Systems Biology

Rye-durum wheat 1BL.1RS translocation: implications for drought tolerance and nutritional status

Wed, 2024-10-23 06:00

Physiol Plant. 2024 Sep-Oct;176(5):e14579. doi: 10.1111/ppl.14579.

ABSTRACT

The translocation of the short chromosome arm 1RS of rye onto the 1B chromosome of common wheat has been shown to improve resistance to stress and yield. Here, translocation was operated in durum wheat and its effects on drought tolerance were evaluated. Both the 1BL.1RS translocation line (Svevo 1BL.1RS) and the corresponding Svevo control were exposed to drought for 7 days. Significant differences were found in root morphology between Svevo and Svevo 1BL.1RS under control and drought conditions. Although Svevo 1BL.1RS experienced more severe growth inhibition due to drought than Svevo, it exhibited greater resilience to oxidative stress. Furthermore, several drought-responsive genes were upregulated in both shoots and roots only in the translocation line. Notably, in roots of Svevo 1BL.1RS, the expression of these genes was also higher in the control condition compared to Svevo, suggesting that these genes could be constitutively expressed at higher levels in the translocation line. Moreover, the 1BL.1RS translocation had a significant impact on the plant's ability to accumulate nutrients under drought. Overall, the impact on sulfate accumulation and the expression of genes associated with its assimilation pathways are particularly noteworthy, highlighting the involvement of sulfur in the plant response to water stress. Additionally, the genetic characterization of Svevo 1BL.1RS revealed variants extending beyond the translocation, located in drought stress-responsive genes.

PMID:39440434 | DOI:10.1111/ppl.14579

Categories: Literature Watch

Senescent Syncytiotrophoblast Secretion During Early Onset Preeclampsia

Wed, 2024-10-23 06:00

Hypertension. 2024 Oct 23. doi: 10.1161/HYPERTENSIONAHA.124.23362. Online ahead of print.

ABSTRACT

BACKGROUND: Preeclampsia is a severe hypertensive disorder in pregnancy that causes preterm delivery, maternal and fetal morbidity, mortality, and life-long sequelae. Understanding the pathogenesis of preeclampsia is a critical first step toward protecting mother and child from this syndrome and increased risk of cardiovascular disease later in life. However, effective early predictive tests and therapies for preeclampsia are scarce.

METHODS: To identify novel markers and signaling pathways for early onset preeclampsia, we profiled human maternal-fetal interface units (fetal villi and maternal decidua) from early onset preeclampsia and healthy controls using single-nucleus RNA sequencing combined with spatial transcriptomics. The placental syncytiotrophoblast is in direct contact with maternal blood and forms the barrier between fetal and maternal circulation.

RESULTS: We identified different transcriptomic states of the endocrine syncytiotrophoblast nuclei with patterns of dysregulation associated with a senescence-associated secretory phenotype and a spatial dysregulation of senescence in the placental trophoblast layer. Elevated senescence markers were validated in placental tissues of clinical multicenter cohorts. Importantly, several secreted senescence-associated secretory phenotype factors were elevated in maternal blood already in the first trimester. We verified the secreted senescence markers, PAI-1 (plasminogen activator inhibitor 1) and activin A, as identified in our single-nucleus RNA sequencing model as predictive markers before clinical preeclampsia diagnosis.

CONCLUSIONS: This indicates that increased syncytiotrophoblast senescence appears weeks before clinical manifestation of early onset preeclampsia, suggesting that the dysregulated preeclamptic placenta starts with higher cell maturation resulting in premature and increased senescence-associated secretory phenotype release. These senescence-associated secretory phenotype markers may serve as an additional early diagnostic tool for this syndrome.

PMID:39440423 | DOI:10.1161/HYPERTENSIONAHA.124.23362

Categories: Literature Watch

A new clinical prognosis model for breast cancer with ADSS as the hub gene

Wed, 2024-10-23 06:00

J Cancer. 2024 Sep 16;15(18):5910-5926. doi: 10.7150/jca.95589. eCollection 2024.

ABSTRACT

Background: Breast cancer (BRCA) is the most common malignant tumor and the leading cause of cancer death worldwide. Adenylosuccinate synthetase (ADSS) is highly expressed in BRCA and its subtypes malignant tumors and is associated with poor prognosis. Methods: By applying ROC curve, survival analysis, WGCNA, enrichment analysis, Cox regression model and other methods, this study explores the role of ADSS in BRCA and constructs a scoring model. Results: In this study, the ADSS demonstrated good diagnostic efficacy and high expression in breast cancer tissues. Further exploration of the role of ADSS in BRCA revealed that its significantly related coexpressed genes are clearly involved in biological functions and signaling pathways associated with cell proliferation and differentiation. Additionally, the ADSS-related scoring model showed a significant prognostic impact on clinical characteristics, such as metastasis to lymph nodes, and it was discovered that the ADSS score and related scoring genes may affect the immune microenvironment of BRCA patients, potentially participating in the occurrence of this disease. Conclusion: In summary, our gene expression analysis of ADSS in BRCA generated a clinical scoring model based on the ADSS that may be used to assess prognostic risk and provide potential clinical applications and rational therapeutic targets.

PMID:39440049 | PMC:PMC11492999 | DOI:10.7150/jca.95589

Categories: Literature Watch

Reciprocal signaling between quorum sensing mutants: A model for division of labor

Wed, 2024-10-23 06:00

MicroPubl Biol. 2024 Oct 8;2024. doi: 10.17912/micropub.biology.001326. eCollection 2024.

ABSTRACT

Division of labor, the specialization of subsets of individuals in complementary tasks, increases population efficiency and fitness. We explored swarming motility in Pseudomonas aeruginosa quorum sensing mutants as a model for studying the division of labor. Deletion of the signal synthesis genes lasI or rhlI disrupts swarming, but co-culturing ΔlasI and ΔrhlI restores it in a density-dependent manner. This indicates a successful division of labor where ΔrhlI produces the signal necessary for the ΔlasI mutant, and the ΔlasI reciprocates. We used RNA sequencing to identify additional genes potentially involved in division of labor. Our findings underscore P. aeruginosa swarming as a tractable bacterial model for the division of labor among cells-a hallmark of differentiated multicellularity.

PMID:39439722 | PMC:PMC11494437 | DOI:10.17912/micropub.biology.001326

Categories: Literature Watch

A longitudinal single-cell atlas of anti-tumour necrosis factor treatment in inflammatory bowel disease

Tue, 2024-10-22 06:00

Nat Immunol. 2024 Oct 22. doi: 10.1038/s41590-024-01994-8. Online ahead of print.

ABSTRACT

Precision medicine in immune-mediated inflammatory diseases (IMIDs) requires a cellular understanding of treatment response. We describe a therapeutic atlas for Crohn's disease (CD) and ulcerative colitis (UC) following adalimumab, an anti-tumour necrosis factor (anti-TNF) treatment. We generated ~1 million single-cell transcriptomes, organised into 109 cell states, from 216 gut biopsies (41 subjects), revealing disease-specific differences. A systems biology-spatial analysis identified granuloma signatures in CD and interferon (IFN)-response signatures localising to T cell aggregates and epithelial damage in CD and UC. Pretreatment differences in epithelial and myeloid compartments were associated with remission outcomes in both diseases. Longitudinal comparisons demonstrated disease progression in nonremission: myeloid and T cell perturbations in CD and increased multi-cellular IFN signalling in UC. IFN signalling was also observed in rheumatoid arthritis (RA) synovium with a lymphoid pathotype. Our therapeutic atlas represents the largest cellular census of perturbation with the most common biologic treatment, anti-TNF, across multiple inflammatory diseases.

PMID:39438660 | DOI:10.1038/s41590-024-01994-8

Categories: Literature Watch

Direct and indirect regulation of β-glucocerebrosidase by the transcription factors USF2 and ONECUT2

Tue, 2024-10-22 06:00

NPJ Parkinsons Dis. 2024 Oct 22;10(1):192. doi: 10.1038/s41531-024-00819-7.

ABSTRACT

Mutations in GBA1 encoding the lysosomal enzyme β-glucocerebrosidase (GCase) are among the most prevalent genetic susceptibility factors for Parkinson's disease (PD), with 10-30% of carriers developing the disease. To identify genetic modifiers contributing to the incomplete penetrance, we examined the effect of 1634 human transcription factors (TFs) on GCase activity in lysates of an engineered human glioblastoma line homozygous for the pathogenic GBA1 L444P variant. Using an arrayed CRISPR activation library, we uncovered 11 TFs as regulators of GCase activity. Among these, activation of MITF and TFEC increased lysosomal GCase activity in live cells, while activation of ONECUT2 and USF2 decreased it. While MITF, TFEC, and USF2 affected GBA1 transcription, ONECUT2 might control GCase trafficking. The effects of MITF, TFEC, and USF2 on lysosomal GCase activity were reproducible in iPSC-derived neurons from PD patients. Our study provides a systematic approach to identifying modulators of GCase activity and deepens our understanding of the mechanisms regulating GCase.

PMID:39438499 | DOI:10.1038/s41531-024-00819-7

Categories: Literature Watch

Accurate and sensitive interactome profiling using a quantitative protein-fragment complementation assay

Tue, 2024-10-22 06:00

Cell Rep Methods. 2024 Oct 21;4(10):100880. doi: 10.1016/j.crmeth.2024.100880.

ABSTRACT

An accurate description of protein-protein interaction (PPI) networks is key to understanding the molecular mechanisms underlying cellular systems. Here, we constructed genome-wide libraries of yeast strains to systematically probe protein-protein interactions using NanoLuc Binary Technology (NanoBiT), a quantitative protein-fragment complementation assay (PCA) based on the NanoLuc luciferase. By investigating an array of well-documented PPIs as well as the interactome of four proteins with varying levels of characterization-including the well-studied nonsense-mediated mRNA decay (NMD) regulator Upf1 and the SCF complex subunits Cdc53 and Met30-we demonstrate that ratiometric NanoBiT measurements enable highly precise and sensitive mapping of PPIs. This work provides a foundation for employing NanoBiT in the assembly of more comprehensive and accurate protein interaction maps as well as in their functional investigation.

PMID:39437715 | DOI:10.1016/j.crmeth.2024.100880

Categories: Literature Watch

Size-reduced DREADD derivatives for AAV-assisted multimodal chemogenetic control of neuronal activity and behavior

Tue, 2024-10-22 06:00

Cell Rep Methods. 2024 Oct 21;4(10):100881. doi: 10.1016/j.crmeth.2024.100881.

ABSTRACT

Designer receptors exclusively activated by designer drugs (DREADDs) are engineered G-protein-coupled receptors that afford reversible manipulation of neuronal activity in vivo. Here, we introduce size-reduced DREADD derivatives miniDq and miniDi, which inherit the basic receptor properties from the Gq-coupled excitatory receptor hM3Dq and the Gi-coupled inhibitory receptor hM4Di, respectively, while being approximately 30% smaller in size. Taking advantage of the compact size of the receptors, we generated an adeno-associated virus (AAV) vector carrying both miniDq and the other DREADD family receptor (κ-opioid receptor-based inhibitory DREADD [KORD]) within the maximum AAV capacity (4.7 kb), allowing us to modulate neuronal activity and animal behavior in both excitatory and inhibitory directions using a single viral vector. We confirmed that expressing miniDq, but not miniDi, allowed activation of striatum activity in the cynomolgus monkey (Macaca fascicularis). The compact DREADDs may thus widen the opportunity for multiplexed interrogation and/or intervention in neuronal regulation in mice and non-human primates.

PMID:39437713 | DOI:10.1016/j.crmeth.2024.100881

Categories: Literature Watch

Epigenetic toxicity of heavy metals - implications for embryonic stem cells

Tue, 2024-10-22 06:00

Environ Int. 2024 Oct 18;193:109084. doi: 10.1016/j.envint.2024.109084. Online ahead of print.

ABSTRACT

Exposure to heavy metals, such as cadmium, nickel, mercury, arsenic, lead, and hexavalent chromium has been linked to dysregulated developmental processes, such as impaired stem cell differentiation. Heavy metals are well-known modifiers of the epigenome. Stem and progenitor cells are particularly vulnerable to exposure to potentially toxic metals since these cells rely on epigenetic reprogramming for their proper functioning. Therefore, exposure to metals can impair stem and progenitor cell proliferation, pluripotency, stemness, and differentiation. In this review, we provide a comprehensive summary of current evidence on the epigenetic effects of heavy metals on stem cells, focusing particularly on DNA methylation and histone modifications. Moreover, we explore the underlying mechanisms responsible for these epigenetic changes. By providing an overview of heavy metal exposure-induced alterations to the epigenome, the underlying mechanisms, and the consequences of those alterations on stem cell function, this review provides a foundation for further research in this critical area of overlap between toxicology and developmental biology.

PMID:39437622 | DOI:10.1016/j.envint.2024.109084

Categories: Literature Watch

Design of Murine Double Minute 2 Proteolysis Targeting Chimera Degraders with a Built-In Tumor-Targeting Ability

Tue, 2024-10-22 06:00

J Med Chem. 2024 Oct 22. doi: 10.1021/acs.jmedchem.4c01228. Online ahead of print.

ABSTRACT

Proteolysis targeting chimeras (PROTACs) are heterobifunctional molecules to induce the proteasomal degradation of target proteins. Currently, there are no tumor-targeting PROTACs for modulating oncogenic murine double minute 2 (MDM2). AS1411 is a tumor-targeting aptamer that specifically recognizes nucleolin (NCL) overexpressed on the surface of tumor cells. We recently repurposed AS1411 as an MDM2 recruiter since it could form an NCL-bridged ternary complex with MDM2. In this study, we design a PROTAC molecule AS1411-VH032 via conjugating AS1411 with a recruiter of von Hippel-Lindau (VHL) ligase VH032. AS1411-VH032 facilitates tumor-selective degradation of MDM2, leading to tumor shrinkage with no detectable toxicity. Besides being a molecular target, MDM2 also serves as an E3 ligase harnessed by PROTACs. Thus, we developed an AS1411-based homo-PROTAC homoAS1411, which induces tumor-specific suicide degradation of MDM2 and prevents tumor progression without causing side effects. Both AS1411-VH032 and homoAS1411 are promising MDM2 degraders with built-in tumor-targeting ability, which balances the antitumor efficacy with a favorable safety profile.

PMID:39437434 | DOI:10.1021/acs.jmedchem.4c01228

Categories: Literature Watch

Rhizobacterial syntrophy between a helper and a beneficiary promotes tomato plant health

Tue, 2024-10-22 06:00

ISME J. 2024 Oct 22:wrae210. doi: 10.1093/ismejo/wrae210. Online ahead of print.

ABSTRACT

None declared.Conflicts of interestMicrobial interactions impact the functioning of microbial communities. However, microbial interactions within host-associated communities remains poorly understood. Here, we report that the beneficiary rhizobacterium Niallia sp. RD1 requires the helper Pseudomonas putida H3 for bacterial growth and beneficial interactions with the plant host. In the absence of the helper H3 strain, the Niallia sp. RD1 strain exhibited weak respiration and elongated cell morphology without forming bacterial colonies. A transposon mutant of H3 in a gene encoding succinate-semialdehyde dehydrogenase displayed much attenuated support of RD1 colony formation. Through subsequent addition of succinate to the media, we found that succinate serves as a public good that supports RD1 growth. Comparative genome analysis highlighted that RD1 lacked the gene for sufficient succinate, suggesting its evolution as a beneficiary of succinate biosynthesis. The syntrophic interaction between RD1 and H3 efficiently protected tomato plants from bacterial wilt and promoted the tomato growth. The addition of succinate to the medium restored complex II-dependent respiration in RD1 and facilitated the cultivation of various bacterial isolates from the rhizosphere. Taken together, we delineate energy auxotrophic beneficiaries ubiquitous in the microbial community, and these beneficiaries could benefit host plants with the aid of helpers in the rhizosphere.

PMID:39437168 | DOI:10.1093/ismejo/wrae210

Categories: Literature Watch

Metabolic Engineering of <em>Corynebacterium glutamicum</em> for the Production of the Four-Carbon Platform Chemicals γ-Hydroxybutyrate and γ-Butyrolactone

Tue, 2024-10-22 06:00

ACS Synth Biol. 2024 Oct 22. doi: 10.1021/acssynbio.4c00603. Online ahead of print.

ABSTRACT

γ-Hydroxybutyrate (GHB) is an important C4 platform chemical, serving as a crucial precursor for the synthesis of various bulk chemicals, including γ-butyrolactone (GBL) and 1,4-butanediol (1,4-BDO). In this study, we report the systematic metabolic engineering of Corynebacterium glutamicum for the biological production of GHB from glucose via the introduction of a glutamate-derived pathway. We showed that C. glutamicum is a promising host for producing GHB due to its higher tolerance to GHB as compared to other chassis. By screening key enzymes capable of converting glutamate into GHB and blocking byproduct synthesis pathways, an engineered C. glutamicum strain was developed that achieved a GHB production titer of 30.6 g/L. Comparative transcriptome analysis was subsequently employed to identify previously uncharacterized aldehyde dehydrogenases responsible for succinate accumulation, and knockout of the corresponding genes led to an increased GHB titer of 33.7 g/L. Ultimately, the integration of a phosphoketolase-mediated nonoxidative glycolysis (NOG) pathway further enhanced GHB production, resulting in an accumulation of 38.3 g/L of GHB with a yield of 0.615 mol/mol glucose during batch fermentation. The GHB in the fermentation broth can be efficiently converted into GBL by acid treatment with a yield of 0.970 mol/mol.

PMID:39437154 | DOI:10.1021/acssynbio.4c00603

Categories: Literature Watch

eIF4F controls ERK MAPK signaling in melanomas with <em>BRAF</em> and <em>NRAS</em> mutations

Tue, 2024-10-22 06:00

Proc Natl Acad Sci U S A. 2024 Oct 29;121(44):e2321305121. doi: 10.1073/pnas.2321305121. Epub 2024 Oct 22.

ABSTRACT

The eIF4F translation initiation complex plays a critical role in melanoma resistance to clinical BRAF and MEK inhibitors. In this study, we uncover a function of eIF4F in the negative regulation of the rat sarcoma (RAS)/rapidly accelerated fibrosarcoma (RAF)/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) signaling pathway. We demonstrate that eIF4F is essential for controlling ERK signaling intensity in treatment-naïve melanoma cells harboring BRAF or NRAS mutations. Specifically, the dual-specificity phosphatase DUSP6/MKP3, which acts as a negative feedback regulator of ERK activity, requires continuous production in an eIF4F-dependent manner to limit excessive ERK signaling driven by oncogenic RAF/RAS mutations. Treatment with small-molecule eIF4F inhibitors disrupts the negative feedback control of MAPK signaling, leading to ERK hyperactivation and EGR1 overexpression in melanoma cells in vitro and in vivo. Furthermore, our quantitative analyses reveal a high spare signaling capacity in the ERK pathway, suggesting that eIF4F-dependent feedback keeps the majority of ERK molecules inactive under normal conditions. Overall, our findings highlight the crucial role of eIF4F in regulating ERK signaling flux and suggest that pharmacological eIF4F inhibitors can disrupt the negative feedback control of MAPK activity in melanomas with BRAF and NRAS activating mutations.

PMID:39436655 | DOI:10.1073/pnas.2321305121

Categories: Literature Watch

Hidden Links Between Skin Microbiome and Skin Imaging Phenome

Tue, 2024-10-22 06:00

Genomics Proteomics Bioinformatics. 2024 Jun 7:qzae040. doi: 10.1093/gpbjnl/qzae040. Online ahead of print.

ABSTRACT

Despite the skin microbiome has been linked to skin health and diseases, its role in modulating human skin appearance remains understudied. Using a total of 1244 face imaging phenomes and 246 cheek metagenomes, we first established three skin age indices by machine learning including skin phenotype age (SPA), skin microbiota age (SMA), and skin integration age (SIA) as surrogates of phenotypic aging, microbial aging, and their combination, respectively. Moreover, we found that besides aging and gender as intrinsic factors, skin microbiome might also play a role in shaping skin imaging phenotypes (SIPs). Skin taxonomic and functional α diversity was positively linked to melanin, pore, pigment, and ultraviolet spot levels, but negatively linked to sebum, lightening, and porphyrins levels. Furthermore, certain species were correlated with specific SIPs, such as sebum and lightening levels negatively correlated with Corynebacterium matruchotii, Staphylococcus capitis, and Streptococcus sanguinis. Notably, we demonstrated skin microbial potential in predicting SIPs, among which the lightening level presented the least error of 1.8%. Lastly, we provided a reservoir of potential mechanisms through which skin microbiome adjusted the SIPs, including the modulation of pore, wrinkle, and sebum levels by cobalamin and heme synthesis pathways, predominantly driven by Cutibacterium acnes. This pioneering study unveils the paradigm for the hidden links between skin microbiome and skin imaging phenome, providing novel insights into how skin microbiome shapes skin appearance and its healthy aging.

PMID:39436239 | DOI:10.1093/gpbjnl/qzae040

Categories: Literature Watch

Scm6A: A Fast and Low-cost Method for Quantifying m6A Modifications at the Single-cell Level

Tue, 2024-10-22 06:00

Genomics Proteomics Bioinformatics. 2024 Jun 7:qzae039. doi: 10.1093/gpbjnl/qzae039. Online ahead of print.

ABSTRACT

It is widely accepted that N6-methyladenosine (m6A) exhibits significant intercellular specificity, which poses challenges for its detection using existing m6A quantitative methods. In this study, we introduced Single-cell m6A Analysis (Scm6A), a machine learning-based approach for single-cell m6A quantification. Scm6A leverages input features derived from the expression levels of m6A trans regulators and cis sequence features, and offers remarkable prediction efficiency and reliability. To further validate the robustness and precision of Scm6A, we applied a winscore-based m6A calculation method to conduct N6-methyladenosine sequencing (m6A-seq) analysis on CD4+ and CD8+ T-cells isolated through magnetic-activated cell sorting (MACS). Subsequently, we employed Scm6A for analysis on the same samples. Notably, the m6A levels calculated by Scm6A exhibited a significant positive correlation with m6A quantified through m6A-seq in different cells isolated by MACS, providing compelling evidence for Scm6A's reliability. Additionally, we performed single-cell level m6A analysis on lung cancer tissues as well as blood samples from the coronavirus disease 2019 (COVID-19) patients, and demonstrated the landscape and regulatory mechanisms of m6A in different T-cell subtypes from these diseases. In summary, our work has yielded a novel, dependable, and accurate method for single-cell m6A detection. We are confident that Scm6A have broad applications in the realm of m6A-related research.

PMID:39436235 | DOI:10.1093/gpbjnl/qzae039

Categories: Literature Watch

Regulation and mechanisms of action of RNA helicases

Tue, 2024-10-22 06:00

RNA Biol. 2024 Jan;21(1):24-38. doi: 10.1080/15476286.2024.2415801. Epub 2024 Oct 22.

ABSTRACT

RNA helicases are an evolutionary conserved class of nucleoside triphosphate dependent enzymes found in all kingdoms of life. Their cellular functions range from transcription regulation up to maintaining genomic stability and viral defence. As dysregulation of RNA helicases has been shown to be involved in several cancers and various diseases, RNA helicases are potential therapeutic targets. However, for selective targeting of a specific RNA helicase, it is crucial to develop a detailed understanding about its dynamics and regulation on a molecular and structural level. Deciphering unique features of specific RNA helicases is of fundamental importance not only for future drug development but also to deepen our understanding of RNA helicase regulation and function in cellular processes. In this review, we discuss recent insights into regulation mechanisms of RNA helicases and highlight models which demonstrate the interplay between helicase structure and their functions.

PMID:39435974 | DOI:10.1080/15476286.2024.2415801

Categories: Literature Watch

Protein composition and bread volume of German common wheat landraces grown under organic conditions

Tue, 2024-10-22 06:00

Curr Res Food Sci. 2024 Oct 1;9:100871. doi: 10.1016/j.crfs.2024.100871. eCollection 2024.

ABSTRACT

Landraces are genetically heterogeneous plant populations that are regionally particularly well adapted to the natural and cultural agricultural environment. Their genetic memory originates from pre-industrial agriculture and food production with consequences for their agronomic and processing performance. Since wheat-related disorders have increased in the population, breeding might have resulted in changes in the protein composition. The aim of this study was to investigate the protein composition and baking quality of 14 German common wheat landraces. Six modern varieties served as a control group. The protein composition was determined using modified Osborne fractionation and reversed-phase high-performance liquid chromatography. In addition, the water absorption and bread volume were determined. The crude protein content, proportions of albumins and globulins, water absorption and bread volume did not differ between modern varieties and landraces. The proportion of gliadins was higher in landraces (64.0%) compared to modern varieties (57.6%), whereas the proportion of glutenins was lower in landraces (17.4%) than in modern varieties (22.0%). The same observation was made for the respective gluten protein types except the proportion of ω1,2-gliadins, where there was no difference between the two groups. This resulted in a significantly higher ratio of gliadins to glutenins of 4.3 in landraces compared to 2.8 in the modern varieties, but no difference in the total gluten proportion. Taken together, there was no clear distinction between landraces and modern varieties. However, a few landraces such as Roter Sächsischer Landweizen showed similar characteristics to modern varieties and are therefore interesting for further investigations.

PMID:39435451 | PMC:PMC11491675 | DOI:10.1016/j.crfs.2024.100871

Categories: Literature Watch

POLQ immunostaining behaves as a prognostic factor for pancreatic carcinoma

Tue, 2024-10-22 06:00

Front Oncol. 2024 Oct 7;14:1433179. doi: 10.3389/fonc.2024.1433179. eCollection 2024.

ABSTRACT

BACKGROUND: DNA polymerase theta (POLQ) is a translesion synthesis polymerase essential for the repair of double strand breaks by the error-prone TMEJ (Theta Mediated End Joining) pathway. Although POLQ participates in maintaining genome stability, several studies have shown that its overexpression correlates with cancer progression and poor prognosis. Due to the fact that its role as a biomarker in pancreatic cancer remains unexplored, we aimed to study the usefulness of POLQ H-score as a prognostic factor in a pancreatic cancer patient cohort.

METHODS: We evaluated POLQ gene expression using a web-based tool to deliver gene expression profiling and interactive analyses based on TCGA and GTEx (GEPIA) and we examined the POLQ immunostaining in 152 biliopancreatic cancer surgical specimens using tissue microarrays. Association with survival was evaluated by Kaplan Meier curves and uni-multivariate Cox regression.

RESULTS: GEPIA analysis showed statistical differences according to POLQ mRNA levels in Disease Free Survival (DFS) (log rank 0.023, HR 2.8, p=0.029) and Overall Survival (OS) (log rank 0.011, HR 3.1, p=0.016). For immunohistochemistry (IHC) evaluation, POLQ H-score was calculated, and showed statistical differences for OS in Kaplan Meier curves (log rank 0.001) and uni-multivariate analysis (HR 2.27; 95% CI 1.24-4.15, p=0.008).

CONCLUSIONS: Our results indicate that POLQ is an independent prognostic factor in pancreatic cancer when analyzed by immunostaining, which is in agreement with the results shown by the POLQ gene expression analysis (GEPIA).

PMID:39435280 | PMC:PMC11491332 | DOI:10.3389/fonc.2024.1433179

Categories: Literature Watch

EcoFAB 3.0: a sterile system for studying sorghum that replicates previous field and greenhouse observations

Tue, 2024-10-22 06:00

Front Plant Sci. 2024 Oct 7;15:1440728. doi: 10.3389/fpls.2024.1440728. eCollection 2024.

ABSTRACT

INTRODUCTION: Studying plant-microbe interactions is one of the key elements in understanding the path to sustainable agricultural practices. These interactions play a crucial role in ensuring survival of healthy plants, soil and microbial communities. Many platforms have been developed over the years to isolate these highly complex interactions however, these are designed for small model plants. This creates a need for complementary devices for larger plants, such as sorghum.

METHODS: This work introduces a novel platform, EcoFAB 3.0, which is designed to enable studying bioenergy plants such as sorghum for up to 4 weeks in a controlled sterile environment. Several other advantages of this platform such as dark root chambers and user-friendly assembly are also discussed in this work.

RESULTS AND DISCUSSION: EcoFAB 3.0 was found to replicate previous greenhouse and field observations when comparing an engineered sorghum line overproducing 4-hydroxybenzoic acid (4-HBA) and wildtype (variety BTx430). Consistent with greenhouse and field observations, it was found that the engineered line of sorghum grown in EcoFAB 3.0 had a higher 4-HBA content and a lower dry biomass.

PMID:39435021 | PMC:PMC11491363 | DOI:10.3389/fpls.2024.1440728

Categories: Literature Watch

Fibrinaloid microclots in long COVID: assessing the actual evidence properly

Tue, 2024-10-22 06:00

Res Pract Thromb Haemost. 2024 Sep 10;8(7):102566. doi: 10.1016/j.rpth.2024.102566. eCollection 2024 Oct.

NO ABSTRACT

PMID:39434957 | PMC:PMC11491705 | DOI:10.1016/j.rpth.2024.102566

Categories: Literature Watch

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