MicroRNA132 Modulates Short-Term Synaptic Plasticity but Not Basal Release Probability in Hippocampal Neurons

MicroRNAs play important regulatory roles in a broad range of cellular processes including neuronal morphology and long-term synaptic plasticity. MicroRNA-132 (miR132) is a CREB-regulated miRNA that is induced by neuronal activity and neurotrophins, and plays a role in regulating neuronal morphology and cellular excitability. Little is known about the effects of miR132 expression on synaptic function. Here we show that overexpression of miR132 increases the paired-pulse ratio and decreases synaptic depression in cultured mouse hippocampal neurons without affecting the initial probability of neurotransmitter release, the calcium sensitivity of release, the amplitude of excitatory postsynaptic currents or the size of the readily releasable pool of synaptic vesicles. These findings are the first to demonstrate that microRNAs can regulate short-term plasticity in neurons

Dose-response effect of Bifidobacterium lactis HN019 on whole gut transit time and functional gastrointestinal symptoms in adults

Objective. To assess the impact of Bifidobacterium lactis HN019 supplementation on whole gut transit time (WGTT) and frequency of functional gastrointestinal (GI) symptoms in adults. Material and methods. We randomized 100 subjects (mean age: 44 years; 64% female) with functional GI symptoms to consume a proprietary probiotic strain, B. lactis HN019 (Fonterra Research Centre, Palmerston North, New Zealand), at daily doses of 17.2 billion colony forming units (CFU) (high dose; n = 33), 1.8 billion CFU (low dose; n = 33), or placebo (n = 34) for 14 days. The primary endpoint of WGTT was assessed by X-ray on days 0 and 14 and was preceded by consumption of radiopaque markers once a day for 6 days. The secondary endpoint of functional GI symptom frequency was recorded with a subject-reported numeric (1–100) scale before and after supplementation. Results. Decreases in mean WGTT over the 14-day study period were statistically significant in the high dose group (49 ± 30 to 21 ± 32 h, p < 0.001) and the low dose group (60 ± 33 to 41 ± 39 h, p = 0.01), but not in the placebo group (43 ± 31 to 44 ± 33 h). Time to excretion of all ingested markers was significantly shorter in the treatment groups versus placebo. Of the nine functional GI symptoms investigated, eight significantly decreased in frequency in the high dose group and seven decreased with low dose, while two decreased in the placebo group. No adverse events were reported in any group. Conclusions. Daily B. lactis HN019 supplementation is well tolerated, decreases WGTT in a dose-dependent manner, and reduces the frequency of functional GI symptoms in adults

A dyadic approach to understanding the impact of breast cancer on relationships between partners during early survivorship

© 2016 The Author(s). Background: The shared impact of breast cancer for women and their male partners is emerging as an important consideration during the experience of a breast cancer diagnosis, particularly during survivorship. This study aimed to explore the experiences of women and their partners during early survivorship and contributes a range of insights into the lives of those intimately affected by breast cancer. Methods: In-depth interviews were completed with Australian women survivors of breast cancer (n = 8) and their partners (n = 8), between six months and five years following cessation of treatment. Questions included a focus on the women and their partners' daily experiences during early survivorship, including the management of ongoing symptoms, engagement in leisure and social interests, returning to work, communicating with each other, maintenance of the current relationship and other important roles and responsibilities. Thematic analysis was employed to determine key themes arising from the dyadic accounts of women and their partners' experiences during early breast cancer survivorship. Results: Women and their partners experienced many changes to their previous roles, responsibilities and relationships during early breast cancer survivorship. Couples also reported a range of communication, intimacy and sexuality concerns which greatly impacted their interactions with each other, adding further demands on the relationship. Three significant themes were determined: (1) a disconnection within the relationship - this was expressed as the woman survivor of breast cancer needing to prioritise her own needs, sometimes at the expense of her partner and the relationship; (2) reformulating the relationship - this reflects the strategies used by couples to negotiate changes within the relationship; and (3) support is needed to negotiate the future of the relationship - couples emphasised the need for additional support and resources to assist them in maintaining their relationship during early survivorship. Conclusion: It can be concluded that the early survivorship period represents a crucial time for both women and their partners and there are currently limited options available to meet their shared needs and preferences for support. Findings indicate that a suitable model of care underpinned by a biopsychosocial framework, access to comprehensive assessment, timely support and the provision of targeted resources are urgently needed to assist women and their partners during this critical time

The Role of Purported Mucoprotectants in Dealing with Irritable Bowel Syndrome, Functional Diarrhea, and Other Chronic Diarrheal Disorders in Adults

Chronic diarrhea is a frequent presenting symptom, both in primary care medicine and in specialized gastroenterology units. It is estimated that more than 5% of the global population suffers from chronic diarrhea. and that about 40% of these subjects are older than 60 years. The clinician is frequently faced with the need to decide which is the best therapeutic approach for these patients. While the origin of chronic diarrhea is diverse, impairment of intestinal barrier function, dysbiosis. and mucosal micro-inflammation are being increasingly recognized as underlying phenomena characterizing a variety of chronic diarrheal diseases. In addition to current pharmacological therapies, there is growing interest in alternative products such as mucoprotectants, which form a mucoadhesive film over the epithelium to reduce and protect against the development of altered intestinal permeability, dysbiosis, and mucosal micro-inflammation. This manuscript focuses on chronic diarrhea in adults, and we will review recent evidence on the ability of these natural compounds to improve symptoms associated with chronic diarrhea and to exert protective effects for the intestinal barrier

Superresolution microscopy of the β-carboxysome reveals a homogeneous matrix

Carbon fixation in cyanobacteria makes a major contribution to the global carbon cycle. The cyanobacterial carboxysome is a proteinaceous microcompartment that protects and concentrates the carbon-fixing enzyme ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) in a paracrystalline lattice, making it possible for these organisms to fix CO2 from the atmosphere. The protein responsible for the organization of this lattice in beta-type carboxysomes of the freshwater cyanobacterium Synechococcus elongatus, CcmM, occurs in two isoforms thought to localize differentially within the carboxysome matrix. Here we use wide-field time-lapse and three-dimensional structured illumination microscopy (3D-SIM) to study the recruitment and localization of these two isoforms. We demonstrate that this superresolution technique is capable of distinguishing the localizations of the outer protein shell of the carboxysome and its internal cargo. We develop an automated analysis pipeline to analyze and quantify 3D-SIM images and generate a population-level description of the carboxysome shell protein, RuBisCO, and CcmM isoform localization. We find that both CcmM isoforms have similar spatial and temporal localization, prompting a revised model of the internal arrangement of the β-carboxysome

Calcium dependence of release is not altered by overexpression of miR132.

<p>External calcium was varied while extracellular magnesium concentration remained constant at 1.5 mM. EPSC peak amplitudes measured in 1 mM and 10 mM were normalized to the values measured in 2.5 mM calcium. miR132 overexpression had no significant effect on the calcium dependence of release (for all groups, <i>n</i> = 9, t-test for 1 mM and 10 mM <i>P</i>>0.05; scale bar for representative traces: 1nA, 10 ms).</p

Overexpression of miR132 decreases synaptic depression in response to a train of stimuli, but does not affect the rate of refilling of the RRP.

<p>(A) Representative traces showing responses to a train of 40 stimuli delivered at 20 Hz. Data were collected at a rate of one train every 60 s to allow full recovery between trains. Traces have been normalized to the amplitude of the first stimulus in the train to facilitate comparison of synaptic depression. (B) The peak amplitude of each EPSC in the train was normalized to the peak amplitude of the first EPSC and plotted versus time to show the rate of depression during the train. The amplitude of a single EPSC evoked 1.5 s after the end of the train was used to measure recovery from depletion of the pool of readily releasable vesicles. Neurons overexpressing miR132 demonstrate significantly reduced synaptic depression during the train relative to EGFP and miR1-overexpressing controls at all time points (<i>P</i><0.05), but no change in recovery after the train.</p