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Biology subjects

Doria, E.

Publications and source records attributed to Doria, E..

4 recordsLinked to original sources

Coordinated control of both microtubule ends regulates mitotic spindle length

The mitotic spindle is a biomechanical structure whose length must be precisely controlled to ensure faithful chromosome segregation. The treadmilling of microtubules towards centrosomes, termed poleward flux, is involved in spindle length control. However, poleward flux has been shown to be both inversely and directly proportional to spindle length, a contradiction that remains unexplained by current mechanisms. Here we introduce a model which demonstrates that length-dependent regulation at both microtubule ends allows plus- and minus-end dynamics to synchronize with one another, enabling pathways of poleward flux-based spindle length control which can rectify previous results. Moreover, our model predicts that spindle length and poleward flux can vary independently via simultaneous perturbations at both microtubule ends, which we experimentally validate with combinations of KIF18A, KIF2A, and KATNB1 depletions in human cells. Our results thus resolve a longstanding paradox and provide mechanistic insight into the reciprocal control of spindle length and poleward flux.

biophysics↗

GIGEM (Group Isolation Gauge Effect Metrics), A Software Suite for Analyzing Social Isolation-Induced Sleep Loss and Multi-Batch Experiments in Drosophila

We introduce Group Isolation Gauge Effect Metrics (GIGEM), a high-throughput software suite for Drosophila sleep analysis designed to manage large population datasets from multi-batch experiments. In this study, we characterized social isolation-induced sleep phenotypes across 38 Sleep Inbred Panel (SIP) lines after both acute and chronic social isolation. Beyond this specific study, GIGEM is broadly suited for diverse Drosophila sleep research involving large-scale and multi-batch datasets. GIGEM enabled an extensive analysis of sleep parameters and allowed systematic identification of sleep changes in response to social isolation. Following acute social isolation, SIP line animals showed heterogeneous responses, including sleep loss, sleep gain, and no change in sleep. In contrast, chronic social isolation led to significant sleep loss in nearly all lines, though to varying degrees. While most SIP lines were sensitive to chronic social isolation, a select few were resistant to it. These results were obtained across 38 SIP lines and wild-type controls (totaling 5670 animals). Collectively, our results demonstrate that chronic social isolation-induced sleep loss is a robust yet variable trait and establish GIGEM as a powerful, generalizable tool for Drosophila sleep phenotyping in large-scale, multi-batch studies.

animal behavior and cognition↗

Transient lagging chromosomes cause primary microcephaly

Primary microcephaly results from the impaired neuronal progenitor proliferation, causing reduced brain size and impaired cognitive abilities. Loss of the most frequently microcephaly genes, WDR62 and ASPM, slows down poleward microtubule flux and results in transient lagging chromosomes in anaphase. Whether these defects cause primary microcephaly is unknown. Here we show that transient lagging chromosomes elicit an Aurora-B-dependent activation of 53BP1 and p21, impairing cell proliferation. Co-depletion of the microtubule depolymerase inhibitor CAMSAP1/Patronin in a WDR62 depletion background, restores normal flux rates, suppresses lagging chromosomes, and allows normal cell proliferation in human cells, while rescuing the small brain and the cognitive defects in fly larvae. We postulate that transient lagging chromosomes in anaphase and 53BP1/p21-dependent response they elicit, are a major driver of primary microcephaly.

cell biology↗

Biochemical properties and in vitro biological activities of extracts from seven folk medicinal plants growing wild in southern Tunisia

Recently, much attention has been paid to the extracts obtained from plant species in order to analyse their biological activities. Due to the climate diversity in Tunisia, the traditional pharmacopoeia consists of a wide arsenal of medicinal plant species since long used in folk medicine, in foods as spices, and in aromatherapy. Although many of these species are nearly facing extinction, only a small proportion of them have been scientifically studied. Therefore, this study explores the biochemical properties of seven spontaneous plants, which were harvested in the arid Tunisian desert: Marrubium vulgare L., Rhus tripartita (Ucria) D.C., Thymelaea hirsute (L.) Endl., Plantago ovata Forsk., Herniaria fontanesii J. Gay., Ziziphus lotus and Hyoscyamus albus. Extracts from these plants were found to contain different types of secondary metabolites (polyphenols, flavonoids, condensed tannins, crude saponins, carotenoids and alkaloids) that are involved in important biological activities. The biological activity of the extracts obtained from each Tunisian plant was assessed: first of all, leukaemia and colon cancer cell lines (K-562 and CaCo-2 respectively) were treated with different concentrations of extracts, and then the anti-proliferative activity was observed. The results showed, in particular, how the plant extract from Rhus tripartita significantly inhibits cell proliferation, especially on the K-562 tumour cell line. Subsequently, the anti-inflammatory activity was also assessed, and the results showed that Herniaria fontanesii and Marrubium vulgare possess the highest activity in the group of analysed plants. Finally, the greatest acetylcholinesterase inhibitory effect was exhibited by the extract obtained from Rhus tripartita. In conclusion, all the Tunisian plants we analysed were shown to contain a remarkable amount of different bio-active compounds, thus confirming their involvement in several biological activities. Rhus tripartita and Ziziphus lotus were shown to be particularly effective in anti-proliferative activity, while Herniaria fontanesii were shown to have the best anti-inflammatory activity.

plant biology↗