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This case series investigated the effect of a combination therapy utilizing connective tissue graft (CTG) in the treatment of periodontal regeneration of mandibular Class III/IV furcation involvement (FI). Six patients diagnosed with periodontitis stage III or IV (grade A to C), presenting with Class III or IV FI, were treated with fibroblast growth factor-2 and carbonate apatite in combination with CTG. The following clinical parameters were evaluated at baseline and after 6, 12, and 18 months: periodontal probing depth, clinical attachment level, furcation invasion, radiographic vertical defect depth, and gingival phenotype. Significant improvements in clinical parameters were observed in all treated FI sites. Four Class III defects and one Class IV defect obtained complete closure, and one Class IV defect was improved to Class I. This case series showed the potential of administering combination regenerative therapy for changing the prognosis of hopeless teeth with severe furcation defects. [ABSTRACT FROM AUTHOR]

Purpose: This prospective study evaluated the marginal bone level and periodontal parameters 6 years after placement of a convergent transmucosal neck implant. Materials and Methods: In total, 71 implants were placed in 60 patients. Of these, 52 implants were placed with a flapless technique and with the convergent neck exposed by 1 mm (early and delayed placement), while 19 implants were placed immediately after extraction (immediate placement). At least 3 months after insertion, customized abutments were applied and provisional resin crowns were cemented, while being careful to prevent any tissue compression. After 3 weeks, definitive metal-ceramic crowns were designed with the finish line at the soft tissue level and free from any compression. The implant survival rate at 6 years, marginal bone level changes (ΔMBL, mm), and Pink Esthetic Score (PES) were evaluated. Gingival phenotype was determined before the implant surgeries (thin/thick). A three-level hierarchical model was examined with a random intercept and random slope on follow-up time at the patient level and a random intercept at the implant level. Results: In all, 57 patients with 67 implants reached the 6-year point; 3 patients (5.0%) dropped out. The implant survival rate was 100%. ΔMBL from baseline to 24 months was 0.58 mm (95% CI: 0.48, 0.68), while ΔMBL from 24 to 72 months was 0.33 mm (95% CI: 0.19, 0.47). PES improved steadily from 6 to 48 months (+0.96; 95% CI: 0.71, 1.20), with overall stability at 72 months. No correlation between MBL and PES was observed. A significant association was found between thick gingival phenotype and less MBL variation. Greater implant diameter offered more MBL stability after 3 years but resulted in lower PES values. Conclusions: The use of convergent transmucosal neck implants placed with a flapless transmucosal approach with the crown margin positioned at the gingival level preserved marginal bone and guided gingival morphology for up to 72 months. The gingival phenotype was the parameter that most affected the soft and hard tissues. In the long term, implant placement timing was not related to MBL. [ABSTRACT FROM AUTHOR]

The management of marked horizontal bone atrophy represents a critical challenge for traditional implantology procedures. For this purpose, clinicians have developed several protocols and procedures to allow the most suitable and accurate surgical and prosthetic implant rehabilitation. Despite the development of guided bone regeneration methods and the use of small-diameter implants, the rehabilitation of thin bone areas is a clinical dilemma for the medium- and long-term survival of implant-prosthetic therapies. This clinical case evaluates the use of wedge-shaped implants for the full-arch rehabilitation of an atrophic maxilla with a thin ridge. This treatment choice allowed a minimally invasive rehabilitation, avoiding regenerative bone surgery, while respecting biologic and prosthetic limits. Furthermore, evaluation of the implant stability quotient and marginal bone loss values during the first year of follow-up allowed analysis of the behavior of this rehabilitation in fullarch maxillary cases. [ABSTRACT FROM AUTHOR]

Gingival recession treatment is one of the major clinical challenges in periodontics, and various surgical techniques have been proposed to correct it. Most of these techniques are suitable for isolated recession sites and involve harvesting an autogenous tissue graft, which increases patient morbidity and might result in inferior esthetics due to incision design. This study assessed the benefit of adding platelet-rich fibrin (PRF) to the vestibular incision subperiosteal tunneling approach (VISTA) in treating multiple gingival recession compared to using VISTA alone. A total of 41 teeth with Miller Class I and II defects were randomized in a split-mouth design. Multiple clinical parameters were tested, including the change in gingival thickness over time, keratinized tissue width, and gingival phenotype (using the transparency of a periodontal probe). Patient-centered outcomes were also assessed via visual analog scale. Multiple Miller Class I and II recessions in the maxilla can be effectively treated with VISTA. However, when used in conjunction with PRF, no significant differences were detected in any parameter. VISTA has been shown to be associated with a low level of postsurgical pain for patients and can be used for patients with high esthetic demands. [ABSTRACT FROM AUTHOR]

Objective: Polycystic ovary syndrome (PCOS) is widely reported among young females, and anti-androgens are used for treating hirsutism and acne in these patients. The protective effects of myo-inositol, oral contraceptives, and insulin sensitizers have been reported on the periodontium and high-sensitivity C-reactive protein (hsCRP) levels in PCOS females. However, cyproterone acetate/ethinyl estradiol (CPA/EE) has not yet been studied. This cross-sectional study explores the periodontal status and systemic inflammation in PCOS women on CPA/EE drug combination compared to females not on medication. Method and materials: A total of 150 participants were enrolled into three groups: 50 newly diagnosed PCOS females not on medication (N-PCOS); 50 PCOS females consuming CPA/EE combination for the last 6 months (PCOS+CPA/EE); and 50 systemically healthy females (control group). Anthropometric, biochemical, periodontal parameters, and health-related quality of life questionnaires were recorded. Results: N-PCOS and PCOS+CPA/EE groups showed a nonsignificant difference in hsCRP levels, Gingival Index, bleeding on probing, waist circumference, and waist-hip ratio (P > .05). Gingival thickness and keratinized tissue width were significantly greater in the PCOS+CPA/EE than the N-PCOS group (P = .05); however, these were comparable with the control group (P > .05). Regression analysis showed significant association of bleeding on probing with Gingival Index, clinical attachment level, and hsCRP (P = .05). Conclusions: CPA/EE combination does not influence the periodontal and systemic inflammatory status in PCOS females, as similar levels of local and systemic inflammation were observed in CPA/EE consumers compared with PCOS females not on medication. However, it might play a role in increasing gingival thickness and keratinized tissue width in these patients. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate bone preservation and esthetic recovery between the socket-shield technique (SST) with different labial bone plate thicknesses and the conventional immediate implant technique (CIIT). Materials and Methods: Patients who underwent immediate implant placement in the anterior region were divided into three groups: the SST with a thickwall phenotype (> 1 mm; SSTA group), the SST with a thin-wall phenotype (< 1 mm; SSTB group), and the CIIT with a thickwall phenotype (> 1 mm; CIIT group). Radiologic images and clinical photos were collected before surgery, immediately postoperatively, and 6 months postoperatively. The labial bone width, labial bone width change (BWC), labial bone volume change (BVC), pink esthetic score (PES), and complication rate were evaluated among the three groups. Statistical analysis was performed using SPSS software. Results: A total of 60 patients (n = 20/group) were enrolled in this 6-month retrospective study. The BWC in the SSTA group (0.22 to 0.30 mm) and the SSTB group (0.18 to 0.33 mm) was less than that in the CIIT group (0.61 to 0.80 mm; P < .004). The SSTA group and the SSTB group had a lower BVC (24.08 vs 21.14 vs 54.81, respectively; P = .004) and greater PES (11.75 vs 11.65 vs 10.65, respectively; P = .009) than the CIIT group. No complications occurred among these patients. Conclusions: With the limitations of this study, it can be concluded that the SST is a reliable method for preserving bone and achieving satisfactory esthetic outcomes. The labial bone plate phenotype associated with the SST has minimal impact on both clinical and radiologic outcomes. [ABSTRACT FROM AUTHOR]

Objectives: Microneedling and injectable platelet-rich fibrin (i-PRF) have been proposed as relatively less invasive alternatives to surgical procedures for augmentation of thin periodontal phenotype. The present study was conducted to evaluate the effect of microneedling and i-PRF alone on gingival thickness in thin periodontal phenotype individuals. Method and materials: Systemically healthy individuals with thin periodontal phenotype in mandibular anterior teeth (n = 21) were treated with microneedling on one side and i-PRF on the contralateral side. Assessment of gingival thickness, keratinized tissue width, and periodontal parameters was done at baseline, and at 1, 3, and 6 months. Results: In intergroup comparison, a statistically significant increase in gingival thickness was observed with microneedling as compared to i-PRF at 6 months (P < .02). Intragroup comparison from baseline to 6 months showed a statistically significant increase in gingival thickness within both the groups: microneedling from 0.78 ± 0.12 mm to 1.00 ± 0.14 mm (P < .000), and i-PRF from 0.77 ± 0.10 mm to 0.93 ± 0.12 mm (P < .000). Intragroup comparison showed a statistically significant increase in keratinized tissue width in the microneedling group (P < .000). A statistically significant decrease in periodontal parameters was observed on intragroup comparison (P < .000). Conclusion: Considering the higher gain in gingival thickness and the added advantage of eliminating need for autologous blood withdrawal, microneedling is potentially better than i-PRF for phenotype modification in thin periodontal phenotype individuals. [ABSTRACT FROM AUTHOR]

Sepsis is a heterogeneous syndrome and phenotypes have been proposed using clinical data. Less is known about the contribution of protein biomarkers to clinical sepsis phenotypes and their importance for treatment effects in randomized trials of resuscitation. The objective is to use both clinical and biomarker data in the Protocol-Based Care for Early Septic Shock (ProCESS) randomized trial to determine sepsis phenotypes and to test for heterogeneity of treatment effect by phenotype comparing usual care to protocolized early, goal-directed therapy(EGDT). In this secondary analysis of a subset of patients with biomarker sampling in the ProCESS trial (n = 543), we identified sepsis phenotypes prior to randomization using latent class analysis of 20 clinical and biomarker variables. Logistic regression was used to test for interaction between phenotype and treatment arm for 60-day inpatient mortality. Among 543 patients with severe sepsis or septic shock in the ProCESS trial, a 2-class model best fit the data (p = 0.01). Phenotype 1 (n = 66, 12%) had increased IL-6, ICAM, and total bilirubin and decreased platelets compared to phenotype 2 (n = 477, 88%, p

Objective: The predictability and long-term success of periodontal regeneration begins with oral hygiene education, disease management, and an individually tailored periodontal maintenance protocol. The treatment outcomes could be enhanced when biologics and bone grafts are combined. The aim of this report was to describe the outcome of two complex infrabony defects in the same patient treated with recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and freeze-dried bone allograft (FDBA) over 10 years. Case presentation: Two complex infrabony defects were treated following guided tissue regeneration principles and procedures. Fullthickness flaps were raised to allow visualization of the defects. The areas were debrided, and exposed root surfaces were planed. FDBA and rhPDGF-BB were combined to fill both defects. A collagen membrane was used over the bone graft in one case. The flaps were reapproximated to achieve primary closure. The patient was seen for regular periodontal maintenance visits and clinical and radiographic follow-ups over 10 years. Throughout the examination periods, the probing depths improved without bleeding on probing, and there was radiographic evidence of bone regeneration. Conclusion: The growth factorinfused bone graft was successfully utilized for periodontal regeneration in complex bony defects. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the study was to evaluate the effect of injectable platelet-rich fibrin (i-PRF) on gingival thickness and gingival recession in individuals with thin periodontal phenotypes. Method and materials: In this prospective study, i-PRF was applied via a semisurgical method to augment 53 tooth regions with thin periodontal phenotypes. In order to ensure that sufficient blood clot formed on the side of the gingiva facing the bone and that i-PRF reached the area, a minimal incision was made with the help of a scalpel in the apical region of the relevant region, and the periosteum was elevated with a microsurgical instrument. To ensure sustained exposure to angiogenetic growth factors and enhance the histoconductive properties, i-PRF injection was applied to the relevant areas in foursessions at 10-dayintervals. Results: An increase in gingival thickness was achieved in 92.5% of the areas treated with i-PRF, and the desired gingival thickness (0.8 mm) was achieved in 44.9% of these areas. In addition, significant reductions in the amount of recession were observed in 83.3% of the 12 gingival recession areas (P= .005). Moreover, complete coverage was achieved in 60% of these regions. Conclusion: With the new i-PRF semisurgical method, it was shown that gingival thickness can be increased in tooth regions with thin gingiva, andthat areas of gingival recession can be covered. Further comprehensive studies are needed to fully understand the role of i-PRF in enhancing angiogenesis and the histoconductive properties of this fully autogenous blood concentrate. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine i) pain phenotypes (PP) in people with early-stage knee osteoarthritis (EKOA); ii) the longitudinal association between the phenotypes and pain worsening at two years. DESIGN: We studied participants with EKOA from the Multicenter Osteoarthritis Study defined as pain intensity ≤3/10, Kellgren and Lawrence grade ≤2, intermittent pain none to sometimes, and no constant pain. Two models of PP were explored. Model A included pressure pain thresholds, temporal summation, conditioned pain modulation, pain catastrophizing, sleep quality, depression, and widespread pain (WSP). In Model B, gait characteristics, quadriceps strength, comorbidities, and magnetic resonance imaging features were added to Model A. Latent Class Analysis was used to create phenotypes, and logistic regression was used to determine their association with pain worsening. RESULTS: 750 individuals (60% females), mean age [standard deviation (SD)]: 60.3 (9.4) were included in Model A and 333 individuals (60% females), mean age (SD): 59.4 (8.1) in Model B. 3-class and 4-class solutions were chosen for Model A and Model B. In Model A, the most severe phenotype was dominated by psychosocial factors, WSP, and measures of nervous system sensitization. Similarly in Model B, the Model A phenotype plus gait variables, quadriceps strength, and comorbidities were dominant. Surprisingly, none of the phenotypes in either model had a significant relationship with pain worsening. CONCLUSION: Phenotypes based upon various factors thought to be important for the pain experience were identified in those with EKOA but were not significantly related to pain worsening. These phenotypes require validation with clinically relevant endpoints.

Objectives: Evaluating gingival thickness is an essential factor for esthetics, function, and the maintenance of soft tissue health around natural teeth and dental implants. This study aimed to evaluate the accuracy of visual inspection procedures used to identify gingival phenotype by clinicians with different expertise and level of experience. Method and materials: The gingival phenotypes of a total of 200 cases were identified as either thick or thin via visual assessment with clinical photographs by eight clinicians. One periodontist examined the gingival phenotype of all subjects based on the translucency of the periodontal probe through the gingival sulcus. The accuracy between these two methods was evaluated using percentile agreement and k statistics. Results: The mean percentage of accurately identified cases was 75% irrespective of the clinician's experience and expertise. Almost half of the thin phenotype cases were misclassified by clinicians. Inter-examiner agreement was generally fair to moderate and intra-examiner agreement was generally moderate. Conclusion: Within the limits of this study, the present findings demonstrated that the visual inspection method misclassified the cases, especially thin gingival phenotype, compared to the probe translucency method. Therefore, there is a need to identify a universally accepted, accurate method and clearclinical definitions. [ABSTRACT FROM AUTHOR]

There is a growing interest in understanding the role of genetics in explaining heterogeneity in behaviors, including those related to information systems (IS). The majority of the recent genetics research focuses on searching the entire genome in genome-wide association studies (GWASs) to link DNA to human traits. The results of GWASs can be used on datasets to compute a measure of genetic propensity known as a polygenic score, or PGS. PGSs are widely viewed as the future of genetics research. We conducted an exploratory study, in the context of information technology (IT) use, to examine if the PGS approach can be used to better understand the role of genetics in IS research. Consistent with our hypotheses, genetic endowments associated with Educational Attainment and General Cognition positively predict technology use, and genetic endowments associated with Neuroticism, Depressive Symptoms, Myocardial Infarction, and Coronary Artery Disease negatively predict technology use more than half a century later (genetic endowments are established at conception and our sample consists of individuals aged 50 to 80). Many of the characteristics known to be associated with heterogeneity in IT use (e.g., trust, education) appear to be mediators linking PGSs to IT use. Nonetheless, a number of PGSs maintain meaningful direct effects. [ABSTRACT FROM AUTHOR]

Misophonic experiences are common in the general population, and they may shed light on everyday emotional reactions to multi-modal stimuli. We performed an online study of a non-clinical sample to understand the extent to which adults who have misophonic reactions are generally reactive to a range of audio-visual emotion-inducing stimuli. We also hypothesized that musicality might be predictive of one's emotional reactions to these stimuli because music is an activity that involves strong connections between sensory processing and meaningful emotional experiences. Participants completed self-report scales of misophonia and musicality. They also watched videos meant to induce misophonia, autonomous sensory meridian response (ASMR) and musical chills, and were asked to click a button whenever they had any emotional reaction to the video. They also rated the emotional valence and arousal of each video. Reactions to misophonia videos were predicted by reactions to ASMR and chills videos, which could indicate that the frequency with which individuals experience emotional responses varies similarly across both negative and positive emotional contexts. Musicality scores were not correlated with measures of misophonia. These findings could reflect a general phenotype of stronger emotional reactivity to meaningful sensory inputs. This article is part of the theme issue 'Sensing and feeling: an integrative approach to sensory processing and emotional experience'. [ABSTRACT FROM AUTHOR]

Background and Objectives Materials and Methods Results Conclusion Missense variants in exon 7 of the ABO gene can lead to the formation of cisAB alleles. These alleles encode glycosyltransferases (GTs) capable of synthesizing both A and B antigens. In this study, we report the discovery of a novel cisAB allele and characterize it at molecular, protein and serological levels.Blood and DNA samples from the proband and seven relatives were examined using standard and modified ABO phenotyping, polymerase chain reaction‐restriction fragment length polymorphism and ABO gene sequencing. We assessed the impact of the p.Leu324Ser variant on the protein structure of the mutant GT using bioinformatics tools.Molecular tests revealed a c.971T>C (p.Leu324Ser) variant in the ABO gene in five of the eight individuals. This variant results in a GT that produces more A antigens and fewer B antigens. Bioinformatics analysis suggests that the amino acid substitution (p.Leu324Ser) could potentially affect enzymatic activity and specificity of the GT.We identified a novel cisAB allele resulting from a c.971T>C variant in the ABO gene. This variant led to the expression of an ABweak phenotype. [ABSTRACT FROM AUTHOR]

The study of evolutionary rates and patterns is the key to understand how natural selection shaped the current and past diversity of phenotypes. Phylogenetic comparative methods offer an array of solutions to undertake this challenging task, and help understanding phenotypic variation in full in most circumstances. However, complex, three-dimensional structures such as the skull and the brain serve disparate goals, and different portions of these phenotypes often fulfil different functions, making it hard to understand which parts truly were recruited by natural selection. In the recent past, we developed tools apt to chart evolutionary rate and patterns directly on three-dimensional shapes, according to their magnitude and direction. Here, we present further developments of these tools, which now allow to restitute the mapping of rates and patterns with full biological realism. The tools are condensed in a new R software package. Evolutionary rates embody the velocity of evolution. Parcellating different velocities across the phenotype is difficult. RRmorph resolves this conundrum by charting evolutionary patterns on 3D shapes, according to their magnitude and direction. [ABSTRACT FROM AUTHOR]

Many of the most highly conserved elements in the human genome are "poison exons," alternatively spliced exons that contain premature termination codons and permit post-transcriptional regulation of mRNA abundance through induction of nonsense-mediated mRNA decay (NMD). Poison exons are widely assumed to be highly conserved due to their presumed importance for organismal fitness, but this functional importance has never been tested in the context of a whole organism. Here, we report that a poison exon in Smndc1 is conserved across mammals and plants and plays a molecular autoregulatory function in both kingdoms. We generated mouse and A. thaliana models lacking this poison exon to find its loss leads to deregulation of SMNDC1 protein levels, pervasive alterations in mRNA processing, and organismal size restriction. Together, these models demonstrate the importance of poison exons for both molecular and organismal phenotypes that likely explain their extraordinary conservation. Author summary: Poison exons are highly conserved elements in the human genome and are known for their roles in regulating mRNA abundance. Despite their assumed importance for organismal fitness, their functional significance has not been tested in whole organisms. Our study focuses on a poison exon in the Smndc1 gene. We discovered that this poison exon is conserved between mammals and plants and sought to test its functional importance. We generated mouse and plant models lacking this specific poison exon. The loss of this exon led to dysregulated SMNDC1 protein levels and widespread disruptions in RNA processing. These molecular changes resulted in a noticeable reduction in organismal size, underscoring the physiological impact of poison exon loss. Our findings demonstrate that poison exons are crucial for maintaining proper protein levels and mRNA processing homeostasis, which may partially explain their remarkable evolutionary conservation. This study highlights the importance of poison exons in both molecular regulation and overall organismal health, providing insights into their conservation across diverse species. [ABSTRACT FROM AUTHOR]

Background: Ripeness is a phenotype that significantly impacts the quality of fruits, constituting a crucial factor in the cultivation and harvesting processes. Manual detection methods and experimental analysis, however, are inefficient and costly. Results: In this study, we propose a lightweight and efficient melon ripeness detection method, MRD-YOLO, based on an improved object detection algorithm. The method combines a lightweight backbone network, MobileNetV3, a design paradigm Slim-neck, and a Coordinate Attention mechanism. Additionally, we have created a large-scale melon dataset sourced from a greenhouse based on ripeness. This dataset contains common complexities encountered in the field environment, such as occlusions, overlapping, and varying light intensities. MRD-YOLO achieves a mean Average Precision of 97.4% on this dataset, achieving accurate and reliable melon ripeness detection. Moreover, the method demands only 4.8 G FLOPs and 2.06 M parameters, representing 58.5% and 68.4% of the baseline YOLOv8n model, respectively. It comprehensively outperforms existing methods in terms of balanced accuracy and computational efficiency. Furthermore, it maintains real-time inference capability in GPU environments and demonstrates exceptional inference speed in CPU environments. The lightweight design of MRD-YOLO is anticipated to be deployed in various resource constrained mobile and edge devices, such as picking robots. Particularly noteworthy is its performance when tested on two melon datasets obtained from the Roboflow platform, achieving a mean Average Precision of 85.9%. This underscores its excellent generalization ability on untrained data. Conclusions: This study presents an efficient method for melon ripeness detection, and the dataset utilized in this study, alongside the detection method, will provide a valuable reference for ripeness detection across various types of fruits. [ABSTRACT FROM AUTHOR]

Summary The alpha‐thalassaemia alleles are very frequent in the world's population. The main molecular mechanism is a large deletion with the loss of one or two alpha genes. Another type of rarer abnormality exists: the gain of alpha genes. The consequence of a gain is an overproduction of alpha‐globin chains, which aggravates a beta‐thalassaemia trait into an intermedia phenotype (non‐transfusion‐dependent thalassaemia, NTDT). Here, we report the case of a young girl referred for a beta‐NTDT with a combination never described in the literature: a heterozygous beta‐thalassaemia mutation associated with a copy number gain of the alpha‐globin locus and ‐alpha 3.7 deletion on the same allele. [ABSTRACT FROM AUTHOR]

Background People with human immunodeficiency virus (HIV) (PWH) have an increased risk of cardiovascular disease (CVD). Cardiac magnetic resonance (CMR) has documented higher myocardial fibrosis, inflammation, and steatosis in PWH, but studies have mostly relied on healthy volunteers as comparators and focused on men. Methods We investigated the associations of HIV and HIV-specific factors with CMR phenotypes in female participants enrolled in the Women's Interagency HIV Study's New York and San Francisco sites. Primary phenotypes included myocardial native (n) T1 (fibro-inflammation), extracellular volume fraction (fibrosis), and triglyceride content (steatosis). Associations were evaluated with multivariable linear regression, and results pooled or meta-analyzed across centers. Results Among 261 women with HIV (WWH, N = 362), 76.2% had undetectable viremia at CMR. For the 82.8% receiving continuous antiretroviral therapy (ART) in the preceding 5 years, adherence was 51.7%, and 69.4% failed to achieve persistent viral suppression (40.7% with peak viral load <200 cp/mL). Overall, WWH showed higher nT1 than women without HIV after full adjustment. This higher nT1 was more pronounced in those with antecedent or current viremia or nadir CD4+ count <200 cells/μL, with the latter also associated with higher extracellular volume fraction. WWH and current CD4+ count <200 cells/μL had less cardiomyocyte steatosis. Cumulative exposure to specific ART showed no associations. Conclusions Compared with sociodemographically similar women without HIV, WWH on ART exhibit higher myocardial fibro-inflammation, which is more prominent with unsuppressed viremia or CD4+ lymphopenia. These findings support the importance of improved ART adherence strategies, along with better understanding of latent infection, to mitigate cardiac end-organ damage in this population. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is an opportunist bacterium that causes acute and chronic infections. During acute infections, the type III secretion system (T3SS) plays a pivotal role in allowing the bacteria to translocate effectors such as ExoS, ExoT, and ExoY into host cells for colonization. Previous research on the involvement of quorum sensing systems Las and Rhl in controlling the T3SS gene expression produced ambiguous results. In this study, we determined the role of the Las and Rhl systems and the PqsE protein on T3SS expression. Our results show that in the wild-type PAO1 strain, the deletion of lasR or pqsE do not affect the secretion of ExoS. However, rhlI inactivation increases the expression of T3SS genes. In contrast to the rhlI deletion, rhlR inactivation decreases both T3SS genes expression and ExoS secreted protein levels, and this phenotype is restored when this mutant is complemented with the exsA gene, which codes for the master regulator of the T3SS. Additionally, cytotoxicity is affected in the rhlR mutant strain compared with its PAO1 parental strain. Overall, our results indicate that neither the Las system nor PqsE are involved in regulating the T3SS. Moreover, the Rhl system components have opposite effects, RhlI participates in negatively controlling the T3SS expression, while RhlR does it in a positive way, and this regulation is independent of C4 or PqsE. Finally, we show that rhlR, rhlI, or pqsE inactivation abolished pyocyanin production in T3SS-induction conditions. The ability of RhlR to act as a positive T3SS regulator in the absence of its cognate autoinducer and PqsE shows that it is a versatile regulator that controls different virulence traits allowing P. aeruginosa to compete for a niche. [ABSTRACT FROM AUTHOR]

Background: Characterizing the condition of patients suffering from knee osteoarthritis is complex due to multiple associations between clinical, functional, and structural parameters. While significant variability exists within this population, especially in candidates for total knee arthroplasty, there is increasing interest in knee kinematics among orthopedic surgeons aiming for more personalized approaches to achieve better outcomes and satisfaction. The primary objective of this study was to identify distinct kinematic phenotypes in total knee arthroplasty candidates and to compare different methods for the identification of these phenotypes. Methods: Three-dimensional kinematic data obtained from a Knee Kinesiography exam during treadmill walking in the clinic were used. Various aspects of the clustering process were evaluated and compared to achieve optimal clustering, including data preparation, transformation, and representation methods. Results: A K-Means clustering algorithm, performed using Euclidean distance, combined with principal component analysis applied on data transformed by standardization, was the optimal approach. Two unique kinematic phenotypes were identified among 80 total knee arthroplasty candidates. The two distinct phenotypes divided patients who significantly differed both in terms of knee kinematic representation and clinical outcomes, including a notable variation in 63.3% of frontal plane features and 81.8% of transverse plane features across 77.33% of the gait cycle, as well as differences in the Pain Catastrophizing Scale, highlighting the impact of these kinematic variations on patient pain and function. Conclusion: Results from this study provide valuable insights for clinicians to develop personalized treatment approaches based on patients' phenotype affiliation, ultimately helping to improve total knee arthroplasty outcomes. [ABSTRACT FROM AUTHOR]

Purpose We describe the implementation and ongoing maintenance of CYP2C19 and CYP2D6 focused pharmacogenetic (PGx) testing to guide antidepressant and antianxiety medication prescriptions in a large rural, nonprofit health system. Summary Depression and anxiety are common psychiatric conditions. Sanford Health implemented PGx testing for metabolism of cytochrome P450 (CYP) isozymes 2C19 and 2D6 in 2014 to inform prescribing for multiple medications, including antidepressant and antianxiety therapies. As guidelines, genotype to phenotype translation, panel offerings, and other resources are updated, we adapt our approach. We make educational and informational materials available to providers and patients. Pharmacogenomic clinical pharmacists review PGx results with discrete values and provide guidance documentation in the electronic medical record. A robust clinical decision support system is in place to provide interruptive alerts, noninterruptive alerts, and genomic indicators. A referral-based interdisciplinary clinic is also available to provide in-depth education to patients regarding PGx results and implications. Additionally, partnering with our health plan has expanded access to PGx testing for patients with anxiety or depression. Conclusion The implementation and maintenance of Sanford Health's PGx program to guide antidepressant and antianxiety medication use continues to evolve and requires a multipronged approach relying on both human and informatics-based resources. [ABSTRACT FROM AUTHOR]

Background: β-Aminobutyric acid (BABA) has been successfully used to prime stress resistance in numerous plant species; however, its effectiveness in forest trees has been poorly explored thus far. This study aimed to investigate the influence of BABA on morphological, physiological, and epigenetic parameters in field elms under various growth conditions. Epigenetic changes were assessed in both DNA and RNA through the use of reversed-phase ultra-performance liquid chromatography (UPLC) coupled with sensitive mass spectrometry. Results: The presented results confirm the influence of BABA on the development, physiology, and stress tolerance in field elms. However, the most important findings are related to the broad epigenetic changes promoted by this amino acid, which involve both DNA and RNA. Our findings confirm, for the first time, that BABA influences not only well-known epigenetic markers in plants, such as 5-methylcytosine, but also several other non-canonical nucleobases, such as 5-hydroxymethyluracil, 5-formylcytosine, 5-hydroxymethylcytosine, N6-methyladenine, uracil (in DNA) and thymine (in RNA). The significant effect on the levels of N6-methyladenine, the main bacterial epigenetic marker, is particularly noteworthy. In this case, the question arises as to whether this effect is due to epigenetic changes in the microbiome, the plant genome, or both. Conclusions: The plant phenotype is the result of complex interactions between the plant's DNA, the microbiome, and the environment. We propose that different types of epigenetic changes in the plant and microbiome may play important roles in the largely unknown memory process that enables plants to adapt faster to changing environmental conditions. [ABSTRACT FROM AUTHOR]

Chilling stress is a major environmental factor that significantly reduces crop production. To adapt to chilling stress, plants activate a series of cellular responses and accumulate an array of metabolites, particularly proline. Here, we report that the transcription factor SlWRKY51 increases proline contents in tomato (Solanum lycopersicum) under chilling stress. SlWRKY51 expression is induced under chilling stress. Knockdown or knockout of SlWRKY51 led to chilling‐sensitive phenotypes, with lower photosynthetic capacity and more reactive oxygen species (ROS) accumulation than the wild type (WT). The proline contents were significantly reduced in SlWRKY51 knockdown and knockout lines under chilling stress, perhaps explaining the phenotypes of these lines. D‐1‐pyrroline‐5‐carboxylate synthetase (P5CS), which catalyses the rate‐limiting step of proline biosynthesis, is encoded by two closely related P5CS genes (P5CS1 and P5CS2). We demonstrate that SlWRKY51 directly activates the expression of P5CS1 under chilling stress. In addition, the VQ (a class of plant‐specific proteins containing the conserved motif FxxhVQxhTG) family member SlVQ10 physically interacts with SlWRKY51 to enhance its activation of P5CS1. Our study reveals that the chilling‐induced transcription factor SlWRKY51 enhances chilling tolerance in tomato by promoting proline accumulation. [ABSTRACT FROM AUTHOR]

SUMMARY Over‐expression (OE) lines for the ER‐tethered NAC transcription factor ANAC017 displayed de‐repression of gun marker genes when grown on lincomycin (lin). RNA‐seq revealed that ANAC017OE2 plants constitutively expressed greater than 40% of the genes induced in wild‐type with lin treatment, including plastid encoded genes ycf1.2 and the gene cluster ndhH‐ndhA‐ndhI‐ndhG‐ndhE‐psaC‐ndhD, documented as direct RNA targets of GUN1. Genes encoding components involved in organelle translation were enriched in constitutively expressed genes in ANAC017OE2. ANAC017OE resulted in constitutive location in the nucleus and significant constitutive binding of ANAC017 was detected by ChIP‐Seq to target genes. ANAC017OE2 lines maintained the ability to green on lin, were more ABA sensitive, did not show photo‐oxidative damage after exposure of de‐etiolated seedlings to continuous light and the transcriptome response to lin were as much as 80% unique compared to gun1‐1. Both double mutants, gun1‐1:ANAC017OE and bzip60:ANAC017OE (but not single bzip60), have a gun molecular gene expression pattern and result in variegated and green plants, suggesting that ANAC017OE may act through an independent pathway compared to gun1. Over‐expression of ANAC013 or rcd1 did not produce a GUN phenotype or green plants on lin. Thus, constitutive ANAC017OE2 establishes an alternative transcriptional program that likely acts through a number of pathways, that is, maintains plastid gene expression, and induction of a variety of transcription factors involved in reactive oxygen species metabolism, priming plants for lin tolerance to give a gun phenotype. [ABSTRACT FROM AUTHOR]

One of the greatest strengths of Drosophila genetics is its easily observable and selectable phenotypic markers. The mini-white marker has been widely used as a transgenic marker for Drosophila transgenesis. Flies carrying a mini-white construct can exhibit various eye colors ranging from pale orange to intense red, depending on the insertion site and gene dosage. Because the two copies of the mini-white marker show a stronger orange color, this is often used for selecting progenies carrying two transgenes together in a single chromosome after chromosomal recombination. However, some GAL4 lines available in the fly community originally have very strong red eyes. Without employing another marker, such as GFP, generating a recombinant chromosome with the strong red-eyed GAL4 and a desired UAS-transgene construct may be difficult. Therefore, we decided to change the red eyes of GAL4 lines to orange color. To change the eye color of the fly, we tested the CRISPR/Cas9 method with a guide RNA targeting the white gene with OK371-GAL4 and elav-GAL4. After a simple screening, we have successfully obtained multiple lines of orange-eyed OK371-GAL4 and elav-GAL4 that still maintain their original expression patterns. All of these simple experiments were performed by undergraduate students, allowing them to learn about a variety of different genetic experiments and genome editing while contributing to the fly research community by creating fruit fly lines that will be used in real-world research. [ABSTRACT FROM AUTHOR]

Background: Decoding human genomic sequences requires comprehensive analysis of DNA sequence functionality. Through computational and experimental approaches, researchers have studied the genotype-phenotype relationship and generate important datasets that help unravel complicated genetic blueprints. Thus, the recently developed artificial intelligence methods can be used to interpret the functions of those DNA sequences. Methods: This study explores the use of deep learning, particularly pre-trained genomic models like DNA_bert_6 and human_gpt2-v1, in interpreting and representing human genome sequences. Initially, we meticulously constructed multiple datasets linking genotypes and phenotypes to fine-tune those models for precise DNA sequence classification. Additionally, we evaluate the influence of sequence length on classification results and analyze the impact of feature extraction in the hidden layers of our model using the HERV dataset. To enhance our understanding of phenotype-specific patterns recognized by the model, we perform enrichment, pathogenicity and conservation analyzes of specific motifs in the human endogenous retrovirus (HERV) sequence with high average local representation weight (ALRW) scores. Results: We have constructed multiple genotype-phenotype datasets displaying commendable classification performance in comparison with random genomic sequences, particularly in the HERV dataset, which achieved binary and multi-classification accuracies and F1 values exceeding 0.935 and 0.888, respectively. Notably, the fine-tuning of the HERV dataset not only improved our ability to identify and distinguish diverse information types within DNA sequences but also successfully identified specific motifs associated with neurological disorders and cancers in regions with high ALRW scores. Subsequent analysis of these motifs shed light on the adaptive responses of species to environmental pressures and their co-evolution with pathogens. Conclusions: These findings highlight the potential of pre-trained genomic models in learning DNA sequence representations, particularly when utilizing the HERV dataset, and provide valuable insights for future research endeavors. This study represents an innovative strategy that combines pre-trained genomic model representations with classical methods for analyzing the functionality of genome sequences, thereby promoting cross-fertilization between genomics and artificial intelligence. [ABSTRACT FROM AUTHOR]

Background: The Lin−Sca1+c-Kit+ (LSK) fraction of the bone marrow (BM) comprises multipotent hematopoietic stem cells (HSCs), which are vital to tissue homeostasis and vascular repair. While diabetes affects HSC homeostasis overall, the molecular signature of mRNA and miRNA transcriptomic under the conditions of long-standing type 2 diabetes (T2D;>6 months) remains unexplored. Methods: In this study, we assessed the transcriptomic signature of HSCs in db/db mice, a well-known and widely used model for T2D. LSK cells of db/db mice enriched using a cell sorter were subjected to paired-end mRNA and single-end miRNA seq library and sequenced on Illumina NovaSeq 6000. The mRNA sequence reads were mapped using STAR (Spliced Transcripts Alignment to a Reference), and the miRNA sequence reads were mapped to the designated reference genome using the Qiagen GeneGlobe RNA-seq Analysis Portal with default parameters for miRNA. Results: We uncovered 2076 out of 13,708 mRNAs and 35 out of 191 miRNAs that were expressed significantly in db/db animals; strikingly, previously unreported miRNAs (miR-3968 and miR-1971) were found to be downregulated in db/db mice. Furthermore, we observed a molecular shift in the transcriptome of HSCs of diabetes with an increase in pro-inflammatory cytokines (Il4, Tlr4, and Tnf11α) and a decrease in anti-inflammatory cytokine IL10. Pathway mapping demonstrated inflammation mediated by chemokine, cytokine, and angiogenesis as one of the top pathways with a significantly higher number of transcripts in db/db mice. These molecular changes were reflected in an overt defect in LSK mobility in the bone marrow. miRNA downstream target analysis unveils several mRNAs targeting leukocyte migration, microglia activation, phagosome formation, and macrophage activation signaling as their primary pathways, suggesting a shift to an inflammatory phenotype. Conclusion: Our findings highlight that chronic diabetes adversely alters HSCs' homeostasis at the transcriptional level, thus potentially contributing to the inflammatory phenotype of HSCs under long-term diabetes. We also believe that identifying HSCs-based biomarkers in miRNAs or mRNAs could serve as diagnostic markers and potential therapeutic targets for diabetes and associated vascular complications. [ABSTRACT FROM AUTHOR]

SUMMARY Strigolactones (SLs) are key regulators of shoot growth and responses to environmental stimuli. Numerous studies have indicated that nitrogen (N) limitation induces SL biosynthesis, suggesting that SLs may play a pivotal role in coordinating systemic responses to N availability, but this idea has not been clearly demonstrated. Here, we generated triple knockout mutants in the SL synthesis gene TaDWARF17 (TaD17) in bread wheat and investigated their phenotypic and transcriptional responses under N limitation, aiming to elucidate the role of SLs in the adaptation to N limitation. Tad17 mutants display typical SL mutant phenotypes, and fail to adapt their shoot growth appropriately to N. Despite exhibiting an increased tillering phenotype, Tad17 mutants continued to respond to N limitation by reducing tiller number, suggesting that SLs are not the sole regulators of tillering in response to N availability. RNA‐seq analysis of basal nodes revealed that the loss of D17 significantly altered the transcriptional response of N‐responsive genes, including changes in the expression profiles of key N response master regulators. Crucially, our findings suggest that SLs are required for the transcriptional downregulation of cytokinin (CK) synthesis and signalling in response to N limitation. Collectively, our results suggest that SLs are essential for the appropriate morphological and transcriptional adaptation to N limitation in wheat, and that the repressive effect of SLs on shoot growth is partly mediated by their repression of CK synthesis. [ABSTRACT FROM AUTHOR]

Invasive species often undergo demographic bottlenecks that cause a decrease in genetic diversity and associated reductions in population fitness. Despite this, they manage to thrive in novel environments. Investigating the effects of inbreeding and genetic bottlenecks on population fitness for invasive species is, therefore, key to understanding how they may survive in new environments. We used the blowfly Calliphora vicina (Sciences, Mathématiques et Physique, 1830, 2, 1), which is native to Europe and was introduced to Australia and New Zealand, to examine the effects of genetic diversity on population fitness. We first collected 59 samples from 15 populations across New Zealand and one in Australia, and used 20,501 biallelic SNPs to investigate population genomic diversity, structure and admixture. We then explored the impacts of repeated experimental bottlenecks on population fitness by creating inbred and outbred lines of C. vicina and measuring a variety of fitness traits. In wild‐caught samples, we found low overall genetic diversity, signals of genetic admixture and limited (<3%) genetic differentiation between North and South Island populations, with genetic links between the South Island and Australia. Following experimental bottlenecks, we found significant reductions in fitness for inbred lines. However, fitness effects were not felt equally across all phenotypic traits. Moreover, they were not enough to cause population collapse in any experimental line, suggesting that C. vicina (when under relaxed selection, as in laboratory settings) may be able to compensate for population bottlenecks even when highly inbred. Our results demonstrate the value of a tractable experimental system for investigating processes that may facilitate or hamper biological invasion. [ABSTRACT FROM AUTHOR]

Ichthyoses comprise a large heterogeneous group of skin disorders, characterized by generalized scaly and hyperkeratotic skin. We investigated a miniature poodle with early onset generalized scaling, dry and irregularly thickened skin, paw pad hyperkeratosis and abnormalities in hair and teeth. The clinical signs of ichthyosis were confirmed by histopathological examination, which revealed mild epidermal hyperplasia and lamellar orthokeratotic hyperkeratosis. A hereditary condition was suspected and a genetic investigation was initiated. We sequenced the whole genome of the affected dog and searched for potentially causative variants in functional candidate genes for the observed phenotype. The analysis revealed a heterozygous in‐frame deletion in DSP, NC_049256.1:g.8804542_8804544del resulting from a de novo mutation event as evidenced by genotyping leukocyte DNA from both parents. The 3 bp deletion is predicted to remove one aspartic acid without disrupting the open reading frame (XM_038584124.1:c.1821_1823del, XP_038440052.1:p.(Asp608del)). The DSP gene encodes desmoplakin, a desmosomal plaque protein, responsible for cell–cell adhesion to provide resistance to mechanical stress in epidermal and cardiac tissues. We hypothesize that the deletion of one amino acid in the N‐terminal globular head domain acts in a dominant negative manner and thus impairs the proper connection with other proteins. Several variants in DSP in humans and cattle have been described to result in different phenotypes associated with hair and skin abnormalities, sometimes in combination with variable cardiac and/or dental manifestations. In conclusion, we characterized a new syndromic ichthyosis phenotype in a dog and identified a de novo 3 bp deletion in the DSP gene as causal variant. [ABSTRACT FROM AUTHOR]

Suitable conditions for species to survive and reproduce constitute their ecological niche, which is built by abiotic conditions and interactions with conspecifics and heterospecifics. Organisms should ideally assess and use information about all these environmental dimensions to adjust their dispersal decisions depending on their own internal conditions. Dispersal plasticity is often considered through its dependence on abiotic conditions or conspecific density and, to a lesser extent, with reference to the effects of interactions with heterospecifics, potentially leading to misinterpretation of dispersal drivers. Here, we first review the evidence for the effects of and the potential interplays between abiotic factors, biotic interactions with conspecifics and heterospecifics and phenotype on dispersal decisions. We then present an experimental test of these potential interplays, investigating the effects of density and interactions with conspecifics and heterospecifics on temperature-dependent dispersal in microcosms of Tetrahymena ciliates. We found significant differences in dispersal rates depending on the temperature, density and presence of another strain or species. However, the presence and density of conspecifics and heterospecifics had no effects on the thermal-dependency of dispersal. We discuss the causes and consequences of the (lack of) interplay between the different environmental dimensions and the phenotype for metacommunity assembly and dynamics. This article is part of the theme issue 'Diversity-dependence of dispersal: interspecific interactions determine spatial dynamics'. [ABSTRACT FROM AUTHOR]

Embryonic temperature has a lasting impact on muscle phenotype in vertebrates, involving complex molecular mechanisms that encompass both protein-coding and non-coding genes. Circular RNAs (circRNAs) are a class of regulatory RNAs that play important roles in various biological processes, but the effect of variable thermal conditions on the circRNA transcriptome and its long-term impact on muscle growth plasticity remains largely unexplored. To fill this knowledge gap, we performed a transcriptomic analysis of circRNAs in fast muscle of Nile tilapia (Oreochromis niloticus) subjected to different embryonic temperatures (24°C, 28°C and 32°C) and then reared at a common temperature (28°C) for 4 months. Nile tilapia embryos exhibited faster development and subsequently higher longterm growth at 32°C compared to those reared at 28°C and 24°C. Nextgeneration sequencing data revealed a total of 5,141 unique circRNAs across all temperature groups, of which 1,604, 1,531, and 1,169 circRNAs were exclusively found in the 24°C, 28°C and 32°C groups, respectively. Among them, circNexn exhibited a 1.7-fold (log2) upregulation in the 24°C group and a 1.3-fold (log2) upregulation in the 32°C group when compared to the 28°C group. Conversely, circTTN and circTTN_;b were downregulated in the 24°C groups compared to their 28°C and 32°C counterparts. Furthermore, these differentially expressed circRNAs were found to have multiple interactions with myomiRs, highlighting their potential as promising candidates for further investigation in the context of muscle growth plasticity. Taken together, our findings provide new insights into the molecular mechanisms that may underlie muscle growth plasticity in response to thermal variation in fish, with important implications in the context of climate change, fisheries and aquaculture. [ABSTRACT FROM AUTHOR]

The article discusses a study on how the MUC5B variant influences idiopathic pulmonary fibrosis (IPF) using a spatial gene expression approach. Topics include the dominant risk factor for the development of IPF, analysis of specimens, and implication of the loss of small airway secretory cells (SASC) markers in small airways of MUC5B variant carriers.

Nearly 50 years after the ground-breaking isolation of the primary Comptonia peregrina microsymbiont under axenic conditions, efforts to isolate a substantial number of Protofrankia and Frankia strains continue with enduring challenges and complexities. This study aimed to streamline genomic insights through comparative and predictive tools to extract traits crucial for isolating specific Frankia in axenic conditions. Pangenome analysis unveiled significant genetic diversity, suggesting untapped potential for cultivation strategies. Shared metabolic strategies in cellular components, central metabolic pathways, and resource acquisition traits offered promising avenues for cultivation. Ecological trait extraction indicated that most uncultured strains exhibit no apparent barriers to axenic growth. Despite ongoing challenges, potential caveats, and errors that could bias predictive analyses, this study provides a nuanced perspective. It highlights potential breakthroughs and guides refined cultivation strategies for these yet-uncultured strains. We advocate for tailored media formulations enriched with simple carbon sources in aerobic environments, with atmospheric nitrogen optionally sufficient to minimize contamination risks. Temperature adjustments should align with strain preferences--28-29°C for Frankia and 32-35°C for Protofrankia--while maintaining an alkaline pH. Given potential extended incubation periods (predicted doubling times ranging from 3.26 to 9.60 days, possibly up to 21.98 days), patience and rigorous contamination monitoring are crucial for optimizing cultivation conditions. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this long-term cohort study in periodontally compromised patients with implants was to analyze the correlation between gingival phenotype and peri-implant crestal bone loss, and between clinical measures and gingival phenotype. Methods: Implant-supported single crowns and bridges were used to rehabilitate 162 implants in 57 patients. Patients were examined over a 2 to 20-year period on a recall schedule of 3 to 6 months. In addition to recording clinical parameters, intraoral radiographs were taken at baseline (immediately after superstructure insertion) and at 1, 3, 5, 10, 15, and 20 years. Patients were differentiated into phenotype 1 with thin, scalloped gingiva and narrow attached gingiva (n = 19), phenotype 2 with thick, flat gingiva and wide attached gingiva (n = 23), or phenotyp 3 with thick, scalloped gingiva and narrow attached gingiva (n = 15). Results: The mean peri-implant crestal bone loss during the first 12 months was 1.3 ± 0.7 mm. Patients with gingival phenotype 1 had a significantly greater rate of increased crestal bone loss at implants (p = 0.016). No significant differences were present in subsequent years. The prevalence of mucositis at all implants was 27.2%, and the prevalence of peri-implantitis 9.3%. Univariate analyses indicated a significantly higher peri-implantitis risk in patients with gingival phenotype 2 (p-OR = 0.001; p-OR = 0.020). The implants of patients with phenotype 2 had significantly greater probing depths (1st year p < 0.001; 3rd year p = 0.016; 10th year p = 0.027; 15th year p < 0.001). Patients with gingival phenotype 3 showed no significantly increased probing depths, signs of inflammation and crestal bone loss. Conclusions: Patients with a gingival phenotype 1 have greater crestal bone loss at implants during the first year of functional loading. Patients with gingival phenotype 2 had significantly greater probing depth at implants and risk of peri-implantitis. [ABSTRACT FROM AUTHOR]

Metabolomics is one of the "omics" sciences that can reveal the metabolic phenotype of organisms. This capability makes it a valuable tool for plant investigation, as plants present a vast chemical diversity. From the analytical point of view, two main techniques are frequently used in metabolomics and are often complementary: Mass spectrometry (MS) and Nuclear Magnetic Resonance (NMR) spectroscopy. Here, we describe NMR and its applications in plant metabolomics. We start by contextualizing the research field to then explore study design, sample collection, sample preparation, NMR data acquisition, and data analysis, showing the key features for achieving quality and relevant results. Within these topics, the most common databases used for plant metabolites identification and assignments are listed, as these help to shorten the laborious task of metabolomics investigation of natural products. Concerning NMR parameters, we discuss the key pulse sequences, recommend acquisition parameters, and examine the data each sequence can provide. Similarly, we delve into data analysis, highlighting the most commonly used chemometric methods and how to achieve high-quality results. Therefore, this review aims to provide a comprehensive guide for NMR-based metabolomics analysis of plants. [ABSTRACT FROM AUTHOR]

The Mediterrane an Sea is a biodiversity hotspot, being home to a vast array of marine species. Furthermore, seawater warming is facilitating the arrival and spread of new thermophilic species, posing a severe threat to biodiversity. Among the species currently extending their range and increasing in abundance in Mediterranean waters, sea chubs (genus Kyphosus) are one of the most enigmatic. One challenge arises from the high phenotypic similarity between the two congeneric species documented in the basin: Kyphosus vaigiensis and Kyphosus sectatrix. Their resemblance has often led to identification challenges, resulting in incorrect or omitted species-level classifications. Therefore, despite the growing presence of these fish in the Mediterranean, it remains unclear whether only one or both species are experiencing a demographic increase and range extension. To date, there have been 26 reports of Kyphosus individuals in the Mediterranean Sea, documented in 24 separate papers. Here, we reviewed the history of the genus in the basin and provided 13 new records of these fish from multiple localities along Mediterranean coasts. In addition, we sequenced the entire mitogenomes of two specimens, assessed their phylogenetic relationships with published Kyphosus mitochondrial DNAs from around the world, and conducted detailed morphological and meristic analyses on one of them, allowing us to provide accurate species-level identifications. Our results indicate that K. vaigiensis is the species currently expanding its range in the Mediterranean Sea, while K. sectatrix is still very rare and only sporadically reported. Notably, our mitogenome data indicate that Mediterranean K. vaigiensis individuals most likely came from Atlantic waters, while there is no evidence to support an entrance through the Red Sea or any other anthropogenic vector. Finally, the potential ecological and fishing impacts associated with the proliferation of these fish in the region are discussed. [ABSTRACT FROM AUTHOR]

Objective: Although the mechanism is unclear, Pseudomonas aeruginosa (PA) infection directly affects the frequency of acute exacerbations in patients with bronchiectasis. The aims of this article are to analyze the genetic mutation characteristics of the algUmucABD operon in PA, isolated from hospitalized patients with bronchiectasis, and to explore independent risk factors for frequent acute exacerbations of bronchiectasis. Methods: Based on the number of acute exacerbations that occurred in the past year, these patients with bronchiectasis were divided into those with frequent acute exacerbations (Group A) and those with non-frequent acute exacerbations (Group B). We identified the distribution of mucoid phenotypes (MPs) and alginate morphotypes (AMs) in PA, and classified them into I--IV categories based on their different AMs; otherwise, the gene mutation types (GMTs) of the algUmucABD operon were tested. Subsequently, the relationship between GMT, MP, and AM and the independent risk factors for frequent acute exacerbations in patients with bronchiectasis were explored. Results: A total of 93 patients and 75 PA strains, fromJanuary 2019 to August 2023, were included in this study. The MP and AM distributions of PA were as follows: 64 strains (85.33%) ofmucoid (the AMs were 38 strains of type I, 3 strains of type II, and 23 strains of type IV) and 11 strains of non-mucoid (the AM was type III only). Mucoid PA with algU, mucA, mucB, and mucD mutations accounted for 19.61%, 74.51%, 31.37%, and 50.98%, respectively. GMT was divided into the following: mucA mutations only, mucA combined with other gene mutations, other gene mutations without mucA mutations, and without gene mutations. In 91.7% of PA with type I of AM, only mucA mutations occurred, and in both separateMP and AM, the GMT differences were statistically significant. Lastly, the number of lung lobes with bronchiectasis and the number of PA with mucA mutations only were the independent risk factors for frequent acute exacerbations. Conclusion: The mucA mutation was primarily responsible for the mucoid of MP and type I of AM in PA, and it was also an independent risk factor for frequent exacerbations of bronchiectasis. [ABSTRACT FROM AUTHOR]

Background: The clinical differentiation between essential tremor plus (ETP) and dystonic tremor (DT) is challenging. This study aimed at the genetic diagnosis of ETP and DT. Methods: Whole exome sequencing was performed on 50 probands (ETP = 25; DT = 25) and analysed to identify variants in known genes linked with dystonia and essential tremor plus phenotypes. Results: We identified pathogenic/likely pathogenic variants [THAP1 (n = 1) and ANO3 (n = 1)] in two patients with DT. In addition, one DT patient had a variant of uncertain significance in FUS and four patients had benign variants [CIZ1 (n = 1), COL6A3 (n = 1), GCH1 (n = 1), TENM4 (n = 1)]. One patient with ETP was detected to have a variant of uncertain significance in TENM4 and five patients with ETP had benign variants [COL6A3 (n = 2), VPS16 (n = 1), TAF1 (n = 1), KMT2B (n = 1)]. Conclusion: Genetic studies may be in an important biomarker in differentiating patients with ET plus from DT which is challenging in a clinical setting. [ABSTRACT FROM AUTHOR]

Occupational crystalline silica (CS) particle exposure leads to silicosis. The burden of CS-associated disease remains high, and treatment options are limited due to vague mechanisms. Here we show that pulmonary CD4+ tissue-resident memory T cells (TRM) accumulate in response to CS particles, mediating the pathogenesis of silicosis. The TRM cells are derived from peripheral lymphocyte recruitment and in situ expansion. Specifically, CD69+CD103+ TRM-Tregs depend more on circulating T cell replenishment. CD69 and CD103 can divide the TRM cells into functionally distinct subsets, mirroring the immuno-balance within CD4+ TRM cells. However, targeting CD103+ TRM-Tregs do not mitigate disease phenotype since the TRM subsets exert immunosuppressive but not pro-fibrotic roles. After identifying pathogenic CD69+CD103- subsets, we highlight IL-7 for their maintenance and function, that present a promising avenue for mitigating silicosis. Together, our findings highlight the distinct role of CD4+ TRM cells in mediating CS-induced fibrosis and provide potential therapeutic strategies. Crystalline silica exposure led to CD4+ tissue-resident memory T-cell accumulation. The imbalance of pulmonary TRM-Teffs and TRM-Tregs promoted silicosis progression. Neutralizing IL-7 alleviated silicosis by disrupting TRM-Teff maintenance. [ABSTRACT FROM AUTHOR]

Powdery mildew (PM), triggered by Oidium neolycopersici, represents a significant threat and a major concern for the productivity of tomato plants (Solanum lycopersicum L.). The presence of susceptibility (S) genes in plants facilitates pathogen proliferation and their dysfunction can lead to a recessively inherited broad-spectrum and durable type of resistance. Past studies have demonstrated that disrupting the function of DND1 (Defense No Death 1) increases plant resilience against various pathogens, such as powdery mildew (PM), but this comes at the cost of negatively affecting the overall health and vigor of the plant. To investigate the possibility of minimizing the adverse effects of the dnd1 mutation while boosting disease resistance, a CRISPR-Cas9 construct with four single guide RNAs targeting three exons of SlDND1 (Solyc02g088560.4.1) was designed and introduced into the tomato variety Moneymaker (MM) through Agrobacterium tumefaciens-mediated transformation. Three T1 lines (named E1, E3 and E4) were crossed with MM and then selfed to produce TF2 families. All the TF2 plants in homozygous state dnd1/dnd1, showed reduced PM symptoms compared to the heterozygous (DND1/dnd1) and wild type (DND1/DND1) ones. Two full knock-out (KO) mutant events (E1 and E4) encoding truncated DND1 proteins, exhibited clear dwarfness and auto-necrosis phenotypes, while mutant event E3 harbouring deletions of 3 amino acids, showed normal growth in height with less auto-necrotic spots. Analysis of the 3D structures of both the reference and the mutant proteins revealed significant conformational alterations in the protein derived from E3, potentially impacting its function. A dnd1/dnd1 TF2 line (TV181848-9, E3) underwent whole-genome sequencing using Illumina technology, which confirmed the absence of off-target mutations in selected genomic areas. Additionally, no traces of the Cas9 gene were detected, indicating its elimination through segregation. Our findings confirm the role of DND1 as an S-gene in tomato because impairment of this gene leads to a notable reduction in susceptibility to O. neolycopersici. Moreover, we provide, for the first time, a dnd1 mutant allele (E3) that exhibits fitness advantages in comparison with previously reported dnd1 mutant alleles, indicating a possible way to breed with dnd1 mutants. [ABSTRACT FROM AUTHOR]

Cancer therapy-related cardiac dysfunction (CTRCD), which commonly includes left ventricular dysfunction and heart failure, is the main adverse effect of anticancer therapy. In recent years several candidate genes studies and genome-wide association studies have identified common genetic variants associated with CTRCD, but evidence remains limited and few genetic variants are robust. A genome-wide meta-analysis of CTRCD was performed with 852 oncology patients receiving cancer therapy. DNA samples were genotyped and imputed to perform a GWAS meta-analysis for case–control (N = 852 (380 cases and 472 controls) and extreme phenotypes (N = 618 (78 cases and 472 controls) looking for genetic variants that predispose to CTRCD. The results were validated in a replicate cohort of 1,191 oncology patients (245 cases and 946 controls). Functional mapping of the replicated loci was then performed. The meta-analysis showed 9 and 17 loci suggestively associated (P-value < 1 × 10–5) with CTRCD in case–control and extreme phenotypes analyses, respectively. The 3q28 locus (rs rs7652759, P = 5.64 × 10–6) in the case–control analysis was the strongest signal, with up to 64 SNPs above the suggestive significance threshold. The rs7652759, an intergenic variant between TPRG1 and TP63 genes, was the only variant validated in the replication cohort (P-value = 0.01). Functional mapping of this significant locus revealed up to 5 new genes potentially involved in the CTRCD. We identified the intergenic region near TP63 as a novel CTRCD susceptibility locus. In the future, the genotyping of these markers could be considered in new CTRCD risk scores to improve preventive strategies in cardio-oncology. [ABSTRACT FROM AUTHOR]

Mutations in the IER3IP1 (Immediate Early Response-3 Interacting Protein 1) gene can give rise to MEDS1 (Microcephaly with Simplified Gyral Pattern, Epilepsy, and Permanent Neonatal Diabetes Syndrome-1), a severe condition leading to early childhood mortality. The small endoplasmic reticulum (ER)-membrane protein IER3IP1 plays a non-essential role in ER-Golgi transport. Here, we employed secretome and cell-surface proteomics to demonstrate that the absence of IER3IP1 results in the mistrafficking of proteins crucial for neuronal development and survival, including FGFR3, UNC5B and SEMA4D. This phenomenon correlates with the distension of ER membranes and increased lysosomal activity. Notably, the trafficking of cargo receptor ERGIC53 and KDEL-receptor 2 are compromised, with the latter leading to the anomalous secretion of ER-localized chaperones. Our investigation extended to in-utero knock-down of Ier3ip1 in mouse embryo brains, revealing a morphological phenotype in newborn neurons. In summary, our findings provide insights into how the loss or mutation of a 10 kDa small ER-membrane protein can cause a fatal syndrome. [ABSTRACT FROM AUTHOR]

Over the last decade, accumulating evidence has suggested that tumor-associated macrophages (TAMs) play a significant role in the tumor development. This commentary wishes to highlight the findings by You, et al. that M1-like TAMs could cascade a mesenchymal/stem-like phenotype of oral squamous cell carcinoma (OSCC) via the IL6/Stat3/THBS1 feedback loop. These unprecedented findings identified M1-like TAMs-regulated processes as potentially tumor-promotion in the context of OSCC immunomicroenvironment. [ABSTRACT FROM AUTHOR]

Mitochondrial diseases (MtDs) present diverse clinical phenotypes, yet large‐scale studies are hindered by their rarity. This retrospective, multicenter study, conducted across five Chinese hospitals' neurology departments from 2009 to 2019, aimed to address this gap. Nationwide, 1351 patients were enrolled, with a median onset age of 14.0 (18.5) years. The predominant phenotype was mitochondrial encephalomyopathy, lactic acidosis, and stroke‐like episodes (MELAS) (45.0%). Mitochondrial DNA (mtDNA) mutations were prevalent (87.4%), with m.3243A>G being the most common locus (48.7%). Meanwhile, POLG mutations in nuclear DNA (nDNA) accounted for 16.5%. Comparative analysis based on age groups (with a cut‐off at 14 years) revealed the highest prevalence of MELAS, with Leigh syndrome (LS) and chronic progressive external ophthalmoplegia (CPEO) being the second most common phenotypes in junior and senior groups, respectively. Notably, the most commonly mutated nuclear genes varied across age groups. In conclusion, MELAS predominated in this Chinese MtD cohort, underscored by m.3243A>G and POLG as principal mtDNA mutations and pathogenic nuclear genes. The phenotypic and genotypic disparities observed among different age cohorts highlight the complex nature of MtDs. [ABSTRACT FROM AUTHOR]

The nematode Caenorhabditis elegans is well known for its ability to support forward genetic screens to identify molecules involved in neuronal viability and signaling. The proteins involved in C. elegans dopamine (DA) regulation are highly conserved across evolution, with prior work demonstrating that the model can serve as an efficient platform to identify novel genes involved in disease‐associated processes. To identify novel players in DA signaling, we took advantage of a recently developed library of pre‐sequenced mutant nematodes arising from the million mutation project (MMP) to identify strains that display the DA‐dependent swimming‐induced‐paralysis phenotype (Swip). Our screen identified novel mutations in the dopamine transporter encoding gene dat‐1, whose loss was previously used to identify the Swip phenotype, as well as multiple genes with previously unknown connections to DA signaling. Here, we present our isolation and characterization of one of these genes, bbs‐1, previously linked to the function of primary cilia in worms and higher organisms, including humans, and where loss‐of‐function mutations result in a human disorder known as Bardet–Biedl syndrome. Our studies of C. elegans BBS‐1 protein, as well as other proteins that are known to be assembled into a higher order complex (the BBSome) reveal that functional or structural disruption of this complex leads to exaggerated C. elegans DA signaling to produce Swip via a cell‐autonomous mechanism. We provide evidence that not only does the proper function of cilia in C. elegans DA neurons support normal swimming behavior, but also that bbs‐1 maintains normal levels of DAT‐1 trafficking or function via a RHO‐1 and SWIP‐13/MAPK‐15 dependent pathway where mutants may contribute to Swip independent of altered ciliary function. Together, these studies demonstrate novel contributors to DA neuron function in the worm and demonstrate the utility and efficiency of forward genetic screens using the MMP library. [ABSTRACT FROM AUTHOR]

Numerous studies have now demonstrated that lncRNAs can influence gene expression programs leading to cell and organismal phenotypes. Typically, lncRNA perturbations and concomitant changes in gene expression are measured on the timescale of many hours to days. Thus, we currently lack a temporally grounded understanding of the primary, secondary, and tertiary relationships of lncRNA-mediated transcriptional and epigenetic regulation—a prerequisite to elucidating lncRNA mechanisms. To begin to address when and where a lncRNA regulates gene expression, we genetically engineer cell lines to temporally induce the lncRNA Firre. Using this approach, we are able to monitor lncRNA transcriptional regulatory events from 15 min to four days. We observe that upon induction, Firre RNA regulates epigenetic and transcriptional states in trans within 30 min. These early regulatory events result in much larger transcriptional changes after 12 h, well before current studies monitor lncRNA regulation. Moreover, Firre-mediated gene expression changes are epigenetically remembered for days. Overall, this study suggests that lncRNAs can rapidly regulate gene expression by establishing persistent epigenetic and transcriptional states. Typically, lncRNA perturbations are measured on the timescale of many hours to days. Here, the authors investigate when and where the lncRNA Firre influences epigenetic and transcriptional states, suggesting that lncRNA-mediated gene regulation occurs within minutes and is retained for days. [ABSTRACT FROM AUTHOR]

Background: The gut microbiota (GM) is widely acknowledged to have a significant impact on cardiovascular health and may act as a residual risk factor affecting cardiac structure and function. However, the causal relationship between GM and cardiac structure and function remains unclear. Objective: This study aims to employ a two-sample Mendelian randomization (MR) approach to investigate the causal association between GM and cardiac structure and function. Methods: Data on 119 GM genera were sourced from a genome-wide association study (GWAS) meta-analysis (13,266 European participants) conducted by the MiBioGen consortium, while data on 16 parameters of cardiac structure and function were obtained from the UK Biobank's GWAS of cardiac magnetic resonance imaging (up to 41,135 European participants). Inverse variance weighted (IVW), MR-Egger, and weighted median (WM) methods were utilized for causal association assessments, with sensitivity analyses conducted to reinforce the findings. Finally, biological annotation was performed on the GWAS data of GM and cardiac phenotypes with causal associations to explore potential mechanisms. Results: The MR analysis, predominantly based on the IVW model, revealed 93 causal associations between the genetically predicted abundance of 44 GM genera and 16 cardiac structure and function parameters. These associations maintained consistent directions in MR-Egger and WM models, with no evidence of pleiotropy detected. Biological annotations suggest that GM may influence cardiac structure and function through pathways involved in myocardial cell development, cardiac contractility, and apoptosis. Conclusion: The MR analysis supports a causal association between certain abundances of genetically predicted GM and cardiac structure and function, suggesting that GM could be a residual risk factor impacting cardiac phenotypes. [ABSTRACT FROM AUTHOR]