The importance of being kinked: role of Pro residues in the selectivity of the helical antimicrobial peptide P5

Antimicrobial peptides (AMPs) are promising compounds for developing new antibiotic drugs against drug‐resistant bacteria. Many of them kill bacteria by perturbing their membranes but exhibit no significant toxicity towards eukaryotic cells. The identification of the features responsible for this selectivity is essential for their pharmacological development. AMPs exhibit few conserved features, but a statistical analysis of an AMP sequence database indicated that many α‐helical AMPs surprisingly have a helix‐breaking Pro residue in the middle of their sequence. To discriminate among the different possible hypotheses for the functional role of this feature, we designed an analogue of the antimicrobial peptide P5, in which the central Pro was deleted (analogue P5Del). Pro removal resulted in a dramatic increase of toxicity. This was explained by the observation that P5Del binds both charged and neutral membranes, whereas P5 has no appreciable affinity towards neutral bilayers. CD and simulative data provided a rationalization of this behavior. In solution P5, due to the presence of Pro, attains compact conformations, in which its apolar residues are partially shielded from the solvent, whereas P5Del is more helical. These structural differences reduce the hydrophobic driving force for association of P5 to neutral membranes, whereas its binding to anionic bilayers can still take place because of electrostatic attraction. After membrane binding, the Pro residue does not preclude the attainment of a membrane‐active amphiphilic helical conformation. These findings shed light on the role of Pro residues in the selectivity of AMPs and provide hints for the design of new, highly selective compounds. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.     

The effects of inbreeding, genetic dissimilarity and phenotype on male reproductive success in a dioecious plant

Pollen fate can strongly affect the genetic structure of populations with restricted gene flow and significant inbreeding risk. We established an experimental population of inbred and outbred Silene latifolia plants to evaluate the effects of (i) inbreeding depression, (ii) phenotypic variation and (iii) relatedness between mates on male fitness under natural pollination. Paternity analysis revealed that outbred males sired significantly more offspring than inbred males. Independently of the effects of inbreeding, male fitness depended on several male traits, including a sexually dimorphic (flower number) and a gametophytic trait (in vitro pollen germination rate). In addition, full-sib matings were less frequent than randomly expected. Thus, inbreeding, phenotype and genetic dissimilarity simultaneously affect male fitness in this animal-pollinated plant. While inbreeding depression might threaten population persistence, the deficiency of effective matings between sibs and the higher fitness of outbred males will reduce its occurrence and counter genetic erosion.     

The projected effects of climatic and vegetation changes on the distribution and diversity of Southeast Asian bats

Southeast‐Asia (SEA) constitutes a global biodiversity hotspot, but is exposed to extensive deforestation and faces numerous threats to its biodiversity. Climate change represents a major challenge to the survival and viability of species, and the potential consequences must be assessed to allow for mitigation. We project the effects of several climate change scenarios on bat diversity, and predict changes in range size for 171 bat species throughout SEA. We predict decreases in species richness in all areas with high species richness (>80 species) at 2050–2080, using bioclimatic IPCC scenarios A2 (a severe scenario, continuously increasing human population size, regional changes in economic growth) and B1 (the ‘greenest’ scenario, global population peaking mid‐century). We also predicted changes in species richness in scenarios that project vegetation changes in addition to climate change up to 2050. At 2050 and 2080, A2 and B1 scenarios incorporating changes in climatic factors predicted that 3–9% species would lose all currently suitable niche space. When considering total extents of species distribution in SEA (including possible range expansions), 2–6% of species may have no suitable niche space in 2050–2080. When potential vegetation and climate changes were combined only 1% of species showed no changes in their predicted ranges by 2050. Although some species are projected to expand ranges, this may be ecologically impossible due to potential barriers to dispersal, especially for species with poor dispersal ability. Only 1–13% of species showed no projected reductions in their current range under bioclimatic scenarios. An effective way to facilitate range shift for dispersal‐limited species is to improve landscape connectivity. If current trends in environmental change continue and species cannot expand their ranges into new areas, then the majority of bat species in SEA may show decreases in range size and increased extinction risk within the next century.     

Systems analysis of primary Sjögren's syndrome pathogenesis in salivary glands identifies shared pathways in human and a mouse model

Bone tissue has an exceptional quality to regenerate to native tissue in response to injury. However, the fracture repair process requires mechanical stability or a viable biological microenvironment or both to ensure successful healing to native tissue. An improved understanding of the molecular and cellular events that occur during bone repair and remodeling has led to the development of biologic agents that can augment the biological microenvironment and enhance bone repair. Orthobiologics, including stem cells, osteoinductive growth factors, osteoconductive matrices, and anabolic agents, are available clinically for accelerating fracture repair and treatment of compromised bone repair situations like delayed unions and nonunions. Preclinical and clinical studies using biologic agents like recombinant bone morphogenetic proteins have demonstrated an efficacy similar or better than that of autologous bone graft in acute fracture healing. A lack of standardized outcome measures for comparison of biologic agents in clinical fracture repair trials, frequent off-label use, and a limited understanding of the biological activity of these agents at the bone repair site have limited their efficacy in clinical applications.     

Simultaneous binding of Guidance Cues NET1 and RGM blocks extracellular NEO1 signaling

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Folding, stability and polymerization properties of FtsZ chimeras with inserted tubulin loops involved in the interaction with the cytosolic chaperonin CCT and in microtubule formation

To attain its native conformation, the cytoskeletal protein tubulin needs the concourse of several molecular chaperones, among others the cytosolic chaperonin CCT. It has been previously described that denatured tubulin interacts with CCT in a quasi-folded conformation using several loops located throughout its sequence. These loops are also involved in microtubule formation and are absent in its prokaryote homologue FtsZ, which in vitro folds by itself and does not interact with CCT. Several FtsZ/tubulin chimeric proteins were generated by inserting consecutively one, two or three of the CCT-binding domains of tubulin into the corresponding sequence of FtsZ from Methanococccus jannaschii. The insertion of any of the CCT-binding loops generates in the FtsZ/tubulin chimeras the ability to interact with CCT. The accumulation of CCT-binding loops induces in the FtsZ/tubulin chimeras unfolding and refolding properties that are more similar to tubulin than to its prokaryote counterpart. Finally, the insertion of some of these loops generates in the FtsZ/tubulin chimeras more complex polymeric structures than those found for FtsZ. These results reinforce the notion that CCT has coevolved with tubulin to deal with the folding problems encountered by the eukaryotic protein with the appearance of the new sequences involved in microtubule formation.     

Mycorrhizal perennials of the "matorral xerófilo" and the "selva baja caducifolia" communities in the semiarid Tehuacán-Cuicatlán Valley,Mexico

We investigated the mycorrhizal status of perennial xeric plant species occurring in the "matorral xerófilo" (arid tropical scrub) and the ecotone of the "selva baja caducifolia" (tropical deciduous forest) communities in the semiarid valley of Tehuacán-Cuicatlán, south-central Mexico. The perennial species examined are dominant/codominant elements within the "matorral xerófilo" and the "selva baja caducifolia", both endangered communities in the Biosphere Reserve Tehuacán-Cuicatlán Valley. Of the 50 sampled species, 45 were mycorrhizal. To our knowledge, we report arbuscular mycorrhizae (AM) for the first time in 37 species, of which 21 are endemic to Mexico and nine are endemic to the Valley. We also report AM for the first time in three genera, Buddleja, Hechtia and Zornia, and in one plant family, Buddlejaceae. Beaucarnea gracilis, a threatened species, and Mimosa purpusii, a potentially rare species, are both mycorrhizal. This is the first study of the mycorrhizal status of plant species within the Valley.     

Barley microgreen incorporation in diet-controlled diabetes and counteracted aflatoxicosis in rats

Increased environmental pollution and unhealthy lifestyle are blamed for escalated chronic diseases. Exposure to aflatoxins was recently suggested to have a role in the increased incidence of type 2 diabetes mellitus. Diet modification and consumption of different functional food are now gaining attention, especially in diabetes management. This study investigates the effect of a diet containing barley microgreen against diabetes induced by streptozotocin with or without aflatoxin administration in rats. Barley microgreen was rich in 3′-Benzyloxy-5,6,7,4′-tetramethoxyflavone (48.8% of total) followed by 5β,7βH,10α-Eudesm-11-en-1α-ol (18.46%). Streptozotocin injection and/or aflatoxin administration significantly elevated glucose level, decreased insulin level, decreased β-cell function, deteriorated liver and kidney function parameters, and induced oxidative stress in the liver. Histopathology revealed irregular small-sized islets and decreased area % of insulin-positive beta cells in the pancreas, hepatic degeneration, nephropathy, and neuropathy in diabetic and/or aflatoxin administered rats compared to control. Barley microgreen diet fed to diabetic rats with or without aflatoxin alleviated all evaluated parameters. Barley microgreen diet also ameliorated the toxic effect of aflatoxin. In conclusion, exposure to aflatoxin aggravated diabetes and its complication. The incorporation of barley microgreen in the diet was able to control type 2 diabetes mellitus and the improved outcomes observed with barley microgreen treatments involved or occurred in conjunction with improved biomarkers of oxidative stress.