Screening Of Lines Research Articles

New high-throughput screening method for Chinese hamster ovary cell lines expressing low reduced monoclonal antibody levels: application of a system controlling the gas phase over cell lysates in miniature bioreactors and facilitating multiple sample setup.

Interchain disulfide bonds in monoclonal antibodies may be reduced during large-scale mAb production using Chinese hamster ovary (CHO) cells. This reaction lowers the mAb product yield and purity; however, it may be prevented by screening cell lines that are unsusceptible to reduction and using them in mAb production. Antibody reduction susceptibility may be cell line-dependent. To the best of our knowledge, however, an efficient method of screening reduction-unsusceptible CHO cell lines has not been previously reported. Here, we report a novel screening method that can simultaneously detect and identify mAb reduction susceptibility in lysates containing ≤ 48 CHO cell lines. This evaluation system was equally effective and generated similar results at all culture scales, including 250 mL, 3L, and 1000L. Furthermore, we discovered that reduction-susceptible cell lines contained higher total intracellular nicotinamide adenine dinucleotide phosphate (NADPH) and NADP+ concentrations than reduction-unsusceptible cell lines, regardless of whether they expressed immunoglobulin (Ig)G4 or IgG1. NADPH or NADP+ supplementation in the lysate of reduction-unsusceptible cells resulted in mAb reduction. Application of the innovative CHO cell line screening approach could mitigate or prevent reductions in large-scale mAb generation from CHO cells.

Molecular Subtypes and Tumor Microenvironment Characteristics of Small-Cell Lung Cancer Associated with Platinum-Resistance.

Although molecular subtypes of small-cell lung cancer (SCLC) have been proposed, their clinical relevance and therapeutic implications are not fully understood. Thus, we aimed to refine molecular subtypes and to uncover therapeutic targets. We classified the subtypes based on gene expression (n = 81) and validated them in our samples (n = 87). Non-SCLC samples were compared with SCLC subtypes to identify the early development stage of SCLC. Single-cell transcriptome analysis was applied to dissect the TME of bulk samples. Finally, to overcome platinum resistance, we performed drug screening of patient-derived cells and cell lines. Four subtypes were identified: the ASCL1+ (SCLC-A) subtype identified as TP53/RB-mutated non-SCLC representing the early development stage of SCLC; the immune activation (SCLC-I) subtype, showing high CD8+/PD-L1+ T-cell infiltration and endothelial-to-mesenchymal transition (EndMT); the NEUROD1 (SCLC-N) subtype, which showed neurotransmission process; and the POU2F3+ (SCLC-P) subtype with epithelial-to-mesenchymal transition (EMT). EndMT was associated with the worst prognosis. While SCLC-A/N exhibited platinum sensitivity, the EndMT signal of SCLC-I conferred platinum resistance. A BET inhibitor suppressed the aggressive angiogenesis phenotype of SCLC-I. We revealed that EndMT development contributed to a poor outcome in SCLC-I. Moreover, heterogenous TME development facilitated platinum resistance. BET inhibitors are novel candidates for overcoming platinum resistance.

Screening of elite lines of sesame (Sesamum indicum L.) against major diseases

Powdery mildew, Alternaria 1eaf spot, root rot and phyllody are the major diseases affecting the cultivation of sesame. Twenty entries under Initial Varietal Trial (IVT) and seven entries under Advanced Varietal Trial (AVT) were screened against important diseases of sesame under field (sick plot) conditions. In IVT entries, the diseasesseverityofroot rot ranged between 21.13% (IVT-20-14) to 62.03% (IVT-20-13) and the susceptible check VRI-1 recorded the disease severity of 66.13%. Incidence of phyllody ranged between 13.0% to 20.9%. The check variety VRI-1 recorded 24.3% disease incidence. Powdery mildew incidence ranged between 0 to 2 grade andAlternaria leaf spot incidence ranged from 1 to 3 grade. Among the seven AVT entries screened under sick plot conditions, root rot incidence ranged between 12.1% (AVT-20-4) to 35.2% (AVT-20-7). The susceptible checkvarietyVRI-1 recorded 67.0 % root rot incidence. Phyllody disease incidence in these entries ranged between 9.7% to 15.8% whereas the susceptible check variety VRI-1 recorded 22.4% incidence.

The New Northern Ireland as a Crime Scene

This article explores the increased attractiveness of a ‘post-conflict’ Belfast as a television setting for British television police series. The Fall (2013, 2016), Bloodlands (2021) and Marcella (2021) are all set in Belfast, while most of the hit series Line of Duty (2012–) has been filmed in Northern Ireland. How do these new Belfast-set crime dramas negotiate the tropes and iconography of twentieth-century Troubles Belfast, while also participating in the transformation of the city associated with the arrival of transnational audiovisual industries? While recognising that much recent scholarship focuses on the creation of the Titanic Quarter through the redevelopment of the Harland & Wolff shipyard and the production of the HBO-Warner series, Game of Thrones, this article pursues the recent appearances of contemporary Belfast on screen in Bloodlands, Marcella (2021) and Line of Duty. Building on scholarship, such as the work of John Hill, Martin McLoone and Ruth Barton which has established the contours of the Troubles film, the history of Belfast on film and genre in the Northern Ireland context, the existence of an identifiable chronotope ‘Troubles Belfast’ is proposed. Is Belfast recognisable as a specific place outside a Troubles chronotope? What are the stories that can be told of Northern Ireland outside a Troubles chronotope? In particular, which is pertinent to an industry desperate to maintain its attractiveness to transnational productions, the tension between the identification of Belfast as a specific place and the generation of new and different stories is explored in the case studies. To what extent is the televisual use of the new screen Belfast caught in the paradox that it is the old Belfast which makes it an attractive setting for crime drama?

An integrated cellular and molecular model of gastric neuroendocrine cancer evolution highlights therapeutic targets.

Gastric neuroendocrine carcinomas (G-NEC) are aggressive malignancies with poorly understood biology and a lack of disease models. Here, we use genome sequencing to characterize the genomic landscapes of human G-NEC and its histologic variants. We identify global and subtype-specific alterations and expose hitherto unappreciated gains of MYC family members in a large part of cases. Genetic engineering and lineage tracing in mice delineate a model of G-NEC evolution, which defines MYC as a critical driver and positions the cancer cell of origin to the neuroendocrine compartment. MYC-driven tumors have pronounced metastatic competence and display defined signaling addictions, as revealed by large-scale genetic and pharmacologic screening of cell lines and organoid resources. We create global maps of G-NEC dependencies, highlight critical vulnerabilities, and validate therapeutic targets, including candidates for clinical drug repurposing. Our study gives comprehensive insights into G-NEC biology.

Ultrasonography as first line imaging for the diagnosis of positional plagiocephaly.

In the last years, numerous studies evaluated different tools for the diagnosis of positional plagiocephaly (PP). The purpose of this study was to evaluate ultrasonography (US) as a first line screening test of lambdoid sutural patency in child with PP and to compare our results with the literature. All consecutive patients who referred to our Institute from January 2016 to October 2017 with the suspicion of PP, were included in the study and performed US examination of the lambdoid sutures. A 3-6-month clinical follow-up was performed by a pediatric neurosurgeon or a pediatrician to confirm the diagnosis of PP. Thirty-five children performed US examination and in all cases the diagnosis of PP was confirmed. No cases of anticipated suture fusion were examined during this period. The concordance between US findings and clinical exam follow-up was 100%. Ultrasonography of the lambdoid sutures represents an ideal first-line screening test and reliable alternative to other diagnostic techniques for lambdoid sutural patency in child with PP, being radiation free, fast and cheap.

Screening of recombinant inbred lines for resistance to bacterial leaf blight pathotypes in rice (Oryza sativa L.)

In the present investigation 16 recombinant inbred lines (RIL’s) developed from the intra-specific cross between YH3 and AKDRMS 21-54 through Marker Assisted Pedigree Breeding Method were screened along with their parents and the checks, namely, BPT 5204, TN1 and Improved Samba Mahsuri (ISM) against IxoPt-20 pathotype at the ICAR-Indian Institute of Rice Research, Hyderabad during Rabi 2021-22 and a new pathotype of Xanthomonas oryzae pv. oryzae causing Bacterial Leaf Blight disease in rice at Regional Agricultural Research Station, Maruteru during Kharif 2022 to identify pathotype specific resistant sources. Morpho-Molecular screening was adopted to evaluate the recombinant inbred lines over two locations in the consecutive seasons of Rabi 2021-22 and Kharif 2022. Based on per cent diseased leaf area, the genotypes were scored and categorised as per the Standard Evaluation System (SES) scale provided by International Rice Research Institute (IRRI). The results revealed all 16 RIL’s to be either resistant (10) or moderately resistant (6) to IxoPt-20 pathotype. However, only five RIL’s were found to be resistant, while four RIL’s were moderately resistant for the new virulent pathotype. Seven RIL’s with resistant to moderately resistant reaction for IxoPt-20 pathotype, showed moderately susceptible reaction for the new virulent pathotype. Among the resistant RIL’s identified for each pathotype, BPT-1901-72-10-6, BPT-1901-108-4-1 and BPT-1901-111-3-2 were found to be uniformly resistant, while, BPT-1901-45-8-6 and BPT-1901-163-1-18 were uniformly moderately resistant to both IXoPt-20 and the new virulent pathotype at Hyderabad and Maruteru, respectively, indicating their potential as genetic stocks for development of new cultivars resistant to bacterial leaf blight disease.

Screening of potato breedung lines for the potato virus Y resistance genes Rychc and Ryadg

Goal. Molecular identification of carriers of the potato virus Y (PVY) resistance genes Rychc and Ryadg among potato lines of the Polissia Research Station of the Institute of Potato Growing of the National Academy of Agrarian Sciences of Ukraine.
 Methods. Seventy potato lines produced by the Polissia Research Station of the Institute of Potato Growing were studied. We used molecular markers indicating the presence of specific Ry genes in the genome of the potato lines. Those genes are responsible for the plant’s response to the pathogen by the extreme resistance (ER) type: the Ryo186 marker for the identification of the Rychc gene, and RYSC-3 for the determination of the Ryadg resistance gene. The gene Ry chc, derives from Solanum chacoense, and the Ryadg gene from S. tuberosum ssp. andigena. For determining the PVY resistance genes, PCR analysis was used, and PCR products were analyzed by electrophoresis in an agarose gel supplemented with ethidium bromide to visualize amplicons.
 Results. Screening of carriers of resistance alleles with the molecular marker Ruo186 showed that 53 lines (75.72%) carried the resistance gene Rychc. The Ryadg resistance allele was identified in 7 lines (10%) using the RYSC-3 marker. Among the analyzed sample, there were three lines (4.2%) which simultaneously carried both PVY resistance genes: P.17.36-8, P.16.21-8, and P.17.21/36. When compared with the studies of other authors, in our sample of potato breeding lines we have mostly a similar percentage of occurrence of the Ryadg gene and a much higher frequency of the Rychc gene.
 Conclusions. Thus, the potato lines of the Polissia Research Station of the Institute of Potato Growing with the identified resistance genes have the potential for extreme resistance to most PVY strains, including the PVYNTN strain.

DIPG-53. LSD1 DEGRADATION SYNERGIZES WITH HDAC INHIBITION IN PEDIATRIC H3K27M DIFFUSE MIDLINE GLIOMA

Abstract H3K27M-mutated diffuse midline glioma (H3K27M DMG) is an aggressive, lethal pediatric brain tumor which resists conventional cancer treatments. To identify new therapeutic targets, our lab executed a focused CRISPR negative selection screen in patient-derived H3K27M cell lines after treatment with the histone deacetylase (HDAC) inhibitor panobinostat, and discovered a strong co-dependence with the histone demethylase LSD1. We further explored the therapeutic potential of this synergistic interaction with a screen of HDAC- and LSD1- targeting drugs to identify synergistic combinations, which show penetration of the blood brain barrier suitable for clinical translation. Interestingly, conventional catalytic LSD1 inhibitors did not seem to synergize with HDAC inhibitors tested on cell viability, while a recently described CoREST/LSD1 degrader phenocopied the effects seen in our CRISPR screen. We hypothesized that the CoREST/LSD1 degrader induces synergy with HDAC inhibitors through elimination of a scaffolding function of LSD1. To prove this, we knocked out LSD1 using CRISPR/Cas9 in H3K27M cells and subsequently treated with a panel of HDAC inhibitors. These showed a significant sensitization compared to controls cells. Further, we confirm the high specificity of the CoREST/LSD1 degrader by performing streptavidin bead pull down with a newly synthesized biotin-conjugated probe. This revealed that it interacts with the entire CoREST complex (members include LSD1, RCOR1, HDAC1/2). In conclusion, we show that degrading CoREST/LSD1 in combination with HDAC inhibition is a synergistic strategy in H3K27M DMG. For future translational studies, we will assess biomarkers upon treatment and analyse compound potency in vivo.

Nucleolar phosphoprotein modifications as a marker of apoptosis induced by RITA treatment

Reactivating p53 and Inducing Tumor Apoptosis (RITA) has been reported to increase the p53 activity and to trigger p53-dependent apoptosis in cancer cells with wild-type p53. Tumor suppressor p53 interacts with nucleolar phosphoproteins nucleophosmin (NPM) and nucleolin (NCL), which have crucial role in many cellular processes. Specific NPM mutations associated with acute myeloid leukemia (AML) cause aberrant localization of NPM and p53 in the cytoplasm with possible impact on the p53 function. We tested an effect of RITA on primary cells, and we found significant RITA-induced changes in NPM and NCL phosphorylation associated with apoptosis in cells of AML patients, but not that of healthy donors. Subsequent screening of several AML cell lines revealed heterogeneous response to RITA, and confirmed an association of the specific phosphorylation with apoptosis. While decreased NCL phosphorylation at Threonines T76 and T84 could be attributed to RITA-induced cell cycle arrest, enhanced NPM phosphorylation at Threonine T199 was not accompanied by the cell cycle changes and it correlated with sensitivity to RITA. Simultaneously, inverse changes occurred at Serine S4 of the NPM. These new findings of RITA mechanism of action could establish the NPM pT199/pS4 ratio as a marker for suitability of RITA treatment of AML cells.

Design and Synthesis of New 4-(3,4,5-Trimethoxyphenyl)Thiazole-Pyrimidine Derivatives as Potential Antiproliferative Agents.

A new series of 3,4,5-trimethoxyphenyl thiazole pyrimidines has been synthesized and biologically evaluated for its in vitro anticancer activity. Compounds 4a, 4b, and 4h with substituted piperazine showed the best antiproliferative activity. In the NCI-60 cell line screening, compound 4b showed promising cytostatic activity against multiple cell lines. Notably, it elicited a GI value of 86.28% against the NSCL cancer cell line HOP-92 at a 10 μM dose. Compounds 4a and 4h at 10 μM showed promising GI values of 40.87% and 46.14% against HCT-116 colorectal carcinoma and SK-BR-3 breast cancer cell lines, respectively. ADME-Tox prediction of compounds 4a, 4b, and 4h revealed their acceptable drug-likeness properties. In addition, compounds 4a, 4b, and 4h showed a high probability of targeting kinase receptors via Molinspiration and Swiss TargetPrediction.

Screening of acid-tolerant hybrid Corn lines and parents using modified acid mineral soil

Screening of hybrid corn parent lines quickly and cheaply compared to hydroponic methods in the laboratory is needed to support the assembly of new high yielding varieties of acid tolerant corn. Addition of CaCO3 as equivalent to 2 t/ha (normal soil), while 0.5 t/ha AlCl3 (acidic). A total of 12 elite maize lines were tested based on relative root growth (RRG). Four sets of experiments were made, namely 2 sets normal soil media (pH 6.5) and 2 sets acid soil media (pH 4.3). Experimental design used in each experimental set was a randomized block with three replications. Results showed that rapid screening of hybrid maize parental lines could be carried out using modified soil acidity method by adding CaCO3 and AlCl3 to acid soil by measuring relative root growth (RRG) as the main variable. Corn obtained by genotypes No.80, MAL03x192, and Bisi-18 were classified as tolerant, MAL03x28, MAL03x182, MAL03x42, MAL03x44, MAL03x107, MAL03x115 were classified as moderately tolerant, while MAL03x100, MAL03x56, classified as sensitive. Screening of hybrid parent lines on acid soil modified to pH 4.3 (acidic) and normal pH 6.5 at seedling age 7 days after planting (dap) was more accurate than at seedling age of maize 14 dap.

First-trimester screening strategies: A balance between costs, efficiency and diagnostic yield.

The introduction of non-invasive prenatal testing (NIPT) by cell-free DNA (cfDNA) has reshaped first-trimester screening (FTS) polices. In most countries NIPT is offered as second line screening, after the combined test (CT). However, there is an increasing tendency to replace the CT by NIPT. In this second case the question arises as to whether a separate first-trimester scan should be offered next to the mid-trimester scan. In this commentary we use evidence from the literature to present the pros and cons of four different first-trimester screening strategies combining NIPT and ultrasound. This article is protected by copyright. All rights reserved.

A study of antibody conjugates for the treatment of inflammatory breast cancer.

e15016 Background: Inflammatory breast cancer (inflammatory carcinoma) is a rare metastatic malignant tumor, it accounts for about 2% of all breast cancer cases. Despite its low incidence, inflammatory breast cancer is highly invasive, its five-year survival rate is less than 41%, making its prognosis the worst of all breast cancer subtypes, and effective drugs are urgently needed in clinical practice. Therefore, our study develops novel antibody conjugate drugs that can target overexpressed-ICAM-1 in inflammatory breast cancer cells as an original molecular target precisely. Methods: In this study, flow cytometry was used to perform precise and quantitative target screening of inflammatory breast cancer cell lines (SUM-149, KPL4), the endocytosis efficiency of ADC drugs was verified by flow cytometry efficiency analysis and single-photon confocal analysis, and the cytotoxicity of different drugs and cell lines was explored by CCK8 experiment. A nude mouse model of orthotopic xenograft inflammatory breast cancer was constructed, and the in vivo therapeutic effect of inflammatory breast cancer was observed by intravenous injection of two ICAM-1 antibody conjugates (ICAM-1-MMAE and ICAM-1-DXD), also the ADC drug structure with the best therapeutic effect for inflammatory breast cancer was screened. Results: ICAM-1 molecule in a variety of inflammatory breast cancer cell lines were highly over-expressed, and the antibody internalization rate was 51% at 4h, and after the peak the endocytosis efficiency slowed down into the plateau stage; ICAM1-MMAE and ICAM1-DXD are safer than first-line chemotherapy agents for breast cancer; The tumor volume was significantly reduced after administration into the orthotopic breast cancer xenograft model, which further verified the obvious effect of ADC drugs in vivo. Conclusions: Both ICAM-1-MMAE and ICAM-1-DXD have shown significant anti-inflammatory breast cancer effects in vitro and in vivo, and this study provides potential antibody conjugate drugs for targeted therapy of inflammatory breast cancer, which is expected to help improve the poor prognosis of inflammatory breast cancer.

Drug mechanism enrichment analysis improves prioritization of therapeutics for repurposing

BackgroundThere is a pressing need for improved methods to identify effective therapeutics for diseases. Many computational approaches have been developed to repurpose existing drugs to meet this need. However, these tools often output long lists of candidate drugs that are difficult to interpret, and individual drug candidates may suffer from unknown off-target effects. We reasoned that an approach which aggregates information from multiple drugs that share a common mechanism of action (MOA) would increase on-target signal compared to evaluating drugs on an individual basis. In this study, we present drug mechanism enrichment analysis (DMEA), an adaptation of gene set enrichment analysis (GSEA), which groups drugs with shared MOAs to improve the prioritization of drug repurposing candidates.ResultsFirst, we tested DMEA on simulated data and showed that it can sensitively and robustly identify an enriched drug MOA. Next, we used DMEA on three types of rank-ordered drug lists: (1) perturbagen signatures based on gene expression data, (2) drug sensitivity scores based on high-throughput cancer cell line screening, and (3) molecular classification scores of intrinsic and acquired drug resistance. In each case, DMEA detected the expected MOA as well as other relevant MOAs. Furthermore, the rankings of MOAs generated by DMEA were better than the original single-drug rankings in all tested data sets. Finally, in a drug discovery experiment, we identified potential senescence-inducing and senolytic drug MOAs for primary human mammary epithelial cells and then experimentally validated the senolytic effects of EGFR inhibitors.ConclusionsDMEA is a versatile bioinformatic tool that can improve the prioritization of candidates for drug repurposing. By grouping drugs with a shared MOA, DMEA increases on-target signal and reduces off-target effects compared to analysis of individual drugs. DMEA is publicly available as both a web application and an R package at https://belindabgarana.github.io/DMEA.

Diagnostic yield in national team football players

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Malta Football Association. Introduction Sudden cardiac death (SCD) is an important cause of morbidity in competitive athletes. Pre-participation evaluation (PPE) is mandatory for most sporting organisations. The ECG plays a very important diagnostic role and is included in most screening algorithms. PPE for athletes ≥14 years registered with the National Football Association is now mandatory. Study objectives: The objective of this study was to assess the diagnostic yield of PPE in a group of elite Maltese football players competing at national level. Methodology Players selected at national level (years 2020-2022) underwent PPE (history, physical examination, and resting ECG). Senior team players also underwent echocardiography (biannually) as per regulations. Data was tabulated and analyzed in Microsoft Excel. Results 300 athletes (69% male) were selected in this timeframe. 10.6% (n=32) required referral for secondary evaluation, equating to 1 in 11 athletes screened. Referrals were more frequent in male vs female athletes (22.1% vs 10.2%, p=0.005). Most referrals were from the men’s senior’s squad (22.5%), followed by the men’s U17 squad (21.7%) and 20% of the men’s U15 team. The ECG was the commonest reason for referral to a sports cardiologist (n=23, 71.8%). The commonest abnormal ECG patterns included anterior TWI (n=9, 3.0%), inferior/lateral TWI (n=6, 2.0%) and WPW (n=2, 0.7%). 108 (36.0%) had echocardiography as a first line screening modality. This was abnormal in a fifth of those referred (n=7, 21.9%), 4 of these had a normal ECG. 3 (1.0%) athletes were diagnosed with a condition linked to SCD (n=2 WPW, n=1 HCM). Another 5 (1.7%) athletes were diagnosed with a cardiac disorder (n=1 left ventricular outflow tract ectopy, n=1 dilated aortic root, n=1 aortic regurgitation, n=1 atrial septal defect, n=1 mitral regurgitation). Echocardiography doubled the diagnostic yield (1.3% vs 2.7%), with 3 athletes having otherwise a normal history, physical examination and ECG. 1 in 38 athletes (2.7%) were given a cardiac diagnosis, 1 in 100 athletes (1.0%) were labelled with a condition linked to SCD. Conclusion The referral rate is comparable to that reported in international screening programs, higher in males. The ECG was the commonest reason for referral. The overall diagnostic yield equates to 2.7%, while 1.0% were given a diagnosis linked to SCD. The higher diagnostic yield in this population highlights the importance of raising awareness about heart disease and PPE in young athletes.

Revealing the different resistance mechanisms of banana ‘Guijiao 9’ to Fusarium oxysporum f. sp. cubense tropical race 4 using comparative proteomic analysis

Fusarium wilt of banana caused by Fusarium oxysporum f. sp. cubense is a worldwide devastating fungal disease in the banana industry. The disease caused by Fusarium oxysporum f. sp. cubense is becoming more and more serious. The pathogen of Fusarium oxysporum f. sp. cubense tropical race 4 (Foc4) is the most harmful one. ‘Guijiao 9’ is a banana cultivar with good resistance to Foc4, which is identified by resistance screening of natural variant lines. It is of great significance to explore the resistance genes and key proteins of ‘Guijiao 9’ for banana cultivar improvement and disease resistance breeding. In this study, iTRAQ (isobaric Tags for Relative and Absolute quantitation) was used to analyze the xylem proteomic data of banana roots from the resistant variety ‘Guijiao 9’ and susceptible variety ‘Williams’, and the differences in protein accumulation profiles between these two varieties at 24, 48, and 72 h after infection with Foc4 were compared. The identified proteins were analyzed by the protein WGCNA (Weighted Gene Correlation Network Analysis), and the differentially expressed proteins (DEPs) were verified by qRT-PCR experiments. Proteomic analysis showed that there were differences in the protein accumulation profiles of the resistant cultivar ‘Guijiao 9’ and the susceptible cultivar ‘Williams’ after infection with Foc4, and there were differences in resistance-related proteins, biosynthesis of secondary metabolites, peroxidase, and pathogenesis-related proteins. The stress response of bananas to pathogens was affected by multiple factors. Protein co-expression analysis showed that there was a high correlation between the MEcyan module and resistance, and ‘Guijiao 9’ had a different resistance mechanism compared with ‘Williams’. Significance‘Guijiao 9’ is a banana variety with good resistance to Foc4, which is identified by screening the resistance of natural variant lines in the farmland where banana plants are seriously infected by Foc4. It is of great significance to excavate the resistance genes and key proteins of ‘Guijiao 9’ for banana variety improvement and disease resistance breeding. The aim of this paper is to identify the proteins and related functional modules controlling the pathogenicity differences of Foc4 by comparative proteomic analysis of ‘Guijiao 9’, so as to understand the resistance mechanism of banana to Fusarium wilt, and offer basis for the final identification, isolation and utilization of Foc4 resistance-related genes in banana variety improvement. The research results will also provide a basis for further understanding the host-pathogen interaction and revealing the resistance mechanism of bananas.

Screening of Tropical Maize Inbred Lines by Artificial Infestation for Resistance against Invasive Fall Armyworm in India

Aim: This study was aimed to find resistance sources against FAW.
 Study Design: Randomised Block Design.
 Place and Duration of Study: The Present study was conducted at Maize Research Centre, Hyderabad with promising germplasm during Kharif-2021, Rabi-2021-22 and Kharif-2022. Methodology: Field-collected FAW egg masses were reared using maize leaf- and stalk-based diet at 27 ± 1 °C, 60 ± 5% relative humidity and 12 h day length. The resulting neonates were used to infest the seedlings of 34 diverse tropical maize inbred genotypes.
 Results: A total of 15 genotypes were found to have recorded a leaf damage score of less than 5 with the least score recorded in BML 2 (3.24), followed by BML 11 (3.34), BML 7(3.37), BML 5 (3.37), BML 8 (3.49), CM 201 (3.60), BML 32-2 (3.91), CM 132 (3.97), BML 10 (4.01), BML 6 (4.02), BML 13 (4.34), CM202 (4.34), CM 131 (4.68), BML 90 (4.82), BML 45 (4.95) and displayed moderate resistance.
 Conclusion: Out of 34 inbred lines studied 15 were found to be moderately resistant to fall armyworm based on LIR and cob damage score under artificial infestation.

The orally bioavailable GSPT1/2 degrader SJ6986 exhibits in vivo efficacy in acute lymphoblastic leukemia

AbstractAdvancing cure rates for high-risk acute lymphoblastic leukemia (ALL) has been limited by the lack of agents that effectively kill leukemic cells, sparing normal hematopoietic tissue. Molecular glues direct the ubiquitin ligase cellular machinery to target neosubstrates for protein degradation. We developed a novel cereblon modulator, SJ6986, that exhibits potent and selective degradation of GSPT1 and GSPT2 and cytotoxic activity against childhood cancer cell lines. Here, we report in vitro and in vivo testing of the activity of this agent in a panel of ALL cell lines and xenografts. SJ6986 exhibited similar cytotoxicity to the previously described GSPT1 degrader CC-90009 in a panel of leukemia cell lines in vitro, resulting in apoptosis and perturbation of cell cycle progression. SJ6986 was more effective than CC-90009 in suppressing leukemic cell growth in vivo, partly attributable to favorable pharmacokinetic properties, and did not significantly impair differentiation of human CD34+ cells ex vivo. Genome-wide CRISPR/Cas9 screening of ALL cell lines treated with SJ6986 confirmed that components of the CRL4CRBN complex, associated adaptors, regulators, and effectors were integral in mediating the action of SJ6986. SJ6986 is a potent, selective, orally bioavailable GSPT1/2 degrader that shows broad antileukemic activity and has potential for clinical development.

Artificial intelligence in diabetic retinopathy screening: clinical assessment using handheld fundus camera in a real-life setting

AimDiabetic retinopathy (DR) represents the main cause of vision loss among working age people. A prompt screening of this condition may prevent its worst complications. This study aims to validate the in-built artificial intelligence (AI) algorithm Selena+ of a handheld fundus camera (Optomed Aurora, Optomed, Oulu, Finland) in a first line screening of a real-world clinical setting.MethodsIt was an observational cross-sectional study including 256 eyes of 256 consecutive patients. The sample included both diabetic and non-diabetic patients. Each patient received a 50°, macula centered, non-mydriatic fundus photography and, after pupil dilation, a complete fundus examination by an experienced retina specialist. All images were after analyzed by a skilled operator and by the AI algorithm. The results of the three procedures were then compared.ResultsThe agreement between the operator-based fundus analysis in bio-microscopy and the fundus photographs was of 100%. Among the DR patients the AI algorithm revealed signs of DR in 121 out of 125 subjects (96.8%) and no signs of DR 122 of the 126 non-diabetic patients (96.8%). The sensitivity of the AI algorithm was 96.8% and the specificity 96.8%. The overall concordance coefficient k (95% CI) between AI-based assessment and fundus biomicroscopy was 0.935 (0.891–0.979).ConclusionsThe Aurora fundus camera is effective in a first line screening of DR. Its in-built AI software can be considered a reliable tool to automatically identify the presence of signs of DR and therefore employed as a promising resource in large screening campaigns.