Cholera and climate: revisiting the quantitative evidence

Cholera dynamics in endemic regions display regular seasonal cycles and pronounced interannual variability. We review here the current quantitative evidence for the influence of climate on cholera dynamics with reference to the early literature on the subject. We also briefly review the incipient status of mathematical models for cholera and argue that these models are important for understanding climatic influences in the context of the population dynamics of the disease. A better understanding of disease risk related to the environment should further underscore the need for changing the socioeconomic conditions conducive to cholera.     

Caspase activation: revisiting the induced proximity model

Caspases execute cell death. The mechanism of effector caspase activation primarily involves reorganization of active site loops following the activation cleavage. The Induced Proximity hypothesis, originally proposed to explain the activation of initiator caspases, has recently been reinterpreted to be proximity-driven dimerization of initiator caspases, and consequently their activation. The evidence supporting these models is critically evaluated and other possible mechanisms for initiator caspase activation are discussed.     

Perspective: revisiting the field dependence of TROSY sensitivity

The discovery of the TROSY effect (Pervushin et al. in Proc Natl Acad Sci USA 94:12366–12371, 1997) for reducing transverse relaxation and line sharpening through selecting pathways in which dipole–dipole and CSA Hamiltonians partially cancel each other had a tremendous impact on solution NMR studies of macromolecules. Together with the methyl TROSY (Tugarinov and Kay in J Biomol NMR 28:165–172, 2004) it enabled structural and functional studies of significantly larger systems. The optimal field strengths for TROSY have been estimated to be on spectrometers operating around 900 MHz (21.14 T) for the ¹H_N TROSY (Pervushin et al. in Proc Natl Acad Sci USA 94:12366–12371, 1997) while the aromatic ¹³C (¹³C_aro) TROSY is posited to be optimal at around 600 MHz (14.09 T) (Pervushin et al. in J Am Chem Soc 120:6394–6400, 1998b; Pervushin in Q Rev Biophys 33:161–197, 2000). The initial rational was based on the consideration of where the quadratic B₀ field dependences of the TROSY relaxation rates reach a minimum. For sensitivity consideration, however, it is interesting to estimate which field strengths yield the tallest peaks. Recent studies of ¹⁵N-detected TROSYs suggested that maximal peak heights are expected at 1.15 GHz (27.01 T) although the slowest relaxation rates or longest transverse relaxation times T₂ are indeed expected around 900 MHz (21.14 T) (Takeuchi in J Biomol NMR 63:323–331, 2015; Takeuchi et al. in J Biomol NMR 64:143–151, 2016). This was based on the fact that the heights of Lorentzian lines are proportional to B _o ^3/2 * T₂ (B_o). Thus, multiplying the parabolic T₂(B_o) dependence with the increasing function of B _o ^3/2 shifts the maxima of peak-height field dependence from the T₂ maximum at 900 MHz to higher fields. Moreover, besides shifting the peak height maximum for ¹⁵N TROSY, this analysis yields estimates for optimal peak heights for ¹H_N detected TROSY to 1.5 GHz, and to 900 MHz for ¹³C-detected ¹³C_aroTROSY as is detailed below. To our knowledge, this aspect of field dependence of TROSY sensitivity has not been in the attention of the NMR community but may affect perspectives of NMR at ultra-high fields.     

Let's go bananas: revisiting the endocytic BAR code

Against the odds of membrane resistance, members of the BIN/Amphiphysin/Rvs (BAR) domain superfamily shape membranes and their activity is indispensable for a plethora of life functions. While crystal structures of different BAR dimers advanced our understanding of membrane shaping by scaffolding and hydrophobic insertion mechanisms considerably, especially life-imaging techniques and loss-of-function studies of clathrin-mediated endocytosis with its gradually increasing curvature show that the initial idea that solely BAR domain curvatures determine their functions is oversimplified. Diagonal placing, lateral lipid-binding modes, additional lipid-binding modules, tilde shapes and formation of macromolecular lattices with different modes of organisation and arrangement increase versatility. A picture emerges, in which BAR domain proteins create macromolecular platforms, that recruit and connect different binding partners and ensure the connection and coordination of the different events during the endocytic process, such as membrane invagination, coat formation, actin nucleation, vesicle size control, fission, detachment and uncoating, in time and space, and may thereby offer mechanistic explanations for how coordination, directionality and effectiveness of a complex process with several steps and key players can be achieved.     

Rhizosphere microbiome: revisiting the synergy of plant-microbe interactions

Sustainable enhancement in food production from less available arable land must encompass a balanced use of inorganic, organic, and biofertilizer sources of plant nutrients to augment and maintain soil fertility and productivity. The varied responses of microbial inoculants across fields and crops, however, have formed a major bottleneck that hinders its widespread adoption. This necessitates an intricate analysis of the inter-relationships between soil microbial communities and their impact on host plant productivity. The concept of “biased rhizosphere,” which evolved from the interactions among different components of the rhizosphere including plant roots and soil microflora, strives to garner a better understanding of the complex rhizospheric intercommunications. Moreover, knowledge on rhizosphere microbiome is essential for developing strategies for shaping the rhizosphere to benefit the plants. With the advent of molecular and “omics” tools, a better understanding of the plant-microbe association could be acquired which could play a crucial role in drafting the future “biofertilizers.” The present review, therefore aims to (a) to introduce the concepts of rhizosphere hotspots and microbiomes and (b) to detail out the methodologies for creating biased rhizospheres for plant-mediated selection of beneficial microorganisms and their roles in improving plant performance.

     

Mutualism and evolutionary multiplayer games: revisiting the Red King

Coevolution of two species is typically thought to favour the evolution of faster evolutionary rates helping a species keep ahead in the Red Queen race, where ‘it takes all the running you can do to stay where you are’. In contrast, if species are in a mutualistic relationship, it was proposed that the Red King effect may act, where it can be beneficial to evolve slower than the mutualistic species. The Red King hypothesis proposes that the species which evolves slower can gain a larger share of the benefits. However, the interactions between the two species may involve multiple individuals. To analyse such a situation, we resort to evolutionary multiplayer games. Even in situations where evolving slower is beneficial in a two-player setting, faster evolution may be favoured in a multiplayer setting. The underlying features of multiplayer games can be crucial for the distribution of benefits. They also suggest a link between the evolution of the rate of evolution and group size.     

Heterosis

Heterosis refers to the phenomenon that progeny of diverse varieties of a species or crosses between species exhibit greater biomass, speed of development, and fertility than both parents. Various models have been posited to explain heterosis, including dominance, overdominance, and pseudo-overdominance. In this Perspective, we consider that it might be useful to the field to abandon these terms that by their nature constrain data interpretation and instead attempt a progression to a quantitative genetic framework involving interactions in hierarchical networks. While we do not provide a comprehensive model to explain the phenomenology of heterosis, we provide the details of what needs to be explained and a direction of pursuit that we feel should be fruitful.     

Nonlinear magic: multiphoton microscopy in the biosciences

Multiphoton microscopy (MPM) has found a niche in the world of biological imaging as the best noninvasive means of fluorescence microscopy in tissue explants and living animals. Coupled with transgenic mouse models of disease and 'smart' genetically encoded fluorescent indicators, its use is now increasing exponentially. Properly applied, it is capable of measuring calcium transients 500 microm deep in a mouse brain, or quantifying blood flow by imaging shadows of blood cells as they race through capillaries. With the multitude of possibilities afforded by variations of nonlinear optics and localized photochemistry, it is possible to image collagen fibrils directly within tissue through nonlinear scattering, or release caged compounds in sub-femtoliter volumes.     

Working memory: imaging the magic number four

Many brain regions have been implicated in memory performance, but the relationship between memory capacity and neural activity has not been clear. Recent studies show that activity in the posterior parietal cortex increases with working memory load, implicating this region in the storage of representations in visual memory.     

ppGpp: magic beyond RNA polymerase

During stress, bacteria undergo extensive physiological transformations, many of which are coordinated by ppGpp. Although ppGpp is best known for enhancing cellular resilience by redirecting the RNA polymerase (RNAP) to certain genes, it also acts as a signal in many other cellular processes in bacteria. After a brief overview of ppGpp biosynthesis and its impact on promoter selection by RNAP, we discuss how bacteria exploit ppGpp to modulate the synthesis, stability or activity of proteins or regulatory RNAs that are crucial in challenging environments, using mechanisms beyond the direct regulation of RNAP activity.