Specific Molecular Patterns Research Articles

Single-cell RNA sequencing comparison of CD4+, CD8+ and TCR-γδ+ cutaneous T-cell lymphomas reveals subset-specific molecular phenotypes.

Malignant clones of primary cutaneous T-cell lymphomas (CTCL) can show a CD4, CD8 or TCR-γδ phenotype, but their individual impact on tumor biology and skin lesion formation remains ill-defined. To perform a comprehensive molecular characterization of CD4+ vs. CD8+ and TCR-γ/δ+ CTCL lesions. We performed scRNA-seq of 18 CTCL skin biopsies to compare classic CD4+ advanced-stage mycosis fungoides (MF) with TCR-γ/δ+MF and primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma (Berti's lymphoma). Malignant clones of TCR-γ/δ+MF and Berti's lymphoma showed similar clustering patterns distinct from CD4+MF, along with increased expression of cytotoxic markers such as NKG7, CTSW, GZMA, and GZMM. Only advanced-stage CD4+MF clones expressed central memory T-cell markers (SELL, CCR7, LEF1), alongside B1/B2 blood involvement, whereas TCR-γ/δ+MF and Berti's lymphoma harbored a more tissue-resident phenotype (CD69, CXCR4, NR4A1) without detectable cells in the blood. CD4+MF and TCR-γ/δ+MF skin lesions harbored strong type 2 immune activation across myeloid cells, while Berti's lymphoma was more skewed towards type 1 immune responses. Both CD4+MF and TCR-γ/δ+MF lesions showed upregulation of keratinocyte hyperactivation markers such as S100As and KRT16 genes. This increase was entirely absent in Berti's lymphoma, possibly reflecting an aberrant keratinocyte response to invading tumor cells, that could contribute to the formation of the typical ulcero-necrotic lesions within this entity. Our scRNAseq profiling study reveals specific molecular patterns associated with distinct CTCL subtypes.

HGG-17. DECIPHERING GENETICS AND EPIGENETICS OF HIGH-GRADE GLIOMAS WITH BRAF ACTIVATING ALTERATION IS SUPPORTING THE DISCOVERY OF A NEW INTRACRANIAL SARCOMA-LIKE BRAF POSITIVE ENTITY

Abstract BACKGROUND The current WHO classification of Central Nervous System tumors recognizes several glioma types driven by the BRAFV600E mutation. These tumors mostly encompass pediatric low-grade gliomas. Nevertheless, a subset of them behaves as anaplastic gliomas and, currently, the unique predictive criterion linked to anaplasia is an elevated mitotic index (more than 2.5 mitoses/mm2). Histologically, the high-grade gliomas harboring BRAFV600E alteration mostly correspond to WHO grade 3 pleomorphic xanthoastrocytoma, IDH wild-type glioblastoma, entering the WHO grade 4 subset like the epithelioid subtype, and the rarer high-grade gliomas with piloïd features. These tumor types share their histomolecular features making differential diagnoses difficult. In this setting, DNA methylation profiling may be very useful to precise the integrative diagnosis. However, some of those high-grade forms failed in our experience to be classified in any methylation class with v11b4 version of the Heidelberg classifier. METHODS To understand the reasons explaining this standard classification failure, we investigated with multi-omics approaches (epigenetics, next-generation sequencing, RNAseq, proteomics and metabolomics) a well clinical characterized cohort of 17 high-grade pediatric intracranial tumors harboring this mutation. RESULTS Interestingly, almost all tumors show similar morphological features and associated passenger molecular alterations mostly CDKN2A homozygous deletion. When using the new v12.5 brain tumor classifier, the methylation profiling of the 2/17 unclassified tumors was clustering with a new MPNST (Malignant Peripheral Nerve Sheath Tumor) methylation entity. The RNAseq and proteomics analyses were showing a different molecular pattern from standard BRAF-mutated high-grade gliomas, even the clinical, radiological and histomolecular characteristics were comparable. CONCLUSION So, methylation profiling should be part of the mandatory molecular assessments to perform when a BRAF-mutated tumor is seen by neuropathologists. Furthermore, the multiomics analyses helped us to define a specific molecular pattern of this new BRAF-driven entity, where frequency and prognosis need to be determined on another larger series.

Damage-associated molecular patterns as a mechanism of sevoflurane-induced neuroinflammation in neonatal rodents.

General anesthesia is inevitable for pediatric patients undergoing surgery, though volatile anesthetic agents may cause neuroinflammation and neurodevelopmental impairment; however, the underlying pathophysiology remains unclear. We aimed to investigate the neuroinflammation mechanism in developing rat brains associated with sevoflurane exposure time, by identifying the specific damage-associated molecular patterns (DAMPs) pathway and evaluating the effects of non-steroidal anti-inflammatory drugs (NSAIDs) in alleviating neuroinflammation. A three-step experiment was conducted to investigate neuroinflammation induced by sevoflurane. First, the exposure time required for sevoflurane to cause neuroinflammation was determined. Next, the specific pathways of DAMPs involved in neuroinflammation by sevoflurane were identified. Finally, the effects of NSAIDs on sevoflurane-induced neuroinflammation were investigated. The expression of various molecules in the rat brain were assessed using immunohistochemistry, immunofluorescence, quantitative real-time polymerase chain reaction, western blot analysis, and enzyme-linked immunosorbent assay. In total, 112 rats (aged 7 days) were used, of which six rats expired during the experiment (mortality rate, 5.3%). Expression of CD68, HMGB-1, galectin-3, TLR4, TLR9, and phosphorylated NF-κB was significantly increased upon 6 h of sevoflurane exposure. Conversely, transcriptional levels of TNF-α and IL-6 significantly increased and IFN-γ significantly decreased after 6 h of sevoflurane exposure. Co-administration of NSAIDs with sevoflurane anesthesia significantly attenuated TNF-α and IL-6 levels and restored IFN-γ levels. In conclusion, 6 h of sevoflurane exposure induces neuroinflammation through the DAMPs pathway, HMGB-1, and galectin-3. Co-administration of ibuprofen reduced sevoflurane-induced neuroinflammation.

Molecular insights into codon usage analysis of mitochondrial fission and fusion gene: relevance to neurodegenerative diseases.

Mitochondrial dysfunction is the leading cause of neurodegenerative disorders like Alzheimer's disease and Parkinson's disease. Mitochondria is a highly dynamic organelle continuously undergoing the process of fission and fusion for even distribution of components and maintaining proper shape, number, and bioenergetic functionality. A set of genes governs the process of fission and fusion. OPA1, Mfn1, and Mfn2 govern fusion, while Drp1, Fis1, MIEF1, and MIEF2 genes control fission. Determination of specific molecular patterns of transcripts of these genes revealed the impact of compositional constraints on selecting optimal codons. AGA and CCA codons were over-represented, and CCC, GTC, TTC, GGG, ACG were under-represented in the fusion gene set. In contrast, CTG was over-represented, and GCG, CCG, and TCG were under-represented in the fission gene set. Hydropathicity analysis revealed non-polar protein products of both fission and fusion gene set transcripts. AGA codon repeats are an integral part of translational regulation machinery and present a distinct pattern of over-representation and under-representation in different transcripts within the gene sets, suggestive of selective translational force precisely controlling the occurrence of the codon. Out of six synonymous codons, five synonymous codons encoding for leucine were used differently in both gene sets. Hence, forces regulating the occurrence of AGA and five synonymous leucine-encoding codons suggest translational selection. A correlation of mutational bias with gene expression and codon bias and GRAVY and AROMA signifies the selection pressure in both gene sets, while the correlation of compositional bias with gene expression, codon bias, protein properties, and minimum free energy signifies the presence of compositional constraints. More than 25% of codons of both gene sets showed a significant difference in codon usage. The overall analysis shed light on molecular features of gene sets involved in fission and fusion.

Electron, hole, and energy transfer dynamics in non-fullerene small-molecule acceptors.

When photoexcited, an organic photovoltaic (OPV) donor/acceptor (D/A) blend is expected to undergo charge separation (CS) through three channels: electron transfer, hole transfer, and energy transfer-induced electron/hole transfer. However, previous spectroscopic studies on various blends based on non-fullerene acceptors (NFAs) have not been able to directly characterize the dynamics of these processes, due to spectral overlap of the involved intermediate species. Herein, we study the excited-state dynamics of D/A blends composed of PBDB-T (D) and a L-series NFA (L4 or L5) and show that the species responsible for these processes in the PBDB-T/L4 blend can be spectroscopically identified, allowing us to disentangle their dynamics. Moreover, we confirm the occurrence of photoinduced CS in neat L4 and L5 films, providing direct evidence that CS can occur under nearly zero driving force in OPV systems. Further density functional theory calculations suggest that specific molecular packing patterns may play an important role in facilitating CS.

Antibody preparation and age-dependent distribution of TLR8 in Bactrian camel spleens

BackgroundToll-like receptor 8 (TLR8) can recognize specific pathogen-associated molecular patterns and exert multiple immunological functions through activation of signaling cascades. However, the precise distribution and age-related alterations of TLR8 in the spleens of Bactrian camels have not yet been investigated. This study aimed to prepare a rabbit anti-Bactrian camel TLR8 polyclonal antibody and elucidate the distribution of TLR8 in the spleens of Bactrian camels at different age groups. The methodology involved the construction of the pET-28a-TLR8 recombinant plasmid, followed by the expression of TLR8 recombinant protein via prokaryotic expression. Subsequently, rabbits were immunized with the purified protein to prepare the TLR8 polyclonal antibody. Finally, twelve Alashan Bactrian camels were categorized into four groups: young (1–2 years), pubertal (3–5 years), middle-aged (6–16 years) and old (17–20 years). These camels received intravenous sodium pentobarbital (20 mg/kg) anesthesia and were exsanguinated to collect spleen samples. Immunohistochemical techniques were employed to observe and analyze the distribution patterns and age-related changes of TLR8 in the spleen.ResultsThe results showed that the TLR8 recombinant protein was expressed in the form of inclusion body with a molecular weight of 52 kDa, and the optimal induction condition involved 0.3 mmol/L IPTG induction for 8 h. The prepared antibody yielded a titer of 1:32 000, and the antibody demonstrated specific binding to TLR8 recombinant protein. TLR8 positive cells exhibited a consistent distribution pattern in the spleen across different age groups of Bactrian camels, primarily scattered within the periarterial lymphatic sheath of the white pulp, marginal zone, and red pulp. The predominant cell type expressing TLR8 was macrophages, with expression also observed in neutrophils and dendritic cells. Statistical analysis revealed that there were significant differences in the distribution density of TLR8 positive cells among different spleen regions at the same age, with the red pulp, marginal zone, and white pulp showing a descending order (P<0.05). Age-related changes indicated that the distribution density in the marginal zone and red pulp exhibited a similar trend of initially increasing and subsequently decreasing from young to old camels. As camels age, there was a significant decrease in the distribution density across all spleen regions (P<0.05).ConclusionsThe results confirmed that this study successfully prepared a rabbit anti-Bactrian camel TLR8 polyclonal antibody with good specificity. TLR8 positive cells were predominantly located in the red pulp and marginal zone of the spleen, signifying their pivotal role in the innate immune response of the spleen. Aging was found to significantly reduce the density of TLR8 positive cells, while leaving their scattered distribution characteristics unaffected. These findings provide valuable support for further investigations into the immunomorphology and immunosenescence of the spleen in Bactrian camels.

Molecular Characteristics and Evolutionary Relationships of Toll-Like Receptor (TLR21) of Indonesian KUB-1 Chicken

In vertebrates, the immune system has several Toll-like receptors (TLRs) to recognize specific pathogen-associated molecular patterns (PAMPs). In aves, TLR21 is known to be a functional homolog of TLR9 in mammals. This study aimed to determine the molecular characteristics of TLR21 in KUB-1 chicken, a superior breed of Indonesian local chicken, and their evolutionary relationship. The TLR21 gene was obtained from the ovarian RNA extraction and synthesized into cDNA by reverse transcription. We found that the cDNA sequence of the TLR21 of KUB-1 chicken has a length of 3504 bp, including a 2823 bp open reading frame (ORF), which encodes a putative protein of 940 amino acids (aa). The deduced KUB-1 chicken TLR21 protein consisted of 720 aa in the extracellular domain containing 20 LRRs, 23 aa in the transmembrane region, and 141 aa of Toll‐IL‐1 receptor in the intracellular domain, and had a molecular weight of 107 kDa. The KUB-1 chicken TLR21 had homology of about 99%, 76%, and 43% with other TLR21 from other breeds of chicken, non-chicken poultry, and fish, respectively. Its molecular character was conserved throughout the evolution of TLR21 in chicken, so the KUB-1 chicken was not much different from the broiler. However, there has been an evolution in duck and goose, although the function is still the same. Evolutionarily, Gallus gallus_KUB-1 TLR21, which belongs to the TLR11 Family, has differentiated from fish TLR21 and formed a paraphyletic relationship with TLR21 in Anser cygnoides and Anas platyrhynchos.

Dendritic Cells Pulsed with Tumor Lysates Induced by Tetracyanotetra(aryl)porphyrazines-Based Photodynamic Therapy Effectively Trigger Anti-Tumor Immunity in an Orthotopic Mouse Glioma Model.

Research in the past decade on immunogenic cell death (ICD) has shown that the immunogenicity of dying tumor cells is crucial for effective anticancer therapy. ICD induction leads to the emission of specific damage-associated molecular patterns (DAMPs), which act as danger signals and as adjuvants to activate specific anti-tumor immune responses, leading to the elimination of tumor cells and the formation of long-term immunological memory. ICD can be triggered by many anticancer treatment modalities, including photodynamic therapy (PDT). However, due to the variety of photosensitizers used and the lack of a universally adopted PDT protocol, there is a need to develop novel PDT with a proven ICD capability. In the present study, we characterized the abilities of two photoactive dyes to induce ICD in experimental glioma in vitro and in vivo. One dye was from the tetracyanotetra(aryl)porphyrazine group with 9-phenanthrenyl (pz I), and the other was from the 4-(4-fluorobenzyoxy)phenyl (pz III) group in the aryl frame of the macrocycle. We showed that after the photosensitizers penetrated into murine glioma GL261 cells, they localized predominantly in the Golgi apparatus and partially in the endoplasmic reticulum, providing efficient phototoxic activity against glioma GL261 cells upon light irradiation at a dose of 20 J/cm2 (λex 630 nm; 20 mW/cm2). We demonstrated that pz I-PDT and pz III-PDT can act as efficient ICD inducers when applied to glioma GL261 cells, facilitating the release of two crucial DAMPs (ATP and HMGB1). Moreover, glioma GL261 cells stimulated with pz I-PDT or pz III-PDT provided strong protection against tumor growth in a prophylactic subcutaneous glioma vaccination model. Finally, we showed that dendritic cell (DC) vaccines pulsed with the lysates of glioma GL261 cells pre-treated with pz-I-PDT or pz-III-PDT could act as effective inducers of adaptive anti-tumor immunity in an intracranial orthotopic glioma mouse model.

NOD-like Receptor Signaling Pathway in Gastrointestinal Inflammatory Diseases and Cancers.

Nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) are intracellular proteins with a central role in innate and adaptive immunity. As a member of pattern recognition receptors (PRRs), NLRs sense specific pathogen-associated molecular patterns, trigger numerous signaling pathways and lead to the secretion of various cytokines. In recent years, cumulative studies have revealed the significant impacts of NLRs in gastrointestinal (GI) inflammatory diseases and cancers. Deciphering the role and molecular mechanism of the NLR signaling pathways may provide new opportunities for the development of therapeutic strategies related to GI inflammatory diseases and GI cancers. This review presents the structures and signaling pathways of NLRs, summarizes the recent advances regarding NLR signaling in GI inflammatory diseases and GI cancers and describes comprehensive therapeutic strategies based on this signaling pathway.

Genome-wide analysis and characterization of the LRR-RLK gene family provides insights into anthracnose resistance in common bean

Anthracnose, caused by the hemibiotrophic fungus Colletotrichum lindemuthianum, is a damaging disease of common beans that can drastically reduce crop yield. The most effective strategy to manage anthracnose is the use of resistant cultivars. There are many resistance loci that have been identified, mapped and associated with markers in common bean chromosomes. The Leucine-rich repeat kinase receptor protein (LRR-RLK) family is a diverse group of transmembrane receptors, which potentially recognizes pathogen-associated molecular patterns and activates an immune response. In this study, we performed in silico analyses to identify, classify, and characterize common bean LRR-RLKs, also evaluating their expression profile in response to the infection by C. lindemuthianum. By analyzing the entire genome of Phaseolus vulgaris, we could identify and classify 230 LRR-RLKs into 15 different subfamilies. The analyses of gene structures, conserved domains and motifs suggest that LRR-RLKs from the same subfamily are consistent in their exon/intron organization and composition. LRR-RLK genes were found along the 11 chromosomes of the species, including regions of proximity with anthracnose resistance markers. By investigating the duplication events within the LRR-RLK family, we associated the importance of such a family with an expansion resulting from a strong stabilizing selection. Promoter analysis was also performed, highlighting cis-elements associated with the plant response to biotic stress. With regard to the expression pattern of LRR-RLKs in response to the infection by C. lindemuthianum, we could point out several differentially expressed genes in this subfamily, which were associated to specific molecular patterns of LRR-RLKs. Our work provides a broad analysis of the LRR-RLK family in P. vulgaris, allowing an in-depth structural and functional characterization of genes and proteins of this family. From specific expression patterns related to anthracnose response, we could infer a direct participation of RLK-LRR genes in the mechanisms of resistance to anthracnose, highlighting important subfamilies for further investigations.

Kiwifruit's Allergy in Children: What Do We Know?

Kiwifruit allergy is an emerging pathological condition in both general and pediatric populations with a wide range of symptoms linked to variable molecular patterns, justifying systemic and cross-reactions with other allergens (i.e., latex, pollen, and fruit). Skin prick test (SPT), specific serum IgE (Act d 1, Act d 2, Act d 5, Act d 8, and Act d 10) directed against five out of thirteen molecular allergens described in the literature, and oral test challenge with kiwifruit are available for defining diagnosis. The management is similar to that of other food allergies, mostly based on an elimination diet. Although kiwi allergy has been on the rise in recent years, few studies have evaluated the clinical characteristics and methods of investigating this form of allergy. Data collected so far show severe allergic reaction to be more frequent in children compared to adults. Therefore, the aim of this review is to collect the reported clinical features and the available association with specific molecular patterns of recognition to better understand how to manage these patients and improve daily clinical practice.

Toll-like receptor 2-mediated downstream cytokine levels as determinant of malaria pathogenesis.

Toll-like receptors (TLRs) are transmembrane proteins that recognize specific molecular patterns and activate downstream cytokine production usually for the eradication of invading pathogens. The objective of this study was to evaluate the genetic polymorphism of TLR2 Arg753Gln (rs 5743708) and soluble cytokines and TLR2 expression levels in malaria disease cases. The study included prospectively collected 2 ml blood samples from 153 individuals clinically suspected for malaria and confirmed by microscopy and RDT from Assam. Stratification of the study groups was done as healthy control (HC, n=150), uncomplicated malaria (UC-M, n=128) and severe malaria (SM, n=25). The PCR-restriction fragment length polymorphism (RFLP) method was applied for the analysis of TLR2 Arg753Gln polymorphism and following the ELISA for soluble serum TLR2 (sTLR2) and its associated downstream cytokines, viz. tumour necrosis factor (TNF)-α and interferon (IFN)-γ levels. Variation in TLR2 Arg753Gln gene showed no association with the susceptibility and the severity of malarial infection. Soluble TLR2 expression was significantly higher in uncomplicated malaria (UC-M) cases compared to healthy controls (P=0.045) and in terms of SM cases, the expression was also found to be higher in UC-M cases (P=0.078). The TNF-α expression was significantly higher in SM cases compared to both UC-M and control (P=0.003 and P=0.004). Similarly, significantly elevated expression of IFN-γ was noted in SM cases compared to both UC-M (P=0.001) and healthy controls (P<0.001). The present study suggests the association of deregulated TLR2 pathway that leads to the deleterious downstream immune response in the development of malarial pathogenicity.

Prospects of toll-like receptors in dairy cattle breeding.

Toll-like receptors (TLRs) play an important role in mediating the immune response against various microbes, such as bacteria, viruses, parasites, and fungi, in innate and adaptive immunity. Ten functional TLRs (TLR1 to TLR10) have been identified and mapped in cattle, with each TLR recognising specific pathogen-associated molecular patterns. The variation in genes controlling the immune response contributes to susceptibility or resistance to various infectious diseases such as mastitis, bovine tuberculosis, and paratuberculosis. Identifying TLR SNPs shows promising results for future marker-assisted breeding strategies, screening for disease risks, and improving the genetic resistance of dairy cattle. This article aims not only to review the research into susceptibility or resistance to infectious diseases and milk production traits in dairy cattle but also to discuss the limitations in current studies and the prospects in dairy cattle breeding.

The captivating role of calcium in plant-microbe interaction.

Plant immune response is fascinating due to the complete absence of a humoral system. The adaptive immune response in plants relies on the intracellular orchestration of signalling molecules or intermediates associated with transcriptional reprogramming. Plant disease response phenomena largely depend on pathogen recognition, signal perception, and intracellular signal transduction. The pathogens possess specific pathogen-associated molecular patterns (PAMP) or microbe-associated molecular patterns (MAMP), which are first identified by pattern recognition receptors (PRRs) of host plants for successful infection. After successful pathogen recognition, the defence response is initiated within plants. The first line of non-specific defence response is called PAMP-triggered immunity (PTI), followed by the specific robust signalling is called effector-triggered immunity (ETI). Calcium plays a crucial role in both PTI and ETI. The biphasic induction of reactive oxygen species (ROS) is inevitable in any plant-microbe interaction. Calcium ions play crucial roles in the initial oxidative burst and ROS induction. Different pathogens can induce calcium accumulation in the cytosol ([Ca2+]Cyt), called calcium signatures. These calcium signatures further control the diverse defence-responsive proteins in the intracellular milieu. These calcium signatures then activate calcium-dependent protein kinases (CDPKs), calcium calmodulins (CaMs), calcineurin B-like proteins (CBLs), etc., to impart intricate defence signalling within the cell. Decoding this calcium ionic map is imperative to unveil any plant microbe interplay and modulate defence-responsive pathways. Hence, the present review is unique in developing concepts of calcium signature in plants and their subsequent decoding mechanism. This review also intends to articulate early sensing of calcium oscillation, signalling events, and comprehensive mechanistic roles of calcium within plants during pathogenic ingression. This will accumulate and summarize the exciting roles of calcium ions in plant immunity and provide the foundation for future research.

Gluten-free diet affects fecal small non-coding RNA profiles and microbiome composition in celiac disease supporting a host-gut microbiota crosstalk

ABSTRACT Current treatment for celiac disease (CD) is adhering to a gluten-free diet (GFD), although its long-term molecular effects are still undescribed. New molecular features detectable in stool may improve and facilitate noninvasive clinical management of CD. For this purpose, fecal small non-coding RNAs (sncRNAs) and gut microbiome profiles were concomitantly explored in CD subjects in relation to strict (or not) GFD adherence over time. In this observational study, we performed small RNA and shotgun metagenomic sequencing in stool from 63 treated CD (tCD) and 3 untreated subjects as well as 66 sex- and age-matched healthy controls. tCD included 51 individuals on strict GFD and with negative transglutaminase (TG) serology (tCD-TG-) and 12 symptomatic with not strict/short-time of GFD adherence and positive TG serology (tCD-TG+). Samples from additional 40 healthy adult individuals and a cohort of 19 untreated pediatric CD subjects and 19 sex/age matched controls were analyzed to further test the outcomes. Several miRNA and microbial profiles were altered in tCD subjects (adj. p < .05). Findings were validated in the external group of adult controls. In tCD-TG-, GFD duration correlated with five miRNA levels (p < .05): for miR-4533-3p and miR-2681-3p, the longer the diet adherence, the less the expression differed from controls. tCD-TG+ and untreated pediatric CD patients showed a similar miRNA dysregulation. Immune-response, trans-membrane transport and cell death pathways were enriched in targets of identified miRNAs. Bifidobacterium longum, Ruminococcus bicirculans, and Haemophilus parainfluenzae abundances shifted (adj. p < .05) with a progressive reduction of denitrification pathways with GFD length. Integrative analysis highlighted 121 miRNA-bacterial relationships (adj. p < .05). Specific molecular patterns in stool characterize CD subjects, reflecting either the long-term GFD effects or the gut inflammatory status, in case of a not strict/short-time adherence. Our findings suggest novel host-microbial interplays and could help the discovery of biomarkers for GFD monitoring over time.

Progress in Brain Magnetic Resonance Imaging of Individuals with Prader-Willi Syndrome.

Prader-Willi syndrome (PWS), a rare epigenetic disease mapping the imprinted chromosomal domain of 15q11.2-q13.3, manifests a regular neurodevelopmental trajectory in different phases. The current multimodal magnetic resonance imaging (MRI) approach for PWS focues on morphological MRI (mMRI), diffusion MRI (dMRI) and functional MRI (fMRI) to uncover brain alterations. This technique offers another perspective to understand potential neurodevelopmental and neuropathological processes of PWS, in addition to specific molecular gene expression patterns, various clinical manifestations and metabolic phenotypes. Multimodal MRI studies of PWS patients demonstrated common brain changes in the volume of gray matter, the integrity of the fiber tracts and the activation and connectivity of some networks. These findings mainly showed that brain alterations in the frontal reward circuit and limbic system were related to molecular genetics and clinical manifestations (e.g., overwhelming eating, obsessive compulsive behaviors and skin picking). Further exploration using a large sample size and advanced MRI technologies, combined with artificial intelligence algorithms, will be the main research direction to study the structural and functional changes and potential pathogenesis of PWS.

Systematic Analysis of Molecular Subtypes Based on the Expression Profile of Immune-Related Genes in Pancreatic Cancer.

Immunotherapy has a good therapeutic effect and provides a new approach for cancer treatment. However, only limited studies have focused on the use of molecular typing to construct an immune characteristic index for gene expression in pancreatic adenocarcinoma (PAAD) and to assess the effectiveness of immunotherapy in patients with PAAD. Clinical follow-up data and gene expression profile of PAAD patients were retrieved from The Cancer Genome Atlas (TCGA) database. Based on 184 immune features, molecular subtypes of pancreatic cancer were found by the "ConsensusClusterPlus" package, and the association between clinical features and immune cell subtype distribution was analysed. In addition, the relationship between the proportion of immune subtypes and the expression of immune checkpoints was analysed. The CIBERSORT algorithm was introduced to evaluate the immune scores of different molecular subtypes. We used the tumor immune dysfunction and exclusion (TIDE) algorithm to assess the potential clinical effect of immunotherapy interventions on single-molecule subtypes. In addition, the oxidative stress index was constructed by linear discriminant analysis DNA (LDA), and weighted correlation network analysis was performed to identify the core module of the index and its characteristic genes. Expression of hub genes was verified by immunohistochemical analysis in an independent PAAD cohort. Pancreatic cancer is divided into three molecular subtypes (IS1, IS2, and IS3), with significant differences in prognosis between multiple cohorts. Expression of immune checkpoint-associated genes was significantly reduced in IS3 and higher in IS1 and IS2, suggesting that the three subgroups have different responsiveness to immunotherapy interventions. The results of the CIBERSORT analysis showed that IS1 exhibited the highest levels of immune infiltration, whereas the results of the TIDE analysis showed that the T-cell dysfunction score of IS1 was higher than that of IS2 and IS3. Furthermore, IS3 was found to be more sensitive to 5-FU and to have a higher immune signature index than IS1 and IS2. Based on WGCNA analysis, 10 potential gene markers were identified, and their expression at the protein level was verified by immunohistochemical analysis. Specific molecular expression patterns in pancreatic cancer can predict the efficacy of immunotherapy and influence the prognosis of patients.

Preliminary Analysis of the Glycolipid Profile in Secondary Brain Tumors.

Glycosphingolipids (GSLs) play numerous roles in cellular processes, including cell proliferation, apoptosis, inflammation, and cell signaling. Alteration of the GSLs metabolism leads to the accumulation of particular species of GSLs, which can lead to various pathologies, including carcinogenesis and metastasis; in essence, all neoplasms are characterized by the synthesis and aberrant organization of GSLs expressed on the cell surface. Secondary brain tumors make up the majority of intracranial cancers and generally present an unfavorable prognosis. In the present work, a native GSL mixture extracted and purified from a secondary brain tumor with primary pulmonary origin was obtained through extraction and purification and analyzed by MALDI TOF mass spectrometry. Research in the field of lipidomics could offer new data for the understanding of brain tropism and metastatic pathways, by studying the glycolipid molecules involved in the process of metastasis in general and in the production of brain metastases in particular. This could shed new light on the pattern of lipid glycosylation in secondary brain tumors, with a great impact on the effectiveness of cancer therapies, which could be adapted to the specific molecular pattern of the tumor.

Environmental perception and control of gastrointestinal immunity by the enteric nervous system.

The enteric nervous system (ENS) forms a versatile sensory system along the gastrointestinal tract that interacts with most cell types in the bowel. Herein, we portray host-environment interactions at the intestinal mucosal surface through the lens of the enteric nervous system. We describe local cellular interactions as well as long-range circuits between the enteric, central, and peripheral nervous systems. Additionally, we discuss recently discovered mechanisms by which enteric neurons and glia respond to biotic and abiotic environmental changes and how they regulate intestinal immunity and inflammation. The enteric nervous system emerges as an integrative sensory system with manifold immunoregulatory functions under both homeostatic and pathophysiological conditions.

Codon Pattern and Compositional Constraints Determination of Genes Associated with Chronic Periodontitis.

Genome-wide association studies showed the relationship of NIN, ABHD12B, WHAMM, AP3B2, and SIGLEC5 with chronic periodontitis. The study's objective was to investigate different molecular patterns and evolutionary forces acting on the mentioned genes. The investigation of molecular patterns encompasses the study of compositional parameters, expression profile, physical properties of genes, codon preferences, degree of codon bias, determination of the most influential codons, and assessment of actions of evolutionary forces, such as mutations and natural selection. The overall compositional analysis revealed the dominance of A and G nucleotides compared to T and C. A relatively low codon usage bias is observed. The CTG codon is the most overused codon, followed by TCC. The genes, AP3B2 and SIGLEC5, preferred GC-ending codons, while NIN, ABHD12B, and WHAMM preferred AT-ending codons. The presence of directional mutational force and natural selection was found to operate codon usage in genes envisaged, and selective forces were dominant over mutational forces. Apart from mutation and selection forces, compositional constraints also played imperative roles. The study enriched our knowledge of specific molecular patterns associated with the set of genes significantly associated with chronic periodontitis. Further studies are warranted to identify more genetic signatures associated with the disease.