Biology subjects

Kruger, M.

Publications and source records attributed to Kruger, M..

5 recordsLinked to original sources

bioRxiv2023

The Silene latifolia genome and its giant Y chromosome

In some species, the Y is a tiny chromosome but the dioecious plant Silene latifolia has a giant [~]550 Mb Y chromosome, which has remained unsequenced so far. Here we used a hybrid approach to obtain a high-quality male S. latifolia genome. Using mutants for sexual phenotype, we identified candidate sex-determining genes on the Y. Comparative analysis of the sex chromosomes with outgroups showed the Y is surprisingly rearranged and degenerated for a [~]11 MY-old system. Recombination suppression between X and Y extended in a stepwise process, and triggered a massive accumulation of repeats on the Y, as well as in the non-recombining pericentromeric region of the X, leading to giant sex chromosomes. One-Sentence SummaryThis work uncovers the structure, function, and evolution of one of the largest giant Y chromosomes, that of the model plant Silene latifolia, which is almost 10 times larger than the human Y, despite similar genome sizes.

genomics↗

bioRxiv2023

In silico mechanics and TGF-β expression of stem cells intramyocardially transplanted with a biomaterial injectate for treatment of myocardial infarction

PurposeBiomaterial and stem cell delivery are promising approaches to treating myocardial infarction. However, the mechanical and biochemical mechanisms underlying the therapeutic benefits require further clarification. This study aimed to assess the deformation of stem cells injected with the biomaterial into the infarcted heart. MethodsA microstructural finite element model of a mid-wall infarcted myocardial region was developed from ex vivo microcomputed tomography data of a rat heart with left ventricular infarct and intramyocardial biomaterial injectate. Nine cells were numerically seeded in the injectate of the microstructural model. The microstructural and a previously developed biventricular finite element model of the same rat heart were used to quantify the deformation of the cells during a cardiac cycle for a biomaterial elastic modulus (Einj) ranging between 4.1 and 405,900 kPa. ResultsThe transplanted cells deformation was largest for Einj = 7.4 kPa, matching that of the cells, and decreased for an increase and decrease in Einj. The cell deformation was more sensitive to Einj changes for softer (Einj [≤] 738 kPa) than stiffer biomaterials. ConclusionsCombining the microstructural and biventricular finite element models enables quantifying micromechanics and signalling of transplanted cells in the heart. The approach offers a broader scope for in silico investigations of biomaterial and cell therapies for myocardial infarction and other cardiac pathologies.

bioengineering↗

bioRxiv2022

The FLOWERING LOCUS T LIKE 2-1 gene of Chenopodium triggers precocious flowering in Arabidopsis seedlings

The FLOWERING LOCUS T (FT) gene is the essential integrator of flowering regulatory pathways in angiosperms. The paralogs of the FT gene may perform antagonistic functions, as exemplified by BvFT1, that suppresses flowering in Beta vulgaris, unlike the paralogous activator BvFT2. The roles of FT genes in other amaranths were less investigated. Here, we transformed Arabidopsis thaliana with the FLOWERING LOCUS T like (FTL) genes of Chenopodium and found, that both FTL1 and FTL2-1 accelerated flowering, despite having been the homologs of the Beta vulgaris floral promoter and suppressor, respectively. The floral promotive effect of FTL2-1 was so strong that it caused lethality when overexpressed under the 35S promoter. FTL2-1 placed in inducible cassette accelerated flowering after the induction with methoxyphenozide. The occasional expression of FTL2-1 led to precocious flowering in some primary transformants even without chemical induction. After the FTL gene duplication in Amaranthaceae, the FTL1 copy maintained the role of floral activator. The second copy FTL2 underwent subsequent duplication and functional diversification, which enabled to control the onset of flowering in amaranths to adapt to variable environments. HIGHLIGHTThe FLOWERING LOCUS T like 2-1 (FTL 2-1) gene of Chenopodium acts as a strong activator of flowering in Arabidopsis, despite being a homolog of floral repressor BvFT1.

plant biology↗

bioRxiv2022

Salt-inducible kinase inhibition promotes the adipocyte thermogenic program and adipose tissue browning

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=137 SRC="FIGDIR/small/514130v2_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@ce743org.highwire.dtl.DTLVardef@122f339org.highwire.dtl.DTLVardef@18e3013org.highwire.dtl.DTLVardef@1f65311_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstractsC_FLOATNO C_FIG ObjectiveNorepinephrine stimulates the adipose tissue thermogenic program through a {beta}-adrenergic receptor ({beta}AR) - cyclic adenosine monophosphate (cAMP) - protein kinase A (PKA) signaling cascade. We discovered that a noncanonical activation of the mechanistic target of rapamycin complex 1 (mTORC1) by PKA is required for the {beta}AR-stimulation of adipose tissue browning. However, the downstream events triggered by PKA-phosphorylated mTORC1 activation that drive this thermogenic response are not well understood. MethodsWe used a proteomic approach of Stable Isotope Labeling by/with Amino acids in Cell culture (SILAC) to characterize the global protein phosphorylation profile in brown adipocytes treated with the {beta}AR agonist. We identified salt-inducible kinase 3 (SIK3) as a candidate mTORC1 substrate and further tested the effect of SIK3 deficiency or SIK inhibition on the thermogenic gene expression program in brown adipocytes and in mouse adipose tissue. ResultsSIK3 interacts with RAPTOR, the defining component of the mTORC1 complex, and is phosphorylated at Ser884 in a rapamycin-sensitive manner. Pharmacological SIK inhibition by a pan-SIK inhibitor (HG-9-91-01) in brown adipocytes increases basal Ucp1 gene expression and restores its expression upon blockade of either mTORC1 or PKA. Short-hairpin RNA (shRNA) knockdown of Sik3 augments, while overexpression of SIK3 suppresses, Ucp1 gene expression in brown adipocytes. The regulatory PKA phosphorylation domain of SIK3 is essential for its inhibition. CRISPR-mediated Sik3 deletion in brown adipocytes increases type IIa histone deacetylase (HDAC) activity and enhances the expression of genes involved in thermogenesis such as Ucp1, Pgc1, and mitochondrial OXPHOS complex protein. We further show that HDAC4 interacts with PGC1 after {beta}AR stimulation and reduces lysine acetylation in PGC1. Finally, a SIK inhibitor well-tolerated in vivo (YKL-05-099) can stimulate the expression of thermogenesis-related genes and browning of mouse subcutaneous adipose tissue. ConclusionsTaken together, our data reveal that SIK3, with the possible contribution of other SIKs, functions as a phosphorylation switch for {beta}-adrenergic activation to drive the adipose tissue thermogenic program and indicates that more work to understand the role of the SIKs is warranted. Our findings also suggest that maneuvers targeting SIKs could be beneficial for obesity and related cardiometabolic disease.

physiology↗

bioRxiv2022

Effect of biomaterial stiffness on cardiac mechanics in a biventricular infarcted rat heart model with microstructural representation of in situ intramyocardial injectate

Intramyocardial delivery of biomaterials is a promising concept for treating myocardial infarction. The delivered biomaterial provides mechanical support and attenuates wall thinning and elevated wall stress in the infarct region. This study aimed at developing a biventricular finite element model of an infarcted rat heart with a microstructural representation of an in situ biomaterial injectate, and a parametric investigation of the effect of the injectate stiffness on the cardiac mechanics. A three-dimensional subject-specific biventricular finite element model of a rat heart with left ventricular infarct and microstructurally dispersed biomaterial delivered one week after infarct induction was developed from ex vivo microcomputed tomography data. The volumetric mesh density varied between 303 mm-3 in the myocardium and 3,852 mm-3 in the injectate region due to the microstructural intramyocardial dispersion. Parametric simulations were conducted with the injectates elastic modulus varying from 4.1 to 405,900 kPa, and myocardial and injectate strains were recorded. With increasing injectate stiffness, the end-diastolic median myocardial fibre and cross-fibre strain decreased in magnitude from 3.6% to 1.1% and from -6.0% to -2.9%, respectively. At end-systole, the myocardial fibre and cross-fibre strain decreased in magnitude from -20.4% to -11.8% and from 6.5% to 4.6%, respectively. In the injectate, the maximum and minimum principal strains decreased in magnitude from 5.4% to 0.001% and from -5.4% to -0.001%, respectively, at end-diastole and from 38.5% to 0.06% and from -39.0% to -0.06%, respectively, at end-systole. With the microstructural injectate geometry, the developed subject-specific cardiac finite element model offers potential for extension to cellular injectates and in silico studies of mechanotransduction and therapeutic signalling in the infarcted heart with an infarct animal model extensively used in preclinical research.

biophysics↗