What do we know about the secretion and degradation of incretin hormones?

The incretin hormones, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) are secreted from endocrine cells located in the intestinal mucosa, and act to enhance meal-induced insulin secretion. GIP and GLP-1 concentrations in the plasma rise rapidly after food ingestion, and the presence of unabsorbed nutrients in the intestinal lumen is a strong stimulus for their secretion. Nutrients can stimulate release of both hormones by direct contact with the K-cell (GIP) and L-cell (GLP-1), and this may be the most important signal. However, nutrients also stimulate GLP-1 and GIP secretion indirectly via other mechanisms. Incretin hormone secretion can be modulated neurally, with cholinergic muscarinic, beta-adrenergic and peptidergic (gastrin-releasing peptide, GRP) fibres generally having positive effects, while secretion is restrained by alpha-adrenergic and somatostatinergic fibres. Hormonal factors may also influence incretin hormone secretion. Somatostatin exerts a local inhibitory effect on the activity of both K- and L-cells via a paracrine mechanism, while, in rodents at least, GIP from the proximal intestine has a stimulatory effect on GLP-1 secretion, possibly mediated via a neural loop involving GRP. Once they have been released, both GLP-1 and GIP are subject to rapid degradation. The ubiquitous enzyme, dipeptidyl peptidase IV (DPP IV) cleaves N-terminally, removing a dipeptide and thereby inactivating both peptides, because the N-terminus is crucial for receptor binding. Subsequently, the peptides may be degraded by other enzymes and extracted in an organ-specific manner. The intact peptides are inactivated during passage across the hepatic bed and further metabolised by the peripheral tissues, while the kidney is important for the final elimination of the metabolites.     

Candida pneumonia: What we know and what we don’t

The diagnosis of Candida pneumonia is a difficult one to make, and some experts often question whether the entity truly exists. This article assimilates the information currently available regarding Candida pulmonary infection to elucidate the presentation of the disease and the hosts in which it occurs. It also describes how to interpret the presence of Candida in respiratory secretions from both immunocompetent and immunocompromised patients. Finally, it describes how the diagnosis of Candida pneumonia can be made, which patients with suspected disease should be treated, and which antifungal agents should be used.     

UV radiation: what we know and do we protect ourselves adequately?

Chronic sun exposure causes degenerative changes in the skin that are recognized as photoaging, immunosuppression and photocarcinogenesis. Sun is necessary for life, so total sun avoidance is impossible. Sun exposure during the first 15 years of life and blistering sunburns before age 20 have been linked to an increased risk of melanoma. Individuals who have outdoor lifestyles, live in sunny climates, and are lightly pigmented will experience the greatest degree of photoaging. In our study, performed four years ago, we have shown the knowledge of more than 4000 people about the effects of UV rays on the skin. The results show us that sun exposure is still exaggerated and uncontrolled due to the lack of knowledge about this topic. Encouraging photoprotection and improving the awareness of the general public about the harmful effects of too much sun exposure must be the leading preventative health strategy.     

What do we know about Hawaiian ferns and lycophytes?

The Hawaiian Islands are home to one of the most distinctive fern and lycophyte floras in the world. Of the 144 native fern species, 76% are endemic and, including subspecies and varieties, 84% of the 167 native fern taxa are endemic. There are 15 native lycophyte species, 47% of which are endemic, and 16 taxa, 50% of which are endemic. I review here most of the available literature on Hawaiian ferns and lycophytes. Few species of ferns or lycophytes have been studied in any kind of detail and, for most, we only know basic classification and general ecological information. Although the total number of studies reviewed here is not large, research has been conducted on a wide range of topics including systematics, floristics, dispersal, phylogeny, biogeography, ecology, form and function, population genetics, microevolution, fern-animal and fern-fungi associations, reproductive biology, demography, ethnobotany, and conservation.     

The molecular biology of recombination in Mycobacteria: what do we know and how can we use it?

Recombination is a ubiquitous genetic process which results in the exchange of DNA between two substrates. Homologous recombination occurs between DNA species with identical sequence whereas illegitimate recombination can occur between DNA with very little or no homology. Site-specific recombination is often used by temperate phages to stably integrate into bacterial chromosomes. Characterisation of the mechanisms of recombination in mycobacteria has mainly focussed on RecA-dependent homologous recombination and phage-directed site-specific recombination. In contrast the high frequency of illegitimate recombination in slow-growing mycobacteria has not been explained. The role of DNA repair in dormancy and infection have not yet been fully established, but early work suggests that RecA-mediated pathways are not required for virulence. All three recombination mechanisms have been utilised in developing genetic techniques for the analysis of the biology and pathogenesis of mycobacteria. A recently developed method for studying essential genes will generate further insights into the biology of these important organisms.     

Skin and diabetes mellitus: what do we know?

Diabetes mellitus (DM) is becoming increasingly prevalent worldwide. Although major complications of this condition involve kidney, retina and peripheral nerves, the skin of diabetic patients is also frequently injured. Hence, interest is mounting in the definition of the structural and molecular profile of non-complicated diabetic skin, i.e., before injuries occur. Most of the available knowledge in this area has been obtained relatively recently and, in part, derives from various diabetic animal models. These include both insulin-dependent and insulin-resistant models. Structural work in human diabetic skin has also been carried out by means of tissue samples or of non-invasive methods. Indications have indeed been found for molecular/structural changes in diabetic skin. However, the overall picture that emerges is heterogeneous, incomplete and often contradictory and many questions remain unanswered. This review aims to detail, as much as possible, the various pieces of current knowledge in a systematic and synoptic manner. This should aid the identification of areas in which key questions are still open and more research is needed. A comprehensive understanding of this field could help in determining molecular targets for the prevention and treatment of skin injuries in DM and markers for the monitoring of cutaneous and systemic aspects of the disease. Additionally, with the increasing development of non-invasive optics-based deep-tissue-imaging diagnostic technologies, precise knowledge of cutaneous texture and molecular structure becomes an important pre-requisite for the use of such methods in diabetic patients.     

Immunological aspects of COVID-19: What do we know?

The newly emerged coronavirus (severe acute respiratory syndrome coronavirus 2 SARS-CoV-2) and the disease that it causes coronavirus disease 2019 (COVID-19) have changed the world we know. Yet, the origin and evolution of SARS-CoV-2 remain mostly vague. Many virulence factors and immune mechanisms contribute to the deteriorating effects on the organism during SARS-CoV-2 infection. Both humoral and cellular immune responses are involved in the pathophysiology of the disease, where the principal and effective immune response towards viral infection is the cell-mediated immunity. The clinical picture of COVID-19, which includes immune memory and reinfection, remains unclear and unpredictable. However, many hopes are put in developing an effective vaccine against the virus, and different therapeutic options have been implemented to find effective, even though not specific, treatment to the disease. We can assume that the interaction between the SARS-CoV-2 virus and the individual's immune system determines the onset and development of the disease significantly.     

Dimensions of global population projections: what do we know about future population trends and structures?

The total size of the world population is likely to increase from its current 7 billion to 8–10 billion by 2050. This uncertainty is because of unknown future fertility and mortality trends in different parts of the world. But the young age structure of the population and the fact that in much of Africa and Western Asia, fertility is still very high makes an increase by at least one more billion almost certain. Virtually, all the increase will happen in the developing world. For the second half of the century, population stabilization and the onset of a decline are likely. In addition to the future size of the population, its distribution by age, sex, level of educational attainment and place of residence are of specific importance for studying future food security. The paper provides a detailed discussion of different relevant dimensions in population projections and an evaluation of the methods and assumptions used in current global population projections and in particular those produced by the United Nations and by IIASA.     

Do we know enough? A scientific and ethical analysis of the basis for genetic-based personalized nutrition

This article discusses the prospects and limitations of the scientific basis for offering personalized nutrition advice based upon individual genetic information. Two divergent scientific positions are presented, with an ethical comment. The crucial question is whether the current knowledge base is sufficiently strong for taking an ethically responsible decision to offer personalized nutrition advice based upon gene–diet–health interaction. According to the first position, the evidence base for translating the outcomes of nutrigenomics research into personalized nutritional advice is as yet immature. There is also limited evidence that genotype-based dietary advice will motivate appropriate behavior changes. Filling the gaps in our knowledge will require larger and better randomized controlled trials. According to the second position, personalized nutrition must be evaluated in relation to generally accepted standard dietary advice—partly derived from epidemiological observations and usually not proven by clinical trials. With personalized nutrition, we cannot demand stronger evidence. In several specific cases of gene–diet interaction, it may be more beneficial for individuals with specific genotypes to follow personalized advice rather than general dietary recommendations. The ethical comment, finally, considers the ethical aspects of deciding how to proceed in the face of such uncertainty. Two approaches for an ethically responsible way forward are proposed. Arguing from a precautionary approach, it is suggested that personalized dietary advice should be offered only when there is strong scientific evidence for health effects, followed by stepwise evaluation of unforeseen behavioral and psychological effects. Arguing from theoretical and applied ethics as well as psychology, it is also suggested that personalized advice should avoid paternalism and instead focus on supporting the autonomous choice of each person.     

Microplastics and freshwater microalgae: what do we know so far?

The constant entry of microplastics in several environmental matrices has been of great concern to the scientific community and to society in general, mainly due to the mysteries that surround the implications of this pollutant in the environment. Freshwater ecosystems are resources especially susceptible to variations in environmental quality, and the lack of data on the impacts caused by plastic fragments exacerbates the vulnerability of this environment. Considering the results of other studies, which demonstrate the increasing entry of polymeric fragments in the aquatic environment can lead to algae growth inhibition, an investigation was carried out to determine the current state of research on the interaction between microplastics and freshwater microalgae. In total, 20 scientific articles were analyzed. Different species were subjected to toxicological tests under controlled conditions in the laboratory with small microplastics (size range between 0.1 and 1000 µm), primary and secondary microplastics of different types of polymer. Four toxicity class of indicators were chosen to assess the microalgae response to exposure to microplastic in the selected studies: growth inhibition; photosynthetic activity; pigment analysis; and enzymatic activity and oxidative stress. In this review, a critical analysis is made on the effects of the shape, size, concentration, and duration of exposure to microplastics and research gaps are identified to guide future research priorities in this area of study.

     

Investigating physiological changes in the aerial parts of AM plants: what do we know and where should we be heading?

Research in the field of arbuscular mycorrhizal (AM) symbiosis has taken a giant leap in the past two decades, as demonstrated by the large amount of literature being published every year. Most of the research efforts have been put towards the understanding of the mechanisms of this symbiosis. However, there are still several unknowns on the systemic effects of the AM symbiosis, and our understanding of non-nutritional effects on the physiological changes occurring in the aerial parts of the host plant is yet quite limited. In this short note, I briefly address the question, if there are any changes in metabolic activities that are triggered by AM fungi, and assess the importance of such changes for mycorrhizal research and application.     

What do we know about the mechanisms of aromatase inhibitor resistance?

Clinical trials have demonstrated the importance of aromatase inhibitor (AI) therapy in the effective treatment of hormone-dependent breast cancers. Yet, as with all prolonged drug therapy, resistance to aromatase inhibitors does develop. To date, the precise mechanism responsible for resistance to aromatase inhibitors is not completely understood. In this paper, several mechanisms of de novo/intrinsic resistance and acquired resistance to AIs are discussed. These mechanisms are hypothesized based on important findings from a number of laboratories.

To better understand this question, our lab has generated, in vitro, breast cancer cell lines that are resistant to aromatase inhibitors. Resistant cell lines were generated over a prolonged period of time using the MCF-7aro (aromatase overexpressed) breast cancer line. These cell lines are resistant to the aromatase inhibitors letrozole, anastrozole and exemestane and the anti-estrogen tamoxifen, for comparison. Two types of resistant cell lines have been generated, those that grow in the presence of testosterone (T) which is needed for cell growth, and resistant lines that are cultured in the presence of inhibitor only (no T). In addition to functional characterization of aromatase and ER in these resistant cell lines, microarray analysis has been employed in order to determine differential gene expression within the aromatase inhibitor resistant cell lines versus tamoxifen, in order to better understand the mechanism responsible for AI resistance on a genome-wide scale. We anticipate that our studies will generate important information on the mechanisms of AI resistance. Such information can be valuable for the development of treatment strategies against AI-resistant breast cancers.     

Ecological and evolutionary consequences of size‐selective harvesting: how much do we know?

Size-selective harvesting, where the large individuals of a particular species are preferentially taken, is common in both marine and terrestrial habitats. Preferential removal of larger individuals of a species has been shown to have a negative effect on its demography, life history and ecology, and empirical studies are increasingly documenting such impacts. But determining whether the observed changes represent evolutionary response or phenotypic plasticity remains a challenge. In addition, the problem is not recognized in most management plans for fish and marine invertebrates that still mandate a minimum size restriction. We use examples from both aquatic and terrestrial habitats to illustrate some of the biological consequences of size-selective harvesting and discuss possible future directions of research as well as changes in management policy needed to mitigate its negative biological impacts.     

Sexual selection and environmental change:what do we know and what comes next?

Anthropogenic environmental change is the most significant threat to biodiversity in the 21st century.Animal populations are experi-encing rapid changes in thei...     

Mechanisms of tolerance to herbivore damage:what do we know?

Identifying mechanisms of tolerance to herbivore damage will facilitate attempts to understand the role of tolerance in the evolutionary and ecological dynamics of plants and herbivores. Investigations of the physiological and morphological changes that occur in plants in response to herbivore damage have identified several potential mechanisms of tolerance. However, it is unlikely that all physiological changes that occur following damage are tolerance mechanisms. Few studies have made direct comparisons between the expression of tolerance and the relative expression of putative mechanisms. I briefly review empirical evidence for some of the better-studied potential mechanisms, including increased photosynthetic activity, compensatory growth, utilization of stored reserves, and phenological delays. For each of these mechanisms I discuss reasons why the relationship between tolerance and these characters may be more complicated than it first appears. I conclude by discussing several empirical approaches, including herbivore manipulations, quantitative trait loci (QTL) analysis, and selection experiments, that will further our understanding of tolerance mechanisms. This revised version was published online in July 2006 with corrections to the Cover Date.     

Do we know the absolute values of intracellular free calcium concentration?

More than 20 years ago, it was shown that the addition of EGTA increases the affinity of the plasma membrane Ca2+ pump for Ca2+ by an order of magnitude. The left-hand shift of Ca2+-dependencies in the presence of EGTA has been also documented in studies of the sarcoplasmic reticulum Ca2+ pump, mitochondrial Ca2+-transporter as well as Ca2+-binding by calmodulin and troponin C. These data allow us to hypothesise that this effect is caused by an admixture of di- and trivalent cations possessing high affinity for EGTA and interacting with Ca2+-transporting and binding proteins. Here, we propose that polyvalent cations affect the estimation of absolute values of free intracellular Ca2+ concentration. Indeed, EGTA sharply increases the apparent affinity of the fluorescent Ca2+ indicators quin-2 and fluo-3 for Ca2+. The impact of polyvalent cations on Ca2+ measurement was further confirmed by the study showing the high sensitivity of Ca2+-induced fluo-3 fluorescence to Mn2+, Fe2+, Cu2+, and Co2+ seen in the absence of EGTA.