Miracle-dz/UniFAR-FTUs huggingface dataset:
Serological Evidence of Ebola Virus Infection in Indonesian Orangutans

Ebola virus (EBOV) and Marburg virus (MARV) belong to the family Filoviridae and cause severe hemorrhagic fever in humans and nonhuman primates. Despite the discovery of EBOV (Reston virus) in nonhuman primates and domestic pigs in the Philippines and the serological evidence for its infection of humans and fruit bats, information on the reservoirs and potential amplifying hosts for filoviruses in Asia is lacking. In this study, serum samples collected from 353 healthy Bornean orangutans (Pongo pygmaeus) in Kalimantan Island, Indonesia, during the period from December 2005 to December 2006 were screened for filovirus-specific IgG antibodies using a highly sensitive enzyme-linked immunosorbent assay (ELISA) with recombinant viral surface glycoprotein (GP) antigens derived from multiple species of filoviruses (5 EBOV and 1 MARV species). Here we show that 18.4% (65/353) and 1.7% (6/353) of the samples were seropositive for EBOV and MARV, respectively, with little cross-reactivity among EBOV and MARV antigens. In these positive samples, IgG antibodies to viral internal proteins were also detected by immunoblotting. Interestingly, while the specificity for Reston virus, which has been recognized as an Asian filovirus, was the highest in only 1.4% (5/353) of the serum samples, the majority of EBOV-positive sera showed specificity to Zaire, Sudan, Cote d’Ivoire, or Bundibugyo viruses, all of which have been found so far only in Africa. These results suggest the existence of multiple species of filoviruses or unknown filovirus-related viruses in Indonesia, some of which are serologically similar to African EBOVs, and transmission of the viruses from yet unidentified reservoir hosts into the orangutan populations. Our findings point to the need for risk assessment and continued surveillance of filovirus infection of human and nonhuman primates, as well as wild and domestic animals, in Asia.
Fabrication of a drug delivery system that enhances antifungal drug corneal penetration

Abstract Fungal keratitis (FK) remains a severe eye disease, and effective therapies are limited by drug shortages and critical ocular barriers. Despite the high antifungal potency and broad spectrum of econazole, its strong irritant and insolubility in water hinder its ocular application. We designed and fabricated a new drug delivery system based on a polymeric vector for the ocular antifungal application of econazole. This novel system integrates the advantages of its constituent units and exhibits superior comprehensive performance. Using the new system, drug content was significantly increased more than 600 folds. The results of in vivo and in vitro experiments demonstrated that the econazole-loaded formulation exhibited significantly enhanced corneal penetration after a single topical ocular administration, excellent antifungal activity, and good tolerance in rabbits. Drug concentrations and ocular relative bioavailability in the cornea were 59- and 29-time greater than those in the control group, respectively. Following the topical administration of one eye drop (50 μL of 0.3% w/v econazole) in fungus-infected rabbits, a high concentration of antimycotic drugs in the cornea and aqueous humor was sustained and effective for 4 h. The mechanism of corneal penetration was also explored using dual fluorescent labeling. This novel drug delivery system is a promising therapeutic approach for oculomycosis and could serve as a candidate strategy for use with various hydrophobic drugs to overcome barriers in the treatment of many other ocular diseases.
Measured and calculated elastic wave speeds in partially equilibrated mafic granulite xenoliths: Implications for the properties of an underplated lower continental crust

Ultrasonic compressional wave velocities measured at 1.0 GPa and room temperature are compared with calculated velocities (based on single-crystal data and modal mineralogy) for a suite of mafic granulite xenoliths from the Chudleigh volcanic province, north Queensland, Australia. The xenoliths have nearly constant major element compositions but widely variable modal mineralogy, reflecting recrystallization under variable pressure-temperature conditions at depth in the continental crust (20–45 km). They thus provide an excellent opportunity to investigate velocity variation with depth in a mafic lower crust. Measured P wave velocities, corrected for the decompression-induced breakdown of garnet, range from 6.9 to 7.6 km/sec and correlate with derivation depth. These velocities are 5–12% lower than the calculated velocities (7.5–8.0 km/sec), apparently as a result of grain boundary alteration as well as irreversible changes that occurred in the xenoliths during rapid decompression. Calculated P wave velocities are similar to those estimated by Furlong and Fountain (1986) and Sobolev and Babeyko (1989) for mafic granulites formed through basaltic underplating of the continental crust. Depending upon in situ temperature, P wave velocities in the deepest samples may be interpreted as crustal (e.g., 7.3–7.6 km/sec, if heat flow is high) or mantle (7.7–7.8 km/sec, in areas of low heat flow). The range of velocities in the xenolith suite is larger than predicted for a fully equilibrated underplated basaltic layer, highlighting the importance of kinetic effects in determining the ultimate velocity profile of magmatically underplated crust. Comparison of our results with seismic profiles illustrates that the lower crust rarely reaches such high velocities, suggesting quartz-bearing rocks (country rocks? ) are present within magmatically underplated layers of the deep crust.
Sporadic naturally occurring melanoma in dogs as a preclinical model for human melanoma

Melanoma represents a significant malignancy in humans and dogs. Different from genetically engineered models, sporadic canine melanocytic neoplasms share several characteristics with human disease that could make dogs a more relevant preclinical model. Canine melanomas rarely arise in sun‐exposed sites. Most occur in the oral cavity, with a subset having intra‐epithelial malignant melanocytes mimicking the in situ component of human mucosal melanoma. The spectrum of canine melanocytic neoplasia includes benign lesions with some analogy to nevi, as well as invasive primary melanoma, and widespread metastasis. Growing evidence of distinct subtypes in humans, differing in somatic and predisposing germ‐line genetic alterations, cell of origin, epidemiology, relationship to ultraviolet radiation and progression from benign to malignant tumors, may also exist in dogs. Canine and human mucosal melanomas appear to harbor BRAF, NRAS, and c‐kit mutations uncommonly, compared with human cutaneous melanomas, although both species share AKT and MAPK signaling activation. We conclude that there is significant overlap in the clinical and histopathological features of canine and human mucosal melanomas. This represents opportunity to explore canine oral cavity melanoma as a preclinical model.
Extrinsic factors can mediate resistance to BRAF inhibition in central nervous system melanoma metastases

Here, we retrospectively review imaging of 68 consecutive unselected patients with BRAF V600‐mutant metastatic melanoma for organ‐specific response and progression on vemurafenib. Complete or partial responses were less often seen in the central nervous system (CNS) (36%) and bone (16%) compared to lung (89%), subcutaneous (83%), spleen (71%), liver (85%) and lymph nodes/soft tissue (83%), P < 0.001. CNS was also the most common site of progression.
Genetic modulation of the iris transillumination defect: a systems genetics analysis using the expanded family of BXD glaucoma strains

We investigated the contributions of Tyrp1 and Gpnmb to the iris transillumination defect (TID) in five age cohorts of BXD mice. Using systems genetics, we also evaluated the role of other known pigmentation genes (PGs). Mapping studies indicate that Tyrp1 contributes to the phenotype at all ages, yet the TID maps to Gpnmb only in the oldest cohort. Composite interval mapping reveals secondary loci viz. Oca2, Myo5a, Prkcz, and Zbtb20 that modulate the phenotype in the age groups up to 10–13 months. The contributions of Tyrp1 and Gpnmb were highly significant in all age cohorts. Moreover, in young mice, all six gene candidates had substantial interactions in our model. Our model accounted for 71–88% of the explained variance of the TID phenotype across the age bins. These results demonstrate that along with Tyrp1 and Gpnmb, Oca2, Myo5a, Prkcz, and Zbtb20 modulate the TID in an age‐dependent manner.
Holocene palaeoflood events recorded by slackwater deposits along the lower Jinghe River valley, middle Yellow River basin, China

Palaeoflood slackwater deposits (SWDs), are the natural record of overbank flooding and are often found within aeolian loess‐soil profiles along the river valleys of the middle Yellow River basin. These pedo‐stratigraphic sequences are studied using a multi‐disciplinarily approach to reconstruct Holocene hydro‐climatic variations. Our field investigations along the lower Jinghe River valley have identified palaeoflood SWDs at several sites along the riverbanks based on sedimentological criteria. Analytical results, including magnetic susceptibility, particle‐size distribution and concentrations of chemical elements, indicate that these well‐sorted palaeoflood SWD beds were deposited from the suspended sediment load in floodwaters. We identify two episodes of extraordinary palaeoflood events along the Jinghe River valley. These hydro‐climatic events were dated to 4200–4000 and 3200–2800 a BP, by using the optically stimulated luminescence method in combination with archaeological dating of retrieved anthropogenic remains, and with pedo‐stratigraphic correlations with the previously studied Holocene pedo‐stratigraphy in the Jinghe River drainage basin. The flooding events are therefore considered to be a regional expression of known climatic events in the northern hemisphere and demonstrate Holocene climate was far from stable. This study provides important data in understanding the interactions between regional hydro‐climatic systems and global change in semi‐arid and sub‐humid regions. Copyright © 2012 John Wiley & Sons, Ltd.
Viscosity in transition zone and lower mantle: Implications for slab penetration

The evolution of a subducting slab is strongly influenced by the viscosity of the mantle which it overlies. However, there is still no consensus about the viscosity in the transition zone and shallower lower mantle. We use a numerical self‐consistent subduction model and run a set of experiments in order to find critical patterns of viscosity that would allow the evolution of the different subduction styles that can actually be found in nature. Our results show that a jump in viscosity of ∼5 times from transition zone to lower mantle gives the most reasonable results. Optimal values of viscosity in the transition zone are in the range of 3 * 1020–1021 Pa s. Higher values would produce piling up of the slab and later sinking or even slab flattening. Lower viscosities result in velocities (>30 cm/yr) that are too high, while the new slab subducts through the upper mantle and transition zone, a phenomenon that is rarely seen in nature. Reduction of the Clapeyron slope, related to the spinel‐perovskite transition, variations in oceanic crustal thickness and in the age of the slab do not influence much the style of subduction. When overriding velocity is applied to the upper plate, the previously penetrating slab tends to lay at the 660 km boundary but does not substantially change the subduction velocity.
Geomorphic and Sedimentological Controls on the Effectiveness of an Extreme Flood

The 1993 flood on the Upper Mississippi River was a rare, large‐magnitude hydrological event. Field and aerial survey analyses and Landsat 5 Thematic Mapper data were used to appraise the thickness of overbank deposits on leveed and unleveed reaches. Results indicate that minimal (<5 mm) overbank sedimentation occurred, except in the immediate vicinity of a levee break. Unleveed sections also lacked overbank sedimentation. Little geomorphological or sedimentological evidence of this extreme event is likely to be preserved. This raises questions about the completeness of the stratigraphic record: in situations where wide floodplains with cohesive soils provide effective resistance and dissipate energy so that erosion is minimized, and/or sediment supply is limited by event timing or sequencing, a large flood may leave little or no substantive evidence of its occurrence.
Social Contact Patterns and Implications for Infectious Disease Transmission: A Systematic Review and Meta-Analysis of Contact Surveys

Background: Transmission of respiratory pathogens such as SARS-CoV-2 depends on patterns of contact and mixing across populations. Understanding this is crucial to predict pathogen spread and the effectiveness of control efforts. Most analyses of contact patterns to date have focussed on high-income settings. Methods: Here, we conduct a systematic review and individual-participant meta-analysis of surveys carried out in low- and middle-income countries and compare patterns of contact in these settings to surveys previously carried out in high-income countries. Using individual-level data from 28,503 participants and 413,069 contacts across 27 surveys we explored how contact characteristics (number, location, duration and whether physical) vary across income settings.Results: Contact rates declined with age in high- and upper-middle-income settings, but not in low-income settings, where adults aged 65+ made similar numbers of contacts as younger individuals and mixed with all age-groups. Across all settings, increasing household size was a key determinant of contact frequency and characteristics, but low-income settings were characterised by the largest, most intergenerational households. A higher proportion of contacts were made at home in low-income settings, and work/school contacts were more frequent in high-income strata. We also observed contrasting effects of gender across income-strata on the frequency, duration and type of contacts individuals made.Conclusions: These differences in contact patterns between settings have material consequences for both spread of respiratory pathogens, as well as the effectiveness of different non-pharmaceutical interventions.Funding: This work is primarily being funded by joint Centre funding from the UK Medical Research Council and DFID (MR/R015600/1).
Effects of Tropomodulin 2 on Dendritic Spine Reorganization and Dynamics

Dendritic spines are actin-rich protrusions that receive a signal from the axon at the synapse. Remodeling of cytoskeletal actin is tightly connected to dendritic spine morphology-mediated synaptic plasticity of the neuron. Remodeling of cytoskeletal actin is required for the formation, development, maturation, and reorganization of dendritic spines. Actin filaments are highly dynamic structures with slow-growing/pointed and fast-growing/barbed ends. Very few studies have been conducted on the role of pointed-end binding proteins in the regulation of dendritic spine morphology. In this study, we evaluated the role played by tropomodulin 2 (Tmod2)—a brain-specific isoform, on the dendritic spine re-organization. Tmod2 regulates actin nucleation and polymerization by binding to the pointed end via actin and tropomyosin (Tpm) binding sites. We studied the effects of Tmod2 overexpression in primary hippocampal neurons on spine morphology using confocal microscopy and image analysis. Tmod2 overexpression decreased the spine number and increased spine length. Destroying Tpm-binding ability increased the number of shaft synapses and thin spine motility. Eliminating the actin-binding abilities of Tmod2 increased the number of mushroom spines. Tpm-mediated pointed-end binding decreased F-actin depolymerization, which may positively affect spine stabilization; the nucleation ability of Tmod2 appeared to increase shaft synapses.
NADPH oxidase expression in active multiple sclerosis lesions in relation to oxidative tissue damage and mitochondrial injury

Multiple sclerosis is a chronic inflammatory disease of the central nervous system, associated with demyelination and neurodegeneration. The mechanisms of tissue injury are poorly understood, but recent data suggest that mitochondrial injury may play an important role in this process. Mitochondrial injury can be triggered by reactive oxygen and nitric oxide species, and we recently provided evidence for oxidative damage of oligodendrocytes and dystrophic axons in early stages of active multiple sclerosis lesions. In this study, we identified potential sources of reactive oxygen and nitrogen species through gene expression in carefully staged and dissected lesion areas and by immunohistochemical analysis of protein expression. Genome-wide microarrays confirmed mitochondrial injury in active multiple sclerosis lesions, which may serve as an important source of reactive oxygen species. In addition, we found differences in the gene expression levels of various nicotinamide adenine dinucleotide phosphate oxidase subunits between initial multiple sclerosis lesions and control white matter. These results were confirmed at the protein level by means of immunohistochemistry, showing upregulation of the subunits gp91phox, p22phox, p47phox, nicotinamide adenine dinucleotide phosphate oxidase 1 and nicotinamide adenine dinucleotide phosphate oxidase organizer 1 in activated microglia in classical active as well as slowly expanding lesions. The subunits gp91phox and p22phox were constitutively expressed in microglia and were upregulated in the initial lesion. In contrast, p47phox, nicotinamide adenine dinucleotide phosphate oxidase 1 and nicotinamide adenine dinucleotide phosphate oxidase organizer 1 expression were more restricted to the zone of initial damage or to lesions from patients with acute or early relapsing/remitting multiple sclerosis. Double labelling showed co-expression of the nicotinamide adenine dinucleotide phosphate oxidase subunits in activated microglia and infiltrated macrophages, suggesting the assembly of functional complexes. Our data suggest that the inflammation-associated oxidative burst in activated microglia and macrophages plays an important role in demyelination and free radical-mediated tissue injury in the pathogenesis of multiple sclerosis.
Mid- to late-Holocene paleoceanographic changes on the southeastern Brazilian shelf based on grain size records

High-resolution grain size analyses of three AMS 14C-dated cores from the Southeastern Brazilian shelf provide a detailed record of mid- to late-Holocene environmental changes in the Southwestern Atlantic Margin.The cores exhibit millennial variability that we associate with the previously described southward shift of the Inter Tropical Convergence Zone (ITCZ) average latitudinal position over the South American continent during the Holocene climatic maximum. This generated changes in the wind-driven current system of the SW Atlantic margin and modified the grain size characteristics of the sediments deposited there. Centennial variations in the grain size are associated with a previously described late-Holocene enhancement of the El Niño-Southern Oscillation (ENSO) amplitude, which led to stronger NNE trade winds off eastern Brazil, favouring SW transport of sediments from the Paraiba do Sul River. This is recorded in a core from off Cabo Frio as a coarsening trend from 3000 cal. BP onwards. The ENSO enhancement also caused changes in precipitation and wind pattern in southern Brazil, allowing high discharge events and northward extensions of the low-saline water plume from Río de la Plata. We propose that this resulted in a net increase in northward alongshore transport of fine sediments, seen as a prominent fine-shift at 2000 cal. BP in a core from ~24°S on the Brazilian shelf. Wavelet- and spectral analysis of the sortable silt records show a significant ~1000-yr periodicity, which we attribute to solar forcing. If correct, this is one of the first indications of solar forcing of this timescale on the Southwestern Atlantic margin.
Anomalous heat flow and geoid across the Cape Verde Rise: evidence for dynamic support from a thermal plume in the mantle

Summary. We describe results from 200 heat flow measurements across the Cape Verde Rise in the North Atlantic. They show that the heat flow through normal, 125 Myr-old crust is 45.5 ± 3.4mWm-2, close to the prediction for a lithospheric plate model. Heat flow increases towards the centre of the Rise, reaching a maximum of 16 ± 4 mW m-2 above the normal oceanic value. The concommitant geoid anomaly at the centre of the Rise is 7.6 ± 0.3 m and the depth anomaly is 1900 ± 200 m. The anomalous heat flow, geoid and bathymetric values are used to constrain a variety of theoretical models of hot spot mechanisms. Lithospheric reheating models alone, whether involving transient or sustained thinning of the lithosphere, fail to model the broad heat flow anomaly and the long duration of uplift and volcanism observed on the Cape Verde Rise. Axisymmetric convection models provide a better fit to the observed data, and suggest that the swell is a consequence primarily of dynamic uplift generated by an ascending thermal plume in the underlying mantle. Uplift caused by expansion of the solid lithosphere is of smaller importance. The observed geoid, bathymetry and heat flow anomalies are reproduced well using convection models with upper mantle viscosities of 2-4 times 1020 Pa s and a coefficient of thermal expansion in the range 2.0 - 2.5 times 10-5 K-1. The effect of melting in the ascending plume is to buffer the heat flow anomalies. In the case of the Cape Verde Rise, partial melting is minimal, but its effect on other hotspots will be to limit observed heat flow anomalies at the surface to less than 20-25 mW m-2.