Two Types of K⁺ Channel Subunit, Erg1 and KCNQ2/3, Contribute to the M-Like Current in a Mammalian Neuronal Cell

The potassium M current was originally identified in sympathetic ganglion cells, and analogous currents have been reported in some central neurons and also in some neural cell lines. It has recently been suggested that the M channel in sympathetic neurons comprises a heteromultimer of KCNQ2 and KCNQ3 (Wang et al., 1998) but it is unclear whether all other M-like currents are generated by these channels. Here we report that the M-like current previously described in NG108–15 mouse neuroblastoma x rat glioma cells has two components, “fast” and “slow”, that may be differentiated kinetically and pharmacologically. We provide evidence from PCR analysis and expression studies to indicate that these two components are mediated by two distinct molecular species of K+ channel: the fast component resembles that in sympathetic ganglia and is probably carried byKCNQ2/3 channels, whereas the slow component appears to be carried by merg1a channels. Thus, the channels generating M-like currents in different cells may be heterogeneous in molecular composition

Agricultural chemical exposures and birth defects in the Eastern Cape Province, South Africa A case – control study

BACKGROUND: South Africa is one of the major users of pesticides on the African continent. The Eastern Cape is the second largest province in South Africa. There has been growing concern about the occurrence of certain birth defects which seemed to have increased in the past few years. In this paper we investigate associations between exposure to agricultural chemicals and certain birth defects. Few such studies have been undertaken in the developing world previously. METHODS: Between September 2000 and March 2001 a case – control study was conducted among rural women in the area of the Eastern cape to investigate the association between women's exposure to pesticides and the occurrence of birth defects. Information on birth defects was obtained from the register of the Paediatrics Department at the Cecilia Makiwane Hospital in Mdantsane, one of the largest referral hospitals in the province. The cases were children who were diagnosed with selected birth defects. The controls were children born in the same areas as the cases. Exposure information on the mothers was obtained by interview concerning from their activities in gardens and fields. Data were analysed using conditional logistic regression. RESULTS: A total of 89 case mothers and 178 control mothers was interviewed. Babies with birth defects were seven times more likely to be born to women exposed to chemicals used in gardens and fields compared to no reported exposure (Odds Ratio 7.18, 95% CI 3.99, 13.25); and were almost twice as likely to be born to women who were involved in dipping livestock used to prevent ticks (OR 1.92, 95% CI 1.15, 3.14). They were also 6.5 times more likely to be born to women who were using plastic containers for fetching water (OR 6.5, 95% CI 2.2, 27.9). Some of these containers had previously contained pesticides (OR 1.87, 95% CI 1.06, 3.31). CONCLUSIONS: These findings suggest a link between exposure to pesticides and certain birth defects among the children of rural South African women who work on the land. Education programmes for women alerting them to the dangers to their babies from the use of pesticides and alternative farming methods and elimination of the reuse of pesticide containers are indicated as preventive measures

Repulsive Casimir forces

We discuss repulsive Casimir forces between dielectric materials with non trivial magnetic susceptibility. It is shown that considerations based on naive pair-wise summation of Van der Waals and Casimir Polder forces may not only give an incorrect estimate of the magnitude of the total Casimir force, but even the wrong sign of the force when materials with high dielectric and magnetic response are involved. Indeed repulsive Casimir forces may be found in a large range of parameters, and we suggest that the effect may be realized in known materials. The phenomenon of repulsive Casimir forces may be of importance both for experimental study and for nanomachinery applications

Should Research Ethics Encourage the Production of Cost-Effective Interventions?

This project considers whether and how research ethics can contribute to the provision of cost-effective medical interventions. Clinical research ethics represents an underexplored context for the promotion of cost-effectiveness. In particular, although scholars have recently argued that research on less-expensive, less-effective interventions can be ethical, there has been little or no discussion of whether ethical considerations justify curtailing research on more expensive, more effective interventions. Yet considering cost-effectiveness at the research stage can help ensure that scarce resources such as tissue samples or limited subject popula- tions are employed where they do the most good; can support parallel efforts by providers and insurers to promote cost-effectiveness; and can ensure that research has social value and benefits subjects. I discuss and rebut potential objections to the consideration of cost-effectiveness in research, including the difficulty of predicting effectiveness and cost at the research stage, concerns about limitations in cost-effectiveness analysis, and worries about overly limiting researchers’ freedom. I then consider the advantages and disadvantages of having certain participants in the research enterprise, including IRBs, advisory committees, sponsors, investigators, and subjects, consider cost-effectiveness. The project concludes by qualifiedly endorsing the consideration of cost-effectiveness at the research stage. While incorporating cost-effectiveness considerations into the ethical evaluation of human subjects research will not on its own ensure that the health care system realizes cost-effectiveness goals, doing so nonetheless represents an important part of a broader effort to control rising medical costs

Complexity without chaos: Plasticity within random recurrent networks generates robust timing and motor control

It is widely accepted that the complex dynamics characteristic of recurrent neural circuits contributes in a fundamental manner to brain function. Progress has been slow in understanding and exploiting the computational power of recurrent dynamics for two main reasons: nonlinear recurrent networks often exhibit chaotic behavior and most known learning rules do not work in robust fashion in recurrent networks. Here we address both these problems by demonstrating how random recurrent networks (RRN) that initially exhibit chaotic dynamics can be tuned through a supervised learning rule to generate locally stable neural patterns of activity that are both complex and robust to noise. The outcome is a novel neural network regime that exhibits both transiently stable and chaotic trajectories. We further show that the recurrent learning rule dramatically increases the ability of RRNs to generate complex spatiotemporal motor patterns, and accounts for recent experimental data showing a decrease in neural variability in response to stimulus onset

When enough should be enough: Improving the use of current agricultural lands could meet production demands and spare natural habitats in Brazil

Providing food and other products to a growing human population while safeguarding natural ecosystems and the provision of their services is a significant scientific, social and political challenge. With food demand likely to double over the next four decades, anthropization is already driving climate change and is the principal force behind species extinction, among other environmental impacts. The sustainable intensification of production on current agricultural lands has been suggested as a key solution to the competition for land between agriculture and natural ecosystems. However, few investigations have shown the extent to which these lands can meet projected demands while considering biophysical constraints. Here we investigate the improved use of existing agricultural lands and present insights into avoiding future competition for land. We focus on Brazil, a country projected to experience the largest increase in agricultural production over the next four decades and the richest nation in terrestrial carbon and biodiversity. Using various models and climatic datasets, we produced the first estimate of the carrying capacity of Brazil's 115 million hectares of cultivated pasturelands. We then investigated if the improved use of cultivated pasturelands would free enough land for the expansion of meat, crops, wood and biofuel, respecting biophysical constraints (i.e., terrain, climate) and including climate change impacts. We found that the current productivity of Brazilian cultivated pasturelands is 32–34% of its potential and that increasing productivity to 49–52% of the potential would suffice to meet demands for meat, crops, wood products and biofuels until at least 2040, without further conversion of natural ecosystems. As a result up to 14.3 Gt CO2 Eq could be mitigated. The fact that the country poised to undergo the largest expansion of agricultural production over the coming decades can do so without further conversion of natural habitats provokes the question whether the same can be true in other regional contexts and, ultimately, at the global scale

Management of abnormal uterine bleeding by northern, rural and isolated primary care physicians: PART II: What do we need?

BACKGROUND: Abnormal uterine bleeding (AUB) is a common problem that affects one in five women during the pre-menopausal years. It is frequently managed by family physicians, especially in northern, rural and isolated areas where severe shortages of gynecologists exist. METHODS: We surveyed 194 family physicians in northern, rural and isolated areas of Ontario, Canada to determine their educational and resource needs for the management of AUB, with a specific focus on the relevance and feasibility of using clinical practice guidelines (CPGs). RESULTS: Most physicians surveyed did not use CPGs for the management of AUB because they did not know that such guidelines existed. The majority were interested in further education on the management of AUB through mailed CPGs and locally held training courses. A major theme among respondents was the need for more timely and effective gynecological referrals. CONCLUSION: A one-page diagnostic and treatment algorithm for AUB would be easy to use and would place minimal restrictions on physician autonomy. As the majority of physicians had Internet access, we recommend emailing and web posting in addition to mailing this algorithm. Local, hands-on courses including options for endometrial biopsy training would also be helpful for northern, rural and isolated physicians, many of whom cannot readily take time away from their practices

Investigating hyper-vigilance for social threat of lonely children

The hypothesis that lonely children show hypervigilance for social threat was examined in a series of three studies that employed different methods including advanced eye-tracking technology. Hypervigilance for social threat was operationalized as hostility to ambiguously motivated social exclusion in a variation of the hostile attribution paradigm (Study 1), scores on the Children’s Rejection-Sensitivity Questionnaire (Study 2), and visual attention to socially rejecting stimuli (Study 3). The participants were 185 children (11 years-7 months to 12 years-6 months), 248 children (9 years-4 months to 11 years-8 months) and 140 children (8 years-10 months to 12 years-10 months) in the three studies, respectively. Regression analyses showed that, with depressive symptoms covaried, there were quadratic relations between loneliness and these different measures of hypervigilance to social threat. As hypothesized, only children in the upper range of loneliness demonstrated elevated hostility to ambiguously motivated social exclusion, higher scores on the rejection sensitivity questionnaire, and disengagement difficulties when viewing socially rejecting stimuli. We found that very lonely children are hypersensitive to social threat