Autophagy and apoptosis: what is the connection?

The therapeutic potential of autophagy for the treatment cancer and other diseases is beset by paradoxes stemming from the complexity of the interactions between the apoptotic and autophagic machinery. The simplest question of how autophagy acts as both a protector and executioner of cell death remains the subject of substantial controversy. Elucidating the molecular interactions between the processes will help us understand how autophagy can modulate cell death, whether autophagy is truly a cell death mechanism, and how these functions are regulated. We suggest that, despite many connections between autophagy and apoptosis, a strong causal relationship wherein one process controls the other, has not been demonstrated adequately. Knowing when and how to modulate autophagy therapeutically depends on understanding these connections.     

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.     

Zebra mussels in Italy: where do they come from?

The zebra mussel Dreissena polymorpha is widely present in Italy, but Italian populations of this bivalve have never been genetically characterized. The mitochondrial Cytochrome Oxidase subunit I gene fragments have been used to determine the genetic structures of 3 populations from Lake Garda (n = 30), the first Italian basin colonized by this species, as well as 2 populations from Lake Constance, Germany (n = 14). A Neighbor-Joining tree and a Maximum Likelihood analysis were performed with 4 new Italian (LG1-LG4) and 3 German (LC1-LC3) haplotypes, also considering all the available Dreissena sequences from GenBank in order to estimate phylogeographic relationships. Almost all Italian haplotypes clustered with German and mid-European samples providing evidences of a mixed origin for Italian mussels. We speculate about Lake Garda colonization, for which the hypothesized "German origin" has been partially confirmed as well as the necessity of more efficient control strategies at least to minimize new colonizations.     

Insect migration: do migrant moths know where they are heading?

Moth migration has been assumed to involve hitching a ride in favorable winds. A new study has shown that silver Y moths migrate only on nights when winds would displace them southward, implying that they detect their direction of movement while airborne, likely by a magnetic sense.     

Fighting in fig wasps: do males avoid killing brothers or do they never meet them?

1. In many fig wasp species, armoured wingless males regularly engage in lethal fights for access to females inside figs, which act as discrete mating patches. 2. Kin selection generally opposes killing brothers, because their reproductive success provides indirect genetic benefits (inclusive fitness). However, siblicide may be avoided if (i) brothers do not occur in the same figs, or (ii) males avoid fighting brothers in the same fig. Alternatively, (iii) siblicide may occur because intense mate competition between brothers at the local scale overcomes kin selection effects, or (iv) males do not recognise kin. 3. A fig may also contain wasps from other closely related species and it is not known if males also fight with these individuals. 4. Nine microsatellite loci were used in the first genetic analysis of fighting in fig wasps. We assigned species and sibling identities to males and tested alternative fighting scenarios for three Sycoscapter wasp species in figs of Ficus rubiginosa. 5. Approximately 60% of figs contained males from more than one Sycoscapter species and approximately 80% of fights were between conspecifics, but a surprising 20% were between heterospecific males. 6. Within species, few figs contained brothers, suggesting that females typically lay one son per fig. Overall, most males do not compete with brothers and all fights observed were between unrelated males.     

Category differences in brain activation studies: where do they come from?

Differences in the neural processing of six categories of pictorial stimuli (maps, body parts, objects, animals, famous faces and colours) were investigated using positron emission tomography. Stimuli were presented either with or without the written name of the picture, thereby creating a naming condition and a reading condition. As predicted, naming increased the demands on lexical processes. This was demonstrated by activation of the left temporal lobe in a posterior region associated with name retrieval in several previous studies. This lexical effect was common to all meaningful stimuli and no category-specific effects were observed for naming relative to reading. Nevertheless, category differences were found when naming and reading were considered together. Stimuli with greater visual complexity (animals, faces and maps) enhanced activation in the left extrastriate cortex. Furthermore, map recognition, which requires greater spatio-topographical processing, also activated the right occipito-parietal and parahippocampal cortices. These effects in the visuo-spatial regions emphasize inevitable differences in the perceptual properties of pictorial stimuli. In the semantic temporal regions, famous faces and objects enhanced activation in the left antero-lateral and postero-lateral cortices, respectively. In addition, we showed that the same posterior left temporal region is also activated by body parts. We conclude that category-specific brain activations depend more on differential processing at the perceptual and semantic levels rather than at the lexical retrieval level.     

Invasive trees and shrubs: where do they come from and what we should expect in the future?

The global database of invasive trees and shrubs has been updated, resulting in a total of 751 species (434 trees and 317 shrubs) from 90 families (Rejmánek and Richardson 2013 Divers Distrib 19:1093–1094). This database is used to assess major trends in human-assisted exchanges of dendrofloras among 15 major geographical regions. Areas most invaded by non-native trees are Pacific Islands (136 species), Southern Africa (118), Australia (116), and North America (114). Areas most invaded by non-native shrubs are North America (98), Australia (87), Pacific Islands (71), and Europe (61). The most important sources of invasive trees are Asia (122–146 species, depending on how many Eurasian species are considered to have been introduced only from Europe), Australia (81), and South America (81). The most important sources of invasive shrubs are Asia (103–118), Europe (68), and South America (54). Mean number of native geographical regions for invasive trees is 1.64, while the mean number of invaded regions by trees is 2.51. The difference is smaller for shrubs: 1.60 versus 2.11. Asia is the major source of invasive Rosaceae shrubs, as well as invasive Arecaceae and Oleaceae species. South America and Australia are major sources of invasive Fabaceae trees. North America and Europe are major sources of invasive Pinaceae. Most of the invasive Salicaceae are of Eurasian origin. The identified trends will very likely continue in this century. Because of increasing interactions with many states in Asia, even more invasive woody species will be introduced from this part of the world.     

The crosstalk between autophagy and apoptosis: where does this lead?

Recent advances in the understanding of the molecular processes contributing to autophagy have provided insight into the relationship between autophagy and apoptosis. In contrast to the concept of “autophagic cell death,” accumulating evidence suggests that autophagy serves a largely cytoprotective role in physiologically relevant conditions. The cytoprotective function of autophagy is mediated in many circumstances by negative modulation of apoptosis. Apoptotic signaling, in turn, serves to inhibit autophagy. While the mechanisms mediating the complex counter-regulation of apoptosis and autophagy are not yet fully understood, important points of crosstalk include the interactions between Beclin-1 and Bcl-2/Bcl-xL and between FADD and Atg5, caspase- and calpain-mediated cleavage of autophagy-related proteins, and autophagic degradation of caspases. Continued investigation of these and other means of crosstalk between apoptosis and autophagy is necessary to elucidate the mechanisms controlling the balance between survival and death both under normal conditions and in diseases including cancer.     

Inbreeding and relatedness coefficients: what do they measure?

This paper reviews and discusses what is known about the relationship between identity in state, allele frequency, inbreeding coefficients, and identity by descent in various uses of these terms. Generic definitions of inbreeding coefficients are given, as ratios of differences of probabilities of identity in state. Then some of their properties are derived from an assumption in terms of differences between distributions of coalescence times of different genes. These inbreeding coefficients give an approximate measurement of how much higher the probability of recent coalescence is for some pair of genes relative to another pair. Such a measure is in general not equivalent to identity by descent; rather, it approximates a ratio of differences of probabilities of identity by descent. These results are contrasted with some other formulas relating identity, allele frequency, and inbreeding coefficients. Additional assumptions are necessary to obtain most of them, and some of these assumptions are not always correct, for example when there is localized dispersal. Therefore, definitions based on such formulas are not always well-formulated. By contrast, the generic definitions are both well-formulated and more broadly applicable.     

Nurse practitioners in accident and emergency departments: what do they do?

OBJECTIVE--To determine the distribution and scope of nurse practitioner schemes in accident and emergency departments in England and Wales; to describe the caseloads of doctors and nurse practitioners on two representative days; and to estimate the number of patients managed by nurse practitioners in the year to 31 March 1991. DESIGN--A postal survey of accident and emergency departments and a content analysis of case notes of new patients attending a representative sample of accident and emergency departments on two days. SETTING--All accident and emergency departments in England and Wales. PARTICIPANTS--Survey: 560 nurses in charge of accident and emergency departments. Census: case notes of 5814 patients in 37 accident and emergency departments. MAIN OUTCOME MEASURES--Survey: number of accident and emergency departments with nurse practitioner schemes. Census: demographic and clinical characteristics of new patients attending and whether nurse practitioner or doctor made diagnoses and ordered investigations, treatments, referrals, discharges. RESULTS--513 replies (92%) from 465 surveyed functioning accident and emergency departments and 48 departments recently closed. 27 (6%) departments used designated nurse practitioners and 159 (34%) "unofficial" nurse practitioners. Only 530 (9%) of the 5814 patients in the census were managed entirely or mainly by nurse practitioners, with higher proportions in ophthalmic departments (nearly 30%) and minor casualty departments (over 40%) than in major departments (3%). Most patients managed by nurse practitioners (86%) had minor trauma. In the year ending 31 March 1991 an estimated 390,000 (95% confidence interval 260,000 to 520,000) patients out of a total of 12.5 million (3.1%, 2.1% to 4.1%) were clinically managed by a nurse practitioner. CONCLUSIONS--Designated nurse practitioner schemes are rare. The volume and range of nurse practitioner work in major general accident and emergency departments is small compared with those in specialised and minor accident and emergency departments.     

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.     

Cytosolic glycosidases: do they exist?

The substrate specificity of the alpha-D-mannosidases of rat liver lysosome and cytosol was examined using oligosaccharides of the oligomannosidic type. The hydrolysis products were characterized by 400 MHz 1H-NMR spectroscopy. Both catabolic pathways occur in ordered ways, but are quite different. In fact, the lysosomal pathway is a two-step process: the first step involves a Zn(2+)-independent alpha-1,2-mannosidase activity, whereas the second involves a Zn(2+)-dependent alpha-1,3- and alpha-1,6-mannosidase activity. The final product is the disaccharide Man(beta 1-4)GlcNAc. In contrast, the cytosolic pathway leads, in one step, to a unique hexasaccharide (Man5GlcNAc) which has the same structure as the polyprenolic intermediate synthesized on the cytosolic face of the rough endoplasmic reticulum during the biosynthesis of N-glycosylprotein glycans: Man(alpha 1-2)-Man(alpha 1-2)Man(alpha 1-3)[Man(alpha 1-6)] Man(beta 1-4)GlcNAc(beta 1-4)-GlcNAc(alpha)P-P-Dol. In addition, the enzymatic parameters of lysosome, endoplasmic reticulum and cytosol alpha-D-mannosidases are quite different. These results lead to the conclusion that the cytosol contains specific alpha-D-mannosidases which do not originate from lysosomes nor from endoplasmic reticulum. The discovery of cytosolic endo-N-acetyl-beta-D-glucosaminidase active on 'immature complex glycans' (glycopeptides of the oligomannosidic type and of the desialylated N-acetyllactosaminic type) as well as on the glycosyl-dolichol pyrophosphate intermediates allows us to hypothesize that these enzymes belong to a control system of N-glycosylprotein biosynthesis, their role being to destroy unfinished glycans. The fate of the formed oligosaccharide structures is discussed: are they destroyed by cytosolic or lysosomal exoglycosidases, or do they carry an 'oligosaccharin-like activity'?     

NMR-based plant metabolomics: where do we stand, where do we go?

NMR-based metabolomics is an important tool for studying biological systems and has been applied in various organisms, including animals, plants and microbes. NMR is able to provide a 'holistic view' of the metabolites under certain conditions, and thus is advantageous for metabolomic studies. To maximize the use of the information obtained, it is also important to create a platform to measure, store and share data. Public databases for storing and sharing information are still lacking for NMR-based metabolomic analysis in plants. Such databases are urgently needed to make metabolic profiling a real omics technology. In addition, to understand metabolic processes in depth, single-cell analysis and the turnover of metabolites in pathways (fluxomics) should be measured.