Graphite Nanoeraser

We present here a method for cleaning intermediate-size (5~50nm) contamination from highly oriented pyrolytic graphite. Electron beam deposition causes a continuous increase of carbonaceous material on graphene and graphite surfaces, which is difficult to remove by conventional techniques. Direct mechanical wiping using a graphite nanoeraser is observed to drastically reduce the amount of contamination. After the mechanical removal of contamination, the graphite surfaces were able to self-retract after shearing, indicating that van der Waals contact bonding is restored. Since contact bonding provides an indication of a level of cleanliness normally only attainable in a high-quality clean-room, we discuss potential applications in preparation of ultraclean surfaces.Comment: 10 pages, two figure

The RNA Helicase Mtr4p Modulates Polyadenylation in the TRAMP Complex

SummaryMany steps in nuclear RNA processing, surveillance, and degradation require TRAMP, a complex containing the poly(A) polymerase Trf4p, the Zn-knuckle protein Air2p, and the RNA helicase Mtr4p. TRAMP polyadenylates RNAs designated for decay or trimming by the nuclear exosome. It has been unclear how polyadenylation by TRAMP differs from polyadenylation by conventional poly(A) polymerase, which produces poly(A) tails that stabilize RNAs. Using reconstituted S. cerevisiae TRAMP, we show that TRAMP inherently suppresses poly(A) addition after only 3–4 adenosines. This poly(A) tail length restriction is controlled by Mtr4p. The helicase detects the number of 3′-terminal adenosines and, over several adenylation steps, elicits precisely tuned adjustments of ATP affinities and rate constants for adenylation and TRAMP dissociation. Our data establish Mtr4p as a critical regulator of polyadenylation by TRAMP and reveal that an RNA helicase can control the activity of another enzyme in a highly complex fashion and in response to features in RNA

Multi-Host Model-Based Identification of \u3ci\u3eArmillifer agkistrodontis\u3c/i\u3e (Pentastomida), a New Zoonotic Parasite from China

Background: Pentastomiasis is a rare parasitic infection of humans. Pentastomids are dioecious obligate parasites requiring multiple hosts to complete their life cycle. Despite their worm-like appearance, they are commonly placed into a separate sub-class of the subphylum Crustacea, phylum Arthropoda. However, their systematic position is not uncontested and historically, they have been considered as a separate phylum. Methodology/Principal Findings: An appraisal of Armillifer agkistrodontis was performed in terms of morphology and genetic identification after its lifecycle had been established in a multi-host model, that is, mice and rats as intermediate hosts, and snakes (Agkistrodon acutus and Python molurus) as definitive hosts. Different stages of the parasite, including eggs, larvae and adults, were isolated and examined morphologically using light and electron microscopes. Phylogenetic and cluster analysis were also undertaken, focusing on the 18S rRNA and the Cox1 gene. The time for lifecycle completion was about 14 months, including 4 months for the development of eggs to infectious larvae in the intermediate host and 10 months for infectious larvae to mature in the final host. The main morphological difference between A. armillatus and Linguatula serrata is the number of abdominal annuli. Based on the 18S rRNA sequence, the shortest hereditary distance was found between A. agkistrodontis and Raillietiella spp. The highest degree of homology in the Cox 1 nucleic acid sequences and predicted amino acid sequences was found between A. agkistrodontis and A. armillatus. Conclusion: This is the first time that a multi-host model of the entire lifecycle of A. agkistrodontis has been established. Morphologic and genetic analyses supported the notion that pentastomids should be placed into the phylum Arthropoda

The human red nucleus and lateral cerebellum in supporting roles for sensory information processing

A functional MRI study compared activation in the red nucleus to that in the lateral cerebellar dentate nucleus during passive and active tactile discrimination tasks. The study pursued recent neuroimaging results suggesting that the cerebellum may be more associated with sensory processing than with the control of movement for its own sake. Because the red nucleus interacts closely with the cerebellum, the possibility was examined that activity in red nucleus might also be driven by the requirement for tactile sensory processing with the fingers rather than by finger movement alone. The red and dentate nuclei were about 300% more active (a combination of activation areas and intensities) during passive (non‐motor) tactile stimulation when discrimination was required than when it was not. Thus, the red nucleus was activated by purely sensory stimuli even in the absence of the opportunity to coordinate finger movements or to use the sensory cues to guide movement. The red and dentate nuclei were about 70% more active during active tactile tasks when discrimination was required than when it was not (i.e., for simple finger movements alone). Thus, the red nucleus was most active when the fingers were being used for tactile sensory discrimination. In both the passive and active tactile tasks, the observed activation had a contralateralized pattern, with stronger activation in the left red nucleus and right dentate nucleus. Significant covariation was observed between activity in the red nucleus and the contralateral dentate during the discrimination tasks and no significant correlation between the red nucleus and the contralateral dentate activity was detected during the two non‐discrimination tasks. The observed interregional covariance and contralateralized activation patterns suggest strong functional connectivity during tactile discrimination tasks. Overall, the pattern of findings suggests that the activity in the red nucleus, as in the lateral cerebellum, is more driven by the requirements for sensory processing than by motor coordination per se

Association of N-nitrosodimethylamine exposure with cognitive impairment based on the clues of mice and humans

N-nitrosodimethylamine (NDMA) is an environmental and food contaminant, but limited data to concern whether NDMA has adverse effects on the brain. This study first determined the concentration of NDMA in foods from aquaculture markets in Shenzhen, then analyzed the effects on C57BL/6 mice and further evaluated on the urine samples of elderly Chinese residents with normal cognition (NC, n = 144), cognitive decline (CD, n = 116) and mild cognitive impairment (MCI, n = 123). The excessive rate of NDMA in foods was 3.32% (27/813), with a exceeding range of 4.78–131.00 μg/kg. Behavioral tests showed that 60 days treatment of mice with 3 mg/kg NDMA reduced cognitive performance. Cognitive impairment in human was significantly associated with sex, educational levels, length of residence in Shenzhen, household registration, passive smoking, rice, fresh vegetables, bacon products. NDMA was detected in 55.4% (212/383) of urine samples, with a median concentration of 0.23 μg/L (1.20 × 10 –7–157.39 μg/L). The median concentration for NC, CD and MCI were 0.32, 0.27, and 0 μg/L, respectively. The urinary NDMA concentration had a strong negative correlation with cognitive impairment (Kendall’s Tau-b = −0.89, P = 0.024). The median estimated daily intake (EDI) of NDMA was determined to be 6.63 ng/kg-bw/day. Taken together, there appears to be an association between NDMA and human and murine cognition, which provides a new clue to Alzheimer’s disease (AD)

Inefficient Translocation of Preproinsulin Contributes to Pancreatic β Cell Failure and Late-onset Diabetes

Among the defects in the early events of insulin biosynthesis, proinsulin misfolding and endoplasmic reticulum (ER) stress have drawn increasing attention as causes of β cell failure. However, no studies have yet addressed potential defects at the cytosolic entry point of preproinsulin into the secretory pathway. Here, we provide the first evidence that inefficient translocation of preproinsulin (caused by loss of a positive charge in the n region of its signal sequence) contributes to β cell failure and diabetes. Specifically, we find that, after targeting to the ER membrane, preproinsulin signal peptide (SP) mutants associated with autosomal dominant late-onset diabetes fail to be fully translocated across the ER membrane. The newly synthesized, untranslocated preproinsulin remains strongly associated with the ER membrane, exposing its proinsulin moiety to the cytosol. Rather than accumulating in the ER and inducing ER stress, untranslocated preproinsulin accumulates in a juxtanuclear compartment distinct from the Golgi complex, induces the expression of heat shock protein 70 (HSP70), and promotes β cell death. Restoring an N-terminal positive charge to the mutant preproinsulin SP significantly improves the translocation defect. These findings not only reveal a novel molecular pathogenesis of β cell failure and diabetes but also provide the first evidence of the physiological and pathological significance of the SP n region positive charge of secretory proteins

Protective role for collectin‐11 in rheumatoid arthritis in mice

OBJECTIVE. Collectin-11 (CL-11) is a soluble C-type lectin, a mediator of innate immunity. Its role in autoimmune disorders is unknown. The goal of this study was to determine the role of CL-11 in a mouse model of rheumatoid arthritis (RA). METHODS. A murine collagen-induced arthritis (CIA) model, combining both gene deletion of Colec11 and recombinant (rCL-11) treatment approaches were employed. Joint inflammation and tissue destruction, circulating levels of inflammatory cytokines and adaptive immune responses were assessed in CIA mice. Splenic CD11c(+) cells were used to examine the influence of CL-11 on antigen presenting cell (APC) function. Serum levels of CL-11 in RA patients were also examined. RESULTS. Colec11(−/−) mice developed more severe arthritis than WT mice (as determined by disease incidence, clinical arthritis scores and histopathology; P<0.05). Disease severity is associated with significantly enhanced APC activation, Th1/Th17 responses, pathogenic IgG2a production and joint inflammation, as well as elevated circulating levels of inflammatory cytokines. In vitro analysis of CD11c(+) cells revealed that CL-11 is critical for suppression of APC activation and function. Pharmacological treatment of mice with rCL-11 reduced the severity of CIA in mice. Analysis of human blood samples revealed that serum levels of CL-11 was lower in RA patients (n=51) compared to healthy controls (n=53), a serum CL-11 reduction also displays a negative relationship with DAS28, ESR and CRP (P<0.05). CONCLUSION. Our findings demonstrate a novel role for CL-11 in protection against RA, suggesting the underlying mechanism involved suppression of APC activation and subsequent T cell responses

A multimodal brain imaging dataset on sleep deprivation in young and old humans

The Stockholm Sleepy Brain Study I is a functional brain imaging study of 48 younger (20-30 years) and 36 older (65-75 years) healthy participants, with magnetic resonance imaging after normal sleep and partial sleep deprivation in a crossover design. We performed experiments investigating emotional mimicry, empathy for pain, and cognitive reappraisal, as well as resting state functional magnetic resonance imaging (fMRI). We also acquired T1- and T2-weighted structural images and diffusion tensor images (DTI). On the night before imaging, participants were monitored with ambulatory polysomnography and were instructed to sleep either as usual or only three hours. Participants came to the scanner the following evening. Besides MRI scanning, participants underwent behavioral tests and contributed blood samples, which have been stored in a biobank and used for DNA analyses. Participants also completed a variety of self-report measures. The resulting multimodal dataset may be useful for hypothesis generation or independent validation of effects of sleep deprivation and aging, as well as investigation of cross-sectional associations between the different outcomesNoneManuscrip