The genus Equus is the only extant genus of the Equidae family, which belongs to Perissodactyla, an order of mammals characterized by an odd number of toes (odd-toes ungulates). Taking advantage of ...the latest release of the genome assembly, we studied, for the first time in two organisms belonging to the Equus genus, the horse ( Equus caballus ) and the donkey ( Equus asinus ), the T cell receptor gamma (TRG) locus encoding the gamma chain of the γδ T cell receptor. Forty-five Variable (TRGV) genes belonging to the seven IMGT-NC validated mammalian TRGV subgroups, 25 Joining (TRGJ) and 17 Constant (TRGC) genes organized in 17 V-J-(J)-C cassettes, in tandem on about 1100 Kb, characterize the horse TRG locus, making the horse TRG locus the one with the greatest extension and with a significantly higher number of genes than the orthologous loci of the other mammalian species. A clonotype analysis of an RNA-seq transcriptomic dataset derived from spleen of an adult healthy horse, using the complete set of the horse TRGJ germline gene sequences as a probe, revealed that, in addition to the most prominent V-J rearrangements within each cassette, there is a relevant proportion of trans-cassette V-J recombination, whereby the same TRGV genes can recombine with different TRGJ genes spliced to the corresponding TRGC genes. This recombinant event strongly contributes to the diversity of the γ chain repertoire. In the donkey TRG locus, 34 TRGV, 21 TRGJ and 14 TRGC genes distributed in 14 V-J-(J)-C cassettes were found in a region of approximately 860 kb. Although the donkey’s TRG is smaller than that of the horse, in Equus genus, this is still the second largest locus so far found in any mammalian species. Finally, the comparative analysis highlighted differences in size and gene content between the horse and donkey TRG loci, despite belonging to the same genus, indicating a good level of diversification within Equus . These data is in agreement with the evolutionary idea of the existence of a Equus recent common ancestor in rapid evolution, for which a mutation rate between horses and donkeys is more comparable to that between species belonging to different genera rather than to species of the same genus.
This special volume collects contributions from leading scholars who scrutinize the challenges digital finance presents for the EU internal market and financial market regulation from multiple public ...policy perspectives. Author contributions aim to provide policy-relevant research and ideas shedding light on the complexities of the digital finance promise. They also offer solid proposals for reform of EU financial services law.
To achieve personalized and optimized treatment for rectal cancer patients, accurate predictions of treatment response based on pre-treatment medical images are essential. However, these images often ...have varying settings. Our study examined the impact of standardizing pixel spacing and slice thickness on predictive accuracy in medical image analysis. Using our custom-built Evolutionary Random Subspace Forest algorithm, we investigated how altering these spatial settings affected the accuracy of tumor regression grade prediction. We examined 16 different adjustments to spacing settings in CT images taken from 139 rectal cancer patients. Furthermore, we explored a Bayesian approach within our random forest algorithm.We utilized the modified data as prior information and employed radiomics data from the same CT images as posterior information. This study revealed that these alterations notably improved both training and validation accuracy, where the Bayesian approach enhanced model generalization, indicating a close alignment between training and validation results.
The histological responses (HRs) after systemic chemotherapy should be used to determine the optimal management of patients with peritoneal and liver metastasis from colorectal cancer (cPM, cLM), in ...curative intent. We aimed to compare HRs of cPM and cLM in metastatic mice model after chemotherapy.
Colon carcinoma CT26-luc cells were transplanted into syngeneic BALB/c mice by intraperitoneal (leading to cPM), intrasplenic (leading to cLM), or intraperitoneal + intrasplenic (leading to cPM cLM) injections and follow up using bioluminescence during 21 days. Bi-chemotherapeutic treatment (5-fluorouracil at D11, D17, and D20, and oxaliplatin at D13 and D19) was administered. The peritoneal cancer index (PCI) and HRs using Peritoneal Regression Grading Score (PRGS) and Tumor Regression Grade (TRG) classifications were analyzed at day 21.
Unlike bioluminescence rate, PCI was reduced after chemotherapy in all treated groups with cPM comparatively to controls (33 ± 9.5 vs. 19.8 ± 5, p = 0.002 for cPM groups; 37.7 ± 3.6 vs. 25.2 ± 10.8, p = 0.0003 for the cPM + cLM groups). The complete or major HR rates were higher in all treated groups compared to the non-treated mice (cPM, 2.29 ± 0.55 vs. 3.56 ± 1.01; cLM, 2.43 ± 1.89 vs. 4.86 ± 0.378; cPM + cLM, 2.73 ± 1.03 and 2.2 ± 0.65 vs. 3.79 ± 0.75 and 4.36 ± 0.43). The complete or major HR rates after chemotherapy were similar across the metastatic sites in 60% for cPM + cLM group.
The efficacy of chemotherapeutic treatment did not differ between the metastatic sites. Murine models are suitable in histological analyses to study tumor development and regression but clinical study will be performed to confirm these results.
Goats (Capra hircus), one of the first domesticated species, are economically important for milk and meat production, and their broad geographical distribution reflects their successful adaptation to ...diverse environmental conditions. Despite the relevance of this species, the genetic research on the goat traits is limited compared to other domestic species. Thanks to the latest goat reference genomic sequence (ARS1), which is considered to be one of the most continuous assemblies in livestock, we deduced the genomic structure of the T cell receptor beta (TRB) and gamma (TRG) loci in this ruminant species.
Our analyses revealed that although the organization of the goat TRB locus is broadly similar to that of the other artiodactyl species, with three in-tandem D-J-C clusters located at the 3' end, a complex and extensive series of duplications have occurred in the V genes at the 5' end, leading to a marked expansion in the number of the TRBV genes. This phenomenon appears to be a feature of the ruminant lineage since similar gene expansions have also occurred in sheep and cattle. Likewise, the general organization of the goat TRG genes is typical of ruminant species studied so far, with two paralogous TRG loci, TRG1 and TRG2, located in two distinct and distant positions on the same chromosome as result of a split in the ancestral locus. Each TRG locus consists of reiterated V-J-J-C cassettes, with the goat TRG2 containing an additional cassette relative to the corresponding sheep and cattle loci.
Taken together, these findings demonstrate that strong evolutionary pressures in the ruminant lineage have selected for the development of enlarged sets of TRB and TRG genes that contribute to a diverse T cell receptor repertoire. However, differences observed among the goat, sheep and cattle TRB and TRG genes indicate that distinct evolutionary histories, with independent expansions and/or contractions, have also affected each ruminant species.
Soil extracts are useful nutrients to enhance the growth of microalgae. Therefore, the present study attempts for the use of virgin soils from Peninsular Malaysia as growth enhancer. Soils collected ...from Raja Musa Forest Reserve (RMFR) and Ayer Hitam Forest Reserve (AHFR) were treated using different extraction methods. The total dissolved nitrogen (TDN), total dissolved phosphorus (TDP), and dissolved organic carbon (DOC) concentrations in the autoclave methods were relatively higher than natural extraction with up to 132.0 mg N/L, 10.7 mg P/L, and 2629 mg C/L, respectively for RMFR. The results of TDN, TDP, and DOC suggested that the best extraction methods are autoclaved at 121 °C twice with increasing 87%, 84%, and 95%, respectively.
TRG 4C dominated the growth at 121 °C twice extraction method in the RMRF and AHRF samples, with increasing 54.3% and 14%, respectively. The specific growth rate (µ) of both microalgae were relatively higher, 0.23 d
in the Ayer Hitam Soil. This extract served well as a microalgal growth promoter, reducing the cost and the needs for synthetic medium. Mass production of microalgae as aquatic feed will be attempted eventually. The high recovery rate of nutrients has a huge potential to serve as a growth promoter for microalgae.
Three Gorges Reservoir (TGR) water fluctuation creates high water level (HWL) and low water level (LWL) condition in TGR aquatic ecosystem. HWL fluies significant nutrients, mainly introducing carbon ...and nitrogen into the ecosystem. The nitrogen input is a concern for water quality management of TGR since the possible eutrophication caused by nitrogen spike. Sediment denitrification is widely recognized as the dominant nitrogen removal process in freshwater ecosystem. Therefore, the response of TGR sediments microbiome to the input nitrogen flucatution is crucial for both nitrogen balance and the eutrophication status of the ecosystem. Using high throughout sequencing of 16S rRNA gene and the predicted denitrification enzyme, and qualitative PCR of denitrification functional genes, we investigated how TGR sediments denitrification microbiome respond to the input nitrogen flux during two seasonal water fluctuation events. Concomitant to expected input carbon and nitrogen, we observed distinct microbial community structure and denitrification microbiota in HWL and LWL, and also in seasonal sampling events. Sediments pH, total nitrogen and nitrate were the significant impact factors in shaping the microbial community structure. Important denitrification microbiota (e.g., Saprospiraceae, Gemmatimonadaceae, Pseudomonas) are the main taxa of the microbial community and also showed water level and seasonal variation. The relative abundance of denitrification enzyme (nar, nir, nor, nos) and function genes (nirS, nirK, nosZ) were higher in LWL than HWL. Denitrification enzyme were significantly (p < 0.05) correlated with the nitrate concentration. In addition, the relative abundance of denitrification enzyme and function genes increased during the transition from 2014 HWL to 2015 LWL. Results suggested that TGR sediments denitrification is nitrate concentration dependent. The denitrification microbiome is initially inhibited due to high nitrate input, then they developed denitrification ability in response to high nitrate concentration.
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•TGR water fluctuation events flux significant nitrogen into the sediments.•Denitrification microbiota showed distinct structure in HWL and LWL.•Denitrification enzyme were significantly correlated with the nitrate concentration.•TRG sediments denitrification is nitrate concentration dependent.
The study aimed to assess if adherence to a total-neoadjuvant-treatment (TNT) protocol followed by observation(watch-and-wait) led to the successful nonoperative-management of low-rectal-cancer.
In ...this study, patients with primary, resectable-T3-T4, N0–N1 distal-rectal-adenocarcinoma underwent-chemoradiotherapy + consolidation-chemotherapy (TNT). During the-TNT-period, endoscopy, MRI, and FDG-PET/CT were performed. We allocated patients with complete-clinical-tumor-regression, who underwent endoscopy every two months, MRI every-four-months, and PET/CT every-six-months-after-treatment, to the observation-group(OG). All other patients were referred for surgery. The OG was followed-up. The primary endpoint was local tumor-ecurrence after allocation to the OG.
Between 2015 and 2018, we enrolled 66-patients. Of 60-patients who were eligible to participate, 39 had complete-clinical-response(cCR) and were allocated to the OG, six underwent local-excision (LE), and 15 underwent total-mesorectal-excision (TME). The median follow-up duration was 22 (9–42) months. The local-recurrence-rate in the OG was 15.3%, and the LE and TME rates were 16.6% and 0%, respectively. All recurrence cases were salvaged through either LE or TME. The-distant-metastasis rate was 5.1%, 16.6%, and 12.5% in the OG, LE, and TME groups, respectively. The endoscopic negative-predictive-value(NPV) was 50%, and the positive-predictive-value(PPV) was 76.9% in the surgery group (LE + TME). MRI; NPV-50%, PPV-76.9%. PET/CT; NPV-100%, PPV-93.3%. Six patients(28.57%) from surgery group achieved complete pathological response (cPR).
Our results indicated a high proportion of selected-rectal-cancers with-cCR after neo-adjuvant-therapy could potentially be managed non-operatively, and major surgery may be avoided.
T lymphocytes are the principal actors of vertebrates' cell-mediated immunity. Like B cells, they can recognize an unlimited number of foreign molecules through their antigen-specific heterodimer ...receptors (TRs), which consist of αβ or γδ chains. The diversity of the TRs is mainly due to the unique organization of the genes encoding the α, β, γ, and δ chains. For each chain, multi-gene families are arranged in a TR locus, and their expression is guaranteed by the somatic recombination process. A great plasticity of the gene organization within the TR loci exists among species. Marked structural differences affect the TR γ (TRG) locus. The recent sequencing of multiple whole genome provides an opportunity to examine the TR gene repertoire in a systematic and consistent fashion. In this review, we report the most recent findings on the genomic organization of TRG loci in mammalian species in order to show differences and similarities. The comparison revealed remarkable diversification of both the genomic organization and gene repertoire across species, but also unexpected evolutionary conservation, which highlights the important role of the T cells in the immune response.
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