Breaking constraint of mammalian axial formulae

The vertebral column of individual mammalian species often exhibits remarkable robustness in the number and identity of vertebral elements that form (known as axial formulae). The genetic mechanism(s) underlying this constraint however remain ill-defined. Here, we reveal the interplay of three regulatory pathways (Gdf11, miR-196 and Retinoic acid) is essential in constraining total vertebral number and regional axial identity in the mouse, from cervical through to tail vertebrae. All three pathways have differing control over Hox cluster expression, with heterochronic and quantitative changes found to parallel changes in axial identity. However, our work reveals an additional role for Hox genes in supporting axial elongation within the tail region, providing important support for an emerging view that mammalian Hox function is not limited to imparting positional identity as the mammalian body plan is laid down. More broadly, this work provides a molecular framework to interrogate mechanisms of evolutionary change and congenital anomalies of the vertebral column.

Transcriptional Regulation and Implications for Controlling Hox Gene Expression

Hox genes play key roles in axial patterning and regulating the regional identity of cells and tissues in a wide variety of animals from invertebrates to vertebrates. Nested domains of Hox expression generate a combinatorial code that provides a molecular framework for specifying the properties of tissues along the A–P axis. Hence, it is important to understand the regulatory mechanisms that coordinately control the precise patterns of the transcription of clustered Hox genes required for their roles in development. New insights are emerging about the dynamics and molecular mechanisms governing transcriptional regulation, and there is interest in understanding how these may play a role in contributing to the regulation of the expression of the clustered Hox genes. In this review, we summarize some of the recent findings, ideas and emerging mechanisms underlying the regulation of transcription in general and consider how they may be relevant to understanding the transcriptional regulation of Hox genes.

Cinchona Alkaloid Derivatives modified Fe3O4 Nanoparticles for Enantioselective Ring Opening of meso- Cyclic Anhydrides

In the present work, the molecular framework of the quinidine was modified at the methoxy functional of C6’ carbon of quinoline moiety with a long-chain carboxylic acid group (-COOH) and...

Transition time

2013 is going to be an interesting year for the High Dilution research field. There is a tendency to revise basic concepts and common beliefs, while refining models and theories. The fundamental research team seems to be open to deeper discussions, aiming to reinforce some hypothesis and discharge others. In somehow, we are stuck in a vicious way of think, trying to manage and describe an informational phenomenon into a molecular framework. The challenge offered to those researchers involved with basic science is to figure out how to deal with such phenomenon, since previous theories and models have not shown to be matched! In the other hand, there is a tendency to explore the HD phenomenon in its technological branch. While basic research is important to describe how things work, the applied research has a more intense social and economic appeal. To develop technology based on HD means to give a different kind of visibility to the field, attracting sponsors, companies, entrepreneurs, always committed to the market regulatory laws. I am expecting for this year some important movements, both in the basic and applied research. Of course, it will be only a new beginning, as these changes require a lot of work, discussions and insights. But this transition time is very welcome!

A new roadmap for the breeding of disease-resistant and high-yield crops

Breeding of disease-resistant and high-yield crops is essential to meet the increasing food demand of the global population. However, the breeding of such crops remains a significant challenge for scientists and breeders. Two recent discoveries may help to overcome this challenge: the discovery of a novel molecular framework to fine-tune disease resistance and yields that includes epigenetic regulation of antagonistic immune receptors, and the discovery of a Ca2+ sensor-mediated immune repression network that enables the transfer of subspecies-specific and broad-spectrum disease resistance. These breakthroughs provide a promising roadmap for the future breeding of disease resistant crops.

The regeneration factors ERF114 and ERF115 act as transducers of mechanical cues to developmental pathways

Plants show an unparalleled regenerative capacity, allowing them to survive severe stress conditions, such as injury, herbivory attack and harsh weather conditions. This potential not only replenishes tissues and restores damaged organs, but can also give rise to whole plant bodies, highlighting the intertwined nature of development and regeneration. It suggests that regeneration and developmental processes respond to the same upstream signals, but how a cell knows which of the two processes to engage is currently unknown. Here, we demonstrate that next to being regulators of regeneration, ETHYENE RESPONSE FACTOR 114 (ERF114) and ERF115 govern developmental growth in the absence of wounding or injury. Increased ERF114 and ERF115 activity is correlated with enhanced xylem maturation and lateral root formation, whereas their knockout results in a decrease in lateral roots and xylem connectivity following grafting. Moreover, we provide evidence that mechanical cues contribute to ERF114 and ERF115 expression in correlation with BZR1 mediated brassinosteroid signaling under both regenerative and developmental conditions. Antagonistically, negative regulation of cell wall extensibility via cell wall-associated mechanosensory FERONIA signaling suppresses their expression under both conditions. Our data suggest a molecular framework in which mechanical perturbations too great to be compensated by adaptive cell wall remodeling results in strong ERF114 and ERF115 expression, switching their role from developmental to regenerative regulators.

A cell wall-associated gene network shapes leaf boundary domains

Boundary domains delimit and organize organ growth throughout plant development almost relentlessly building plant architecture and morphogenesis. Boundary domains display reduced growth and orchestrate development of adjacent tissues in a non-cell autonomous manner. How these two functions are achieved remains elusive despite the identification of several boundary-specific genes. Here, we show using morphometrics at the organ and cellular levels that leaf boundary domain development requires SPINDLY (SPY), an O-fucosyltransferase, to act as cell growth repressor. Further we show that SPY acts redundantly with the CUP-SHAPED COTYLEDON transcription factors (CUC2 and CUC3), which are major determinants of boundaries development. Accordingly at the molecular level, CUC2 and SPY repress a common set of genes involved in cell wall loosening providing a molecular framework for the growth repression associated with boundary domains. Atomic force microscopy (AFM) confirmed that young leaf boundary domain cells have stiffer cell walls than marginal outgrowth. This differential cell wall stiffness was reduced in spy mutant. Taken together our data reveal a concealed CUC2 cell wall associated gene network linking tissue patterning with cell growth and mechanics.

Potentiating the Benefits of Melatonin through Chemical Functionalization: Possible Impact on Multifactorial Neurodegenerative Disorders

Although melatonin is an astonishing molecule, it is possible that chemistry will help in the discovery of new compounds derived from it that may exceed our expectations regarding antioxidant protection and perhaps even neuroprotection. This review briefly summarizes the significant amount of data gathered to date regarding the multiple health benefits of melatonin and related compounds. This review also highlights some of the most recent directions in the discovery of multifunctional pharmaceuticals intended to act as one-molecule multiple-target drugs with potential use in multifactorial diseases, including neurodegenerative disorders. Herein, we discuss the beneficial activities of melatonin derivatives reported to date, in addition to computational strategies to rationally design new derivatives by functionalization of the melatonin molecular framework. It is hoped that this review will promote more investigations on the subject from both experimental and theoretical perspectives.

Annotation depth confounds direct comparison of gene expression across species

Background Comparisons of the molecular framework among organisms can be done on both structural and functional levels. One of the most common top-down approaches for functional comparisons is RNA sequencing. This estimation of organismal transcriptional responses is of interest for understanding evolution of molecular activity, which is used for answering a diversity of questions ranging from basic biology to pre-clinical species selection and translation. However, direct comparison between species is often hindered by evolutionary divergence in structure of molecular framework, as well as large difference in the depth of our understanding of the genetic background between humans and other species. Here, we focus on the latter. We attempt to understand how differences in transcriptome annotation affect direct gene abundance comparisons between species. Results We examine and suggest some straightforward approaches for direct comparison given the current available tools and using a sample dataset from human, cynomolgus monkey, dog, rat and mouse with a common quantitation and normalization approach. In addition, we examine how variation in genome annotation depth and quality across species may affect these direct comparisons. Conclusions Our findings suggest that further efforts for better genome annotation or computational normalization tools may be of strong interest.

A molecular framework for proximal secondary vein branching in the Arabidopsis thaliana embryo

The establishment of a closed vascular network in foliar organs is achieved through the coordinated specification of newly recruited procambial cells, their proliferation and elongation. An important, yet poorly understood component of this process, is secondary vein branching; a mechanism employed in Arabidopsis thaliana cotyledons to extend vascular tissues throughout the organ surface by secondary vein formation. To investigate the underlying molecular mechanism in vein branching, we analyzed at a single-cell level the discontinuous vein network of cotyledon vascular pattern 2 (cvp2) cvp2-like 1 (cvl1). Utilizing live-cell imaging and genetic approaches we uncovered two distinct branching mechanisms during embryogenesis. Similar to wild type, distal veins in cvp2 cvl1 embryos emerged from the bifurcation of cell files contained in the midvein. However, the branching events giving rise to proximal veins are absent in this mutant. Restoration of proximal branching in cvp2 cvl1 cotyledons could be achieved by increasing OCTOPUS dosage as well as by silencing of RECEPTOR LIKE PROTEIN KINASE 2 (RPK2) expression. The RPK2-mediated restriction of proximal branching is auxin and CLE-independent. Our work defines a genetic network conferring plasticity to Arabidopsis embryos to adapt the spatial configuration of vascular tissues to organ growth.