1,181 research outputs found
AMBRA1: When autophagy meets cell proliferation
No full textA growing amount of evidence reported in the literature in recent years strongly supports the relevance of the interplay between autophagy and other pathways. In this context, the study of the link between autophagy and cell proliferation regulation has been among the most challenging. In our recent publications, we finely characterize a role for the pro-autophagic protein AMBRA1 in the regulation of cell proliferation. AMBRA1 modulates autophagy and interacts with PPP2/PP2A (protein phosphatase 2), thus also modulating MYC protein levels and the cell proliferation rate. Interestingly, this pathway of regulation is controlled by the master regulator of autophagy and cell growth, MTORC1. Notably, in our study we demonstrate the relevance of the AMBRA1-mediated regulation of MYC in tumorigenesis, also identifying AMBRA1 as a tumor suppressor gene
AMBRA1-Mediated Regulation of C-MYC and Its Relevance to Cancer
No full textWhen coping with nutrient shortage and cellular stressors, cells simultaneously induce autophagy and inhibit cell proliferation in order to attempt to preserve homeostasis and energy balance. Although the interplay between autophagy and cell proliferation is known to be relevant to both physiology and human diseases, very few molecules coordinating these two pathways have been identified so far. Notably, in a recent work, we introduced AMBRA1 as a key molecule in the crosstalk between autophagy and cell proliferation. In particular, we finely characterized AMBRA1 role in the modulation of C-MYC phosphorylation and stability, an event driving both cell proliferation and oncogenesis. Consistently, AMBRA1 is a haploinsufficient tumor suppressor gene, and its alterations are associated with human cancers, thus strongly supporting the relevance of the AMBRA1-mediated regulation of C-MYC in tumorigenesis. Hence, it is important to control AMBRA1 levels/activity in normal cells, in order to prevent transformation. Indeed, AMBRA1 is in an intricate relationship with regulators of autophagy and cell proliferation, establishing feedback loops and parallel/epistatic regulations. All of this evidence and its relevance to cancer and cancer-treatment strategies are discussed in this chapter
Aβ toxicity in Alzheimer's disease
No full textAlzheimer's Disease (AD), the most common age-related neurodegenerative disorder, is characterized by progressive cognitive decline, synaptic loss, the formation of extracellular β-amyloid plaques and intracellular neurofibrillary tangles, and neuronal cell death. Despite the massive neuronal loss in the 'late stage' of disease, dendritic spine loss represents the best pathological correlate to the cognitive impairment in AD patients. The 'amyloid hypothesis' of AD recognizes the Aβ peptide as the principal player in the pathological process. Many lines of evidence point out to the neurotoxicity of Aβ, highlighting the correlation between soluble Aβ oligomer accumulation, rather than insoluble Aβ fibrils and disease progression. Pathological increase of Aβ in AD brains, resulting from an imbalance between its production, aggregation and clearance, might target mitochondrial function promoting a progressive synaptic impairment. The knowledge of the exact mechanisms by which Aβ peptide impairs neuronal function will help us to design new pharmacological tools for preventing AD neurodegeneration
Procontarinia matteiana Kieffer & Cecconi
No full textProcontarinia matteiana Kieffer & Cecconi [Figs 33 a–i] Procontarinia matteiana Kieffer & Cecconi, 1906: 135 Material. Male, female, pupal and larval syntypes were reared from pustulate leaf galls on Mangifera indica L. in the Botanical Gardens, Palermo, Sicily, Italy, v-1906 (Kieffer & Cecconi 1906). The syntypes are presumed lost (Gagné & Jaschhof 2017). One of us (PK) visited the Botanical Gardens in Palermo, ix-2018, but found only young, recently planted, mango trees with no galls on their leaves. Harris (1966) described adults from an undisclosed country and locality, possibly India. The presence of P. matteiana in Indonesia is based on the presence of galls recorded by DvLR & DvL (1926, gall No. 801). Description (based on Kieffer & Cecconi (1906) and Harris (1966). Adult: Wing: 1.5–2.0 mm long, R 1 joining C at basal half, R 5 slightly curved, joining at near wing apex [Fig. 33i]. palpus 4-segmented [Fig. 33g]. Antenna with 12 flagellomeres; in male binodal, internode very short, each node with whorl of looped circumfila [Fig. 33f]; in female nodes cylindrical, not longer than wide, neck shorter than wide, circumfila simple. Tarsal claws according to Harris (1966) toothed on some, possibly all legs. Kieffer & Cecconi (1906) recorded simple claws, but teeth in other Procontarinia spp. are very thin so conceivably were overlooked by them. Male terminalia: gonocoxite long, narrow, cylindrical except for pronounced obtusely triangular mesobasal lobe; gonostylus narrow, curved medially; aedeagus long, evenly broad, bearing many asetose papillae; cerci ovate, well-separated; hypoproct slightly wider and much shorter than aedeagus, deeply bilobed [Figs 33d, h]. Ovipositor barely protrusible, cerci stout [Fig. 33e]. Pupa without antennal horns. Larva unknown. DNA. Three COI sequences (GenBank numbers JQ823235 – JQ823237) are available for the Réunion Island population (Amouroux et al. 2013). Remarks. The genus Procontarinia contains 16 described (Gagné & Jaschhof 2017, Jiao et al. 2018) and over 10 undescribed (Kolesik et al. 2009, 2017) species, all restricted to mango where they feed on leaves, young stems, flowers or fruit. While only two species are currently reported from Indonesia (P. matteiana and P. robusta) it is likely that many more occur there. Procontarinia matteiana differs from P. robusta in several characters of the male: flagellomeral internode bare, narrow gonocoxite bearing acute mesobasal lobe, long and narrow gonostylus, blunt aedeagus of even width, deeply divided hypoproct and triangular cerci in P. matteiana as opposed to flagellomeral internode setulose, robust gonocoxite without mesobasal lobe, short and proximally wide gonostylus, tapering aedeagus, shallowly divided hypoproct and shallowly divided round cerci in P. robusta. Biology. This species causes leaf galls on Mangifera indica (Anacardiaceae) (Kieffer & Cecconi (1906, Fig. 3 [Fig. 33a]), DvLR & DvL (1926, gall No. 801, Fig. 577 [Fig. 33b])). Tiny circular galls, about 1.5–2 mm across and 1 mm high, developed on both sides of the leaf or on young twigs. Galls are pale green at first [Fig. 33c], later becoming pink and purple, finally black. Inside, there is a single larval chamber. The larva pupates in the gall (Augustyn et al. 2013). Procontarinia matteiana is a pest not only on the Indian subcontinent, where mango was first domesticated, but also in other countries of the world where it is cultivated now (Kolesik et al. 2017). Resistant mango varieties (Githure et al. 1998) and the presence of natural enemies (Sankaran 1988) are currently the major control strategies. Geographical distribution. Procontarinia matteiana has been confirmed in Italy [Fig. 33a], India, Indonesia, Mauritius, Réunion, Kenya and South Africa [Fig. 33c] (Gagné & Jaschhof 2017), and reported also from Oman, Trinidad and Iran (Kolesik et al. 2017). In Indonesia it was found in Java at the following localities (DvLR & DvL 1926): Mangkang, near Semarang, vii-1910; Candi, near Semarang, alt. 50 m, iii-1911; Mt Muria, alt. 500 m, ix- 1912; Bandung, alt. 600 m, vi-1916 & vi-1918; Jakarta, v-1917; Bogor, alt. 250 m, ix-1918; Mt Pancar, near Bogor, alt. 500 m, xii-1923.Published as part of Kolesik, Peter & Gagné, Raymond J., 2020, A review of the gall midges (Diptera: Cecidomyiidae) of Indonesia: taxonomy, biology and adult key to genera, pp. 1-82 in Zootaxa 4847 (1) on pages 57-58, DOI: 10.11646/zootaxa.4847.1.1, http://zenodo.org/record/440685
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