Implications of GWTC-3 on primordial black holes from vacuum bubbles

The population of black holes inferred from the detection of gravitational waves by the LIGO-Virgo-KAGRA collaboration has revealed interesting features in the properties of black holes in the universe. We analyze the GWTC-3 dataset assuming the detected black holes in each event had an either astrophysical or primordial origin. In particular, we consider astrophysical black holes described by the fiducial \textsc{Power Law + Peak} distribution and primordial black holes whose mass function obeys a broken power law. These primordial black holes can be generated by vacuum bubbles that nucleate during inflation. We find that astrophysical black holes dominate the events with mass less than $\sim 30M_\odot$, whereas primordial black holes are responsible for the massive end, and also for the peak at $\sim 30M_\odot$ in the mass distribution. More than half of the observed events could come from primordial black hole mergers. We also discuss the implications on the primordial black hole formation mechanism and the underlying inflationary model.Comment: The ABH model has been update

A genome-wide study of two-component signal transduction systems in eight newly sequenced mutans streptococci strains

<p>Abstract</p> <p>Background</p> <p>Mutans streptococci are a group of gram-positive bacteria including the primary cariogenic dental pathogen <it>Streptococcus mutans </it>and closely related species. Two component systems (TCSs) composed of a signal sensing histidine kinase (HK) and a response regulator (RR) play key roles in pathogenicity, but have not been comparatively studied for these oral bacterial pathogens.</p> <p>Results</p> <p>HKs and RRs of 8 newly sequenced mutans streptococci strains, including <it>S. sobrinus </it>DSM20742, <it>S. ratti </it>DSM20564 and six <it>S. mutans </it>strains, were identified and compared to the TCSs of <it>S. mutans </it>UA159 and NN2025, two previously genome sequenced <it>S. mutans </it>strains. Ortholog analysis revealed 18 TCS clusters (HK-RR pairs), 2 orphan HKs and 2 orphan RRs, of which 8 TCS clusters were common to all 10 strains, 6 were absent in one or more strains, and the other 4 were exclusive to individual strains. Further classification of the predicted HKs and RRs revealed interesting aspects of their putative functions. While TCS complements were comparable within the six <it>S. mutans </it>strains, <it>S. sobrinus </it>DSM20742 lacked TCSs possibly involved in acid tolerance and fructan catabolism, and <it>S. ratti </it>DSM20564 possessed 3 unique TCSs but lacked the quorum-sensing related TCS (ComDE). Selected computational predictions were verified by PCR experiments.</p> <p>Conclusions</p> <p>Differences in the TCS repertoires of mutans streptococci strains, especially those of <it>S. sobrinus </it>and <it>S. ratti </it>in comparison to <it>S. mutans</it>, imply differences in their response mechanisms for survival in the dynamic oral environment. This genomic level study of TCSs should help in understanding the pathogenicity of these mutans streptococci strains.</p

Severe Maternal Hyperglycemia Exacerbates the Development of Insulin Resistance and Fatty Liver in the Offspring on High Fat Diet

Background. Adverse maternal environments may predispose the offspring to metabolic syndrome in adulthoods, but the underlying mechanism has not been fully understood. Methods. Maternal hyperglycemia was induced by streptozotocin (STZ) injection while control (CON) rats received citrate buffer. Litters were adjusted to eight pups per dam and then weaned to standard diet. Since 13 weeks old, a subset of offspring from STZ and CON dams were switched to high fat diet (HFD) for another 13 weeks. Glucose and insulin tolerance tests (GTT and ITT) and insulin secretion assay were performed; serum levels of lipids and leptin were measured. Hepatic fat accumulation and islet area were evaluated through haematoxylin and eosin staining. Results. STZ offspring exhibited lower survival rate, lower birth weights, and growth inhibition which persisted throughout the study. STZ offspring on HFD showed more severe impairment in GTT and ITT, and more profound hepatic steatosis and more severe hyperlipidemia compared with CON-HFD rats. Conclusions. Offspring from diabetic dams would be prone to exhibit low birth weight and postnatal growth inhibition, but could maintain normal glucose tolerance and insulin sensitivity. HFD accelerates development of insulin resistance in the offspring of diabetic dams mainly via a compensatory response of islets

Transcriptomic response of the mycoparasitic fungus Trichoderma atroviride to the presence of a fungal prey

<p>Abstract</p> <p>Background</p> <p>Combating the action of plant pathogenic microorganisms by mycoparasitic fungi has been announced as an attractive biological alternative to the use of chemical fungicides since two decades. The fungal genus <it>Trichoderma </it>includes a high number of taxa which are able to recognize, combat and finally besiege and kill their prey. Only fragments of the biochemical processes related to this ability have been uncovered so far, however.</p> <p>Results</p> <p>We analyzed genome-wide gene expression changes during the begin of physical contact between <it>Trichoderma atroviride </it>and two plant pathogens <it>Botrytis cinerea </it>and <it>Rhizoctonia solani</it>, and compared with gene expression patterns of mycelial and conidiating cultures, respectively. About 3000 ESTs, representing about 900 genes, were obtained from each of these three growth conditions. 66 genes, represented by 442 ESTs, were specifically and significantly overexpressed during onset of mycoparasitism, and the expression of a subset thereof was verified by expression analysis. The upregulated genes comprised 18 KOG groups, but were most abundant from the groups representing posttranslational processing, and amino acid metabolism, and included components of the stress response, reaction to nitrogen shortage, signal transduction and lipid catabolism. Metabolic network analysis confirmed the upregulation of the genes for amino acid biosynthesis and of those involved in the catabolism of lipids and aminosugars.</p> <p>Conclusion</p> <p>The analysis of the genes overexpressed during the onset of mycoparasitism in <it>T. atroviride </it>has revealed that the fungus reacts to this condition with several previously undetected physiological reactions. These data enable a new and more comprehensive interpretation of the physiology of mycoparasitism, and will aid in the selection of traits for improvement of biocontrol strains by recombinant techniques.</p

Mendelian randomization analysis identified tumor necrosis factor as being associated with severe COVID-19

Background: Observational studies have shown that anti-tumor necrosis factor (TNF) therapy may be beneficial for patients with coronavirus disease 2019 (COVID-19). Nevertheless, because of the methodological restrictions of traditional observational studies, it is a challenge to make causal inferences. This study involved a two-sample Mendelian randomization analysis to investigate the causal link between nine TNFs and COVID-19 severity using publicly released genome-wide association study summary statistics.Methods: Summary statistics for nine TNFs (21,758 cases) were obtained from a large-scale genome-wide association study. Correlation data between single-nucleotide polymorphisms and severe COVID-19 (18,152 cases vs. 1,145,546 controls) were collected from the COVID-19 host genetics initiative. The causal estimate was calculated by inverse variance-weighted (IVW), MR–Egger, and weighted median methods. Sensitivity tests were conducted to assess the validity of the causal relationship.Results: Genetically predicted TNF receptor superfamily member 6 (FAS) positively correlated with the severity of COVID-19 (IVW, odds ratio = 1.10, 95% confidence interval = 1.01–1.19, p = 0.026), whereas TNF receptor superfamily member 5 (CD40) was protective against severe COVID-19 (IVW, odds ratio = 0.92, 95% confidence interval = 0.87–0.97, p = 0.002).Conclusion: Genetic evidence from this study supports that the increased expression of FAS is associated with the risk of severe COVID-19 and that CD40 may have a potential protective effect against COVID-19

GSK-3alpha directly regulates beta-adrenergic signaling and the response of the heart to hemodynamic stress in mice.

The glycogen synthase kinase-3 (GSK-3) family of serine/threonine kinases consists of 2 highly related isoforms, alpha and beta. Although GSK-3beta has an important role in cardiac development, much remains unknown about the function of either GSK-3 isoform in the postnatal heart. Herein, we present what we believe to be the first studies defining the role of GSK-3alpha in the mouse heart using gene targeting. Gsk3a(-/-) mice over 2 months of age developed progressive cardiomyocyte and cardiac hypertrophy and contractile dysfunction. Following thoracic aortic constriction in young mice, we observed enhanced hypertrophy that rapidly transitioned to ventricular dilatation and contractile dysfunction. Surprisingly, markedly impaired beta-adrenergic responsiveness was found at both the organ and cellular level. This phenotype was reproduced by acute treatment of WT cardiomyocytes with a small molecule GSK-3 inhibitor, confirming that the response was not due to a chronic adaptation to LV dysfunction. Thus, GSK-3alpha appears to be the central regulator of a striking range of essential processes, including acute and direct positive regulation of beta-adrenergic responsiveness. In the absence of GSK-3alpha, the heart cannot respond effectively to hemodynamic stress and rapidly fails. Our findings identify what we believe to be a new paradigm of regulation of beta-adrenergic signaling and raise concerns given the rapid expansion of drug development targeting GSK-3

Artificial local magnetic field inhomogeneity enhances T2 relaxivity

磁性探针作为分子影像技术中的磁共振成像（MRI）造影剂在医学诊断中发挥着重要作用。为满足实际诊断中的准确性和精确性要求，科研工作者们长期致力于发展高性能的MRI造影剂以降低高剂量的使用带来的潜在风险。该文章指出了探针聚集体中局域磁场不均匀性是影响T2弛豫效能的关键因素。该文章首次利用磁场不均匀性因素阐明了单个探针和它们聚集体的MRI造影剂之间的相互关系，将可能成为弥补探针聚集体的造影剂理论的空白，并为发展新型高效的MRI造影剂提供重要参考。 该论文共同第一作者为博士后周子健和博士生田蕊，通讯作者为陈小元教授和聂立铭博士，部分工作得到我校物理学系王瑞方教授和化学化工学院高锦豪教授的支持。【Abstract】Clustering of magnetic nanoparticles (MNPs) is perhaps the most effective, yet intriguing strategy to enhance T2 relaxivity in magnetic resonance imaging (MRI). However, the underlying mechanism is still not fully understood and the attempts to generalize the classic outersphere theory from single particles to clusters have been found to be inadequate. Here we show that clustering of MNPs enhances local field inhomogeneity due to reduced field symmetry, which can be further elevated by artificially involving iron oxide NPs with heterogeneous geometries in terms of size and shape. The r2 values of iron oxide clusters and Landau–Lifshitz–Gilbert simulations confirmed our hypothesis, indicating that solving magnetic field inhomogeneity may become a powerful way to build correlation between magnetization and T2 relaxivity of MNPs, especially magnetic clusters. This study provides a simple yet distinct mechanism to interpret T2 relaxivity of MNPs, which is crucial to the design of high-performance MRI contrast agents.This work was supported by the National Science Foundation of China (81571744 and 81601489), the National Basic Research Program of China (863 Program 2015AA020502), the Fundamental Research Funds for the Central Universities (20720170065), the Science Foundation of Fujian Province (No. 2014Y2004), and by the Intramural Research Program (IRP), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH). 研究工作得到了国家自然科学基金委、国家高技术研究发展计划863项目、福建省重大研发平台项目和美国NIH Intramural Research Program的资助

Artificial local magnetic field inhomogeneity enhances T2 relaxivity

磁性探针作为分子影像技术中的磁共振成像（MRI）造影剂在医学诊断中发挥着重要作用。为满足实际诊断中的准确性和精确性要求，科研工作者们长期致力于发展高性能的MRI造影剂以降低高剂量的使用带来的潜在风险。该文章指出了探针聚集体中局域磁场不均匀性是影响T2弛豫效能的关键因素。该文章首次利用磁场不均匀性因素阐明了单个探针和它们聚集体的MRI造影剂之间的相互关系，将可能成为弥补探针聚集体的造影剂理论的空白，并为发展新型高效的MRI造影剂提供重要参考。 该论文共同第一作者为博士后周子健和博士生田蕊，通讯作者为陈小元教授和聂立铭博士，部分工作得到我校物理学系王瑞方教授和化学化工学院高锦豪教授的支持。【Abstract】Clustering of magnetic nanoparticles (MNPs) is perhaps the most effective, yet intriguing strategy to enhance T2 relaxivity in magnetic resonance imaging (MRI). However, the underlying mechanism is still not fully understood and the attempts to generalize the classic outersphere theory from single particles to clusters have been found to be inadequate. Here we show that clustering of MNPs enhances local field inhomogeneity due to reduced field symmetry, which can be further elevated by artificially involving iron oxide NPs with heterogeneous geometries in terms of size and shape. The r2 values of iron oxide clusters and Landau–Lifshitz–Gilbert simulations confirmed our hypothesis, indicating that solving magnetic field inhomogeneity may become a powerful way to build correlation between magnetization and T2 relaxivity of MNPs, especially magnetic clusters. This study provides a simple yet distinct mechanism to interpret T2 relaxivity of MNPs, which is crucial to the design of high-performance MRI contrast agents.This work was supported by the National Science Foundation of China (81571744 and 81601489), the National Basic Research Program of China (863 Program 2015AA020502), the Fundamental Research Funds for the Central Universities (20720170065), the Science Foundation of Fujian Province (No. 2014Y2004), and by the Intramural Research Program (IRP), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH). 研究工作得到了国家自然科学基金委、国家高技术研究发展计划863项目、福建省重大研发平台项目和美国NIH Intramural Research Program的资助

Self-assembled plasmonic vesicles of amphiphilic gold nanocrystals for traceable drug delivery

Research in this thesis developed a new class of plasmonic vesicular nanostructures assembled from amphiphilic gold nanocrystals (nanoparticles and nanorods) coated with mixed hydrophilic and hydrophobic polymer brushes. The integration of gold nanocrystals with two types of chemically distinct polymer grafts, which are analogous to block copolymers as a whole, creates a new type of hybrid building blocks inheriting the amphiphilicity-driven self-assembly of block copolymers to form vesicular structures. The disruption of the plasmonic vesicles can be triggered by stimuli mechanisms inherent to either of the polymer or the nanocrystal. To fulfill the different requirements of drug delivery, three types of plasmonic vesicles were prepared by using amphiphilic gold nanocrystals with pH responsive, photo-active and biodegradable polymers as hydrophobic brush, respectively, while the hydrophilic brush was maintained as poly(ethylene glycol) PEG. These plasmonic vesicles with hollow cavity can play multifunctional roles as traceable delivery carriers for anticancer drugs and plasmonic imaging probes to specifically label targeted cancer cells and trace intracellular drug delivery. Furthermore, integration of photothermal effect of gold nanorods and large loading capacity of the vesicles provides opportunities for localized synergistic photothermal ablation and photo-activated chemotherapy, which have shown higher efficiency in killing targeted cancer cells than either single therapeutic modality.Doctor of Philosophy (SCBE