Additional Lines Research Articles

Physiologic specialization of Puccinia triticina, the causal agent of wheat leaf rust, in Canada in 2020–2023

Wheat nurseries and fields throughout Canada were surveyed annually, from 2020 to 2023, for the presence of leaf rust, caused by Puccinia triticina Erikss. Infected leaves were collected, then single pustule isolates were analyzed for virulence on a set of 16 differential lines. In 2020 there were 29 unique virulence phenotypes found among 230 isolates, in 2021 there were 37 unique virulence phenotypes found from 153 isolates, in 2022, 47 unique phenotypes were found among 246 isolates, and there were 69 unique phenotypes among 384 isolates in 2023. The most common virulence phenotypes over this 4-year period from Manitoba and Saskatchewan were MNPS, TNBJ, MBDS and MLPS. In Ontario these were TCTS, MBTN and TBRD, while in Quebec these were MBTN, TCTS, MBPS and TBSJ. The smaller samples from Ontario and Quebec were more diverse than the larger samples from Manitoba and Saskatchewan. There were only 25 isolates analyzed from British Columbia, but four of the five unique virulence phenotypes found there, LBDS, LCDS, CCPN and NBDS, were not found in the rest of Canada during this period. Only eight isolates from Alberta were analyzed and they were similar to virulence phenotypes found in Manitoba and Saskatchewan. The frequencies of virulence to Lr9, Lr24 and Lr21 were higher in Manitoba and Saskatchewan than in Ontario and Quebec, though the reverse was true for Lr2a, Lr2c and Lr18. When representative isolates were tested on additional differential lines there was no virulence detected to Lr19, Lr29, Lr32, Lr52 and Lr22a.

Engrailed-2 (EN2) protein in cervical mucus: a novel biomarker for endometrial carcinoma.

This study aims to demonstrate that the EN2 protein in cervical mucus may serve as a novel biomarker for screening endometrial cancer. This study included 133 patients who were treated at Beijing Obstetrics and Gynecology Hospital. According to the pathological results of hysteroscopy endometrial biopsy, the patients were divided into endometrial cancer group (n = 55), endometrial atypical hyperplasia group (n = 16), benign lesion group (n = 28), and control group (n = 34). All patients collected cervical mucus before hysteroscopy, and the level of EN2 protein in cervical mucus was detected by ELISA in the four groups of patients. Nine patients who underwent surgical treatment for endometrial cancer were included, and endometrial cancer lesions and adjacent tissues without endometrial cancer infiltration were taken from the endometrial cancer lesions and cervical tissues. Fifteen patients who underwent hysterectomy for benign lesions were included, and endometrial and cervical tissues were taken from the endometrial cancer lesions and adjacent tissues without endometrial cancer infiltration. PT-PCR, immunohistochemistry, and WB were used to verify the expression differences of EN2 protein in cancerous lesions and endometrial tissues without endometrial infiltration, cervical tissues, and endometrial tissues without endometrial lesions. In addition, HEC1B, KLE, and HeLa cell lines were used to characterize EN2 overexpression in endometrial cancer cells. Immunohistochemistry, RT-PCR, and confocal analysis were used to detect the expression of EN2 protein in different cell lines. In different groups, the average concentration of EN2 protein in cervical mucus in the EC group was significantly higher than that in the benign group and the normal control group (573.9 ± 123.4ng/mL vs 153.5 ± 106.2ng/mL and 153.0 ± 107.5ng/mL, P < 0.001). The concentration of EN2 protein in EIN3 case specimens was significantly higher than that in the normal control group (P < 0.001). ROC analysis showed that the optimal threshold for diagnosing endometrial cancer in cervical mucus was 321.1ng/ml, with a sensitivity of 92.6% and specificity of 95.4% for distinguishing EINIII, EC, and non-cancerous cases. In clinical specimens, the expression level of EN2 protein in endometrial cancer tissues was significantly higher than that in endometrial tissues and cervical tissues without endometrial cancer infiltration. In addition, PT-PCR, immunohistochemistry, suggest that EN2 protein is overexpressed in endometrial cancer cell lines compared to cervical adenocarcinoma cells (P < 0.01). The concentration of EN2 protein in cervical mucus can effectively identify endometrial cancer and precancerous lesions. The increased expression of EN2 protein in endometrial cancer lesions leads to an increase in the concentration of EN2 protein in the cervical mucus of endometrial cancer patients.This is a small single-center study, and larger studies are needed to determine the role of EN2 protein in the diagnosis of endometrial cancer.

Statistical Data on Myelodysplastic Syndrome in the Russian Federation

Introduction. Myelodysplastic syndrome (MDS) is a nosology that requires examination using cytogenetic, molecular-genetic and immunophenotypic analysis of bone marrow and/or blood, as well as mandatory bone marrow trepan biopsy with pathomorphological and immunohistochemically studies. Until recently, there was no official statistical data on MDS in Russia.Aim: to present data on the incidence and prevalence of MDS in Russia based on official statistical forms.Materials and methods. Information from statistical form №7 «Information on malignant neoplasms» (SF No. 7) for 2022 and 2023 on the incidence and prevalence of MDS, updated at the initiative of the National Medical Research Center for Hematology, is presented. For the first time, additional lines (35–37) with information on the movement of patients, including MDS (code D46 according to ICD-10), have been introduced into table 2100.Results. According to SF No. 7, in 2022 and 2023, 2,827 and 3,411 cases of MDS were registered, respectively. The estimated primary incidence in the Russian Federation was 0.58 and 0.50 per 100 thousand of the adult population in 2022 and 2023, respectively, and the prevalence was 2.4 per 100 thousand of the adult population. The estimated incidence of MDS by federal districts in 2022 ranged from 0.13 to 1.05 with variations from 0.03 to 2.57 per 100 thousand of the adult population, depending on the region of residence. At the end of 2023, 3001 (88 %) patients with MDS were registered under dispensary observation, of which 860 (28.7 %) were under observation for 5 years or more.Conclusion. The obtained statistical data on the incidence and prevalence of MDS showed the high significance of the work carried out both for the subsequent improvement of the system of registration of patients with diseases of the blood system in general, and MDS, particularly the Russian Federation, and will make it possible to use this data in the planning of healthcare in the Russia.

Cytogenetic features of intergeneric amphydiploids and genome-substituted forms of wheat

Synthetic intergeneric amphydiploids and genome-substituted wheat forms are an important source for transferring agronomically valuable genes from wild species into the common wheat (Triticum aestivum L.) genome. They can be used both in academic research and for breeding purposes as an original material for developing wheatalien addition and substitution lines followed by translocation induction with the aid of irradiation or nonhomologous chromosome pairing. The chromosome sets and genome constitutions of allopolyploids are usually verified in early hybrid generations, whereas the subsequent fate of these hybrids remains unknown in most cases. Here we analyze karyotypes of five hexa- (2n = 6x = 42) and octoploid (2n = 8x = 56) amphydiploids of wheat with several species of the Aegilops, Haynaldia, and Hordeum genera, and six genome-substituted wheat–Aegilops forms, which were developed over 40 years ago and have been maintained in different gene banks. The analyses involve C-banding and fluorescence in situ hybridization (FISH) with pAs1 and pSc119.2 probes. We have found that most accessions are cytologically stable except for Avrodes (genome BBAASS, a hexaploid genome-substituted hybrid of wheat and Aegilops speltoides), which segregated with respect to chromosome composition after numerous reproductions. Chromosome analysis has not confirmed the presence of the N genome from Ae. uniaristata Vis. in the genome-substituted hybrid Avrotata. Instead, Avrotata carries the D genome. Our study shows that octoploid hybrids, namely AD 7, AD 7147 undergo more complex genome reorganizations as compared to hexaploids: the chromosome number of two presumably octoploid wheatAegilops hybrids were reduced to the hexaploid level. Genomes of both forms lost seven chromosome pairs, which represented seven homoeologous groups and derived from different parental subgenomes. Thus, each of the resulting hexaploids carries a synthetic/hybrid genome consisting of a unique combination of chromosomes belonging to different parental subgenomes.

Cytological mapping of a powdery mildew resistance locus PmRc1 based on wheat-Roegneria ciliaris structural rearrangement library.

A powdery mildew (Pm) resistance locus PmRc1 was identified and transferred from Roegneria ciliaris into wheat. Two compensative translocation lines carrying PmRc1 were developed. Powdery mildew (Pm), caused by the biotrophic fungal pathogen Blumeria graminis f.sp. tritici (Bgt), is a global destructive disease of bread wheat (Triticum aestivum L.). Identifying and utilizing new Pm resistance gene(s) is the most fundamental work for disease control. Roegneria ciliaris (2n = 4 x= 28, genome ScScYcYc) is a wild relative species of cultivated wheat. In this work, we evaluated wheat-R. ciliaris disomic chromosome addition lines for Pm resistance in multiple years. The introduction of R. ciliaris chromosome 1Sc into wheat enhanced resistance. The resistance locus on 1Sc was designated as PmRc1. To cytologically map PmRc1, we induced structural rearrangements using ion irradiation and increasinghomoeologous chromosomal recombination. The identified 43 1Sc translocation or deletion lines were usedto construct 1Sc cytological bin map bymarker analysis using 111 molecular markers. Based on the Pm resistance of thecharacterized structural rearrangement lines, the PmRc1 locus was cytologically mapped to bin 1ScS-8 of 1Sc short arm, flanked by markers CMH93-2 and CMH114-1. Two compensatory chromosomal translocation lines (T1ScS 1BL and T1ScS-1AS 1AL) carrying PmRc1 were developed and assessed for theiragronomic traits. Translocation chromosome T1ScS 1BL hadenhanced Pm resistance accompanied by negative effects on grain number and single plant yield. Translocation chromosome T1ScS-1AS 1AL hadenhanced Pm resistance and increased spikelet number per spike, without any obvious negativeeffect on other tested traits. Thus, T1ScS-1AS 1AL is recommended preferentiallyused in wheat breedingfor Pm resistance.

Multi-layered proteomics identifies insulin-induced upregulation of the EphA2 receptor via the ERK pathway which is dependent on low IGF1R level

Insulin resistance impairs the cellular insulin response, and often precedes metabolic disorders, like type 2 diabetes, impacting an increasing number of people globally. Understanding the molecular mechanisms in hepatic insulin resistance is essential for early preventive treatments. To elucidate changes in insulin signal transduction associated with hepatocellular resistance, we employed a multi-layered mass spectrometry-based proteomics approach focused on insulin receptor (IR) signaling at the interactome, phosphoproteome, and proteome levels in a long-term hyperinsulinemia-induced insulin-resistant HepG2 cell line with a knockout of the insulin-like growth factor 1 receptor (IGF1R KO). The analysis revealed insulin-stimulated recruitment of the PI3K complex in both insulin-sensitive and -resistant cells. Phosphoproteomics showed attenuated signaling via the metabolic PI3K-AKT pathway but sustained extracellular signal-regulated kinase (ERK) activity in insulin-resistant cells. At the proteome level, the ephrin type-A receptor 2 (EphA2) showed an insulin-induced increase in expression, which occurred through the ERK signaling pathway and was concordantly independent of insulin resistance. Induction of EphA2 by insulin was confirmed in additional cell lines and observed uniquely in cells with high IR-to-IGF1R ratio. The multi-layered proteomics dataset provided insights into insulin signaling, serving as a resource to generate and test hypotheses, leading to an improved understanding of insulin resistance.

A Multicenter Phase II Trial of Ruxolitinib for Treatment of Corticosteroid Refractory Sclerotic Chronic Graft-Versus-Host Disease.

Sclerotic chronic graft-versus-host disease (cGVHD) represents a highly morbid and refractory form of cGVHD, and novel therapies for sclerotic cGVHD are critically needed. This study aimed to determine the efficacy of ruxolitinib in patients with corticosteroid refractory sclerotic cGVHD. In a single-arm multicenter phase II trial (N = 47), adults with sclerotic cGVHD refractory to corticosteroids and ≥one additional line of systemic therapy for cGVHD received ruxolitinib for ≥six months (ClinicalTrials.gov identifier: NCT03616184). The primary end point was complete or partial response (PR) in skin and/or joint defined according to the 2014 National Institute of Health cGVHD Consensus Criteria. Following the use of ruxolitinib for a median of 11 months, PR in skin and/or joints was noted in 49% (95% CI, 34 to 64) at 6 months, with 45% having joint and fascia response and 19% having skin response. The duration of skin/joint response was 77% (95% CI, 48 to 91) at 12 months. Overall cGVHD PR was noted in 47% (95% CI, 32 to 61). Improvement in Lee Symptom Scale summary and skin subscale scores was noted in 38% of patients. With a cumulative incidence of treatment failure of 20.8% (95% CI, 10.0 to 34.1), nonrelapse mortality (NRM) of 2.2% (95% CI, 0.17 to 10.3), and no recurrent malignancy, failure-free survival (FFS) was 77.1% (95% CI, 61.3 to 87.0) at 12 months. Ruxolitinib was overall well tolerated with no new safety signals. The use of ruxolitinib was associated with relatively high rates of skin/joint responses and overall cGVHD responses, improvement in patient-reported outcomes, low NRM, and high FFS in patients with refractory sclerotic cGVHD. Ruxolitinib offers an effective treatment option for refractory sclerotic cGVHD.

Cytogenetic and molecular identification of novel wheat-Elymus sibiricus addition lines with resistance to leaf rust and the presence of leaf pubescence trait.

Emerging new races of leaf rust (Puccinia triticina Eriks) are threatening global wheat (Triticum aestivum L.) production. Identifying additional resistance genes from all available gene pools is crucial to expanding wheat resistance to these virulent leaf rust races. Siberian wild rye (Elymus sibiricus L.) possesses numerous beneficial traits that can be valuable in wheat improvement. Three new wheat-E. sibiricus addition lines, O27-2 (BC8), O27-3 (BC12) and O193-3 (BC12), were developed through a backcrossing scheme in this study, using leaf rust field evaluations, molecular marker assays and cytogenetic analysis. These three lines were derived from progeny of the bread wheat cultivar 'Obriy' (2n = 6x = 42, AABBDD) and partial octoploid amphiploid wheat-E. sibiricus (2n = 8x = 56, AABBDDStSt). The lines (O27-2, O27-3 and O193-3) demonstrated strong specific leaf pubescence (hairiness) and resistance at the adult stage to a local population of leaf rust races. The response to leaf rust in these three lines significantly differed from that of the Lr24 gene, providing evidence for a distinct resistance mechanism associated with the 3St chromosome. This study is the first to report the transfer of an E. sibiricus chromosome into wheat that confers leaf rust resistance. Molecular marker analysis and genomic in situ hybridization confirmed that lines O27-2, O27-3 and O193-3 each possess one pair of E. sibiricus 3St chromosomes. The resistance gene was determined to be on the additional alien chromosome in these lines. Molecular markers (Xwmc221, Lr29F18, Sr24/Lr24) confirmed that the lines O27-2, O27-3, and O193-3 each contain a pair of E. sibiricus 3St chromosomes carrying leaf rust resistance genes. These findings demonstrate that the E. sibiricus 3St chromosome carries the leaf rust resistance gene and that the O27-2, O27-3, and O193-3 lines can serve as novel germplasm sources for introducing this resistance into wheat breeding programs. This study contributes to broadening the genetic diversity of resistance genes available for combating leaf rust in wheat.

DDDR-32. EXPLORING ANDROGENIC MODULATION IN GLIOBLASTOMA: POTENCY AND SELECTIVITY OF NOVEL NORETHINDRONE DERIVATIVES

Abstract BACKGROUND Glioblastoma (GBM) represents the most frequently diagnosed malignant CNS tumor in adults and remains incurable. Despite the identification of several oncogenic drivers contributing to tumor formation, targeted therapy with brain-penetrant inhibitors has afforded little progress in survival outcomes. Interestingly, gender has been shown to increase the incidence of GBM, with men having roughly a 50-60% increase in incidence compared to women in the US. This statistic led to research on the involvement of and subsequent inhibition of androgen synthesis and signaling in cell culture models and tumor samples. METHODS To further investigate the potential involvement of steroidal hormones in GBM proliferation, our lab synthesized a series of norethindrone (NE) derivatives with varied molecular weights, steric bulk, and lipophilicity to modulate the androgenic activity of NE. The small library was tested in several GBM cell lines, including U87, A172, and T98G cells, using cell viability assays. RESULTS One derivative, a lipophilically modified version of NE synthesized via a one-pot click reaction, was shown to have improved potency compared with parental NE (&amp;gt;5-fold). The lipophilic NE derivative had IC50 value of 22 uM, 15 uM, and 35 uM in the U87, A172, and T98G cells, respectively. This molecule was tested in immortalized normal human astrocyte (NHA) cells and found to have an IC50 value of 34 uM suggesting some selectivity. DISCUSSION Given this derivative’s activity in GBM models and modest selectivity, we plan to screen it in additional GBM cell lines (LN-18 and U251) and eventually in glioma stem cell models. Future research will focus on identifying key targets involved in the mechanism of action, including the impact of lipophilic addition to the steroid nucleus and its effect on androgenic activity and downstream signaling. We will investigate these effects using RPPA and co-treatments with androgen receptor antagonists and 5-alpha reductase inhibitors.

CTIM-22. MEDIAN AND 2 YEARS SURVIVAL OF NEWLY DIAGNOSED UNMETHYLATED MGMT GLIOBLASTOMA PATIENTS TREATED WITH TEMFERON IMMUNO-GENE THERAPY

Abstract TEM-GBM is an open-label, Phase 1/2a dose-escalation study aimed to evaluate the safety and efficacy of a myeloid cell-targeted therapy (Temferon) in up to 27 newly diagnosed GBM patients with unmethylated MGMT (uMGMT). Temferon, consists of autologous Hematopoietic Stem Progenitor Cells (HSPCs) genetically modified with a lentiviral vector to deliver IFN-α2 within the tumor microenvironment by Tie-2 expressing macrophages. As of 21st May 2024, 24 GBM patients in 8 cohorts received incremental doses of Temferon and 6 are still alive. For all patients, median overall survival (OS) and median progression free survival reach 17 months and 8.3 months from first surgery, respectively. The interim survival rate at 2 years in Temferon-treated patients is 30% (6 of 20 patients; 3 patients excluded as follow-up is below 1 year). The mOS and the % of patients surviving up to 2 years are currently higher than previously reported for uMGMT patients treated as per standard practice (12.7 months and 14,8%, respectively). Two out of the six patients did not receive any additional treatment lines up to two years after 1st surgery. The other four patients instead received a 2nd treatment line (bevacizumab, regorafenib, Gamma-Knife, metronomic Temozolomide, Lomustine) as per the PI judgment, on average after 443 days from 1st surgery (333 days from Temefron - range 223-1030 days from first surgery). Specifically, Bevacizumab administration started 12 months after 1st surgery for one patient and 19 months for the other 2 patients at 5 mg/kg. The data further confirms the initial evidence on safety and tolerability of Temferon and highlight the potential to prolong the survival of patients affected by uMGMT GBM.

Alterations in the microenvironment of junctional epidermolysis bullosa keratinocytes: a gene expression study

Integrin α6β4 subunits and type XVII collagen are critical transmembrane proteins involved in cell-matrix adhesion in skin, while laminin 332 serves as their ligand in the basement membrane zone (BMZ). Those proteins contribute to the composition of hemidesmosomes (HDs) and pathogenic variants in their corresponding genes cause junctional epidermolysis bullosa (JEB). Although the genotype-phenotype relationships in JEB have been extensively studied, the pathogenetic changes of extracellular matrix (ECM) and cell-matrix adhesion resulting from gene mutations remain unclear. We conducted a global unbiased transcriptome analysis using bulk RNA sequencing (RNA-seq) on selected JEB donor-derived cell lines lacking integrin β4 subunit (ITGB4-), type XVII collagen (COL17-) and laminin β3 chain (LAMB3-), respectively. Additional JEB cell lines and JEB donor skin samples were used for validation of relevant findings. Collectively, the results revealed similar dysregulation patterns of ECM and focal adhesion (FAs) associated genes in ITGB4- and COL17- cell lines, while LAMB3- cells displayed a relatively opposite tendency. Importantly, key nodes in the dysregulated network were associated with ECM proteins involved in wound healing processes. Additionally, a group of inflammatory-associated genes was disclosed to be up-regulated in JEB keratinocytes and could not be normalized by the adhesion rescue. The functional assay further revealed the hierarchy of stable adhesion among mutant cell lines COL17->ITGB4->LAMB3-, which correlates with the severity of their clinical manifestations. Our results indicated a wound healing associated ECM and inflammatory microenvironment established by JEB keratinocytes.

Designing ballastless high-speed railways in frozen regions: A dynamic analysis using three-dimensional numerical modelling

Many high-speed railways (HSRs) have been constructed in the frozen regions of China, with additional lines expected to be developed in the future. However, research into the dynamic response of embankments in these regions under moving train loads has been limited, particularly in view of potentially increased train speeds. Therefore, this study developed an indirect thermal–dynamic coupled three-dimensional finite-element model to investigate the dynamic responses of railway subgrades induced by high-speed trains in frozen regions. The study examined dynamic responses in relation to underlying layer stiffness, frost depth, and train speed. Dynamic amplification factors for train speed and frost depth were derived from statistical analysis of simulation results. A potential method was proposed to predict the long-term track performance of HSRs in frozen regions under conditions of higher train speeds. The study suggests practical recommendations, providing essential guidance to railway engineers in devising optimal strategies for railway design in frozen regions.

Advances in Triticale (X Triticosecale) Improvement: Chromosome Manipulation and Biotechnological Approaches

Triticale (X Triticosecale) is a hybrid cereal crop with great potential for enhancing food security. It is a synthetic cereal. Meanwhile, certain genetic instabilities arising from the merging of the rye and wheat genomes have impeded the advancement of triticale, chromosome engineering advancements along with biotechnological approaches might potentially unleash the full potential of triticale. This article provides a comprehensive summary of the historical development and current status of research on conventional and molecular breeding and manipulating triticale chromosomes in order to introduce beneficial traits, correct genetic abnormalities, and accelerate breeding. Among the major strategies covered are chromosomal doubling, addition, replacement, translocation, and deletion. Beneficial genes from rye for quality of grain, yield, and disease resistance were incorporated into triticale backgrounds using addition and replacement lines. In general, using chromosome-modifying technologies within an integrated breeding framework may help with genetic stabilization, the planned evolution of triticale for greater productivity and robustness, and strategic trait integration. This study looks at the advantages, disadvantages, and potential benefits of using chromosomal engineering to enhance triticales.

A novel high-z submm galaxy efficient line survey in ALMA Bands 3 through 8 – an ANGELS pilot

ABSTRACT We use the Atacama Large sub/Millimetre Array (ALMA) to efficiently observe spectral lines across Bands 3, 4, 5, 6, 7, and 8 at high-resolution (0.5–0.1 arcsec) for 16 bright southern Herschel sources at $1.5 \lt z \lt 4.2$. With only six and a half hours of observations, we reveal 66 spectral lines in 17 galaxies. These observations detect emission from CO (3−2) to CO(18−17), as well as atomic ([C i](1−0), (2−1), [O i] 145 $\mu$m and [N ii] 205 $\mu$m) lines. Additional molecular lines are seen in emission (${\rm H_2O}$ and ${\rm H_2O^+}$) and absorption (OH$^+$ and CH$^+$). The morphologies based on dust continuum ranges from extended sources to strong lensed galaxies with magnifications between 2 and 30. CO line transitions indicate a diverse set of excitation conditions with a fraction of the sources ($\sim 35$ per cent) showcasing dense, warm gas. The resolved gas to star formation surface densities vary strongly per source, and suggest that the observed diversity of dusty star-forming galaxies could be a combination of lensed, compact dusty starbursts and extended, potentially merging galaxies. The predicted gas depletion time-scales are consistent with 100 Myr to 1 Gyr, but require efficient fuelling from the extended gas reservoirs onto the more central starbursts, in line with the Doppler-shifted absorption lines that indicate inflowing gas for two out of six sources. This pilot paper explores a successful new method of observing spectral lines in large samples of galaxies, supports future studies of larger samples, and finds that the efficiency of this new observational method will be further improved with the planned ALMA Wideband Sensitivity Upgrade.

Six type-I PKS classes and highly conserved melanin and elsinochrome gene clusters found in diverse Elsinoë species

Elsinoë species are phytopathogenic fungi that cause serious scab diseases on economically important plants. The disease symptoms arise from the effects of a group of phytotoxins known as elsinochromes, produced via a type-I polyketide synthase (PKS) biosynthetic pathway. The elsinochrome gene cluster was first annotated in Elsinoë fawcettii where the main type-I PKS gene was characterized as EfPKS1. A later study showed that this gene and the associated cluster had not been correctly annotated, and that EfPKS1 was actually the anchor gene of the melanin biosynthetic pathway. A new type-I PKS gene EfETB1 associated with elsinochrome production was also identified. The aim of this study was to identify all type-I PKS genes in the genomes of seven Elsinoë species with the goal of independently verifying the PKS containing clusters for both melanin and elsinochrome production. A total of six type-I PKS classes were identified, although there was variation between the species in the number and type of classes present. Genes similar to the E. fawcettii EfPKS1 and EfETB1 type-I PKS genes were associated with melanin and elsinochrome production respectively in all species. The complete melanin and elsinochrome PKS containing clusters were subsequently annotated in all the species with high levels of synteny across Elsinoë species. This study provides a genus-level overview of type-I PKS distribution in Elsinoë species, including an additional line of support for the annotation of the melanin and elsinochrome PKS containing clusters in these important plant pathogens.

In vitro effects of l-kynurenine and quinolinic acid on adhesion, migration and apoptosis in B16 F10 melanoma cells

IntroductionThe inhibition of melanoma adhesion through adhesion molecules, such as integrins and E-cadherin, may represent a promising strategy for managing melanoma metastasis. Compounds, namely l-kynurenine (L-kyn) and quinolinic acid (Quin), previously displayed anti-cancer effects at half-maximal inhibitory concentration (IC50) against B16 F10 melanoma cells in vitro. However, the role of these compounds in B16 F10 melanoma cell adhesion, migration and apoptosis remain unknown. MethodsPost-exposure to the compounds, flow cytometry was used to analyse the expression of very late antigen-5 (VLA-5), E-cadherin and cleaved caspase-3 in B16 F10 melanoma and RAW 264.7 murine macrophage cells. An adhesion assay was used to quantify the adhesion of both cell lines to vitronectin. A scratch migration assay was used to measure the possible inhibition of cell migration in B16 F10 cells in response to L-kyn and Quin. ResultsIn both B16 F10 and RAW 264.7 cells, neither L-kyn nor Quin induced significant effects on VLA-5 expression or cell adhesion to vitronectin. In B16 F10 cells, both L-kyn and Quin elevated E-cadherin expression and displayed a trend of suppressed migration. However, only L-kyn elevated E-cadherin in RAW 264.7 cells. L-kyn induced apoptosis by elevating cleaved caspase-3 expression in both cell lines. ConclusionL-kyn and Quin demonstrated promising antimetastatic effects in their ability to elevate E-cadherin expression and induce apoptosis in B16 F10 melanoma cells. However, these effects did not occur in response to vitronectin or VLA-5 integrin alterations. Furthermore, it cannot be excluded that L-kyn also induced apoptosis in RAW 264.7 cells. As such, these effects should be confirmed in additional control cell lines and substantiated with in vivo models.

Factors associated with quality of life among newly diagnosed acute ischemic stroke patients: a community-based case-control study.

Stroke burden is expected to increase and surviving a bout of stroke may leave one with a chronic or disabling outcome decreasing significantly the quality of life of the sufferer. The study aimed to explore the association between quality of life (QoL) in stroke and non-stroke individuals in a predominantly agricultural community. A community-based case-control study was conducted among 154 cases aged 18 and 75 diagnosed with incident stroke. Controls were 554 non-stroke individuals (n = 554) recruited from a community where cases resided. Cases and controls were matched for age, gender and residential area. Using a self-reported questionnaire of the World Health Organization Quality of Life (WHOQOL-BREF), socio-demographic characteristics and lifestyle habits were measured in association with QoL. Statistical analyses included multivariable logistic regression models, adjusted odds ratio (aOR) and 95% confidence interval (CI). Significant predictors associated with low-medium QoL were having a larger waist circumference (aOR = 1.619, 95%CI [1.003-2.612]) and being a farmer (aOR = 2.976, 95%CI [1.143-7.750]) but having a current smoking habit and being male were at lesser odds with low-medium QoL (aOR = 0.381, 95%CI [0.191-0.757]) and (aOR = 0.564, 95%CI [0.323-0.985]) respectively. In all domains, women were at a higher risk of low-medium QoL while in physical health and environment domains, it was having a larger waist circumference. In both physical health and psychological domains, being married was protective to low-medium QoL so also being age 39 or younger and having a higher education in social relationship domain. Waist circumference, occupation, smoking habit and gender are associated with low-medium QoL. Addressing the influence of such factors could create an additional therapeutic line in the primary prevention of stroke in at-risk populations.

RNA sequencing and functional analysis uncover key long non-coding RNAs involved in regulating pollen fertility during the process of gametocidal action in wheat.

Gametocidal (Gc) chromosomes have been widely utilized in genetic breeding due to their ability to induce chromosomal breakage and eliminate gametes that lack them. Long noncoding RNAs (lncRNAs) have various functional mechanisms in regulating pollen and anther development; however, their regulatory contributions to Gc action are still unknown. Here, we identified 2824 differentially expressed lncRNAs (DE-lncRNAs) from the anther tissues of Triticum aestivum cv. Chinese Spring (CS) and Chinese Spring-Gc 3C chromosome monosomic addition line (CS-3C) through sequencing. In this study, we predicted 161 target mRNAs for 145 DE-lncRNAs, including 104 cis-regulatory, 60 trans-regulatory, and three both cis-regulatory and trans-regulatory manner. Combined with our previous miRNA sequencing data, 241 DE-lncRNAs functioned as potential endogenous target mimics (eTMs) for 84 differentially expressed microRNAs (DE-miRNAs, including 12 novel miRNAs). The results of transient transformation in tobacco leaves indicated that L006278 could bind to MTCONS_00006277, which encoded a calcineurin CBL-interacting protein kinase 19-like, and suppress its expression. Furthermore, L117735 could function as an eTM for tae-miR9657b-3p, and L056972 could function as an eTM for gc-m2240-5p. To explore the function of lncRNAs in the process of Gc action, we transformed L006278, an up-regulated lncRNA in CS-3C, into rice to analyze its effect on pollen fertility. Overexpression of L006278 led to a reduction in rice pollen fertility. Overall, our findings indicate that lncRNAs can contribute to the regulation of pollen fertility during the process of Gc action by regulating the expression levels of target mRNAs and acting as eTMs for certain key miRNAs.

GOG-3097/ENGOT-ov81/GTG-UK/RAMP 301: a phase 3, randomized trial evaluating avutometinib plus defactinib compared with investigator’s choice of treatment in patients with recurrent low grade serous ovarian cancer

BackgroundThere are no approved treatments specifically for low grade serous ovarian cancer; current standard of care treatment options are limited in efficacy and tolerability. The combination of avutometinib with defactinib...

Optical and X-ray studies of the Be/X-ray binary IGR J06074+2205

ABSTRACT We present the results obtained from X-ray and optical analysis of the Be/X-ray binary IGR J06074+2205, focusing on before, during, and after the X-ray outbursts in 2023 October and December. The properties of the neutron star in the binary are investigated using NICER and NuSTAR observations during the X-ray outbursts. The pulse profiles across a broad energy range, are found to be strongly dependent on luminosity and energy, revealing the complex nature of the emitting region. An absorbed power law can describe each NICER spectrum in the 1–7 keV band. The 3–79 keV NuSTAR spectrum can be well described by a negative and positive power law with an exponential cut-off model. Utilizing the MAXI/GSC long-term light curve, we estimate the probable orbital period to be 80 or 80/n (n = 2, 3, 4) d. We investigate the evolution of the circumstellar disc around the Be star by using optical spectroscopic observations of the system between 2022 and 2024. We observe variable H $\alpha$ and Fe ii emission lines with an increase in equivalent width, indicating the presence of a dynamic circumstellar disc. A distinct variation in the V/R value for H $\alpha$ and Fe ii lines is also observed. The appearance of additional emission lines, such as He i (5875.72 Å), He i (6678 Å), and He i (7065 Å), during the post-outburst observation in 2024 February suggests the growing of a larger or denser circumstellar disc. The disc continues to grow without any noticeable mass-loss, even during the 2023 X-ray outbursts, which may lead to a future giant X-ray outburst.