Epithelial cell shedding and barrier function: a matter of life and death at the small intestinal villus tip

The intestinal epithelium is a critical component of the gut barrier. Composed of a single layer of intestinal epithelial cells (IECs) held together by tight junctions, this delicate structure prevents the transfer of harmful microorganisms, antigens, and toxins from the gut lumen into the circulation. The equilibrium between the rate of apoptosis and shedding of senescent epithelial cells at the villus tip, and the generation of new cells in the crypt, is key to maintaining tissue homeostasis. However, in both localized and systemic inflammation, this balance may be disturbed as a result of pathological IEC shedding. Shedding of IECs from the epithelial monolayer may cause transient gaps or microerosions in the epithelial barrier, resulting in increased intestinal permeability. Although pathological IEC shedding has been observed in mouse models of inflammation and human intestinal conditions such as inflammatory bowel disease, understanding of the underlying mechanisms remains limited. This process may also be an important contributor to systemic and intestinal inflammatory diseases and gut barrier dysfunction in domestic animal species. This review aims to summarize current knowledge about intestinal epithelial cell shedding, its significance in gut barrier dysfunction and host-microbial interactions, and where research in this field is directed

Global Ethics and Nanotechnology: A Comparison of the Nanoethics Environments of the EU and China

The following article offers a brief overview of current nanotechnology policy, regulation and ethics in Europe and The People’s Republic of China with the intent of noting (dis)similarities in approach, before focusing on the involvement of the public in science and technology policy (i.e. participatory Technology Assessment). The conclusions of this article are, that (a) in terms of nanosafety as expressed through policy and regulation, China PR and the EU have similar approaches towards, and concerns about, nanotoxicity—the official debate on benefits and risks is not markedly different in the two regions; (b) that there is a similar economic drive behind both regions’ approach to nanodevelopment, the difference being the degree of public concern admitted; and (c) participation in decision-making is fundamentally different in the two regions. Thus in China PR, the focus is on the responsibility of the scientist; in the EU, it is about government accountability to the public. The formulation of a Code of Conduct for scientists in both regions (China PR’s predicted for 2012) reveals both similarity and difference in approach to nanotechnology development. This may change, since individual responsibility alone cannot guide S&T development, and as public participation is increasingly seen globally as integral to governmental decision-making

A lifetime’s adventure in extracellular K+ regulation: the Scottish connection

In a career that has spanned 45 years and shows no signs of slowing down, Dr Bruce Ransom has devoted considerable time and energy to studying regulation of interstitial K+. When Bruce commenced his studies in 1969 virtually nothing was known of the functions of glial cells, but Bruce’s research contributed to the physiological assignation of function to mammalian astrocytes, namely interstitial K+ buffering. The experiments that I describe in this review concern the response of the membrane potential (Em) of in vivo cat cortical astrocytes to changes in [K+]o, an experimental manoeuvre that was achieved in two different ways. The first involved recording the Em of an astrocyte while the initial aCSF was switched to one with different K+, whereas in the second series of experiments the cortex was stimulated and the response of the astrocyte Em to the K+ released from neighbouring neurons was recorded. The astrocytes responded in a qualitatively predictable manner, but quantitatively the changes were not as predicted by the Nernst equation. Elevations in interstitial K+ are not sustained and K+ returns to baseline rapidly due to the buffering capacity of astrocytes, a phenomenon studied by Bruce, and his son Chris, published 27 years after Bruce’s initial publications. Thus, a lifetime spent investigating K+ buffering has seen enormous advances in glial research, from the time cells were identified as ‘presumed’ glial cells or ‘silent cells’, to the present day, where glial cells are recognised as contributing to every important physiological brain function

Predators reduce extinction risk in noisy metapopulations

Background Spatial structure across fragmented landscapes can enhance regional population persistence by promoting local “rescue effects.” In small, vulnerable populations, where chance or random events between individuals may have disproportionately large effects on species interactions, such local processes are particularly important. However, existing theory often only describes the dynamics of metapopulations at regional scales, neglecting the role of multispecies population dynamics within habitat patches. Findings By coupling analysis across spatial scales we quantified the interaction between local scale population regulation, regional dispersal and noise processes in the dynamics of experimental host-parasitoid metapopulations. We find that increasing community complexity increases negative correlation between local population dynamics. A potential mechanism underpinning this finding was explored using a simple population dynamic model. Conclusions Our results suggest a paradox: parasitism, whilst clearly damaging to hosts at the individual level, reduces extinction risk at the population level

Coupled down-regulation of mTOR and telomerase activity during fluorouracil-induced apoptosis of hepatocarcinoma Cells

<p>Abstract</p> <p>Background</p> <p>Hepatocellular carcinoma (HCC) is the most invasive and frequently diagnosed malignancy and the second leading cause of cancer death in many regions of Asia. The PI3K/Akt/mTOR signal pathway is involved in multiple cellular functions including proliferation, differentiation, tumorigenesis, and apoptosis. Up-regulation of telomerase activity is thought to be a critical step leading to cell transformation.</p> <p>Methods</p> <p>This study investigated changes in mTOR pathway and telomerase activity in hepatocarcinoma cell line SMMC-7721 treated with chemotherapeutic agent 5-fluorouracil (5-Fu). We detected apoptosis of hepatocarcinoma cells by TUNEL assay. Telomerase activity, hTERT transcription level and p- p70 S6k was demonstrated by the telomeric repeat amplification protocol and silver staining assay, Dual-Luciferase Reporter Assay and Western blot analysis respectively.</p> <p>Results</p> <p>Treating SMMC-7721 cells with 5-Fu leads to apoptosis of the cells, and reduction in telomerase activity, as well as a dramatic reduction in the activated form of p70 S6 kinase, a mTOR substrate. The 5-Fu treatment nearly abolishes transcription of hTERT (the major component of telomerase) mRNA. Treating SMMC-7721 cells with Rapamycin, a specific mTOR inhibitor, significantly reduce hTERT protein level but did not affect hTERT transcription. 5-Fu and rapamycin were synergistic in regards to down-regulation of telomerase activity in hepatocarcinoma cells.</p> <p>Conclusion</p> <p>These results suggest that chemotherapeutic agent 5-Fu may down-regulate telomerase activity at both transcriptional level and PI3K/Akt/mTOR pathway-dependent post-transcriptional level to facilitate hepatocellular carcinoma cell apoptosis.</p

Commentary: the role of cytologic analysis of voided urine in the work-up of asymptomatic microhematuria

Microscopic hematuria is a common finding in patients presenting to both primary care doctors as well as urologists. Sources of microscopic hematuria include infection, stones, inflammatory disorders as well as cancer of the genitourinary tract, particularly urothelial cancer. A primary focus in the urologic workup of hematuria is to rule out cancer. This is done using radiographic studies as well as procedures such as cystoscopy and bladder biopsy. As the authors state in their article titled "The utility of serial urinary cytology in the initial evaluation of the patient with microscopic hematuria", cytologic analysis of voided urine, though attractive due to its noninvasive nature, has been found to have the neither the sensitivity, cost-effectiveness, nor the ease of administration necessary to replace more invasive diagnostics in the evaluation of microscopic hematuria

Management of Hypertriglyceridemia in the Diabetic Patient

The hypertriglyceridemia of diabetes can be classified into mild to moderate (triglycerides between 150–499 mg/dL) and severe hypertriglyceridemia (triglycerides ≥500 mg/dL). As in any other individuals with hypertriglyceridemia, secondary causes need to be excluded. The management of severe hypertriglyceridemia (chylomicronemia syndrome) includes aggressive reduction of triglycerides with intravenous insulin, fibrates, omega-3 fatty acids, and/or niacin therapy to avert the risk of pancreatitis. In patients with mild to moderate hypertriglyceridemia, the treatment of choice is statin therapy to achieve the low-density lipoprotein (LDL) and non-high-density lipoprotein (HDL) target goals. The evidence base would favor niacin therapy in combination with statin therapy to achieve the goals pertaining to LDL cholesterol and non-HDL cholesterol. The data about the combination of fibrate therapy with statin therapy are disappointing

Panoramic Human Structure Maintenance based on Invariant Features of Video Frames

[[abstract]]Panoramic photography is becoming a very popular and commonly available feature in the mobile handheld devices nowadays. In traditional panoramic photography, the human structure often becomes messy if the human changes position in the scene or during the combination step of the human structure and natural background. In this paper, we present an effective method in panorama creation to maintain the main structure of human in the panorama. In the proposed method, we use an automatic method of feature matching, and the energy map of seam carving is used to avoid the overlapping of human with the natural background. The contributions of this proposal include automated panoramic creation method and it solves the human ghost generation problem in panorama by maintaining the structure of human by energy map. Experimental results prove that the proposed system can be effectively used to compose panoramic photographs and maintain human structure in panorama.[[incitationindex]]SCI[[booktype]]電子

Efficacy of a multifaceted podiatry intervention to improve balance and prevent falls in older people: study protocol for a randomised trial

<p>Abstract</p> <p>Background</p> <p>Falls in older people are a major public health problem, with at least one in three people aged over 65 years falling each year. There is increasing evidence that foot problems and inappropriate footwear increase the risk of falls, however no studies have been undertaken to determine whether modifying these risk factors decreases the risk of falling. This article describes the design of a randomised trial to evaluate the efficacy of a multifaceted podiatry intervention to reduce foot pain, improve balance, and reduce falls in older people.</p> <p>Methods</p> <p>Three hundred community-dwelling men and women aged 65 years and over with current foot pain and an increased risk of falling will be randomly allocated to a control or intervention group. The "usual cae" control group will receive routine podiatry (i.e. nail care and callus debridement). The intervention group will receive usual care plus a multifaceted podiatry intervention consisting of: (i) prefabricated insoles customised to accommodate plantar lesions; (ii) footwear advice and assistance with the purchase of new footwear if current footwear is inappropriate; (iii) a home-based exercise program to strengthen foot and ankle muscles; and (iv) a falls prevention education booklet. Primary outcome measures will be the number of fallers, number of multiple fallers and the falls rate recorded by a falls diary over a 12 month period. Secondary outcome measures assessed six months after baseline will include the Medical Outcomes Study Short Form 12 (SF-12), the Manchester Foot Pain and Disability Index, the Falls Efficacy Scale International, and a series of balance and functional tests. Data will be analysed using the intention to treat principle.</p> <p>Discussion</p> <p>This study is the first randomised trial to evaluate the efficacy of podiatry in improving balance and preventing falls. The trial has been pragmatically designed to ensure that the findings can be generalised to clinical practice. If found to be effective, the multifaceted podiatry intervention will be a unique addition to common falls prevention strategies already in use.</p> <p>Trial registration</p> <p>Australian New Zealand Clinical Trials Registry: ACTRN12608000065392</p

Information transmission in oscillatory neural activity

Periodic neural activity not locked to the stimulus or to motor responses is usually ignored. Here, we present new tools for modeling and quantifying the information transmission based on periodic neural activity that occurs with quasi-random phase relative to the stimulus. We propose a model to reproduce characteristic features of oscillatory spike trains, such as histograms of inter-spike intervals and phase locking of spikes to an oscillatory influence. The proposed model is based on an inhomogeneous Gamma process governed by a density function that is a product of the usual stimulus-dependent rate and a quasi-periodic function. Further, we present an analysis method generalizing the direct method (Rieke et al, 1999; Brenner et al, 2000) to assess the information content in such data. We demonstrate these tools on recordings from relay cells in the lateral geniculate nucleus of the cat.Comment: 18 pages, 8 figures, to appear in Biological Cybernetic