scholarly journals Analogous mechanism regulating formation of neocortical basal radial glia and cerebellar Bergmann glia

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Xin Heng ◽  
Qiuxia Guo ◽  
Alan W Leung ◽  
James YH Li
Keyword(s):  
Radial Glia ◽  
Bergmann Glia ◽  
Erk Signaling ◽  
Striking Similarity ◽  
Common Mechanism ◽  
Molecular Characteristics ◽  
Cortical Folding ◽  
Molecular Features ◽  
Human And Mouse ◽  
Analogous Mechanism

Neocortical basal radial glia (bRG) and cerebellar Bergmann glia (BG) are basal progenitors derived from ventricular apical radial glia (aRG) that selectively lose their apical processes. bRG and BG have been implicated in the expansion and folding of the cerebrum and cerebellum, respectively. Here, we analyzed the molecular characteristics and development of bRG and BG. Transcriptomic comparison revealed striking similarity of the molecular features of bRG and BG. We found that heightened ERK signaling activity in aRG is tightly linked to the temporal formation and the relative abundance of bRG in human and mouse cortices. Forced activation of an FGF-ERK-ETV axis that is crucial to BG induction specifically induced bRG with canonical human bRG features in mice. Therefore, our data point to a common mechanism of bRG and BG generation, bearing implications to the role for these basal progenitors in the evolution of cortical folding of the cerebrum and cerebellum.

scholarly journals Insights on Molecular Characteristics of Hydrochars by 13C-NMR and Off-Line TMAH-GC/MS and Assessment of Their Potential Use as Plant Growth Promoters

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1026 ◽  
Author(s):  
Laís G. Fregolente ◽  
João Vitor dos Santos ◽  
Giovanni Vinci ◽  
Alessandro Piccolo ◽  
Altair B. Moreira ◽  
...  
Keyword(s):  
Plant Growth ◽  
Phosphoric Acid ◽  
13C Nmr ◽  
Chemical Properties ◽  
Water Soluble ◽  
Molecular Characteristics ◽  
Initial Growth ◽  
Growth Promoters ◽  
Molecular Features ◽  
Potential Use

Hydrochar is a carbon-based material that can be used as soil amendment. Since the physical-chemical properties of hydrochar are mainly assigned to process parameters, we aimed at evaluating the organic fraction of different hydrochars through 13C-NMR and off-line TMAH-GC/MS. Four hydrochars produced with sugarcane bagasse, vinasse and sulfuric or phosphoric acids were analyzed to elucidate the main molecular features. Germination and initial growth of maize seedlings were assessed using hydrochar water-soluble fraction to evaluate their potential use as growth promoters. The hydrochars prepared with phosphoric acid showed larger amounts of bioavailable lignin-derived structures. Although no differences were shown about the percentage of maize seeds germination, the hydrochar produced with phosphoric acid promoted a better seedling growth. For this sample, the greatest relative percentage of benzene derivatives and phenolic compounds were associated to hormone-like effects, responsible for stimulating shoot and root elongation. The reactions parameters proved to be determinant for the organic composition of hydrochar, exerting a strict influence on molecular features and plant growth response.

scholarly journals Nongenotoxic ABCB1 activator tetraphenylphosphonium can contribute to doxorubicin resistance in MX-1 breast cancer cell line

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Raimonda Kubiliute ◽  
Indre Januskeviciene ◽  
Ruta Urbanaviciute ◽  
Kristina Daniunaite ◽  
Monika Drobniene ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Protein Level ◽  
Copy Number ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Common Mechanism ◽  
Dna Hypomethylation ◽  
Mesenchymal Transition ◽  
Molecular Features

AbstractHyperactivation of ABC transporter ABCB1 and induction of epithelial–mesenchymal transition (EMT) are the most common mechanism of acquired cancer chemoresistance. This study describes possible mechanisms, that might contribute to upregulation of ABCB1 and synergistically boost the acquisition of doxorubicin (DOX) resistance in breast cancer MX-1 cell line. DOX resistance in MX-1 cell line was induced by a stepwise increase of drug concentration or by pretreatment of cells with an ABCB1 transporter activator tetraphenylphosphonium (TPP+) followed by DOX exposure. Transcriptome analysis of derived cells was performed by human gene expression microarrays and by quantitative PCR. Genetic and epigenetic mechanisms of ABCB1 regulation were evaluated by pyrosequencing and gene copy number variation analysis. Gradual activation of canonical EMT transcription factors with later activation of ABCB1 at the transcript level was observed in DOX-only treated cells, while TPP+ exposure induced considerable activation of ABCB1 at both, mRNA and protein level. The changes in ABCB1 mRNA and protein level were related to the promoter DNA hypomethylation and the increase in gene copy number. ABCB1-active cells were highly resistant to DOX and showed morphological and molecular features of EMT. The study suggests that nongenotoxic ABCB1 inducer can possibly accelerate development of DOX resistance.

scholarly journals Isolation and characterization of Pseudomonas syringae isolates affecting stone fruits and almond in Montenegro

2021 ◽  
Author(s):  
Tamara Popović ◽  
Jelena Menković ◽  
Anđelka Prokić ◽  
Nevena Zlatković ◽  
Aleksa Obradović
Keyword(s):  
Pseudomonas Syringae ◽  
Housekeeping Genes ◽  
Molecular Characteristics ◽  
Biochemical Tests ◽  
High Genetic Diversity ◽  
Leaf Petiole ◽  
Molecular Features ◽  
Isolation And Characterization ◽  
Genomic Species

AbstractIn Montenegro, stone fruit species are grown on intensive and semi-intensive commercial plantations. However, almond production is mainly organized on family gardens and for household consumption. During two seasons (2017–2018), we surveyed apricot, peach, nectarine, sweet cherry, Japanese plum, and almond orchards for the presence of bacterial diseases at different geographical locations in Montenegro. From leaf, petiole and fruit lesions, branch or twig cankers, and necrotizing buds, a total of 29 isolates were obtained and subjected to identification based on their morphological, pathogenic, biochemical, and molecular characteristics. Pathogenicity of the isolates was confirmed by reproducing the symptoms on leaves, fruits, and twigs of the corresponding host plants. The biochemical tests indicated that the isolates belong to Pseudomonas syringae. However, isolates’ characterization showed variation in their phenotypic and molecular features. The presence of the syrB gene and ice nucleation activity grouped most of the isolates within pathovar syringae. The results of rep-PCR using the BOX primer revealed high genetic diversity of isolates. Multilocus sequence analysis (MLSA), using four housekeeping genes, showed that 27 isolates belong to the genomic species 1, P. syringae sensu stricto, corresponding to P. syringae phylogroup 2. However, isolates from the same phylogroup 2 did not form a monophyletic group. One strain isolated from apricot was most distinct and similar to members of genomic species 2, phylogroup 3. All tested isolates showed significant levels of resistance to copper sulfate and high level of sensitivity to streptomycin sulfate in vitro.

scholarly journals Molecular Forces Governing the Biological Function of Per-Arnt-Sim-B (PAS-B) Domains: A Comparative Computational Study

Biophysica ◽  
2021 ◽  
Vol 1 (1) ◽  
pp. 1-14
Author(s):  
João Victor de Souza ◽  
Piotr Zaborniak ◽  
Sylvia Reznikov ◽  
Matthew Kondal ◽  
Ruidi Zhu ◽  
...  
Keyword(s):  
Juvenile Hormone ◽  
Hormone Receptor ◽  
Redox Regulation ◽  
Biological Function ◽  
Computational Study ◽  
Sequence Similarity ◽  
Molecular Characteristics ◽  
Drosophila Suzukii ◽  
Xenobiotic Stress ◽  
Molecular Features

Per-Arnt-Sim (PAS) domains are evolutionarily-conserved regions found in proteins in all living systems, involved in transcriptional regulation and the response to hypoxic and xenobiotic stress. Despite having low primary sequence similarity, they show an impressively high structural conservation. Nonetheless, understanding the underlying mechanisms that drive the biological function of the PAS domains remains elusive. In this work, we used molecular dynamics simulations and bioinformatics tools in order the investigate the molecular characteristics that govern the intrinsic dynamics of five PAS-B domains (human AhR receptor, NCOA1, HIF1α, and HIF2α transcription factors, and Drosophila Suzukii (D. Suzukii) juvenile hormone receptor JHR). First, we investigated the effects of different length of N and C terminal regions of the AhR PAS-B domain, showing that truncation of those segments directly affects structural stability and aggregation propensity of the domain. Secondly, using the recently annotated PAS-B located in the methoprene-tolerant protein/juvenile hormone receptor (JHR) from D. Suzukii, we have shown that the mutation of the highly conserved “gatekeeper” tyrosine to phenylalanine (Y322F) does not affect the stability of the domain. Finally, we investigated possible redox-regulation of the AhR PAS-B domain by focusing on the cysteinome residues within PAS-B domains. The cysteines in AhR PAS-B are directly regulating the dynamics of the small molecule ligand-gating loop (residues 305 to 326). In conclusion, we comprehensibly described several molecular features governing the behaviour of PAS-B domains in solution, which may lead to a better understanding of the forces driving their biological functions.

scholarly journals Clinical, Pathological and Molecular Characteristics of Chilean Patients with Early-, Intermediate- and Late-Onset Colorectal Cancer

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 631
Author(s):  
Karin Alvarez ◽  
Alessandra Cassana ◽  
Marjorie De La Fuente ◽  
Tamara Canales ◽  
Mario Abedrapo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Family History ◽  
Age Of Onset ◽  
Late Onset ◽  
Molecular Characteristics ◽  
Family History Of Cancer ◽  
Molecular Features ◽  
Age Of Diagnosis ◽  
History Of ◽  
History Of Cancer

Colorectal cancer (CRC) is the second most frequent neoplasm in Chile and its mortality rate is rising in all ages. However, studies characterizing CRC according to the age of onset are still lacking. This study aimed to identify clinical, pathological, and molecular features of CRC in Chilean patients according to the age of diagnosis: early- (≤50 years; EOCRC), intermediate- (51–69 years; IOCRC), and late-onset (≥70 years; LOCRC). The study included 426 CRC patients from Clinica Las Condes, between 2007 and 2019. A chi-square test was applied to explore associations between age of onset and clinicopathological characteristics. Body Mass Index (BMI) differences according to age of diagnosis was evaluated through t-test. Overall (OS) and cancer-specific survival (CSS) were estimated by the Kaplan–Meier method. We found significant differences between the age of onset, and gender, BMI, family history of cancer, TNM Classification of Malignant Tumors stage, OS, and CSS. EOCRC category was characterized by a family history of cancer, left-sided tumors with a more advanced stage of the disease but better survival at 10 years, and lower microsatellite instability (MSI), with predominant germline mutations. IOCRC has shown clinical similarities with the EOCRC and molecular similarities to the LOCRC, which agrees with other reports.

Clinical and molecular characteristics of ARIEL3 patients who derived exceptional benefit from rucaparib maintenance treatment for high-grade ovarian cancer (HGOC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5537-5537
Author(s):  
Tanya Kwan ◽  
Amit M. Oza ◽  
Domenica Lorusso ◽  
Carol Aghajanian ◽  
Ana Oaknin ◽  
...  
Keyword(s):  
Clinical Characteristics ◽  
Maintenance Treatment ◽  
Parp Inhibitor ◽  
Progression Free Survival ◽  
Molecular Characteristics ◽  
Brca Mutations ◽  
Molecular Features ◽  
Brca1 Promoter Methylation ◽  
Genome Wide ◽  
To Receive

5537 Background: ARIEL3 is a placebo-controlled randomized trial of the PARP inhibitor (PARPi) rucaparib as maintenance treatment in HGOC patients (pts) who responded to the latest line of platinum therapy (NCT01968213). Rucaparib improved progression-free survival (PFS) across all predefined subgroups. Here, we present an exploratory analysis of clinical and molecular characteristics associated with exceptional benefit from rucaparib. Methods: Pts were randomized 2:1 to receive rucaparib 600 mg BID or placebo. At the data cutoff of Dec 31, 2019, 33/375 (9%) and 1/189 (0.5%) pts were still ongoing and receiving rucaparib or placebo, respectively. Molecular features (genomic alterations, BRCA1 promoter methylation) and baseline clinical characteristics were compared between pts who derived exceptional benefit (PFS ≥2 yrs), and those with disease progression on first scan (≈12 wks; the short-term [ST] subgroup) within each treatment arm. Results: Of 564 pts, 83 (15%) showed exceptional benefit: 79/375 (21%) in the rucaparib arm and 4/189 (2%) in the placebo arm. Within the rucaparib arm, exceptional benefit pts had more favorable clinical prognostic factors at baseline compared with the ST subgroup (Table). While BRCA mutations were enriched in the rucaparib exceptional benefit subgroup, 34/79 (43%) of these pts were BRCA wild type. Among other biomarkers, RAD51C/D mutations were associated with exceptional benefit; low genome-wide loss of heterozygosity was enriched within the ST subgroup; and high BRCA1 methylation was present at similar fractions. Trends were similar in the placebo arm (Table). Conclusions: Exceptional benefit in ARIEL3 was more common in, but not exclusive to, pts with favorable clinical characteristics and known mechanisms of PARPi sensitivity. Our results suggest that rucaparib can deliver exceptional benefit to a diverse set of HGOC pts. Clinical trial information: NCT01968213. [Table: see text]

scholarly journals Left-Sided Colorectal Cancer Distinct in Indigenous African Patients Compared to Other Ethnic Groups in South Africa.

2021 ◽  
Author(s):  
M. McCabe ◽  
C. Penny ◽  
P. Magangane ◽  
S. Mirza ◽  
Y. Perner
Keyword(s):  
Colorectal Cancer ◽  
South Africa ◽  
Ethnic Groups ◽  
Mirna Expression ◽  
Expression Profiling ◽  
Expression Patterns ◽  
Molecular Characteristics ◽  
Anatomical Site ◽  
Molecular Features ◽  
Mirna Expression Profiling

Abstract Introduction: A large proportion of indigenous African (IA) colorectal cancer (CRC) patients in South Africa are young (<50years), with no unique histopathological or molecular characteristics. Anatomical site as well as microsatellite instability (MSI) status have shown to be associated with different clinicopathological and molecular features. This study aimed to ascertain key histopathological and miRNA expression patterns in microsatellite stable (MSS) and low-frequency MSI (MSI-L) patients, to provide insight into the mechanism of the disease. Methods: A retrospective cohort (2011-2015) of MSS/MSI-L CRC patient samples diagnosed at Charlotte Maxeke Johannesburg Academic Hospital was analyzed. Samples were categorized by site [Right colon cancer (RCC) versus left (LCC)], ethnicity [IA versus other ethnic groups (OEG)] and MSI status (MSI-L vs MSS). T-test, Fischer’s exact and Chi-square tests were conducted. Additional miRNA expression profiling was performed on IA patient samples. Results: IA patients with LCC demonstrated an increased prevalence in males, sigmoid colon, signet-ring-cell morphology, MSI-L with BAT25/26 marker instability and advanced disease association. MiRNA expression profiling revealed unique clustering, with dysregulation of let-7 and miRNA-125. Conclusion: This study revealed distinct histopathological features for LCC, and suggests BAT25/26, miRNAs let-7a-5p and miRNA-125a/b-5p as negative prognostic markers in African CRC patients. Larger confirmatory studies are recommended.

NrasQ61R/+ and Kras-/- cooperate to downregulate Rasgrp1 and promote lympho-myeloid leukemia in early T-cell precursors

Blood ◽  
2021 ◽  
Author(s):  
Zhi Wen ◽  
Grant Yun ◽  
Alexander Hebert ◽  
Guangyao Kong ◽  
Erik A. Ranheim ◽  
...  
Keyword(s):  
T Cell ◽  
Lymphoblastic Leukemia ◽  
Transcript Level ◽  
Negative Regulator ◽  
Erk Signaling ◽  
Ras Signaling ◽  
Nucleotide Exchange ◽  
Promote Cell Proliferation ◽  
Oncogenic Ras ◽  
Molecular Features

Early T cell precursor acute lymphoblastic leukemia (ETP-ALL) is an aggressive subtype of T-ALL. Although genetic mutations hyperactivating cytokine receptor/Ras signaling are prevalent in ETP-ALL, it remains unknown how activated Ras signaling contributes to ETP-ALL. Here, we find that in addition to the frequent oncogenic RAS mutations, wild-type (WT) KRAS transcript level was significantly downregulated in human ETP-ALL cells. Similarly, loss of WT Kras in NrasQ61R/+ mice promoted hyperactivation of ERK signaling, thymocyte hyperproliferation, and expansion of ETP compartment. Kras-/-;NrasQ61R/+ mice developed early onset of T-cell malignancy that recapitulates many biological and molecular features of human ETP-ALL. Mechanistically, RNA-Seq analysis and quantitative proteomics study identified that Rasgrp1, a Ras guanine nucleotide exchange factor, was greatly downregulated in mouse and human ETP-ALL. Unexpectedly, hyperactivated Nras/ERK signaling suppressed Rasgrp1 expression and reduced Rasgrp1 level led to increased ERK signaling, thereby establishing a positive feedback loop to augment Nras/ERK signaling and promote cell proliferation. Corroborating our cell line data, Rasgrp1 haploinsufficiency induced Rasgrp1 downregulation, increased pERK level, and ETP expansion in NrasQ61R/+ mice. Our study identifies Rasgrp1 as a negative regulator of Ras/ERK signaling in oncogenic Nras-driven ETP-like leukemia.

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