Carnegie Supernova Project II: The slowest rising Type Ia supernova LSQ14fmg and clues to the origin of super-Chandrasekhar/03fg-like events

The Type Ia supernova (SN Ia) LSQ14fmg exhibits exaggerated properties which may help to reveal the origin of the "super-Chandrasekhar" (or 03fg-like) group. The optical spectrum is typical of a 03fg-like SN Ia, but the light curves are unlike those of any SNe Ia observed. The light curves of LSQ14fmg rise extremely slowly. At -23 rest-frame days relative to B-band maximum, LSQ14fmg is already brighter than $M_V$=-19 mag before host extinction correction. The observed color curves show a flat evolution from the earliest observation to approximately one week after maximum. The near-infrared light curves peak brighter than -20.5 mag in the J and H bands, far more luminous than any 03fg-like SNe Ia with near-infrared observations. At one month past maximum, the optical light curves decline rapidly. The early, slow rise and flat color evolution are interpreted to result from an additional excess flux from a power source other than the radioactive decay of the synthesized $^{56}Ni$. The excess flux matches the interaction with a typical superwind of an asymptotic giant branch (AGB) star in density structure, mass-loss rate, and duration. The rapid decline starting at around one month past B-band maximum may be an indication of rapid cooling by active carbon monoxide (CO) formation, which requires a low temperature and high density environment. These peculiarities point to an AGB progenitor near the end of its evolution and the core degenerate scenario as the likely explosion mechanism for LSQ14fmg.Comment: 22 pages, 15 figures, accepted for publication in Ap

Differential Differences in Methylation Status of Putative Imprinted Genes among Cloned Swine Genomes

DNA methylation is a major epigenetic modification in the mammalian genome that regulates crucial aspects of gene function. Mammalian cloning by somatic cell nuclear transfer (SCNT) often results in gestational or neonatal failure with only a small proportion of manipulated embryos producing live births. Many of the embryos that survive to term later succumb to a variety of abnormalities that are likely due to inappropriate epigenetic reprogramming. Aberrant methylation patterns of imprinted genes in cloned cattle and mice have been elucidated, but few reports have analyzed the cloned pig genome. Four surviving cloned sows that were created by ear fibroblast nuclear transfer, each with a different life span and multiple organ defects, such as heart defects and bone growth delay, were used as epigenetic study materials. First, we identified four putative differential methylation regions (DMR) of imprinted genes in the wild-type pig genome, including two maternally imprinted loci (INS and IGF2) and two paternally imprinted loci (H19 and IGF2R). Aberrant DNA methylation, either hypermethylation or hypomethylation, commonly appeared in H19 (45% of imprinted loci hypermethylated vs. 30% hypomethylated), IGF2 (40% vs. 0%), INS (50% vs. 5%), and IGF2R (15% vs. 45%) in multiple tissues from these four cloned sows compared with wild-type pigs. Our data suggest that aberrant epigenetic modifications occur frequently in the genome of cloned swine. Even with successful production of cloned swine that avoid prenatal or postnatal death, the perturbation of methylation in imprinted genes still exists, which may be one of reason for their adult pathologies and short life. Understanding the aberrant pattern of gene imprinting would permit improvements in future cloning techniques

Global Mapping of DNA Methylation in Mouse Promoters Reveals Epigenetic Reprogramming of Pluripotency Genes

DNA methylation patterns are reprogrammed in primordial germ cells and in preimplantation embryos by demethylation and subsequent de novo methylation. It has been suggested that epigenetic reprogramming may be necessary for the embryonic genome to return to a pluripotent state. We have carried out a genome-wide promoter analysis of DNA methylation in mouse embryonic stem (ES) cells, embryonic germ (EG) cells, sperm, trophoblast stem (TS) cells, and primary embryonic fibroblasts (pMEFs). Global clustering analysis shows that methylation patterns of ES cells, EG cells, and sperm are surprisingly similar, suggesting that while the sperm is a highly specialized cell type, its promoter epigenome is already largely reprogrammed and resembles a pluripotent state. Comparisons between pluripotent tissues and pMEFs reveal that a number of pluripotency related genes, including Nanog, Lefty1 and Tdgf1, as well as the nucleosome remodeller Smarcd1, are hypomethylated in stem cells and hypermethylated in differentiated cells. Differences in promoter methylation are associated with significant differences in transcription levels in more than 60% of genes analysed. Our comparative approach to promoter methylation thus identifies gene candidates for the regulation of pluripotency and epigenetic reprogramming. While the sperm genome is, overall, similarly methylated to that of ES and EG cells, there are some key exceptions, including Nanog and Lefty1, that are highly methylated in sperm. Nanog promoter methylation is erased by active and passive demethylation after fertilisation before expression commences in the morula. In ES cells the normally active Nanog promoter is silenced when targeted by de novo methylation. Our study suggests that reprogramming of promoter methylation is one of the key determinants of the epigenetic regulation of pluripotency genes. Epigenetic reprogramming in the germline prior to fertilisation and the reprogramming of key pluripotency genes in the early embryo is thus crucial for transmission of pluripotency

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

New lupane glycosides from Pulsatilla chinensis

Two new lupane glycosides along with five known triterpenoids were isolated from the roots of Pulsatilla chinensis (Ranunculaceae). The structures of the new glycosides were determined to be 3-O-beta-D-glucopyranosyl(1-->3)-alpha-L-arabinopyranosyl-23-hydroxybetu linic acid 28-O-alpha-L-rhamnopyranosyl(1-->4)-beta-D-glucopyranosyl(1-->6)-beta-D- glucopyranosyl ester (pulsatilloside D, 6) and 3-O-[beta-D-glucopyranosyl(1-->4)][alpha-L-rhamnopyranosyl(1-->2)]-a lpha-L-arabinopyranosyl-23-hydroxybetulinic acid 28-O-alpha-L-rhamnopyranosyl(1-->4)-beta-D-glucopyranosyl(1-->6)-beta-D- glucopyranosyl ester (pulsatilloside E, 7) by spectroscopic analysis and chemical methods. The compounds were evaluated for cytotoxic activities against K-562 human leukemia and HeLa cells

Chemical characterization, toxicity and source apportionment of respirable atmospheric particles in Hong Kong (ECF Project No. 3/97: The Environmental Health Impact of Respirable Atmospheric Particles (PM-2.5) in Hong Kong)

In this report, findings on the respirable suspended particulates (RSP) in Hong Kong are presented. RSP in this context is defined as atmospheric particulates smaller than 10 μm in aerodynamic diameter (PM10). Atmospheric particles in four different size cuts were collected in this study: <0.49, 0.49-0.95, 0.95-2.5, and 2.5-10 μm. PM2.5 (smaller than 2.5 μm in aerodynamic diameter) and PM10 were also collected. The detailed chemical (metals and solvent-extractable organic compounds) characteristics and seasonal variations of these categories of particles were studied. The toxicity of the PM2.5 and PM10 were also measured. The sources of these aerosols were apportioned using several different methods including Chemical Mass Balance and Conventional Factor Analysis, and correlations between the tracers of the inorganic and organic species were determined. The dry and wet deposition fluxes were determined from the corresponding deposition measurements directly and by modeling using atmospheric aerosol concentration measurements. Inorganic and organic characterization of the dry and wet deposition samples were conducted. The results of this study enhance the understanding of the particulate behavior and they can be used in future health impact studies

Cloning, characterization and functional analysis of the rat frizzled related protein

Frizzled related protein (Frp) is a new family of secreted proteins that contain a region homologous to the extracellular cysteine-rich domain of the frizzled family proteins. The functional role of Frp is far from clear. A few studies have indicated that Frp may play a role in modulating the Wnt-signaling pathway. In our previous study, a rat Frp (rFrp) gene was found to be differentially expressed in Rat 6 fibroblasts overexpressing p53^va1135 (R6#13-8). The rFrp gene was otherwise silent in normal parental Rat 6 cells. To elucidate the molecular basis of the transcriptional activation of rFrp, we have isolated and analyzed a 2-kilobase pair promoter region of the rFrp gene. The rFrp gene contains a TATA box and multiple initiation sites. The proximal promoter region contains DNA binding motifs of MZF1, Lyf-1. GATA, IK2, and STAT3 transcriptional factors, which regulate mostly hematopoietic-restricted genes; and SRY and SOX-5 binding motifs known to be involved in sex-determination. Reporter assays and mobility shift assays revealed that the core nucleotides TTTGGGGG in -196 to -189 and GATGATGT in -149 to -142 play a critical role in regulating rFrp expression. In our study, we also demonstrated that rFrp was down regulated in the majority of human invasive breast tumors. The down-regulation of rFrp seemed to correlate with high incidence of lymph node metastasis in breast cancer

Bifidobacterium animalis: the missing link for the cancer-preventive effect of Gynostemma pentaphyllum

Colorectal cancer (CRC) ranks the third most common cancer type in both men and women. Besides the known genetic and epigenetic changes in the gut epithelial cells, we now know that disturbed gut microbes could also contribute to the onset and progression of CRC. Hence, keeping a balanced gut microbiota (GM) has become a novel pursue in the medical field, particularly in the area of gastrointestinal disorders. Gynostemma pentaphyllum (Gp) is a dietary herbal medicine. In our previous study, Gp saponins (GpS) displayed prebiotic and cancer-preventive properties through the modulation of GM in ApcMin/+ mice. However, the specific group(s) of GM links to the health effects of GpS remains unknown. To track down the missing link, we first investigated and found that inoculation with fecal materials from GpS-treated ApcMin/+ mice effectively reduces polyps in ApcMin/+ mice. From the same source of the fecal sample, we successfully isolated 16 bacterial species. Out of the 16 bacteria, Bifidobacterium animalis stands out as the responder to the GpS-growth stimulus. Biochemical and RNAseq analysis demonstrated that GpS enhanced expressions of a wide range of genes encoding biogenesis and metabolic pathways in B. animalis culture. Moreover, we found that colonization of B. animalis markedly reduces the polyp burden in ApcMin/+ mice. These findings reveal a mutualistic interaction between the prebiotic and a probiotic to achieve anticancer and cancer-preventive activities. Our result, for the first time, unveils the anticancer function of B. animalis and extend the probiotic horizon of B. animalis