Mathematical models of neuronal growth

The establishment of a functioning neuronal network is a crucial step in neural development. During this process, neurons extend neurites—axons and dendrites—to meet other neurons and interconnect. Therefore, these neurites need to migrate, grow, branch and find the correct path to their target by processing sensory cues from their environment. These processes rely on many coupled biophysical effects including elasticity, viscosity, growth, active forces, chemical signaling, adhesion and cellular transport. Mathematical models offer a direct way to test hypotheses and understand the underlying mechanisms responsible for neuron development. Here, we critically review the main models of neurite growth and morphogenesis from a mathematical viewpoint. We present different models for growth, guidance and morphogenesis, with a particular emphasis on mechanics and mechanisms, and on simple mathematical models that can be partially treated analytically.

A Glossary for Chemical Approaches towards Unlocking the Trove of Metabolic Treasures in Actinomycetes

Actinobacterial natural products showed a critical basis for the discovery of new antibiotics as well as other lead secondary metabolites. Varied environmental and physiological signals touch the antibiotic machinery that faced a serious decline in the last decades. The reason was exposed by genomic sequencing data, which revealed that Actinomycetes harbor a large portion of silent biosynthetic gene clusters in their genomes that encrypt for secondary metabolites. These gene clusters are linked with a great reservoir of yet unknown molecules, and arranging them is considered a major challenge for biotechnology approaches. In the present paper, we discuss the recent strategies that have been taken to augment the yield of secondary metabolites via awakening these cryptic genes in Actinomycetes with emphasis on chemical signaling molecules used to induce the antibiotics biosynthesis. The rationale, types, applications and mechanisms are discussed in detail, to reveal the productive path for the unearthing of new metabolites, covering the literature until the end of 2020.

Prophylactic Activation of Shh Signaling Attenuates TBI-Induced Seizures in Zebrafish by Modulating Glutamate Excitotoxicity through Eaat2a

Approximately 2 million individuals experience a traumatic brain injury (TBI) every year in the United States. Secondary injury begins within minutes after TBI, with alterations in cellular function and chemical signaling that contribute to excitotoxicity. Post-traumatic seizures (PTS) are experienced in an increasing number of TBI individuals that also display resistance to traditional anti-seizure medications (ASMs). Sonic hedgehog (Shh) is a signaling pathway that is upregulated following central nervous system damage in zebrafish and aids injury-induced regeneration. Using a modified Marmarou weight drop on adult zebrafish, we examined PTS following TBI and Shh modulation. We found that inhibiting Shh signaling by cyclopamine significantly increased PTS in TBI fish, prolonged the timeframe PTS was observed, and decreased survival across all TBI severities. Shh-inhibited TBI fish failed to respond to traditional ASMs, but were attenuated when treated with CNQX, which blocks ionotropic glutamate receptors. We found that the Smoothened agonist, purmorphamine, increased Eaat2a expression in undamaged brains compared to untreated controls, and purmorphamine treatment reduced glutamate excitotoxicity following TBI. Similarly, purmorphamine reduced PTS, edema, and cognitive deficits in TBI fish, while these pathologies were increased and/or prolonged in cyclopamine-treated TBI fish. However, the increased severity of TBI phenotypes with cyclopamine was reduced by cotreating fish with ceftriaxone, which induces Eaat2a expression. Collectively, these data suggest that Shh signaling induces Eaat2a expression and plays a role in regulating TBI-induced glutamate excitotoxicity and TBI sequelae.

Reactive/Less-cooperative individuals advance population’s synchronization: Modeling of Dictyostelium discoideum concerted signaling during aggregation phase

Orchestrated chemical signaling of single cells sounds to be a linchpin of emerging organization and multicellular life form. The social amoeba Dictyostelium discoideum is a well-studied model organism to explore overall pictures of grouped behavior in developmental biology. The chemical waves secreted by aggregating Dictyostelium is a superb example of pattern formation. The waves are either circular or spiral in shape, according to the incremental population density of a self-aggregating community of individuals. Here, we revisit the spatiotemporal patterns that appear in an excitable medium due to synchronization of randomly firing individuals, but with a more parsimonious attitude. According to our model, a fraction of these individuals are less involved in amplifying external stimulants. Our simulations indicate that the cells enhance the system’s asymmetry and as a result, nucleate early sustainable spiral territory zones, provided that their relative population does not exceed a tolerable threshold.

Loss of wings induces the expression of the worker-like phenotype in queens of a ponerine ant

Many highly-eusocial insect species are characterized by morphological differences between females. This is especially pronounced in ants where queens usually possess a fully developed thorax with wings and are specialized for reproduction while workers have a reduced thorax without wings and show various levels of reproductive degeneration that is associated with their helper role in the colony. Despite their morphological differentiation, queens and workers still show some plasticity leading to overlapping behavioral and physiological phenotypes. We investigated the level of queen plasticity and the factor that induces a worker-like phenotype in the ant species Harpegnathos saltator that has limited queen-worker dimorphism and workers that can assume the reproductive role of a queen in the colony. By comparing alate and dealate young queens, so-called gynes, we found that the loss of wings initiated the expression of behavioral and physiological characteristics of ant workers. In contrast to alate gynes, dealate gynes displayed higher frequencies of worker-like behaviors. In addition, dealate gynes showed a worker-like range of reproductive states unlike alate gynes. Like workers, dealate gynes lost the chemical signaling that is characteristic of alate gynes. Since gynes can activate this worker-like phenotype after wing loss, the essential difference between the ant queens and workers in this species with limited queen-worker dimorphism is a dispersal polyphenism. If the phenotypic plasticity observed in H. saltator is representative of the early stages of ant eusociality, an emerging dispersal dimorphism rather than a distinct reproductive dimorphism might represent one of the first steps in ant evolution.

Angiogenin and Copper Crossing in Wound Healing

Angiogenesis plays a key role in the wound healing process, involving the migration, growth, and differentiation of endothelial cells. Angiogenesis is controlled by a strict balance of different factors, and among these, the angiogenin protein plays a relevant role. Angiogenin is a secreted protein member of the ribonuclease superfamily that is taken up by cells and translocated to the nucleus when the process of blood vessel formation has to be promoted. However, the chemical signaling that activates the protein, normally present in the plasma, and the transport pathways through which the protein enters the cell are still largely unclear. Copper is also an angiogenic factor that regulates angiogenin expression and participates in the activation of common signaling pathways. The interaction between angiogenin and copper could be a relevant mechanism in regulating the formation of new blood vessel pathways and paving the way to the development of new drugs for chronic non-healing wounds.

Do Odontomachus brunneus nestmates request for help and are taken care of when caught?

In social insects, situations can arise that threaten an individual or an entire colony. When the call for help goes out, different behavioral responses are elicited by signals emitted from nestmates. In ants, the response can be one of redemptive behavior by the worker receiving it. However, little is known about the evolution of this behavior and in which group of ants it manifests. Therefore, this study investigates whether workers of Odontomachus brunneus Patton can act as rescuers, able to detect and respond to calls for help from nestmates. Laboratory experiments were carried out in which the legs of ants were trapped by tape, simulating capture by a predator. Nearby were nestmates able to receive and respond to a request for help. Two experiments were performed: 1. Calls for help were made at different distances, in order to test the response latency. 2. Evaluation of whether rescuers would respond differently to calls for help from nestmates, non-nestmates of the same species, and ants of another species. Finally, evaluation was made of the behaviors of the rescuers when they responded to requests for help from nestmates and ants of another species. It could be concluded from the results that O. brunneus workers respond to signals emitted by workers who may have been captured by a potential predator, prompting the performance of behaviors related to rescue attempts. The signals involved appear to have an optimal range and are species-specific. When exposed to a capture situation, this species transmits audible signals by stridulation, so it is possible that this type of signal may be involved, in addition to chemical signaling.

A conserved rhizobial peptidase that interacts with host-derived symbiotic peptides

In the Medicago truncatula-Sinorhizobium meliloti symbiosis, chemical signaling initiates rhizobial infection of root nodule tissue, where a large portion of the bacteria are endocytosed into root nodule cells to function in nitrogen-fixing organelles. These intracellular bacteria are subjected to an arsenal of plant-derived nodule-specific cysteine-rich (NCR) peptides, which induce the physiological changes that accompany nitrogen fixation. NCR peptides drive these intracellular bacteria toward terminal differentiation. The bacterial peptidase HrrP was previously shown to degrade host-derived NCR peptides and give the bacterial symbionts greater fitness at the expense of host fitness. The hrrP gene is found in roughly 10% of Sinorhizobium isolates, as it is carried on an accessory plasmid. The objective of the present study is to identify peptidase genes in the core genome of S. meliloti that modulate symbiotic outcome in a manner similar to the accessory hrrP gene. In an overexpression screen of annotated peptidase genes, we identified one such symbiosis-associated peptidase (sap) gene, sapA (SMc00451). When overexpressed, sapA leads to a significant decrease in plant fitness. Its promoter is active in root nodules, with only weak expression evident under free-living conditions. The SapA enzyme can degrade a broad range of NCR peptides in vitro.