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Hide and seek: de novo identification in sugar beet reveals impact of non-autonomous LTR retrotransposons.

Plant genomes are filled with retrotransposons and their derivatives, constantly undergoing sequence diversification and structural rearrangement. Among them, short, non-autonomous retrotransposons lack full coding capacity and often form subfamilies. As a result, non-autonomous retrotransposons are incompletely identified in most to all genome assemblies.Here, we capitalize on our comprehensive understanding of the transposable element (TE) landscape in sugar beet (Beta vulgaris) to assess the extent of the blind spot for non-autonomous long terminal repeat (LTR) retrotransposons. This use case serves to answer if all of these sequences are derivatives of easier-to-identify full-length elements or if there is more variability that is currently overlooked.For this we applied a semi-automated structural discovery workflow followed by in-depth manual verification to characterize non-autonomous LTR retrotransposons in sugar beet. We retrieve more than 100 non-autonomous LTR retrotransposon families that lack complete autonomous coding capacity, including canonical terminal-repeat retrotransposons in miniature (TRIMs), elongated non-coding derivatives and families retaining fragmented coding remnants. The identified families span a broad range, including elements exceeding 15,000 bp in length and display evidence for reshuffling and modular evolution. Only a subset of families could be confidently linked to autonomous retrotransposons, showing sequence diversification within the non-autonomous LTR retrotransposon fraction beyond the autonomous genomic templates.We highlight that a large fraction of non-autonomous LTR retrotransposons is incompletely recovered with the current TE identification workflows, even if the output is well-curated and condensed into TE libraries and suggest procedures to remedy this gap. This study gives a genome-wide view into the non-autonomous LTR retrotransposon landscape of a single plant genome and highlights the importance of structure-based approaches for their identification and classification.

LTR retrotransposons

Thyroid-stimulating immunoglobulins do not cause non-autonomous, autonomous, or toxic multinodular goitres.

Thyroid-stimulating immunoglobulins (TSIs) were measured by radioreceptor assay in serum from 51 patients with a multinodular goitre, divided into four groups according to thyroid function, and in 30 normal people. In 9 patients who were euthyroid and had non-autonomous thyroid function and in 6 patients who were hyperthyroid, TSI index was normal . Of 21 euthyroid patients with autonomous function only 2 had a slightly abnormal TSI index (66 in both, normal greater than or equal to 68). Another series of 15 clinically euthyroid patients also had a normal TSI index. These results suggest that TSIs do not contribute to the pathogenesis of multinodular goitre, as has been suggested by others.

Adult

Spermatogenesis-specific Argonautes ALG-3/4 promote LEA-1 expression in oocytes.

Small interfering RNAs bound to Argonautes ALG-3 and ALG-4 ( ALG-3 /4) in spermatocytes regulate fertility and aging in C. elegans . ALG-3 /4 cell non-autonomously repress DAF-18 /PTEN in the oocyte, thereby limiting the activity of DAF-16 /FOXO and longevity. We find that the DAF-16 and ALG-3 /4 target gene lea-1 is downregulated in precursor germ cells and oocytes of alg-3 /4 mutants while being upregulated in age-1 ( hx546 ) PI3K mutants, where DAF-16 is activated. The downregulation of lea-1 in alg-3 /4 mutants is inherited, unlike the elevation in DAF-18 levels. We therefore propose that ALG-3 /4 regulate LEA-1 and DAF-18 through distinct non-autonomous mechanisms.

Journal Article

Valsalva vasoconstrictor reflex in human hypertension in after beta-adrenoreceptor blockade in conscious rabbits.

1. A Valsalva-like manoeuvre was used to elicit graded rises in total peripheral resistance (TPR) in conscious rabbits. The rises were reflex and mediated through sympathetic constrictors. Propranolol infused at different rates reaching plasma concentrations up to 240 (SEM 33) ng/ml had no effect on this reflex but reduced mean arterial pressure. However, the response was attenuated by clonidine in a dose-dependent manner. 2. Valsalva manoeuvres were used to elicit graded sympathetically mediated rises in TPR index in twenty-nine subjects with mean arterial pressure ranging from 75 to 165 mmHg. Absolute sensitivity of the constrictor response increased with rising resting TPR index, resulting in some enhancement of constrictor responses in the hypertensive subjects. It seems likely that non-autonomic factors (e.g. vessel structure) rather than hyperactive neural constrictor effects are involved in the enhanced constrictor responses in essential hypertension.

Adrenergic beta-Antagonists

Spatially ordered zygotic genome activation fulfills embryo quality control.

Early embryo development features autonomous, maternally-driven cell divisions that self- organize the multicellular blastula or blastocyst tissue. Maternal control cedes to the zygote starting with the onset of widespread zygotic genome activation (ZGA), which is essential for subsequent cell fate determination and morphogenesis. Intriguingly, although the onset of ZGA is highly regulated at the level of an embryo, it can be non-homogenous and precisely patterned at the single-cell level. We previously demonstrated a stereotyped spatial and temporal ordering of ZGA in a model vertebrate embryo. Unknown, however, was whether this precise ZGA patterning was required for development. To address this fundamental question, we devised a strategy to spatially control cell divisions in the embryo that perturb blastula embryo organization. We demonstrate the feasibility of spatially inverting the cell size pattern of embryos and find that these inverted embryos undergo a flipped pattern of ZGA. Mispatterned ZGA along the animal-vegetal axis causes embryo apoptosis, revealing that gastrula embryos have a built-in quality control system to sense inappropriate ZGA patterning, including regional defects in transcriptional onset. The quality control response is non-autonomous which may depend on anti-apoptotic signals that repress cell death outside of the animal hemisphere. These results reveal the requirement of properly patterned ZGA for normal development and the existence of an embryo quality control response exquisitely tuned to the spatial and temporal ordering of genome activation and zygotic gene expression.

Journal Article