Distinctive chemotactic responses of three marine herbivore protists to DMSP and related compounds.

Marine planktonic predator-prey interactions occur in microscale seascapes, where diffusing chemicals may act either as chemotactic cues that enhance or arrest predation, or as elemental resources that are complementary to prey ingestion. The phytoplankton osmolyte dimethylsulfoniopropionate (DMSP) and its degradation products dimethylsulfide (DMS) and acrylate are pervasive compounds with high chemotactic potential, but there is a longstanding controversy over whether they act as grazing enhancers or deterrents. Here, we investigated the chemotactic responses of three herbivorous dinoflagellates to point-sourced, microscale gradients of dissolved DMSP, DMS, and acrylate. We found no evidence for acrylate being a chemotactic repellent and observed a weak attractor role of DMS. DMSP behaved as a strong chemoattractor whose potential for grazing facilitation through effects on swimming patterns and aggregation depends on the grazer's feeding mode and ability to incorporate DMSP. Our study reveals that predation models will fail to predict grazing impacts unless they incorporate chemotaxis-driven searching and finding of prey.

Biofiltration of gaseous mixtures of dimethyl sulfide, dimethyl disulfide and dimethyl trisulfide: Effect of operational conditions and microbial analysis.

The efficient removal of volatile sulfur compounds (VSCs), such as dimethyl sulfide (DMS), dimethyl disulfide (DMDS) and dimethyl trisulfide (DMTS), is crucial due to their foul odor and corrosive potential in sewer systems. Biofilters (BFs) offer promise for VSCs removal, but face challenges related to pH control and changing conditions at full scale. Two BFs, operated under acidophilic conditions for 78 days, were evaluated for their performance at varying inlet concentrations and empty bed residence times (EBRTs). BF1, incorporating 4-6 mm marble limestone for pH control, outperformed BF2, which used NaHCO3 in the nutrient solution. BF1 displayed better resilience, maintained a stable pH of 4.6 ± 0.6, and achieved higher maximum elimination capacities (ECmax, 41 mg DMS m-3 h-1 (RE 38.3%), 146 mg DMDS m-3 h-1 (RE 83.1%), 47 mg DMTS m-3 h-1 (RE 93.1%)) at an EBRT of 56 s compared to BF2 (9 mg DMS m-3 h-1 (RE 7.1%), 9 mg DMDS m-3 h-1 (RE 4.8%) and 11 mg DMTS m-3 h-1 (RE 26.6%)). BF2 exhibited pH stratification and decreased performance after feeding interruptions. The biodegradability of VSCs followed the order DMTS > DMDS > DMS, and several microorganisms were identified contributing to VSCs degradation in BF1, including Bacillus (14%), Mycobacterium (11%), Acidiphilium (7%), and Acidobacterium (3%).

An Improved Method to Compute the Mutual Capacitance between Interdigital Transducers in Radio Frequency Surface Acoustic Wave Filters.

This paper proposes an improved method to calculate the mutual capacitance between interdigital transducer (IDT) electrodes to enhance the accuracy of the traditional coupling-of-modes (COM) model, which is commonly used to simulate surface acoustic wave (SAW) filters and duplexers. In this method, the boundary element method (BEM) is adopted to obtain the capacitance per unit length in a layered medium, while the partial capacitance (PC) method is used to derive the effective relative permittivity of the multi-layered IDT. Numerical results from commercially available software are provided for comparison with the results calculated using the proposed method. The consistent results verify the validity and accuracy of this method, which also demonstrates significantly faster calculation speed compared to commercially available software. Precise electrical response prediction of a dual-mode SAW (DMS) filter can be achieved by applying this method to the COM model, and this ultra-fast calculation method can also be included in filter design optimization.

PRKN-linked familial Parkinson's disease: cellular and molecular mechanisms of disease-linked variants.

Parkinson's disease (PD) is a common and incurable neurodegenerative disorder that arises from the loss of dopaminergic neurons in the substantia nigra and is mainly characterized by progressive loss of motor function. Monogenic familial PD is associated with highly penetrant variants in specific genes, notably the PRKN gene, where homozygous or compound heterozygous loss-of-function variants predominate. PRKN encodes Parkin, an E3 ubiquitin-protein ligase important for protein ubiquitination and mitophagy of damaged mitochondria. Accordingly, Parkin plays a central role in mitochondrial quality control but is itself also subject to a strict protein quality control system that rapidly eliminates certain disease-linked Parkin variants. Here, we summarize the cellular and molecular functions of Parkin, highlighting the various mechanisms by which PRKN gene variants result in loss-of-function. We emphasize the importance of high-throughput assays and computational tools for the clinical classification of PRKN gene variants and how detailed insights into the pathogenic mechanisms of PRKN gene variants may impact the development of personalized therapeutics.

Neuroinflammation Plays a Potential Role in the Medulla Oblongata After Moderate Traumatic Brain Injury in Mice as Revealed by Nontargeted Metabonomics Analysis.

Moderate traumatic brain injury (mTBI) involves a series of complex pathophysiological processes in not only the area in direct contact with mechanical violence but also in other brain regions far from the injury site, which may be important factors influencing subsequent neurological dysfunction or death. The medulla oblongata (MO) is a key area for the maintenance of basic respiratory and circulatory functions, whereas the pathophysiological processes after mTBI have rarely drawn the attention of researchers. In this study, we established a closed-head cortical contusion injury model, identified 6 different time points that covered the acute, subacute, and chronic phases, and then used nontargeted metabolomics to identify and analyze the changes in differential metabolites (DMs) and metabolic pathways in the MO region. Our results showed that the metabolic profile of the MO region underwent specific changes over time: harmaline, riboflavin, and dephospho-coenzyme A were identified as the key DMs and play important roles in reducing inflammation, enhancing antioxidation, and maintaining homeostasis. Choline and glycerophospholipid metabolism was identified as the key pathway related to the changes in MO metabolism at different phases. In addition, we confirmed increases in the levels of inflammatory factors and the activation of astrocytes and microglia by Western blot and immunofluorescence staining, and these findings were consistent with the nontargeted metabolomic results. These findings suggest that neuroinflammation plays a central role in MO neuropathology after mTBI and provide new insights into the complex pathophysiologic mechanisms involved after mTBI.

A Performance Analysis of Security Protocols for Distributed Measurement Systems Based on Internet of Things with Constrained Hardware and Open Source Infrastructures.

The widespread adoption of Internet of Things (IoT) devices in home, industrial, and business environments has made available the deployment of innovative distributed measurement systems (DMS). This paper takes into account constrained hardware and a security-oriented virtual local area network (VLAN) approach that utilizes local message queuing telemetry transport (MQTT) brokers, transport layer security (TLS) tunnels for local sensor data, and secure socket layer (SSL) tunnels to transmit TLS-encrypted data to a cloud-based central broker. On the other hand, the recent literature has shown a correlated exponential increase in cyber attacks, mainly devoted to destroying critical infrastructure and creating hazards or retrieving sensitive data about individuals, industrial or business companies, and many other entities. Much progress has been made to develop security protocols and guarantee quality of service (QoS), but they are prone to reducing the network throughput. From a measurement science perspective, lower throughput can lead to a reduced frequency with which the phenomena can be observed, generating, again, misevaluation. This paper does not give a new approach to protect measurement data but tests the network performance of the typically used ones that can run on constrained hardware. This is a more general scenario typical for IoT-based DMS. The proposal takes into account a security-oriented VLAN approach for hardware-constrained solutions. Since it is a worst-case scenario, this permits the generalization of the achieved results. In particular, in the paper, all OpenSSL cipher suites are considered for compatibility with the Mosquitto server. The most used key metrics are evaluated for each cipher suite and QoS level, such as the total ratio, total runtime, average runtime, message time, average bandwidth, and total bandwidth. Numerical and experimental results confirm the proposal's effectiveness in foreseeing the minimum network throughput concerning the selected QoS and security. Operating systems yield diverse performance metric values based on various configurations. The primary objective is identifying algorithms to ensure suitable data transmission and encryption ratios. Another aim is to explore algorithms that ensure wider compatibility with existing infrastructures supporting MQTT technology, facilitating secure connections for geographically dispersed DMS IoT networks, particularly in challenging environments like suburban or rural areas. Additionally, leveraging open firmware on constrained devices compatible with various MQTT protocols enables the customization of the software components, a crucial necessity for DMS.

Characterizing glucokinase variant mechanisms using a multiplexed abundance assay.

BACKGROUND: Amino acid substitutions can perturb protein activity in multiple ways. Understanding their mechanistic basis may pinpoint how residues contribute to protein function. Here, we characterize the mechanisms underlying variant effects in human glucokinase (GCK) variants, building on our previous comprehensive study on GCK variant activity. RESULTS: Using a yeast growth-based assay, we score the abundance of 95% of GCK missense and nonsense variants. When combining the abundance scores with our previously determined activity scores, we find that 43% of hypoactive variants also decrease cellular protein abundance. The low-abundance variants are enriched in the large domain, while residues in the small domain are tolerant to mutations with respect to abundance. Instead, many variants in the small domain perturb GCK conformational dynamics which are essential for appropriate activity. CONCLUSIONS: In this study, we identify residues important for GCK metabolic stability and conformational dynamics. These residues could be targeted to modulate GCK activity, and thereby affect glucose homeostasis.

Minimum information and guidelines for reporting a multiplexed assay of variant effect.

Multiplexed assays of variant effect (MAVEs) have emerged as a powerful approach for interrogating thousands of genetic variants in a single experiment. The flexibility and widespread adoption of these techniques across diverse disciplines have led to a heterogeneous mix of data formats and descriptions, which complicates the downstream use of the resulting datasets. To address these issues and promote reproducibility and reuse of MAVE data, we define a set of minimum information standards for MAVE data and metadata and outline a controlled vocabulary aligned with established biomedical ontologies for describing these experimental designs.

Biodegradable Microspheres for Transarterial Chemoembolization in Malignant Liver Disease.

Transarterial chemoembolization (TACE) has revolutionized the treatment landscape for malignant liver disease, offering localized therapy with reduced systemic toxicity. This manuscript delves into the use of degradable microspheres (DMS) in TACE, exploring its potential advantages and clinical applications. DMS-TACE emerges as a promising strategy, offering temporary vessel occlusion and optimized drug delivery. The manuscript reviews the existing literature on DMS-TACE, emphasizing its tolerability, toxicity, and efficacy. Notably, DMS-TACE demonstrates versatility in patient selection, being suitable for both intermediate and advanced stages. The unique properties of DMS provide advantages over traditional embolic agents. The manuscript discusses the DMS-TACE procedure, adverse events, and tumor response rates in HCC, ICC, and metastases.

GLP-1 receptor agonists alleviate colonic inflammation by modulating intestinal microbiota and the function of group 3 innate lymphoid cells.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs), which are drugs used for treating type 2 diabetes, have been reported to exert anti-inflammatory effects on inflammatory bowel disease (IBD), the mechanism of which remains elusive. Here, we report that GLP-1RAs ameliorate dextran sulfate sodium (DSS)-induced colitis in both wild-type and T/B-cell-deficient mice through modulating group 3 innate lymphoid cells (ILC3s), a subset of innate lymphoid cells that regulate intestinal immunity. GLP-1RAs promote IL-22 production by ILC3, and the protective effect of GLP-1RAs on DSS-induced colitis was abrogated in ILC3-deficient RORgtgfp/gfp mice. Furthermore, the treatment effect of GLP-RAs on colitis, as well as the generation of IL-22-producing ILC3s by GLP-RAs, is dependent on the gut microbiota. GLP-1RAs increase the abundance of Firmicutes and Proteobacteria in the gut, particularly beneficial bacteria such as Lactobacillus reuteri, and decrease the abundance of enteropathogenic Staphylococcus bacteria. The untargeted gas chromatography (GC)/liquid chromatography (LC)-mass spectrometry (MS) of faecal metabolites further revealed enrichment of N,N-dimethylsphingosine (DMS), an endogenous metabolite derived from sphingosine, in the GLP-1RA-treated group. Strikingly, DMS ameliorates colitis while promoting intestinal IL-22-producing ILC3s. Taken together, our findings show that GLP-1RAs exert a therapeutic effect on colitis possibly by regulating the microbiota-DMS-IL-22+ILC3 axis, highlighting the potential beneficial role of GLP-RAs in inflammatory intestinal disorders with diabetes complications.

Rugged fitness landscapes minimize promiscuity in the evolution of transcriptional repressors.

How a protein's function influences the shape of its fitness landscape, smooth or rugged, is a fundamental question in evolutionary biochemistry. Smooth landscapes arise when incremental mutational steps lead to a progressive change in function, as commonly seen in enzymes and binding proteins. On the other hand, rugged landscapes are poorly understood because of the inherent unpredictability of how sequence changes affect function. Here, we experimentally characterize the entire sequence phylogeny, comprising 1,158 extant and ancestral sequences, of the DNA-binding domain (DBD) of the LacI/GalR transcriptional repressor family. Our analysis revealed an extremely rugged landscape with rapid switching of specificity, even between adjacent nodes. Further, the ruggedness arises due to the necessity of the repressor to simultaneously evolve specificity for asymmetric operators and disfavors potentially adverse regulatory crosstalk. Our study provides fundamental insight into evolutionary, molecular, and biophysical rules of genetic regulation through the lens of fitness landscapes.

Structured 3' UTRs destabilize mRNAs in plants.

BACKGROUND: RNA secondary structure (RSS) can influence the regulation of transcription, RNA processing, and protein synthesis, among other processes. 3' untranslated regions (3' UTRs) of mRNA also hold the key for many aspects of gene regulation. However, there are often contradictory results regarding the roles of RSS in 3' UTRs in gene expression in different organisms and/or contexts. RESULTS: Here, we incidentally observe that the primary substrate of miR159a (pri-miR159a), when embedded in a 3' UTR, could promote mRNA accumulation. The enhanced expression is attributed to the earlier polyadenylation of the transcript within the hybrid pri-miR159a-3' UTR and, resultantly, a poorly structured 3' UTR. RNA decay assays indicate that poorly structured 3' UTRs could promote mRNA stability, whereas highly structured 3' UTRs destabilize mRNA in vivo. Genome-wide DMS-MaPseq also reveals the prevailing inverse relationship between 3' UTRs' RSS and transcript accumulation in the transcriptomes of Arabidopsis, rice, and even human. Mechanistically, transcripts with highly structured 3' UTRs are preferentially degraded by 3'-5' exoribonuclease SOV and 5'-3' exoribonuclease XRN4, leading to decreased expression in Arabidopsis. Finally, we engineer different structured 3' UTRs to an endogenous FT gene and alter the FT-regulated flowering time in Arabidopsis. CONCLUSIONS: We conclude that highly structured 3' UTRs typically cause reduced accumulation of the harbored transcripts in Arabidopsis. This pattern extends to rice and even mammals. Furthermore, our study provides a new strategy of engineering the 3' UTRs' RSS to modify plant traits in agricultural production and mRNA stability in biotechnology.

Test procedure for the evaluation of partially automated driving HMI including driver monitoring systems in driving simulation.

The proposed test procedure presents an approach for the evaluation of the usability of partial automated driving HMI including driver monitoring systems in driving simulation. This procedure is based on a definition of requirements that a Level 2 HMI and its included driver monitoring system must fulfill in order to guarantee that the drivers understand their responsibilities of continuously monitoring the driving environment and the status of the partial automated driving system. These requirements are used to define the evaluation criteria that have to be validated in the test as well as the use cases in which these criteria can be assessed. The result is a detailed and comprehensive test guide including the specification of the test drives, the necessary instructions, the test environment and the recruiting criteria for the test sample.•Evaluation of usability aspects of level 2 automated driving HMI including driver monitoring systems•Based on the definition of requirements for L2 HMI•Test guide including the definition of use cases, evaluation criteria and testing conditions in driving simulation.

Revealing the Marine Cycles of Volatile Sulfur Compounds and Their Biogeochemical Controls: A Case of the Western North Pacific.

Volatile sulfur compounds, such as dimethyl sulfide (DMS), carbonyl sulfide (OCS), and carbon disulfide (CS2), have significant implications for both atmospheric chemistry and climate change. Despite the crucial role of oceans in regulating their atmospheric budgets, our comprehension of their cycles in seawater remains insufficient. To address this gap, a field investigation was conducted in the western North Pacific to clarify the sources, sinks, and biogeochemical controls of these gases in two different marine environments, including relatively eutrophic Kuroshio-Oyashio extension (KOE) and oligotrophic North Pacific subtropical gyre. Our findings revealed higher concentrations of these gases in both seawater and the atmosphere in the KOE compared to the subtropical gyre. In the KOE, nutrient-rich upwelling stimulated rapid DMS biological production, while reduced seawater temperatures hindered the removal of OCS and CS2, leading to their accumulation. Furthermore, we have quantitatively evaluated the relative contribution of each pathway to the source and sink of DMS, OCS, and CS2 within the mixed layer and identified vertical exchange as a potential sink in most cases, transporting substantial amounts of these gases from the mixed layer to deeper waters. This research advances our understanding of sulfur gas source-sink dynamics in seawater, contributing to the assessment of their marine emissions and atmospheric budgets.

Relationships among the climate-relevant gases during the Southern Ocean bloom season.

The ocean plays an essential role in regulating the sources and sinks of climate-relevant gases, like CO2, N2O and dimethyl sulfide (DMS), thus influencing global climate change. Although the Southern Ocean is known to be a strong carbon sink, a significant DMS source and possibly a large source of N2O, our understanding of the interaction among these climate-relevant gases and their potential impacts on climate change is still insufficient in the Southern Ocean. Herein, we analyzed parameters, including surface water pCO2, dissolved inorganic carbon (DIC), alkalinity (TA), DMS and N2O in the water column, collected during the austral summer of 2015-2016 in the 32nd Chinese Antarctic Research Expedition (CHINARE) at the tip of Antarctic Peninsula. A positive correlation between DMS and pCO2 (indicated by deficit of DIC, ∆DIC, refer to values in 100 m) was observed in waters above 75 m, whereas no correlation between N2O saturation anomaly (SA) and DMS, ∆DIC was found. In the area with stable stratification with phytoplankton bloom, significant DMS source and strong CO2 uptake with weak N2O emission were observed. Conversely, strong mixing or upwelling area was shown to be a strong marine CO2 source and significant N2O release with weak DMS source.

Fabrication and structural and magnetic properties of spark plasma sintered group-IV diluted magnetic semiconductor Fe-doped SiGe alloys.

Fe-doped SiGe bulk alloys are fabricated using non-equilibrium spark plasma sintering (SPS) and their structure and ferromagnetic and magneto-transport properties are investigated. X-ray diffraction and high-resolution transmission electron microscope measurements show that the obtained alloys are composed of SiGe polycrystals. Magnetization measurements reveal that the Fe-doped SiGe alloys exhibit ferromagnetism up to 259 K, and their Curie temperature increases with Fe doping concentration up to 8%. Moreover, transport measurements of the Fe-doped SiGe alloys show typical metal-insulator transition characteristics of doped semiconductors as well as anomalous Hall effect and intriguing positive-to-negative magnetoresistance, indicating that the obtained alloys are diluted magnetic semiconductors (DMSs). Our results provide insight into the SPS-prepared Fe-doped SiGe bulk alloys and may be useful for the design, fabrication, and application of group-IV DMSs.

Dimethyl Sulfide (DMS) in Amarone Wines: Influence of Aging, Withering, Grape Variety, and Geographical Origin.

Occurrence of dimethyl sulfide (DMS), a potent aroma compound accumulating during aging, was investigated in commercial and experimental Amarone wines. In commercial Amarone, DMS was observed in concentrations ranging from 2.9 to 64.3 µg/L. Model aging studies on experimental wines indicated that DMS in Amarone is strongly associated with aging and that wines from different vineyards can vary significantly in their ability to accumulate DMS during aging. The capacity of certain vineyards to give wines with higher DMS-forming potential was consistent across three consecutive vintages, representing a true terroir factor to be expressed with aging. Wine content of primary amino acids (PAN), a commonly analyzed enological parameter of grape must, was shown to be positively correlated with DMS accumulation during aging. Grape withering also increased DMS-forming potential mostly due to increased PAN resulting from concentration due to water loss. Increased pH due to withering also contributed to a higher DMS content of withered wines, but to a lower extent. In certain vineyard sites, an influence of vintage conditions on DMS-forming potential was also observed.

Analysis of Telomerase RNA Structure in Physcomitrium patens Indicates Functionally Relevant Transitions Between OPEN and CLOSED Conformations.

Telomerase RNA (TR) conformation determines its function as a template for telomere synthesis and as a scaffold for the assembly of the telomerase nucleoprotein complex. Experimental analyses of TR secondary structure using DMS-Map Seq and SHAPE-Map Seq techniques show its CLOSED conformation as the consensus structure where the template region cannot perform its function. Our data show that the apparent discrepancy between experimental results and predicted TR functional conformation, mostly ignored in published studies, can be explained using data analysis based on single-molecule structure prediction from individual sequencing reads by the recently established DaVinci method. This method results in several clusters of secondary structures reflecting the structural dynamics of TR, possibly related to its multiple functional states. Interestingly, the presumed active (OPEN) conformation of TR corresponds to a minor fraction of TR under in vivo conditions. Therefore, structural polymorphism and dynamic TR transitions between CLOSED and OPEN conformations may be involved in telomerase activity regulation as a switch that functions independently of total TR transcript levels.

The production of dimethylsulfoniopropionate by bacteria with mmtN linked to non-ribosomal peptide synthase gene.

Dimethylsulfoniopropionate (DMSP) is a vital sulfur-containing compound with worldwide significance, serving as the primary precursor for dimethyl sulfide (DMS), a volatile sulfur compound that plays a role in atmospheric chemistry and influences the Earth's climate on a global scale. The study investigated the ability of four bacterial strains, namely Acidimangrovimonas sediminis MS2-2 (MS2-2), Hartmannibacter diazotrophicus E18T (E18T), Rhizobium lusitanum 22705 (22705), and Nitrospirillum iridis DSM22198 (DSM22198), to produce and degrade DMSP. These strains were assessed for their DMSP synthesis ability with the mmtN linked to non-ribosomal peptide synthase (NRPS) gene. The results showed that MS2-2, and E18T bacteria, which contained the mmtN but not linked to an NRPS gene, increased DMSP production with increasing salinity. The highest production of DMSP was achieved at 25 PSU when either methionine was added or low nitrogen conditions were present, yielding 1656.03 ± 41.04 and 265.59 ± 9.17 nmol/mg protein, respectively, and subsequently under the conditions of methionine addition or low nitrogen, both strains reached their maximum DMSP production at 25 PSU. Furthermore, the strains MS2-2, E18T, and 22705 with the mmtN gene but not linked to an NRPS gene were found to be involved in DMS production. This research contributes to the understanding of the genes involved in DMSP biosynthesis in bacteria that produce DMSP.

Dimethyl sulfate poisoning in China: a fatal case and a 45-year retrospective study.

Dimethyl sulfate (DMS) is a highly toxic chemical that appears innocuous and is commonly used as a methylating agent in industry. It can be readily absorbed leading to poisoning or death through the skin or mucous membranes of the respiratory tract in the process of production or transportation. Although there are some articles on treatment for DMS poisoning, reports of death resulting from acute fatal DMS poisoning are very rare. Here, we present a case of a 50-year-old Chinese man who died accidentally from DMS poisoning after he broke a plastic storage tank full of DMS during transportation. The patient complained of eye irritation. In addition, the corrosive damage could be seen in his corneas and skin. The autopsy revealed erosions and ulcers in the respiratory tract, as well as massive congestion, necrosis, edema, and pseudomembrane formation on the mucous layer of the trachea and main bronchi. Histopathological examination confirmed extensive pulmonary edema, multifocal hemorrhages, whole-cell swelling in the brain, as well as disintegration of the neuronal cell. We inferred that DMS poisoning caused the symptoms resulting from the production of methanol and sulfate through hydrolysis, including respiratory toxicity and neurotoxicity, and these symptoms had temporal continuity. Toxicological analysis revealed no DMS or methanol, but formic acid was detected in the brain, both qualitatively and quantitatively. In this report, we also present a retrospective study of 8 similar cases of DMS poisoning in literature in China, including some clinical data and autopsy information.