Biology subjects

Fu, Q.

Publications and source records attributed to Fu, Q..

7 recordsLinked to original sources

bioRxiv2018

The population history of northeastern Siberia since the Pleistocene

Far northeastern Siberia has been occupied by humans for more than 40 thousand years. Yet, owing to a scarcity of early archaeological sites and human remains, its population history and relationship to ancient and modern populations across Eurasia and the Americas are poorly understood. Here, we analyze 34 ancient genome sequences, including two from fragmented milk teeth found at the ~31.6 thousand-year-old (kya) Yana RHS site, the earliest and northernmost Pleistocene human remains found. These genomes reveal complex patterns of past population admixture and replacement events throughout northeastern Siberia, with evidence for at least three large-scale human migrations into the region. The first inhabitants, a previously unknown population of \"Ancient North Siberians\" (ANS), represented by Yana RHS, diverged ~38 kya from Western Eurasians, soon after the latter split from East Asians. Between 20 and 11 kya, the ANS population was largely replaced by peoples with ancestry related to present-day East Asians, giving rise to ancestral Native Americans and \"Ancient Paleosiberians\" (AP), represented by a 9.8 kya skeleton from Kolyma River. AP are closely related to the Siberian ancestors of Native Americans, and ancestral to contemporary communities such as Koryaks and Itelmen. Paleoclimatic modelling shows evidence for a refuge during the last glacial maximum (LGM) in southeastern Beringia, suggesting Beringia as a possible location for the admixture forming both ancestral Native Americans and AP. Between 11 and 4 kya, AP were in turn largely replaced by another group of peoples with ancestry from East Asia, the \"Neosiberians\" from which many contemporary Siberians derive. We detect gene flow events in both directions across the Bering Strait during this time, influencing the genetic composition of Inuit, as well as Na Dene-speaking Northern Native Americans, whose Siberian-related ancestry components is closely related to AP. Our analyses reveal that the population history of northeastern Siberia was highly dynamic throughout the Late Pleistocene and Holocene. The pattern observed in northeastern Siberia, with earlier, once widespread populations being replaced by distinct peoples, seems to have taken place across northern Eurasia, as far west as Scandinavia.

genomics↗

bioRxiv2018

Mesenchymal stem cells protect retinal ganglion cells from degeneration via mitochondrial donation

Retinal ganglion cell (RGC) degeneration is extremely hard to repair or regenerate and is often coupled with mitochondrial dysfunction. Mesenchymal stem cells (MSCs)-based treatment has been demonstrated beneficial for RGC against degeneration. However, underlying mechanisms of MSC-provided RGC protection are largely unknown other than neuropectective paracrine actions. In this study, we sought to investigate whether mitochondrial donation can preserve RGC functions, in a mitochondrial Ndufs4 deficient mouse model of RGC degeneration. The results revealed intravitreal transplanted by induced pluripotent stem cell derived-MSCs (iPSC-MSC) could donate their mitochondria through crossing inner limited membrane to host RGCs. Furthermore, the donated mitochondria effectively protected against RGC death and largely preserved retinal function in Ndufs4-KO mice. Importantly, the protective effects of mitochondrial donation from MSCs were associated with management of pro-inflammatory cytokines. Our data identified a novel role of MSCs-mitochondrial donation in protection of RGC from degeneration, and highlight a viable therapeutic strategy by manipulating stem cell mitochondrial donation for the treatment of retina degeneration in future.

cell biology↗

bioRxiv2018

Sae2/CtIP prevents R-loop accumulation in eukaryotic cells

The Sae2/CtIP protein is required for efficient processing of DNA double-strand breaks that initiate homologous recombination in eukaryotic cells. Sae2/CtIP is also important for survival of single-stranded Top1-induced lesions and CtIP is known to associate directly with transcription-associated complexes in mammalian cells. Here we investigate the role of Sae2/CtIP at single-strand lesions in budding yeast and in human cells and find that depletion of Sae2/CtIP promotes the accumulation of stalled RNA polymerase and RNA-DNA hybrids at sites of highly expressed genes. Overexpression of the RNA-DNA helicase Senataxin suppresses DNA damage sensitivity and R-loop accumulation in Sae2/CtIP-deficient cells, and a catalytic mutant of CtIP fails to complement this sensitivity, indicating a role for CtIP nuclease activity in the repair process. Based on this evidence, we propose that R-loop processing by 5 flap endonucleases is a necessary step in the stabilization and removal of nascent R-loop initiating structures in eukaryotic cells.

molecular biology↗

bioRxiv2018

RNAi screening identifies a new Toll from shrimp that restricts WSSV infection through activating Dorsal to induce antimicrobial peptides

The function of Toll pathway defense against bacterial infection has been well established in shrimp, however how this pathway responds to viral infection is still largely unknown. In this study, we report the Toll4-Dorsal-AMPs cascade restricts the white spot syndrome virus (WSSV) infection of shrimp. A total of nine Tolls from Litopenaeus vannamei namely Toll1-9 are identified, and RNAi screening in vivo reveals the Toll4 is important for shrimp to oppose WSSV infection. Knockdown of Toll4 results in elevated viral loads and renders shrimp more susceptible to WSSV. Furthermore, Toll4 could be a one of upstream pattern recognition receptor (PRR) to detect WSSV, and thereby leading to nuclear translocation and phosphorylation of Dorsal, the known NF-{kappa}B transcription factor of the canonical Toll pathway. More importantly, silencing of Toll4 and Dorsal contributes to impaired expression of a specific set of antimicrobial peptides (AMPs) such as anti-LPS-factor (ALF) and lysozyme (LYZ) family, which exert potent anti-WSSV activity. Two AMPs of ALF1 and LYZ1 as representatives are demonstrated to have the ability to interact with several WSSV structural proteins. Taken together, we therefore identify the Toll4-Dorsal pathway mediates strong resistance to WSSV infection by inducing some specific AMPs.\n\nAuthor summaryThe TLR pathway mediated antiviral immune response is well identified in mammals, yet, Toll pathway governing this protection in invertebrates remains unknown. In the present study, we uncover that a shrimp Toll4 from a total of nine Tolls in L. vannamei confers resistance to WSSV thought inducing the NF-{kappa}B transcription factor Dorsal to inspiring the production of some antimicrobial peptides (AMPs) with antiviral activity. The anti-LPS-factor (ALF) and lysozyme (LYZ) family are identified as the Toll4-Dorsal pathway targeted genes with the ability to interact with viral structural proteins in response to WSSV infection. These results suggest that the Toll receptor induces the expression of AMPs with antiviral activity could be a general antiviral mechanism in invertebrates and Toll pathway established antiviral defense could be conserved during evolution.

immunology↗

bioRxiv2018

Canine transmissible venereal tumor genome reveals ancient introgression from coyotes to arctic sled dogs

Dear Editor,\n\nAncient genome-sequencing studies have extensively refined our understanding of the genetic histories and adaptive evolution of humans1, as well as the domestic process of livestock and crops2. Recent studies about ancient and modern canids all indicate that canids have intricate histories, and lots of canine populations disappeared during evolution3-6. Thus, ancient genomes from canine fossils are in high demand to clarify canine evolution and the processes leading to dog domestication. Canine transmissible venereal tumor (CTVT), the oldest known somatic cell line, is a living fossil, originating from cancer cells transmitted from a host to other canids during the mating process7. Clonal origin analyses hints that the original dog infected with CTVT (CTVT founder) came from an ancient sled dog or wolf population ...

evolutionary biology↗

bioRxiv2018

Let-7i-5p regulation of cell morphology and migration through distinct signaling pathways in normal and pathogenic fibroblasts from urethra

Pelvic fracture urethral distraction defects (PFUDD) is a common disease that could severely affect patients life quality, yet little is known about the molecular mechanism associated with pathogenic fibrosis in PFUDD. In this study, we found that let-7i-5p could regulate different cellular events in normal and pathogenic fibroblasts through three distinct signaling pathways. Interestingly, those regulations are compromised during the translation from mRNA to protein, and partially based on pathogenic status of the fibroblasts. By analyzing the molecular mechanism associated with its function, we conclude that let-7i-5p plays an essential role in regulating cell shape and tissue elasticity, cell migration, cell morphology and cytoskeleton, and could serve as a potential target for clinical treatment of urethral stricture patients.

molecular biology↗

bioRxiv2017

Resting heart rate and psychopathy: Findings from the Add Health Survey

Despite the prior linkages of low resting heart rate to antisocial behavior broadly defined, less work has been done examining possible associations between heart rate to psychopathic traits. The small body of research on the topic that has been conducted so far seems to suggest an inverse relationship between the two constructs. A smaller number of studies have found the opposite result, however, and some of the previous studies have been limited by small sample sizes and unrepresentative samples. The current study attempts to help clarify the relationship between resting heart rate and psychopathic traits in a large, nationally representative sample (analytical N ranged from 14,173-14,220) using an alternative measure of psychopathic traits that is less focused on antisocial processes, and rooted in personality traits. No significant relationship between heart rate and psychopathic traits, or heart rate and a measure of cold heartedness, was found after controlling for age, sex, and race. Implications of the findings, study limitations, and directions for future research are discussed.

physiology↗