On the Hopf Problem and a Conjecture of Liu-Maxim-Wang

We discuss an approach towards the Hopf problem for aspherical smooth projective varieties recently proposed by Liu, Maxim, and Wang in [LMW21]. In complex dimension two, we point out that this circle of ideas suggests an intriguing conjecture regarding the geography of aspherical surfaces of general type.Comment: This new version includes some changes following the feedback of J\'anos Koll\'ar. Added acknowledgments and references updated. 12 pages, no figure

HUWE1 controls MCL1 stability to unleash AMBRA1-induced mitophagy

Receptor-mediated mitophagy is a crucial process involved in mitochondria quality control. AMBRA1 is a mitophagy receptor for the selective removal of damaged mitochondria in mammalian cells. A critical unresolved issue is how AMBRA1-mediated mitophagy is controlled in response to cellular stress. Here, we investigated the role of BCL2-family proteins on AMBRA1-dependent mitophagy and showed that MCL1 delays AMBRA1-dependent mitophagy. Indeed, MCL1 overexpression is sufficient to inhibit recruitment to mitochondria of the E3 Ubiquitin ligase HUWE1, a crucial dynamic partner of AMBRA1, upon AMBRA1-mediated mitophagy induction. In addition, we found that during mitophagy induced by AMBRA1, MCL1 levels decreased but were sustained by inhibition of the GSK-3β kinase, which delayed AMBRA1-mediated mitophagy. Also, we showed that MCL1 was phosphorylated by GSK-3β at a conserved GSK-3 phosphorylation site (S159) during AMBRA1-mediated mitophagy and that this event was accompanied by HUWE1-dependent MCL1 degradation. Altogether, our results demonstrate that MCL1 stability is regulated by the kinase GSK-3β and the E3 ubiquitin ligase HUWE1 in regulating AMBRA1-mediated mitophagy. Our work thus defines MCL1 as an upstream stress-sensitive protein, functional in AMBRA1-mediated mitophagy

Correction to: HUWE1 controls MCL1 stability to unleash AMBRA1-induced mitophagy

An amendment to this paper has been published and can be accessed via a link at the top of the paper

8000 years of coastal changes on a western Mediterranean Island: A multi proxy approach from the Posada plain of Sardinia

A multi-proxy palaeoenvironmental investigation was conducted to reconstruct the Holocene history of coastal landscape change in the lower Posada coastal plain of eastern Sardinia. In this paper, millennial-scale human-sea level-environment interactions are investigated near Posada. Biostratigraphic and palynological approaches were used to interpret the chromo-stratigraphy exhibited by a series of new clothes taken from the coastal plain. This new study elucidates the main palaeoecologiocal changes, phases of shoreline migration and relative sea-level change during the lat 8000 years. The results indicate the major role of sea-level stabilisation and high sediment supply in driving major landscape changes, especially during the Neolithic period (6-4th millennia BC), and the long-term settlement history of this coastal area. It is concluded that human occupation of the coastal plain, from prehistoric to historical times, was most likely constrained by the rapid evolution if this coastal landscape.LR/7 2010 Regione Sardegn

Esophageal atresia in newborns: a wide spectrum from the isolated forms to a full VACTERL phenotype?

Background: VATER association was first described in 1972 by Quan and Smith as an acronym which identifies a non-random co-occurrence of Vertebral anomalies, Anal atresia, Tracheoesophageal fistula and/or Esophageal atresia, Radial dysplasia. It is even possible to find out Cardiovascular, Renal and Limb anomalies and the acronym VACTERL was adopted, also, embodying Vascular, as single umbilical artery, and external genitalia anomalies. Methods: Data on patients with esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) admitted in the Neonatal Intensive Care Unit (NICU) between January 2003 and January 2013 were evaluated for the contingent occurrence of typical VACTERL anomalies (VACTERL-type) and non tipical VACTERL anomalies (non-VACTERL-type). The inclusion criterion was the presence of EA with or without TEF plus two or more of the following additional malformations: vertebral defects, anal atresia, cardiovascular defects, renal anomalies and lower limb deformities, like radial dysplasia. Results: Among 52 patients with EA/TEF, 20 (38,4%) had isolated EA and 7 (21,8%) had a recognized etiology such a syndrome and therefore were excluded. Among 32 infants with EA and associated malformations, 15 (46,8%) had VACTERL association. The most common anomalies were congenital heart defects (73,3%), followed by vertebral anomalies (66,6%). Many patients also had additional non-VACTERL-type defects. Single umbilical artery was the most common one followed by nervous system abnormalities and anomalies of toes. Between the groups of infants with VACTERL type and non-VACTERL-type anomalies, there are several overlapping data regarding both the tipically described spectrum and the most frequently reported non-VACTERL-type malformations. Thus, it is possible to differentiate infants with a full phenotype (VACTERL full phenotype) and patients that do not meet all the criteria mentioned above, but with some homologies with the first group (VACTERL partial phenotype). Conclusion: The high frequency of non-VACTERL-type anomalies encountered in full and partial phenotype patients would suggest the need for an extension of the clinical criteria for the diagnosis of VACTERL association and also for pre- and post-operative management and follow-up in the short and long term

Automated Analysis of MUTEX Algorithms with FASE

In this paper we study the liveness of several MUTEX solutions by representing them as processes in PAFAS s, a CCS-like process algebra with a specific operator for modelling non-blocking reading behaviours. Verification is carried out using the tool FASE, exploiting a correspondence between violations of the liveness property and a special kind of cycles (called catastrophic cycles) in some transition system. We also compare our approach with others in the literature. The aim of this paper is twofold: on the one hand, we want to demonstrate the applicability of FASE to some concrete, meaningful examples; on the other hand, we want to study the impact of introducing non-blocking behaviours in modelling concurrent systems.Comment: In Proceedings GandALF 2011, arXiv:1106.081

Linking worldwide past and present conifer vulnerability

Inventories of species recently extinct or threatened with extinction may be found in global databases. However, despite the large number of published fossil based-studies, specific databases on the vulnerability of species in the past are not available. We compiled a worldwide database of published fossil records of plant range losses over the last 30 ka across all continents. Widespread range losses of plant taxa across all latitudes were identified, with the majority representing gymnosperms. Focusing on conifers, a group of plants with well understood distribution and conservation status, we found that past range losses often overlapped areas where species are endangered at present, suggesting that such areas have been prone to biodiversity loss through time. During phases of past rapid climate change, even areas that currently have low levels of endangered species were affected by plant range losses, in some cases with disappearance of taxa from entire continents, islands or major geographic regions. Integration of modern and palaeoecological data enhance our understanding of the complex processes underlying the modes, rates, and extent of threats to plants under changing climate and increasing human pressure, which is vital information for effective conservation actions

Human peopling of Italian intramontane basins: The early Middle Pleistocene site of Pagliare di Sassa (L’Aquila, central Italy)

Multidisciplinary investigations at Pagliare di Sassa (L’Aquila, central Italy) suggest that the local succession accumulated from the late Early to the early Middle Pleistocene in a lacustrine environment. In the upper part, clastic sediments are part of an alluvial fan prograding into the lake, grading to a braided fluvial system. The pollen record confirms that a significant glacial phase occurred just before the onset of the Jaramillo inversion. These data, coupled with evidence from the nearby but earlier Madonna della Strada sequence, allow reconstruction of part of the environmental evolution of L’Aquila basin before the Jaramillo Subchron. The mammal species of Pagliare di Sassa include Stephanorhinus hundsheimensis, mostly of open environments, already present at Madonna della Strada. The faunal turnover characterizing the Early to Middle Pleistocene transition is indicated by the appearances of taxa typical of the Italian early to middle Galerian faunas, such as Praemegaceros verticornis, together with Megaloceros savini. The occurrence of Mimomys savini together with Microtus ex gr. Microtus hintonigregaloides suggests that this assemblage is earlier than the Isernia La Pineta fauna. A flint implement and a fragmentary herbivore femur with impact scars probably linked to human activity give evidence of the human peopling of intramontane basins of the Apennine chain since the early Middle Pleistocene.Published170-1782.2. Laboratorio di paleomagnetismoJCR Journalrestricte

JNK1 and ERK1/2 modulate lymphocyte homeostasis via BIM and DRP1 upon AICD induction

The Activation-Induced Cell Death (AICD) is a stimulation-dependent form of apoptosis used by the organism to shutdown T-cell response once the source of inflammation has been eliminated, while allowing the generation of immune memory. AICD is thought to progress through the activation of the extrinsic Fas/FasL pathway of cell death, leading to cytochrome-C release through caspase-8 and Bid activation. We recently described that, early upon AICD induction, mitochondria undergo structural alterations, which are required to promote cytochrome-C release and execute cell death. Here, we found that such alterations do not depend on the Fas/FasL pathway, which is instead only lately activated to amplify the cell death cascade. Instead, such alterations are primarily dependent on the MAPK proteins JNK1 and ERK1/2, which, in turn, regulate the activity of the pro-fission protein Drp1 and the pro-apoptotic factor Bim. The latter regulates cristae disassembly and cooperate with Drp1 to mediate the Mitochondrial Outer Membrane Permeabilization (MOMP), leading to cytochrome-C release. Interestingly, we found that Bim is also downregulated in T-cell Acute Lymphoblastic Leukemia (T-ALL) cells, this alteration favouring their escape from AICD-mediated control

Correction: JNK1 and ERK1/2 modulate lymphocyte homeostasis via BIM and DRP1 upon AICD induction

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