An inhibitory pull-push circuit in frontal cortex.

Push-pull is a canonical computation of excitatory cortical circuits. By contrast, we identify a pull-push inhibitory circuit in frontal cortex that originates in vasoactive intestinal polypeptide (VIP)-expressing interneurons. During arousal, VIP cells rapidly and directly inhibit pyramidal neurons; VIP cells also indirectly excite these pyramidal neurons via parallel disinhibition. Thus, arousal exerts a feedback pull-push influence on excitatory neurons-an inversion of the canonical push-pull of feedforward input

Collection of Epithelial Cells from Rodent Mammary Gland Via Laser Capture Microdissection Yielding High-Quality RNA Suitable for Microarray Analysis

Laser capture microdissection (LCM) enables collection of cell populations highly enriched for specific cell types that have the potential of yielding critical information about physiological and pathophysiological processes. One use of cells collected by LCM is for gene expression profiling. Samples intended for transcript analyses should be of the highest quality possible. RNA degradation is an ever-present concern in molecular biological assays, and LCM is no exception. This paper identifies issues related to preparation, collection, and processing in a lipid-rich tissue, rodent mammary gland, in which the epithelial to stromal cell ratio is low and the stromal component is primarily adipocytes, a situation that presents numerous technical challenges for high-quality RNA isolation. Our goal was to improve the procedure so that a greater probe set present call rate would be obtained when isolated RNA was evaluated using Affymetrix microarrays. The results showed that the quality of RNA isolated from epithelial cells of both mammary gland and mammary adenocarcinomas was high with a probe set present call rate of 65% and a high signal-to-noise ratio

Characterization of the Fungal Microbiota (Mycobiome) in Healthy and Dandruff-Afflicted Human Scalps

The human scalp harbors a vast community of microbial mutualists, the composition of which is difficult to elucidate as many of the microorganisms are not culturable using current culture techniques. Dandruff, a common scalp disorder, is known as a causative factor of a mild seborrheic dermatitis as well as pityriasis versicolor, seborrheic dermatitis, and atopic dermatitis. Lipophilic yeast Malassezia is widely accepted to play a role in dandruff, but relatively few comprehensive studies have been reported. In order to investigate fungal biota and genetic resources of dandruff, we amplified the 26S rRNA gene from samples of healthy scalps and dandruff-afflicted scalps. The sequences were analyzed by a high throughput method using a GS-FLX 454 pyrosequencer. Of the 74,811 total sequence reads, Basidiomycota (Filobasidium spp.) was the most common phylum associated with dandruff. In contrast, Ascomycota (Acremonium spp.) was common in the healthy scalps. Our results elucidate the distribution of fungal communities associated with dandruff and provide new avenues for the potential prevention and treatment of dandruff

Phaeochromocytoma and functioning paraganglioma in childhood and adolescence: role of iodine 131 metaiodobenzylguanidine

Phaeochromocytomas and functioning paragangliomas are rare tumours in childhood and adolescence. We review our experience of 43 cases (24 men, 19 women) who were first diagnosed at the age of ⩽ 18 years. All patients were evaluated at some point in their illness with iodine 131 metaiodobenzylguanidine ( 131 I-mIBG) scintigraphy. Eight patients (19%) had bilateral adrenal tumours, 12 (28%) had solitary extra-adrenal tumours, and 8 (19%) had multiple tumours. In 10 patients (23%), the tumours were associated with a familial neurocristopathic syndrome. Thirteen of 24 (54%) unifocal tumours which were initially considered to be benign ultimately proved to be multi-focal and/or malignant. The final prevalence of malignancy was 60% − 26 patients, of whom only 15 (57%) had obviously malignant tumours at the time of diagnosis. Primary tumour size ⋝5 cm was more commonly associated with a malignant course in adrenal but not extra-adrenal tumours. No other clinical, biochemical or morphological characteristic was significantly associated with malignancy. Although the high prevalence of malignancy in this series at least partly reflects referral bias, the need for lifelong follow-up of these patients is underscored. 131 I-mIBG scintigraphy was positive in 36 patients (84%), with a somewhat lower false-negative rate (12%) than X-ray computed tomography (20%). Eight patients with malignant tumours received therapeutic doses of 131 I-mIBG, with partial tumour responses in 3. Thus, 131 I-mIBG is an efficacious, non-invasive, localising agent and may be considered as a palliative therapeutic agent when alternatives have failed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46831/1/259_2005_Article_BF02262730.pd

Critique of the review of 'Water fluoridation for the prevention of dental caries' published by the Cochrane Collaboration in 2015

The Cochrane Review on water fluoridation for the prevention of dental caries was published in 2015 and attracted considerable interest and comment, especially in countries with extensive water fluoridation programmes. The Review had two objectives: (i) to evaluate the effects of water fluoridation (artificial or natural) on the prevention of dental caries, and (ii) to evaluate the effects of water fluoridation (artificial or natural) on dental fluorosis. The authors concluded, inter alia, that there was very little contemporary evidence, meeting the Review's inclusion criteria, that evaluated the effectiveness of water fluoridation for the prevention of dental caries. The purpose of this critique is to examine the conduct of the above Review, and to put it into context in the wider body of evidence regarding the effectiveness of water fluoridation. While the overall conclusion that water fluoridation is effective in caries prevention agrees with previous reviews, many important public health questions could not be answered by the Review because of the restrictive criteria used to judge adequacy of study design and risk of bias. The potential benefits of using wider criteria in order to achieve a fuller understanding of the effectiveness of water fluoridation are discussed

Investigating large-scale brain dynamics using field potential recordings: Analysis and interpretation

New technologies to record electrical activity from the brain on a massive scale offer tremendous opportunities for discovery. Electrical measurements of large-scale brain dynamics, termed field potentials, are especially important to understanding and treating the human brain. Here, our goal is to provide best practices on how field potential recordings (EEG, MEG, ECoG and LFP) can be analyzed to identify large-scale brain dynamics, and to highlight critical issues and limitations of interpretation in current work. We focus our discussion of analyses around the broad themes of activation, correlation, communication and coding. We provide best-practice recommendations for the analyses and interpretations using a forward model and an inverse model. The forward model describes how field potentials are generated by the activity of populations of neurons. The inverse model describes how to infer the activity of populations of neurons from field potential recordings. A recurring theme is the challenge of understanding how field potentials reflect neuronal population activity given the complexity of the underlying brain systems