Plant biology: do DELLAs do defence?

DELLA proteins repress plant growth and developmental processes. Recent data suggest that DELLAs improve survival by imposing growth restraint during plant stress, enabling limited resources to be diverted to pathogen defence.     

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.     

POPP the question: what do LEA proteins do?

Late embryogenesis abundant (LEA) proteins are produced in maturing seeds and anhydrobiotic plants, animals and microorganisms, in which their expression correlates with desiccation tolerance. However, their function has remained obscure for 20 years. We argue that novel computational tools devised for non-globular proteins might now overcome this problem. Predictions arising from bioinformatics fit well with recent data on Group 3 proteins, which potentially form cytoskeletal filaments, and suggest experimentally testable functions for these and other LEA protein groups.     

Pathogen effectors: What do they do at plasmodesmata?

Plants perceive an assortment of external cues during their life cycle, including abiotic and biotic stressors. Biotic stress from a variety of pathogens, including viruses, oomycetes, fungi, and bacteria, is considered to be a substantial factor hindering plant growth and development. To hijack the host cell's defence machinery, plant pathogens have evolved sophisticated attack strategies mediated by numerous effector proteins. Several studies have indicated that plasmodesmata (PD), symplasmic pores that facilitate cell-to-cell communication between a cell and neighbouring cells, are one of the targets of pathogen effectors. However, in contrast to plant-pathogenic viruses, reports of fungal- and bacterial-encoded effectors that localize to and exploit PD are limited. Surprisingly, a recent study of PD-associated bacterial effectors has shown that a number of bacterial effectors undergo cell-to-cell movement via PD. Here we summarize and highlight recent advances in the study of PD-associated fungal/oomycete/bacterial effectors. We also discuss how pathogen effectors interfere with host defence mechanisms in the context of PD regulation.     

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.     

Human immunodeficiency virus-1 vaccine design: where do we go now?

Numerous human immunodeficiency virus (HIV)-1 vaccines have been developed over the last three decades, but to date an effective HIV-1 vaccine that can be used for prophylactic or therapeutic purposes in humans has not been identified. The failures and limited successes of HIV-1 vaccines have highlighted the gaps in our knowledge with regard to fundamental immunity against HIV-1 and have provided insights for vaccine strategies that may be implemented for designing more effective HIV-1 vaccines in the future. Recent studies have shown that robust mucosal immunity, high avidity and polyfunctional T cells, and broadly neutralizing antibodies are important factors governing the induction of protective immunity against HIV-1. Furthermore, optimization of vaccine delivery methods for DNA or live viral vector-based vaccines, elucidating the immune responses of individuals who remain resistant to HIV-1 infections and also understanding the core immune responses mediating protection against simian immunodeficiency viruses (SIV) and HIV-1 in animal models following vaccination, are key aspects to be regarded for designing more effective HIV-1 vaccines in the future.     

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.     

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.     

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'?     

Pathogenic archaea: do they exist?

Archaea are microorganisms that are distinct from bacteria and eukaryotes. They are prevalent in extreme environments, and yet found in most ecosystems. They are a natural component of the microbiota of most, if not all, humans and other animals. Despite their ubiquity and close association with humans, animals and plants, no pathogenic archaea have been identified. Because no archaeal pathogens have yet been identified, there is a general assumption that archaeal pathogens do not exist. This review examines whether this is a good assumption by investigating the potential for archaea to be or become pathogens. This is achieved by addressing: the diversity of archaea versus known pathogens, opportunities for archaea to demonstrate pathogenicity and be detected as pathogens, reports linking archaea with disease, and immune responses to archaea. In addition, molecular and genomic data are examined for the presence of systems utilised in pathogenesis. The view of this report is that, although archaea can presently be described as non-pathogenic, they have the potential to be (discovered as) pathogens. The present optimistic view that there are no archaeal pathogens is tainted by a severe lack of relevant knowledge, which may have important consequences in the future.