ABSTRACT
Read-through chimeric RNAs are being recognized as a means to expand the functional transcriptome and contribute to cancer tumorigenesis when mis-regulated. However, current software tools often fail to predict them. We have developed RTCpredictor, utilizing a fast ripgrep tool to search for all possible exon-exon combinations of parental gene pairs. We also added exonic variants allowing searches containing common SNPs. To our knowledge, it is the first read-through chimeric RNA specific prediction method that also provides breakpoint coordinates. Compared with 10 other popular tools, RTCpredictor achieved high sensitivity on a simulated and three real datasets. In addition, RTCpredictor has less memory requirements and faster execution time, making it ideal for applying on large datasets.
Subject(s)
Sequence Analysis, RNA , Software , Sequence Analysis, RNA/methods , Humans , RNA/genetics , Computational Biology/methods , Exons , Algorithms , Polymorphism, Single NucleotideABSTRACT
BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDA) is a highly lethal disease characterized by a spatially heterogeneous tumor microenvironment. Within the PDA microenvironment, cells organize into communities where cell fate is influenced by neighboring cells of diverse ontogeny and function. However, it remains unclear how cell neighborhoods in the tumor microenvironment evolve with treatment and impact clinical outcomes. METHODS: Here, using automated chromogenic multiplex immunohistochemistry and unsupervised computational image analysis of human PDA tumors, we investigated cell neighborhoods in surgically resected tumors from patients with chemotherapy-naïve PDA (n = 59) and neoadjuvant chemotherapy-treated PDA (n = 57). Single cells were defined by lineage markers (CD3, CD8, Foxp3, CD68, CK19), proliferation (Ki67), and neighboring cells. RESULTS: Distinct intratumoral immune and tumor cell subsets were defined by neighboring cells. Higher content of stromal-associated macrophages was seen in chemotherapy-naïve tumors from long-term survivors (overall survival >3 years) compared with short-term survivors (overall survival <1 year), whereas immune-excluded tumor cells were higher in short-term survivors. Chemotherapy-treated vs -naïve tumors showed lower content of tumor-associated T cells and macrophages but similar densities of stromal-associated immune cells. However, proliferating tumor cell subsets with immune-rich neighborhoods were higher in chemotherapy-treated tumors. In a blinded analysis of tumors from patients treated with neoadjuvant chemotherapy, a composite index comprising lower quantities of immune-excluded tumor cells and higher spatially distinct immune cell subsets was associated with prolonged survival. CONCLUSIONS: Together, these data provide new insights into discrete cell communities in PDA and show their clinical relevance.
Subject(s)
Carcinoma, Pancreatic Ductal , Neoadjuvant Therapy , Pancreatic Neoplasms , Tumor Microenvironment , Humans , Carcinoma, Pancreatic Ductal/pathology , Carcinoma, Pancreatic Ductal/immunology , Carcinoma, Pancreatic Ductal/mortality , Carcinoma, Pancreatic Ductal/therapy , Carcinoma, Pancreatic Ductal/surgery , Tumor Microenvironment/immunology , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/immunology , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/therapy , Pancreatic Neoplasms/drug therapy , Male , Female , Aged , Middle Aged , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/analysis , Chemotherapy, Adjuvant , Tumor-Associated Macrophages/immunology , Tumor-Associated Macrophages/metabolism , Treatment Outcome , Lymphocytes, Tumor-Infiltrating/immunology , Cell Proliferation , ImmunohistochemistryABSTRACT
Over half of human genomic DNA is composed of repetitive sequences generated throughout evolution by prolific mobile genetic parasites called transposable elements (TEs). Long disregarded as "junk" or "selfish" DNA, TEs are increasingly recognized as formative elements in genome evolution, wired intimately into the structure and function of the human genome. Advances in sequencing technologies and computational methods have ushered in an era of unprecedented insight into how TE activity impacts human biology in health and disease. Here we discuss the current views on how TEs have shaped the regulatory landscape of the human genome, how TE activity is implicated in human cancers, and how recent findings motivate novel strategies to leverage TE activity for improved cancer therapy. Given the crucial role of methodological advances in TE biology, we pair our conceptual discussions with an in-depth review of the inherent technical challenges in studying repeats, specifically related to structural variation, expression analyses, and chromatin regulation. Lastly, we provide a catalog of existing and emerging assays and bioinformatic software that altogether are enabling the most sophisticated and comprehensive investigations yet into the regulation and function of interspersed repeats in cancer genomes.
Subject(s)
DNA Transposable Elements , Neoplasms , Humans , DNA Transposable Elements/genetics , Computational Biology , Genome, Human , Neoplasms/genetics , Evolution, MolecularABSTRACT
Hybrid sterility, a hallmark of postzygotic isolation, arises from parental genome divergence disrupting meiosis. While chromosomal incompatibility is often implicated, the underlying mechanisms remain unclear. This study investigated meiotic behavior and genome-wide divergence in bighead catfish (C. macrocephalus), North African catfish (C. gariepinus), and their sterile male hybrids (important in aquaculture). Repetitive DNA analysis using bioinformatics and cytogenetics revealed significant divergence in satellite DNA (satDNA) families between parental species. Notably, one hybrid exhibited successful meiosis and spermatozoa production, suggesting potential variation in sterility expression. Our findings suggest that genome-wide satDNA divergence, rather than chromosome number differences, likely contributes to meiotic failure and male sterility in these catfish hybrids.
Subject(s)
Catfishes , DNA, Satellite , Fish Diseases , Hybridization, Genetic , Infertility, Male , Meiosis , Animals , Male , Catfishes/genetics , DNA, Satellite/genetics , Genome , Infertility, Male/genetics , Infertility, Male/veterinary , Africa, Northern , Fish Diseases/geneticsABSTRACT
Lead halide perovskite solar cells have been emerging as very promising candidates for applications in indoor photovoltaics. To maximize their indoor performance, it is of critical importance to suppress intrinsic defects of the perovskite active layer. Herein, a facile solvent-engineering strategy is developed for effective suppression of both surface and bulk defects in lead halide perovskite indoor solar cells, leading to a high efficiency of 35.99% under the indoor illumination of 1000 lux Cool-white light-emitting diodes. Replacing dimethylformamide (DMF) with N-methyl-2-pyrrolidone (NMP) in the perovskite precursor solvent significantly passivates the intrinsic defects within the thus-prepared perovskite films, prolongs the charge carrier lifetimes and reduces non-radiative charge recombination of the devices. Compared to the DMF, the much higher interaction energy between NMP and formamidinium iodide/lead halide contributes to the markedly improved quality of the perovskite thin films with reduced interfacial halide deficiency and non-radiative charge recombination, which in turn enhances the device performance. This work paves the way for developing efficient indoor perovskite solar cells for the increasing demand for power supplies of Internet-of-Things devices.
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Pancreatic adenocarcinoma is an aggressive disease marked by high rates of both local and distant failure. In the minority of patients with potentially resectable disease, multimodal treatment paradigms have allowed for prolonged survival in an increasingly larger pool of well-selected patients. Therefore, it is critical for surgical oncologists to be abreast of current guideline recommendations for both surgical management and multimodal therapy for pancreas cancer. We discuss these guidelines, as well as the underlying data supporting these positions, to offer surgical oncologists a framework for managing patients with pancreatic adenocarcinoma.
Subject(s)
Adenocarcinoma , Pancreatic Neoplasms , Humans , Pancreatic Neoplasms/surgery , Adenocarcinoma/surgery , Neoadjuvant Therapy , Combined Modality TherapyABSTRACT
BACKGROUND: Postoperative adverse events (AEs) in patients with borderline resectable pancreatic ductal adenocarcinoma (BR-PC) treated with neoadjuvant therapy and pancreatectomy in the national cooperative group setting have not been previously characterized. We conducted a preplanned secondary analysis of patients enrolled on the Alliance A021501 clinical trial to quantify perioperative AE rates. METHODS: The A021501 phase 2 trial randomized patients with BR-PC to receive 8 doses of mFOLFIRINOX (Arm 1) or 7 doses of mFOLFIRINOX and hypofractionated radiotherapy (Arm 2), followed by pancreatectomy (December 31, 2016 to May 31, 2019). Adverse events were assessed 90 days after pancreatectomy. RESULTS: Of 126 enrolled patients, 51 (40%) underwent pancreatectomy (n = 32, Arm 1; n = 19, Arm 2) at 28 institutions. Five (10%) patients required reoperation within 90 days; 56% of patients (n = 27/48) experienced at least one grade 3 or higher AE (50% vs. 67%, p = 0.37). Ninety-day mortality was 2.0%. Readmission was less frequent in Arm 1 (16% vs. 42%, p = 0.05), but there were no differences between study arms in rates of reoperation (13% vs. 5%), pancreatic fistula or intra-abdominal abscess requiring drainage (9% vs. 16%), or wound infection (6% vs. 16%). Pancreatic fistula or intra-abdominal abscess requiring drainage was associated with receipt of adjuvant therapy (p = 0.012). No difference in overall survival was observed based on occurrence of postoperative AEs (hazard ratio = 1.1; 95% confidence interval 0.5-2.6). CONCLUSIONS: In this multicenter study, rates of postoperative AEs were consistent with those previously reported. Multimodality trials of preoperative therapy for BR-PC may be performed in the cooperative group setting with careful quality assurance and safety monitoring. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02839343.
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Social media has become omnipresent in society, especially given that it enables the rapid and widespread communication of news, events, and information. Social media platforms have become increasingly used by numerous surgical societies to promote meetings and surgical journals to increase the visibility of published content. In September 2020, Annals of Surgical Oncology (ASO) established its Social Media Committee (SMC), which has worked to steadily increase the visibility of published content on social media platforms, namely X (formerly known as Twitter). The purpose of this review is to highlight the 10 ASO original articles with the most engagement on X, based on total number of mentions, since the founding of the SMC. These articles encompass a wide variety of topics from various oncologic disciplines including hepatopancreatobiliary, breast, and gynecologic surgery.
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Coumarin 7'-hydroxylase activity, a specific marker of CYP2A5 activity, and the protein level were measured in liver microsomes of male mice after chronic exposure to e-cigarettes (e-cigs) (2.4% nicotine). After exposure for 240 minutes per day for 5 days, the activity and the protein level in preproenkephalin (ppENK)-heterozygous [ppENK (+/-)] mice were significantly elevated (P <0.05) compared with the untreated control. This elevation was not due to deletion of the ppENK gene because the activity did not differ among untreated ppENK (+/-), ppENK (-/-), and wild-type ppENK (+/+) controls. Hence, the elevation can reasonably be attributed to nicotine exposure. The production of reactive oxygen species (ROS) upon incubation of the hepatic microsomes of these mice with cotinine was higher in microsomes from the e-cig-treated mice compared with the untreated controls (P < 0.01). Liquid chromatography mass spectrometry assay showed three oxidation products of cotinine, viz trans 3'-hydroxycotinine (3'-HC), 5'-hydroxycotinine (5'-HC), and cotinine N-oxide (CNO) in the plasma of these mice. The result identifies these three oxidation reactions as the source of the observed ROS and also shows that, in nicotine-treated mice, the appropriate "nicotine metabolite ratio" is (3'-HC + 5'-HC + CNO)/cotinine. The results suggest intriguing possibilities that 1) this metabolite ratio may correlate with plasma nicotine clearance and hence impact nicotine's psychoactive effects and 2) chronic e-cig treatment causes ROS-induced oxidative stress, which may play a major role in the regulation of CYP2A5 expression. Our present results clearly show that both the activity and the protein level of CYP2A5 are elevated by repeated exposure to nicotine. SIGNIFICANCE STATEMENT: Nicotine, the psychoactive ingredient of tobacco, is eliminated as the oxidation products of cotinine in reactions catalyzed by the enzymes CYP2A5 in mice and CYP2A6 in humans. This study shows that repeated exposure to e-cigarettes elevates the level of CYP2A5 and the formation of reactive oxygen species. The results suggest an intriguing possibility that CYP2A5 may be upregulated by chronic nicotine exposure due to oxidative stress caused by the oxidation of cotinine in this preclinical model of human smokers.
Subject(s)
Aryl Hydrocarbon Hydroxylases , Electronic Nicotine Delivery Systems , Male , Humans , Animals , Mice , Cotinine/metabolism , Nicotine/metabolism , Reactive Oxygen Species/metabolism , Microsomes, Liver/metabolism , Aryl Hydrocarbon Hydroxylases/metabolism , Cytochrome P-450 CYP2A6/metabolismABSTRACT
The histopathological lesions, minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are entities without immune complex deposits which can cause podocyte injury, thus are frequently grouped under the umbrella of podocytopathies. Whether MCD and FSGS may represent a spectrum of the same disease remains a matter of conjecture. Both frequently require repeated high-dose glucocorticoid therapy with alternative immunosuppressive treatments reserved for relapsing or resistant cases and response rates are variable. There is an unmet need to identify patients who should receive immunosuppressive therapies as opposed to those who would benefit from supportive strategies. Therapeutic trials focusing on MCD are scarce, and the evidence used for the 2021 Kidney Disease: Improving Global Outcomes (KDIGO) guideline for the management of glomerular diseases largely stems from observational and pediatric trials. In FSGS, the differentiation between primary forms and those with underlying genetic variants or secondary forms further complicates trial design. This article provides a perspective of the Immunonephrology Working Group (IWG) of the European Renal Association (ERA) and discusses the KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases focusing on the management of MCD and primary forms of FSGS in the context of recently published evidence, with a special emphasis on the role of rituximab, cyclophosphamide, supportive treatment options and ongoing clinical trials in the field.
Subject(s)
Glomerulosclerosis, Focal Segmental , Kidney Diseases , Nephrosis, Lipoid , Podocytes , Adult , Humans , Child , Glomerulosclerosis, Focal Segmental/complications , Kidney/pathology , Kidney Diseases/pathology , Podocytes/pathologyABSTRACT
BACKGROUND: Neoadjuvant therapy (NT) is increasingly used for patients with pancreatic ductal adenocarcinoma (PDAC), and yet reasons for not undergoing subsequent pancreatectomy are poorly understood. Given the importance of completing multimodality therapy, we investigated factors associated with failure to undergo surgical resection following NT for PDAC. METHODS: SWOG S1505 was a multicenter phase II randomized trial of preoperative mFOLFIRINOX or gemcitabine/nab-paclitaxel prior to planned pancreatectomy for patients with potentially resectable PDAC. Associations between clinical, demographic, and hospital-level characteristics and receipt of surgical resection were estimated via multiple logistic regression. Differences in overall survival from 18 weeks postrandomization (scheduled time of surgery) according to resection status were assessed via Cox regression models. RESULTS: Among 102 eligible patients, 73 (71.6%) underwent successful pancreatectomy, whereas 29 (28.4%) did not, primarily because of progression (n=11; 10.8%) or toxicity during NT (n=9; 8.8%). Weight loss during NT (odds ratio [OR], 0.34; 95% CI, 0.11-0.93) and the hospital's city size (small: OR, 0.24 [95% CI, 0.07-0.80] and large: OR, 0.28 [95% CI, 0.10-0.79] compared with midsize) were significantly associated with a lower probability of surgical resection in adjusted models, whereas age, sex, race, body mass index, performance status, insurance type, geographic region, treatment arm, tumor location, chemotherapy delays/modifications, and hospital characteristics were not. Surgical resection following NT was associated with improved overall survival (median, 23.8 vs 10.8 months; P<.01) even after adjusting for grade 3-5 adverse events during NT, performance status, and body mass index (hazard ratio, 0.55; 95% CI, 0.32-0.95). CONCLUSIONS: Failure to undergo resection following NT was relatively common among patients with potentially resectable PDAC and associated with worse survival. Although few predictive factors were identified in this secondary analysis of the SWOG S1505 randomized trial, further research must focus on risk factors for severe toxicities during NT that preclude surgical resection so that patient-centered interventions can be delivered or alternate treatment sequencing can be recommended.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Neoadjuvant Therapy , Pancreatectomy , Pancreatic Neoplasms , Humans , Neoadjuvant Therapy/methods , Neoadjuvant Therapy/statistics & numerical data , Female , Male , Pancreatic Neoplasms/therapy , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Middle Aged , Aged , Pancreatectomy/methods , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Leucovorin/therapeutic use , Leucovorin/administration & dosage , Carcinoma, Pancreatic Ductal/therapy , Carcinoma, Pancreatic Ductal/mortality , Carcinoma, Pancreatic Ductal/pathology , Paclitaxel/therapeutic use , Paclitaxel/administration & dosage , Fluorouracil/therapeutic use , Fluorouracil/administration & dosage , Irinotecan/therapeutic use , Irinotecan/administration & dosage , Oxaliplatin/therapeutic use , Oxaliplatin/administration & dosage , Deoxycytidine/analogs & derivatives , Deoxycytidine/therapeutic use , Gemcitabine , Adult , AlbuminsABSTRACT
INTRODUCTION: Surgery followed by pathology-guided adjuvant therapy is standard treatment for colon cancer. Data from the FOxTROT clinical trial showed potential benefit of a 6-wk neoadjuvant chemotherapy (NACT) in T3/T4 patients. The present study evaluated real-world outcomes of neoadjuvant therapy in a national cohort of patients with resectable colon cancer. METHODS: 169,120 patients with clinical stage I, II, or III colon cancer from the National Cancer Database registry were included. Patients were categorized as having received neoadjuvant therapy followed by surgery (NACT), surgery then adjuvant chemotherapy (AC), or surgery alone. Factors associated with treatment sequencing and outcomes were assessed. RESULTS: Of identified patients, 1.4% received NACT including 0.5% of stage I, 1.8% of stage II, and 3.0% of stage III. For stage I, 5-y overall survival (OS) was 74.7% after AC, 62.2% after NACT, and 76.4% after SA. For stage II, 5-y OS was 73.2% after AC, 66.8% after NACT, and 64.3% after SA. For stage III, 5-y OS was 67.3% after AC, 67.7% after NACT, and 42.4% after SA. Cox proportional-hazards model suggested NACT had worse outcomes versus AC in clinical stages I (hazard ratio [HR] = 1.59, 95% confidence interval [CI] 1.39-1.85, P < 0.01) and II (HR = 1.37, 95% CI 1.23-1.52, P < 0.01). In stage III, there was no difference in OS between NACT and AC (HR = 1.1, 95% CI 0.99-1.22, P = 0.05). CONCLUSIONS: In a real-world national cohort of patients with resectable colon cancer, NACT had no OS benefit over AC. Future studies should examine which subset of patients might benefit from neoadjuvant approaches.
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INTRODUCTION: Grade-C postoperative pancreatic fistulas (POPFs) are dreaded complications following pancreaticoduodenectomy. The aim of this study was to quantify the incidence and risk factors associated with grade C POPF in a national database. METHODS: The National Surgical Quality Improvement Program targeted user files were queried for patients who underwent elective pancreaticoduodenectomy (2014-2020). Outcomes were compared between clinically relevant (CR) grade B POPF and grade C POPF. RESULTS: Twenty-six thousand five hundred fifty-two patients were included, of which 90.1% (n = 23,714) had No CR POPF, 8.7% (n = 2287) suffered grade B POPF, and 1.2% (n = 327) suffered grade C POPF. There was no change in the rate Grade-C fistula overtime (m = 0.06, P = 0.63), while the rate of Grade-B fistula significantly increased (m = +1.40, P < 0.01). Fistula Risk Scores were similar between grade B and C POPFs (high risk: 34.9% versus 31.2%, P = 0.21). Associated morbidity was increased with grade C POPF, including delayed gastric emptying, organ space infections, wound dehiscence, respiratory complications, renal complications, myocardial infarction, and bleeding. On multivariate logistic regression, diabetes mellitus (odds ratio: 1.41 95% confidence interval: 1.06-1.87, P = 0.02) was associated with grade C POPF. CONCLUSIONS: This study represents the largest contemporary series evaluating grade C POPFs. Of those suffering CR POPF, the presence of diabetes mellitus was associated with grade C POPF. While modern management has led to grade C POPF in 1% of cases, they remain associated with alarmingly high morbidity and mortality, requiring further mitigation strategies to improve outcomes.
Subject(s)
Diabetes Mellitus , Pancreatic Fistula , Humans , Pancreatic Fistula/epidemiology , Pancreatic Fistula/etiology , Pancreatic Fistula/surgery , Pancreas/surgery , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/surgery , Pancreaticoduodenectomy/adverse effects , Risk Factors , Diabetes Mellitus/etiology , Retrospective StudiesABSTRACT
BACKGROUND: In patients with localized pancreatic ductal adenocarcinoma (PDAC) undergoing neoadjuvant therapy (NAT) and resection, selection of adjuvant chemotherapy (AC) is typically guided by high-risk features on histopathologic examination. We evaluated the interaction between post-NAT lymph node metrics and AC receipt on survival. METHODS: Patients who received NAT followed by pancreatectomy (2010-2020) at seven centers were reviewed. Overall survival (OS) in patients receiving AC or not was stratified by lymph node positivity (LNP) or lymph node ratio (LNR) dichotomized at 0.1. Cox models evaluated the independent association between these nodal metrics, AC receipt, and OS. RESULTS: Of 464 patients undergoing NAT and resection, 264 (57%) received AC. Patients selected for AC were younger (median 63 vs. 67 years; p < 0.001), received shorter duration of NAT (2.8 vs. 3.2 months; p = 0.01), had fewer postoperative complications (Clavien-Dindo grade > 3: 1.2% vs. 11.7%; p < 0.001), and lower rates of pathologic complete response (4% vs. 11%; p = 0.01). The median number of nodes evaluated was similar between cohorts (n = 20 in both; p = 0.9). Post-NAT LNP rates were not different, and median LNR was 0.1, in AC and non-AC cohorts. Both LNP (hazard ratio [HR]: 2.1, p < 0.001) and LNR (0 < LNR ≤ 0.1: HR: 1.98, p = 0.002; LNR > 0.1: HR 2.46, p < 0.001) were independently associated with OS on Cox modeling, although receipt of AC was not associated with improved OS (median 30.6 vs. 29.4 months; p = 0.2). In patients with LNR > 0.1, receipt of AC was associated with significantly longer OS compared to non-AC (24 vs. 20 months, respectively; p = 0.04). CONCLUSIONS: LNR following NAT, not simply nodal positivity, may be useful to refine selection of AC in resected PDAC.
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Eukaryotes have varying numbers and structures of characteristic chromosomes across lineages or species. The evolutionary trajectory of species may have been affected by spontaneous genome rearrangements. Chromosome fusion drastically alters karyotypes. However, the mechanisms and consequences of chromosome fusions, particularly in muntjac species, are poorly understood. Recent research-based advancements in three-dimensional (3D) genomics, particularly high-throughput chromatin conformation capture (Hi-C) sequencing, have allowed for the identification of chromosome fusions and provided mechanistic insights into three muntjac species: Muntiacus muntjak, M. reevesi, and M. crinifrons. This study aimed to uncover potential genome rearrangement patterns in the threatened species Fea's muntjac (Muntiacus feae), which have not been previously examined for such characteristics. Deep Hi-C sequencing (31.42 × coverage) was performed to reveal the 3D chromatin architecture of the Fea's muntjac genome. Patterns of repeated chromosome fusions that were potentially mediated by high-abundance transposable elements were identified. Comparative Hi-C maps demonstrated linkage homology between the sex chromosomes in Fea's muntjac and autosomes in M. reevesi, indicating that fusions may have played a crucial role in the evolution of the sex chromosomes of the lineage. The species-level dynamics of topologically associated domains (TADs) suggest that TAD organization could be altered by differential chromosome interactions owing to repeated chromosome fusions. However, research on the effect of TADs on muntjac genome evolution is insufficient. This study generated Hi-C data for the Fea's muntjac, providing a genomic resource for future investigations of the evolutionary patterns of chromatin conformation at the chromosomal level.
Subject(s)
Chromatin , Muntjacs , Animals , Muntjacs/genetics , Chromatin/genetics , Chromosome Mapping/methods , Genome , Sex ChromosomesABSTRACT
Microsatellites are short tandem DNA repeats, ubiquitous in genomes. They are believed to be under selection pressure, considering their high distribution and abundance beyond chance or random accumulation. However, limited analysis of microsatellites in single taxonomic groups makes it challenging to understand their evolutionary significance across taxonomic boundaries. Despite abundant genomic information, microsatellites have been studied in limited contexts and within a few species, warranting an unbiased examination of their genome-wide distribution in distinct versus closely related-clades. Large-scale comparisons have revealed relevant trends, especially in vertebrates. Here, "MicrosatNavigator", a new tool that allows quick and reliable investigation of perfect microsatellites in DNA sequences, was developed. This tool can identify microsatellites across the entire genome sequences. Using this tool, microsatellite repeat motifs were identified in the genome sequences of 186 vertebrates. A significant positive correlation was noted between the abundance, density, length, and GC bias of microsatellites and specific lineages. The (AC)n motif is the most prevalent in vertebrate genomes, showing distinct patterns in closely related species. Longer microsatellites were observed on sex chromosomes in birds and mammals but not on autosomes. Microsatellites on sex chromosomes of non-fish vertebrates have the lowest GC content, whereas high-GC microsatellites (≥ 50 M% GC) are preferred in bony and cartilaginous fishes. Thus, similar selective forces and mutational processes may constrain GC-rich microsatellites to different clades. These findings should facilitate investigations into the roles of microsatellites in sex chromosome differentiation and provide candidate microsatellites for functional analysis across the vertebrate evolutionary spectrum.
Subject(s)
Genome , Vertebrates , Animals , Vertebrates/genetics , Microsatellite Repeats , Sex Chromosomes/genetics , Genomics , Mammals/geneticsABSTRACT
The spin coating method was used to deposit MAPbI2Br films on FTO-glass substrates. Zn2+ (zinc) doping was used for these films at intensity rates of 2% and 4%, respectively. XRD analysis proved that MAPbI2Br films had a cubic structure and a crystalline character. 2% Zn doping into the MAPbI2Br film had a modest large grain size (38.09 nm), Eg (1.95 eV), high refractive index (2.66), and low extinction coefficient (1.67), according to XRD and UV-vis analyses. To facilitate and enhance carrier transit, at contacts as well as throughout the bulk material, the perovskite's trap-state densities decreased. The predicted MAPbI2Br valence and conduction band edges are -5.44 and -3.52, respectively. The conduction band (CB) edge of the film that was exposed to Zn atoms has been pressed towards the lower value, assembly it a better material for solar cells. EIS is particularly useful for understanding charge carrier transport, recombination mechanisms, and the influence of different interfaces within the device structure. Jsc is 11.09 mA cm-2, Voc is 1.09, PCE is 9.372% and FF is 0.777. The cell made with the 2% Zn doped into the MAPbI2Br film demonstrated a superior device.
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This review explores recent progress in sequencing batch reactors (SBRs) and hybrid systems for wastewater treatment, emphasizing their adaptability and effectiveness in managing diverse wastewater compositions. Through extensive literature analysis from 1985 to 2024, the integration of advanced technologies like photocatalysis within hybrid systems is highlighted, showing promise for improved pollutant removal efficiencies. Insights into operational parameters, reactor design, and microbial communities influencing SBR performance are discussed. Sequencing batch biofilm reactors (SBBRs) demonstrate exceptional efficiency in Chemical Oxygen Demand, nitrogen, and phosphorus removal, while innovative anaerobic-aerobic-anoxic sequencing batch reactors (AOA-SBRs) offer effective nutrient removal strategies. Hybrid systems, particularly photocatalytic sequencing batch reactors (PSBRs), show potential for removing persistent pollutants like antibiotics and phenols, underscoring the significance of advanced oxidation processes. However, research gaps persist, including the need for comparative studies between different SBR types and comprehensive evaluations of long-term performance, environmental variability, and economic viability. Addressing these gaps will be vital for the practical deployment of SBRs and hybrid systems. Further exploration of synergies, economic considerations, and reactor stability will enhance the sustainability and scalability of these technologies for efficient and eco-friendly wastewater treatment.
Subject(s)
Bioreactors , Waste Disposal, Fluid , Wastewater , Wastewater/microbiology , Waste Disposal, Fluid/methods , Phosphorus/analysis , Water Pollutants, Chemical/analysis , Biofilms , Water Purification/methods , NitrogenABSTRACT
Skeletal muscle (SM) contains a diverse population of muscle stem (or satellite) cells, which are essential for the maintenance of muscle tissue and positively regulated by prostaglandin E2 (PGE2). However, in aged SM, PGE2 levels are reduced due to increased prostaglandin catabolism by 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a negative regulator of SM tissue repair and regeneration. Screening of a library of 80,617 natural compounds in the ZINC database against 15-PGDH was conducted from PyRx. Further, drug-likeness rules, including those of Lipinski, Ghose, Veber, Egan, and Muegge were performed. The selected complex was forwarded for MD simulations up to 100ns. Based on free energy of binding obtained from docking revealed that ZINC14557836 and ZINC14638400 more potently inhibiting to 15-PGDH than SW033291 (the control and high-affinity inhibitor of 15-PGDH). The free energies of binding obtained from PyRx for 15-PGDH-ZINC14557836, 15-PGDH-ZINC14638400, and 15-PGDH-SW033291 complexes were - 10.30, -9.80, and - 8.0 kcal/mol, respectively. Root mean square deviations (RMSDs), root mean square fluctuations (RMSFs), radii of gyration (Rg), solvent-accessible surface areas (SASAs), and H-bond parameters obtained by 100 ns MD simulations predicted ZINC14557836 and ZINC14638400 more stably complexed with 15-PGDH than SW033291. The several parameters, including physicochemical properties and drug-likenesses, were within acceptable limits, and ZINC14557836 and ZINC14638400 also satisfied other drug-likeness rules, including those of Lipinski, Ghose, Veber, Egan, and Muegge. These findings suggest that ZINC14557836 and ZINC14638400 provide starting points for the development of medications that increase SM regeneration and muscle stem (or satellite) cell numbers by inhibiting 15-PGDH.
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Originating in Thailand, the Thai Ridgeback dog is known for its unique fur ridge that grows in the opposite direction along its back. Selective breeding and a limited populations in Thailand have led to significant close inbreeding among related individuals. The current Thai Ridgeback population is assumed to have experienced a loss of genetic diversity and bottleneck events. Furthermore, studies on the genetic diversity and structure of Thai Ridgeback dogs are limited. Therefore, the aim of this study was to assess the genetic diversity in Thai Ridgeback dogs. Microsatellite genotyping and mitochondrial DNA D-loop sequences were used to assess genetic diversity in 105 Thai Ridgeback dogs from various farms throughout Thailand. Significant genetic diversity and minimal inbreeding were observed in the current Thai Ridgeback population. Signs of bottlenecks were not observed because the exchange of genetic material among Thai Ridgeback owners effectively preserved the genetic diversity. Moreover, the genetic parameters in this study supported owner-to-owner exchanges animals for mating programs. To sustain the genetic diversity of Thai Ridgeback dogs, the use of genetic parameters to manage genetic closeness while preserving breed characteristics is essential. These data are crucial for ensuring demographic stability, which is pivotal for long-term conservation and effective population management.