Miracle-dz/UniFAR-FTUs huggingface dataset:
Proteome Profiling of Developing Murine Lens Through Mass Spectrometry

Purpose We previously completed a comprehensive profile of the mouse lens transcriptome. Here, we investigate the proteome of the mouse lens through mass spectrometry–based protein sequencing at the same embryonic and postnatal time points. Methods We extracted mouse lenses at embryonic day 15 (E15) and 18 (E18) and postnatal day 0 (P0), 3 (P3), 6 (P6), and 9 (P9). The lenses from each time point were preserved in three distinct pools to serve as biological replicates for each developmental stage. The total cellular protein was extracted from the lens, digested with trypsin, and labeled with isobaric tandem mass tags (TMT) for three independent TMT experiments. Results A total of 5404 proteins were identified in the mouse ocular lens in at least one TMT set, 4244 in two, and 3155 were present in all three TMT sets. The majority of the proteins exhibited steady expression at all six developmental time points; nevertheless, we identified 39 proteins that exhibited an 8-fold differential (higher or lower) expression during the developmental time course compared to their respective levels at E15. The lens proteome is composed of diverse proteins that have distinct biological properties and functional characteristics, including proteins associated with cataractogenesis and autophagy. Conclusions We have established a comprehensive profile of the developing murine lens proteome. This repository will be helpful in identifying critical components of lens development and processes essential for the maintenance of its transparency.
Thorough QT study of the effect of intravenous amisulpride on QTc interval in Caucasian and Japanese healthy subjects

Aim The D2/D3 antagonist amisulpride has shown promising efficacy against postoperative nausea and vomiting (PONV) at low doses. We investigated whether intravenous amisulpride has an effect on the QTc interval in a formal Thorough QT study (TQT). Methods This was a randomized, double‐blind, placebo and positive‐controlled, four‐way crossover study. Forty healthy Caucasian and Japanese subjects were included to receive a single administration of 5 mg and 40 mg of i.v. amisulpride or a single oral dose of moxifloxacin or placebo per period. Results The therapeutic dose of 5 mg amisulpride was associated with a slight, transient increase in mean ΔΔQTcF, from 2.0 ms prior to dosing to a peak of 5 ms (90% CI: 2.8, 7.1 ms) at 8 min, decreasing to 2.1 ms at 30 min after dosing. The supra‐therapeutic dose of 40 mg given at twice the infusion rate was associated with prolongation in ΔΔQTcF peaking at 23.4 ms (90% CI: 21.3, 25.5 ms) at the end of infusion (8 min), returning below 10 ms within 1.5 h. Assay sensitivity was confirmed; ΔΔQTcF had increased by 12.3 ms (90% CI 10.1, 14.6 ms) at 4 h post‐dose. The PK‐PD relationship revealed no differences between Caucasian and Japanese subjects (p‐value > 0.5). Conclusions Amisulpride has a plasma concentration‐dependent effect on the QTc interval. The proposed therapeutic dose for management of PONV does not lead to a prolongation of QTcF above the threshold of regulatory concern, while such effect could not be excluded for the supratherapeutic dose.
Runoff generation from logged and burnt convergent hillslopes: rainfall simulation and modelling

This paper reports results from field experiments and hydrological modelling on the dynamics of runoff generation in highly convergent parts of the landscape in a logged and burnt eucalypt forest in south‐eastern Victoria, Australia. Large‐scale rainfall simulation experiments were conducted to explore runoff generating mechanisms from harvested areas, and to assess the effectiveness of standard water quality protective measures, here a disturbed filter strip, in preventing accession of sediment to near‐stream areas. We then examined the likely effects of varying antecedent moisture conditions on surface and subsurface runoff generating mechanisms. Very small volumes of surface runoff were generated only at very high rainfall intensity rates that exceeded a 100 year recurrence interval event during the simulated experiments. There was little or no identifiable impact of either compaction from logging operations or fire‐induced hydrophobicity on surface infiltration or generation of surface runoff. Measured soil hydraulic properties and soil depths explained the paucity of surface runoff, and the dominance of subsurface storm flow as the prime runoff generating mechanism. Deep lateral subsurface flow was observed from the cut‐face of a fire access track and into a streamhead downslope of the experimental plots. Water balance modelling using Topog_Dynamic indicated the conditions under which saturated overland flow in this environment could be generated are rare, but that care should be taken in siting of roads and tracks in lower parts of convergent landscapes. Copyright © 2004 John Wiley & Sons, Ltd.
Protein Kinase C β Controls Nuclear Factor κB Activation in B Cells Through Selective Regulation of the IκB Kinase α

Activation of the nuclear factor (NF)-κB transcription complex by signals derived from the surface expressed B cell antigen receptor controls B cell development, survival, and antigenic responses. Activation of NF-κB is critically dependent on serine phosphorylation of the IκB protein by the multi-component IκB kinase (IKK) containing two catalytic subunits (IKKα and IKKβ) and one regulatory subunit (IKKγ). Using mice deficient for protein kinase C β (PKCβ) we show an essential role of PKCβ in the phosphorylation of IKKα and the subsequent activation of NF-κB in B cells. Defective IKKα phosphorylation correlates with impaired B cell antigen receptor–mediated induction of the pro-survival protein Bcl-xL. Lack of IKKα phosphorylation and defective NF-κB induction in the absence of PKCβ explains the similarity in immunodeficiencies caused by PKCβ or IKKα ablation in B cells. Furthermore, the well established functional cooperation between the protein tyrosine kinase Bruton's tyrosine kinase (Btk), which regulates the activity of NF-κB and PKCβ, suggests PKCβ as a likely serine/threonine kinase component of the Btk-dependent NF-κB activating signal transduction chain downstream of the BCR.
Neural Cell Adhesion Molecule-secreting Transgenic Mice Display Abnormalities in Gabaergic Interneurons and Alterations in Behavior

The extracellular region of the transmembrane neural cell adhesion molecule (NCAM-EC) is shed as a soluble fragment at elevated levels in the schizophrenic brain. A novel transgenic mouse line was generated to identify consequences on cortical development and function of expressing soluble NCAM-EC from the neuron-specific enolase promoter in the developing and mature neocortex and hippocampus. NCAM-EC transgenic mice exhibited a striking reduction in synaptic puncta of GABAergic interneurons in the cingulate, frontal association cortex, and amygdala but not hippocampus, as shown by decreased immunolabeling of glutamic acid decarboxylase-65 (GAD65), GAD67, and GABA transporter 1. Interneuron cell density was unaltered in the transgenic mice. Affected subpopulations of interneurons included basket interneurons evident in NCAM-EC transgenic mice intercrossed with a reporter line expressing green fluorescent protein and by parvalbumin staining. In addition, there appeared to be a reduction in excitatory synapses, as revealed by synaptophysin staining and apical dendritic spine density of cortical pyramidal cells. Behavioral analyses demonstrated higher basal locomotor activity of NCAM-EC mice and enhanced responses to amphetamine and
Surface deformation due to shear and tensile faults in a half-space

Abstract A complete suite of closed analytical expressions is presented for the surface displacements, strains, and tilts due to inclined shear and tensile faults in a half-space for both point and finite rectangular sources. These expressions are particularly compact and free from field singular points which are inherent in the previously stated expressions of certain cases. The expressions derived here represent powerful tools not only for the analysis of static field changes associated with earthquake occurrence but also for the modeling of deformation fields arising from fluid-driven crack sources.
Distinct functional determinants of influenza hemagglutinin-mediated membrane fusion

Membrane fusion is the critical step for infectious cell penetration by enveloped viruses. We have previously used single-virion measurements of fusion kinetics to study the molecular mechanism of influenza-virus envelope fusion. Published data on fusion inhibition by antibodies to the 'stem' of influenza virus hemagglutinin (HA) now allow us to incorporate into simulations the provision that some HAs are inactive. We find that more than half of the HAs are unproductive even for virions with no bound antibodies, but that the overall mechanism is extremely robust. Determining the fraction of competent HAs allows us to determine their rates of target-membrane engagement. Comparison of simulations with data from H3N2 and H1N1 viruses reveals three independent functional variables of HA-mediated membrane fusion closely linked to neutralization susceptibility. Evidence for compensatory changes in the evolved mechanism sets the stage for studies aiming to define the molecular constraints on HA evolvability. DOI: http://dx.doi. org/10.7554/eLife.11009. 001
PEST sequences from a cactus dehydrin regulate its proteolytic degradation

Dehydrins (DHNs) are intrinsically disordered proteins expressed under cellular dehydration-related stresses. In this study, we identified potential proteolytic PEST sequences located at the central and C-terminal regions from the Opuntia streptacantha OpsDHN1 protein. In order to evaluate these PEST sequences as proteolytic tags, we generated a translational fusion with the GUS reporter protein and OpsDHN1 coding sequence. We found a GUS degradation effect in tobacco agro-infiltrated leaves and Arabidopsis transgenic lines that expressed the fusion GUS::OpsDHN1 full-length. Also, two additional translational fusions between OpsDHN1 protein fragments that include the central (GUS::PEST-1) or the C-terminal (GUS::PEST-2) PEST sequences were able to decrease the GUS activity, with PEST-2 showing the greatest reduction in GUS activity. GUS signal was abated when the OpsDHN1 fragment that includes both PEST sequences (GUS::PEST-1-2) were fused to GUS. Treatment with the MG132 proteasome inhibitor attenuated the PEST-mediated GUS degradation. Point mutations of phosphorylatable residues in PEST sequences reestablished GUS signal, hence these sequences are important during protein degradation. Finally, in silico analysis identified potential PEST sequences in other plant DHNs. This is the first study reporting presence of PEST motifs in dehydrins.
Global study of seismic wave attenuation in the upper mantle behind island arcs using pP waves

Observations of striking and consistent differences in the attenuation of pP phases produced by mantle earthquakes and recorded by the World-Wide Standard Seismograph Network (WWSSN) provide data for mapping variations in the attenuation of high-frequency (0.5- to 2-Hz) compressional waves in the wedge of mantle above nearly all of the inclined seismic zones on earth. The data reveal several zones of high attenuation that in nearly all cases correspond to major presently active tectonic features above or near the inclined seismic zones. Zones of high attenuation behind the Tonga, New Hebrides, Mariana, and Japanese island arcs coincide with zones of presently or recently active crustal extension and creation of marginal basins. In western South America a zone of high attenuation underlies most of the broad uplifted terrain of the Andean Altiplano. In contrast to the zones beneath active marginal basins this zone is not related to crustal spreading. A high-attenuation zone exists beneath the Sea of Okhotsk that, although it is near, is offset from the Kuril-Kamchatka arc and thus may not be directly related to that system. This zone may instead be related to possible offshore continuations of the Baykal-Aldan rift system or the postulated plate boundary between Asia and North America. Where they are determined, the high-attenuation zones seem to exist in the upper 200–300 km of the mantle. Wherever data are available, they show that the zones of high compressional wave attenuation correspond to zones of high attenuation for shear waves, low seismic wave velocities, and high heat flow. These properties, in addition to the geological evidence of crustal extension or uplift, suggest that the compressional wave attenuation results from high temperatures and/or partial melting of the upper mantle material. Although all the high-attenuation zones occur near inclined seismic zones that reach depths greater than 300 km, the absence of such zones in the Indonesian, Philippine, Izu-Bonin, and New Britain-Solomon regions shows that lithospheric subduction to great depths is not a sufficient condition for their occurrence. The zones of high attenuation are also not systematically related to the distributions of active volcanos; this condition, together with other data, indicates that large bodies of partially melted material probably do not exist beneath the volcanos of island arcs.
Genesis of Vanadium Ores in the Otavi Mountainland, Namibia

Zn-Cu-Pb vanadate ores (descloizite, mottramite, and vanadinite) in the Otavi Mountainland, Namibia, once were considered the greatest vanadium deposits in the world, with resources estimated at several million tons of vanadium ore. The deposits, now mostly exhausted, occurred in collapse breccias and solution cavities related to a karstic network associated with the post-Gondwana land surfaces in carbonate rocks of the Neoproterozoic Otavi Group, which already contained primary sulfide orebodies. Although a supergene, post-Damaran origin has been generally accepted, the timing and genesis of this mineralization style remains controversial. Mottramite and Cu descloizite are particularly abundant around Cu sulfide deposits (Tsumeb type), whereas descloizite occurs in the areas surrounding primary sphalerite-willemite orebodies (Berg Aukas type). The V deposits the Otavi Mountainland represent a special low-temperature, weathering-related, non-sulfide ore type, also fairly widespread in other areas of southern Africa (e.g., Zambia, Angola). Here we describe the geologic setting of the main V deposits and their ore mineralogy, present some comprehensive major and trace element data for the vanadate ore minerals and gangue carbonates, as well as fluid inclusion microthermometry, O, C, Sr, and Pb isotope analyses, and direct (U-Th)/He descloizite thermochronometry. The vanadates are considered to have formed during a late phase in the depositional history of the post-Damaran supergene ores. Calcite and dolomite gangue are paragenetically coeval with the vanadates, occurring with the vein- and breccia-related ores and as cement in the deeper parts of the recent karst infills. The acidic conditions of sulfide alteration, coupled with a low Eh caused by the influence of organic matter, could have been favorable for vanadate precipitation. Geochemical results and isotope data indicate that most vanadate deposits were formed at temperatures of ~40° to 50°C by meteoric waters interacting with Neo-proterozoic shales, carbonates, and related primary sulfide ores, which were subjected to multiple weathering events in a karst environment. The age of most deposits appears to be generally confined to the Tertiary, with a distinct period of descloizite formation dated at 24 to 33 Ma. The V ores are genetically related to post-Gondwanan erosional episodes, controlled by tectonomorphological evolution following rifting phases in the Atlantic realm and spanning the period from the end of the Cretaceous to Pleistocene.
Crustal structure across the northern Cordillera, Yukon Territory, from seismic wide-angle studies: Omineca Belt to Intermontane Belt

A seismic refraction  wide-angle reflection experiment shot in 1997 in the southern Yukon Territory crosses the Omineca Belt, which includes the strike-slip Tintina Fault, and terminates within the Intermontane Belt of the northern Canadian Cordillera. Lithospheric structure is interpreted from two-dimensional forward and inverse modelling of traveltimes, combined with forward-amplitude modelling, and from 2.5-dimensional modelling of gravity data. Beneath the Cassiar terrane and the North America miogeocline, average velocities in the upper 20 km of crust are < 6.1 km/s. In the west beneath the accreted Cache Creek, Slide Mountain, and YukonTanana terranes, average velocities increase to ∼6.3 km/s. In the upper crust, the velocity model beneath these terranes thus correlates with more mafic accreted material and not with a subsurface extension of the Cassiar terrane. The Tintina Fault is a crustal-scale structure across which significant structural differences occur. A mid-crustal reflector terminates .
A geophysical study of the Earth's crust in central Virginia: Implications for Appalachian crustal structure

A regional seismic reflection line (I-64) across the Virginia Piedmont has provided a stacked section suitable for an integrated interpretation of geophysical data in the region. A highly reflective upper crust, an allochthonous Blue Ridge Province, underlying thrust sheets including the Blue Ridge master decollement, and a basal decollement at a depth of about 9 km (3 s) are confirmed on the seismic data. Immediately east of the Blue Ridge Province, Appalachian structures plunge to as much as 12 km (4 s) depth. The Evington Group, Hardware terrane, and Chopawamsic metavolcanic rocks (Carolina terrane) crop out in the Piedmont Province, and numerous eastward dipping reflections originate from these rocks in the subsurface. These eastward dipping reflectors overlie a gently west dipping (10°–15°), highly reflective zone that varies in depth from 1.5 s (4.5 km) beneath the Goochland terrane to 4 s (12 km) beneath the rocks of the Evington Group. Some of the overlying eastward dipping reflections apparently root in this zone. The zone may include decollement surfaces along which the overlying rocks were transported. Relatively few reflections originate from within autochthonous Grenville basement at the western end of the profile. The Goochland granulite terrane is interpreted to be a westward thrust nappe structure that has overridden a portion of the Chopawamsic metavolcanic rocks. A broad zone of east dipping (20°–45°) reflections bounds the Goochland terrane on the east. These reflections may originate from deformation zones and continue to Moho depths. They appear to be correlative with similar events seen on other Appalachian lines. The pervasiveness of the zone of east dipping events on other seismic reflection lines and the continuity of the adjacent Piedmont gravity high suggest continuity of crustal features along the length of the Appalachians. A major conclusion of this study is that crustal thinning is responsible for the main components of the gravity field in Virginia, that is, the Appalachian gravity gradient and the Piedmont gravity high. The crust thins from about 52 km beneath the Appalachian mountains to about 35 km beneath Richmond, Virginia, and then rethickens by up to 10 km beneath the zone of east dipping reflections (mylonites? ) east of Richmond. The I-64 seismic data also contain a sequence of reflections at about 9–12 s, indicative of lower crustal layering; the base of this zone of reflections coincides almost exactly with the Mohorovicic discontinuity interpreted from earlier refraction work. The layering extends about 70 km west from Richmond, Virginia, and is interpreted as a lower crustal transition zone that is believed to persist across most of Virginia.
Toxicogenomics Data: The Road to Acceptance

Regulatory agencies believe microarray data could be extremely useful in testing prospective chemical products and investigating safety problems after chemicals have been marketed. However, it has not yet been clearly established how this information will be used by agencies in the approval of pharmaceuticals and other chemicals--or even whether companies will be required to submit microarray data. Although some private companies are already voluntarily submitting microarray data along with their drug and pesticide applications, others are hesitant to do so. Most of the stakeholders involved agree that standardization of microarray experiment procedures and of genomic signatures are key to the broad acceptance and use of these data.
A case study of hydrocarbon transport along active faults and production-related stress changes in the Monterey Formation, California

Abstract Recent field studies show that critically stressed faults, that is, faults that are close to frictional failure in the current stress field, serve as conduits for fluid flow. Similarly, geological field studies of the low permeability siliceous shales in the Monterey Formation, California, clearly indicate that faults influence hydrocarbon transport. We report here a study of the Antelope Shale, a low permeability siliceous shale hydrocarbon reservoir in the Buena Vista Hills field in the southern San Joaquin Valley to determine the influence of the stress state on the relative hydraulic conductivity of the fractures and faults present in the subsurface. Because production has both lowered reservoir pressure and the horizontal stresses, it was necessary to “restore” the reservoir stress state to initial conditions in order to identify correctly the most highly productive intervals. This analysis demonstrates that prior to production, faults in the reservoir were active in a transitional reverse/strike-slip faulting stress state, consistent with regional tectonics. Initial production rates in the field were 2000 barrels of oil per day, principally from intervals where critically stressed faults were encountered.
Early gene expression events in the laminar abscission zone of abscission-promoted citrus leaves after a cycle of water stress/rehydration: involvement of CitbHLH1

Leaf abscission is a common response of plants to drought stress. Some species, such as citrus, have evolved a specific behaviour in this respect, keeping their leaves attached to the plant body during water stress until this is released by irrigation or rain. This study successfully reproduced this phenomenon under controlled conditions (24h of water stress followed by 24h of rehydration) and used it to construct a suppression subtractive hybridization cDNA library enriched in genes involved in the early stages of rehydration-promoted leaf abscission after water stress. Sequencing of the library yielded 314 unigenes, which were spotted onto nylon membranes. Membrane hybridization with petiole (Pet)- and laminar abscission zone (LAZ)-enriched RNA samples corresponding to early steps in leaf abscission revealed an almost exclusive preferential gene expression programme in the LAZ. The data identified major processes such as protein metabolism, cell-wall modification, signalling, control of transcription and vesicle production, and transport as the main biological processes activated in LAZs during the early steps of rehydration-promoted leaf abscission after water stress. Based on these findings, a model for the early steps of citrus leaf abscission is proposed. In addition, it is suggested that CitbHLH1, the putative citrus orthologue of Arabidopsis BIGPETAL, may play major roles in the control of abscission-related events in citrus abscission zones.