Miracle-dz/UniFAR-FTUs huggingface dataset:
The Primed Ebolavirus Glycoprotein (19-Kilodalton GP1,2): Sequence and Residues Critical for Host Cell Binding

ABSTRACT Entry of ebolavirus (EBOV) into cells is mediated by its glycoprotein (GP1,2), a class I fusion protein whose structure was recently determined (J. E. Lee et al., Nature 454:177-182, 2008). Here we confirmed two major predictions of the structural analysis, namely, the residues in GP1 and GP2 that remain after GP1,2 is proteolytically primed by endosomal cathepsins for fusion and residues in GP1 that are critical for binding to host cells. Mass spectroscopic analysis indicated that primed GP1,2 contains residues 33 to 190 of GP1 and all residues of GP2. The location of the receptor binding site was determined by a two-pronged approach. We identified a small receptor binding region (RBR), residues 90 to 149 of GP1, by comparing the cell binding abilities of four RBR proteins produced in high yield. We characterized the binding properties of the optimal RBR (containing GP1 residues 57 to 149) and then conducted a mutational analysis to identify critical binding residues. Substitutions at four lysines (K95, K114, K115, and K140) decreased binding and the ability of RBR proteins to inhibit GP1,2-mediated infection. K114, K115, and K140 lie in a small region modeled to be located on the top surface of the chalice following proteolytic priming; K95 lies deeper in the chalice bowl. Combined with those of Lee et al., our findings provide structural insight into how GP1,2 is primed for fusion and define the core of the EBOV RBR (residues 90 to 149 of GP1) as a highly conserved region containing a two-stranded β-sheet, the two intra-GP1 disulfide bonds, and four critical Lys residues.
The detection of dementia in the primary care setting.

BACKGROUND Recognition and medical record documentation of dementia in the primary care setting are thought to be poor. To our knowledge, previous studies have not examined these issues in private practice office settings within the United States. OBJECTIVE To determine the rate of unrecognized and undocumented dementia in a primary care internal medicine private practice. METHODS This was a cross-sectional study of 297 ambulatory persons aged 65 years and older attending an internal medicine private group practice within an Asian American community of Honolulu, Hawaii. Of the subjects, 95% had been with their current primary care physician for at least 1 year. Each subject's primary care physician noted the presence or absence of dementia by questionnaire at the time of an office visit. An investigating physician (V.G.V.) subsequently assessed cognitive function using the Cognitive Abilities Screening Instrument, and confirmed the presence of dementia and its severity, if present, using Benson and Cummings' criteria and the Clinical Dementia Rating Scale, respectively. A trained research assistant completed telephone interviews to proxy informants for collateral information concerning cognition, behavior, and occupational or social function. Subjects' outpatient medical records were reviewed for documentation of problems with cognition. RESULTS Twenty-six cases of dementia were identified. Of these 26, 17 (65%) (95% confidence interval, 44.3-82.8) were not documented in outpatient medical records; of 18 patients, 12 (67%) (95% confidence interval, 40.9-86.7) were not thought to have dementia by their physicians at the time of the office visit. Recognition and documentation rates increased with advancing stage of disease. CONCLUSION Dementia is often unrecognized and undocumented in private practice settings. Arch Intern Med. 2000;160:2964-2968
Mutation screening of the IL-1 receptor antagonist gene in chronic non-bacterial osteomyelitis of childhood and adolescence.

OBJECTIVES Chronic non-bacterial osteomyelitis CNO is an inflammatory disorder of the musculoskeletal system with unknown etiology. In addition to bone inflammation, patients may present with inflammatory involvement of other tissues including, e.g., skin. Recently, a novel syndrome due to deficiency of interleukin-1 receptor antagonist (IL1RN), DIRA has been identified. Clinically the syndrome is characterized by neonatal onset of pustular dermatosis, periostitis and chronic sterile multifocal osteomyelitis, strongly resembling CNO. Homozygous mutations of IL1RN have been identified and resulted in a truncated protein that is not secreted, hence leaving the action of interleukin-1 unopposed. METHODS Because of similar clinical, radiological and histological features of CNO and DIRA, we hypothesized that both disorders might share a common autoinflammatory process. Thus, we searched for the presence of mutations in the interleukin-1 receptor antagonist gene in 60 patients diagnosed with CNO. RESULTS In one patient with chronic multifocal osteomyelitis a heterozygous missense variant: c.281G>T (p.Cys94Phe) was detected. In the other patients only frequent polymorphisms were found. CONCLUSIONS Our findings were not able to confirm mutations in IL1RN being an important contributing factor to the pathogenesis of CNO.
Brain oscillations: ideal scenery to understand the neurovascular coupling.

PURPOSE OF REVIEW This review discusses our current understanding of the neurovascular coupling in the neocortex with particular emphasis on brain oscillations. RECENT FINDINGS After two decades of developments in neuroimaging, we do not know thus far how blood perfusion is regulated regionally in our brain, a statement endorsed by the existing uncertainty about the strategies it employs for dynamic housekeeping and oxidative metabolism readjustment during evoked and ongoing processing. What is more, we have no clear idea why such a regulation is inhomogeneous for the entire neocortex, with special distinctions in those brain areas belonging to what has been named the resting default networks. In the light of recent findings about blood supplying mechanisms during brain oscillations, we have to regrettably admit that further experiments need yet to be carried out to have a better understanding of the neurovascular coupling in the cerebral cortex of mammals. SUMMARY Understanding the neurovascular coupling, and hence the associated blood oxygenation level-dependent signal, will help us to design revolutionary therapies for several brain disorders as well as to establish new protocols for their diagnosis through neuroimaging. The brain oscillations provide us an ideal scenario for that end.
Astrocyte dysfunction in Alzheimer disease

Astrocytes are glial cells that are distributed throughout the central nervous system in an arrangement optimal for chemical and physical interaction with neuronal synapses and brain blood supply vessels. Neurotransmission modulates astrocytic excitability by activating an array of cell surface receptors and transporter proteins, resulting in dynamic changes in intracellular Ca2+ or Na+. Ionic and electrogenic astrocytic changes, in turn, drive vital cell nonautonomous effects supporting brain function, including regulation of synaptic activity, neuronal metabolism, and regional blood supply. Alzheimer disease (AD) is associated with aberrant oligomeric amyloid β generation, which leads to extensive proliferation of astrocytes with a reactive phenotype and abnormal regulation of these processes. Astrocytic morphology, Ca2+ responses, extracellular K+ removal, glutamate transport, amyloid clearance, and energy metabolism are all affected in AD, resulting in a deleterious set of effects that includes glutamate excitotoxicity, impaired synaptic plasticity, reduced carbon delivery to neurons for oxidative phosphorylation, and dysregulated linkages between neuronal energy demand and regional blood supply. This review summarizes how astrocytes are affected in AD and describes how these changes are likely to influence brain function. © 2017 Wiley Periodicals, Inc.
Transcription-Dependent Increase in Multiple Classes of Base Substitution Mutations in Escherichia coli

ABSTRACT We showed previously that transcription in Escherichia coli promotes C · G-to-T · A transitions due to increased deamination of cytosines to uracils in the nontranscribed but not the transcribed strand (A. Beletskii and A. S. Bhagwat, Proc. Natl. Acad. Sci. USA 93:13919-13924, 1996). To study mutations other than that of C to T, we developed a new genetic assay that selects only base substitution mutations and additionally excludes C · G to T · A transitions. This novel genetic reversion system is based on mutations in a termination codon and involves positive selection for resistance to bleomycin or kanamycin. Using this genetic system, we show here that transcription from a strong promoter increases the level of non-C-to-T as well as C-to-T mutations. We find that high-level transcription increases the level of non-C-to-T mutations in DNA repair-proficient cells in three different sequence contexts in two genes and that the rate of mutation is higher by a factor of 2 to 4 under these conditions. These increases are not caused by a growth advantage for the revertants and are restricted to genes that are induced for transcription. In particular, high levels of transcription do not create a general mutator phenotype in E. coli. Sequence analysis of the revertants revealed that the frequency of several different base substitutions increased upon transcription of the bleomycin resistance gene and that G · C-to-T · A transversions dominated the spectrum in cells transcribing the gene. These results suggest that high levels of transcription promote many different spontaneous base substitutions in E. coli.
Endothelial cell effect on smooth muscle cell collagen synthesis.

UNLABELLED Extracellular matrix (ECM) constitutes the bulk of mature intimal hyperplastic lesions. To determine if endothelial cells (ECs) inhibit smooth muscle cell (SMC) collagen synthesis, bovine aortic SMCs were cultured on plastic semipermeable membranes either alone or opposite ECs. SMCs were pulsed with 4 microCi/ml [3H]proline for 3 days and collagen synthesis was measured as trichloroacetic acid-precipitable counts in conditioned media and in cell lysate fractions. Each was standardized to SMC DNA (cpm/microgram DNA). EC effect on SMC gene expression of type I collagen was studied using Northern analysis. To determine whether TGF-beta 1 activation is involved in collagen synthesis regulation, parallel studies were performed in the presence of a neutralizing antibody to TGF-beta 1 (25 micrograms/ml) or aprotinin (a plasmin inhibitor, 200 micrograms/ml). SMCs cocultured with ECs were either untreated or treated with 5 ng/ml TGF-beta 1. The effect of culture substrate on EC-SMC interaction was studied by repeating experiments on type I collagen (CI), matrigel (MG), fibronectin (FN), and type IV collagen (CIV). RESULTS Compared to SMCs cultured alone, ECs inhibited SMC collagen synthesis by 40 +/- 5% (P < 0.01) and gene expression of type I collagen by 60 +/- 4% (P < 0.01). The addition of neutralizing TGF-beta 1 Ab or aprotinin to SMCs cultured alone had no effect on collagen synthesis. Collagen synthesis in SMCs cultured alone on MG was reduced by 49% and by 16% on CIV when compared to SMCs cultured on plastic (plastic: 100 +/- 12% vs MG: 51 +/- 15% vs CIV: 84 +/- 18%, P = 0.10). Collagen synthesis was increased in SMCs cultured alone on FN (195 +/- 14% vs plastic: 100 +/- 12, P < 0.001) and CI (207 +/- 17 vs plastic: 100 +/- 12, P < 0.001). ECs decreased SMC collagen synthesis by 18 +/- 4% when cocultured on CI (P < 0.05) and by 22 +/- 2% when cocultured on MG (P < 0.05). FN prevented EC inhibition of SMC collagen synthesis. CONCLUSIONS ECs inhibit SMC collagen synthesis and downregulate SMC type I collagen gene expression. TGF-beta 1 does not appear to be involved in this process. Culture substrate composition can affect SMC collagen synthesis and EC modulation of this process.
Redox-Regulated Recruitment of the Transcriptional Coactivators CREB-Binding Protein and SRC-1 to Hypoxia-Inducible Factor 1α

ABSTRACT Hypoxia-inducible factor 1α (HIF-1α) functions as a transcription factor that is activated by decreased cellular oxygen concentrations to induce expression of a network of genes involved in angiogenesis, erythropoiesis, and glucose homeostasis. Here we demonstrate that two members of the SRC-1/p160 family of transcriptional coactivators harboring histone acetyltransferase activity, SRC-1 and transcription intermediary factor 2 (TIF2), are able to interact with HIF-1α and enhance its transactivation potential in a hypoxia-dependent manner. HIF-1α contains within its C terminus two transactivation domains. The hypoxia-inducible activity of both these domains was enhanced by either SRC-1 or the CREB-binding protein (CBP)/p300 coactivator. Moreover, at limiting concentrations, SRC-1 produced this effect in synergy with CBP. Interestingly, this effect was strongly potentiated by the redox regulatory protein Ref-1, a dual-function protein harboring DNA repair endonuclease and cysteine reducing activities. These data indicate that all three proteins, CBP, SRC-1, and Ref-1, are important components of the hypoxia signaling pathway and have a common function in regulation of HIF-1α function in hypoxic cells. Given the absence of cysteine residues in one of the Ref-1-regulated transactivation domains of HIF-1α, it is thus possible that Ref-1 functions in hypoxic cells by targeting critical steps in the recruitment of the CBP–SRC-1 coactivator complex.
DUST: Dual Union of Spatio-Temporal Subspaces for Monocular Multiple Object 3D Reconstruction

We present an approach to reconstruct the 3D shape of multiple deforming objects from incomplete 2D trajectories acquired by a single camera. Additionally, we simultaneously provide spatial segmentation (i.e., we identify each of the objects in every frame) and temporal clustering (i.e., we split the sequence into primitive actions). This advances existing work, which only tackled the problem for one single object and non-occluded tracks. In order to handle several objects at a time from partial observations, we model point trajectories as a union of spatial and temporal subspaces, and optimize the parameters of both modalities, the non-observed point tracks and the 3D shape via augmented Lagrange multipliers. The algorithm is fully unsupervised and results in a formulation which does not need initialization. We thoroughly validate the method on challenging scenarios with several human subjects performing different activities which involve complex motions and close interaction. We show our approach achieves state-of-the-art 3D reconstruction results, while it also provides spatial and temporal segmentation.
Overlap of Interaction Domains Indicates a Central Role of the P Protein in Assembly and Regulation of the Borna Disease Virus Polymerase Complex*

The active polymerase complex of Borna disease virus is composed of the viral proteins N, P, and L. The viral X (negative regulatory factor) protein acts as a regulator of polymerase activity. Interactions of P with N and X were previously studied, but interactions with L were poorly defined. Using a mammalian two-hybrid system, we observed that L specifically interacts with P but not with N, X, or itself. Mapping of the L-binding domain in the P molecule revealed that it overlaps with two adjacent domains required for multimerization and interaction with N. Competition experiments showed that the interaction between L and P was inefficient when N was present, indicating that L may preferentially interact with free P in infected cells. Interestingly, a multimerization-defective P mutant maintained the ability to interact with L, N, and X but failed to support reporter gene expression from an artificial Borna disease virus minigenome. Furthermore, dominant negative effects on minigenome activity were only observed when P mutants with an intact multimerization domain were used, suggesting that P multimers, rather than monomers, exhibit biological activity. P mutants lacking functional interaction domains for L or N still formed complexes with these viral proteins when wild-type P was available as a bridging molecule, indicating that P multimers have the potential to act as scaffolds on which the RNA polymerase complex is assembled.
Iron Transport and Metabolism in Escherichia, Shigella, and Salmonella

Iron is an essential element for Escherichia, Salmonella, and Shigella species. The acquisition of sufficient amounts of iron is difficult in many environments, including the intestinal tract, where these bacteria usually reside. ABSTRACT Iron is an essential element for Escherichia, Salmonella, and Shigella species. The acquisition of sufficient amounts of iron is difficult in many environments, including the intestinal tract, where these bacteria usually reside. Members of these genera have multiple iron transport systems to transport both ferrous and ferric iron. These include transporters for free ferrous iron, ferric iron associated with chelators, and heme. The numbers and types of transport systems in any species reflect the diversity of niches that it can inhabit. Many of the iron transport genes are found on mobile genetic elements or pathogenicity islands, and there is evidence of the spread of the genes among different species and pathotypes. This is notable among the pathogenic members of the genera in which iron transport systems acquired by horizontal gene transfer allow the bacteria to overcome host innate defenses that act to restrict the availability of iron to the pathogen. The need for iron is balanced by the need to avoid iron overload since excess iron is toxic to the cell. Genes for iron transport and metabolism are tightly regulated and respond to environmental cues, including iron availability, oxygen, and temperature. Master regulators, the iron sensor Fur and the Fur-regulated small RNA (sRNA) RyhB, coordinate the expression of iron transport and cellular metabolism genes in response to the availability of iron.
Hemispatial neglect reflected on visual memory.

PURPOSE Recent studies of hemispatial neglect have revealed both lateralized and nonlateralized attention mechanisms contributing to the syndrome. In addition, neglect patients show impaired spatial working memory and diminished working memory capacity. The aim of this study was to investigate, how neglect would be reflected in their performances in commonly used clinical visual memory tests. METHODS Twelve patients with right hemisphere lesions and left neglect and twelve matched controls were assessed with the Behavioural Inattention Test, the visual reproduction of the WMS-R, the object memory test, the Rey figure test and the list learning test. Visuo-spatial span was explored with the Corsi block test. RESULTS The severity of neglect was significantly associated with the naming of objects from the left side, with the copying of the Rey figure and with the immediate visual reproduction of the WMS-R. In comparison to the matched controls, the patients named and copied fewer items from both sides and showed impaired immediate and delayed recall of visual material, more so from the left side. After recovery, patients were still impaired in their visual search, whereas their immediate reproduction of visual material was no longer significantly different from the control subjects. The deficit in delayed recall of visual material persisted and was lateralized to the left side of the recollected memories. The role of hemianopia was analyzed. CONCLUSIONS Patients with neglect exhibited spatial working memory bias and diminished nonlateralized attention capacity in encoding and immediate recall. The deficit in delayed recall was lateralized to the left side of memorized material.
Sleep deprivation effects on the activity of the hypothalamic–pituitary–adrenal and growth axes: potential clinical implications

Although several studies have shown that sleep deprivation is associated with increased slow wave sleep during the recovery night, the effects of sleep deprivation on cortisol and growth hormone (GH) secretion the next day and recovery night have not been assessed systematically. We hypothesized that increased slow wave sleep postsleep deprivation is associated with decreased cortisol levels and that the enhanced GH secretion is driven by the decreased activity of the HPA axis.
Fully embedded board-level guided-wave optoelectronic interconnects

A fully embedded board-level guided-wave optical interconnection is presented to solve the packaging compatibility problem. All elements involved in providing high-speed optical communications within one board are demonstrated. Experimental results on a 12-channel linear array of thin-film polyimide waveguides, vertical-cavity surface-emitting lasers (VCSELs) (42 /spl mu/m), and silicon MSM photodetectors (10 /spl mu/m) suitable for a fully embedded implementation are provided. Two types of waveguide couplers, titled gratings and 45/spl deg/ total internal reflection mirrors, are fabricated within the polyimide waveguides. Thirty-five to near 100% coupling efficiencies are experimentally confirmed. By doing so, all the real estate of the PC board surface are occupied by electronics, and therefore one only observes the performance enhancement due to the employment of optical interconnection but does not worry about the interface problem between electronic and optoelectronic components unlike conventional approaches. A high speed 1-48 optical clock signal distribution network for Cray T-90 super computer is demonstrated. A waveguide propagation loss of 0.21 dB/cm at 850 nm was experimentally confirmed for the 1-48 clock signal distribution and for point-to-point interconnects. The feasibility of using polyimide as the interlayer dielectric material to form hybrid three-dimensional interconnects is also demonstrated. Finally, a waveguide bus architecture is presented, which provides a realistic bidirectional broadcasting transmission of optical signals. Such a structure is equivalent to such IEEE standard bus protocols as VME bus and FutureBus.