Miracle-dz/UniFAR-FTUs huggingface dataset:
Assay for Fusion of L . pneumophila-containing Vacuoles with L ysosomes Using Acid Phosphatase Q

Legionella pneumophila multiplies in a novel intracellular vacuole in mononuclear phagocytes (1). In this paper, the interaction between this L. pneumophilacontaining vacuole and host cell lysosomes is examined. Some intracellular pathogens, such as Toxoplasma gondii (2), Mycobacterium tuberculosis (3, 4), Mycobacterium microti (5), Chlamydia psittaci (6), and Encephalitozoon cuniculi (7, 8) have been repor ted to inhibit fusion o f phagosomes with lysosomes. Others, such as Leishmania (9-13) and Mycobacterium lepraemurium (5), have been repor ted not to inhibit fusion, and they are apparently able to survive within the normally inhospitable milieu of the phagolysosome. Still o ther intracellular pathogens such as Trypanosoma cruzi have been shown to avoid the unfavorable env i ronment o f the phagolysosome al together by escaping into the host cell cytoplasm (14, 15). T h e host cells in these studies have almost invariably been mouse peri toneal macrophages or mouse cell lines. This paper demonstra tes that (a) L. pneumophila inhibits phagosome-lysosome fusion in human monocytes. T h e L. pneumophila-containing vacuole does not fuse with ei ther pr imary or secondary lysosomes; (b) this inhibition is partially overcome by coating the bacteria with ant ibody or activating the monocytes; and (c) the inhibition is not influenced by inhibiting bacterial protein synthesis with erythromycin.
Multi-Factored Gene-Gene Proximity Measures Exploiting Biological Knowledge Extracted from Gene Ontology: Application in Gene Clustering

To describe the cellular functions of proteins and genes, a potential dynamic vocabulary is Gene Ontology (GO), which comprises of three sub-ontologies namely, Biological-process, Cellular-component, and Molecular-function. It has several applications in the field of bioinformatics like annotating/measuring gene-gene or protein-protein semantic similarity, identifying genes/proteins by their GO annotations for disease gene and target discovery, etc. To determine semantic similarity between genes, several semantic measures have been proposed in literature, which involve information content of GO-terms, GO tree structure, or the combination of both. But, most of the existing semantic similarity measures do not consider different topological and information theoretic aspects of GO-terms collectively. Inspired by this fact, in this article, we have first proposed three novel semantic similarity/distance measures for genes covering different aspects of GO-tree. These are further implanted in the frameworks of well-known multi-objective and single-objective based clustering algorithms to determine functionally similar genes. For comparative analysis, 10 popular existing GO based semantic similarity/distance measures and tools are also considered. Experimental results on Mouse genome, Yeast, and Human genome datasets evidently demonstrate the supremacy of multi-objective clustering algorithms in association with proposed multi-factored similarity/distance measures. Clustering outcomes are further validated by conducting some biological/statistical significance tests. Supplementary information is available at https://www.iitp. ac.in/sriparna/journals.html.
Progressive Muscular Dystrophy in (cid:97) -Sarcoglycan–deficient Mice

Limb-girdle muscular dystrophy type 2D (LGMD 2D) is an autosomal recessive disorder caused by mutations in the (cid:97) -sarcoglycan gene. To determine how (cid:97) -sarcoglycan deficiency leads to muscle fiber degeneration, we generated and analyzed (cid:97) -sarcoglycan– deficient mice. Sgca- null mice developed progressive muscular dystrophy and, in contrast to other animal models for muscular dystrophy, showed ongoing muscle necrosis with age, a hallmark of the human disease. Sgca- null mice also revealed loss of sarcolemmal integrity, elevated serum levels of muscle enzymes, increased muscle masses, and changes in the generation of absolute force. Molecular analysis of Sgca- null mice demonstrated that the absence of (cid:97) -sarcoglycan resulted in the complete loss of the sarcoglycan complex, sarcospan, and a disruption of (cid:97) -dystroglycan association with membranes. In contrast, no change in the expression of (cid:101) -sarcoglycan ( (cid:97) -sarcoglycan homologue) was observed. Recombinant (cid:97) -sarcoglycan adenovirus injection into Sgca -deficient muscles restored the sarcoglycan complex and sarcospan to the membrane. We propose that the sarcoglycan–sarcospan complex is requisite for stable association of (cid:97) -dystroglycan with the sarcolemma. The Sgca -deficient mice will be a valuable model for elucidating the pathogenesis of sarcoglycan deficient limb-girdle muscular dystrophies and for the development of therapeutic strategies for this disease.
Negative affective environments improve complex solving performance

Based on recent affect–cognition theories (Bless et al., 1996; Fiedler, 2001; Sinclair, 1988), the present study predicted and showed a differentiated influence of nice and nasty environments on complex problem solving (CPS). Environments were constructed by manipulating the target value “capital” of a complex scenario: Participants in the nice environment (N=42) easily raised the capital and received positive feedback, whereas those in the nasty environment (N=42) hardly enhanced the capital and got negative feedback. The results showed that nasty environments increased negative and decreased positive affect. The reverse was true for nice environments. Furthermore, nasty environments influenced CPS by leading to a higher information retrieval and a better CPS performance. Surprisingly, the influence of environment on CPS was not mediated through affect (cf. Soldat & Sinclair, 2001), as recent affect–cognition theories suggest. The missing influence of affect and the strong impact of environment are discussed.
What are the P-type Asteroids Made Of?

The P-type asteroids, together with the D asteroids, had been believed to be one of the most primitive asteroid classes having surface materials rich in carbon and/or organics. Upon a fall of a new type of meteorite, Tagish Lake in 2000, we came to have a possible sample of the D (and/or T) asteroids. In both spectrally and distance from the sun, the P asteroids are located in between the C/G/B/F asteroids and the D asteroids. Because it is believed that the former group are similar to (thermally metamorphosed) CI/CM chondrites and the latter the Tagish Lake meteorite, the surface material of the P asteroids may be understood in combination of those two meteorite groups. Taking that direction, this paper presents possibly the first quantitative characterization of the P asteroids in terms of carbonaceous chondrites and their experimental derivatives.
Epigenome-wide association study of rheumatoid arthritis identifies differentially methylated loci in B cells

Epigenetic regulation of immune cell types could be critical for the development and maintenance of autoimmune diseases like rheumatoid arthritis (RA). B cells are highly relevant in RA, since patients express autoantibodies and depleting this cell type is a successful therapeutic approach. Epigenetic variation, such as DNA methylation, may mediate the pathogenic activity of B cells. In this study, we performed an epigenome-wide association study (EWAS) for RA with three different replication cohorts, to identify disease-specific alterations in DNA methylation in B cells. CpG methylation in isolated B lymphocytes was assayed on the Illumina HumanMethylation450 BeadChip in a discovery cohort of RA patients (N = 50) and controls (N = 75). Differential methylation was observed in 64 CpG sites (q < 0.05). Six biological pathways were also differentially methylated in RA B cells. Analysis in an independent cohort of patients (N = 15) and controls (N = 15) validated the association of 10 CpG sites located on 8 genes CD1C, TNFSF10, PARVG, NID1, DHRS12, ITPK1, ACSF3 and TNFRSF13C, and 2 intergenic regions. Differential methylation at the CBL signaling pathway was replicated. Using an additional case-control cohort (N = 24), the association between RA risk and CpGs cg18972751 at CD1C (P = 2.26 × 10-9) and cg03055671 at TNFSF10 (P = 1.67 × 10-8) genes was further validated. Differential methylation at genes CD1C, TNFSF10, PARVG, NID1, DHRS12, ITPK1, ACSF3, TNFRSF13C and intergenic region chr10p12.31 was replicated in a cohort of systemic lupus erythematosus (SLE) patients (N = 47) and controls (N = 56). Our results highlight genes that may drive the pathogenic activity of B cells in RA and suggest shared methylation patterns with SLE.
Seismic anisotropy in the boundary layers of the mantle

This chapter discusses seismic anisotropy in the mantle, highlighting mechanisms, observations and interpretations. Although evidence of anisotropy in the Earth is now commonplace, it can be difficult to uniquely identify its underlying cause. Part of the difficulty is due to the nature of wave propagation in anisotropic media; intuition based on wave propagation in isotropic media can be misleading. Observations suggest that anisotropy is not uniform throughout the mantle, but appears to be concentrated in the boundary layers of the convecting mantle where deformation is largest. Studies of surface waves and shear-wave splitting in phases like SKS have provided abundant evidence of anisotropy in the uppermost boundary-layer. In continental settings, the magnitude of the anisotropy is quite variable and its orientation mimics trends in surface geology, suggesting the crust and mantle are coupled during orogenic deformation. In contrast, upper-mantle anisotropy in oceanic settings appears to be quite consistent over large regions and reflects large-scale flow patterns in the mantle. Deeper in the mantle, there is some evidence of anisotropy in the upper-mantle transition zone suggesting that in places a boundary layer may exist between the upper and lower mantle. The bulk of the lower mantle seems to be isotropic except for the D region, the lowermost boundary layer. Here the anisotropy exhibits regional variations on scales similar to those in the lithosphere. As it appears that there are regions of azimuthal anisotropy in D , there is a potential problem separating the effects of upper-mantle anisotropy from lower-mantle anisotropy in data interpretations. At present, observations of seismic anisotropy lack global coverage, but as this improves we are faced with the challenging task of including anisotropy in global seismic models.
The Effects of Land Use Diversity on Pest Pressure and Insecticide Application in Cotton: A County Level Analysis for China

1 Environment and Production Technology Division, International Food Policy Research Institute, Washington DC, USA (Wei ZHANG w.zhang@cgiar.org; Mark ROSEGRANT m.rosegrant@cgiar.org) 2 Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing, China (Yanhui LU yhlu@ippcaas.cn; Kongming WU kmwu@ippcaas.cn) 3 Regional Environment Change Research Division, Institute of Geographical Sciences and Natural Resources Research, Chinese Academy of Sciences, Beijing, China (wuf.igsnrr@gmail.com) 4 Center for Chinese Agricultural Policy, Institute of Geographical Sciences and Natural Resources Research, Chinese Academy of Sciences, Beijing, China (Jikun HUANG jkhuang.ccap@igsnrr.ac.cn; Ke ZHOU zkccap@gmail.com; Xiangzheng DENG dengxz.ccap@igsnrr.ac.cn) 5 Centre for Crop Systems Analysis, Wageningen University, Wageningen, the Netherlands (Wopke.vanderWerf@wur.nl)
LEUKEMIA-ASSOCIATED TRANSPLANTATION ANTIGENS RELATED TO MURINE LEUKEMIA VIRUS

In the last few years we have encountered some remarkable instances in which transplanted mouse leukemias that elicit no discernible resistance in mice of the same inbred strain have been strongly rejected by F1 hybrid recipients. As described below, a detailed study of one such system revealed that the leukemia cells carry a strong leukemia-related transplantation antigen (called X.1) to which the inbred host of origin appears genetically incapable of responding. Hybrids are evidently resistant to the same leukemia cells because they possess appropriate Ir (immune response) 1 genes, one of these being linked to H-2, introduced by the outcross parent. The results imply an immunological role for the Rgv-1 (resistance to Gross virus) locus (ref. 1 for review) in linkage group IX (LG IX).
Postglacial rebound and the focal mechanisms of eastern Canadian earthquakes

A detailed numerical model of postglacial rebound for the eastern Canadian Arctic is described with special attention being paid to Baffin Island. This numerical model is able to account for the observed uplift patterns as recorded by the relative sea-level histories of discrete sites distributed throughout the study area. These uplift patterns show regional trends, so the same model can be used to interpolate between data sites and to estimate the uplift history at any arbitrary site within the study area.By treating the lithosphere as a thin elastic plate, spatial variations in the uplift pattern can be translated into estimates of lithospheric stress. The model predicts the variations in uplift as a function of both space and time since deglaciation and can therefore be used to estimate the temporal evolution of lithospheric stress following deglaciation.The stress so calculated is treated as a perturbation to an ambient stress field having its origin in other processes. Postglacial rebound is shown to.
Mitochondria Damage and Kidney Disease

In human body, the kidney receives 20% of cardiac output and consumes 10% of the body’s oxygen to perform its functions. The kidney is composed of multiple cell populations which are involved in several vital functions that maintain body’s homeostasis such as acid-base and electrolytes balance, blood pressure regulation, nutrients reabsorption and hormone secretion [1]. The human adult kidney is composed with about 3 million functional units, or “nephrons”, and their primary functions and structures are subdivided into a glomerular filtration unit and several tubular segments. The glomerular filtration is a process of filtering blood circulation, retaining circulating cells and useful macromolecules. The tubular segments are involved in active transport processes to reabsorb water, electrolytes, and nutrients to maintain fluid and osmolarity homeostasis. The coordination of both processes maintains body homeostasis and results in metabolic waste excretion with only trace amount of proteins in the urine output [2]. Hence, kidney dysfunction often results in kidney disease with systemic complications.
New strength criteria for rocks under polyaxial compression

Rock mechanics abounds with a great number of strength criteria, among which the Hoek-Brown (HB) criterion is one of the most commonly used. However, it takes no account of the influence of the intermediate principal stress and therefore cannot be used in conditions where the intermediate principal stress does influence the rock strength. In this paper, a comment on the HB criterion and existing enhanced Hoek-Brown (EHB) criteria is presented. Then, two general methods to derive new criteria for rocks under polyaxial compression according to the HB criterion are proposed by which existing EHB criteria can be obtained. and three new criteria are introduced using the second method. Comparisons including smoothness and convexity of the failure envelope surface between proposed criteria and existing ones are made. The valid- ities of the new criteria are checked according to polyaxial tests for eight different rock types from published literature and show good agreement with the test data.
Animal influences on soil properties and plant cover in the Chafarinas Islands (NW Africa).

9 paginas, 1 figura, 3 tablas. El congreso tuvo lugar en Valencia, del 28 de marzo al 1 de abril de 2000. We thank Georgina Alvarez for the organization support, Tomas Gomez, Manolo Igual, Jesus Charco, and Paco Robles for field assistance, Jose M" Alegre for processing plant samples, Rafael Lopez and the IRNAS Analysis Lab staff for chemical analyses, and J. Cara for his help with data and manuscript processing.
Prediction of Eastern and Central Pacific ENSO Events and Their Impacts on East Asian Climate by the NCEP Climate Forecast System

AbstractThe eastern Pacific (EP) El Nino–Southern Oscillation (ENSO) and the central Pacific (CP) ENSO exert different influences on climate. In this study, the authors analyze the hindcasts of the NCEP Climate Forecast System, version 2 (CFSv2), and assess the skills of predicting the two types of ENSO and their impacts on East Asian climate. The possible causes of different prediction skills for different types of ENSO are also discussed.CFSv2 captures the spatial patterns of sea surface temperature (SST) related to the two types of ENSO and their different climate impacts several months in advance. The dynamical prediction of the two types of ENSO by the model, whose skill is season dependent, is better than the prediction based on the persistency of observed ENSO-related SST, especially for summer and fall. CFSv2 performs well in predicting EP ENSO and its impacts on the East Asian winter monsoon and on the Southeast Asian monsoon during its decaying summer. However, for both EP ENSO and CP ENSO, the .
Evidence of small-volume igneous diapirism in the shallow crust of the Colorado Plateau, San Rafael Desert, Utah

Magma is transported through Earth9s solid crust by two different processes, diking and diapirism, although other mechanisms, such as porous and channeled flow, can transport melt through partially molten crustal areas. Dikes are ubiquitous indicators of the transport of magma in the shallow crust by brittle fracture, and there is ample geological and geophysical evidence supporting diking as a magma-ascent mechanism through the crust. On the other hand, igneous diapirism, involving magma ascent by gravitational instability and requiring viscous or plastic flow of country rock (“hot Stokes” diapirs), is often invoked as a magma-transport mechanism restricted to the ductile upper mantle or lower crust. However, unequivocal geological field evidence for igneous diapirism has proven elusive and has been a matter of considerable debate. We report geological and geophysical evidence showing that Pliocene sills emplaced in the upper levels of brittle continental crust of the Colorado Plateau in the San Rafael subvolcanic field (Utah) became gravitationally unstable by mechanically altering the overlying sedimentary rocks. These sills grew into structures that we recognize as domes and plugs at the current level of exposure. Some of these plugs continued to transport magma to shallower levels of the continental crust and eventually acted as conduits feeding volcanic eruptions. Our geological and geophysical findings indicate that gravitational instability is a viable mechanism for the initiation of magma ascent in the upper continental crust for small volumes of basaltic magma under specific conditions.
Intraocular pressure reduction in normal-tension glaucoma patients. The Normal Tension Glaucoma Study Group.

BACKGROUND In a collaborative study, patients with untreated normal-tension glaucoma were randomly assigned to a marked intraocular pressure reduction group or to a no therapy group. It was anticipated that medical therapy and laser trabeculoplasty would generally not achieve adequate pressure lowering and that fistulizing surgery would be required. This hypothesis was examined using current observations in the study. METHODS Patients randomized to the therapy group had a pressure reduction of at least 30% from their last prerandomization level. This was achieved within 6 months by means of fistulizing surgery or with pilocarpine and/or laser trabeculoplasty. Beta-blockers and adrenergic agonists were excluded from both eyes. RESULTS Of 30 patients with documented stable 30% pressure reduction, 17 (57%) achieved this with topical medication and/or laser trabeculoplasty: 8 with pilocarpine alone, 2 with laser trabeculoplasty alone, and 7 with laser trabeculoplasty after initial topical medication. The remaining 13 (43%) patients required a single fistulizing procedure. There was no statistically significant difference between the mean follow-up time for the nonfistulized group (533.8 +/- 437.6 days) and for the fistulized group (502.7 +/- 344.7 days). Both treatment groups had similar baseline profiles. CONCLUSION Marked pressure reduction can be achieved and maintained on a long-term basis by means other than fistulizing surgery in a large proportion of patients with untreated normal-tension glaucoma.
Impact of molecular diffusion on the CO2 distribution and the temperature in the mesosphere

Modelling the energy budget in the mesosphere and lower thermosphere requires a precise evaluation of CO2 distribution in this region. This distribution is primarily determined by competition between vertical eddy diffusion and molecular diffusion. A simple algorithm is proposed to take into account both processes, at all altitudes. Using the SOCRATES bi‐dimensional model of the middle atmosphere, we show that molecular diffusion has a direct impact on CO2 vertical distribution down to approximately 80 km altitude, i.e. well into the mesosphere and below the turbopause altitude. A sensitivity study with regard to different aeronomical processes shows that molecular diffusion has the deepest influence in the mesospheric polar night region. Our model shows that molecular diffusion of CO2 is responsible for a polar night mesopause 12 K warmer than if this process was neglected. Hence, dynamical models should take this process in account across the whole mesospheric altitude range.
The Structural Flexibility of MAD1 Facilitates the Assembly of the Mitotic Checkpoint Complex

The spindle assembly checkpoint (SAC) safeguards the genome during cell division by generating an effector molecule known as the Mitotic Checkpoint Complex (MCC). The MCC comprises two subcomplexes, and during its assembly, formation of the CDC20:MAD2 subcomplex is the rate-limiting step. Recent studies show that the rate of CDC20:MAD2 formation is significantly accelerated by the cooperative binding of CDC20 to SAC proteins MAD1 and BUB1. However, the molecular basis for this acceleration is not fully understood. Here, we demonstrate that the structural flexibility of MAD1 at a conserved hinge near the C-terminus is essential for catalytic MCC assembly. This MAD1 hinge enables the MAD1:MAD2 complex to assume a folded conformation in vivo. Importantly, truncating the hinge reduces the rate of MCC assembly in vitro and SAC signaling in vivo. Conversely, mutations that preserve hinge flexibility retain SAC signaling, indicating that the structural flexibility of the hinge, rather than a specific amino acid sequence, is important for SAC signaling. We summarize these observations in a “knitting” model that explains how the folded conformation of MAD1:MAD2 promotes CDC20:MAD2 assembly.