to CU/A− (defined as reference group). Participants were 1627 CU and MCI individuals aged ≥ 50 years (54% males; median age 73 years). All participants underwent NPS assessment (Neuropsychiatric Inventory Questionnaire (NPI-Q); Beck Depression Inventory II (BDI-II); Beck Anxiety Inventory (BAI)) and 11C-PiB-PET. Participants with an SUVR > 1.42 were classified as A+. We conducted multivariable logistic regression analyses adjusted for age, sex, education, and APOE ε4 genotype status. The sample included 997 CU/A−, 446 CU/A+, 78 MCI/A−, and 106 MCI/A+ persons. For most NPS, the highest frequency of NPS was found in MCI/A+ and the lowest in CU/A−. The odds ratios of having NPS, depression (BDI ≥ 13), or anxiety (BAI ≥ 8, ≥ 10) were consistently highest for MCI/A+ participants. In conclusion, MCI with Aβ burden of the brain is associated with an increased risk of having NPS as compared to MCI without Aβ burden. This implies that the underlying Alzheimer’s disease biology (i.e., cerebral Aβ amyloidosis) may drive both cognitive and psychiatric symptoms

Phenolic, polysaccharidic and lipidic fractions of mushrooms from northeast Portugal: chemical compounds with antioxidant properties

Mushrooms do not constitute a significant portion of the human diet, but their consumption continues to increase due to their functional benefits and presence of bioactive compounds. Some of those compounds can be found in the phenolic, polysaccharidic and lipidic fractions of edible and inedible species. Herein, those fractions of five wild mushrooms (Coprinopsis atramentaria, Lactarius bertillonii, Lactarius vellereus, Rhodotus palmatus and Xerocomus chrysenteron) from Northeast Portugal were studied for their chemical composition and antioxidant properties. Protocatechuic, p-hydroxybenzoic, p-coumaric and cinnamic acids were found in the phenolic fraction, ramnose, xylose, fucose, arabinose, fructose, glucose, manose, mannitol, sucrose, maltose and trehalose were quantified in polysaccharidic fraction, linoleic and stearic (only in Lactarius sp.) acids, and β- and γ-tocopherols were the main compounds in the lipidic fraction. C. atramentaria and X. chrysenteron phenolic fractions gave the highest free radical scavenging activity, reducing properties and lipid peroxidation inhibition in brain homogenates, which is in agreement with its highest content in total phenolics. Furthermore, among the polysaccharidic fractions C. atramentaria also gave the highest antioxidant activity, which is accordingly with its highest total polysaccharides content and sugars obtained after hydrolysis.The authors are grateful to Fundação para a Ciência e a Tecnologia (FCT, Portugal) and COMPETE/QREN/EU (research project PTDC/AGR-ALI/110062/2009) for financial support. L. Barros (BPD/4609/2008) and S.A. Heleno (BD/70304/2010) also thank FCT, POPH-QREN and FSE. The GIP-USAL is financially supported by the Spanish Ministerio de Ciencia e Innovación through the Consolider-Ingenio 2010 Programme (FUN-C-FOOD, CSD2007-00063), and Junta de Castilla y León (Grupo de Investigación de Excelencia, GR133)

Staphylococcus aureus forms spreading dendrites that have characteristics of active motility

Staphylococcus aureus is historically regarded as a non-motile organism. More recently it has been shown that S. aureus can passively move across agar surfaces in a process called spreading. We re-analysed spreading motility using a modified assay and fo- cused on observing the formation of dendrites: branching structures that emerge from the central colony. We discovered that S. aureus can spread across the surface of media in struc- tures that we term ‘comets’, which advance outwards and precede the formation of dendrites. We observed comets in a diverse selection of S. aureus isolates and they exhibit the following behaviours: (1) They consist of phenotypically distinct cores of cells that move forward and seed other S. aureus cells behind them forming a comet ‘tail’; (2) they move when other cells in the comet tail have stopped moving; (3) the comet core is held together by a matrix of slime; and (4) the comets etch trails in the agar as they move forwards. Comets are not con- sistent with spreading motility or other forms of passive motility. Comet behaviour does share many similarities with a form of active motility known as gliding. Our observations therefore suggest that S. aureus is actively motile under certain conditions