Miracle-dz/UniFAR-FTUs huggingface dataset:
The La and related RNA‐binding proteins (LARPs): structures, functions, and evolving perspectives

La was first identified as a polypeptide component of ribonucleic protein complexes targeted by antibodies in autoimmune patients and is now known to be a eukaryote cell‐ubiquitous protein. Structure and function studies have shown that La binds to a common terminal motif, UUU‐3′‐OH, of nascent RNA polymerase III (RNAP III) transcripts and protects them from exonucleolytic decay. For precursor‐tRNAs, the most diverse and abundant of these transcripts, La also functions as an RNA chaperone that helps to prevent their misfolding. Related to this, we review evidence that suggests that La and its link to RNAP III were significant in the great expansions of the tRNAomes that occurred in eukaryotes. Four families of La‐related proteins (LARPs) emerged during eukaryotic evolution with specialized functions. We provide an overview of the high‐resolution structural biology of La and LARPs. LARP7 family members most closely resemble La but function with a single RNAP III nuclear transcript, 7SK, or telomerase RNA. A cytoplasmic isoform of La protein as well as LARPs 6, 4, and 1 function in mRNA metabolism and translation in distinct but similar ways, sometimes with the poly(A)‐binding protein, and in some cases by direct binding to poly(A)‐RNA. New structures of LARP domains, some complexed with RNA, provide novel insights into the functional versatility of these proteins. We also consider LARPs in relation to ancestral La protein and potential retention of links to specific RNA‐related pathways. One such link may be tRNA surveillance and codon usage by LARP‐associated mRNAs. WIREs RNA 2017, 8:e1430. doi: 10.1002/wrna.1430
Restoration of thalamo‐cortical connectivity after brain injury: recovery of consciousness, complex behavior, or passage of time?

In 2000, a landmark case report described the concurrent restoration of consciousness and thalamo‐frontal connectivity after severe brain injury (Laureys et al., ). Being a single case however, this study could not disambiguate whether the result was specific to the restoration of consciousness per se as opposed to the return of complex cognitive function in general or simply the temporal evolution of post‐injury pathophysiological events. To test whether the restoration of thalamo‐cortical connectivity is specific to consciousness, 20 moderate‐to‐severe brain injury patients (from a recruited sample of 42) underwent resting‐state functional magnetic resonance imaging within a week after injury and again six months later. As described in the single case report, we find thalamo‐frontal connectivity to be increased at the chronic, compared with the acute, time‐point. The increased connectivity was independent of whether patients had already recovered consciousness prior to the first assessment or whether they recovered consciousness in‐between the two. Conversely, we did find an association between restoration of thalamo‐frontal connectivity and the return of complex cognitive function. While we did replicate the findings of Laureys et al. ( ), our data suggests that the restoration of thalamo‐frontal connectivity is not as tightly linked to the reemergence of consciousness per se. However, the degree to which the return of connectivity is linked to the return of complex cognitive function, or to the evolution of other time‐dependent post‐injury mechanisms, remains to be understood.
Neoallergens in Heated Soybean Hull

Background: During the process of harvest, transport and storage, microbial and mold contamination can raise the temperature of soybeans to 75°C or higher. The purposes of this study were (1) to evaluate the allergenicity of fresh and stored soybean hulls and (2) to ascertain whether heat alters the allergenicity of stored soybean hulls. Methods: Allergen extracts were prepared from (1) stored soybean hulls, (2) fresh soybean hulls and (3) stored soybean hulls heated to 37°C (E1), 55°C (E2) and 80°C (E3) or kept at room temperature (E4) for 16 h. Individual serum from 68 soybean asthmatic (SA) subjects, 30 nonallergic subjects and two serum pools made from 4 SA sera and 4 sera from asthmatics not sensitive to soybean were studied. All sera and serum pools were assayed for content of specific IgE (radioallergosorbent test) and IgG4 (ELISA). The following additional studies were done for extracts E1–E4: (1) SDS–PAGE, (2) SDS–PAGE/Western blot for specific IgE and IgG4 using both serum pools, and (3) study of the effects of heat on inhibiting activity of the extracts prepared from stored soybean hulls using the pool of SA sera. Results: Test results demonstrated a reduced binding of specific IgE and IgG4 to fresh soybean hull extract compared to stored soybean hull extract, and an increased binding for heated extracts (E1–E3) compared to unheated ones (E4). Moreover, there was an increase in potency for IgE and IgG4 bindings for the heated (E1–E3) compared to unheated (E4) extract, as measured by the amount of protein to produce 50% inhibition. Several protein bands with a molecular weight (MW) higher than 20 kD were absent from the SDS–PAGE for E3 but were present in E1, E2 and E4, and a new protein band (MW 15.3 kD) appeared for E3 only. Two new protein bands, with MWs of 15.3 and 10 kD, which bind specific IgE, were present on Western blot and one of the 3 main soybean hull allergens, probably Gly m 2, disappeared in E3. IgG4 Western blot showed similar results, but only the 10 kD protein band was present. Conclusion: The results demonstrate that soybean hull allergenicity is affected by heat, and suggest that the heat generated during storage and transport of soybeans could generate 2 new allergen determinants or increases in epitope exposure as a result of conformational changes. The significance of these new IgE and IgG4 binding proteins has yet to be determined.
Morphological fine tuning of the feeding apparatus to proboscis length in Hesperiidae (Lepidoptera)

The form and function of the hesperiid feeding apparatus was studied in detail. The butterflies in the family Hesperiidae are of particular interest because the longest proboscis ever recorded in Papilionoidea was found in the Neotropical genus Damas. We focused on the functional morphology by comparing proboscis morphology as well as size and composition of both the stipes pump and the cibarial suction pump in skippers with short and extremely long proboscis. Results revealed that all studied Hesperiidae have the same proboscis micromorphology and sensilla endowment regardless of the proboscis length. However, the numbers of internal muscles of the proboscis, the morphology of the stipes pump as well as the pumping organs for nectar uptake are related to the proboscis length. We conclude that the low number of tip sensilla compared to proboscis length is responsible for remarkably longer manipulation times of long‐proboscid species during flower visits. The organs for proboscis movements and nectar uptake organs are well tuned to the respective proboscis length and are accordingly bigger in species with a proboscis that measures twice the body length.
Dealing With Information Overload in Multifaceted Personal Informatics Systems

Personal informatics systems are tools that capture, aggregate, and analyze data from distinct facets of their users’ lives. This article adopts a mixed-methods approach to understand the problem of information overload in personal informatics systems. We report findings from a 3-month study in which 20 participants collected multifaceted personal tracking data and used a system called Exist to reveal statistical correlations within their data. We explore the challenges that participants faced in reviewing the information presented by Exist, and we identify characteristics that exemplify “interesting” correlations. Based on these findings, we develop automated filtering mechanisms that aim to prevent information overload and support users in extracting interesting insights. Our approach deals with information overload by reducing the number of correlations shown to users by about 55% on average and increases the percentage of displayed correlations rated as interesting to about 81%, representing a 34 percentage point improvement over filters that only consider statistical significance at p < . 05. We demonstrate how this curation can be achieved using objective data harvested by the system, including the use of Google Trends data as a proxy for subjective user interest.
Development and External Validation of Prediction Models for 10-Year Survival of Invasive Breast Cancer. Comparison with PREDICT and CancerMath

Purpose: To compare PREDICT and CancerMath, two widely used prognostic models for invasive breast cancer, taking into account their clinical utility. Furthermore, it is unclear whether these models could be improved. Experimental Design: A dataset of 5,729 women was used for model development. A Bayesian variable selection algorithm was implemented to stochastically search for important interaction terms among the predictors. The derived models were then compared in three independent datasets (n = 5,534). We examined calibration, discrimination, and performed decision curve analysis. Results: CancerMath demonstrated worse calibration performance compared with PREDICT in estrogen receptor (ER)–positive and ER-negative tumors. The decline in discrimination performance was −4.27% (−6.39 to −2.03) and −3.21% (−5.9 to −0.48) for ER-positive and ER-negative tumors, respectively. Our new models matched the performance of PREDICT in terms of calibration and discrimination, but offered no improvement. Decision curve analysis showed predictions for all models were clinically useful for treatment decisions made at risk thresholds between 5% and 55% for ER-positive tumors and at thresholds of 15% to 60% for ER-negative tumors. Within these threshold ranges, CancerMath provided the lowest clinical utility among all the models. Conclusions: Survival probabilities from PREDICT offer both improved accuracy and discrimination over CancerMath. Using PREDICT to make treatment decisions offers greater clinical utility than CancerMath over a range of risk thresholds. Our new models performed as well as PREDICT, but no better, suggesting that, in this setting, including further interaction terms offers no predictive benefit. Clin Cancer Res; 24(9); 2110–5. ©2018 AACR.
All-In-Focus Synthetic Aperture Imaging Using Image Matting

“Seeing through” occluders is one of the most important effects that can be achieved with synthetic aperture imaging. As well, the occlusion problem, a challenging task for many computer vision applications, can be easily handled. Synthetic aperture imaging takes advantage of the property that only objects on the focal plane are sharp. The resulting image that is obtained by averaging images from different views consists of blurry objects away from the focal plane and sharp objects on the focal plane. Removing the blurriness caused by defocusing in synthetic aperture images to achieve an all-in-focus “seeing through” image is a challenging research problem. In this paper, we propose a novel method to improve the image quality of synthetic aperture imaging using image matting via energy minimization by estimating the foreground and the background. In particular, we first estimate the out-of-focus region by focusing on the background objects in each camera view using energy minimization. Next, we utilize a labeling method to create a sharp “see through” synthetic aperture image of the hidden objects. Then, image matting is used to extract the alpha matte of the hidden objects. Finally, by compositing the hidden objects with the estimated background regions, a sharp “see through” synthetic aperture image is created. The experimental results show that the proposed method outperforms the traditional synthetic aperture imaging method <xref ref-type="bibr" rid="ref1">[1]</xref> as well as its improved versions <xref ref-type="bibr" rid="ref2">[2]</xref>–<xref ref-type="bibr" rid="ref3"/><xref ref-type="bibr" rid="ref4">[4]</xref>, which simply dim and blur the area in the image that is out of focus, and a recent all-in-focus method <xref ref-type="bibr" rid="ref5">[5]</xref>. We show that both the occluded objects and the background can be combined using our method to create a sharp synthetic aperture image.
The Human Vocal Cords: A Mathematical Model

Abstract A mathematical model for digital computer simulation of human-like utterances is developed. The overall system consists of a period structure of 16 coupled masses for each of the vocal cords, an 18-section cylindrical tube approximation of the pharynx and mouth, and a similar 12-section nasal tract. Special care has been taken to model separately the functions of the vocal ligament, the vocalic muscle, and the mucosa. Simulated phonation in modal, mixed and falsetto registers is possible. The parameters which control the nature of the phonation are lung pressure, external tension applied to ligament, vocalis, and mucosa, and the internal muscular action of the vocalis. Applications are cited in areas which include vocal physiology, pathology, and pedagogy.
Histological scoring of immune and stromal features in breast and axillary lymph nodes is prognostic for distant metastasis in lymph node‐positive breast cancers

The prognostic importance of lymph node (LN) status and tumour‐infiltrating lymphocytes (TILs), is well established, particularly TILs in triple negative breast cancers (TNBCs). So far, few studies have interrogated changes in involved and uninvolved LNs and evaluated if their morphological patterns add valuable information for the prediction of disease progression in breast cancer. In a cohort of 309 patients enriched for TNBCs (170/309), we histologically characterised immune and stromal features in primary tumours and associated involved and uninvolved axillary LNs on routine haematoxylin and eosin stained sections. Of the 309 patients, 143 had LN‐positive disease. Twenty‐five histopathological features were assessed, including the degree of TIL presence, quantitative and qualitative assessment of germinal centres (GCs) and sinus histiocytosis. Multivariate and cross‐validated proportional hazard regression analyses were used to identify optimal covariate sets for prediction of distant metastasis‐free survival (DMFS). The degree of intratumoural and peritumoural immune infiltrate was associated with architectural changes in both uninvolved and involved LNs. By including clinicopathological characteristics as well as tumour and LN histopathological features in L2‐regularised proportional hazard models, the prediction of 5‐year DMFS was improved by 3–15% over the baseline in all cancers and in TNBCs. In LN‐positive cancers, the combination of Salgado's classification, lymphocytic lobulitis, size and number of GCs in the uninvolved LNs and location of GCs in the involved LNs carried significant prognostic information. From these features, a multivariate cross‐validation‐stable risk signature was constructed, which identified low‐risk groups within both LN‐positive breast cancers and the LN‐positive TNBCs group with a 10‐year DMFS probability of 78 and 87%, respectively. This study illustrates that, by incorporating histopathological patterns of involved and uninvolved LNs combined with primary tumour immune and stromal features, the prediction of developing distant metastasis in LN‐positive breast cancers can be estimated more accurately.
Correlative studies of growth hormone and insulin plasma concentrations with metabolic abnormalities in acromegaly.

Abstract Growth hormone concentrations were measured in the plasma of 59 individuals with acromegaly. In addition, 12 acromegalic patients were studied during oral glucose, intravenous insulin, and intravenous tolbutamide tolerance tests for changes in blood glucose and plasma insulin, nonesterified fatty acids (NEFA), and growth hormone concentrations. The acromegalic subjects had higher than normal plasma growth hormone concentrations which did not change following hypoglycemia or hyperglycemia to the same degree as those of the control subjects. As a consequence of chronic hypersecretion of growth hormone, the acromegalic patients manifested impaired glucose tolerance, despite a mean plasma insulin response which was 3 times normal. This antagonism to insulin cannot be attributed to alterations in fasting plasma NEFA levels.
ZOO-FISH analysis in insectivores: “Evolution extols the virtue of the status quo”

In evolutionary terms, insectivores are thought to be close to primates. Through ZOO-FISH analysis using human chromosome-specific painting probes, the syntenic relationship between the human and common shrew, Sorex araneus, karyotypes was studied. The human karyotype was found to be conserved in the shrew, with 32 autosomal segments of common synteny. Special arrangements, already known from similar studies on other species, were noted: fusions of HSA 16 and 19, HSA 3 and 21, and HSA 14 and 15. Only 10 breaks are necessary to transform the human karyotype into the karyotype of the common shrew. Together with known ZOO-FISH data from species belonging to other orders, this puts the human karyotype arrangement near the basis of all mammalian karyotypes. Human chromosome 2 was found to be conserved in its entirety as a single chromosome arm in the shrew. Evidence is presented that the same fusion of two original chromosomal segments formed the shrew chromosome ortholog of HSA 2 as the fusion that occurred during primate evolution to form human chromosome 2. This is a remarkable example of chromosomal coevolution.
Analysis of pH–Driven Disruption of Oral Microbial Communities in vitro

Previously, a mixed culture chemostat system was used to demonstrate that the pH generated from carbohydrate metabolism, rather than carbohydrate availability per se, was responsible for the shifts observed in the oral microflora which are associated with high carbohydrate diets and the development of dental caries. The aim of this study was to determine more accurately the microbially generated pH at which such shifts occurred. Nine oral bacteria were grown in three independent chemostats, and pulsed with glucose on 10 consecutive days. In one chemostat, pH control was discontinued for 6 h, and the pH fall was restricted to a minimum value of pH 5.5; the pH fall was arrested in the other two chemostats at either pH 5.0, or at pH 4.5. When the pH was allowed to fall, the numbers and proportions of Streptococcus mutans and Lactobacillus rhamnosus increased; this increase was directly related to the magnitude of the pH fall. Veillonella dispar was the most numerous organism following all glucose pulsing regimes, especially at low pH. The increase in proportions of acidogenic bacteria was accompanied by a fall in the proportions of acid–sensitive species (Fusobacterium nucleatum, Prevotella nigrescens, Streptococcus gordonii and Streptococcus oralis). The counts of these species were relatively stable between pH 5.5 and 4.5, but were markedly reduced when the pH fell below pH 4.5; Neisseria subflava could not persist in the culture at pH 4.5 or below. The data suggest that the disruption of communities associated with glucose metabolism and low pH can be explained in terms of a two–stage process. A fall in pH to a value between pH 5.5 and 4.5 may allow the enrichment of potentially cariogenic species, whilst permitting species associated with health to remain relatively unaffected. A further reduction in pH (<pH 4.5) may not only enhance the competitiveness of odontopathogens, but inhibit the growth and metabolism of non–caries–associated species. The results also indicate that species other that mutans streptococci or lactobacilli are competitive at pH values low enough to demineralise enamel, and thus suggest that a broader range of micro–organisms may be associated with caries initiation.
Isoenzymatic characterization of Phlebotomus ariasi and P. perniciosus of canine leishmaniasis foci from Eastern Pyrenean regions and comparison with other populations from Europe

An entomological survey was carried out in 2007 in two Pyrenean counties of Lleida province (north-eastern Spain), where cases of autochthonous canine leishmaniasis have been recently reported. Phlebotomus ariasi and P. perniciosus, vectors of Leishmania infantum in the Mediterranean area, were captured. The aim of the present study was to compare these phlebotomine populations with others captured in known leishmaniasis foci in Europe. Populations of these species were studied by analysing the polymorphism of seven enzymatic systems (HK, PGI, PGM, MDH, 6PGD, FUM and ACO) and compared with other specimens from endemic regions of France, Italy, Malta, Portugal and Spain captured in other campaigns, and also with previously published results. Phlebotomus ariasi was more polymorphic than P. perniciosus. Only the ACO locus had diagnostic alleles, but some other alleles show high characteristic frequencies for each species. The neighbour-joining trees separated two population groups in both species. On the basis of the isoenzyme study results, sand fly populations of the Pyrenean region in Lleida province are closely related to those of other nearby leishmaniasis endemic regions in France and Spain.
Hierarchical Organization of Tau and Amyloid Deposits in the Cerebral Cortex

Importance Abnormal accumulation of tau and amyloid-&bgr; (A&bgr;) proteins in the human brain are 2 pathologic hallmarks of Alzheimer disease (AD). Because pathologic processes begin decades before the onset of the clinical manifestations, the study of the cortical distribution of early-stage pathologic alterations is critical in understanding the underpinnings of the disease. Objectives To identify the in vivo brain spatial distributions of tau and A&bgr; deposits in a sample of cognitively normal participants in the Harvard Aging Brain Study, determine spatial patterns of pathologic alterations, and provide means for improved individual in vivo staging. Design, Setting, and Participants Eighty-eight individuals from the general community underwent flortaucipir 18 T807 (18F-T807) and carbon 11–labeled Pittsburgh Compound B (11C-PiB) positron emission tomographic (PET) imaging. A voxel-level hierarchical clustering approach was used to obtain the main clustering partitions corresponding to the cortical distribution maps of 18F-T807 and 11C-PiB. Hierarchical relationships between areas of distinctive pathologic deposits were then studied. Using cerebellar gray reference, 18F-T807 data were expressed as standardized uptake value ratio, and 11C-PiB were given as distribution volume ratio. Main Outcomes and Measures Main in vivo and hierarchically organized tau and A&bgr; deposits in the elderly brain. Results Of the 88 study participants, 39 (44%) were men, with a mean (SD) age of 76.2 (6.2) years. The tau and A&bgr; maps both displayed optimal cortical partitions at 4 clusters. The tau deposits were grouped in the temporal lobe, distributed in heteromodal areas, medial and visual regions, and primary somatomotor cortex; the A&bgr; deposits were clustered in the heteromodal areas and rather patchy in distributed regions involving the primary cortices, medial structures, and temporal areas. Moreover, tau deposits in the temporal lobe and distributed heteromodal areas were tightly nested. Conclusions and Relevance Tau and A&bgr; deposits in the elderly brain generally display well-defined hierarchical cortical relationships as well as overlaps between the principal clusters of both pathologic alterations in the heteromodal association regions. These findings represent systematic, large-scale mechanisms of early AD pathology.