Galectin-7 Expression in the Placentas of Women with Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is a common condition during pregnancy. The prevalence of GDM is continuously increasing worldwide. Due to accessible diagnostic methods and a clear understanding of risk factors, GDM can be effectively diagnosed and managed.

Interface-guided phenotyping of coding variants in the transcription factor RUNX1.

Single-gene missense mutations remain challenging to interpret. Here, we deploy scalable functional screening by sequencing (SEUSS), a Perturb-seq method, to generate mutations at protein interfaces of RUNX1 and quantify their effect on activities of downstream cellular programs. We evaluate single-cell RNA profiles of 115 mutations in myelogenous leukemia cells and categorize them into three functionally distinct groups, wild-type (WT)-like, loss-of-function (LoF)-like, and hypomorphic, that we validate in orthogonal assays.

Placental expression of inflammatory Galectin-12 is associated with gestational diabetes.

Objectives: Gestational diabetes mellitus (GDM) is a growing health concern. Since members of the galectin-family are identified to play a role in the pathogenesis of GDM, we determined galectin-12 as an essential protein due to its influence in lipolysis and inflammation processes. This study investigates the expression of galectin-12 in the placentas of women with GDM.

Target fishing reveals PfPYK-1 and PfRab6 as potential targets of an antiplasmodial 4-anilino-2-trichloromethylquinazoline hit compound.

We present investigations about the mechanism of action of a previously reported 4-anilino-2-trichloromethylquinazoline antiplasmodial hit-compound (Hit A), which did not share a common mechanism of action with established commercial antimalarials and presented a stage-specific effect on the erythrocytic cycle of P. falciparum at 8 < t < 16 h. The target of Hit A was searched by immobilising the molecule on a solid support via a linker and performing affinity chromatography on a plasmodial lysate.

Controlling intracavity dual-comb soliton motion in a single-fiber laser.

Ultrafast science builds on dynamic compositions of precisely timed light pulses, and evolving groups of pulses are observed in almost every mode-locked laser. However, the underlying physics has rarely been controlled or used until now. Here, we demonstrate a general approach to control soliton motion inside a dual-comb laser and the programmable synthesis of ultrashort pulse patterns.

Comparing malignant monocytosis across the updated WHO and ICC classifications of 2022.

The World Health Organization (WHO) classification of hematolymphoid tumors and the International Consensus Classification (ICC) of 2022 introduced major changes to the definition of chronic myelomonocytic leukemia (CMML). To assess its qualitative and quantitative implications for patient care, we started with 3311 established CMML cases (according to WHO 2017 criteria) and included 2130 oligomonocytosis cases fulfilling the new CMML diagnostic criteria. Applying both 2022 classification systems, 356 and 241 of oligomonocytosis cases were newly classified as myelodysplastic (MD)-CMML (WHO and ICC 2022, respectively), most of which were diagnosed as myelodysplastic syndrome (MDS) according to the WHO 2017 classification.

Galectin-10 Expression in Placentas of Women with Gestational Diabetes.

Galectins are known to play an important role in immunoregulatory processes and autoimmune diseases. Galectin-10 is a cytoplasmic protein of human eosinophils and is involved in various eosinophilic diseases. Since increased galectin expression is already detected in the placentas of mothers with gestational diabetes mellitus (GDM), this study focuses on the specific role of galectin-10 and hints at consequences for the diagnosis and therapeutic options of GDM.

Novel thienopyrimidones targeting hepatic and erythrocytic stages of Plasmodium parasites with increased microsomal stability.

Based on the structure of a previously identified hit, Gamhepathiopine 1, which showed promising antiplasmodial activity, but poor microsomal stability, several strategies were investigated to improve the metabolic stability of the compounds. This included the introduction of fluorine or deuterium atoms, as well as carbocyclic groups. Among the new compounds, the 2-aminocyclobutyl derivative 5g demonstrated enhanced microsomal stability compared to compound 1, while retaining antiplasmodial activity against erythrocytic and hepatic stages of Plasmodium, without significant cytotoxicity against primary hepatocytes.

Germ line variant GFI1-36N affects DNA repair and sensitizes AML cells to DNA damage and repair therapy.

Growth factor independence 1 (GFI1) is a DNA-binding transcription factor and a key regulator of hematopoiesis. GFI1-36N is a germ line variant, causing a change of serine (S) to asparagine (N) at position 36. We previously reported that the GFI1-36N allele has a prevalence of 10% to 15% among patients with acute myeloid leukemia (AML) and 5% to 7% among healthy Caucasians and promotes the development of this disease.

Interface-guided phenotyping of coding variants in the transcription factor RUNX1 with SEUSS.

Understanding the consequences of single amino acid substitutions in cancer driver genes remains an unmet need. Perturb-seq provides a tool to investigate the effects of individual mutations on cellular programs. Here we deploy SEUSS, a Perturb-seq like approach, to generate and assay mutations at physical interfaces of the RUNX1 Runt domain.

Interplay of TP53 allelic state, blast count, and complex karyotype on survival of patients with AML and MDS.

Several clinical and genetic factors impact overall survival (OS) in myelodysplastic neoplasms (MDS) and acute myeloid leukemia (AML), including complex karyotype (CK), TP53 allelic state, and blast count. We analyzed the interplay of these factors by performing Cox regression analysis and by determining the frequency of TP53 single-hit (sh) and double-hit (dh) events and OS in MDS (n = 747) with <5% blasts, with ≥5% but <10% blasts, and ≥10% but <20% blasts and AML (n = 772). MDS with <5% blasts showed the best outcome, followed by with ≥5% but <10% blasts, and ≥10% but <20% blasts, and AML (median OS: 75, 54, 27, and 18 months, respectively).

Myeloid NGS Analyses of Paired Samples from Bone Marrow and Peripheral Blood Yield Concordant Results: A Prospective Cohort Analysis of the AGMT Study Group.

: Next generation sequencing (NGS) has become indispensable for diagnosis, risk stratification, prognostication, and monitoring of response in patients with myeloid neoplasias. Guidelines require bone marrow evaluations for the above, which are often not performed outside of clinical trials, indicating a need for surrogate samples. : Myeloid NGS analyses (40 genes and 29 fusion drivers) of 240 consecutive, non-selected, prospectively collected, paired bone marrow/peripheral blood samples were compared.

AML classification in the year 2023: How to avoid a Babylonian confusion of languages.

In parallel to the 5th edition of the World Health Organization Classification of Haematolymphoid Tumours (WHO 2022), an alternative International Consensus Classification (ICC) has been proposed. To evaluate the impact of the new classifications on AML diagnoses and ELN-based risk classification, we analyzed 717 MDS and 734 AML non-therapy-related patients diagnosed according to the revised 4th WHO edition (WHO 2017) by whole genome and transcriptome sequencing. In both new classifications, the purely morphologically defined AML entities decreased from 13% to 5%.

ARF suppression by MYC but not MYCN confers increased malignancy of aggressive pediatric brain tumors.

Medulloblastoma, the most common malignant pediatric brain tumor, often harbors MYC amplifications. Compared to high-grade gliomas, MYC-amplified medulloblastomas often show increased photoreceptor activity and arise in the presence of a functional ARF/p53 suppressor pathway. Here, we generate an immunocompetent transgenic mouse model with regulatable MYC that develop clonal tumors that molecularly resemble photoreceptor-positive Group 3 medulloblastoma.