Temporal and spatial regulation of the phosphatidate phosphatases lipin 1 and 2

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Lipid partitioning at the nuclear envelope controls membrane biogenesis.

Partitioning of lipid precursors between membranes and storage is crucial for cell growth, and its disruption underlies pathologies such as cancer, obesity, and type 2 diabetes. However, the mechanisms and signals that regulate this process are largely unknown. In yeast, lipid precursors are mainly used for phospholipid synthesis in nutrient-rich conditions in order to sustain rapid proliferation but are redirected to triacylglycerol (TAG) stored in lipid droplets during starvation. Here we investigate how cells reprogram lipid metabolism in the endoplasmic reticulum. We show that the conserved phosphatidate (PA) phosphatase Pah1, which generates diacylglycerol from PA, targets a nuclear membrane subdomain that is in contact with growing lipid droplets and mediates TAG synthesis. We find that cytosol acidification activates the master regulator of Pah1, the Nem1-Spo7 complex, thus linking Pah1 activity to cellular metabolic status. In the absence of TAG storage capacity, Pah1 still binds the nuclear membrane, but lipid precursors are redirected toward phospholipids, resulting in nuclear deformation and a proliferation of endoplasmic reticulum membrane. We propose that, in response to growth signals, activation of Pah1 at the nuclear envelope acts as a switch to control the balance between membrane biogenesis and lipid storage.This work was supported by grants from the Medical Research Council (G0701446) to S.S; a Wellcome Trust Strategic Award (100140) and equipment grant (093026) to the Cambridge Institute for Medical Research; the National Institutes of Health (GM050679) to G.M.C.; a ALW Open Program (822.02.014), DFG-NWO cooperation (DN82-303), SNSF Sinergia (CRSII3_154421) and ZonMW VICI (016.130.606) grants to F.R; and a PhD fellowship from the Fundação para a Ciência e a Tecnologia (FCT) to S.A.This is the final version of the article. It first appeared from the American Society for Cell Biology via http://dx.doi.org/10.1091/mbc.E15-03-017

Towards the Assessment of Realistic Hybrid Precoding in Millimeter Wave MIMO Systems with Hardware Impairments

Funding Information: This work was supported by the University of Hertfordshire's 5‐year Vice Chancellor's Research Fellowship and by the National Research Fund, Luxembourg, under the projects ECLECTIC and 5G‐SKY. Publisher Copyright: © 2021 The Authors. IET Communications published by John Wiley & Sons Ltd on behalf of The Institution of Engineering and TechnologyHybrid processing in millimeter wave (mmWave) communication has been proposed as a solution to reduce the cost and energy consumption by reducing the number of radio-frequency (RF) chains. However, the impact of the inevitable residual transceiver hardware impairments (RTHIs), including the residual additive transceiver hardware impairments (RATHIs) and the amplified thermal noise (ATN), has not been sufficiently studied in mmWave hybrid processing. In this work, the hybrid precoder and combiner are designed, which include both digital and analog processing by taking into account the RATHIs and the ATN. In particular, a thorough study is provided to shed light on the degradation of the spectral efficiency (SE) of the practical system. The outcomes show the steady degradation of the performance by the ATN across all SNR values, which becomes increasingly critical for higher values of its variance. Furthermore, it is shown that RATHIs result in degradation of the system only in the high SNR regime. Hence, their impact in mmWave system operating at low SNRs might be negligible. Moreover, an increase concerning the number of streams differentiates the impact between the transmit and receive RATHIs with the latter having a more severe effect.Peer reviewe

Full-duplex-enabled joint communications and sensing with reconfigurable intelligent surfaces

peer reviewedThe full-duplex (FD) technology has the potential to radically evolve wireless systems, facilitating the integration of both communications and radar functionalities into a single device, thus, enabling joint communication and sensing (JCAS). In this paper, we present a novel approach for JCAS that incorporates a reconfigurable intelligent surface (RIS) in the near-field of an FD multiple-input multiple-output (MIMO) node, which is jointly optimized with the digital beamformers to enable JSAC and efficiently handle self-interference (SI). We propose a novel problem formulation for FD MIMO JCAS systems to jointly minimize the total received power at the FD node’s radar receiver, while maximizing the sum rate of downlink communications subject to a Cramér-Rao bound (CRB) constraint. In contrast to the typically used CRB in the relevant literature, we derive a novel, more accurate, target estimation bound that fully takes into account the RIS deployment. The considered problem is solved using alternating optimization, which is guaranteed to converge to a local optimum. The simulation results demonstrate that the proposed scheme achieves significant performance improvement both for communications and sensing. It is showcased that, jointly designing the FD MIMO beamformers and the RIS phase configuration to be SI aware can significantly loosen the requirement for additional SI cancellation

CK1δ restrains lipin-1 induction, lipid droplet formation and cell proliferation under hypoxia by reducing HIF-1α/ARNT complex formation.

Proliferation of cells under hypoxia is facilitated by metabolic adaptation, mediated by the transcriptional activator Hypoxia Inducible Factor-1 (HIF-1). HIF-1α, the inducible subunit of HIF-1 is regulated by oxygen as well as by oxygen-independent mechanisms involving phosphorylation. We have previously shown that CK1δ phosphorylates HIF-1α in its N-terminus and reduces its affinity for its heterodimerization partner ARNT. To investigate the importance of this mechanism for cell proliferation under hypoxia, we visually monitored HIF-1α interactions within the cell nucleus using the in situ proximity ligation assay (PLA) and fluorescence recovery after photobleaching (FRAP). Both methods show that CK1δ-dependent modification of HIF-1α impairs the formation of a chromatin binding HIF-1 complex. This is confirmed by analyzing expression of lipin-1, a direct target of HIF-1 that mediates hypoxic neutral lipid accumulation. Inhibition of CK1δ increases lipid droplet formation and proliferation of both cancer and normal cells specifically under hypoxia and in an HIF-1α- and lipin-1-dependent manner. These data reveal a novel role for CK1δ in regulating lipid metabolism and, through it, cell adaptation to low oxygen conditions.This work was supported by the “ARISTEIA ΙΙ” Action of the “OPERATIONAL PROGRAMME EDUCATION AND LIFELONG LEARNING” and was co-funded by the European Social Fund (ESF) and National Resources. Partial support was provided by the Proof of Concept Studies for the ESFRI project Euro-BioImaging (Greek BioImaging Facility, PCS facility Nr. 9, Unit 2). N.-N.G., M.A.R. and Z.L. were supported by a grant from the European Research Council and S.S. was supported by a Medical Research Council Senior Fellowship (grant number G0701446).This is the final published version. It first appeared at http://www.sciencedirect.com/science/article/pii/S0898656815000637

Redundant roles of the phosphatidate phosphatase family in triacylglycerol synthesis in human adipocytes.

AIMS/HYPOTHESIS: In mammals, the evolutionary conserved family of Mg(2+)-dependent phosphatidate phosphatases (PAP1), involved in phospholipid and triacylglycerol synthesis, consists of lipin-1, lipin-2 and lipin-3. While mutations in the murine Lpin1 gene cause lipodystrophy and its knockdown in mouse 3T3-L1 cells impairs adipogenesis, deleterious mutations of human LPIN1 do not affect adipose tissue distribution. However, reduced LPIN1 and PAP1 activity has been described in participants with type 2 diabetes. We aimed to characterise the roles of all lipin family members in human adipose tissue and adipogenesis. METHODS: The expression of the lipin family was analysed in adipose tissue in a cross-sectional study. Moreover, the effects of lipin small interfering RNA (siRNA)-mediated depletion on in vitro human adipogenesis were assessed. RESULTS: Adipose tissue gene expression of the lipin family is altered in type 2 diabetes. Depletion of every lipin family member in a human Simpson-Golabi-Behmel syndrome (SGBS) pre-adipocyte cell line, alters expression levels of adipogenic transcription factors and lipid biosynthesis genes in early stages of differentiation. Lipin-1 knockdown alone causes a 95% depletion of PAP1 activity. Despite the reduced PAP1 activity and alterations in early adipogenesis, lipin-silenced cells differentiate and accumulate neutral lipids. Even combinatorial knockdown of lipins shows mild effects on triacylglycerol accumulation in mature adipocytes. CONCLUSIONS/INTERPRETATION: Overall, our data support the hypothesis of alternative pathways for triacylglycerol synthesis in human adipocytes under conditions of repressed lipin expression. We propose that induction of alternative lipid phosphate phosphatases, along with the inhibition of lipid hydrolysis, contributes to the maintenance of triacylglycerol content to near normal levels.This study was supported by research grants from the ‘Instituto de Salud Carlos III’ (ISCIII, Spanish Ministry of Economy and Competitiveness) (PI10/00967 and CP11/0 0021 to MM); the R. Barri Private Foundation (PV12142S to MM); the Medical Research Council (G0701446 to SS); and National Institutes of Health Grant (GM028140 to GMC). CIBER de Diabetes y Enfermedades Metabólicas asociadas (CB07708/0012) is an initiative of the ISCIII. MM acknowledges support from the ‘Miguel Servet’ tenure track programme (CP11/00021), from the Fondo de Investigación Sanitaria (FIS) co-financed by the European Regional Development Fund (ERDF), and supported by a Salvador de Madariaga Mobility fellowship from the Spanish Ministry of Education (PR2011-0584). AT is the recipient of a FI-DGR fellowship (9015-97318/2012) from the Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR)This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Springer

FRCSyn Challenge at WACV 2024:Face Recognition Challenge in the Era of Synthetic Data

Despite the widespread adoption of face recognition technology around the world, and its remarkable performance on current benchmarks, there are still several challenges that must be covered in more detail. This paper offers an overview of the Face Recognition Challenge in the Era of Synthetic Data (FRCSyn) organized at WACV 2024. This is the first international challenge aiming to explore the use of synthetic data in face recognition to address existing limitations in the technology. Specifically, the FRCSyn Challenge targets concerns related to data privacy issues, demographic biases, generalization to unseen scenarios, and performance limitations in challenging scenarios, including significant age disparities between enrollment and testing, pose variations, and occlusions. The results achieved in the FRCSyn Challenge, together with the proposed benchmark, contribute significantly to the application of synthetic data to improve face recognition technology.Comment: 10 pages, 1 figure, WACV 2024 Workshop

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three genomic nomenclature systems to all sequence data from the World Health Organization European Region available until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation, compare the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2

Global wealth disparities drive adherence to COVID-safe pathways in head and neck cancer surgery

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