Temporal Diffeomorphic Free-Form Deformation for Strain Quantification in 3D-US Images

International audienceThis paper presents a new diffeomorphic temporal registration algorithm and its application to motion and strain quantification from a temporal sequence of 3D images. The displacement field is computed by forward eulerian integration of a non-stationary velocity field. The originality of our approach resides in enforcing time consistency by representing the velocity field as a sum of continuous spatiotemporal B-Spline kernels. The accuracy of the developed diffeomorphic technique was first compared to a simple pairwise strategy on synthetic US images with known ground truth motion and with several noise levels, being the proposed algorithm more robust to noise than the pairwise case. Our algorithm was then applied to a database of cardiac 3D+t Ultrasound (US) images of the left ventricle acquired from height healthy volunteers and three Cardiac Resynchronization Therapy (CRT) patients. On healthy cases, the measured regional strain curves provided uniform strain patterns over all myocardial segments in accordance with clinical literature. On CRT patients, the obtained normalization of the strain pattern after CRT agreed with clinical outcome for the three cases

Influence of SIGLEC9 polymorphisms on COPD phenotypes including exacerbation frequency.

BACKGROUND AND OBJECTIVE: The exacerbation-prone phenotype of COPD is particularly important, as exacerbations lead to poor quality of life and disease progression. We previously found that COPD patients who lack Siglec-14, a myeloid cell protein that recognizes bacteria and triggers inflammatory responses, are less prone to exacerbation. We hypothesized that the variations in other SIGLEC genes could also influence COPD exacerbation frequency, and investigated the association between SIGLEC9 polymorphisms and the exacerbation-prone phenotype of COPD. METHODS: We examined whether SIGLEC9 polymorphisms affect the frequency of COPD exacerbation in 135 subjects within our study population, and also analysed the correlation between the genotypes and the severity of airflow obstruction and emphysema in 362 Japanese smokers including 244 COPD patients. The association between these single nucleotide polymorphisms (SNPs) and COPD phenotypes were also assessed in a Caucasian population of ECLIPSE study. The effects of these coding SNPs (cSNPs) on Siglec-9 protein functions were analysed using in vitro assays. RESULTS: The G allele of rs2075803 and rs2075803 G/rs2258983 A(GA) haplotype in SIGLEC9 was associated with higher frequency of exacerbations and the extent of emphysema in COPD. These results did not replicate in the ECLIPSE study. A myeloid cell line expressing the Siglec-9 variant corresponding to GA haplotype produced more TNF-α than the one expressing the variant corresponding to the other major haplotype. CONCLUSION: The SIGLEC9 rs2075803 G/rs2258983 A haplotype, which corresponds to a Siglec-9 variant that is less effective at suppressing inflammatory response, may be a risk factor for the development of emphysema

Hepatic lipocalin 2 promotes liver fibrosis and portal hypertension

Advanced fibrosis and portal hypertension influence short-term mortality. Lipocalin 2 (LCN2) regulates infection response and increases in liver injury. We explored the role of intrahepatic LCN2 in human alcoholic hepatitis (AH) with advanced fibrosis and portal hypertension and in experimental mouse fibrosis. We found hepatic LCN2 expression and serum LCN2 level markedly increased and correlated with disease severity and portal hypertension in patients with AH. In control human livers, LCN2 expressed exclusively in mononuclear cells, while its expression was markedly induced in AH livers, not only in mononuclear cells but also notably in hepatocytes. Lcn2−/− mice were protected from liver fibrosis caused by either ethanol or CCl4 exposure. Microarray analysis revealed downregulation of matrisome, cell cycle and immune related gene sets in Lcn2−/− mice exposed to CCl4, along with decrease in Timp1 and Edn1 expression. Hepatic expression of COL1A1, TIMP1 and key EDN1 system components were elevated in AH patients and correlated with hepatic LCN2 expression. In vitro, recombinant LCN2 induced COL1A1 expression. Overexpression of LCN2 increased HIF1A that in turn mediated EDN1 upregulation. LCN2 contributes to liver fibrosis and portal hypertension in AH and could represent a new therapeutic target

Hepatic lipocalin 2 promotes liver fibrosis and portal hypertension

Advanced fibrosis and portal hypertension influence short-term mortality. Lipocalin 2 (LCN2) regulates infection response and increases in liver injury. We explored the role of intrahepatic LCN2 in human alcoholic hepatitis (AH) with advanced fibrosis and portal hypertension and in experimental mouse fibrosis. We found hepatic LCN2 expression and serum LCN2 level markedly increased and correlated with disease severity and portal hypertension in patients with AH. In control human livers, LCN2 expressed exclusively in mononuclear cells, while its expression was markedly induced in AH livers, not only in mononuclear cells but also notably in hepatocytes. Lcn2-/- mice were protected from liver fibrosis caused by either ethanol or CCl4 exposure. Microarray analysis revealed downregulation of matrisome, cell cycle and immune related gene sets in Lcn2-/- mice exposed to CCl4, along with decrease in Timp1 and Edn1 expression. Hepatic expression of COL1A1, TIMP1 and key EDN1 system components were elevated in AH patients and correlated with hepatic LCN2 expression. In vitro, recombinant LCN2 induced COL1A1 expression. Overexpression of LCN2 increased HIF1A that in turn mediated EDN1 upregulation. LCN2 contributes to liver fibrosis and portal hypertension in AH and could represent a new therapeutic target

Long-Term Increased Carnitine Palmitoyltransferase 1A Expression in Ventromedial Hypotalamus Causes Hyperphagia and Alters the Hypothalamic Lipidomic Profile

Lipid metabolism in the ventromedial hypothalamus (VMH) has emerged as a crucial pathway in the regulation of feeding and energy homeostasis. Carnitine palmitoyltransferase (CPT) 1A is the rate-limiting enzyme in mitochondrial fatty acid boxidation and it has been proposed as a crucial mediator of fasting and ghrelin orexigenic signalling. However, the relationship between changes in CPT1A activity and the intracellular downstream effectors in the VMH that contribute to appetite modulation is not fully understood. To this end, we examined the effect of long-term expression of a permanently activated CPT1A isoform by using an adeno-associated viral vector injected into the VMH of rats. Peripherally, this procedure provoked hyperghrelinemia and hyperphagia, which led to overweight, hyperglycemia and insulin resistance. In the mediobasal hypothalamus (MBH), long-term CPT1AM expression in the VMH did not modify acyl-CoA or malonyl-CoA levels. However, it altered the MBH lipidomic profile since ceramides and sphingolipids increased and phospholipids decreased. Furthermore, we detected increased vesicular c-aminobutyric acid transporter (VGAT) and reduced vesicular glutamate transporter 2 (VGLUT2) expressions, both transporters involved in this orexigenic signal. Taken together, these observations indicate that CPT1A contributes to the regulation of feeding by modulating the expression of neurotransmitter transporters and lipid components that influence the orexigenic pathways in VMH

A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction

The developmental and physiological complexity of the auditory system is likely reflected in the underlying set of genes involved in auditory function. In humans, over 150 non-syndromic loci have been identified, and there are more than 400 human genetic syndromes with a hearing loss component. Over 100 non-syndromic hearing loss genes have been identified in mouse and human, but we remain ignorant of the full extent of the genetic landscape involved in auditory dysfunction. As part of the International Mouse Phenotyping Consortium, we undertook a hearing loss screen in a cohort of 3006 mouse knockout strains. In total, we identify 67 candidate hearing loss genes. We detect known hearing loss genes, but the vast majority, 52, of the candidate genes were novel. Our analysis reveals a large and unexplored genetic landscape involved with auditory function

Evidence for increasing global wheat yield potential

Wheat is the most widely grown food crop, with 761 Mt produced globally in 2020. To meet the expected grain demand by mid-century, wheat breeding strategies must continue to improve upon yield-advancing physiological traits, regardless of climate change impacts. Here, the best performing doubled haploid (DH) crosses with an increased canopy photosynthesis from wheat field experiments in the literature were extrapolated to the global scale with a multi-model ensemble of process-based wheat crop models to estimate global wheat production. The DH field experiments were also used to determine a quantitative relationship between wheat production and solar radiation to estimate genetic yield potential. The multi-model ensemble projected a global annual wheat production of 1050 ± 145 Mt due to the improved canopy photosynthesis, a 37% increase, without expanding cropping area. Achieving this genetic yield potential would meet the lower estimate of the projected grain demand in 2050, albeit with considerable challenges.Fil: Guarin, Jose Rafael. National Aeronautics and Space Administration; Estados Unidos. Columbia University; Estados Unidos. Florida State University; Estados UnidosFil: Martre, Pierre. Institut Agro Montpellier SupAgro; FranciaFil: Ewert, Frank. Universitat Bonn; Alemania. Leibniz Centre for Agricultural Landscape Research; AlemaniaFil: Webber, Heidi. Universitat Bonn; Alemania. Leibniz Centre for Agricultural Landscape Research; AlemaniaFil: Dueri, Sibylle. Institut Agro Montpellier SupAgro; FranciaFil: Calderini, Daniel Fernando. Universidad Austral de Chile; ChileFil: Reynolds, Matthew. International Maize and Wheat Improvement Center ; MéxicoFil: Molero, Gemma. KWS; FranciaFil: Miralles, Daniel Julio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura; ArgentinaFil: Garcia, Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura; ArgentinaFil: Slafer, Gustavo Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura; Argentina. Universitat de Lleida; España. Institució Catalana de Recerca i Estudis Avancats; EspañaFil: Giunta, Francesco. Consiglio Nazionale Delle Ricerche. Istituto Di Scienze Dell Atmosfera E del Clima.; ItaliaFil: Pequeno, Diego N.L.. International Maize and Wheat Improvement Center; MéxicoFil: Stella, Tommaso. Universitat Bonn; Alemania. Leibniz Centre for Agricultural Landscape Research; AlemaniaFil: Ahmed, Mukhtar. University Of Pakistan; PakistánFil: Alderman, Phillip D.. Oklahoma State University; Estados UnidosFil: Basso, Bruno. Michigan State University; Estados UnidosFil: Berger, Andres G.. Instituto Nacional de Investigacion Agropecuaria;Fil: Bindi, Marco. Università degli Studi di Firenze; ItaliaFil: Bracho-Mujica, Gennady. Universität Göttingen; AlemaniaFil: Cammarano, Davide. Purdue University; Estados UnidosFil: Chen, Yi. Chinese Academy of Sciences; República de ChinaFil: Dumont, Benjamin. Université de Liège; BélgicaFil: Rezaei, Ehsan Eyshi. Leibniz Institute Of Plant Genetics And Crop Plant Research.; AlemaniaFil: Fereres, Elias. Universidad de Córdoba; EspañaFil: Ferrise, Roberto. Michigan State University; Estados UnidosFil: Gaiser, Thomas. Universitat Bonn; AlemaniaFil: Gao, Yujing. Florida State University; Estados UnidosFil: Garcia Vila, Margarita. Universidad de Córdoba; EspañaFil: Gayler, Sebastian. Universidad de Hohenheim; Alemani