Global insights into keloid formation: An international systematic review of regional genetic risk factors and commonalities.

Keloid disorder is a morbid and disfiguring benign fibroproliferative disease with a higher incidence in groups with darker skin pigmentation. Predicting keloidogenesis in patients is difficult with treatment primarily aimed at preventing further scar expansion and improving aesthetics without addressing their unknown underlying pathophysiology. We aimed to identify potential genetic predispositions to keloid scarring in the literature. A search was conducted on 21 August 2023, by the first and second authors independently from 1985 to August 2023 using PubMed, MEDLINE, Embase, Web of Science, Scopus and CINAHL. The following MeSH terms were used: 'Keloid', 'Risk' and 'Genetic'. Two researchers independently searched for studies based on titles and abstracts and screened filtered articles by reviewing full text. If no agreement could be reached, a third senior author designated whether the article should be included. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement as the basis of our organisation. Human studies with genetic analysis to determine an association of a protein or gene to keloidogenesis were selected for inclusion. Studies in languages other than English, reviews, conference articles, and book chapters were excluded. Fifty studies met inclusion criteria. The human leukocyte antigen (HLA) system was broadly implicated, and the DRB1*15 allele was associated with an increased risk of keloid in three separate ethnic groups. Some HLA Class I alleles were associated with keloid in one population but not in others. Additionally, polymorphisms in the E3 ubiquitin-protein ligase (NEDD4) signal cascade and vitamin D receptor (VDR) have been implicated in diverse groups. No current genetic test can predict keloid risk. Our review identified candidate predisposing genes, including NEDD4, VDR and components of the HLA system. Further studies in heterogeneous populations are needed to identify reliable screening targets.

Development of an electrochemical sensor for the quantification of ascorbic acid and acetaminophen in pharmaceutical samples.

This work presents the modification of glassy carbon electrodes (GCE) by using a dispersion resulting from the non-covalent functionalization of multi-walled carbon nanotubes (MWCNT) with polyarginine (polyArg). MWCNT-polyArg is used for the quantification of ascorbic acid (AA) in the presence of acetaminophen (APAP) and viceversa. Since ascorbic acid and acetaminophen are strongly absorbed on GCE/MWCNT-polyArg, they can be detected in the presence of 4.0×10-5 M acetaminophen (and 3.0×10-5 M ascorbic acid) by using adsorptive stripping with media exchange and differential pulse voltammetry. Using water as the solvent for the MWCNT dispersion, the result was Z-potential of 0.053 ± 0.006 V. The developed sensor showed excellent specificity, sensitivity, stability and reproducibility compared to previously published sensors. The GCE/MWCNT-polyArg sensor shows a fast response time of ∼5 minutes, low limits of detection and quantification for AA (0.95 and 2.9 µM respectively) and APAP (0.27 and 0.82µM, respectively), high sensitivity of 0.0616 µA/M for AA or APAP 0.240µA/M. It was used to test its practicability by determining the concentration of AA or APAP (AA and APAP) in pharmaceutical samples. Finally, the simultaneous measurement of ascorbic acid and acetaminophen in pharmaceuticals showed a good correlation, with a maximum error and RSD of 4.5 and 5.1 %, respectively.

APTES functionalization in SBA-15: the effect on SO2 capture and detection applications.

The development of adsorbents for air pollutant remediation and effective monitoring is of interest. Then, the effect of the APTES functionalization ratio on the impact of the adsorption and detection of SO2 molecules was evaluated. The higher APTES functionalization material (SBA-15_6.1APTES) shows a high uptake of 1.15 mmol g-1 at 0.001 bar and 298 K. Fluorescence, time-resolved photoluminescence, and quantum yield experiments revealed a turn-on effect specifically for SO2 molecules, indicating high selectivity, suggesting host-to-guest energy transfer. Attractively, XPS measurement provided an understanding of the mechanism, suggesting hydrogen bonding and dipole-dipole interactions as the main interactions between SO2 molecules and SBA-15_6.1APTES. DFT calculations were performed to confirm these interactions. Furthermore, this study highlights the application of SBA-15 materials with different amino modifications for SO2 treatment and provides insight into the interaction mechanism using experimental techniques.

Cooling rate uncovers epimer-dependent supramolecular organization of carbohydrate amphiphiles.

We show distinct CH-π interactions and assembly pathways for the amphiphile N-(fluorenylmethoxycarbonyl)-galactosamine and its epimer N-(fluorenylmethoxycarbonyl)-glucosamine. These differences result in the formation of supramolecular nanofibrous systems with opposite chirality. Our results showcase the importance of the carbohydrates structural diversity for their specific biointeractions and the opportunity that their ample interactome offers for synthesis of versatile and tunable supramolecular (bio) materials.

Early mutational signatures and transmissibility of SARS-CoV-2 Gamma and Lambda variants in Chile.

Genomic surveillance (GS) programmes were crucial in identifying and quantifying the mutating patterns of SARS-CoV-2 during the COVID-19 pandemic. In this work, we develop a Bayesian framework to quantify the relative transmissibility of different variants tailored for regions with limited GS. We use it to study the relative transmissibility of SARS-CoV-2 variants in Chile. Among the 3443 SARS-CoV-2 genomes collected between January and June 2021, where sampling was designed to be representative, the Gamma (P.1), Lambda (C.37), Alpha (B.1.1.7), B.1.1.348, and B.1.1 lineages were predominant. We found that Lambda and Gamma variants' reproduction numbers were 5% (95% CI: [1%, 14%]) and 16% (95% CI: [11%, 21%]) larger than Alpha's, respectively. Besides, we observed a systematic mutation enrichment in the Spike gene for all circulating variants, which strongly correlated with variants' transmissibility during the studied period (r = 0.93, p-value = 0.025). We also characterised the mutational signatures of local samples and their evolution over time and with the progress of vaccination, comparing them with those of samples collected in other regions worldwide. Altogether, our work provides a reliable method for quantifying variant transmissibility under subsampling and emphasises the importance of continuous genomic surveillance.

Fasting glucose: a cardiometabolic indicator for subclinical atherosclerosis on excess weight adolescents

Abstract Objective: To build a model based on cardiometabolic indicators that allow the identification of overweight adolescents at higher risk of subclinical atherosclerotic disease (SAD). Methods: Cross-sectional study involving 161 adolescents with a body mass index ≥ + 1 z-Score, aged 10 to 19 years. Carotid intima-media complex thickness (IMT) was evaluated using ultrasound to assess subclinical atherosclerotic disease. Cardiometabolic indicators evaluated included nutritional status, central adiposity, blood pressure, lipidic profile, glycemic profile, as well as age and sex. Data was presented using measures of central tendency and dispersion, as well as absolute and relative frequency. The relationship between IMT measurement (outcome variable) and other variables (independent variables) was assessed using Pearson or Spearman correlation, followed by multiple regression modeling with Gamma distribution to analyze predictors of IMT. Statistical analysis was performed using SPSS and R software, considering a significance level of 5 %. Results: It was observed that 23.7 % had Carotid thickening, and the prevalence of abnormal fasting glucose was the lowest. Age and fasting glucose were identified as predictors of IMT increase, with IMT decreasing with age by approximately 1 % per year and increasing with glucose by around 0.24 % per mg/dL. Conclusion: The adolescent at higher risk is younger with higher fasting glycemia levels.

Photorhabdus africana sp. nov. isolated from Heterorhabditis entomopathogenic nematodes.

One Gram-negative, rod-shaped bacterial strain, isolated from an undescribed Heterorhabditis entomopathogenic nematode species was characterized to determine its taxonomic position. The 16S rRNA gene sequences indicate that it belongs to the class Gammaproteobacteria, to the family Morganellaceae, to the genus Photorhabdus, and likely represents a novel bacterial species. This strain, designated here as CRI-LCT, was therefore molecularly, biochemically, and morphologically characterized to describe the novel bacterial species. Phylogenetic reconstructions using 16S rRNA gene sequences show that CRI-LCT is closely related to P. laumondii subsp. laumondii TT01T and to P. laumondii subsp. clarkei BOJ-47T. The 16rRNA gene sequences between CRI-LCT and P. laumondii subsp. laumondii TT01T are 99.1% identical, and between CRI-LCT and P. laumondii subsp. clarkei BOJ-47T are 99.2% identical. Phylogenetic reconstructions using whole genome sequences show that CRI-LCT is closely related to P. laumondii subsp. laumondii TT01T and to P. laumondii subsp. clarkei BOJ-47T. Moreover, digital DNA-DNA hybridization (dDDH) values between CRI-LCT and its two relative species P. laumondii subsp. laumondii TT01T and P. laumondii subsp. clarkei BOJ-47T are 65% and 63%, respectively. In addition, we observed that average nucleotide identity (ANI) values between CRI-LCT and its two relative species P. laumondii subsp. laumondii TT01T and P. laumondii subsp. clarkei BOJ-47T are 95.8% and 95.5%, respectively. These values are below the 70% dDDH and the 95-96% ANI divergence thresholds that delimits prokaryotic species. Based on these genomic divergence values, and the phylogenomic separation, we conclude that CRI-LCT represents a novel bacterial species, for which we propose the name Photorhabdus africana sp. nov. with CRI-LCT (= CCM 9390T = CCOS 2112T) as the type strain. The following biochemical tests allow to differentiate P. africana sp. nov. CRI-LCT from other species of the genus, including its more closely related taxa: ß-Galactosidase, citrate utilization, urease and tryptophan deaminase activities, indole and acetoin production, and glucose and inositol oxidation. Our study contributes to a better understanding of the taxonomy and biodiversity of this important bacterial group with great biotechnological and agricultural potential.

Mode of Onset Modifies the Effect of Time to Endovascular Reperfusion on Clinical Outcomes after Acute Ischemic Stroke: An Analysis of the DAWN Trial.

OBJECTIVE: We aimed to assess the impact of time to endovascular thrombectomy (EVT) on clinical outcomes in the DAWN trial, while also exploring the potential effect modification of mode of stroke onset on this relationship. METHODS: The association between every 1-h treatment delay with 90-day functional independence (modified Rankin Scale [mRS] score 0-2), symptomatic intracranial hemorrhage, and 90-day mortality was explored in the overall population and in three modes of onset subgroups (wake-up vs. witnessed vs. unwitnessed). RESULTS: Out of the 205 patients, 98 (47.8%) and 107 (52.2%) presented in the 6 to 12 hours and 12 to 24 hours time window, respectively. Considering all three modes of onset together, there was no statistically significant association between time last seen well to randomization with either functional independence or mortality at 90 days in either the endovascular thrombectomy (mRS 0-2 1-hour delay OR 1.07; 95% CI 0.93-1.24; mRS 6 OR 0.84; 95% CI 0.65-1.03) or medical management (mRS 0-2 1-hour delay OR 0.98; 95% CI 0.80-1.14; mRS 6 1-hour delay OR 0.94; 95% CI 0.79-1.09) groups. Moreover, there was no significant interaction between treatment effect and time (p = 0.439 and p = 0.421 for mRS 0-2 and 6, respectively). However, within the thrombectomy group, the models that tested the association between time last seen well to successful reperfusion (modified Treatment in Cerebral Infarction ≥2b) and 90-day functional independence showed a significant interaction with mode of presentation (p = 0.013). This appeared to be driven by a nominally positive slope for both witnessed and unwitnessed strokes versus a significantly (p = 0.018) negative slope in wake-up patients. There was no association between treatment times and symptomatic intracranial hemorrhage. INTERPRETATION: Mode of onset modifies the effect of time to reperfusion on thrombectomy outcomes, and should be considered when exploring different treatment paradigms in the extended window. ANN NEUROL 2024;96:356-364.

Exploring the role of casein kinase 1α splice variants across cancer cell lines.

Casein kinase 1α (CK1α) is a serine/threonine protein kinase that acts in various cellular processes affecting cell division and signal transduction. CK1α is present as multiple splice variants that are distinguished by the presence or absence of a long insert (L-insert) and a short carboxyl-terminal insert (S-insert). When overexpressed, zebrafish CK1α splice variants exhibit different biological properties, such as subcellular localization and catalytic activity. However, whether endogenous, alternatively spliced CK1α gene products also differ in their biological functions has yet to be elucidated. Here, we identify a panel of splice variant specific CK1α antibodies and use them to show that four CK1α splice variants are expressed in mammals. We subsequently show that the relative abundance of CK1α splice variants varies across distinct mouse tissues and between various cancer cell lines. Furthermore, we identify pathways whose expression is noticeably altered in cell lines enriched with select splice variants of CK1α. Finally, we show that the S-insert of CK1α promotes the growth of HCT 116 cells as cells engineered to lack the S-insert display decreased cell growth. Together, we provide tools and methods to identify individual CK1α splice variants, which we use to begin to uncover the differential biological properties driven by specific splice variants of mammalian CK1α.

Latin-American guidelines of recommendations at discharge from an acute coronary syndrome.

The diagnostic criteria, treatments at the time of admission, and drugs used in patients with acute coronary syndrome are well defined in countless guidelines. However, there is uncertainty about the measures to recommend during patient discharge planning. This document brings together the most recent evidence and the standardized and optimal treatment for patients at the time of discharge from hospitalization for an acute coronary syndrome, for comprehensive and safe care in the patient's transition between care from the acute event to the outpatient care, with the aim of optimizing the recovery of viable myocardium, guaranteeing the most appropriate secondary prevention, reducing the risk of a new coronary event and mortality, as well as the adequate reintegration of patients into daily life.

Los criterios diagnósticos, los tratamientos en el momento de la admisión y los fármacos utilizados en pacientes con síndrome coronario agudo están bien definidos en innumerables guías. Sin embargo, existe incertidumbre acerca de las medidas para recomendar durante la planificación del egreso de los pacientes. Este documento reúne las evidencias más recientes y el tratamiento estandarizado y óptimo para los pacientes al momento del egreso de una hospitalización por un síndrome coronario agudo, para un cuidado integral y seguro en la transición del paciente entre la atención del evento agudo y el cuidado ambulatorio, con el objetivo de optimizar la recuperación de miocardio viable, garantizar la prevención secundaria más adecuada, reducir el riesgo de un nuevo evento coronario y la mortalidad, así como la adecuada reinserción de los pacientes en la vida cotidiana.

Sustainable Plantwide Optimizing Control for an Acrylic Acid Process.

This paper presents a sustainable control strategy from a plantwide control (PWC) perspective. The proposed strategy is subjected to testing within an operational environment of an acrylic acid plant. To integrate sustainability tools into the plantwide optimizing control (PWOC) formulation, the present proposal suggests the utilization of green chemistry principles. These principles will be incorporated as constraints within the optimization problem. A comparative analysis is conducted between the proposed sustainable PWOC approach and two alternative structures: a PWOC framework that does not take sustainability issues into account and a conventional PWC structure. The findings indicate that the sustainable PWOC demonstrates superior economic performance from a financial standpoint, reaching the highest cumulative profitability(1.6274 × 105 USD), exceeding 11.94% in comparison to the PWOC without sustainability concerns, which reach a cumulative profitability of 1.4330 × 105 USD, and surpassing 13.01% when compared to the decentralized PWC approach, which reach a cumulative profitability of 1.4158 × 105 USD. Additionally, the sustainable PWOC demonstrated a reduced emission impact on the process, with a decrease of 6.17% compared to the unsustainable PWOC and a 9.79% decrease compared to the decentralized approach. This demonstrates that the incorporation of the proposed green chemistry metrics as an explicit component of the formulated PWC problem significantly mitigates the impacts of global warming and human health.

The Fe-MAN Challenge: Ferrates-Microkinetic Assessment of Numerical Quantum Chemistry.

Organometallic species, such as organoferrate ions, are prototypical nucleophiles prone to reacting with a wide range of electrophiles, including proton donors. In solution, the operation of dynamic equilibria and the simultaneous presence of several organometallic species severely complicate the analysis of these fundamentally important reactions. This can be overcome by gas-phase experiments on mass-selected ions, which allow for the determination of the microscopic reactivity of the target species. In this contribution, we focus on the reactivity of a series of trisarylferrate complexes toward 2,2,2-trifluoroethanol and 2,2-difluoroethanol. By means of mass-spectrometric measurements, we determined the experimental bimolecular rate constants kexp of the gas-phase protolysis reactions of the trisarylferrate anions FePh3- and FeMes3- with the aforementioned acids. Based on these experiments, we carried out a dual blind challenge, inviting theoretical groups to submit their best predictions for the activation barriers and/or theoretical rate constants ktheo. This provides a unique opportunity to evaluate different computational protocols under minimal bias and sets the stage for further benchmarking of quantum chemical methods and data-driven approaches in the future.

Multicenter early United States feasibility study and periprocedural safety of LVIS EVO for the treatment of unruptured intracranial aneurysms.

BACKGROUND: Stent development has focused recently on low-profile, self-expandable stents compatible with 0.0165 inch microcatheters. The LVIS EVO is the second-generation version of the Low-Profile Visualized Intraluminal Support (LVIS) with improved visibility and resheathability. The LVIS EVO underwent a limited premarket release (PMR) in December 2023. This study aims to report the early safety and feasibility experience with the LVIS EVO stent for the treatment of intracranial aneurysms in the United States (US). METHODS: This was a multicenter, retrospective, observational study evaluating patients who underwent treatment of an intracranial aneurysm with an LVIS EVO stent after the limited PMR. All physicians who had placed an LVIS EVO stent were asked to input their cases after institutional review board approval was obtained. The data were then sent to a single center for analysis. Any patient aged 18 years or older who underwent treatment of an intracranial aneurysm with a LVIS EVO stent in the US was included from the initial PMR in December 2023 until April 2024. Patient age (or ≤90 years old), sex, preoperative modified Rankin Scale (mRS), aneurysm location, aneurysm measurements, and information about preoperative antiplatelet management were all collected. Data on periprocedural complications, 30-day mortality, discharge mRS, and length of stay were also collected. RESULTS: Some 53 patients with 55 aneurysms underwent treatment with the LVIS EVO stent at 15 institutions. All aneurysms were unruptured. The most common location was the anterior communicating artery (35%) followed by the middle cerebral artery bifurcation (31%). All patients were on dual antiplatelet therapy. The average aneurysm size was 5.2 mm with a neck size of 3.7 mm. The smallest distal parent vessel size was 1.2 mm and 36% of stents were deployed in distal parent vessels <2 mm. All (100%) cases had successful deployment and the stent was repositioned in 10% of cases. A single stent was utilized in 91% of cases. Coils were placed in 48 cases (87.2%) and a microcatheter was jailed in 98% of those cases. Immediate Raymond Roy (RR) Class I occlusion was obtained in 33%, Class II in 22%, Class IIIa in 37%, and Class IIIb in 8% of cases. There were no delayed thromboembolic or hemorrhagic complications. CONCLUSIONS: The LVIS EVO is a braided, self-expanding, retrievable stent with enhanced visibility and smaller cell size. The drawn filled tube (DFT) technology results in improved visibility of the stent, allowing for more controlled stent positioning and visualization of vessel wall apposition. All cases in our series had complete neck coverage and good wall apposition. There were no thromboembolic or hemorrhagic complications.

Optimizing Safety and Aesthetics in Facial Feminization: Laryngoscopic-Assisted Chondrolaryngoplasty (2019-2023).

INTRODUCTION: The thyroid cartilage, an androgen-sensitive structure, enlarges during puberty in individuals assigned male at birth, often resulting in a pronounced neck protuberance. This feature can exacerbate gender dysphoria in transfeminine patients. Chondrolaryngoplasty, commonly known as tracheal shave, is a procedure incorporated into facial feminization surgery (FFS) to address this issue. This study reports on the implementation of an endoscopic-assisted chondrolaryngoplasty technique, its safety, and the outcomes observed. METHODS: The authors conducted a retrospective review of chondrolaryngoplasty cases at our center, examining patient outcomes and procedural safety. The analysis included a breakdown of concurrent gender-affirming surgeries performed. An endoscopic-guided technique was utilized, and its procedural steps were documented in a video. RESULTS: In the past five years, 32 patients received chondrolaryngoplasty at our facility. Postoperative complications were minimal, with no infections, wound separations, or surgical site complications reported. Only one patient experienced temporary hoarseness, which resolved within 6 weeks without intervention. The procedure was frequently combined with other surgical interventions, with the average patient undergoing 3 additional procedures, the most common being augmentation mammaplasty, brow lifting, and frontal bone reduction. CONCLUSIONS: Tracheal shave is an effective surgical technique for alleviating gender dysphoria in transfeminine patients. Keys to its success include the accurate identification of thyroid cartilage, especially in patients with enlarged cricoid cartilages, intraoperative coordination with anesthesia for laryngoscopic vocal cord visualization, sub-perichondrial cartilage excision to minimize the risk of bleeding and damage near the vocal cords, and carefully layered closure to optimize scar healing.

Bacterial communities associated with Acrobeles complexus nematodes recovered from tomato crops in South Africa.

The productivity of agricultural ecosystems is heavily influenced by soil-dwelling organisms. To optimize agricultural practices and management, it is critical to know the composition, abundance, and interactions of soil microorganisms. Our study focused on Acrobeles complexus nematodes collected from tomato fields in South Africa and analyzed their associated bacterial communities utilizing metabarcoding analysis. Our findings revealed that A. complexus forms associations with a wide range of bacterial species. Among the most abundant species identified, we found Dechloromonas sp., a bacterial species commonly found in aquatic sediments, Acidovorax temperans, a bacterial species commonly found in activated sludge, and Lactobacillus ruminis, a commensal motile lactic acid bacterium that inhabits the intestinal tracts of humans and animals. Through principal component analysis (PCA), we found that the abundance of A. complexus in the soil is negatively correlated with clay content (r = -0.990) and soil phosphate levels (r = -0.969) and positively correlated with soil sand content (r = 0.763). This study sheds light on the bacterial species associated to free-living nematodes in tomato crops in South Africa and highlights the occurrence of various potentially damaging and beneficial nematode-associated bacteria, which can in turn, impact soil health and tomato production.

Cell-Based Therapies Induce Tolerance of Vascularized Composite Allotransplants: A Systematic Review.

INTRODUCTION: Vascularized composite allotransplantation (VCA) is the transplantation of multiple tissue types as a solution for devastating injuries. Despite the highly encouraging functional outcomes of VCA, the consequences of long-term immunosuppression remain the main obstacle in its application. In this review, we provide researchers and surgeons with a summary of the latest advances in the field of cell-based therapies for VCA tolerance. METHODS: Four electronic databases were searched: PubMed, Scopus, Cumulative Index to Nursing and Allied Health Literature , and Web of Science. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis as the basis of our organization. RESULTS: Hematopoietic stem cells prolonged VCA survival. A combination of immature dendritic cells and tacrolimus was superior to tacrolimus alone. T cell Ig domain and mucin domain modified mature dendritic cells increased VCA tolerance. Bone marrow-derived mesenchymal stem cells prolonged survival of VCAs. A combination of adipose-derived mesenchymal stem cells, cytotoxic T-lymphocyte antigen 4 immunoglobulin, and antilymphocyte serum significantly improved VCA tolerance. Ex-vivo allotransplant perfusion with recipient's bone marrow-derived mesenchymal stem cells increased VCA survival. Recipient's adipose-derived mesenchymal stem cells and systemic immunosuppression prolonged VCA survival more than any of those agents alone. Additionally, a combination of peripheral blood mononuclear cells shortly incubated in mitomycin and cyclosporine significantly improved VCA survival. Finally, a combination of donor recipient chimeric cells, anti-αß-T cell receptor (TCR), and cyclosporine significantly prolonged VCA tolerance. CONCLUSIONS: Evidence from animal studies shows that cell-based therapies can prolong survival of VCAs. However, there remain many obstacles for these therapies, and they require rigorous clinical research given the rarity of the subjects and the complexity of the therapies. The major limitations of cell-based therapies include the need for conditioning with immunosuppressive drugs and radiation, causing significant toxicity. Safety concerns also persist as most research is on animal models. While completely replacing traditional immunosuppression with cell-based methods is unlikely soon, these therapies could reduce the need for high doses of immunosuppressants and improve VCA tolerance.

Autotrophic adaptive laboratory evolution of the acetogen Clostridium autoethanogenum delivers the gas-fermenting strain LAbrini with superior growth, products, and robustness.

Microbes able to convert gaseous one-carbon (C1) waste feedstocks are increasingly important to transition to the sustainable production of renewable chemicals and fuels. Acetogens are interesting biocatalysts since gas fermentation using Clostridium autoethanogenum has been commercialised. However, most acetogen strains need complex nutrients, display slow growth, and are not robust for bioreactor fermentations. In this work, we used three different and independent adaptive laboratory evolution (ALE) strategies to evolve the wild-type C. autoethanogenum to grow faster, without yeast extract and to be robust in operating continuous bioreactor cultures. Multiple evolved strains with improved phenotypes were isolated on minimal media with one strain, named "LAbrini", exhibiting superior performance regarding the maximum specific growth rate, product profile, and robustness in continuous cultures. Whole-genome sequencing of the evolved strains identified 25 mutations. Of particular interest are two genes that acquired seven different mutations across the three ALE strategies, potentially as a result of convergent evolution. Reverse genetic engineering of mutations in potentially sporulation-related genes CLAU_3129 (spo0A) and CLAU_1957 recovered all three superior features of our ALE strains through triggering significant proteomic rearrangements. This work provides a robust C. autoethanogenum strain "LAbrini" to accelerate phenotyping and genetic engineering and to better understand acetogen metabolism.

LRRK2 G2019S variant is associated with transcriptional changes in Parkinson's disease human myeloid cells under proinflammatory environment.

The G2019S mutation in the leucine-rich repeat kinase 2 (LRRK2) gene is a major risk factor for the development of Parkinson's disease (PD). LRRK2, although ubiquitously expressed, is highly abundant in cells of the innate immune system. Given the importance of central and peripheral immune cells in the development of PD, we sought to investigate the consequences of the G2019S mutation on microglial and monocyte transcriptome and function. We have generated large-scale transcriptomic profiles of isogenic human induced microglial cells (iMGLs) and patient derived monocytes carrying the G2019S mutation under baseline culture conditions and following exposure to the proinflammatory factors IFNγ and LPS. We demonstrate that the G2019S mutation exerts a profound impact on the transcriptomic profile of these myeloid cells, and describe corresponding functional differences in iMGLs. The G2019S mutation led to an upregulation in lipid metabolism and phagolysosomal pathway genes in untreated and LPS/IFNγ stimulated iMGLs, which was accompanied by an increased phagocytic capacity of myelin debris. We also identified dysregulation of cell cycle genes, with a downregulation of the E2F4 regulon. Transcriptomic characterization of human-derived monocytes carrying the G2019S mutation confirmed alteration in lipid metabolism associated genes. Altogether, these findings reveal the influence of G2019S on the dysregulation of the myeloid cell transcriptome under proinflammatory conditions.