The class III ribonucleotide reductase from Neisseria bacilliformis can utilize thioredoxin as a reductant

The class III anaerobic ribonucleotide reductases (RNRs) studied to date couple the reduction of ribonucleotides to deoxynucleotides with the oxidation of formate to CO[subscript 2]. Here we report the cloning and heterologous expression of the Neisseria bacilliformis class III RNR and show that it can catalyze nucleotide reduction using the ubiquitous thioredoxin/thioredoxin reductase/NADPH system. We present a structural model based on a crystal structure of the homologous Thermotoga maritima class III RNR, showing its architecture and the position of conserved residues in the active site. Phylogenetic studies suggest that this form of class III RNR is present in bacteria and archaea that carry out diverse types of anaerobic metabolism.Singapore. Agency for Science, Technology and ResearchNational Science Foundation (U.S.). Graduate Research Fellowship Program (Grant 0645960)United States. Dept. of Energy. Office of Basic Energy Sciences (Contract DE-AC02-06CH11357)National Institutes of Health (U.S.) (Grant GM29595

sj-pdf-1-pus-10.1177_09636625231217080 – Supplemental material for Communicating uncertainties regarding COVID-19 vaccination: Moderating roles of trust in science, government, and society

Supplemental material, sj-pdf-1-pus-10.1177_09636625231217080 for Communicating uncertainties regarding COVID-19 vaccination: Moderating roles of trust in science, government, and society by Jarim Kim, Jiyeon Lee, Jinha Baek and Jiyeon Ju in Public Understanding of Science</p

Validation of cost-efficient EEG experimental setup for neural tracking in an auditory attention task

Abstract When individuals listen to speech, their neural activity phase-locks to the slow temporal rhythm, which is commonly referred to as “neural tracking”. The neural tracking mechanism allows for the detection of an attended sound source in a multi-talker situation by decoding neural signals obtained by electroencephalography (EEG), known as auditory attention decoding (AAD). Neural tracking with AAD can be utilized as an objective measurement tool for diverse clinical contexts, and it has potential to be applied to neuro-steered hearing devices. To effectively utilize this technology, it is essential to enhance the accessibility of EEG experimental setup and analysis. The aim of the study was to develop a cost-efficient neural tracking system and validate the feasibility of neural tracking measurement by conducting an AAD task using an offline and real-time decoder model outside the soundproof environment. We devised a neural tracking system capable of conducting AAD experiments using an OpenBCI and Arduino board. Nine participants were recruited to assess the performance of the AAD using the developed system, which involved presenting competing speech signals in an experiment setting without soundproofing. As a result, the offline decoder model demonstrated an average performance of 90%, and real-time decoder model exhibited a performance of 78%. The present study demonstrates the feasibility of implementing neural tracking and AAD using cost-effective devices in a practical environment

Genetic Dissection of a Supergene Implicates Tfap2a in Craniofacial Evolution of Threespine Sticklebacks

In nature, multiple adaptive phenotypes often coevolve and can be controlled by tightly linked genetic loci known as supergenes. Dissecting the genetic basis of these linked phenotypes is a major challenge in evolutionary genetics. Multiple freshwater populations of threespine stickleback fish (Gasterosteus aculeatus) have convergently evolved two constructive craniofacial traits, longer branchial bones and increased pharyngeal tooth number, likely as adaptations to dietary differences between marine and freshwater environments. Prior QTL mapping showed that both traits are partially controlled by overlapping genomic regions on chromosome 21 and that a regulatory change in Bmp6 likely underlies the tooth number QTL. Here, we mapped the branchial bone length QTL to a 155 kb, eight-gene interval tightly linked to, but excluding the coding regions of Bmp6 and containing the candidate gene Tfap2a Further recombinant mapping revealed this bone length QTL is separable into at least two loci. During embryonic and larval development, Tfap2a was expressed in the branchial bone primordia, where allele specific expression assays revealed the freshwater allele of Tfap2a was expressed at lower levels relative to the marine allele in hybrid fish. Induced loss-of-function mutations in Tfap2a revealed an essential role in stickleback craniofacial development and show that bone length is sensitive to Tfap2a dosage in heterozygotes. Combined, these results suggest that closely linked but genetically separable changes in Bmp6 and Tfap2a contribute to a supergene underlying evolved skeletal gain in multiple freshwater stickleback populations

Toll-Like Receptor 3 Contributes to Wallerian Degeneration after Peripheral Nerve Injury

Objective: It is well known that Schwann cells play an important role in Wallerian degeneration after peripheral nerve injury. Previously, we reported that toll-like receptor 3 (TLR3) is expressed on Schwann cells, implicating its role in Schwann cell activation during Wallerian degeneration. In this study, we tested this possibility using TLR3 knock-out mice. Methods: Sciatic nerve-crush injury was induced in wild-type and TLR3 knock-out mice. Histological sections of the sciatic nerve were analyzed for Wallerian degeneration on days 3 and 7 after injury. The level of macrophage infiltration was measured by real-time RT-PCR, flow cytometry and immunohistochemistry. The macrophage-recruiting chemokine gene expressions in the injured nerve were determined by real-time RT-PCR. Results: In TLR3 knock-out mice, the nerve injury-induced axonal degeneration and subsequent axonal debris clearance were reduced compared to in wild-type mice. In addition, nerve injury-induced macrophage infiltration into injury sites was attenuated in TLR3 knock-out mice and was accompanied by reduced expression of macrophage-recruiting chemokines such as CC-chemokine ligands (CCL)2/MCP-1, CCL4/MIP-1β and CCL5/RANTES. These macrophage-recruiting chemokines were induced in primary Schwann cells upon TLR3 stimulation. Finally, intraneural injection of polyinosinic-polycytidylic acid, a synthetic TLR3 agonist, induced macrophage infiltration into the sciatic nerve in vivo. Conclusion: These data show that TLR3 signaling contributes to Wallerian degeneration after peripheral nerve injury by affecting Schwann cell activation and macrophage recruitment to injured nerves. © 2016 S. Karger AG, Basel.FALS

MALT Lymphoma of the Tongue in a Patient with Sjögren’s Syndrome: A Case Report and Literature Review

Sjögren’s syndrome (SS) is a systemic chronic autoimmune disorder characterized by lymphocytic infiltration of the exocrine glands, as well as oral and ocular dryness. Among the late complications, malignant lymphoma is the most serious complication of SS. The risk of lymphoma in patients with SS has been estimated to be approximately 7–19 times higher than that in a generally healthy population. Although various histologic subtypes of lymphoma can occur in patients with SS, mucosa-associated lymphoid tissue (MALT) lymphoma accounts for 48–75% of malignant lymphomas that are frequently located in the parotid gland. However, MALT lymphoma affecting the tongue in patients with SS is extremely rare. Here, we share our experience with a unique case of MALT lymphoma of the tongue, originating from the minor salivary gland tissue in a patient with SS. Through this case report, we emphasize that MALT lymphoma should be considered in the differential diagnosis of a tongue mass in patients with SS

Genetic Dissection of a Supergene Implicates Tfap2a

In nature, multiple adaptive phenotypes often coevolve and can be controlled by tightly linked genetic loci known as supergenes. Dissecting the genetic basis of these linked phenotypes is a major challenge in evolutionary genetics. Multiple freshwater populations of threespine stickleback fish (Gasterosteus aculeatus) have convergently evolved two constructive craniofacial traits, longer branchial bones and increased pharyngeal tooth number, likely as adaptations to dietary differences between marine and freshwater environments. Prior QTL mapping showed that both traits are partially controlled by overlapping genomic regions on chromosome 21 and that a regulatory change in Bmp6 likely underlies the tooth number QTL. Here, we mapped the branchial bone length QTL to a 155 kb, eight-gene interval tightly linked to, but excluding the coding regions of Bmp6 and containing the candidate gene Tfap2a Further recombinant mapping revealed this bone length QTL is separable into at least two loci. During embryonic and larval development, Tfap2a was expressed in the branchial bone primordia, where allele specific expression assays revealed the freshwater allele of Tfap2a was expressed at lower levels relative to the marine allele in hybrid fish. Induced loss-of-function mutations in Tfap2a revealed an essential role in stickleback craniofacial development and show that bone length is sensitive to Tfap2a dosage in heterozygotes. Combined, these results suggest that closely linked but genetically separable changes in Bmp6 and Tfap2a contribute to a supergene underlying evolved skeletal gain in multiple freshwater stickleback populations

Tcf7l2 plays crucial roles in forebrain development through regulation of thalamic and habenular neuron identity and connectivity

The thalamus acts as a central integrator for processing and relaying sensory and motor information to and from the cerebral cortex, and the habenula plays pivotal roles in emotive decision making by modulating dopaminergic and serotonergic circuits. These neural compartments are derived from a common developmental progenitor domain, called prosomere 2, in the caudal forebrain. Thalamic and habenular neurons exhibit distinct molecular profile, neurochemical identity, and axonal circuitry. However, the mechanisms of how their progenitors in prosomere 2 give rise to these two populations of neurons and contribute to the forebrain circuitry remains unclear. In this study, we discovered a previously unrecognized role for Tcf7l2, a transcription factor known as the canonical Wnt nuclear effector and diabetes risk-conferring gene, in establishing neuronal identity and circuits of the caudal forebrain. Using genetic and chemical axon tracers, we showed that efferent axons of the thalamus, known as the thalamocortical axons (TCAs), failed to elongate normally and strayed from their normal course to inappropriate locations in the absence of Tcf7l2. Further experiments with thalamic explants revealed that the pathfinding defects of Tcf7l2-deficient TCAs were associated at least in part with downregulation of guidance receptors Robo1 and Robo2 expression. Moreover, the fasciculus retroflexus, the main habenular output tract, was missing in embryos lacking Tcf7l2. These axonal defects may result from dysregulation of Nrp2 guidance receptor. Strikingly, loss of Tcf7l2 caused a post-mitotic identity switch between thalamic and habenular neurons. Despite normal acquisition of progenitor identity in prosomere 2, Tcf7l2-deficient thalamic neurons adopted a molecular profile of a neighboring forebrain derivative, the habenula. Conversely, habenular neurons failed to maintain their normal post-mitotic neuronal identity and acquired a subset of thalamic neuronal features in the absence of Tcf7l2. Our findings suggest a unique role for Tcf7l2 in generating distinct neuronal phenotypes from homogeneous progenitor population, and provide a better understanding of the mechanism underlying neuronal specification, differentiation, and connectivity of the developing caudal forebrain