What we talk about when we talk with medical students

In this article, we review how we interact with medical students in our efforts to teach blood pressure regulation and systemic cardiovascular control along with related elements of respiratory and exercise physiology. Rather than provide a detailed lecture with key facts, we attempted to outline our approach to teaching integrative cardiovascular physiology to medical students, which includes five major themes. First, focus on questions versus answers and facts. We believe that this offers both the learner and teacher a number of advantages. Second, avoid teaching dogma in the name of clarity (i.e., heavy focus on teaching "facts" that have not yet been fully investigated). This is especially important because of the way knowledge evolves over time. Third, include laboratory-based experiences in human integrative physiology. Fourth, provide students with intellectual frameworks versus a list of "facts" to serve as a platform for question generation. Finally, focus on the role of integration and regulatory redundancy in physiology and the idea that physiology is a narrative that can help. In this article, we discuss the philosophy behind the themes outlined above and argue that questions, and not answers, are where the action is for both research and education.     

What we talk about when we talk about capacitance measured with the voltage-clamp step method

Capacitance is a fundamental neuronal property. One common way to measure capacitance is to deliver a small voltage-clamp step that is long enough for the clamp current to come to steady state, and then to divide the integrated transient charge by the voltage-clamp step size. In an isopotential neuron, this method is known to measure the total cell capacitance. However, in a cell that is not isopotential, this measures only a fraction of the total capacitance. This has generally been thought of as measuring the capacitance of the ??well-clamped?? part of the membrane, but the exact meaning of this has been unclear. Here, we show that the capacitance measured in this way is a weighted sum of the total capacitance, where the weight for a given small patch of membrane is determined by the voltage deflection at that patch, as a fraction of the voltage-clamp step size. This quantifies precisely what it means to measure the capacitance of the ??well-clamped?? part of the neuron. Furthermore, it reveals that the voltage-clamp step method measures a well-defined quantity, one that may be more useful than the total cell capacitance for normalizing conductances measured in voltage-clamp in nonisopotential cells.     

What settler Australians talk about when they talk about Aborigines: reflections on an in-depth interview study

Drawing upon in-depth interviews, this article explores the cultural resources that settler Australians use to explain Aboriginal issues. It is argued that the ‘whiteness studies’ approach has only limited value in explaining contemporary settler/indigenous relations. Focusing upon race categories and race prejudice produces a partial explanation. Other important explanatory frameworks and resources include Australian nationalism, egalitarianism and political culture more generally.     

What do we mean when we refer to Bacteroidetes populations in the human gastrointestinal microbiota?

Recent large-scale cloning studies have shown that the ratio of Bacteroidetes to Firmicutes may be important in the obesity-associated gut microbiota, but the species these phyla represent in this ecosystem has not been examined. The Bacteroidetes data from the recent Turnbaugh study were examined to determine those members of the phylum detected in human faecal samples. In addition, FISH analysis was performed on faecal samples from 17 healthy, nonobese donors using probe Bac303, routinely used by gut microbiologists to enumerate Bacteroides – Prevotella populations in faecal samples, and another probe (CFB286) whose target range has some overlap with that of Bac303. Sequence analysis of the Turnbaugh data showed that 23/519 clones were chimeras or erroneous sequences; all good sequences were related to species of the order Bacteroidales , but no one species was present in all donors. FISH analysis demonstrated that approximately one-quarter of the healthy, nonobese donors harboured high numbers of Bacteroidales not detected by probe Bac303. It is clear that Bacteroidales populations in human faecal samples have been underestimated in FISH-based studies. New probes and complementary primer sets should be designed to examine numerical and compositional changes in the Bacteroidales during dietary interventions and in studies of the obesity-associated microbiota in humans and animal model systems.     

What we (don't) know about global plant diversity

The era of big biodiversity data has led to rapid, exciting advances in the theoretical and applied biological, ecological and conservation sciences. While large genetic, geographic and trait databases are available, these are neither complete nor random samples of the globe. Gaps and biases in these databases reduce our inferential and predictive power, and this incompleteness is even more worrisome because we are ignorant of both its kind and magnitude. We performed a comprehensive examination of the taxonomic and spatial sampling in the most complete current databases for plant genes, locations and functional traits. To do this, we downloaded data from The Plant List (taxonomy), the Global Biodiversity Information Facility (locations), TRY (traits) and GenBank (genes). Only 17.7% of the world's described and accepted land plant species feature in all three databases, meaning that more than 82% of known plant biodiversity lacks representation in at least one database. Species coverage is highest for location data and lowest for genetic data. Bryophytes and orchids stand out taxonomically and the equatorial region stands out spatially as poorly represented in all databases. We have highlighted a number of clades and regions about which we know little functionally, spatially and genetically, on which we should set research targets. The scientific community should recognize and reward the significant value, both for biodiversity science and conservation, of filling in these gaps in our knowledge of the plant tree of life.     

Understanding decision-making deficits in neurological conditions: insights from models of natural action selection

Models of natural action selection implicate fronto-striatal circuits in both motor and cognitive 'actions'. Dysfunction of these circuits leads to decision-making deficits in various populations. We review how computational models provide insights into the mechanistic basis for these deficits in Parkinson's patients and those with ventromedial frontal damage. We then consider implications of the models for understanding behaviour and cognition in attention-deficit/hyperactivity disorder (ADHD). Incorporation of cortical noradrenaline function into the model improves action selection in noisy environments and accounts for response variability in ADHD. We close with more general clinical implications.     

What holds us together? Why do some of us fall apart? What can we do about it?

One of the intriguing questions about complex organisms is, What holds them together? One of the principal answers is the rough, fibrous material known as collagen. A related question is, How is collagen made? The biosynthesis of the protein has several unusual features. One is the extensive use of the principle of spontaneous self-assembly seen in the formation of crystals. The three polypeptide chains of the protein fold into a triple-helical conformation by a process that begins with the formation of a small nucleus of triple helix at the C-terminus of the molecule and then propagation of the nucleus in a zipper-like fashion. Also, the self-assembly of the collagen monomers into fibrils is an entropy driven, crystallization-like process. Why do some of them fall apart? Mutations that alter the expression or primary structure of collagen are the predominant causes of severe skeletal defects such as osteogenesis imperfecta and chondrodysplasias. Mutations that have milder effects on the synthesis or structure of the protein are found in a subset of patients with more common diseases such as osteoporosis and early onset osteoarthritis. What can we do about the defects in collagen? Recent results have emphasized the importance of earlier observations that bone marrow contains a small subset of cells that are progenitors of osteoblasts, chondroblasts and several other types of non-hematopoietic cells. After systemic infusion into irradiated mice, the infused cells slowly replace a small fraction of the cells in bone, cartilage, lung and several other tissues. Therefore, the results suggest that the cells, known as mesenchymal stem cells or marrow stromal cells, can be used for both cell and gene therapy of diseases in which bone, cartilage and other connective tissues fall apart.     

Genus Pseudonocardia: What we know about its biological properties,abilities and current application in biotechnology

The genus Pseudonocardia belongs to a group of Actinomycetes, and is a member of the family Pseudonocardiacea. The members of this genus are aerobic, Gram-positive, non-motile bacteria that are commonly found in soil, plant and environment. Although this genus has a low clinical significance; however, it has an important role in biotechnology due to the production of secondary metabolites, some of which have anti-bacterial, anti-fungal and anti-tumour effects. The use of phenotypic tests, such as gelatinase activity, starch hydrolysis, catalase and oxidase tests, as well as molecular methods, such as polymerase chain reaction, are necessary for Pseudonocardia identification at the genus and species levels.     

Mother's little helpers: What we know (and don't know) about cooperative infant care in callitrichines

Since Darwin ( 1859 ), scientists have been puzzled by how behaviors that impose fitness costs on helpers while benefiting their competitors could evolve through natural selection. Hamilton's ( 1964 ) theory of inclusive fitness provided an explanation by showing how cooperative behaviors could be adaptive if directed at closely related kin. Recent studies, however, have begun to question whether kin selection is sufficient to explain cooperative behavior in some species (Bergmüller, Johnstone, Russell, & Bshary, 2007 ). Many researchers have instead emphasized the importance of direct fitness benefits for helpers in the evolution of cooperative breeding systems. Furthermore, individuals can vary in who, when, and how much they help, and the factors that affect this variation are poorly understood (Cockburn, 1998 ; Heinsohn, 2004 ). Cooperative breeders thus provide excellent models for the study of evolutionary theories of cooperation and conflict (Cant, 2012 ).     

What does optimization theory actually predict about crown profiles of photosynthetic capacity when models incorporate greater realism?

Measured profiles of photosynthetic capacity in plant crowns typically do not match those of average irradiance: the ratio of capacity to irradiance decreases as irradiance increases. This differs from optimal profiles inferred from simple models. To determine whether this could be explained by omission of physiological or physical details from such models, we performed a series of thought experiments using a new model that included more realism than previous models. We used ray‐tracing to simulate irradiance for 8000 leaves in a horizontally uniform canopy. For a subsample of 500 leaves, we simultaneously optimized both nitrogen allocation (among pools representing carboxylation, electron transport and light capture) and stomatal conductance using a transdermally explicit photosynthesis model. Few model features caused the capacity/irradiance ratio to vary systematically with irradiance. However, when leaf absorptance varied as needed to optimize distribution of light‐capture N, the capacity/irradiance ratio increased up through the crown – that is, opposite to the observed pattern. This tendency was counteracted by constraints on stomatal or mesophyll conductance, which caused chloroplastic CO₂ concentration to decline systematically with increasing irradiance. Our results suggest that height‐related constraints on stomatal conductance can help to reconcile observations with the hypothesis that photosynthetic N is allocated optimally.     

Thematic review series: patient-oriented research. What we have learned about VLDL and LDL metabolism from human kinetics studies

Lipoprotein metabolism is the result of a complex network of many individual components. Abnormal lipoprotein concentrations can result from changes in the production, conversion, or catabolism of lipoprotein particles. Studies in hypolipoproteinemia and hyperlipoproteinemia have elucidated the processes that control VLDL secretion as well as VLDL and LDL catabolism. Here, we review the current knowledge regarding apolipoprotein B (apoB) metabolism, focusing on selected clinically relevant conditions. In hypobetalipoproteinemia attributable to truncations in apoB, the rate of secretion is closely linked to the length of apoB. On the other hand, in patients with the metabolic syndrome, it appears that substrate, in the form of free fatty acids, coupled to the state of insulin resistance can induce hypersecretion of VLDL-apoB. Studies in patients with familial hypercholesterolemia, familial defective apoB, and mutant forms of proprotein convertase subtilisin/kexin type 9 show that mutations in the LDL receptor, the ligand for the receptor, or an intracellular chaperone for the receptor are the most important determinants in regulating LDL catabolism. This review also demonstrates the variance of results within similar, or even the same, phenotypic conditions. This underscores the sensitivity of metabolic studies to methodological aspects and thus the importance of the inclusion of adequate controls in studies.     

What do we know about biological nitrogen fixation in insects? Evidence and implications for the insect and the ecosystem

Many insects feed on a low‐nitrogen diet, and the origin of their nitrogen supply is poorly understood. It has been hypothesized that some insects rely on nitrogen‐fixing bacteria (diazotrophs) to supplement their diets. Nitrogen fixation by diazotrophs has been extensively studied and convincingly demonstrated in termites, while evidence for the occurrence and role of nitrogen fixation in the diet of other insects is less conclusive. Here, we summarize the methods to detect nitrogen fixation in insects and review the available evidence for its occurrence (focusing on insects other than termites). We distinguish between three aspects of nitrogen fixation investigations: (i) detecting the presence of potential diazotrophs; (ii) detecting the activity of the nitrogen‐fixing enzyme; and (iii) detecting the assimilation of fixed nitrogen into the insect tissues. We show that although evidence from investigations of the first aspect reveals ample opportunities for interactions with potential diazotrophs in a variety of insects, demonstrations of actual biological nitrogen fixation and the assimilation of fixed nitrogen are restricted to very few insect groups, including wood‐feeding beetles, fruit flies, leafcutter ants, and a wood wasp. We then discuss potential implications for the insect's fitness and for the ecosystem as a whole. We suggest that combining these multiple approaches is crucial for the study of nitrogen fixation in insects, and argue that further demonstrations are desperately needed in order to determine the relative importance of diazotrophs for insect diet and fitness, as well as to evaluate their overall impact on the ecosystem.     

Sequences,stratigraphy and scenarios: what can we say about the fossil record of the earliest tetrapods?

Past research on the emergence of digit-bearing tetrapods has led to the widely accepted premise that this important evolutionary event occurred during the Late Devonian. The discovery of convincing digit-bearing tetrapod trackways of early Middle Devonian age in Poland has upset this orthodoxy, indicating that current scenarios which link the timing of the origin of digited tetrapods to specific events in Earth history are likely to be in error. Inspired by this find, we examine the fossil record of early digit-bearing tetrapods and their closest fish-like relatives from a statistical standpoint. We find that the Polish trackways force a substantial reconsideration of the nature of the early tetrapod record when only body fossils are considered. However, the effect is less drastic (and often not statistically significant) when other reliably dated trackways that were previously considered anachronistic are taken into account. Using two approaches, we find that 95 per cent credible and confidence intervals for the origin of digit-bearing tetrapods extend into the Early Devonian and beyond, spanning late Emsian to mid Ludlow. For biologically realistic diversity models, estimated genus-level preservation rates for Devonian digited tetrapods and their relatives range from 0.025 to 0.073 per lineage-million years, an order of magnitude lower than species-level rates for groups typically considered to have dense records. Available fossils of early digited tetrapods and their immediate relatives are adequate for documenting large-scale patterns of character acquisition associated with the origin of terrestriality, but low preservation rates coupled with clear geographical and stratigraphic sampling biases caution against building scenarios for the origin of digits and terrestrialization tied to the provenance of particular specimens or faunas.     

What can we Learn from Patients’ Ethical Thinking about the right ‘not to know’ in Genomics? Lessons from Cancer Genetic Testing for Genetic Counselling

This article is based on a qualitative empirical project about a distinct kinship group who were among the first identified internationally as having a genetic susceptibility to cancer (Lynch Syndrome). 50 were invited to participate (42 were tested; eight declined genetic testing). 15, who had all accepted testing, were interviewed. They form a unique case study. This study aimed to explore interviewees’ experiences of genetic testing and how these influenced their family relationships. A key finding was that participants framed the decision to be tested as ‘common sense’; the idea of choice around the decision was negated and replaced by a moral imperative to be tested. Those who did not follow ‘common sense’ were judged to be imprudent. Family members who declined testing were discussed negatively by participants. The article addresses what is ethically problematic about how test decliners were discussed and whether these ethical concerns extend to others who are offered genetic testing. Discussions showed that genetic testing was viewed as both an autonomous choice and a responsibility. Yet the apparent conflict between the right to autonomy and the moral imperative of responsibility allowed participants to defend test decliners’ decisions by expressing a preference for or defending choice over responsibility. The ‘right not to know’ seemed an important moral construct to help ethically manage unpopular decisions made by close family who declined testing. In light of this research, the erosion of the ‘right not to know’ in the genomic age could have subtle yet profound consequences for family relationships.