Functional association between the nef gene product and gag-pol region of HIV-1

AbstractNef gene function is diverse among virus isolates of primate immunodeficiency viruses. We found differential effects of nef mutation on the virus replication between two HIV-1 clones, NL432 and LAI. The nef mutation in NL432 affected the infectivity more severely compared with that in LAI, although the Nef functions of both clones were comparable. Analysis with a series of chimeric viruses between NL432 and LAI revealed that the gag-pol region was responsible for the differential effect of nef mutation. The functional association between Nef and gag-pol suggested that one of the potential targets of Nef was located within the gag-pol region

The complete mitochondrial genome of Anisakis pegreffii Campana-Rouget & Biocca, 1955, (Nematoda, Chromadorea, Rhabditida, Anisakidae) - clarification of mitogenome sequences of the Anisakis simplex species complex

The complete mitochondrial genome of Anisakis pegreffii (former A. simplex A) was determined using the Illumina HiSeq platform. The genome was 14,002 bp in length made up of 36 mitochondrial genes (12 CDSs, 22 tRNAs, and 2 rRNAs). Phylogenetic analysis clarified the mitogenome sequences of the three sibling species of the A. simplex species complex, A. pegreffii, A. simplex sensu stricto and A. berlandi (former A. simplex C)

USP8 prevents aberrant NF-κB and Nrf2 activation by counteracting ubiquitin signals from endosomes

K63-linked ubiquitin chains attached to plasma membrane proteins serve as tags for endocytosis and endosome-to-lysosome sorting. USP8 is an essential deubiquitinase for the maintenance of endosomal functions. Prolonged depletion of USP8 leads to cell death, but the major effects on cellular signaling pathways are poorly understood. Here, we show that USP8 depletion causes aberrant accumulation of K63-linked ubiquitin chains on endosomes and induces immune and stress responses. Upon USP8 depletion, two different decoders for K63-linked ubiquitin chains, TAB2/3 and p62, were recruited to endosomes and activated the TAK1-NF-κB and Keap1-Nrf2 pathways, respectively. Oxidative stress, an environmental stimulus that potentially suppresses USP8 activity, induced accumulation of K63-linked ubiquitin chains on endosomes, recruitment of TAB2, and expression of the inflammatory cytokine. The results demonstrate that USP8 is a gatekeeper of misdirected ubiquitin signals and inhibits immune and stress response pathways by removing K63-linked ubiquitin chains from endosomes.</p

Diagonistic Apraxia: A Unique Case of Corpus Callosal Disconnection Syndrome and Neuromyelitis Optica Spectrum Disorder

Diagonistic apraxia is a corpus callosal disconnection syndrome. Callosal lesions in Neuromyelitis optica spectrum disorder (NMOSD) have been reported, but callosal disconnection syndrome are rare. A 48-year-old woman was treated for fever and a cough before hospitalization. Her fever abated immediately, but she had balance problems in walking and standing. She also had slurred speech. On neurological examination, she had diagonistic apraxia. Her left hand moved in an uncoordinated way when she moved her right hand: changing her clothes for example or using a knife and fork. She had to instruct her left hand to stop. She had dysarthria and her gait was wide-based. She also had many callosal disconnection syndrome symptoms such as alexia of left visual field, left ear extinction, crossed optic ataxia. Using FLAIR and DWI MRI, a mixture of low and high signals, a so-called “marbled pattern,” was seen in the corpus callosum. Since the patient was positive for anti-aquaporin-4 antibody, she was diagnosed with NMOSD. After two courses of steroid pulse therapy, the symptoms improved. Here we report diagonistic apraxia and other symptoms of callosal disconnection syndrome in anti-AQP4-positive NMOSD

Impaired cognitive modification for estimating time duration in Parkinson’s disease

Parkinson\u27s disease (PD) is associated with various cognitive impairments. However, the nature of cognitive modification in patients with PD remains to be elucidated. In the present study, we examined whether patients with PD could correct and maintain subjective time duration and line length estimation. After training sessions, in which participants repeatedly memorized either a duration or a length, we compared a learning performance in 20 PD patients with 20 healthy controls. In the case of duration in the PD patients, the learned durations immediately returned to baseline of pre-training within a few minutes. However, the patients’ ability to learn length estimation remained unimpaired. In contrast, healthy controls were able to retain the learned duration and length estimations. Time compression in PD\u27s internal clock may become entrained to their altered duration estimation even after learning of accurate time duration. These deficits may be associated with disrupting cognitive modification in PD

RNA Modulators of Complex Phenotypes in Mammalian Cells

RNA-mediated gene silencing, in the form of RNA interference (RNAi) or microRNAs (miRNAs) has provided novel tools for gene discovery and validation in mammalian cells. Here, we report on the construction and application of a random small RNA expression library for use in identifying small interfering RNA (siRNA) effectors that can modify complex cellular phenotypes in mammalian cells. The library is based in a retroviral vector and uses convergent promoters to produce unique small complementary RNAs. Using this library, we identify a range of small RNA-encoding gene inserts that overcome resistance to 5-fluorouracil (5-FU)- or tumour necrosis factor alpha (TNF-α)- induced cell death in colorectal cancer cells. We demonstrate the utility of this technology platform by identifying a key RNA effector, in the form of a siRNA, which overcomes cell death induced by the chemotherapeutic 5-FU. The technology described has the potential to identify both functional RNA modulators capable of altering physiological systems and the cellular target genes altered by these modulators

EMPRESS. IX. Extremely Metal-Poor Galaxies are Very Gas-Rich Dispersion-Dominated Systems: Will JWST Witness Gaseous Turbulent High-z Primordial Galaxies?

We present kinematics of 6 local extremely metal-poor galaxies (EMPGs) with low metallicities ($0.016-0.098\ Z_{\odot}$) and low stellar masses ($10^{4.7}-10^{7.6} M_{\odot}$). Taking deep medium-high resolution ($R\sim7500$) integral-field spectra with 8.2-m Subaru, we resolve the small inner velocity gradients and dispersions of the EMPGs with H$\alpha$ emission. Carefully masking out sub-structures originated by inflow and/or outflow, we fit 3-dimensional disk models to the observed H$\alpha$ flux, velocity, and velocity-dispersion maps. All the EMPGs show rotational velocities ($v_{\rm rot}$) of 5--23 km s$^{-1}$ smaller than the velocity dispersions ($\sigma_{0}$) of 17--31 km s$^{-1}$, indicating dispersion-dominated ($v_{\rm rot}/\sigma_{0}=0.29-0.80<1$) systems affected by inflow and/or outflow. Except for two EMPGs with large uncertainties, we find that the EMPGs have very large gas-mass fractions of $f_{\rm gas}\simeq 0.9-1.0$. Comparing our results with other H$\alpha$ kinematics studies, we find that $v_{\rm rot}/\sigma_{0}$ decreases and $f_{\rm gas}$ increases with decreasing metallicity, decreasing stellar mass, and increasing specific star-formation rate. We also find that simulated high-$z$ ($z\sim 7$) forming galaxies have gas fractions and dynamics similar to the observed EMPGs. Our EMPG observations and the simulations suggest that primordial galaxies are gas-rich dispersion-dominated systems, which would be identified by the forthcoming James Webb Space Telescope (JWST) observations at $z\sim 7$.Comment: Submitted to ApJ; After revisio

EMPRESS. XII. Statistics on the Dynamics and Gas Mass Fraction of Extremely-Metal Poor Galaxies

We present demography of the dynamics and gas-mass fraction of 33 extremely metal-poor galaxies (EMPGs) with metallicities of $0.015-0.195~Z_\odot$ and low stellar masses of $10^4-10^8~M_\odot$ in the local universe. We conduct deep optical integral-field spectroscopy (IFS) for the low-mass EMPGs with the medium high resolution ($R=7500$) grism of the 8m-Subaru FOCAS IFU instrument by the EMPRESS 3D survey, and investigate H$\alpha$ emission of the EMPGs. Exploiting the resolution high enough for the low-mass galaxies, we derive gas dynamics with the H$\alpha$ lines by the fitting of 3-dimensional disk models. We obtain an average maximum rotation velocity ($v_\mathrm{rot}$) of $15\pm3~\mathrm{km~s^{-1}}$ and an average intrinsic velocity dispersion ($\sigma_0$) of $27\pm10~\mathrm{km~s^{-1}}$ for 15 spatially resolved EMPGs out of the 33 EMPGs, and find that all of the 15 EMPGs have $v_\mathrm{rot}/\sigma_0<1$ suggesting dispersion dominated systems. There is a clear decreasing trend of $v_\mathrm{rot}/\sigma_0$ with the decreasing stellar mass and metallicity. We derive the gas mass fraction ($f_\mathrm{gas}$) for all of the 33 EMPGs, and find no clear dependence on stellar mass and metallicity. These $v_\mathrm{rot}/\sigma_0$ and $f_\mathrm{gas}$ trends should be compared with young high-$z$ galaxies observed by the forthcoming JWST IFS programs to understand the physical origins of the EMPGs in the local universe.Comment: 18 pages, 9 figures, accepted for publication in Ap