Acetylcholinesterase: how is structure related to function?

In accordance with its biological role, termination of neurotransmission at cholinergic synapses by rapid hydrolysis of the neurotransmitter, acetylcholine, acetylcholinesterase is one of nature's most efficient enzymes. Solution of its three-dimensional structure revealed that its active site is located at the bottom of a deep and narrow gorge. Such an architecture was unanticipated in view of its high turnover number. The present review examines how the highly specialized structure of acetylcholinesterase, with its sequestered active site, contributes to its catalytic efficacy, and discusses how the traffic of substrate and products to and from the active site is controlled.     

Pannexin: to gap or not to gap, is that a question?

Vertebrates express two families of gap junction proteins: the well characterized connexins and the recently discovered pannexins. The latter are related to invertebrate innexins. Here we present the hypothesis that pannexins, rather than providing a redundant system to gap junctions formed by connexins, exert a physiological role as nonjunctional membrane channels. Specifically, we propose that pannexins can serve as ATP release channels. This function presumptively is also performed by innexins in invertebrates, in addition to their traditional gap junction role.     

Perceptual learning: is V1 up to the task?

Our ability to make fine visual discriminations improves with practice, and so at some level so must our visual system. A new paper reports that the receptive field structure of a neuron can be fine-tuned for different visual tasks. These findings raise important questions about the circuitry and mechanisms that underly perceptual learning.     

Antitumor vaccines: is it possible to prevent a tumor?

The main medical use of vaccines is to induce a state of immunity in healthy individuals to protect them from deadly or dangerous diseases. In the field of cancer immunology, however, vaccines are being used in patients as therapy, often with a very poor success rate against advanced disease. This paper reviews recent preclinical evidence in favor of the prophylactic use of immunological approaches to cancer. Successful attempts at immunological cancer prevention in HER-2/neu transgenic mice are described as an example. The specific properties of the HER-2/neu gene product as a tumor antigen, and the nature of the immune responses induced by effective preventive treatments are reviewed. Although the very high rate of mammary carcinoma prevention in mice has generated enthusiasm, it should not be forgotten that such treatments, when administered to healthy humans at risk of cancer, may carry the risk of inducing autoimmunity. These issues can be addressed in preclinical studies in appropriate animal models.     

Mexical plant phenology: is it similar to Mediterranean communities?

The sclerophyllous, evergreen vegetation found in Mexico under tropical climate is named 'Mexical' (MEX) and presents many traits that have been thought to converge under a Mediterranean climate. Flowering phenology is strongly similar across Mediterranean-type ecosystems (MTEs) and this paper investigates MEX plant phenology in this context. The common history of the vegetation and the differences in the climatic conditions experienced by MEX and MTE taxa provide an ideal scenario to infer the relative importance of natural selection and historical constraints in the phenological response of plants to climatic conditions. This study has involved collecting field and bibliographic data on flowering phenology of MEX communities to detect (1) similarities at the community level between MTEs and MEX, (2) similarities between Tertiary and Quaternary taxa in MTEs and MEX, and (3) similarities between congeneric taxa from MEX and MTEs (taxa sharing a common ancestor but having evolved under different climates). Flowering in MEX does not occur mainly in spring, as in MTEs, but in summer, suggesting a response that maximizes water use in the rainy season. Flowering phenology of MEX species differed from their MTE congeneric species, suggesting that even though a common ancestor is shared, environmental pressures have led to different phenological responses in MEX and MTE plants. The flowering season for species that originated in the Tertiary and Quaternary did not differ in MEX, as expected, because of climatic uniformity along the whole time line. In MTEs, flowering differences between Tertiary and Quaternary species were not congruent, suggesting that the balance between the historical constraints and the selective force of the Mediterranean climate is different among the three MTEs, and a particular explanation is needed for each. © 2002 The Linnean Society of London, Botanical Journal of the Linnean Society , 2002, 138 , 297–303.     

Bats and moths: what is there left to learn?

Abstract.  Over 14 families of moths have ears that are adapted to detect the ultrasonic echolocation calls of bats. On hearing a bat, these moths respond with an escape response that reduces their chances of being caught. As an evolutionary response, bats may then have evolved behavioural strategies or changes in call design to overcome the moth's hearing. The nature of this interaction is reviewed. In particular, the role of the echolocation calls of bats in the shaping of the structure, neurophysiology and behavioural responses of moths is discussed. Unresolved issues, such as the structural complexity of the moth's auditory system, the nature of temporal integration and the role of the non-auditory B cell, are described. Issues in which the interactions between bats and moths may be of more general interest to biologists, such as noise filtering within the central nervous system, protean behaviours and coevolution between predator and prey, are also discussed. The interaction between bats and moths has much to interest general biologists, and may provide a useful model in understanding the neurophysiological basis of behaviour, including protean escape behaviours. The validity of the term coevolution as applied to this system is discussed, as there is no doubt that the auditory system of moths is a response to the echolocation calls of bats, although the evolutionary response of bats to moths is more ambiguous.     

Cattle MHC nomenclature: is it possible to assign sequences to discrete class I genes?

The cattle major histocompatibility complex (MHC) region contains a variable number of classical class I genes encoding polymorphic molecules involved in antigen presentation. Six classical class I genes have been described, but assigning sequences to these genes has proved problematic. We propose a refinement of the existing nomenclature, which currently names the 97 known classical class I sequences in a single series. Phylogenetic analysis of the 3' portion of the coding region allows segregation of these into six groups; thus, we have prefixed existing names with the appropriate number. Although it is clear that some of these groups correspond to discrete genes, it is currently not possible to state definitively that all do. However, the main groupings are consistent, and in conjunction with other evidence, we feel it is now appropriate to rename the sequences accordingly. Segregation of sequences into groups in this way will facilitate ongoing research and future use of the cattle MHC section of the Immuno Polymorphism Database.     

Mucus liquid crystallinity: is function related to microstructural domain size?

The size of liquid crystalline domains formed in partially dried giraffe saliva is found to be an order of magnitude greater than that previously documented for slug pedal mucus. A correlation between (a) intrinsic liquid crystalline domain size and (b) the scale of surface topography over which the mucus is required to provide lubrication is postulated. The scale of mucus microstructure can be related, via a simple model, to two significant material constants: the elastic constant K for distortion of molecular alignment in the liquid crystalline state, and the anchoring energy I at the liquid crystal/substrate interface. In turn, the quantity K is expected to depend on fundamental molecular characteristics of the constituent mucin, such as molecular weight and degree of glycosylation. The possibility that observations of mucus microstructure might serve as a diagnostic tool for mucus defects at the molecular level is suggested.     

Biogas from Macroalgae: is it time to revisit the idea?

The economic and environmental viability of dedicated terrestrial energy crops is in doubt. The production of large scale biomass (macroalgae) for biofuels in the marine environment was first tested in the late 1960’s. The culture attempts failed due to the engineering challenges of farming offshore. However the energy conversion via anaerobic digestion was successful as the biochemical composition of macroalgae makes it an ideal feedstock. The technology for the mass production of macroalgae has developed principally in China and Asia over the last 50 years to such a degree that it is now the single largest product of aquaculture. There has also been significant technology transfer and macroalgal cultivation is now well tried and tested in Europe and America. The inherent advantage of production of biofuel feedstock in the marine environment is that it does not compete with food production for land or fresh water. Here we revisit the idea of the large scale cultivation of macroalgae at sea for subsequent anaerobic digestion to produce biogas as a source of renewable energy, using a European case study as an example.     

Visiting sick people: is it really detrimental to our health?

Intuitively, keeping ones distance from a source of infection would appear to be the best way to limit the occurrence of disease. However, this overlooks the importance of repeated infections in maintaining efficient immune defenses. When acquired immunity has partly waned, re-exposure to the pathogenic agent may lead to mild disease that boosts the immune system. This prevents the total loss of immunity that would lead to classical disease in cases of re-infection. Here, using a mathematical model, we show that avoiding the pathogenic agent is detrimental in some situations, e.g. for pathogens that are highly transmissible, are not excessively lethal and that induce rapidly waning immunity. Reducing exposure to pathogenic agents is among the objectives of most, if not all, public health measures. A better understanding of the factors influencing the severity of a disease is required before applying measures that reduce the circulation of pathogenic agents.     

Correction to: Who is the ocean? Preface to the future seas 2030 special issue

Reviews in Fish Biology and Fisheries - A correction to this paper has been published: https://doi.org/10.1007/s11160-021-09657-9     

Lipid screening: is it enough to measure total cholesterol concentration?

OBJECTIVES--To determine whether measurement of total cholesterol concentration is sufficient to identify most patients at lipoprotein mediated risk of coronary heart disease without measurement of triglyceride and high density lipoprotein (HDL) cholesterol concentrations. DESIGN--Cross sectional screening programme. SETTING--Six general practices in Oxfordshire. PATIENTS--1901 Men and 2068 women aged 25-59. MAIN OUTCOME MEASURE--Cardiovascular risk as assessed by fasting venous plasma concentrations of total cholesterol, triglyceride, and HDL cholesterol. RESULTS--2931 Patients (74% of those screened) had a total cholesterol concentration of less than 6.5 mmol/l. If the triglyceride concentration had not been measured in these patients isolated hypertriglyceridaemia (greater than or equal to 2.3 mmol/l) would have remained undetected in 185. Among these 185 patients, however, 123 were overweight or obese and only 18 (0.6% of those screened) had an increased risk associated with both a raised triglyceride concentration (greater than or equal to 2.3 mmol/l) and a low HDL cholesterol concentration (less than 0.9 mmol/l). Conversely, in the 790 patients with predominant hypercholesterolaemia (cholesterol concentration greater than or equal to 6.5 mmol/l and triglyceride concentration less than 2.3 mmol/l) measurement of HDL cholesterol concentration showed that 348 (9% of those screened) had only a moderately increased risk with a ratio of total to HDL cholesterol of less than 4.5 and 104 had a low risk with a ratio of less than 3.5. CONCLUSIONS--Fasting triglyceride and HDL cholesterol concentrations identify few patients at increased risk of coronary heart disease if the total cholesterol concentration is less than 6.5 mmol/l. HDL cholesterol and triglyceride concentrations should, however, be measured in patients with a total cholesterol concentration exceeding this value. Total cholesterol concentration alone may overestimate risk in a considerable number of these patients, and measurement of HDL cholesterol concentration allows a more precise estimate of risk. Measurement of the triglyceride concentration is required to characterise the lipoprotein abnormality. A patient should not be started on a drug that lowers lipid concentrations without having had a full lipoprotein assessment including measurement of HDL cholesterol concentration.     

Somatic recombination in adult tissues: What is there to learn?

Somatic recombination is essential to protect genomes of somatic cells from DNA damage but it also has important clinical implications, as it is a driving force of tumorigenesis leading to inactivation of tumor suppressor genes. Despite this importance, our knowledge about somatic recombination in adult tissues remains very limited. Our recent work, using the Drosophila adult midgut has demonstrated that spontaneous events of mitotic recombination accumulate in aging adult intestinal stem cells and result in frequent loss of heterozygosity (LOH). In this Extra View article, we provide further data supporting long-track chromosome LOH and discuss potential mechanisms involved in the process. In addition, we further discuss relevant questions surrounding somatic recombination and how the mechanisms and factors influencing somatic recombination in adult tissues can be explored using the Drosophila midgut model.