Identifying canonical and replicable multi-scale intrinsic connectivity networks in 100k+ resting-state fMRI datasets.

Despite the known benefits of data-driven approaches, the lack of approaches for identifying functional neuroimaging patterns that capture both individual variations and inter-subject correspondence limits the clinical utility of rsfMRI and its application to single-subject analyses. Here, using rsfMRI data from over 100k individuals across private and public datasets, we identify replicable multi-spatial-scale canonical intrinsic connectivity network (ICN) templates via the use of multi-model-order independent component analysis (ICA). We also study the feasibility of estimating subject-specific ICNs via spatially constrained ICA. The results show that the subject-level ICN estimations vary as a function of the ICN itself, the data length, and the spatial resolution. In general, large-scale ICNs require less data to achieve specific levels of (within- and between-subject) spatial similarity with their templates. Importantly, increasing data length can reduce an ICN's subject-level specificity, suggesting longer scans may not always be desirable. We also find a positive linear relationship between data length and spatial smoothness (possibly due to averaging over intrinsic dynamics), suggesting studies examining optimized data length should consider spatial smoothness. Finally, consistency in spatial similarity between ICNs estimated using the full data and subsets across different data lengths suggests lower within-subject spatial similarity in shorter data is not wholly defined by lower reliability in ICN estimates, but may be an indication of meaningful brain dynamics which average out as data length increases.

Acute objective and subjective intoxication effects of legal-market high potency THC-dominant versus CBD-dominant cannabis concentrates.

As the market for cannabis concentrate products grows, the lack of research regarding the effects of concentrated THC and CBD becomes more glaring. The present study analyzes cannabinoid blood levels and subjective outcomes of physical sensation and affective state after ad libitum use of legal-market concentrate products. Recreational cannabis users were randomly assigned to THC- or CBD-dominant concentrate products, completing a baseline session, and an experimental mobile laboratory session consisting of timepoints before, immediately after, and one-hour after concentrate use. THC-dominant concentrates induced higher intoxication, and higher ratings of drug effect and drug liking than the CBD-dominant concentrate. Both products induced immediate feelings of elation, diminishing over the subsequent hour. Subjective outcomes in the CBD-dominant group revealed immediate decreases in tension and anxiety relative to pre-use, while the THC-dominant group only saw significant decreases in anxiety after one hour. Paranoia spiked immediately post-use in THC-dominant concentrate users, returning to baseline within an hour. Overall, the CBD-dominant concentrate invoked positive mood effects, lower intoxication and an absence of undesirable effects experienced with the THC-dominant concentrate, potentially mitigating negative effects when combined. Results support the need for further investigation into harm-reduction potential of concentrated CBD when used alone and with THC.

THC and CBD effects on alcohol use among alcohol and cannabis co-users.

OBJECTIVE: Conflicting evidence exists regarding the effects of cannabis on alcohol consumption, with some studies suggesting that cannabis is a substitute for alcohol, whereas others suggest that cannabis complements alcohol, thereby increasing drinking. Cannabidiol (CBD) has shown preclinical promise in decreasing alcohol consumption. This study explores the effects of cannabis containing different potencies of CBD and delta-9-tetrahydrocannabinol (THC) on alcohol consumption. METHOD: In this naturalistic observational study, 120 cannabis and alcohol-using adults (mean age = 33.2 years, 39.2% female, 83.3% white) were assigned to use one of three legal-market cannabis strains (predominantly THC, predominantly CBD, and CBD + THC) ad libitum for 5 days. Timeline Followback data on drinking and cannabis use were collected at a baseline session pertaining to the 30 days prior to the ad libitum period, and data regarding alcohol and cannabis use during the 5-day period were collected at follow-up (FU), immediately following the 5-day period. RESULTS: Regression models tested strain differences in drinking outcomes during the ad libitum period. Orthogonal contrast codes were created comparing the CBD group with the other two groups and comparing the THC group with the CBD + THC group. The CBD group drank fewer drinks per drinking day (p < .05), had fewer alcohol use days (p < .05), and fewer alcohol and cannabis co-use days (p < .05) compared with the other groups. No differences emerged between the THC and the CBD + THC group. CONCLUSIONS: Cannabinoid content should be considered in studies of alcohol and cannabis co-use. Findings are consistent with preclinical work, suggesting that CBD may be associated with decreased alcohol consumption. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Dilute-coat-color locus of mice: nucleotide sequence analysis of the d+2J and d+Ha revertant alleles.

The unstable dilute-coat-color mutation (d) of DBA/2J mice has been shown to be the result of integration of an ecotropic murine leukemia virus within the mouse genome. Molecular cloning and restriction enzyme analysis of the dilute allele and the viral preintegration site (+ allele), as well as two independent dilute revertants (d+2J and d+Ha), suggested that reversion is due to virus excision occurring by homologous recombination involving the viral long terminal repeats. The DNA sequence has now been determined for the cell-virus junctions of the provirus associated with the d mutation, for the viral preintegration site, and for the two revertant sites. These data (i) indicate that the d mutation was caused by a normal virus integration, (ii) confirm that virus excision occurs by precise homologous recombination, as exactly one long terminal repeat is present in each revertant site, and (iii) suggest that the virus induced the d mutation by integration into a noncoding sequence.

A repeated segment on the mouse Y chromosome is composed of retroviral-related, Y-enriched and Y-specific sequences.

We report the isolation and characterization of two recombinant clones containing DNA derived from the Y chromosome of the C57BL/10 inbred mouse strain. Both clones were isolated from a lambda phage library derived from a partial EcoRI digest of C57BL/10 male DNA using the murine retrovirus M720. Characterization of these clones showed they were derived from a repeated segment present on the C57BL/10J Y chromosome that contains sequences found elsewhere in the genome. In addition, one clone contained a sequence, designated YB10, that is unique to the Y chromosome and present in approximately 500 copies on the C57BL/10J Y chromosome. Analysis of Southern blots containing DNAs prepared from females and males of representative species from four subgenera of Mus probed with pYB10 and the 3'LTR from one of the Y-associated retroviruses (MuRVY) revealed that, with the exception of a single fragment observed in both female and male DNA of Mus saxicola, hybridization to pYB10 was observed only to male DNA of the species Mus spretus, Mus hortulanus, Mus musculus, Mus domesticus and Mus abbotti. In addition, the pattern and intensity of hybridization to YB10 and the MuRVY-LTR indicated that sequence of divergence was followed by amplification of Y chromosome sequences containing YB10 and MuRVY. The divergence and amplification occurred separately in each of the ancestral lineages leading to M. spretus, M. hortulanus, M. abbotti, M. musculus and M. domesticus. We suggest that acquisition and amplification of DNA sequences by the mammalian Y chromosome has contributed to its evolution and may imply that the mammalian Y chromosome is evolving at a faster rate than the rest of the genome.

Steroid receptor folding by heat-shock proteins and composition of the receptor heterocomplex.

Over the past 2 years, reports from several laboratories have supported the proposal that the steroid receptors are bound through the hormone-binding domain to a protein complex that contains three heat-shock proteins-hsp90, hsp70, and hsp56. This receptor-heat-shock-protein heterocomplex accounts for the behavior of the classic 9 S, non-DNA-binding form of the adrenocorticoid, sex hormone, and dioxin receptors. The receptor heterocomplex has now been reconstituted by an enzymatic system in reticulocyte lysate. This represents the first in vitro system for reversing receptor transformation, and this ability to reconstitute the receptor heterocomplex promises rapid advances in our understanding of how these receptors are folded, transported, and regulated by hormone in the cell.

Cloning of randomly sheared DNA fragments from a phi 105 lysogen of Bacillus subtilis identification of prophage-containing clones.

A gene bank for Bacillus subtilis has been developed by cloning randomly sheared DNA fragments of a B. subtilis (phi 105) lysogen DNA in Escherichia coli employing the pMB9 plasmid vector. The DNA was inserted by the oligo(dA)-oligo(dT) method, and the average insert size of the cloned DNA was 7 kilobase pairs (kb). Three clones have been identified which carry DNA from the phi 105 prophage. None of these clones contain the phage-chromosome junction.

Study design and baseline characteristics of the study to evaluate carotid ultrasound changes in patients treated with ramipril and vitamin E: SECURE.

Atherosclerotic cardiovascular disease remains a major cause of mortality and morbidity in most developed countries. Experimental and clinical evidence suggests that angiotensin-converting enzyme inhibitors and vitamin E therapy may retard the atherosclerotic process; however, definitive proof in humans is lacking. The Study to Evaluate Carotid Ultrasound Changes in Patients Treated with Ramipril and Vitamin E (SECURE) is designed to assess the effects of ramipril--an angiotensin-converting enzyme inhibitor, at 2 doses: 2.5 mg daily (which has little effect on lowering blood pressure) and 10 mg daily--and the antioxidant vitamin E, 400 IU daily, on atherosclerosis progression in 732 patients using a factorial 3 x 2 study design. High-risk patients with a documented history of significant cardiovascular disease or with diabetes and additional risk factors were enrolled and will be followed for 4 years. The extent and progression of atherosclerosis are assessed noninvasively by B-mode carotid ultrasonography. The SECURE trial is a substudy of the larger Heart Outcomes Prevention Evaluation (HOPE) study of 9,541 high-risk patients evaluating the effects of ramipril and vitamin E on major cardiovascular events (cardiovascular death, myocardial infarction, and stroke). The 2 studies are complementary. Whereas HOPE is expected to provide information on major clinical outcomes, SECURE will shed light on the mechanisms by which these effects may be mediated.

Comparison of the effects of I.C.I. 50172 and propranolol on the cardiovascular responses to adrenaline, isoprenaline and exercise.

1. The intravenous infusion of I.C.I. 50172 in doses up to 20 mg reduced, although not significantly, the increase in heart rate produced by the infusion of isoprenaline in healthy volunteers; the response to adrenaline was significantly reduced. The infusion of 1 mg propranolol abolished these responses2. After the pre-treatment of subjects with atropine or hexamethonium, I.C.I. 50172 produced a significant reduction in an isoprenaline tachycardia. This reduction was not competitive and did not exceed 50%.3. The intravenous injection of 4 mg I.C.I. 50172 reduced an exercise tachycardia; its effect was less than that of 4 mg propranolol. This difference became greater as the doses of the two drugs were increased. The dextro isomer of propranolol had no effect on the exercise tachycardia; I.C.I. 45763 reduced it to the same extent as propranolol.4. The intravenous injection of I.C.I. 50172 reduced the increase in heart rate produced by tilting a normal subject from the supine to 80 degrees head-up position. After the administration of atropine, I.C.I. 50172 almost abolished the response. In the presence of atropine, I.C.I. 50172 was as active as propranolol in reducing the increase in heart rate on tilting.5. The reason for the differences in the effects of I.C.I. 50172 on the increases in heart rate brought about by the three procedures is not clear.6. The increase in forearm blood flow produced by the infusion of isoprenaline into the brachial artery was not reduced by the intra-arterial administration of I.C.I. 50172.

Effect of d-amphetamine on prepulse inhibition of the startle reflex in humans.

RATIONALE: Prepulse inhibition of the startle reflex (PPI) is attenuated in animals after administration of d-amphetamine and other drugs that stimulate mesolimbic dopamine activity. OBJECTIVE: The aim of the present study was to evaluate the effects of d-amphetamine (20 mg) on a variety of psychophysiological and subjective measures, including PPI, in humans. METHOD: Thirty-six participants (18 women) participated in a double-blind, placebo controlled, repeated measures study. In one session, participants received d-amphetamine (20 mg) orally, and in the other session, participants received an identical appearing placebo. Participants were assessed at 60, 90, and 120 min after ingestion with a 5-min block of startle trials (six control trials and six prepulse trials) followed by subjective measures of stimulation and mood. RESULTS: d-Amphetamine increased subjective measures of stimulation and euphoria, attenuated PPI, and increased heart rate, relative to placebo treatment. CONCLUSIONS: The effect of d-amphetamine on the subjective measures was substantial and consistent over time, while the effect on PPI was only observed at 90 min after ingestion, and the effect on heart rate was limited to 90 and 120 min after ingestion.