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Comprehensive Psychoneuroendocrinology Nov 2023In this article, I am going through my scientific and personal journey using my work on oxytocin as a compass. I recount how my scientific questions were shaped over the... (Review)
Review
In this article, I am going through my scientific and personal journey using my work on oxytocin as a compass. I recount how my scientific questions were shaped over the years, and how I studied them through the lens of different fields ranging from linguistics and neuroscience to comparative and population genomics in a wide range of vertebrate species. I explain how my evolutionary findings and proposal for a universal gene nomenclature in the oxytocin-vasotocin ligand and receptor families have impacted relevant fields, and how my studies in the oxytocin and vasotocin system in songbirds, humans and non-human primates have led me to now be testing intranasal oxytocin as a candidate treatment for speech deficits. I also discuss my projects on the neurobiology of dance and where oxytocin fits in the picture of studying speech and dance in parallel. Lastly, I briefly communicate the challenges I have been facing as a woman and an international scholar in science and academia, and my personal ways to overcome them.
PubMed: 38108035
DOI: 10.1016/j.cpnec.2023.100193 -
Biology Letters Jul 2020is the study of how animal vocalizations reflect their body size. A key aim of this research is to identify outliers to acoustic allometry principles and pinpoint the... (Review)
Review
is the study of how animal vocalizations reflect their body size. A key aim of this research is to identify outliers to acoustic allometry principles and pinpoint the evolutionary origins of such outliers. A parallel strand of research investigates species capable of , the experience-driven ability to produce novel vocal signals through imitation or modification of existing vocalizations. Modification of vocalizations is a common feature found when studying both acoustic allometry and vocal learning. Yet, these two fields have only been investigated separately to date. Here, we review and connect acoustic allometry and vocal learning across mammalian clades, combining perspectives from bioacoustics, anatomy and evolutionary biology. Based on this, we hypothesize that, as a precursor to vocal learning, some species might have evolved the capacity for volitional vocal modulation via sexual selection for 'dishonest' signalling. We provide preliminary support for our hypothesis by showing significant associations between allometric deviation and vocal learning in a dataset of 164 mammals. Our work offers a testable framework for future empirical research linking allometric principles with the evolution of vocal learning.
Topics: Acoustics; Animals; Body Size; Mammals; Vocalization, Animal
PubMed: 32634374
DOI: 10.1098/rsbl.2020.0081 -
JCI Insight Jun 2023Innate and adaptive immune cells modulate the severity of autosomal dominant polycystic kidney disease (ADPKD), a common kidney disease with inadequate treatment...
Innate and adaptive immune cells modulate the severity of autosomal dominant polycystic kidney disease (ADPKD), a common kidney disease with inadequate treatment options. ADPKD has parallels with cancer, in which immune checkpoint inhibitors have been shown to reactivate CD8+ T cells and slow tumor growth. We have previously shown that in PKD, CD8+ T cell loss worsens disease. This study used orthologous early-onset and adult-onset ADPKD models (Pkd1 p.R3277C) to evaluate the role of immune checkpoints in PKD. Flow cytometry of kidney cells showed increased levels of programmed cell death protein 1 (PD-1)/cytotoxic T lymphocyte associated protein 4 (CTLA-4) on T cells and programmed cell death ligand 1 (PD-L1)/CD80 on macrophages and epithelial cells in Pkd1RC/RC mice versus WT, paralleling disease severity. PD-L1/CD80 was also upregulated in ADPKD human cells and patient kidney tissue versus controls. Genetic PD-L1 loss or treatment with an anti-PD-1 antibody did not impact PKD severity in early-onset or adult-onset ADPKD models. However, treatment with anti-PD-1 plus anti-CTLA-4, blocking 2 immune checkpoints, improved PKD outcomes in adult-onset ADPKD mice; neither monotherapy altered PKD severity. Combination therapy resulted in increased kidney CD8+ T cell numbers/activation and decreased kidney regulatory T cell numbers correlative with PKD severity. Together, our data suggest that immune checkpoint activation is an important feature of and potential novel therapeutic target in ADPKD.
Topics: Adult; Humans; Animals; Mice; Polycystic Kidney, Autosomal Dominant; B7-H1 Antigen; Polycystic Kidney Diseases; Kidney; Combined Modality Therapy; B7-1 Antigen
PubMed: 37345660
DOI: 10.1172/jci.insight.161318 -
BMC Bioinformatics May 2021Statistical geneticists employ simulation to estimate the power of proposed studies, test new analysis tools, and evaluate properties of causal models. Although there...
BACKGROUND
Statistical geneticists employ simulation to estimate the power of proposed studies, test new analysis tools, and evaluate properties of causal models. Although there are existing trait simulators, there is ample room for modernization. For example, most phenotype simulators are limited to Gaussian traits or traits transformable to normality, while ignoring qualitative traits and realistic, non-normal trait distributions. Also, modern computer languages, such as Julia, that accommodate parallelization and cloud-based computing are now mainstream but rarely used in older applications. To meet the challenges of contemporary big studies, it is important for geneticists to adopt new computational tools.
RESULTS
We present TraitSimulation, an open-source Julia package that makes it trivial to quickly simulate phenotypes under a variety of genetic architectures. This package is integrated into our OpenMendel suite for easy downstream analyses. Julia was purpose-built for scientific programming and provides tremendous speed and memory efficiency, easy access to multi-CPU and GPU hardware, and to distributed and cloud-based parallelization. TraitSimulation is designed to encourage flexible trait simulation, including via the standard devices of applied statistics, generalized linear models (GLMs) and generalized linear mixed models (GLMMs). TraitSimulation also accommodates many study designs: unrelateds, sibships, pedigrees, or a mixture of all three. (Of course, for data with pedigrees or cryptic relationships, the simulation process must include the genetic dependencies among the individuals.) We consider an assortment of trait models and study designs to illustrate integrated simulation and analysis pipelines. Step-by-step instructions for these analyses are available in our electronic Jupyter notebooks on Github. These interactive notebooks are ideal for reproducible research.
CONCLUSION
The TraitSimulation package has three main advantages. (1) It leverages the computational efficiency and ease of use of Julia to provide extremely fast, straightforward simulation of even the most complex genetic models, including GLMs and GLMMs. (2) It can be operated entirely within, but is not limited to, the integrated analysis pipeline of OpenMendel. And finally (3), by allowing a wider range of more realistic phenotype models, TraitSimulation brings power calculations and diagnostic tools closer to what investigators might see in real-world analyses.
Topics: Aged; Cloud Computing; Computer Simulation; Genetic Testing; Humans; Pedigree; Phenotype
PubMed: 33941078
DOI: 10.1186/s12859-021-04086-8 -
Science Advances Jul 2022pH controls a large repertoire of chemical and biochemical processes in water. Densely arrayed pH microenvironments would parallelize these processes, enabling their...
pH controls a large repertoire of chemical and biochemical processes in water. Densely arrayed pH microenvironments would parallelize these processes, enabling their high-throughput studies and applications. However, pH localization, let alone its arrayed realization, remains challenging because of fast diffusion of protons in water. Here, we demonstrate arrayed localizations of picoliter-scale aqueous acids, using a 256-electrochemical cell array defined on and operated by a complementary metal oxide semiconductor (CMOS)-integrated circuit. Each cell, comprising a concentric pair of cathode and anode with their current injections controlled with a sub-nanoampere resolution by the CMOS electronics, creates a local pH environment, or a pH "voxel," via confined electrochemistry. The system also monitors the spatiotemporal pH profile across the array in real time for precision pH control. We highlight the utility of this CMOS pH localizer-imager for high-throughput tasks by parallelizing pH-gated molecular state encoding and pH-regulated enzymatic DNA elongation at any selected set of cells.
PubMed: 35895813
DOI: 10.1126/sciadv.abm6815 -
Molecular Biology and Evolution Mar 2022Bioinformatic research relies on large-scale computational infrastructures which have a nonzero carbon footprint but so far, no study has quantified the environmental...
Bioinformatic research relies on large-scale computational infrastructures which have a nonzero carbon footprint but so far, no study has quantified the environmental costs of bioinformatic tools and commonly run analyses. In this work, we estimate the carbon footprint of bioinformatics (in kilograms of CO2 equivalent units, kgCO2e) using the freely available Green Algorithms calculator (www.green-algorithms.org, last accessed 2022). We assessed 1) bioinformatic approaches in genome-wide association studies (GWAS), RNA sequencing, genome assembly, metagenomics, phylogenetics, and molecular simulations, as well as 2) computation strategies, such as parallelization, CPU (central processing unit) versus GPU (graphics processing unit), cloud versus local computing infrastructure, and geography. In particular, we found that biobank-scale GWAS emitted substantial kgCO2e and simple software upgrades could make it greener, for example, upgrading from BOLT-LMM v1 to v2.3 reduced carbon footprint by 73%. Moreover, switching from the average data center to a more efficient one can reduce carbon footprint by approximately 34%. Memory over-allocation can also be a substantial contributor to an algorithm's greenhouse gas emissions. The use of faster processors or greater parallelization reduces running time but can lead to greater carbon footprint. Finally, we provide guidance on how researchers can reduce power consumption and minimize kgCO2e. Overall, this work elucidates the carbon footprint of common analyses in bioinformatics and provides solutions which empower a move toward greener research.
Topics: Algorithms; Carbon Footprint; Computational Biology; Genome-Wide Association Study; Software
PubMed: 35143670
DOI: 10.1093/molbev/msac034 -
Gut Microbes 2022The human gut microbiota is highly heterogenous between individuals and also exhibits considerable day-to-day variation within individuals. We hypothesized that diet...
The human gut microbiota is highly heterogenous between individuals and also exhibits considerable day-to-day variation within individuals. We hypothesized that diet contributed to such inter- and/or intra-individual variance. Hence, we investigated the extent to which diet normalization impacted microbiota heterogeneity. We leveraged the control arm of our recently reported controlled-feeding study in which nine healthy individuals consumed a standardized additive-free diet for 10 days. Diet normalization did not impact inter-individual differences but reduced the extent of intra-individual day-to-day variation in fecal microbiota composition. Such decreased heterogeneity reflected individual-specific enrichment and depletion of an array of taxa microbiota members and was paralleled by a trend toward reduced intra-individual variance in fecal LPS and flagellin, which, collectively, reflect microbiota's pro-inflammatory potential. Yet, the microbiota of some subjects did not change significantly over the course of the study, suggesting heterogeneity in microbiota resilience to dietary stress or that baseline diets of some subjects were perhaps similar to our study's standardized diet. Collectively, our results indicate that short-term diet heterogeneity contributes to day-to-day intra-individual microbiota composition variance.
Topics: Humans; Gastrointestinal Microbiome; Diet; Microbiota; Feces; Reference Standards
PubMed: 36426908
DOI: 10.1080/19490976.2022.2149047 -
Biochimica Et Biophysica Acta.... Jan 2021Lanthanides are relative newcomers to the field of cell biology of metals; their specific incorporation into enzymes was only demonstrated in 2011, with the isolation of... (Review)
Review
Lanthanides are relative newcomers to the field of cell biology of metals; their specific incorporation into enzymes was only demonstrated in 2011, with the isolation of a bacterial lanthanide- and pyrroloquinoline quinone-dependent methanol dehydrogenase. Since that discovery, the efforts of many investigators have revealed that lanthanide utilization is widespread in environmentally important bacteria, and parallel efforts have focused on elucidating the molecular details involved in selective recognition and utilization of these metals. In this review, we discuss the particular chemical challenges and advantages associated with biology's use of lanthanides, as well as the currently known lanthano-enzymes and -proteins (the lanthanome). We also review the emerging understanding of the coordination chemistry and biology of lanthanide acquisition, trafficking, and regulatory pathways. These studies have revealed significant parallels with pathways for utilization of other metals in biology. Finally, we discuss some of the many unresolved questions in this burgeoning field and their potentially far-reaching applications.
Topics: Alcohol Oxidoreductases; Bacteria; Bacterial Proteins; Lanthanoid Series Elements; Metals; Protein Transport
PubMed: 32979423
DOI: 10.1016/j.bbamcr.2020.118864 -
RSC Advances Aug 2020We studied parallel G4-mediated protein dimerization and activation by incorporating a RHAU peptide with a fluorescent protein FRET pair CFP/YFP and an apoptotic casp9....
We studied parallel G4-mediated protein dimerization and activation by incorporating a RHAU peptide with a fluorescent protein FRET pair CFP/YFP and an apoptotic casp9. Occurrence of energy tranfer (from donor CFP to acceptor YFP) and enhancement of 60-fold cleavage efficiency of casp9 were observed in the presence of parallel G4, which indicated that parallel G4 can induce dimerization and activation of proteins. This novel approach holds a great promise for studying G4-targeting functional dimeric proteins in celllular biology.
PubMed: 35518224
DOI: 10.1039/d0ra06173e -
Frontiers in Plant Science 2022The concept of "cell type," though fundamental to cell biology, is controversial. Cells have historically been classified into types based on morphology, physiology, or... (Review)
Review
The concept of "cell type," though fundamental to cell biology, is controversial. Cells have historically been classified into types based on morphology, physiology, or location. More recently, single cell transcriptomic studies have revealed fine-scale differences among cells with similar gross phenotypes. Transcriptomic snapshots of cells at various stages of differentiation, and of cells under different physiological conditions, have shown that in many cases variation is more continuous than discrete, raising questions about the relationship between cell type and cell state. Some researchers have rejected the notion of fixed types altogether. Throughout the history of discussions on cell type, cell biologists have compared the problem of defining cell type with the interminable and often contentious debate over the definition of arguably the most important concept in systematics and evolutionary biology, "species." In the last decades, systematics, like cell biology, has been transformed by the increasing availability of molecular data, and the fine-grained resolution of genetic relationships have generated new ideas about how that variation should be classified. There are numerous parallels between the two fields that make exploration of the "cell types as species" metaphor timely. These parallels begin with philosophy, with discussion of both cell types and species as being either individuals, groups, or something in between (e.g., homeostatic property clusters). In each field there are various different types of lineages that form trees or networks that can (and in some cases do) provide criteria for grouping. Developing and refining models for evolutionary divergence of species and for cell type differentiation are parallel goals of the two fields. The goal of this essay is to highlight such parallels with the hope of inspiring biologists in both fields to look for new solutions to similar problems outside of their own field.
PubMed: 36072310
DOI: 10.3389/fpls.2022.868565