Miracle-dz/UniFAR-FTUs huggingface dataset:
Heat shock proteins in retinal neurogenesis: identification of the PM1 antigen as the chick Hsc70 and its expression in comparison to that of other chaperones

While the role of heat shock proteins under experimental stress conditions is clearly characterized, their expression in unstressed cells and tissues and their functions in normal cell physiology, besides their chaperone action, remain largely undetermined. We report here the identification in chicken of the antigen recognized by the monoclonal antibody PM1 [Hernández‐Sánchez et al. (1994) Eur. J. Neurosci.6,1801–1810) as the non‐inducible chaperone heat‐shock cognate 70 (Hsc70). Its identity was determined by partial peptide sequencing, immuno‐crossreactivity & two‐dimensional gel‐electrophoresis. In addition, we examined its expression during chick embryo retinal neurogenesis. The early widespread Hsc70 immunostaining corresponding to most, if not all, of the neuroepithelial cells becomes restricted to a subpopulation of these cells in the peripheral retina as development proceeds. On the other hand, retinal ganglion cells, differentiating in the opposite central‐to‐peripheral gradient, retained Hsc70 immunostaining. Other molecular chaperones, the heat‐shock proteins Hsp40, Hsp60 & Hsp90, did not seem to compensate the loss of Hsc70. They also showed decreasing immunostaining patterns as neurogenesis proceeds, although distinctive from that of Hsc70, whereas Hsp70 was not detected in the embryonic retina. This precise cellular & developmental regulation of Hsc70, a generally considered constitutive molecular chaperone, in unstressed embryos, together with the expression of other chaperones, provides new tools & a further insight on neural precursor heterogeneity & suggests possible specific cellular roles of chaperone function during vertebrate neurogenesis.
The lux autoinducer regulates the production of exoenzyme virulence determinants in Erwinia carotovora and Pseudomonas aeruginosa.

Erwinia carotovora and Pseudomonas aeruginosa secrete exoenzymes that contribute to the pathogenesis of plant and mammalian infections respectively. E.carotovora mutants defective in synthesis of the pectinase, cellulase and protease exoenzymes were isolated and classified into two groups. Group 2 mutants were found to be defective in the production of a small freely diffusible molecule, N‐3‐(oxohexanoyl)‐L‐homoserine, lactone (HSL), and were avirulent. Addition of exogenous HSL to these group 2 mutants restores synthesis of the exoenzymes and virulence in planta. Of the exoenzymes of P.aeruginosa the metalloprotease, elastase, is an established virulence determinant. Mutants of P.aeruginosa that are defective in elastase production have been isolated and were again found to fall into two groups. Analogous to the group 2 mutants of E.carotovora, group 2 mutants of P. aeruginosa are defective in the synthesis of HSL and exogenous HSL restores elastase production. HSL has now been linked to the control of bioluminescence in Vibrio fischeri, carbapenem antibiotic production of E.carotovora and the above exoenzyme virulence determinants. This information significantly enhances our understanding of the extent and nature of pheromone mediated gene expression control in prokaryotes.
Influence of soil pH on the sorption of ionizable chemicals: Modeling advances

The soil–water distribution coefficient of ionizable chemicals (Kd) depends on the soil acidity, mainly because the pH governs speciation. Using pH‐specific Kd values normalized to organic carbon (KOC) from the literature, a method was developed to estimate the KOC of monovalent organic acids and bases. The regression considers pH‐dependent speciation and species‐specific partition coefficients, calculated from the dissociation constant (pKa) and the octanol–water partition coefficient of the neutral molecule (log Pn). Probably because of the lower pH near the organic colloid–water interface, the optimal pH to model dissociation was lower than the bulk soil pH. The knowledge of the soil pH allows calculation of the fractions of neutral and ionic molecules in the system, thus improving the existing regression for acids. The same approach was not successful with bases, for which the impact of pH on the total sorption is contrasting. In fact, the shortcomings of the model assumptions affect the predictive power for acids and for bases differently. We evaluated accuracy and limitations of the regressions for their use in the environmental fate assessment of ionizable chemicals.
Effects of Spontaneous Deamidation on the Cytotoxic Activity of the Bacillus anthracis Protective Antigen*

Protective antigen (PA) is a central virulence factor of Bacillus anthracis and a key component in anthrax vaccines. PA binds to target cell receptors, is cleaved by the furin protease, self-aggregates to heptamers, and finally internalizes as a complex with either lethal or edema factors. Under mild room temperature storage conditions, PA cytotoxicity decreased (t½ ≈ 7 days) concomitant with the generation of new acidic isoforms, probably through deamidation of Asn residues. Ranking all 68 Asn residues in PA based on their predicted deamidation rates revealed five residues with half-lives of <60 days, and these residues were further analyzed: Asn10 in the 20-kDa region, Asn162 at P6 vicinal to the furin cleavage site, Asn306 in the pro-pore translocation loop, and both Asn713 and Asn719 in the receptor-binding domain. We found that PA underwent spontaneous deamidation at Asn162 upon storage concomitant with decreased susceptibility to furin. A panel of model synthetic furin substrates was used to demonstrate that Asn162 deamidation led to a 20-fold decrease in the bimolecular rate constant (kcat/Km) of proteolysis due to the new negatively charged residue at P6 in the furin recognition sequence. Furthermore, reduced PA cytotoxicity correlated with a decrease in PA cell binding and also with deamidation of Asn713 and Asn719. On the other hand, neither deamidation of Asn10 or Asn306 nor impairment of heptamerization could be observed upon prolonged PA storage. We suggest that PA inactivation during storage is associated with susceptible deamidation sites, which are intimately involved in both mechanisms of PA cleavage by furin and PA-receptor binding.
Hierarchy of binding sites for Grb2 and Shc on the epidermal growth factor receptor

We analyzed the binding site(s) for Grb2 on the epidermal growth factor (EGF) receptor (EGFR), using cell lines overexpressing EGFRs containing various point and deletion mutations in the carboxy-terminal tail. Results of co-immunoprecipitation experiments suggest that phosphotyrosines Y-1068 and Y-1173 mediate the binding of Grb2 to the EGFR. Competition experiments with synthetic phosphopeptides corresponding to known autophosphorylation sites on the EGFR demonstrated that phosphopeptides containing Y-1068, and to a lesser extent Y-1086, were able to inhibit the binding of Grb2 to the EGFR, while a Y-1173 peptide did not. These findings were confirmed by using a dephosphorylation protection assay and by measuring the dissociation constants of Grb2's SH2 domain to tyrosine-phosphorylated peptides, using real-time biospecific interaction analysis (BIAcore). From these studies, we concluded that Grb2 binds directly to the EGFR at Y-1068, to a lesser extent at Y-1086, and indirectly at Y-1173. Since Grb2 also binds Shc after EGF stimulation, we investigated whether Y-1173 is a binding site for the SH2 domain of Shc on the EGFR. Both competition experiments with synthetic phosphopeptides and dephosphorylation protection analysis demonstrated that Y-1173 and Y-992 are major and minor binding sites, respectively, for Shc on the EGFR. However, other phosphorylation sites in the carboxy-terminal tail of the EGFR are able to compensate for the loss of the main binding sites for Shc. These analyses reveal a hierarchy of interactions between Grb2 and Shc with the EGFR and indicate that Grb2 can bind the tyrosine-phosphorylated EGFR directly, as well as indirectly via Shc.
Characterization of the data access behavior for TPC-C traces

In this paper, we look into the characteristics of the reference stream of TPC-C workloads from the buffer pool point of view. We analyze a trace coming from DB2 UDB version 8.1 fix pack 4 and compare it to a trace from DB2 UDB version 8.1 GA. We perform three types of analysis. A static analysis of the number of reads and writes for index and data pages. We conclude that index pages receive less references than data pages by are more frequently accessed individually. Then, we analyze how DB2 processes access those pages. Index pages have more references than data pages when accessed by more than one process. Finally, we understand the accesses along the life of a page. We conclude that there is a significant burstiness in the reference stream, where, each burst is caused by one process.
Interactions between mitoNEET and NAF-1 in cells

The NEET proteins mitoNEET (mNT) and nutrient-deprivation autophagy factor-1 (NAF-1) are required for cancer cell proliferation and resistance to oxidative stress. NAF-1 and mNT are also implicated in a number of other human pathologies including diabetes, neurodegeneration and cardiovascular disease, as well as in development, differentiation and aging. Previous studies suggested that mNT and NAF-1 could function in the same pathway in mammalian cells, preventing the over-accumulation of iron and reactive oxygen species (ROS) in mitochondria. Nevertheless, it is unknown whether these two proteins directly interact in cells, and how they mediate their function. Here we demonstrate, using yeast two-hybrid, in vivo bimolecular fluorescence complementation (BiFC), direct coupling analysis (DCA), RNA-sequencing, ROS and iron imaging, and single and double shRNA lines with suppressed mNT, NAF-1 and mNT/NAF-1 expression, that mNT and NAF-1 directly interact in mammalian cells and could function in the same cellular pathway. We further show using an in vitro cluster transfer assay that mNT can transfer its clusters to NAF-1. Our study highlights the possibility that mNT and NAF-1 function as part of an iron-sulfur (2Fe-2S) cluster relay to maintain the levels of iron and Fe-S clusters under control in the mitochondria of mammalian cells, thereby preventing the activation of apoptosis and/or autophagy and supporting cellular proliferation.
Classification and quantification of the petrosal approach to the petroclival region.

OBJECT The petrosal approach to the petroclival region has been used by a variety of authors in various ways and the terminology has become quite confusing. A systematic assessment of the benefits and limitations of each approach is also lacking. The authors classify their approach to the middle and upper clivus, review the applications for each, and test their hypotheses on a cadaver model by using frameless stereotactic guidance. METHODS The petrosal approach to the upper and middle clivus is divided into four increasingly morbidity-producing steps: retrolabyrinthine, transcrusal (partial labyrinthectomy), transotic, and transcochlear approaches. Four latex-injected cadaveric heads (eight sides) underwent dissection in which frameless stereotactic guidance was used. An area of exposure 10 cm superficial to a central target (working area) was calculated. The area and length of clival exposure with each subsequent dissection was also calculated. The retrolabyrinthine approach spares hearing and facial function but provides for only a small window of upper clival exposure. The view afforded by what we have called the transcrusal approach provides for up to four times this exposure. The transotic and transcochlear procedures, although producing more morbidity, add little in terms of a larger clival window. However, with each step, the surgical freedom for manipulation of instruments increases. CONCLUSIONS The petrosal approach to the upper and middle clivus is useful but should be used judiciously, because levels of morbidity can be high. The retrolabyrinthine approach has limited utility. For tumors without bone invasion, the transcrusal approach provides a much more versatile exposure with an excellent chance of hearing and facial nerve preservation. The transotic approach provides for greater versatility in treating lesions but clival exposure is not greatly enhanced. Transcochlear exposure adds little in terms of intradural exposure and should be reserved for cases in which access to the petrous carotid artery is necessary.
Constrained energy efficiency optimization for robotic manipulators using neuro-dynamics approach

In the paper, a neurodynamic-based energy efficiency optimization strategy (NEE-OS) is proposed to decrease the energy expenditure of robotic manipulators. Different from the traditional approaches, the proposed NEE-OS integrates several necessary constrains from the environment and the robotic manipulator, which could affect energy consumptions of the robotic manipulator in engineering applications to a large extent. To handle the constraints formulated as equalities and inequalities, the energy efficiency optimization problem is converted into a constrained quadratic programming (QP) problem, which is solved using a linear variable inequality-based primal-dual neural network (PDNN) efficiently.
Activation of JNK1, RSK2, and MSK1 Is Involved in Serine 112 Phosphorylation of Bad by Ultraviolet B Radiation*

The Bcl-2 family member Bad is a pro-apoptotic protein, and phosphorylation of Bad by cytokines and growth factors promotes cell survival in many cell types. Induction of apoptosis by UV radiation is well documented. However, little is known about UV activation of cell survival pathways. Here, we demonstrate that UVB induces Bad phosphorylation at serine 112 in JNK1, RSK2, and MSK1-dependent pathways. Inhibition of mitogen-activated protein (MAP) kinases including ERKs, JNKs, and p38 kinase by the use of their respective dominant negative mutant or a specific inhibitor for MEK1 or p38 kinase, PD98059 or SB202190, resulted in abrogation of UVB-induced phosphorylation of Bad at serine 112. Incubation of active MAP kinase members with Bad protein showed serine 112 phosphorylation of Bad by JNK1 only. However, activated RSK2 and MSK1, downstream kinases of ERKs and p38 kinase, respectively, also phosphorylated Bad at serine 112 in vitro. Cells from a Coffin-Lowry syndrome patient (deficient in RSK2) or expressing an N-terminal or C-terminal kinase-dead mutant of MSK1 were defective for UVB-induced serine 112 phosphorylation of Bad. Furthermore, MAP kinase pathway-dependent serine 112 phosphorylation was shown to be required for dissociation of Bad from Bcl-XL. These data illustrated that UVB-induced phosphorylation of Bad at serine 112 was mediated through MAP kinase signaling pathways in which JNK1, RSK2, and MSK1 served as direct mediators.
The “Window t test”: a simple and powerful approach to detect differentially expressed genes in microarray datasets

This work focuses on differential expression analysis of microarray datasets. One way to improve such statistical analyses is to integrate biological information in the design of these analyses. In this paper, we will use the relationship between the level of gene expression and variability. Using this biological information, we propose to integrate the information from multiple genes to get a better estimate of individual gene variance, when a small number of replicates are available, to increase the power of the statistical analysis. We describe a strategy named the “Window t test” that uses multiple genes which share a similar expression level to compute the variance which is then incorporated a classic t test. The performances of this new method are evaluated by comparison with classic and widely-used methods for differential expression analysis (the classic Student t test, the Regularized t test (reg t test), SAM, Limma, LPE and Shrinkage t). In each case tested, the results obtained were at least equivalent to the best performing method and, in most cases, outperformed it. Moreover, the Window t test relies on a very simple procedure requiring small computing power compared with other methods designed for microarray differential expression analysis.
The Effect of Repeated Prime-Target Presentation in Manipulating Attention-Induced Priming in Persons with Dementia of the Alzheimer′s Type

The present experiment manipulated attention-induced semantic priming in seven persons with dementia of the Alzheimer's type (DAT) and 16 healthy aged controls in a word-nonword lexical decision task by means of repeated prime-target presentations. The experimental paradigm allowed for the simultaneous comparison of automatic processing and attention-induced strategic processing. The results showed that both the healthy aged subjects and the subjects with DAT demonstrated semantic facilitation in the automatic processing of information. The two groups differed, however, on the attention-induced component of the task. The control subjects consciously generated a strategic response bias favoring the real word targets and thus used their processing of the prime to induce an expectancy about the following target. The DAT subjects showed no such attention-dependent expectancy, a deficit which is most probably related to the general cognitive impairments which are a hallmark of the disease.
Research on aeroengine rub-impact fault analysis based on wavelet transform and the local binary patterns

The local binary patterns statistical characteristics of the continuous wavelet transform scalogram of the aeroengine vibration signal are explored in this paper. The method is based on recognizing that certain uniform local binary patterns which are fundamental properties of local image texture and their occurrence histogram is proven to be a very powerful texture feature. Three patterns are studied on the rub-impact faulty signals from the aeroengine test. The analysis indicates that these features are suitable to reflect the local information of the scalogram and can reveal the characteristic of vibration signals well.
Enhanced induction of RPE lineage markers in pluripotent neural stem cells engrafted into the adult rat subretinal space.

PURPOSE To investigate the differentiation of rat neural stem cells (rNSCs) into cells of retinal pigment epithelial (RPE) lineage both in vitro and in vivo, after subretinal transplantation into normal rats and in a sodium iodate (NaIO(3)) model of RPE loss. METHODS rNSCs prepared from the cortex of embryonic day (E)14 Fisher F344 rats were cocultured with different concentrations of vasoactive intestinal peptide (VIP), adult rat RPE cells, or neurosensory retina (NSR) for 5 days. Cell morphology and expression of RPE-specific markers (cytokeratin, CD68, microphthalmia-inducing transcription factor [MITF]) were studied. Additional antibodies used to characterize the rNSCs were markers for stem cells (nestin), immature neurons (betaIII-tubulin), astrocytes (glial fibrillary acidic protein [GFAP]), and oligodendrocytes (Rip). In in vivo studies, 10(6) green fluorescent protein [GFP]-labeled rNSCs were injected subretinally in either normal adult Lewis rats or NaIO(3)-treated rats (70 mg/mL NaIO(3) administered intravenously 7 days before transplantation). RESULTS In vitro VIP-treated rNSCs changed from round cells to glia-like cells with processes that stained for both GFAP and nestin. In addition, small clusters of flattened, polygonal cells with an epithelial-cell-like shape that stained for cytokeratin and CD68 were observed. Coculture of rNSCs with RPE cells, but not with NSR, also led to cells of this phenotype. After transplantation, nestin(+) and GFP(+) rNSCs were visible subretinally as a transplant. In addition, more than 50% of transplanted rNSCs were cytokeratin(+) and CD68(+). CONCLUSIONS Very few rNSCs differentiate in vitro into epithelial-like cells that express RPE-specific markers. In vivo, this differentiation is remarkably enhanced after subretinal engraftment. Thus, transplantation of NSCs into the subretinal space may be a therapy for retinal diseases involving an RPE abnormality.
Cellular Sequestration of Cadmium in the Hyperaccumulator Plant Species Sedum alfredii1[C][W]

Spatial imaging of cadmium (Cd) in the hyperaccumulator Sedum alfredii was investigated in vivo by laser ablation inductively coupled plasma mass spectrometry and x-ray microfluorescence imaging. Preferential Cd accumulation in the pith and cortex was observed in stems of the Cd hyperaccumulating ecotype (HE), whereas Cd was restricted to the vascular bundles in its contrasting nonhyperaccumulating ecotype. Cd concentrations of up to 15,000 μg g−1 were measured in the pith cells, which was many fold higher than the concentrations in the stem epidermis and vascular bundles in the HE plants. In the leaves of the HE, Cd was mainly localized to the mesophyll and vascular cells rather than the epidermis. The distribution pattern of Cd in both stems and leaves of the HE was very similar to calcium but not zinc, irrespective of Cd exposure levels. Extended x-ray absorption fine structure spectroscopy analysis showed that Cd in the stems and leaves of the HE was mainly associated with oxygen ligands, and a larger proportion (about 70% in leaves and 47% in stems) of Cd was bound with malic acid, which was the major organic acid in the shoots of the plants. These results indicate that a majority of Cd in HE accumulates in the parenchyma cells, especially in stems, and is likely associated with calcium pathways and bound with organic acid (malate), which is indicative of a critical role of vacuolar sequestration of Cd in the HE S. alfredii.
Using nonlinear time warping to estimate North Pacific right whale calling depths in the Bering Sea.

Calling depth distributions are estimated for two types of calls produced by critically endangered eastern North Pacific right whales (NPRWs) in the Bering Sea, using passive acoustic data collected with bottom-mounted hydrophone recorders. Nonlinear time resampling of 12 NPRW "upcalls" and 20 "gunshots" recorded in a critical NPRW habitat isolated individual normal mode arrivals from each call. The relative modal arrival times permitted range estimates between 1 and 40 km, while the relative modal amplitudes permitted call depth estimates, provided that environmental inversions were obtained from high signal-to-noise ratio calls. Gunshot sounds were generally only produced at a few meters depth, while upcall depths clustered between 10 and 25 m, consistent with previously published bioacoustic tagging results from North Atlantic right whales. A Wilcoxon rank sum test rejected the null hypothesis that the mean calling depths of the two call types were the same (p = 2.9 × 10-5); the null hypothesis was still rejected if the sample set was restricted to one call per acoustic encounter (p = 0.02). Propagation modeling demonstrates that deeper depths enhance acoustic propagation and that source depth estimates impact both NPRW upcall source level and detection range estimates.