Publications by authors named "Harder L"

Article Synopsis
  • The CDAA-HFD mouse model is utilized to study metabolic dysfunction-associated steatohepatitis (MASH) by simulating disease progression and testing various treatments.
  • The study evaluated several drugs, including semaglutide and lanifibranor, for their effectiveness in reversing fibrosis and improving liver conditions after different time points on the CDAA-HFD diet.
  • Findings indicate that while semaglutide and lanifibranor showed partial benefits when used preventively, elafibranor was the only drug that improved fibrosis significantly, highlighting the importance of timing in pharmacological interventions.
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Background: Young children treated for central nervous system (CNS) malignancies are at high risk for difficulties with academic functioning due to increased vulnerability of the developing brain and missed early developmental opportunities. Extant literature examining academics in this population is limited. We investigated academic readiness, its clinical and demographic predictors, and its relationship with distal academic outcomes among patients treated for CNS tumors during early childhood.

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The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) is increasing, and translational animal models are needed to develop novel treatments for this disease. The physiology and metabolism of pigs have a relatively high resemblance to humans, and the present study aimed to characterize choline-deficient and high-fat diet (CDAHFD)-fed Göttingen Minipigs as a novel animal model of MASLD/MASH. Göttingen Minipigs were fed CDAHFD for up to 5 mo, and the phenotype was investigated by the analysis of plasma parameters and repeated collection of liver biopsies.

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Deciphering the striatal interneuron diversity is key to understanding the basal ganglia circuit and to untangling the complex neurological and psychiatric diseases affecting this brain structure. We performed snRNA-seq and spatial transcriptomics of postmortem human caudate nucleus and putamen samples to elucidate the diversity and abundance of interneuron populations and their inherent transcriptional structure in the human dorsal striatum. We propose a comprehensive taxonomy of striatal interneurons with eight main classes and fourteen subclasses, providing their full transcriptomic identity and spatial expression profile as well as additional quantitative FISH validation for specific populations.

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Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, encompasses steatosis and metabolic dysfunction-associated steatohepatitis (MASH), leading to cirrhosis and hepatocellular carcinoma. Preclinical MASLD research is mainly performed in rodents; however, the model that best recapitulates human disease is yet to be defined. We conducted a wide-ranging retrospective review (metabolic phenotype, liver histopathology, transcriptome benchmarked against humans) of murine models (mostly male) and ranked them using an unbiased MASLD 'human proximity score' to define their metabolic relevance and ability to induce MASH-fibrosis.

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Article Synopsis
  • Thyroid hormones (THs) play a crucial role in regulating energy metabolism, particularly in the liver, where they influence lipid and cholesterol levels as well as overall energy availability.
  • A study using a mouse model of hypothyroidism found that low TH levels reduced activity, food intake, and body temperature primarily during the active phase, with minimal effects on liver gene expression compared to high TH levels.
  • Circadian analysis revealed changes in gene expression patterns related to cholesterol metabolism in low-TH mice, identifying 516 genes as potential markers for assessing liver TH state throughout the day.
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Distinct diagnostic entities within BCR::ABL1-positive acute lymphoblastic leukemia (ALL) are currently defined by the International Consensus Classification of myeloid neoplasms and acute leukemias (ICC): "lymphoid only", with BCR::ABL1 observed exclusively in lymphatic precursors, vs "multilineage", where BCR::ABL1 is also present in other hematopoietic lineages. Here, we analyzed transcriptomes of 327 BCR::ABL1-positive patients with ALL (age, 2-84 years; median, 46 years) and identified 2 main gene expression clusters reproducible across 4 independent patient cohorts. Fluorescence in situ hybridization analysis of fluorescence-activated cell-sorted hematopoietic compartments showed distinct BCR::ABL1 involvement in myeloid cells for these clusters (n = 18/18 vs n = 3/16 patients; P < .

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Background And Objectives: Elevated intracranial pressure (ICP) in myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) has been largely unexplored. The objectives of this study were to determine the frequency of increased ICP in MOGAD and its association with disease course and outcomes and to highlight cases requiring medical and/or surgical management of increased ICP.

Methods: In this retrospective, single-center cohort study, we examined the clinical and paraclinical data from the initial presentation and follow-up data of children diagnosed with MOGAD.

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Article Synopsis
  • Maternal thyroid hormones significantly influence fetal development, but the effects of maternal hyperthyroidism on offspring are not well understood.
  • In a mouse study, maternal treatment with the thyroid hormone T3 during pregnancy improved glucose tolerance in male offspring and increased thermogenesis in brown adipose tissue (BAT) in both sexes.
  • The study found that proper maternal thyroid hormone receptor β (TRβ) signaling is crucial for these benefits, and alterations in maternal serum metabolites like choline were also observed, linking maternal TRβ activation to specific adaptations in offspring thermoregulation.
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Mating success of flowering plants depends strongly on the efficiencies of pollen removal from flowers and its subsequent dispersal to conspecific stigmas. We characterized the economy of pollen dispersal in flowering plants by analysing pollen fates and their correlates for 228 species. The mean percentage of pollen removed from flowers (removal efficiency) varied almost twofold according to the type of pollen-dispersal unit, from less than 45% for orchids and milkweeds with solid pollinia, to greater than 80% for species with granular monads or sectile (segmented) pollinia.

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Objective: The primary aim of this paper is to accelerate the number of randomized experimental studies of the reliability and validity in-home tele-neuropsychological testing (tele-np-t).

Method: We conducted a critical review of the tele-neuropsychology literature. We discuss this research in the context of the United States' public and private healthcare payer systems, including the Centers for Medicare & Medicaid Services (CMS) and Current Procedural Terminology (CPT) coding system's telehealth lists, and existing disparities in healthcare access.

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Background: The present study aimed to investigate possible influences of body weight and sex on adrenal gland size in endocrinologically healthy dogs. Possible factors influencing the adrenal size are discussed in relation to a universal upper reference value from the literature of 7.4 mm as the thickness in the caudal pole of the adrenal gland.

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Deciphering the striatal interneuron diversity is key to understanding the basal ganglia circuit and to untangle the complex neurological and psychiatric diseases affecting this brain structure. We performed snRNA-seq of postmortem human caudate nucleus and putamen samples to elucidate the diversity and abundance of interneuron populations and their transcriptional structure in the human dorsal striatum. We propose a new taxonomy of striatal interneurons with eight main classes and fourteen subclasses and provide their specific markers and some quantitative FISH validation, particularly for a novel PTHLH-expressing population.

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Premise: The relative per-flower production of ovules and pollen varies broadly with angiosperm mating systems, with outcrossing types commonly producing more pollen grains per ovule than selfing types. The evolutionary causes of this variation are contentious, especially the relevance of pollination risk. Resolution of this debate may have been hampered by its focus on pollen:ovule (P:O) ratios rather than on the evolution of pollen and ovule numbers per se.

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Reproductive systems of flowering plants are evolutionarily fluid, with mating patterns changing in response to shifts in abiotic conditions, pollination systems, and population characteristics. Changes in mating should be particularly evident in species with sexual polymorphisms that become ecologically destabilized, promoting transitions to alternative reproductive systems. Here, we decompose female mating portfolios (incidence of selfing, outcross mate number, and intermorph mating) in eight populations of a self-compatible insect-pollinated herb.

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Article Synopsis
  • Diurnal physiological rhythms are regulated by circadian clock genes/proteins and influenced by various factors like temperature, food intake, and thyroid hormones (THs), which impact processes like energy metabolism.
  • A study on mice indicated that high levels of triiodothyronine (T) affected body temperature and oxygen consumption in relation to the time of day, with 37 transcripts identified as potential markers for TH state in the liver.
  • Analysis revealed that changes in the liver's transcript rhythms were mainly related to overall expression levels, and TH levels altered metabolic processes, leading to a loss of rhythmicity in genes related to glucose and fatty acid metabolism, indicating increased energy turnover in the liver.
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The first cases of coronavirus disease-19 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were reported by Chinese authorities at the end of 2019. The disease spread quickly and was declared a global pandemic shortly thereafter. To respond effectively to infection and prevent viral spread, it is important to delineate the factors that affect protective immunity.

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Premise: Fecundity and mating outcomes commonly differ among plant populations occupying contrasting environments. If self-pollination occurs primarily among flowers within plants, contrasting reproductive outcomes among populations must reflect environmental effects on plant-pollinator interactions. Specifically, local conditions could affect features of plant phenotypes that influence pollinator behavior, in turn modifying plant reproductive outcomes.

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In a recent paper, Renner et al. (Oecologia 195:825-831, 2021) concluded, without supporting statistical evidence, that increased density of managed honey-bee hives between 2019 and 2020 intensified competitive effects of honey bees on non-Apis bee species in the Munich Botanic Garden. Analysis of Renner et al.

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While feeding, foragers can alter their environment. Such alteration constitutes ecological niche construction (ENC) if it enables future benefits for the constructor and conspecific individuals. The environmental modification may also affect non-constructing, bystander species, especially if they share resources with constructor species.

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Prostate cancer (PCa) in dogs is a highly malignant disease akin to its human counterpart. In contrast to the situation in humans, multi-gene approaches facilitating risk stratification of canine PCa are barely established. The aims of this study were the characterization of the transcriptional landscape of canine PCa and the identification of diagnostic, prognostic and/or therapeutic biomarkers through a multi-step screening approach.

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Epstein-Barr virus (EBV)-associated diffuse large B-cell lymphoma not otherwise specified (DLBCL NOS) constitute a distinct clinicopathological entity in the current World Health Organization (WHO) classification. However, its genomic features remain sparsely characterized. Here, we combine whole-genome sequencing (WGS), targeted amplicon sequencing (tNGS), and fluorescence in situ hybridization (FISH) from 47 EBV + DLBCL (NOS) cases to delineate the genomic landscape of this rare disease.

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Purpose: Infants treated for CNS malignancies experience a significantly poorer response to treatment and are particularly at risk for neuropsychological deficits. The literature is limited and inconsistent regarding cognitive outcomes among this group. We investigated predictors of cognitive outcomes in children treated for brain tumors during infancy as part of a large, prospective, multisite, longitudinal trial.

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Oncogene-induced senescence provides a barrier against malignant transformation. However, it can also promote cancer through the secretion of a plethora of factors released by senescent cells, called the senescence associated secretory phenotype (SASP). We have previously shown that in proliferating cells, nuclear lncRNA MIR31HG inhibits p16/CDKN2A expression through interaction with polycomb repressor complexes and that during BRAF-induced senescence, MIR31HG is overexpressed and translocates to the cytoplasm.

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