Publications by authors named "Tim Holler"

To fully exploit the potential of human pluripotent stem cell-derived cardiomyocytes, ideally they should acquire a mature, adult ventricular-like phenotype. Predominant expression of the β-isoform of myosin heavy chain (β-MyHC) and the ventricular isoform of myosin regulatory light chain 2 (MLC2v) is a marker of human adult cardiac ventricle. Yet predominant co-expression of these isoforms is rarely reported by current culture protocols.

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Hypertrophic Cardiomyopathy (HCM) is often caused by heterozygous mutations in β-myosin heavy chain (MYH7, β-MyHC). In addition to hyper- or hypocontractile effects of HCM-mutations, heterogeneity in contractile function (contractile imbalance) among individual cardiomyocytes was observed in end-stage HCM-myocardium. Contractile imbalance might be induced by burst-like transcription, leading to unequal fractions of mutant versus wildtype mRNA and protein in individual cardiomyocytes (allelic imbalance).

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Myosin heavy chain (MyHC) is the main determinant of contractile function. Human ventricular cardiomyocytes (CMs) predominantly express the β-isoform. We previously demonstrated that ∼80% of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) express exclusively β-MyHC after long-term culture on laminin-coated glass coverslips.

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Disorganization of the basic contractile unit of muscle cells, i.e., the sarcomeres, leads to suboptimal force generation and is a hallmark of muscle atrophy.

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Transcriptional bursting is a common expression mode for most genes where independent transcription of alleles leads to different ratios of allelic mRNA from cell to cell. Here we investigated burst-like transcription and its consequences in cardiac tissue from Hypertrophic Cardiomyopathy (HCM) patients with heterozygous mutations in the sarcomeric proteins cardiac myosin binding protein C (cMyBP-C, ) and cardiac troponin I (cTnI, ). Using fluorescence hybridization (RNA-FISH) we found that both, and are transcribed burst-like.

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Cachexia is associated with poor prognosis in chronic heart failure patients, but the underlying mechanisms of cachexia triggered disease progression remain poorly understood. Here, we investigate whether the dysregulation of myokine expression from wasting skeletal muscle exaggerates heart failure. RNA sequencing from wasting skeletal muscles of mice with heart failure reveals a reduced expression of Ostn, which encodes the secreted myokine Musclin, previously implicated in the enhancement of natriuretic peptide signaling.

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Background: Chemotherapy is the first line of treatment for cancer patients. However, the side effects cause severe muscle atrophy or chemotherapy-induced cachexia. Previously, the NF-κB/MuRF1-dependent pathway was shown to induce chemotherapy-induced cachexia.

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Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) represent an attractive model to investigate CM function and disease mechanisms. One characteristic marker of ventricular specificity of human CMs is expression of the ventricular, slow β-myosin heavy chain (MyHC), as opposed to the atrial, fast α-MyHC. The main aim of this study was to investigate at the single-cell level whether contraction kinetics and electrical activity of hESC-CMs are influenced by the relative expression of α-MyHC versus β-MyHC.

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Precise assembly of the sarcomere, a force-generating unit in striated muscles, is critical for muscle contraction. Defective sarcomere organization is linked to myopathies and cachexia. The molecular mechanisms concerning sarcomere assembly are poorly understood.

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Endoparasitoid larvae may eliminate heterospecific competitors by physical or physiological means. The outcomes of these intrinsic competitions are often predictable with one species typically eliminating the other. The opiine braconids Doryctobracon areolatus (Szepligeti) and Utetes anastrephae (Viereck) are among the most common native parasitoids of frugivorous Tephritidae in the Neotropics and subtropics.

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Tests were conducted on wild Mediterranean fruit flies, Ceratitis capiata (Wiedemann), in Hawaii, Italy, and Kenya, and on sterile released flies in Florida and California with a new male attractant, (-)-ceralure B1. Compared on an equal dosage basis, Mediterranean fruit fly males were significantly more attracted to the (-)-ceralure B1 than to trimedlure in each of the sites tested except for California. Compared with the standard commercial 2 g trimedlure plug, 10 mg applied on cotton wicks (Kauai) was as attractive to wild males as trimedlure after the first 2 d of the test but not after 7 d.

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