Biology subjects
Publications and source records attributed to Hansen, J..
Kubelka et al. (Science, 9 November 2018, p. 680-683) claim that climate change has disrupted patterns of nest predation in shorebirds. They report that predation rates have increased since the 1950s, especially in the Arctic. We describe methodological problems with their analyses and argue that there is no solid statistical support for their claims.
Species range expansion is a complex process whose outcome depends on the interplay of demographic, environmental and genetic factors. In plants, self-fertilizing species that do not require a mate to reproduce usually show higher invasive ability. However, this comes at a cost as both selfing and bottlenecks occurring during colonization lead to an increase in deleterious mutations accumulation (genetic load). Although they are theoretically clearly spelled out, the relationships between genomic and phenotypic characteristics of expanding populations have hitherto rarely been characterized. In the present study we analyzed how different accessions of the shepherds purse, C. bursa-pastoris, coming from the front of colonization or from the core of the natural range performed under increasing density of competitors. We first showed that, as expected, accessions from the front of colonization performed the worst for most life history traits compared with accessions from core populations. Second, competitor density had a negative impact on both vegetative growth and reproductive output in term of fruits production for all accessions. However, somewhat unexpectedly given their higher genetic load and their lower absolute performance, accessions from the front of colonization were less affected by competition than accessions from the core of the species range. This could be due to phenotypic tradeoffs and a shift in phenology that allow the accessions from the front of colonization to avoid competition. These results are discussed in terms of ecological strategies of expanding populations.
Neurite outgrowth is an integrated whole cell process that represents the earliest steps in neuronal differentiation. We studied cannabinoid-1 receptor regulated neurite outgrowth to identify the different subcellular processes (SCPs) involved and how they come together to produce a whole cell response. We identified the genes that were differentially expressed after CB1 receptor stimulation. From the differentially expressed components we identified the SCPs involved and how the SCPs connect to one another both horizontally and vertically. We used these SCP networks to identify genes, which when knocked down would validate the involvement of the SCP in neurite outgrowth. We identified a varied list of SCPs including those involved in pyrimidine metabolism, lipid biosynthesis, mitochondrial transport function, mRNA splicing and stability in addition to those involved in membrane vesicle production, transport and fusion and microtubule dynamics. Overall these data and computational analyses show that the downstream SCPs required for neurite outgrowth are widely distributed and involve a range of normal cellular functions. Additionally, several of these processes can be considered distal in terms of their proximity to cell signaling pathways and the microtubule and membrane vesicle dynamics, the proximal SCPs required for neurite outgrowth. Hence we conclude that receptor regulation of neurite outgrowth is distributed and deep.
Switchgrass (Panicum virgatum L.), a northern native perennial grass, suffers from yield reduction from Bipolaris leaf spot caused by Bipolaris oryzae (Breda de Haan) Shoe-maker. This study aimed for determining the resistant populations via multiple phenotyping approaches and identifying potential resistance genes to the disease from genome-wide association studies in the switchgrass northern association panel. The disease resistance was evaluated from both natural (field evaluations in NY and PA) and artificial inoculations (detached leaf and leaf disk assays). There are ten out of the 66 populations showed the most resistant based on a combination of detached leaf, leaf disk, and mean from two locations. The GWAS from five subgroups from the association panel to different disease evaluation combinations yielded 27 significant SNPs on 12 chromosomes: 1K, 2K, 2N, 3K, 3N, 4N, 5K, 5N, 6N, 7K, 7N, and 9N accumulatively explaining phenotypic variance of BLUPs of detached leaf percent lesion via image analysis 26.52% at most and BLUPs of leaf disk percent lesion via image analysis 3.28% at least. Within linkage disequilibrium of 20 kb, these SNP markers linked with the potential resistance genes including genes encoding for NBS-LRR, PPR, cell wall related proteins, homeostatic proteins, anti-apoptotic proteins, and ABC transporters.
There are no known drugs or drug combinations that promote substantial central nervous system axonal regeneration after injury. We used systems pharmacology approaches to model pathways underlying axonal growth and identify a four-drug combination that regulates multiple subcellular processes in the cell body and axon using the optic nerve crush model in rats. We intravitreally injected agonists HU-210 (cannabinoid receptor-1) and IL-6 (interleukin 6 receptor) to stimulate retinal ganglion cells for axonal growth. We applied, in gel foam at the site of nerve injury, Taxol to stabilize growing microtubules, and activated protein C to clear the debris field since computational models predicted that this drug combination regulating two subcellular processes at the growth cone produces synergistic growth. Morphology experiments show that the four-drug combination promotes axonal regrowth to the optic chiasm and beyond. Physiologically, drug treatment restored pattern electroretinograms and some of the animals had detectable visual evoked potentials in the brain and behavioral optokinetic responses. We conclude that spatially targeted drug treatment can promote robust axonal regeneration and can restore limited functional recovery.
Whole cell responses involve multiple subcellular processes (SCPs). To understand how balance between SCPs controls the dynamics of whole cell responses we studied neurite outgrowth in rat primary cortical neurons in culture. We used a combination of dynamical models and experiments to understand the conditions that permitted growth at a specified velocity and when aberrant growth could lead to the formation of dystrophic bulbs. We hypothesized that dystrophic bulb formation is due to quantitative imbalances between SCPs. Simulations predict redundancies between lower level sibling SCPs within each type of high level SCP. In contrast, higher level SCPs, such as vesicle transport and exocytosis or microtubule growth characteristic of each type need to be strictly coordinated with each other and imbalances result in stalling of neurite outgrowth. From these simulations, we predicted the effect of changing the activities of SCPs involved in vesicle exocytosis or microtubule growth could lead to formation of dystrophic bulbs. siRNA ablation experiments verified these predictions. We conclude that whole cell dynamics requires balance between the higher-level SCPs involved and imbalances can terminate whole cell responses such as neurite outgrowth.
Whole cell responses arise from coordinated interactions between diverse human gene products functioning within various pathways underlying sub-cellular processes (SCP). Lower level SCPs interact to form higher level SCPs, often in a context specific manner to give rise to whole cell function. We sought to determine if capturing such relationships enables us to describe the emergence of whole cell functions from interacting SCPs. We developed the \"Molecular Biology of the Cell\" ontology based on standard cell biology and biochemistry textbooks and review articles. Currently, our ontology contains 5,392 genes, 753 SCPs and 19,182 expertly curated gene-SCP associations. Our algorithm to populate the SCPs with genes enables extension of the ontology on demand and the adaption of the ontology to the continuously growing cell biological knowledge. Since whole cell responses most often arise from the coordinated activity of multiple SCPs, we developed a dynamic enrichment algorithm that flexibly predicts SCP-SCP relationships beyond the current taxonomy. This algorithm enables us to identify interactions between SCPs as a basis for higher order function in a context dependent manner, allowing us to provide a detailed description of how SCPs together can give rise to whole cell functions. We conclude that this ontology can, from omics data sets, enable the development of detailed multidimensional SCP networks for predictive modeling of emergent whole cell functions.
Under physiological conditions, strength and persistence of memory must be regulated in order to produce behavioral flexibility. In fact, impairments in memory flexibility are associated with pathologies such as post-traumatic stress disorder or autism; however the underlying mechanisms that enable memory flexibility are still poorly understood. Here we identified the transcriptional repressor Wilms Tumor 1 (WT1) as a critical synaptic plasticity regulator that decreases memory strength, promoting memory flexibility. WT1 was activated in the hippocampus following induction of long-term potentiation (LTP) or learning. WT1 knockdown enhanced CA1 neuronal excitability, LTP and long-term memory whereas its over-expression weakened memory retention. Moreover, forebrain WT1-deficient mice showed deficits in both reversal, sequential learning tasks and contextual fear extinction, exhibiting impaired memory flexibility. We conclude that WT1 limits memory strength or promotes memory weakening, thus enabling memory flexibility, a process that is critical for learning from new experience.
Deep mRNA sequencing (mRNAseq) is the state-of-the-art for whole transcriptome measurements. A key step is creating a library of cDNA sequencing fragments from RNA. This is generally done by random priming, creating multiple sequencing fragments along the length of each transcript. A 3 end-focused library approach cannot detect differential splicing, but has potentially higher throughput at lower cost (~10-fold lower), along with the ability to improve quantification by using transcript molecule counting with unique molecular identifiers (UMI) to correct for PCR bias. Here, we compare implementation of such a 3-digital gene expression (3-DGE) approach with \"conventional\" random primed mRNAseq, which has not yet been done. We find that while conventional mRNAseq detects ~15% more genes, the resulting lists of differentially expressed genes and therefore biological conclusions and gene signatures are highly concordant between the two techniques. We also find good quantitative agreement on the level of individual genes between the two techniques in terms of both read counts and fold change between two conditions. We conclude that for high-throughput applications, the potential cost savings associated with the 3-DGE approach are a very reasonable tradeoff for modest reduction in sensitivity and inability to observe alternative splicing, and should enable much larger scale studies focused on not only differential expression analysis, but also quantitative transcriptome profiling. The computational scripts and programs, along with experimental standard operating procedures used in our pipeline presented here, are freely available on our website (www.dtoxs.org).