Miracle-dz/UniFAR-FTUs huggingface dataset:
The human protein atlas: A spatial map of the human proteome

The correct spatial distribution of proteins is vital for their function and often mis‐localization or ectopic expression leads to diseases. For more than a decade, the Human Protein Atlas (HPA) has constituted a valuable tool for researchers studying protein localization and expression in human tissues and cells. The centerpiece of the HPA is its unique antibody collection for mapping the entire human proteome by immunohistochemistry and immunocytochemistry. By these approaches, more than 10 million images showing protein expression patterns at a single‐cell level were generated and are publicly available at www.proteinatlas. org. The antibody‐based approach is combined with transcriptomics data for an overview of global expression profiles. The present article comprehensively describes the HPA database functions and how users can utilize it for their own research as well as discusses the future path of spatial proteomics.
Pediatric Chronic Rhinosinusitis Management in Rhinologists and Pediatric Otolaryngologists

Objective: To compare the management of pediatric chronic rhinosinusitis (PCRS) between members of the American Rhinologic Society (ARS) and the American Society of Pediatric Otolaryngology (ASPO). Study Design: Comparison of surveys. Methods: A web-based survey was distributed to ASPO membership twice in September-October 2016. Data were compared to previously published data from ARS membership in March-April 2016. Results: ASPO survey completion rate was 22%. ARS members were more likely to employ oral steroids in initial (P = .025) and maximal medical management (P = .001). ASPO members more commonly performed adenoidectomy before computed tomography (CT) (P < .001). Both groups commonly included adenoidectomy as part of initial surgical management (90% vs 94%, P = .316), while ASPO members more frequently performed adenoidectomy alone (70% vs 43%, P = .001). If initial surgical treatment failed, both groups commonly performed endoscopic sinus surgery (ESS; 81% vs 88%, P = .56) with a similar extent including frontal (P ≥ .207) and sphenoid (P ≥ .304) surgery. Conclusions: Pediatric chronic rhinosinusitis management is similar between groups, yet there are differences including oral steroid use, relative order of CT versus adenoidectomy, and performing concomitant procedures with adenoidectomy. Both groups commonly perform ESS with similar surgical extent if prior surgical treatment fails. Management by both groups is largely in agreement with published consensus statements.
Structural characterization of the catalytic γ and regulatory β subunits of phosphorylase kinase in the context of the hexadecameric enzyme complex

In the tightly regulated glycogenolysis cascade, the breakdown of glycogen to glucose‐1‐phosphate, phosphorylase kinase (PhK) plays a key role in regulating the activity of glycogen phosphorylase. PhK is a 1.3 MDa hexadecamer, with four copies each of four different subunits (α, β, γ and δ), making the study of its structure challenging. Using hydrogen‐deuterium exchange, we have analyzed the regulatory β subunit and the catalytic γ subunit in the context of the intact non‐activated PhK complex to study the structure of these subunits and identify regions of surface exposure. Our data suggest that within the non‐activated complex the γ subunit assumes an activated conformation and are consistent with a previous docking model of the β subunit within the cryoelectron microscopy envelope of PhK.
A structural overview of mycobacterial adhesins: Key biomarkers for diagnostics and therapeutics

Adherence, colonization, and survival of mycobacteria in host cells require surface adhesins, which are attractive pharmacotherapeutic targets. A large arsenal of pilus and non‐pilus adhesins have been identified in mycobacteria. These adhesins are capable of interacting with host cells, including macrophages and epithelial cells and are essential to microbial pathogenesis. In the last decade, several structures of mycobacterial adhesins responsible for adhesion to either macrophages or extra cellular matrix proteins have been elucidated. In addition, key structural and functional information have emerged for the process of mycobacterial adhesion to epithelial cells, mediated by the Heparin‐binding hemagglutinin (HBHA). In this review, we provide an overview of the structural and functional features of mycobacterial adhesins and discuss their role as important biomarkers for diagnostics and therapeutics. Based on the reported data, it appears clear that adhesins are endowed with a variety of different structures and functions. Most adhesins play important roles in the cell life of mycobacteria and are key virulence factors. However, they have adapted to an extracellular life to exert a role in host‐pathogen interaction. The type of interactions they form with the host and the adhesin regions involved in binding is partly known and is described in this review.
Possible Influences on the Interpretation of Functional Domain (FD) Near-Infrared Spectroscopy (NIRS): An Explorative Study

The influence of subcutaneous adipose tissue (ATT) and oxygen (O2) delivery has been poorly defined in frequency domain (FD) near-infrared spectroscopy (NIRS). Therefore, the aim of this study was to investigate the possible influence of these variables on all FD NIRS responses using a reliable protocol. Moreover, these influences were also investigated when using relative oxy- and deoxyhemoglobin and -myoglobin (oxy[Hb + Mb] and deoxy[Hb + Mb]) values (in %). A regression analysis was carried out for ATT and maximal–minimum oxy[Hb + Mb], deoxy[Hb + Mb], oxygen saturation (SmO2), and total hemoglobin (totHb) amplitudes during an incremental cyclic contraction protocol (ICCP) in a group of 45 participants. Moreover, the same analysis was carried out between subcutaneous ATT and the relative oxy- and deoxy[Hb + Mb] values (in %). In the second part of this study, a regression analysis was performed for peak forearm blood flow (FBF) during ICCP and the absolute and relative NIRS values in a group of 37 participants. Significant exponential correlation coefficients were found between ATT and deoxy[Hb + Mb] (r = 0.53; P < 0.001), oxy[Hb + Mb] (r = 0.57; P < 0.001), and SmO2 amplitudes (r = 0.57; P < 0.001). No significant relations were found between ATT and relative oxy[Hb + Mb] (r = 0.37; P = 0.07) and deoxy[Hb + Mb] (r = 0.09; P = 0.82). Significant positive correlation coefficients were found between force at exhaustion and maximal FBF (r = 0.66; P < 0.001), maximal differences in deoxy[Hb + Mb] (r = 0.353; P = 0.032) and totHb (r = 0.512; P = 0.002) while no significant correlation coefficients were found between these maximal force values and maximal differences in oxy[Hb + Mb] (r = −0.267; P = 0.111) and SmO2 (r = −0.267; P = 0.111). Significant linear correlation coefficients were found between FBF and deoxy[Hb + Mb] (r = 0.51; P = 0.001), oxy[Hb + Mb] (r = −0.50; P = 0.001), SmO2 (r = −0.54; P = 0.001), and totHb amplitude (r = 0.61; P < 0.001). No significant correlations were found when using relative oxy[Hb + Mb] (r = −0.01; P = 0.957) and deoxy[Hb + Mb] (r = −0.02; P = 0.895). Based on these findings, caution is advised when using NIRS values, as subcutaneous ATT and O2 delivery significantly influence NIRS measurements. To eliminate these influences, use of relative deoxy[Hb + Mb] is advised, especially in clinical settings or in people with a higher subcutaneous ATT layer.
Assessment of Fatigue in Undifferentiated Spondyloarthritis (USpA)

Objectives: This study aimed to evaluate the fatigue in patients with undifferentiated spondyloarthritis [USpA], and its relationship with disease-specific variables, spinal mobility measures and healthy related quality of life [HRQOL]. Methods: Eighty patients with USpA and forty healthy subjects were included in this study. The multidimensional assessment of fatigue [MAF] and the generic instrument Short Form 36 [SF 36] were used in patient and control groups to assess fatigue and [HRQOL]. Fatigue was also assessed with the Bath ankylosing spondylitis disease activity index [BASDAI] fatigue item. The evaluation included the activity of the disease [BASDAI], functional status [Bath ankylosing spondylitis functional index], and visual analog scale [VAS] of axial and joint pain. Demographics and disease-related data were obtained. Results: Patients with USpA had higher scores in MAF total and in all MAF subgroup scales than controls. All SF-36 subgroups scores were also found to be significantly lower in patients. Severe fatigue experienced 60% in patients. MAF total scores were found to be significantly correlated with morning stiffness, BASDAI, Bath ankylosing spondylitis functional index (BASFI), BASDAI fatigue, VAS-axial, and SF-36 subgroups scores in patients [p < 0.05]. Conclusions: The patients with USpA defined significantly more fatigue and lower HRQOL when compared with healthy persons. MAF was found to be related with the clinical and functional status and health-related quality of life of patients with USpA.
Design, selection, and characterization of a split chorismate mutase

Split proteins are versatile tools for detecting protein–protein interactions and studying protein folding. Here, we report a new, particularly small split enzyme, engineered from a thermostable chorismate mutase (CM). Upon dissecting the helical‐bundle CM from Methanococcus jannaschii into a short N‐terminal helix and a 3‐helix segment and attaching an antiparallel leucine zipper dimerization domain to the individual fragments, we obtained a weakly active heterodimeric mutase. Using combinatorial mutagenesis and in vivo selection, we optimized the short linker sequences connecting the leucine zipper to the enzyme domain. One of the selected CMs was characterized in detail. It spontaneously assembles from the separately inactive fragments and exhibits wild‐type like CM activity. Owing to the availability of a well characterized selection system, the simple 4‐helix bundle topology, and the small size of the N‐terminal helix, the heterodimeric CM could be a valuable scaffold for enzyme engineering efforts and as a split sensor for specifically oriented protein–protein interactions.
The influence of open access on journal cancellations in university libraries in South Africa

Purpose – The purpose of the paper is to present the influence open access initiatives (OAIs) have on journal cancellations in university libraries in South Africa. Design/methodology/approach – The paper is based on part of a doctoral research project which examined the crisis in scholarly communication and its effect on university libraries in South Africa that was carried out at the University of KwaZulu-Natal from 2005 to 2009. Part of the investigation focused on open access (OA) and how it influenced journal cancellations. The survey methodology was adopted and the study used a quantitative approach to collect data on the influence of OA. Findings – The findings revealed that OAIs had a very limited influence on journal cancellations in South African university libraries. Practical implications – The study presents data that can be used by university libraries to develop, support and facilitate access to local research. Originality/value – The study provides data on which future developments in OA a.
A mutant form of PTEN linked to autism

The tumor suppressor, phosphatase, and tensin homologue deleted on chromosome 10 (PTEN), is a phosphoinositide (PI) phosphatase specific for the 3‐position of the inositol ring. PTEN has been implicated in autism for a subset of patients with macrocephaly. Various studies identified patients in this subclass with one normal and one mutated PTEN gene. We characterize the binding, structural properties, activity, and subcellular localization of one of these autism‐related mutants, H93R PTEN. Even though this mutation is located at the phosphatase active site, we find that it affects the functions of neighboring domains. H93R PTEN binding to phosphatidylserine‐bearing model membranes is 5.6‐fold enhanced in comparison to wild‐type PTEN. In contrast, we find that binding to phosphatidylinositol‐4,5‐bisphosphate (PI(4,5)P2) model membranes is 2.5‐fold decreased for the mutant PTEN in comparison to wild‐type PTEN. The structural change previously found for wild‐type PTEN upon interaction with PI(4,5)P2, is absent for H93R PTEN. Consistent with the increased binding to phosphatidylserine, we find enhanced plasma membrane association of PTEN‐GFP in U87MG cells. However, this enhanced plasma membrane association does not translate into increased PI(3,4,5)P3 turnover, since in vivo studies show a reduced activity of the H93R PTEN‐GFP mutant. Because the interaction of PI(4,5)P2 with PTEN's N‐terminal domain is diminished by this mutation, we hypothesize that the interaction of PTEN's N‐terminal domain with the phosphatase domain is impacted by the H93R mutation, preventing PI(4,5)P2 from inducing the conformational change that activates phosphatase activity.
Human thymidylate synthase with loop 181–197 stabilized in an inactive conformation: Ligand interactions, phosphorylation, and inhibition profiles

Thymidylate synthase (TS) is a well‐validated cancer target that undergoes conformational switching between active and inactive states. Two mutant human TS (hTS) proteins are predicted from crystal structures to be stabilized in an inactive conformation to differing extents, with M190K populating the inactive conformation to a greater extent than A191K. Studies of intrinsic fluorescence and circular dichroism revealed that the structures of the mutants differ from those of hTS. Inclusion of the substrate dUMP was without effect on M190K but induced structural changes in A191K that are unique, relative to hTS. The effect of strong stabilization in an inactive conformation on protein phosphorylation by casein kinase 2 (CK2) was investigated. M190K was highly phosphorylated by CK2 relative to an active‐stabilized mutant, R163K hTS. dUMP had no detectable effect on phosphorylation of M190K; however, dUMP inhibited phosphorylation of hTS and R163K. Studies of temperature dependence of catalysis revealed that the Eact and temperature optimum are higher for A191K than hTS. The potency of the active‐site inhibitor, raltitrexed, was lower for A191K than hTS. The response of A191K to the allosteric inhibitor, propylene diphosphonate (PDPA) was concentration dependent. Mixed inhibition was observed at low concentrations; at higher concentrations, A191K exhibited nonhyperbolic behavior with respect to dUMP and inhibition of catalysis was reversed by substrate saturation. In summary, inactive‐stabilized mutants differ from hTS in thermal stability and response to substrates and PDPA. Importantly, phosphorylation of hTS by CK2 is selective for the inactive conformation, providing the first indication of physiological relevance for conformational switching.
Performance of Aphasic Patients on Dichotic Listening Tests

Research Associate, Department of Otolaryngology, University of Minnesota, Minneapolis, Minnesota Dichotic listening involves the simultaneous presentation of a different auditory stimulus to each ear. This paradigm was originally developed by Broadbent (1954) to study selective attention. He was the first to report that when the system was overloaded in this fashion, listeners tended to report more accurately stimuli presented to the right ear than that presented to the left ear. However, Kimura (1961a) was the first to hypothesize a relationship between this observed right ear advantage (REA) on verbal dichotic listening tests and left hemisphere dominance for language processing. Her model reflected two assumptions: that the left hemisphere was the dominant hemisphere for language processing in most listeners, and that the contralateral pathways were functionally prepotent over the ipsilateral pathways. This simple model is represented in Figure 1. In support of this model, Kimura reported in a companion paper (1961b) that 13 listeners who had been shown to have right hemisphere dominance for speech and/or language on the basis of sodium amytal tests had left ear advantages (LEAs) on verbal dichotic listening tests. Furthermore, a few years later, Kimura (1964) reported finding LEAs on a dichotic listening test in which melodies were the stimuli. Milner (1962) previously had found that performance on certain subtests of the Seashore Measures of Musical Talents were depressed by removal of the right temporal lobe, but not by removal of the left temporal lobe, a finding interpreted by many as evidence of right hemisphere dominance for perception of music. Thus, dichotic listening seemed to provide a noninvasive technique for establishing hemispheric dominance. That is, it was assumed that the dominant hemisphere for processing a particular class of stimuli was the one contralateral to the ear with the higher score on dichotic listening tests. In addition to the ' 'dominance effect," interpretation of dichotic listening results, Kimura (1961a) also described a "lesion effect. " She found that scores were reduced more for the ear contralateral to an excised temporal lobe than for the ear ipsilateral to
Characterization of Developmental Immature Fiber (im) Mutant and Texas Marker-1 (TM-1) Cotton Fibers Using Attenuated Total Reflection Fourier Transform Infrared (ATR FT-IR) Spectroscopy

The immature fiber (im) mutant is one type of cotton fiber mutant with unique characteristics of non-fluffy cotton bolls. Compared to its near-isogenic wild type Texas Marker-1 (TM-1), im fiber has a thin secondary cell wall and is less mature. In this work, we applied the previously proposed principal component analysis (PCA) and simple algorithms to analyze the attenuated total reflection Fourier transform infrared (ATR FT-IR) spectra of developmental im and TM-1 fibers. The results from these approaches could not effectively and consistently indicate the inherent difference between TM-1 and im fibers at the same developmental stage. The difference between TM-1 and corresponding im fibers was detected when comparing the normalized intensity variations of the 730 cm−1 bands. The 730 cm−1 band intensities in developmental im fibers are temporally lower than those in developmental TM-1 fibers although they became similar when the TM-1 and im fibers are fully mature. The observation might imply the likelihood of temporal reduction of amorphous regions in developmental im fibers rather than in developmental TM-1 fibers.
A structure‐based benchmark for protein–protein binding affinity

We have assembled a nonredundant set of 144 protein–protein complexes that have high‐resolution structures available for both the complexes and their unbound components, and for which dissociation constants have been measured by biophysical methods. The set is diverse in terms of the biological functions it represents, with complexes that involve G‐proteins and receptor extracellular domains, as well as antigen/antibody, enzyme/inhibitor, and enzyme/substrate complexes. It is also diverse in terms of the partners' affinity for each other, with Kd ranging between 10−5 and 10−14M. Nine pairs of entries represent closely related complexes that have a similar structure, but a very different affinity, each pair comprising a cognate and a noncognate assembly. The unbound structures of the component proteins being available, conformation changes can be assessed. They are significant in most of the complexes, and large movements or disorder‐to‐order transitions are frequently observed. The set may be used to benchmark biophysical models aiming to relate affinity to structure in protein–protein interactions, taking into account the reactants and the conformation changes that accompany the association reaction, instead of just the final product.
The Effect of Moderate Temperatures on Latent Fingerprint Chemistry

The effect of moderate temperatures (25–75 ℃) on latent fingerprints over a five-hour period was examined using Fourier transform infrared (FT-IR) microspectroscopy. The aim of the study was to detect changes in IR spectra due to any changes in fingerprint chemistry; these results were then compared to pure compounds found in sebum that was subjected to 75 ℃ for 5 h. Latent fingerprints deposited on CaF2 microscope slides and placed on a Peltier pump heating stage showed that higher temperatures significantly reduced the quantity of sebaceous compounds after 5 h, whereas temperatures below 45 ℃ had little effect on the quantity of these compounds over the same time period. Fourier transform infrared microspectroscopy allowed for the real-time detection of changes to the IR spectra and demonstrated an increase in the OH stretch band (3250 cm–1) over 5 h at all temperatures investigated, suggesting various oxidation processes were taking place. Pure samples analyzed included squalene, fatty acids, wax esters, and mixed triglycerides. Unsaturated lipids showed a similar increase in the OH stretch band to the latent fingerprints whereas saturated compounds showed no change over time. This information is required to better understand the effect of moderate temperatures on latent fingerprints and how these temperatures could affect aged print composition.
Parental Overprotection Predicts the Development of Functional Somatic Symptoms in Young Adolescents

Objective To examine whether parental overprotection contributes to the development of functional somatic symptoms (FSS) in young adolescents. In addition, we aimed to study whether this potential effect of parental overprotection is mediated by parenting distress and/or moderated by the adolescent’s sex. Study design FSS were measured in 2230 adolescents (ages 10 to 12 years from the Tracking Adolescents’ Individual Lives Survey) by the Somatic Complaints subscale of the Youth Self Report at baseline and at follow-up 2 1 ⁄ 2 years later. Parental overprotection as perceived by the child was assessed by means of the EMBU-C (Swedish acronym for my memories of upbringing–child version). Parents completed the Parenting Stress Index. Linear regression analyses were performed adjusted for FSS at baseline and sex.