Unique Functional Roles Research Articles

The Structures, Functions, and Roles of Class III HDACs (Sirtuins) in Neuropsychiatric Diseases.

Over the past two decades, epigenetic regulation has become a rapidly growing and influential field in biology and medicine. One key mechanism involves the acetylation and deacetylation of lysine residues on histone core proteins and other critical proteins that regulate gene expression and cellular signaling. Although histone deacetylases (HDACs) have received significant attention, the roles of individual HDAC isoforms in the pathogenesis of psychiatric diseases still require further research. This is particularly true with regard to the sirtuins, class III HDACs. Sirtuins have unique functional activity and significant roles in normal neurophysiology, as well as in the mechanisms of addiction, mood disorders, and other neuropsychiatric abnormalities. This review aims to elucidate the differences in catalytic structure and function of the seven sirtuins as they relate to psychiatry.

Prevalent Fast Evolution of Genes Involved in Heterochromatin Functions.

Heterochromatin is a gene-poor and repeat-rich genomic compartment universally found in eukaryotes. Despite its low transcriptional activity, heterochromatin plays important roles in maintaining genome stability, organizing chromosomes, and suppressing transposable elements. Given the importance of these functions, it is expected that genes involved in heterochromatin regulation would be highly conserved. Yet, a handful of these genes were found to evolve rapidly. To investigate whether these previous findings are anecdotal or general to genes modulating heterochromatin, we compile an exhaustive list of 106 candidate genes involved in heterochromatin functions and investigate their evolution over short and long evolutionary time scales in Drosophila. Our analyses find that these genes exhibit significantly more frequent evolutionary changes, both in the forms of amino acid substitutions and gene copy number change, when compared to genes involved in Polycomb-based repressive chromatin. While positive selection drives amino acid changes within both structured domains with diverse functions and intrinsically disordered regions, purifying selection may have maintained the proportions of intrinsically disordered regions of these proteins. Together with the observed negative associations between the evolutionary rate of these genes and the genomic abundance of transposable elements, we propose an evolutionary model where the fast evolution of genes involved in heterochromatin functions is an inevitable outcome of the unique functional roles of heterochromatin, while the rapid evolution of transposable elements may be an effect rather than cause. Our study provides an important global view of the evolution of genes involved in this critical cellular domain and provides insights into the factors driving the distinctive evolution of heterochromatin.

Mapping the blood vasculature in an intact human kidney using hierarchical phase-contrast tomography.

The architecture of the kidney vasculature is essential for its function. Although structural profiling of the intact rodent kidney vasculature has been performed, it is challenging to map vascular architecture of larger human organs. We hypothesised that hierarchical phase-contrast tomography (HiP-CT) would enable quantitative analysis of the entire human kidney vasculature. Combining label-free HiP-CT imaging of an intact kidney from a 63-year-old male with topology network analysis, we quantitated vasculature architecture in the human kidney down to the scale of arterioles. Although human and rat kidney vascular topologies are comparable, vascular radius decreases at a significantly faster rate in humans as vessels branch from artery towards the cortex. At branching points of large vessels, radii are theoretically optimised to minimise flow resistance, an observation not found for smaller arterioles. Structural differences in the vasculature were found in different spatial zones of the kidney reflecting their unique functional roles. Overall, this represents the first time the entire arterial vasculature of a human kidney has been mapped providing essential inputs for computational models of kidney vascular flow and synthetic vascular architectures, with implications for understanding how the structure of individual blood vessels collectively scales to facilitate organ function.

Preliminary Single-Cell RNA-Sequencing Analysis Uncovers Adipocyte Heterogeneity in Lipedema.

Background: Despite its increasing incidence and prevalence throughout Western countries, lipedema continues to be a very enigmatic disease, often misunderstood or misdiagnosed by the medical community and with an intrinsic pathology that is difficult to trace. The nature of lipedemic tissue is one of hypertrophic adipocytes and poor tissue turnover. So far, there are no identified pathways responsible, and little is known about the cell populations of lipedemic fat. Methods: Adipose tissue samples were collected from affected areas of both lipedema and healthy participants. For single-cell RNA sequencing analysis, the samples were dissociated into single-cell suspensions using enzymatic digestion and then encapsulated into nanoliter-sized droplets containing barcoded beads. Within each droplet, cellular mRNA was converted into complementary DNA. Complementary DNA molecules were then amplified for downstream analysis. Results: The single-cell RNA-sequencing analysis revealed three distinct adipocyte populations at play in lipedema. These populations have unique gene signatures which can be characterized as a lipid generating adipocyte, a disease catalyst adipocyte, and a lipedemic adipocyte. Conclusions: The single-cell RNA sequencing of lipedemic tissue samples highlights a triad of distinct adipocyte subpopulations, each characterized by unique gene signatures and functional roles. The interplay between these adipocyte subtypes offers promising insights into the complex pathophysiology of lipedema.

Island biodiversity in peril: Anticipating a loss of mammals' functional diversity with future species extinctions.

Islands are biodiversity hotspots that host unique assemblages. However, a substantial proportion of island species are threatened and their long-term survival is uncertain. Identifying and preserving vulnerable species has become a priority, but it is also essential to combine this information with other facets of biodiversity like functional diversity, to understand how future extinctions might affect ecosystem stability and functioning. Focusing on mammals, we (i) assessed how much functional space would be lost if threatened species go extinct, (ii) determined the minimum number of extinctions that would cause a significant functional loss, (iii) identified the characteristics (e.g., biotic, climatic, geographic, or orographic) of the islands most vulnerable to future changes in the functional space, and (iv) quantified how much of that potential functional loss would be offset by introduced species. Using trait information for 1474 mammal species occurring in 318 islands worldwide, we built trait probability density functions to quantify changes in functional richness and functional redundancy in each island if the mammals categorized by IUCN as threatened disappeared. We found that the extinction of threatened mammals would reduce the functional space in 63% of the assessed islands, although these extinctions in general would cause a reduction of less than 15% of their overall functional space. Also, on most islands, the extinction of just a few species would be sufficient to cause a significant loss of functional diversity. The potential functional loss would be higher on small, isolated, and/or species-rich islands, and, in general, the functional space lost would not be offset by introduced species. Our results show that the preservation of native species and their ecological roles remains crucial for maintaining the current functioning of island ecosystems. Therefore, conservation measures considering functional diversity are imperative to safeguard the unique functional roles of threatened mammal species on islands.

Elucidating the structure, and composition of bacterial symbionts in the gut regions of wood-feeding termite, Coptotermes formosanus and their functional profile towards lignocellulolytic systems

The wood-feeding termite, Coptotermes formosanus, presents an efficient lignocellulolytic system, offering a distinctive model for the exploration of host-microbial symbiosis towards lignocellulose degradation. Despite decades of investigation, understanding the diversity, community structure, and functional profiles of bacterial symbionts within specific gut regions, particularly the foregut and midgut of C. formosanus, remains largely elusive. In light of this knowledge gap, our efforts focused on elucidating the diversity, community composition and functions of symbiotic bacteria inhabiting the foregut, midgut, and hindgut of C. formosanus via metagenomics. The termite harbored a diverse community of bacterial symbionts encompassing 352 genera and 26 known phyla, exhibiting an uneven distribution across gut regions. Notably, the hindgut displayed a higher relative abundance of phyla such as Bacteroidetes (56.9%) and Spirochetes (23.3%). In contrast, the foregut and midgut were predominantly occupied by Proteobacteria (28.9%) and Firmicutes (21.2%) after Bacteroidetes. The foregut harbored unique phyla like Candidate phylum_TM6 and Armatimonadetes. At the family level, Porphyromonadaceae (28.1, 40.6, and 53.5% abundance in foregut, midgut, and hindgut, respectively) and Spirochaetaceae (foregut = 9%, midgut = 16%, hindgut = 21.6%) emerged as dominant families in the termite’s gut regions. Enriched operational taxonomic units (OTUs) were most abundant in the foregut (28), followed by the hindgut (14), while the midgut exhibited enrichment of only two OTUs. Furthermore, the functional analyses revealed distinct influences of bacterial symbionts on various metabolic pathways, particularly carbohydrate and energy metabolisms of the host. Overall, these results underscore significant variations in the structure of the bacterial community among different gut regions of C. formosanus, suggesting unique functional roles of specific bacteria, thereby inspiring further investigations to resolve the crosstalk between host and microbiomes in individual gut-regions of the termite.

The molecular classification of cancer-associated fibroblasts on a pan-cancer single-cell transcriptional atlas.

Cancer-associated fibroblasts (CAFs), integral to the tumour microenvironment, are pivotal in cancer progression, exhibiting either pro-tumourigenic or anti-tumourigenic functions. Their inherent phenotypic and functional diversity allows for the subdivision of CAFs into various subpopulations. While several classification systems have been suggested for different cancer types, a unified molecular classification of CAFs on a single-cell pan-cancer scale has yet to be established. We employed a comprehensive single-cell transcriptomic atlas encompassing 12 solid tumour types. Our objective was to establish a novel molecular classification and to elucidate the evolutionary trajectories of CAFs. We investigated the functional profiles of each CAF subtype using Single-Cell Regulatory Network Inference and Clustering and single-cell gene set enrichment analysis. The clinical relevance of these subtypes was assessed through survival curve analysis. Concurrently, we employed multiplex immunofluorescence staining on tumour tissues to determine the dynamic changes of CAF subtypes across different tumour stages. Additionally, we identified the small molecule procyanidin C1 (PCC1) as a target for matrix-producing CAF (matCAF) using molecular docking techniques and further validated these findings through in vitro and in vivo experiments. In our investigation of solid tumours, we identified four molecular clusters of CAFs: progenitor CAF (proCAF), inflammatory CAF (iCAF), myofibroblastic CAF (myCAF) and matCAF, each characterised by distinct molecular traits. This classification was consistently applicable across all nine studied solid tumour types. These CAF subtypes displayed unique evolutionary pathways, functional roles and clinical relevance in various solid tumours. Notably, the matCAF subtype was associated with poorer prognoses in several cancer types. The targeting of matCAF using the identified small molecule, PCC1, demonstrated promising antitumour activity. Collectively, the various subtypes of CAFs, particularly matCAF, are crucial in the initiation and progression of cancer. Focusing therapeutic strategies on targeting matCAF in solid tumours holds significant potential for cancer treatment.

Mapping the macrostructure and microstructure of the in vivo human hippocampus using diffusion MRI.

The hippocampus is classically divided into mesoscopic subfields which contain varying microstructure that contribute to their unique functional roles. It has been challenging to characterize this microstructure with current magnetic resonance based neuroimaging techniques. In this work, we used diffusion magnetic resonance imaging (dMRI) and a novel surface-based approach in the hippocampus which revealed distinct microstructural distributions of neurite density and dispersion, T1w/T2w ratio as a proxy for myelin content, fractional anisotropy, and mean diffusivity. We used the neurite orientation dispersion and density imaging (NODDI) model optimized for grey matter diffusivity to characterize neurite density and dispersion. We found that neurite dispersion was highest in the cornu ammonis (CA) 1 and subiculum subfields which likely captures the large heterogeneity of tangential and radial fibres, such as the Schaffer collaterals, perforant path, and pyramidal neurons. Neurite density and T1w/T2w were highest in the subiculum and CA3 and lowest in CA1, which may reflect known myeloarchitectonic differences between these subfields. Using a simple logistic regression model, we showed that neurite density, dispersion, and T1w/T2w measures were separable across the subfields, suggesting that they may be sensitive to the known variability in subfield cyto- and myeloarchitecture. We report macrostructural measures of gyrification, thickness, and curvature that were in line with ex vivo descriptions of hippocampal anatomy. We employed a multivariate orthogonal projective non-negative matrix factorization (OPNNMF) approach to capture co-varying regions of macro- and microstructure across the hippocampus. The clusters were highly variable along the medial-lateral (proximal-distal) direction, likely reflecting known differences in morphology, cytoarchitectonic profiles, and connectivity. Finally, we show that by examining the main direction of diffusion relative to canonical hippocampal axes, we could identify regions with stereotyped microstructural orientations that may map onto specific fibre pathways, such as the Schaffer collaterals, perforant path, fimbria, and alveus. These results highlight the value of combining in vivo dMRI with computational approaches for capturing hippocampal microstructure, which may provide useful features for understanding cognition and for diagnosis of disease states.

Effect of central PxxP motif in amphipathic alpha-helical peptides on antimicrobial activity and mode of action

Amphipathic α-helical peptides (AHPs) have shown potential as a therapeutic approach against multi-drug-resistant bacterial infections due to their broad-spectrum antimicrobial activity by disrupting bacterial membranes. However, their nonspecific interactions with membranes often result in cytotoxicity toward mammalian cells. Previous studies have shown that a PxxP motif near the middle of cathelicidin-derived antimicrobial peptides contributes to potent and selective antibacterial activity. In this study, we compared KL18 with KL-PxxP to examine the effects of the central PxxP motif in AHPs on their structure, antibiotic activity, and mode of action. In a membrane-mimetic environment, we observed that KL18 had a much higher helical content compared to KL-PxxP. In aqueous buffer, KL18 adopted a highly ordered α-helical conformation, while KL-PxxP exhibited a disordered conformation. We found that KL-PxxP exhibited 4–16 times higher antibacterial activity than KL18 and significantly reduced the hemolytic activity. These findings suggest that the dynamic conformational behaviors caused by the central PxxP motif conferred the antibacterial selectivity of AHPs. Additionally, KL-PxxP showed strong binding to anionic liposomes and weak binding to zwitterionic liposomes, explaining its selectivity for bacteria over mammalian cells. Despite having a low ability to dissipate the bacterial membrane potential, KL-PxxP translocated efficiently across lipid membranes. Therefore, we propose that the central PxxP motif in AHPs provides dynamic conformational behavior in aqueous and membrane-mimetic environments, enhances binding to anionic membranes, and facilitates translocation across lipid bilayers, resulting in improved antibacterial potency and selectivity. Understanding the unique structural characteristics and functional roles of the PxxP motif in the antimicrobial mechanism of action holds great potential for advancing the development of novel peptide antibiotics.

Abstract B058: Exploring the oncogenic role of six-transmembrane epithelial antigen of the prostate in the context of androgen receptor signaling

Abstract Prostate cancer is the second leading cause of death among American men, where pathogenesis is predominantly driven by dysregulation of the Androgen Receptor (AR). The current standard of care for metastatic disease includes a regime of androgen deprivation therapy (ADT) and AR antagonists, which increases survival to 24-48 months. Selective pressure of the therapy often leads to resurgence of AR activity resulting in castrate resistant disease, for which there are no curative treatment options. Moreover, once the disease has progressed to castrate resistance, AR directed therapies are no longer viable as a sole treatment option. Six-Transmembrane Epithelial Antigen of the Prostate 1-4 (STEAP) proteins are a family of ferric metalloreductases involved in maintaining iron homeostasis. STEAP expression is enriched in androgen sensitive and hormone refractory disease states, where increased expression correlates with high Gleason Score. STEAP proteins display greater intratumoral homogeneity at both primary and metastatic sites than the canonically used Prostate Specific Membrane Antigen (PSMA), indicating attractive diagnostic and therapeutic potential. Differential expression profiles have been observed among the STEAP family members depending on AR status in-vitro, suggesting a dependence on the AR signaling network. Previous literature indicates silencing of STEAPs in-vitro decreased cell viability and reduced proliferative, invasive, and migratory phenotypes; moreover in-vivo xenografts in which STEAPs are knocked down exhibited a significant reduction in tumor growth. Preliminary data suggests that treatment with Enzalutamide reduces the expression of STEAP proteins, implying a mechanistic link to the AR signaling axis. AMG509, a bispecific STEAP1-CD3 antibody, is the only STEAP directed therapeutic actively in clinical trials for prostate cancer (NCT04221542). There is limited mechanistic data regarding how STEAP directed therapies exert their anti-tumor function. Despite sharing similar architecture, localization, and biological implications, each STEAP protein retains unique functional roles within the cell. We plan to perform a systematic investigation on the oncogenic roles of individual STEAP protein in the context of AR dependent and independent prostate cancer models. In-vitro pharmacological AR manipulations will be used to evaluate changes in STEAP expression in multiple disease models. Genetic manipulations of STEAPs will be carried out under normal growth and ADT conditions to investigate the effects on growth, migration, oxidative stress, and cell cycle regulation. Given their principal role as ferric reductases, iron supplementation and iron drop-out will be examined in parallel. Novel treatment regimens will be explored using a combination of AR and STEAP directed therapeutics. Collectively, this study aims to uncover both the overlapping and distinct functions of STEAP proteins within the AR signaling axis and to illuminate their usefulness as a therapeutic target. Citation Format: Candice Bizzaro, Latese Evens, Moriah Cunningham, Jasibel Vasquez Gonzalez, Matthew Schiewer. Exploring the oncogenic role of six-transmembrane epithelial antigen of the prostate in the context of androgen receptor signaling [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr B058.

Neotropical mixed-species bird flocks in a community context.

Mixed-species flocks are an important component of bird communities, particularly in the Neotropics, where flocks reach their highest diversity. The extent to which mixed-species flocks represent unique functional or ecological roles within communities, and how these attributes change over environmental gradients, however, is not well understood. We use a trait-based approach to examine functional aspects of flocking assemblages as they relate to those observed in the larger avian community across a 3000 m elevational gradient. Our results reveal similar ecological strategies among flocking species and the communities in which they occur, at the scale of the regional pool and across elevations. Trait variation in flocking and non-flocking assemblages is structured along two major axes defined by size- and resource-related traits. The trait space occupied by flocking species, however, represents only half (51%) that of the larger community. Similarly, the trait space of flocks across elevations is restricted compared to non-flocking species. The shared trait space across flock types represents small-bodied invertivores foraging in lower forest strata, traits associated with increased vulnerability to predation. The concentration of flocking species in functional trait space suggests high niche packing and either more overlap in ecological strategies or more finely divided niches relative to non-flocking species. This article is part of the theme issue 'Mixed-species groups and aggregations: shaping ecological and behavioural patterns and processes'.

Single-cell analysis of human nasal mucosal IgE antibody secreting cells reveals a newly minted phenotype

Immunoglobulin (Ig) E is central to the pathogenesis of allergic conditions, including allergic fungal rhinosinusitis. However, little is known about IgE antibody secreting cells (ASCs). We performed single-cell RNA sequencing from cluster of differentiation (CD)19+ and CD19- ASCs of nasal polyps from patients with allergic fungal rhinosinusitis (n=3). Nasal polyps were highly enriched in CD19+ ASCs. Class-switched IgG and IgA ASCs were dominant (95.8%), whereas IgE ASCs were rare (2%) and found only in the CD19+ compartment. Through Ig gene repertoire analysis, IgE ASCs shared clones with IgD-CD27- "double-negative" B cells, IgD+CD27+ unswitched memory B cells, and IgD-CD27+ switched memory B cells, suggesting ontogeny from both IgD+ and memory B cells. Transcriptionally, mucosal IgE ASCs upregulate pathways related to antigen presentation, chemotaxis, B cell receptor stimulation, and survival compared with non-IgE ASCs. Additionally, IgE ASCs have a higher expression of genes encoding lysosomal-associated protein transmembrane 5 (LAPTM5) and CD23, as well as upregulation of CD74 (receptor for macrophage inhibitory factor), store-operated Calcium entry-associated regulatory factor (SARAF), and B cell activating factor receptor (BAFFR), which resemble an early minted ASC phenotype. Overall, these findings reinforce the paradigm that human ex vivo mucosal IgE ASCs have a more immature plasma cell phenotype than other class-switched mucosal ASCs and suggest unique functional roles for mucosal IgE ASCs in concert with Ig secretion.

CA2 orchestrates hippocampal network dynamics.

The hippocampus is composed of various subregions: CA1, CA2, CA3, and the dentate gyrus (DG). Despite the abundant hippocampal research literature, until recently, CA2 received little attention. The development of new genetic and physiological tools allowed recent studies characterizing the unique properties and functional roles of this hippocampal subregion. Despite its small size, the cellular content of CA2 is heterogeneous at the molecular and physiological levels. CA2 has been heavily implicated in social behaviors, including social memory. More generally, the mechanisms by which the hippocampus is involved in memory include the reactivation of neuronal ensembles following experience. This process is coordinated by synchronous network events known as sharp-wave ripples (SWRs). Recent evidence suggests that CA2 plays an important role in the generation of SWRs. The unique connectivity and physiological properties of CA2 pyramidal cells make this region a computational hub at the core of hippocampal information processing. Here, we review recent findings that support the role of CA2 in coordinating hippocampal network dynamics from a systems neuroscience perspective.

Exploring the Antibiotic Production Potential of Heterotrophic Bacterial Communities Isolated from the Marine Sponges Crateromorpha meyeri, Pseudaxinella reticulata, Farrea similaris, and Caulophacus arcticus through Synergistic Metabolomic and Genomic Analyses.

The discovery of novel secondary metabolites is actively being pursued in new ecosystems. Sponge-associated bacteria have been in the limelight in recent years on account of their ability to produce bioactive compounds. In this study, heterotrophic bacteria associated with four sponge species were isolated, taxonomically identified, and subjected to screening for the production of bioactive entities against a panel of nine microorganisms, including Gram-positive and negative bacteria, as well as yeast and fungi. Of the 105 isolated strains, 66% were represented by Proteobacteria, 16% by Bacteriodetes, 7% by Actinobacteria, and 11% by Firmicutes. Bioactivity screening revealed that 40% of the total isolated strains showed antimicrobial activity against one or more of the target microorganisms tested. Further, active extracts from selective species were narrowed down by bioassay-guided fractionation and subsequently identified by HR-ESI-MS analyses to locate the active peaks. Presumably responsible compounds for the observed bioactivities were identified as pentadecenoic acid, oleic acid, and palmitoleic acid. One isolate, Qipengyuania pacifica NZ-96T, based on 16S rRNA novelty, was subjected to comparative metabolic reconstruction analysis with its closest phylogenetic neighbors, revealing 79 unique functional roles in the novel isolate. In addition, genome mining of Qipengyuania pacifica NZ-96T revealed three biosynthetic gene clusters responsible for the biosynthesis of terpene, beta lactone, lasso peptide, and hserlactone secondary metabolites. Our results demonstrate the ability to target the sponge microbiome as a potential source of novel microbial life with biotechnological potential.

Dynamics and functional roles of splicing factor autoregulation.

SUMMARYNon-core spliceosome components are essential, conserved regulators of alternative splicing. They provide concentration-dependent control of diverse pre-mRNAs. Many splicing factors direct unproductive splicing of their own pre-mRNAs through negative autoregulation. However, the impact of such feedback loops on splicing dynamics at the single-cell level remains unclear. Here, we developed a system to quantitatively analyze negative autoregulatory splicing dynamics by splicing factor SRSF1 in response to perturbations in single HEK293 cells. We show that negative autoregulatory splicing provides critical functions for gene regulation, establishing a ceiling of SRSF1 protein concentration, reducing cell-cell heterogeneity in SRSF1 levels, and buffering variation in transcription. Most important, it adapts SRSF1 splicing activity to variations in demand from other pre-mRNA substrates. A minimal mathematical model of autoregulatory splicing explains these experimentally observed features and provides values for effective biochemical parameters. These results reveal the unique functional roles that splicing negative autoregulation plays in homeostatically regulating transcriptional programs.

Functional structure of European forest beetle communities is enhanced by rare species

Biodiverse communities have been shown to sustain high levels of multifunctionality and thus a loss of species likely negatively impacts ecosystem functions. For most taxa, however, roles of individual species are poorly known. Rare species, often most likely to go extinct, may have unique traits and functional roles. Alternatively, rare species may be functionally redundant, such that their loss would not disrupt ecosystem functions. We quantified the functional role of rare species by using captures of wood-living (saproxylic) beetle species, combined with recent databases of morphological and ecological traits, from three regions in central and northern Europe. Using a rarity index based on species' local abundance, geographic range, and habitat breadth, we used local and regional species removal simulations to examine the contributions of both the rarest and the most common beetle species to three measures of community functional structure: functional richness, functional specialization, and functional originality. Both regionally and locally, all three measures declined more rapidly when rare species were removed than under common (or random) species removal scenarios. These consistent patterns across scales and among forest types give evidence that rare species provide unique functional contributions, and their loss may disproportionately impact ecosystem functions. This implies that conservation measures targeting rare and endangered species, such as preserving intact forests with dead wood and mature trees, can provide broader ecosystem-level benefits. Experimental research linking functional structure to ecosystem processes should be prioritized to increase understanding of the functional consequences of species loss and to develop more effective conservation strategies.

Multifunctional Organic Single‐Crystalline Microwire Arrays toward Optical Applications

AbstractSingle‐crystalline micro‐/nanostructures based on organic stimulus‐responsive materials have attracted wide interests for their unique functional roles in various photonic applications including optical wave guiding, optical vapor sensing, and miniaturized lasing. Yet one imminent challenge is to pattern micro‐/nanostructured organic 1D arrays with controlled geometry, precise alignment, and pure crystallographic orientation owing to the uncontrollable dewetting dynamics in the solution processes. Herein, a smart assembly method is employed to regulate a confined crystallization of organic molecules. Sensitive, stable, and reproducible optical 1D‐array vapor sensors can detect the alkaline and acidic vapors based on the proton transfer process. As‐fabricated vapor sensors based on organic 1D arrays also selectively identify four similar amine vapors. Meanwhile, based on these 1D microstructure arrays, high‐performing Fabry–Pérot resonators with deep‐red laser emission, a low lasing threshold of 0.31 µJ, and high quality factor Q (≈2243) are realized. Owing to these multiple functions, organic microwire arrays not only provide intrinsic insight into optical vapor sensing but also offer guidance for the development of miniaturized lasers with specific functionalities, which show considerable potential in multifunctional photonic integrated circuits.

Cloning of the xylanase gene from soil Streptomyces into Escherichia coli for the poultry industry application

Streptomyces are gram-positive aerobic strains that are isolated from soil, water, sediments, and various sources. The bacteria are capable of producing secondary metabolites, such as enzymes that sometimes play unique functional roles in industry, and are one of the important bio-control agents. This study aimed to isolate and clone thexylanase gene from soil Streptomyces. Soil samples were collected from Markazi Province, Iranafter specific biochemical examinations, isolation of bacteria, and DNA extraction. PCR was then performed to identify the strains containing the xylanase gene. The gene from the positive strains was cloned into an E.coli host-vector by TA cloning technique and finally, the expression of genes in E. coli origami was measured by Real-Time PCR technique. ClustalX and Mega5 software were used to draw the phylogenetic tree. A total of twelve Streptomyces isolates were identified from the soil samples. Among all the isolates, threeones had the xylanase gene. After cloning the xylanase genes, the cloned strains were isolated. To confirm the DNA cloning, Real-Time PCR was performed, and finally, the PCR product where sequenced. In this study, Streptomyces was identified as a native strain for the expression of xylanase after generating recombinant plasmid and TA cloning. It can be stated that cloning of the xylanase gene from soil Streptomyces in E. coli can be used in the poultry industry.

Flexible Recruitments of Fundamental Muscle Synergies in the Trunk and Lower Limbs for Highly Variable Movements and Postures.

The extent to which muscle synergies represent the neural control of human behavior remains unknown. Here, we tested whether certain sets of muscle synergies that are fundamentally necessary across behaviors exist. We measured the electromyographic activities of 26 muscles, including bilateral trunk and lower limb muscles, during 24 locomotion, dynamic and static stability tasks, and we extracted the muscle synergies using non-negative matrix factorization. Our results show that 13 muscle synergies that may have unique functional roles accounted for almost all 24 tasks by combinations of single and/or merging of synergies. Therefore, our results may support the notion of the low dimensionality in motor outputs, in which the central nervous system flexibly recruits fundamental muscle synergies to execute diverse human behaviors. Further studies are required to validate the neural representation of the fundamental components of muscle synergies.

Dynamics and Functional Roles of Splicing Factor Autoregulation

Non-spliceosomal splicing factors are essential, conserved regulators of alternative splicing. They provide concentration-dependent control of diverse pre-mRNAs. Many splicing factors direct unproductive splicing of their own pre-mRNAs through negative autoregulation. However, the impact of such feedback loops on splicing dynamics at the single cell level remains unclear. Here, we developed a system to quantitatively analyze negative autoregulatory splicing dynamics by splicing factor SRSF1 in response to perturbations in single HEK293 cells. We show that negative autoregulatory splicing provides critical functions for gene regulation, establishing a ceiling of SRSF1 protein concentration, reducing cell-cell heterogeneity in SRSF1 levels, and buffering variation in transcription. Most importantly, it adapts SRSF1 splicing activity to variations in demand from other pre-mRNA substrates. A minimal mathematical model of autoregulatory splicing explains these experimentally observed features and provides values for effective biochemical parameters. These results reveal unique functional roles that splicing negative autoregulation plays in homeostatically regulating transcriptional programs.