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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 -
Frontiers in Chemistry 2023G-quadruplex-forming nucleic acids have evolved to have applications in biology, drug design, sensing, and nanotechnology, to name a few. Together with the structural...
G-quadruplex-forming nucleic acids have evolved to have applications in biology, drug design, sensing, and nanotechnology, to name a few. Together with the structural understanding, several attempts have been made to discover and design new classes of chemical agents that target these structures in the hope of using them as future therapeutics. Here, we report the binding of aminoglycosides, in particular neomycin, to parallel G-quadruplexes that exist as G-quadruplex monomers, dimers, or compounds that have the propensity to form dimeric G-quadruplex structures. Using a combination of calorimetric and spectroscopic studies, we show that neomycin binds to the parallel G-quadruplex with affinities in the range of K ∼ 10-10 M, which depends on the base composition, ability to form dimeric G-quadruplex structures, salt, and pH of the buffer used. At pH 7.0, the binding of neomycin was found to be electrostatically driven potentially through the formation of ion pairs formed with the quadruplex. Lowering the pH resulted in neomycin's association constants in the range of K ∼ 10-10 M in a salt dependent manner. Circular dichroism (CD) studies showed that neomycin's binding does not cause a change in the parallel conformation of the G-quadruplex, yet some binding-induced changes in the intensity of the CD signals were seen. A comparative binding study of neomycin and paromomycin using d(UGT) showed paromomycin binding to be much weaker than neomycin, highlighting the importance of ring I in the recognition process. , our results expanded the binding landscape of aminoglycosides where parallel G-quadruplexes have been discovered as one of the high-affinity sites. These results may offer a new understanding of some of the undesirable functions of aminoglycosides and help in the design of aminoglycoside-based G-quadruplex binders of high affinity.
PubMed: 37671393
DOI: 10.3389/fchem.2023.1232514 -
Royal Society Open Science Jan 2024Sperm whale society is structured into clans that are primarily distinguished by vocal dialects, which may be symbolic markers of clan identity. However, clans also... (Review)
Review
Sperm whale society is structured into clans that are primarily distinguished by vocal dialects, which may be symbolic markers of clan identity. However, clans also differ in non-vocal behaviour. These distinctive behaviours, as well as clan membership itself, are learned socially, largely within matrilines. The clans can contain thousands of whales and span thousands of kilometres. Two or more clans typically use an area, but the whales only socialize with members of their own clan. In many respects the closest parallel may be the ethno-linguistic groups of humans. Patterns and processes of human prehistory that may be instructive in studying sperm whale clans include: the extreme variability of human societies; no clear link between modes of resource acquisition and social structure; that patterns of vocalizations may not map well onto other behavioural distinctions; and that interacting societies may deliberately distinguish their behaviour (schismogenesis). Conversely, while the two species and their societies are very different, the existence of very large-scale social structures in both sperm whales and humans supports some primary drivers of the phenomenon that are common to both species (such as cognition, cooperation, culture and mobility) and contraindicates others (e.g. tool-making and syntactic language).
PubMed: 38204796
DOI: 10.1098/rsos.231353 -
International Journal of Molecular... Nov 2023Pathogens, especially invasive species, have caused significant global ecological, economic, and social losses in forests. Plant disease research has traditionally... (Review)
Review
Pathogens, especially invasive species, have caused significant global ecological, economic, and social losses in forests. Plant disease research has traditionally focused on direct interactions between plants and pathogens in an appropriate environment. However, recent research indicates that the microbiome can interact with the plant host and pathogens to modulate plant resistance or pathogen pathogenicity, thereby altering the outcome of plant-pathogen interactions. Thus, this presents new opportunities for studying the microbial management of forest diseases. Compared to parallel studies on human and crop microbiomes, research into the forest tree microbiome and its critical role in forest disease progression has lagged. The rapid development of microbiome sequencing and analysis technologies has resulted in the rapid accumulation of a large body of evidence regarding the association between forest microbiomes and diseases. These data will aid the development of innovative, effective, and environmentally sustainable methods for the microbial management of forest diseases. Herein, we summarize the most recent findings on the dynamic structure and composition of forest tree microbiomes in belowground and aboveground plant tissues (i.e., rhizosphere, endosphere, and phyllosphere), as well as their pleiotropic impact on plant immunity and pathogen pathogenicity, highlighting representative examples of biological control agents used to modulate relevant tree microbiomes. Lastly, we discuss the potential application of forest tree microbiomes in disease control as well as their future prospects and challenges.
Topics: Humans; Microbiota; Plants; Rhizosphere; Plant Diseases; Introduced Species; Soil Microbiology; Plant Roots
PubMed: 38003306
DOI: 10.3390/ijms242216118 -
EMBO Molecular Medicine Sep 2023SARS-CoV-2 may directly and indirectly damage lung tissue and other host organs, but there are few system-wide, untargeted studies of these effects on the human body....
SARS-CoV-2 may directly and indirectly damage lung tissue and other host organs, but there are few system-wide, untargeted studies of these effects on the human body. Here, we developed a parallelized mass spectrometry (MS) proteomics workflow enabling the rapid, quantitative analysis of hundreds of virus-infected FFPE tissues. The first layer of response to SARS-CoV-2 in all tissues was dominated by circulating inflammatory molecules. Beyond systemic inflammation, we differentiated between systemic and true tissue-specific effects to reflect distinct COVID-19-associated damage patterns. Proteomic changes in the lungs resembled those of diffuse alveolar damage (DAD) in non-COVID-19 patients. Extensive organ-specific changes were also evident in the kidneys, liver, and lymphatic and vascular systems. Secondary inflammatory effects in the brain were related to rearrangements in neurotransmitter receptors and myelin degradation. These MS-proteomics-derived results contribute substantially to our understanding of COVID-19 pathomechanisms and suggest strategies for organ-specific therapeutic interventions.
Topics: Humans; COVID-19; SARS-CoV-2; Proteomics; Inflammation; Lung
PubMed: 37519267
DOI: 10.15252/emmm.202317459 -
Neuroscience May 2024Despite recent advances in acute stroke management, most patients experiencing a stroke will suffer from residual brain damage and functional impairment. Addressing... (Review)
Review
Despite recent advances in acute stroke management, most patients experiencing a stroke will suffer from residual brain damage and functional impairment. Addressing those residual deficits would require neurorestoration, i.e., rebuilding brain tissue to repair the structural brain damage caused by stroke. However, there are major pathobiological, anatomical and technological hurdles making neurorestorative approaches remarkably challenging, and true neurorestoration after larger ischemic lesions could not yet be achieved. On the other hand, there has been steady advancement in our understanding of the limits of tissue regeneration in the adult mammalian brain as well as of the fundamental organization of brain tissue growth during embryo- and ontogenesis. This has been paralleled by the development of novel animal models to study stroke, advancement of biomaterials that can be used to support neurorestoration, and in stem cell technologies. This review gives a detailed explanation of the major hurdles so far preventing the achievement of neurorestoration after stroke. It will also describe novel concepts and advancements in biomaterial science, brain organoid culturing, and animal modeling that may enable the investigation of post-stroke neurorestorative approaches in translationally relevant setups. Finally, there will be a review of recent achievements in experimental studies that have the potential to be the starting point of research and development activities that may eventually bring post-stroke neurorestoration within reach.
PubMed: 38763225
DOI: 10.1016/j.neuroscience.2024.05.009 -
Molecular and Cellular Endocrinology Apr 2024Animals have evolved a multitude of signaling pathways that enable them to orchestrate diverse physiological processes to tightly regulate systemic homeostasis. This... (Review)
Review
Animals have evolved a multitude of signaling pathways that enable them to orchestrate diverse physiological processes to tightly regulate systemic homeostasis. This signaling is mediated by various families of peptide hormones and cytokines that are conserved across the animal kingdom. In this review, we primarily focus on the unpaired (Upd) family of proteins in Drosophila which are evolutionarily related to mammalian leptin and the cytokine interleukin 6. We summarize expression patterns of Upd in Drosophila and discuss the parallels in structure, signaling pathway, and functions between Upd and their mammalian counterparts. In particular, we focus on the roles of Upd in governing metabolic homeostasis, growth and development, and immune responses. We aim to stimulate future studies on leptin-like signaling in other phyla which can help bridge the evolutionary gap between insect Upd and vertebrate leptin and cytokines like interleukin 6.
Topics: Animals; Drosophila; Drosophila Proteins; Leptin; Interleukin-6; Cytokines; Drosophila melanogaster; Mammals
PubMed: 38266772
DOI: 10.1016/j.mce.2024.112165 -
The Journal of Pain Jan 2024In this clinical and skin biopsy study, we aimed to investigate whether fibromyalgia-associated small-fiber pathology (SFP), consisting of an intraepidermal nerve fiber...
In this clinical and skin biopsy study, we aimed to investigate whether fibromyalgia-associated small-fiber pathology (SFP), consisting of an intraepidermal nerve fiber loss, implies damage of dermal autonomic nerve fibers and how this damage is associated with autonomic symptoms that patients with fibromyalgia syndrome experience. Using skin biopsy, we investigated intraepidermal nerve fiber density, piloerector muscle, and sweat gland nerve fiber density (SGNFD) in 138 participants, that is, 58 patients with fibromyalgia syndrome, 48 healthy subjects, and 32 patients with small-fiber neuropathy. In patients with fibromyalgia-associated SFP, we also investigated how the different skin biopsy variables correlated with autonomic symptoms, as assessed with the Composite Autonomic Symptom Score 31 questionnaire. We found that in patients with fibromyalgia-associated SFP, the piloerector muscle and SGNFD were lower than that in healthy subjects. However, the autonomic small-fiber damage had no correlation with autonomic symptoms severity. In patients with SFP, the intraepidermal, piloerector muscle, and SGNFD were higher than that in patients with small-fiber neuropathy. Our clinical and skin biopsy study shows that patients with fibromyalgia have a reduction of dermal autonomic small fibers paralleling the intraepidermal nerve fiber loss, thus indicating that SFP also implies autonomic small nerve fiber damage. However, the autonomic small-fiber damage we found had no correlation with the severity of autonomic symptoms, and thus its clinical impact is still undetermined. PERSPECTIVE: In patients with fibromyalgia, SFP also affects autonomic fibers. These novel data provide additional insights into the pathophysiology of fibromyalgia syndrome, highlighting the complex role of small-fiber damage in the clinical picture of fibromyalgia.
Topics: Humans; Fibromyalgia; Skin; Nerve Fibers; Small Fiber Neuropathy; Autonomic Nervous System; Biopsy
PubMed: 37524221
DOI: 10.1016/j.jpain.2023.07.020 -
Chemical Science Aug 2023We present an automated droplet reactor platform possessing parallel reactor channels and a scheduling algorithm that orchestrates all of the parallel hardware...
We present an automated droplet reactor platform possessing parallel reactor channels and a scheduling algorithm that orchestrates all of the parallel hardware operations and ensures droplet integrity as well as overall efficiency. We design and incorporate all of the necessary hardware and software to enable the platform to be used to study both thermal and photochemical reactions. We incorporate a Bayesian optimization algorithm into the control software to enable reaction optimization over both categorical and continuous variables. We demonstrate the capabilities of both the preliminary single-channel and parallelized versions of the platform using a series of model thermal and photochemical reactions. We conduct a series of reaction optimization campaigns and demonstrate rapid acquisition of the data necessary to determine reaction kinetics. The platform is flexible in terms of use case: it can be used either to investigate reaction kinetics or to perform reaction optimization over a wide range of chemical domains.
PubMed: 37621435
DOI: 10.1039/d3sc02082g