Humanized NOD/SCID/IL2Rgamma(null) mice transplanted with hematopoietic stem cells under nonmyeloablative conditions show prolonged life spans and allow detailed analysis of human immunodeficiency virus type 1 pathogenesis

In a previous study, we demonstrated that humanized NOD/SCID/IL2Rγ^null (hNOG) mice constructed with human hematopoietic stem cells (HSCs) allow efficient human immunodeficiency virus type 1 (HIV-1) infection. However, HIV-1 infection could be monitored for only 43 days in the animals due to their short life spans. By transplanting HSCs without any myeloablation methods, the mice successfully survived longer than 300 days with stable engraftment of human cells. The mice showed high viremia state for more than the 3 months examined, with systemic HIV-1 infection and gradual decrease of CD4⁺ T cells analogous to that in humans. These capacities of the hNOG mice are very attractive for modeling mechanisms of AIDS progression and therapeutic strategy.     

Visual feedback is not necessary for the learning of novel dynamics

Background

When learning to perform a novel sensorimotor task, humans integrate multi-modal sensory feedback such as vision and proprioception in order to make the appropriate adjustments to successfully complete the task. Sensory feedback is used both during movement to control and correct the current movement, and to update the feed-forward motor command for subsequent movements. Previous work has shown that adaptation to stable dynamics is possible without visual feedback. However, it is not clear to what degree visual information during movement contributes to this learning or whether it is essential to the development of an internal model or impedance controller.

Methodology/Principle Findings

We examined the effects of the removal of visual feedback during movement on the learning of both stable and unstable dynamics in comparison with the case when both vision and proprioception are available. Subjects were able to learn to make smooth movements in both types of novel dynamics after learning with or without visual feedback. By examining the endpoint stiffness and force after learning it could be shown that subjects adapted to both types of dynamics in the same way whether they were provided with visual feedback of their trajectory or not. The main effects of visual feedback were to increase the success rate of movements, slightly straighten the path, and significantly reduce variability near the end of the movement.

Conclusions/Significance

These findings suggest that visual feedback of the hand during movement is not necessary for the adaptation to either stable or unstable novel dynamics. Instead vision appears to be used to fine-tune corrections of hand trajectory at the end of reaching movements.     

Natural attenuation of dissolved uranium within a small stream of central Japan

In this study, we investigated the natural attenuation of the uranium (U) load in the surface water within a humid forest in Japan. Surface water and sediments that had accumulated behind dams in the area were investigated in terms of their mineralogy and chemistry. The chemistry of the surface water was analyzed by field measurements of pH, dissolved oxygen (DO) concentration, and electrical conductivity (EC), as well as laboratory analyses via inductively coupled plasma mass spectrometry and ion chromatography. We determined U levels in the surface water; the distribution of U in phases within the sediment was estimated using a sequential extraction procedure. The results of this investigation indicate that U, which within the study area is derived from pegmatites at a mine, is attenuated by uptake onto the surface of organic material and uptake by amorphous material that forms over time within the dammed sediments. The U concentration within the sediment was as great as 8 mg kg⁻¹, whereas the downstream U concentrations and loads in surface water decreased from 1.69 μg l⁻¹ and 11.0 mg min⁻¹ to 0.115 μg l⁻¹ and 2.31 mg min⁻¹, respectively.     

Cocaine Modulates the Neuronal Endosomal System and Extracellular Vesicles in a Sex-Dependent Manner

Neurochemical Research - In multiple neurodevelopmental and neurodegenerative disorders, endosomal changes correlate with changes in exosomes. We examined this linkage in the brain of mice that...     

Transmission of genomic instability from a single irradiated human chromosome to the progeny of unirradiated cells

Ionizing radiation can induce chromosome instability that is transmitted over many generations after irradiation in the progeny of surviving cells, but it remains unclear why this instability can be transmitted to the progeny. To acquire knowledge about the transmissible nature of genomic instability, we transferred an irradiated human chromosome into unirradiated mouse recipient cells by microcell fusion and examined the stability of the transferred human chromosome in the microcell hybrids. The transferred chromosome was stable in all six microcell hybrids in which an unirradiated human chromosome had been introduced. In contrast, the transferred chromosome was unstable in four out of five microcell hybrids in which an irradiated human chromosome had been introduced. The aberrations included changes in the irradiated chromosome itself and rearrangements with recipient mouse chromosomes. Thus the present study demonstrates that genomic instability can be transmitted to the progeny of unirradiated cells by a chromosome exposed to ionizing radiation, implying that the instability is caused by the irradiated chromosome itself and also that the instability is induced by the nontargeted effect of radiation.     

Molecular characterization of GDD1/TMEM16E, the gene product responsible for autosomal dominant gnathodiaphyseal dysplasia

The human GDD1/TMEM16E gene has been found to be mutated in gnathodiaphyseal dysplasia, an unusual skeletal syndrome with autosomal dominant inheritance. The molecular and biochemical function(s) of GDD1 protein has not yet been elucidated. In this study, we examined the murine GDD1 gene expression pattern during embryonic development, and characterized the cellular and tissue localizations of its gene product using a GDD1-specific antibody. In the developing embryos, GDD1 mRNA expression was principally associated with differentiating and developing somites, with a highly complex spatiotemporal pattern that involved the myotomal and sclerotomal lineages of somites. Biochemical studies indicated that GDD1 protein is an integral membrane glycoprotein that resides predominantly in intracellular vesicles. Immunohistochemical analysis showed a high level of murine GDD1 protein expression in cardiac and skeletal muscle tissues, and in growth-plate chondrocytes and osteoblasts in bone. These observations suggest diverse cellular role(s) of GDD1 in the development of musculoskeletal system.     

Adjuvant effect of CpG-oligodeoxynucleotide in anti-fungal chemotherapy against fatal infection with Cryptococcus neoformans in mice

Cryptococcal meningoencephalitis is a life-threatening infectious disease in immunocompromised patients. Unmethylated CpG-oligodeoxynucleotides (CpG-ODN) protects hosts in a mouse model. In the present study, we tested the adjuvant effect of CpG-ODN in anti-fungal chemotherapy. Administration of either fluconazole (FLCZ) or CpG-ODN was effective in extending survival, accelerating clearance of fungi and preventing disseminated infection. Combination of both agents provided more beneficial effect than either agent alone. Cytokine balance in the infected lungs was biased to Th1-type response by CpGODN, while FLCZ did not further promote. These results suggest that CpG-ODN is a promising adjuvant in chemotherapy against this infection.     

Site-specific and asymmetric hydrolysis of prochiral 2-phenyl-1,3-propanediol diacetate by a bacterial esterase from an isolated strain

Bacillus cereus 809A and Burkholderia sp. 711C were isolated from soil. These strains demonstrate hydrolysis activity towards prochiral 2-phenyl-1,3-propanediol diacetate and accumulated the corresponding chiral monoacetates into the reaction mixture. When 2-phenyl 1,3-propanediol diacetate was used as a substrate, the produced monoacetates with Burkholderia sp. 711C were obtained in a racemic form but that produced by Bacillus cereus 809A showed an excess of the (S)-form. The resting cell reaction revealed that for Bacillus cereus 809A, there was an enrichment of one of the enantiomers of the monoacetate such that the enantiomeric excess (e.e.) of the (S)-form was over 95%. The purified enzyme from Bacillus cereus 809A hydrolyzed diacetate to monoacetate, and the e.e. value of the (S)-form increased by prolonged reaction in a way similar to the resting cell reaction. From N-terminal amino acids, this esterase is conserved in some strains of Bacillus for which the genomic sequences have been reported.     

Temporal and spatial variation of the phytoplankton assemblage in the eastern Indian sector of the Southern Ocean in summer 2001/2002

The abundance and species composition of phytoplankton were investigated at stations in a permanently ice-free (61°S) and seasonally ice-covered area (64°S and 66°30′S) in the eastern Indian sector of the Southern Ocean between November 2001 and March 2002. Although a phytoplankton bloom occurred just after retreat of the sea ice at both stations in the seasonally ice-covered area, vertical stability of the water column during the bloom was weak at the most southerly station. This shows that a bloom can form even under weak vertical stability. In the bloom, diatoms dominated under weak vertical stability and Phaeocystis under strong vertical stability. In the latter case, ice algae largely contributed to development of the bloom. In the later observation period, a subsurface chlorophyll maximum (SCM) was observed at 61°S and 64°S. Species composition was different between the mixed layer and SCM at 64°S, but was uniform with depth at 61°S, indicating that the SCM is formed by different mechanisms.