Molecular shredders: how proteasomes fulfill their role

The 20S proteasome is a large, cylinder-shaped protease that is found in all domains of life and plays a crucial role in cellular protein turnover. It has multiple catalytic centers located within the hollow cavity of a molecular cage. This architecture prevents unwanted degradation of endogenous proteins and promotes processive degradation of substrates by restricting the dissociation of partially digested polypeptides. Although this kind of self-compartmentalization is generally conserved, the proteasomes of bacteria, archaea and eukaryotes show many differences in architecture, subunit composition and regulation. The structure of the 20S proteasome and its inherent role in the regulation of proteasome function are gradually being elucidated.     

The primary physician: A unique role

The article reviews some of the current roles of primary care physicians. It is suggested that training programs set up their objectives so that the graduate can simultaneously assess and manage organic and psychological problems in the non-differentiated patient. An overview of one of the current programs is described.     

On how the conformation of biliverdins influences their reduction to bilirubins: a biological and molecular modeling study

The cyclic 2,18-bridged biliverdin (2) is excreted in rat bile without reduction to the corresponding bilirubin. Conformational analysis, employing an optimized Monte Carlo method and a mixed Monte Carlo/stochastic dynamics, reveals that biliverdin IXalpha (1) and the cyclic analogue 2 adopt 'lock washer' conformations, stabilized by the presence of intramolecular hydrogen bonds between N23...H22N and, to a lesser extent, between N23...H24N. Although 2 is very similar in overall shape to 1, the former adopts a 'locked lock washer' conformation unable to undergo fluctuations, thus possibly hampering a proper recognition by biliverdin reductase.     

Predicting invasive alien plant distributions: how geographical bias in occurrence records influences model performance

Aim To investigate the impact of geographical bias on the performance of ecological niche models for invasive plant species. Location South Africa and Australia. Methods We selected 10 Australian plants invasive in South Africa and nine South African plants invasive in Australia. Geographical bias was simulated in occurrence records obtained from the native range of a species to represent two scenarios. For the first scenario (A, worst‐case) a proportion of records were excluded from a specific region of a species’ range and for the second scenario (B, less extreme) only some records were excluded from that specific region of the range. Introduced range predictions were produced with the Maxent modelling algorithm where models were calibrated with datasets from these biased occurrence records and 19 bioclimatic variables. Models were evaluated with independent test data obtained from the introduced range of the species. Geographical bias was quantified as the proportional difference between the occurrence records from a control and a biased dataset, and environmental bias was expressed as either the difference in marginality or tolerance between these datasets. Model performance [assessed using the conventional and modified AUC (area under the curve of receiver‐operating characteristic plots) and the maximum true skill statistic] was compared between models calibrated with occurrence records from a biased dataset and a control dataset. Results We found considerable variation in the relationship between geographical and environmental bias. Environmental bias, expressed as the difference in marginality, differed significantly across treatments. Model performance did not differ significantly among treatments. Regions predicted as suitable for most of the species were very similar when compared between a biased and control dataset, with only a few exceptions. Main conclusions The geographical bias simulated in this study was sufficient to result in significant environmental bias across treatments, but despite this we did not find a significant effect on model performance. Differences in the environmental spaces occupied by the species in their native and invaded ranges may explain why we did not find a significant effect on model performance.     

Leptin and the immune system: how nutritional status influences the immune response

Several observations suggest the presence of an interaction between immune and the endocrine systems. Leptin is an adipocyte-derived hormone, that belongs structurally to the long-chain helical cytokine family such as interleukin-2 (IL-2), interleukin-12 (IL-12), growth hormone (GH), and signals by a class I cytokine receptor (Ob-R). This cytokine represents an important link between fat mass on the one side and the regulation of energy balance and reproductive function on the other. Indeed, obese leptin-deficient ob/ob mice display low body temperature, hyperphagia, infertility and evidence of immune defects with lymphoid organ atrophy, mainly affecting thymic size and cellularity. Acute starvation, associated with decreased leptin levels, causes thymic atrophy and reduces the delayed type hypersensitivity (DTH) reaction to antigens in normal mice, resembling that observed in ob/ob mice. Leptin replacement reverses the immunosuppressive effects of acute starvation in mice. Leptin differentially affects the in vitro proliferation and cytokine production by naive and memory T cells, increasing IL-2 secretion and proliferation of naive T cells, while inducing IFN-g production in memory T cells with little effect on their proliferation. Presence of leptin seems to be necessary for the induction and maintenance of the pro-inflammatory Th1 immune response. These findings support the hypothesis that leptin plays a key role in linking nutritional state to the T cell function. According to this view, leptin might represent an important target for immune intervention in a variety of pathophysiological conditions.     

Legionella natural biofilms and their role in epidemiology of the infection: methods of study and modelling

Ability of Legionella species to form biofilms in association with other microorganisms is the key factor of their spreading in potentially dangerous water systems. Ability of different strains of Legionella to form monospecies biofilms as well as biofilms in association with Pseudomonas aeruginosa in constant conditions was analyzed. It was shown that ability of Legionella strains to form monospecies biofilms correlates with their ability to persist in biofilms formed by P. aeruginosa.     

Cryptochromes in the field: how blue light influences crop development

Light is a pivotal environmental element capable of influencing multiple physiological processes across the entire plant life cycle. Over the course of their evolution, plants have developed several families of photoreceptors such as phytochromes, phototropins, ultraviolet (UV) resistance locus 8 and cryptochromes (crys), in order to sense light stimuli and respond to their changes. Numerous genetic studies have demonstrated that functional alterations to these photoreceptors cause a change in important agronomical traits. In particular, crys, which absorb UVA/blue light, can influence seed germination, flowering induction, plant architecture, fruit metabolic content and resistance to biotic and abiotic stresses. In the years to come, the rising temperatures and alterations to precipitation patterns generated by climate change will present a dramatic challenge for our agricultural system, with its few varieties characterized by a narrow genetic pool derived from artificial selection. Here, we review the main roles of crys in determining important agronomic traits in crops, we discuss the opportunities of using these photoreceptors as genetic targets for tuning plant physiological responses to environmental change, and the molecular strategies used so far to manipulate this family of photoreceptors.     

Beyond connectivity: how the structure of dispersal influences metacommunity dynamics

Dispersal within metacommunities can play a major role in species persistence by promoting asynchrony between communities. Understanding this role is crucial both for explaining species coexistence and managing landscapes that are increasingly fragmented by human activities. Here, we demonstrate that spatial patterning of dispersal connections can drastically alter both the tendency toward asynchrony and the effect of asynchrony on metacommunity dynamics commonly used to infer the potential for persistence. We also demonstrate that changes in dispersal connections in strictly homogeneous predator-prey metacommunities can generate an extremely rich variety of dynamics even when previously investigated properties of connectivity such as the magnitude and distribution of dispersal among patches are held constant. Furthermore, the dynamics we observe depend strongly on initial conditions. Our results illustrate the effectiveness of measures of spatial structure for predicting asynchrony and its effects on community dynamics, providing a deeper understanding of the relationship between spatial structure and species persistence in metacommunities.     

Implications of recent hypertension trials for the generalist physician: whom do we treat, and how?

The publication of the results of the Swedish Trial in Old Patients with Hypertension-2 (STOP-2) and the termination of the doxazocin arm of the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack (ALLHAT) study again raise the question of whether all antihypertensives deliver equal cardiovascular outcome benefits. Data from research on congestive heart failure and from the Heart Outcomes Prevention Evaluation (HOPE) trial illuminate the roles and possible mechanisms of humoral mediators of vascular damage, suggesting, first, that some antihypertensives (thiazides, beta-blockers, and angiotensin-converting enzyme inhibitors) can deliver more improvement in outcomes than other agents and, second, that decisions on whom to treat are best made based on risk appraisal, not merely pressures.     

The teacher writing toolkit: enhancing undergraduate teaching of scientific writing in the biological sciences

ABSTRACT

Teaching scientific writing in biology classes is challenging for both teachers and students. This article offers and reviews several useful ‘toolkit’ items that instructors of science writing can use to improve college student success. The tools in this kit are both conceptual and practical, and include: 1) Understanding the role of student metacognition, cognitive instruction, and strategic teaching, 2) Recognition of different student writing levels, 3) Applying the writing process, 4) Demonstrational classroom revision and editing, 5) Student-teacher sentence editing, 6) Student peer editing and guided student editing, 7) Student copy-editing, 8) Reflective writing, 9) Addressing plagiarism, paraphrasing, and proper in-text citations and referencing, and 10) Using external, on campus and online resources. Additionally, we discuss the new challenges of teaching scientific writing online versus face-to-face. The discussions, approaches, and exercises presented in this paper empower teachers in assisting students in their development of a personal writing style, while simultaneously building student confidence. The tools we present augment our previous presentation of the student writing toolkit, and can improve and enhance the teaching of scientific writing to undergraduate students.     

The mycobacterial glycopeptidolipids: structure, function, and their role in pathogenesis

Glycopeptidolipids (GPLs) are a class of glycolipids produced by several nontuberculosis-causing members of the Mycobacterium genus including pathogenic and nonpathogenic species. GPLs are expressed in different forms with production of highly antigenic, typeable serovar-specific GPLs in members of the Mycobacterium avium complex (MAC). M. avium and M. intracellulare, which comprise this complex, are slow-growing mycobacteria noted for producing disseminated infections in AIDS patients and pulmonary infections in non-AIDS patients. Previous studies have defined the gene cluster responsible for GPL biosynthesis and more recent work has characterized the function of the individual genes. Current research has also focused on the GPL's role in colony morphology, sliding motility, biofilm formation, immune modulation and virulence. These topics, along with new information on the enzymes involved in GPL biosynthesis, are the subject of this review.     

Preaching about the converted: how meiotic gene conversion influences genomic diversity

Meiotic crossover (CO) recombination involves a reciprocal exchange between homologous chromosomes. COs are often associated with gene conversion at the exchange site where genetic information is unidirectionally transferred from one chromosome to the other. COs and independent assortment of homologous chromosomes contribute significantly to the promotion of genomic diversity. What has not been appreciated is the contribution of another product of meiotic recombination, noncrossovers (NCOs), which result in gene conversion without exchange of flanking markers. Here, we review our comprehensive analysis of recombination at a highly polymorphic mouse hotspot. We found that NCOs make up ～90% of recombination events. Preferential recombination initiation on one chromosome allowed us to estimate the contribution of CO and NCO gene conversion to transmission distortion, a deviation from Mendelian inheritance in the population. While NCO gene conversion tracts are shorter, and thus have a more punctate effect, their higher frequency translates into an approximately two-fold greater contribution than COs to gene conversion-based allelic shuffling and transmission distortion. We discuss the potential impact of mammalian NCO characteristics on evolution and genomic diversity.     

The morphogenesis checkpoint: how yeast cells watch their figures

The morphogenesis checkpoint maintains coordination between the process of bud formation and the nuclear events of the cell cycle in yeast. This checkpoint regulates the Wee1 homolog, Swe1p, to induce cell-cycle delay or arrest when aspects of bud formation are defective. A variety of studies have suggested that this checkpoint can monitor actin organization, septin organization, the presence of a bud and even the size of a bud. The evidence for these proposals is reviewed, highlighting recent findings indicating that Swe1p degradation is controlled by the cell shape change that accompanies bud emergence.