Mechanosensitive channels: what can they do and how do they do it?

While mechanobiological processes employ diverse mechanisms, at their heart are force-induced perturbations in the structure and dynamics of molecules capable of triggering subsequent events. Among the best characterized force-sensing systems are bacterial mechanosensitive channels. These channels reflect an intimate coupling of protein conformation with the mechanics of the surrounding membrane; the membrane serves as an adaptable sensor that responds to an input of applied force and converts it into an output signal, interpreted for the cell by mechanosensitive channels. The cell can exploit this information in a number of ways: ensuring cellular viability in the presence of osmotic stress and perhaps also serving as a signal transducer for membrane tension or other functions. This review focuses on the bacterial mechanosensitive channels of large (MscL) and small (MscS) conductance and their eukaryotic homologs, with an emphasis on the outstanding issues surrounding the function and mechanism of this fascinating class of molecules.     

Birds do it. Bees do it. So why not single women and lesbians?

Infertile couples have come to take assisted reproductive technologies (ART) for granted. An increasing number of single women and lesbian couples also desire to have children and turn to ART, especially donor insemination, to fulfill this desire. While most married couples find that access to ART is limited primarily by the ability to pay, for single women and lesbian couples, the story may be much different. In the United States, they may find that doctors and infertility clinics view their desires as immoral and refuse to accept them as patients, although other doctors and clinics readily accept them. In most other countries, however, it is against the law for single women and lesbian couples to make use of ART, including donor insemination.
In this paper I will argue that marital status and sexual orientation should not serve as a barrier to accessing the world of reproductive medicine. I will base this conclusion on two arguments. First, that justice requires that we treat like cases alike. Just as we would not accept or reject patients for cardiac rehabilitation programs based on factors such as a history of poor eating habits, so too we should not look at nonmedical factors such as marital status when deciding whether to treat infertility. For the second justification for the conclusion of equal access to ART, I will examine the concept of the family. I will argue that it is morally acceptable for single women and lesbian couples to have children and to head families.     

Examining the developing bone: What do we measure and how do we do it?

The clinical tools available to evaluate bone development in children are often ambiguous, and difficult to interpret. Unfortunately bone densitometry methods (i.e., dual energy X-ray absorptiometry, DXA) which have a relatively straightforward application in adult osteoporosis, are far more difficult to evaluate in the growing skeleton. Even with adequate "adjustment" for bone size or maturity, bone "density" (areal or volumetric) alone often gives an inaccurate assessment of bone strength--especially in children. Ideally, we would like to measure both material and geometric properties of bone to accurately estimate "strength". Mechanically meaningful measures of bone geometry (bone cross-sectional area, cortical thickness) and estimates of bending strength (section modulus, or SSI) are available with non-invasive techniques such as (p)QCT and some DXA software. With new technology it might be possible to also measure bone material properties, which will be especially important in some pediatric disorders. In children, we also need to know something about the loads imposed on a child's bone and consider not only absolute bone strength, but also the strength of bone relative to the physiologic loads. Interpreting bone strength in light of the loads imposed (particularly muscle force) is critical for an accurate diagnosis of the developing bone.     

What is geometric information and how do animals use it?

Unlike investigations of animals’ use of spatial cues such as landmarks, studies of sensitivity to the geometry of surfaces in an enclosure have proceeded mostly as an attempt to explain a laboratory finding with few direct tests of how animals use such a cue in nature. In this brief review, I discuss the current debate over whether global or local information from the enclosure drives the typical rotational error pattern in such studies. A consideration of the form and function of geometric cues in natural settings suggests that the natural boundaries for which arena walls are considered analogous might better be thought as landmarks. With a clearer picture of what geometric information is and how it might be used in nature, the generality of findings from laboratory studies of geometry enclosure can be better assessed.     

What to do, or how to do it?

In this issue of Neuron, Ajemian et al. present a computational model of the activity of neurons in primary motor cortex (M1) during isometric movements in different postures. By modeling the output of M1 neurons in terms of their influence on muscles, they find each M1 neuron maps its output into a particular pattern of muscle actions.     

Why do we need to regulate autophagy (and how can we do it)? A cartoon depiction

In a recent issue of this journal I attempted to explain the purpose of macroautophagy/autophagy to a non-specialist audience through the use of cartoons. In the present article, I am continuing this approach by considering the topic of autophagy regulation—why does the cell need to modulate the autophagic response, and what are the basic morphological mechanisms that can be used to attain different levels of autophagy activity?     

Online immunoaffinity LC/MS/MS. A general method to increase sensitivity and specificity: How do you do it and what do you need?

There is an increased emphasis on hyphenated techniques such as immunoaffinity LC/MS/MS (IA-LC/MS/MS) or IA-LC/MRM. These techniques offer competitive advantages with respect to sensitivity and selectivity over traditional LC/MS and are complementary to ligand binding assays (LBA) or ELISA's. However, these techniques are not entirely straightforward and there are several tips and tricks to routine sample analysis. We describe here our methods and procedures for how to perform online IA-LC/MS/MS including a detailed protocol for the preparation of antibody (Ab) enrichment columns. We have included sample trapping and Ab methods. Furthermore, we highlight tips, tricks, minimal and optimal approaches. This technology has been shown to be viable for several applications, species and fluids from small molecules to proteins and biomarkers to PK assays.     

What has faith got to do with it? Religion and child survival in Ghana

Using pooled children data from the 1998 and 2003 Ghana Demographic and Health Surveys, this study examines religious differences in child survival in Ghana. Guided by the particularized theology and selectivity theses, a piecewise constant hazard model with gamma-shared frailty is used to explore if there are denominational differences in child mortality, and whether these could be explained through other characteristics. At the bivariate level, children whose mothers identified as Muslim and Traditional were found to have a significantly higher risk of death compared with their counterparts whose mothers identified as Christians. In the multivariate models, however, the religious differences disappeared after the mediating and confounding influence of socioeconomic factors were controlled. The findings provide support for the selectivity hypothesis, which is based on the notion that religious variations mainly reflect differential access to social and human capital rather than religious theology per se.     

The timing of hibernation in Tasmanian echidnas: why do they do it when they do?

We investigated the patterns of hibernation and arousals in seven free-ranging echidnas Tachyglossus aculeatus setosus (two male, five female) in Tasmania using implanted temperature data loggers. All echidnas showed a ‘classical’ pattern of mammalian hibernation, with bouts of deep torpor interrupted by periodic arousals to euthermia (mean duration 1.04±0.05 (n=146). Torpor bout length increased as body temperature fell during the hibernation season, and became more variable as temperature rose again. Hibernation started in late summer (February 28±5 days, n=6) and males aroused just before the winter solstice (June 15±3 days, n=3), females that subsequently produced young aroused 40 days later (July 25±3, n=4) while females that did not produce young hibernated for a further two months (arousal Sept 27±5, n=7). We suggest that hibernation in Tasmanian echidnas can be divided into two phases, the first phase, marked by declining minimum body temperatures as ambient temperature falls, appears to be obligatory for all animals, while the second phase is ‘optional’ and is utilised to varying amounts by females. We suggest that early arousal and breeding is the favoured option for females in good condition, and that the ability to completely omit breeding in some years, and hibernate through to spring is an adaptation to an uncertain climate.     

Diagnosing dementia: do we get it right?

To find out whether the diagnosis of dementia agreed with findings at necropsy a detailed assessment of 27 elderly patients (mean age 82 (range 70-94] presenting with dementia was conducted at a combined department of geriatric medicine and psychiatry for the elderly. On the basis of the results the cause of the dementia was diagnosed clinically. Neuropathological examinations were performed after death. The clinical diagnosis made during life was not supported by the findings at necropsy in 11 cases. Alzheimer''s disease was overdiagnosed in life (13 cases, of which only six were confirmed at necropsy). Although the clinical investigation was limited by availability of resources, neither cranial computed tomography nor the Hachinski score helped to distinguish between multi-infarct dementia and Alzheimer''s disease in this age group. This study confirms the value of neuropathological studies in the precise diagnosis of dementia.     

Why do men marry and why do they stray?

Humans are quite unusual compared to other great apes in that reproduction typically takes place within long-term, iteroparous pairings--social arrangements that have been culturally reified as the institution of marriage. With respect to male behaviour, explanations of marriage fall into two major schools of thought. One holds that marriage facilitates a sexual division of labour and paternal investment, both important to the rearing of offspring that are born helpless and remain dependent for remarkably long periods (provisioning model). And the other suggests that the main benefits which men receive from entering into marriage derive from monopolizing access to women's fertility (mating effort model). In this paper, we explore extramarital sexual relationships and the conditions under which they occur as a means of testing predictions derived from these two models. Using data on men's extramarital sexual relationships among Tsimane forager-horticulturists in lowland Bolivia, we tested whether infidelity was more common when men had less of an opportunity to invest in their children or when they risked losing less fertility. We found that Tsimane men appear to be biasing the timing of their affairs to when they are younger and have fewer children, supporting the provisioning model.