Miracle-dz/UniFAR-FTUs huggingface dataset:
Activation and Desensitization Induce Distinct Conformational Changes at the Extracellular-Transmembrane Domain Interface of the Glycine Receptor*

Background: Despite its physiological significance, the structural basis of desensitization in Cys-loop receptors is unknown. Results: Fluorescent reporters attached to residues at the interface of the glycine receptor ligand binding and transmembrane domains indicate that activation and desensitization induce distinct local conformational changes. Conclusion: Desensitization induces an interfacial conformational change incompatible with activation. Significance: This provides a mechanism for understanding desensitization. Most ligand-gated channels exhibit desensitization, which is the progressive fading of ionic current in the prolonged presence of agonist. This process involves conformational changes that close the channel despite continued agonist binding. Despite the physiological and pathological importance of desensitization, little is known about the conformational changes that underlie this process in any Cys-loop ion channel receptor. Here we employed voltage clamp fluorometry to identify conformational changes that occur with a similar time course as the current desensitization rate in both slow- and fast-desensitizing α1 glycine receptor chloride channels. Voltage clamp fluorometry provides a direct indication of conformational changes that occur in the immediate vicinity of residues labeled with environmentally sensitive fluorophores. We compared the rates of current desensitization and fluorescence changes at nine labeled extracellular sites in both wild type slow-desensitizing and mutated (A248L) fast-desensitizing glycine receptors. As labels attached to three sites at the interface between the ligand binding domain and transmembrane domain reported fluorescence responses that changed in parallel with the current desensitization rate, we concluded that they experienced local conformational changes associated with desensitization. These labeled sites included A52C in loop 2, Q219C in the pre-M1 domain, and M227C in the M1 domain. Activation and desensitization were accompanied by physically distinct conformational changes at each labeled site. Because activation is mediated by a specific reorganization of molecular interactions at the extracellular-transmembrane domain interface, we propose that desensitization is mediated by a distinct set of conformational changes that prevents this reorganization from occurring, thereby favoring channel closure.
Clinicopathologic analysis of ocular adnexal lymphomas: Extranodal marginal zone b‐cell lymphoma constitutes the vast majority of ocular lymphomas among Koreans and affects younger patients

The majority of ocular adnexal lymphomas (OAL) are primary marginal zone B‐cell lymphomas (MALT lymphomas). The present study correlated the clinicopathological variables with the histologic subtypes by World Health Organization (WHO) classification with emphasis on MALT lymphomas in OALs of Koreans. There were 68 cases (31 males and 37 females), with a mean age of 45.9 years (range 7–89 years). Histologically, 61 MALT‐type, 2 diffuse large B‐cell (DLBCL), 2 mantle cell type (MCL), 1 anaplastic large‐cell (ALCL), and 2 NK/T‐cell lymphomas (NK/T‐L) were counted among them. Fifty‐seven were primary cases (P‐OAL), and 11 were secondary cases (S‐OAL). Nearly all P‐OALs were MALT lymphomas (n = 56, 98%), with an exception of 1 MCL. Eleven S‐OALs included 5 MALT type, 2 DLBCL, 1 ALCL, 1 MCL, and 2 NK/T‐L. All MALT lymphoma patients were alive (n = 59) except for 2 after a mean duration of follow‐up of 27.6 months (range: 0–108 months): one died of an unrelated cause and one died of recurrence. One non‐MALT type P‐OAL was alive with no evidence of disease (42 months). Of the 11 S‐OAL, 4 had marrow involvement and 5 had progression or relapse outside the orbit. Compared with the other subtypes, MALT lymphoma was more likely to present with local disease (P = 0.001), achieve complete remission (CR) (0.022), and be alive at last follow‐up (0.197), and less likely to experience recurrence (P = 0.06). In conclusion, OALs in Koreans are characterized by a preponderance of primary lymphomas over systemic lymphomas, striking predominance of MALT type lymphomas, and young age of occurrence. Histologic subtype by WHO classification has a significant correlation with the final outcome, with the most favorable outcome associated with OALs of the MALT type. Am. J. Hematol. 73:87–96, 2003. © 2003 Wiley‐Liss, Inc.
Urological malignancy after renal transplantation

Immunosuppression in solid‐organ recipients is associated with a greater risk of de novo malignancy after transplantation; herein we report the UK transplant registry (UKTR) database of urological cancer after renal transplantation in the UK transplant population. From September 1999 to January 2006 there were 10 847 kidney recipients with at least one period of follow‐up reported after a kidney transplant (mean age at transplantation 42.4 years, sd 15.5; 6685 male, 61.6%, and 4162 female, 38.3%). The recipients represent a homogenous group who received different immunosuppression regimens. Skin cancer was excluded from the study. Unfortunately, the UKTR does not collect information about the presence or absence of cancer, either at registration onto the transplant waiting list or at transplantation. In all, 214 (1.9%) patients were reported to have a subsequent urological malignancy diagnosed among the 10 847 recipients. The UKTR was used to identify patients who developed urological malignancies after renal transplantation, which is a challenging event after solid‐organ transplantation. Regular surveillance to diagnose early occurrence and adjustment of immunosuppression might be beneficial. In the presence of metastatic disease, chemotherapy treatment with adjustment or cessation of immunosuppressive therapy is required.
Role of Iron in Human Serum Resistance of the Clinical and Environmental Vibrio vulnificus Genotypes

ABSTRACT We recently reported a simple PCR procedure that targets a sequence variation of the virulence-correlated gene locus vcg. It was found that 90% of all clinical isolates possessed the vcgC sequence variant, while 93% of all environmental isolates possessed the vcgE sequence variant. Here we report that the clinical genotype of Vibrio vulnificus is significantly better able to survive in human serum than is the environmental genotype. The presence of a siderophore-encoding gene, viuB, influenced serum survivability among all isolates of V. vulnificus tested. Those strains positive for viuB (all C-type strains but very few E-type strains) showed greater serum survivability than those lacking viuB (most E-type strains). The addition of iron (in the form of ferric ammonium citrate) to human serum restored the survival of E-type strains lacking viuB to levels not significantly different from those of C-type and E-type strains that possess viuB. These findings suggest that viuB may dictate serum survival in both C- and E-type strains of V. vulnificus and may explain why some strains (C- and E-type strains) are pathogenic and others (predominately E-type strains) are not. Additionally, C-type strains exhibited a cross-protective response against human serum, not exhibited by E-type strains, after incubation under nutrient and osmotic downshift conditions that mimicked estuarine waters. This suggests that the nutrient/osmotic environment may influence the survival of V. vulnificus following entry into the human body, leading to selection of the C genotype over the E genotype.
Selected Contemporary Challenges of Ageing Policy

This volume-"Selected Contemporary Challenges of Aging Policy"-is the most international of all published monographs from the series "Czech-Polish-Slovak Studies in Andragogy and Social Gerontology. " Among the scholars trying to grasp the nuances and trends of social policy, there are diverse perspectives, resulting not only from the extensive knowledge of the authors on the systematic approach to the issue of supporting older people but also from the grounds of the represented social gerontology schools. In the texts of Volume VII interesting are both distinct and coherent elements presenting the role of local, regional and global policies in the prism of the countries from which the authors originate: the Czech Republic, Slovenia, Lithuania, Latvia, Poland, Slovakia, Italy, Turkey, and the United States. The chapters show a wealth of methodological approaches to the perception of social policy and its tools. In the texts there are issues related to the idea of active ageing, discrimination against older people in the workplace, comparability of solutions friendly to employment of older adults in the Czech Republic, Poland, and Slovakia as well as focused on the importance of educational forms (universities of the third age, senior clubs, folk high schools, and other non-formal solutions) determining an active life in old age. This monograph also attempted to answer the question regarding how to transfer the idea of intergenerational learning into the realm of practice. This issue complements the chapter on the implementation of intergenerational programs in institutions providing long-term care support. The book also outlines a public policy on ageing in the perspective of the changes over the last few decades (Slovenia) and the case demonstrating solutions to accelerate self-reliance as a key to active ageing (Turkey). We hope that seventh volume of our series will be an intellectual stimulus for further international research on change in social policy and will contribute to the dissemination of best practices as well as contribute to positive social change.
Regional attitudes of generalists, specialists, and subspecialists about management of atrial fibrillation.

BACKGROUND It is unknown whether physicians' attitudes about the management of atrial fibrillation (AF) reflect the recommendations of published guidelines. METHODS To obtain information about physicians' attitudes about management of AF, a questionnaire was returned by 904 (20.1%) of 4500 physicians involved in managing AF (385 cardiologists, 326 internists, and 193 electrophysiologists). The cardiologists and internists were from Massachusetts or California; the electrophysiologists were from around the United States. The questionnaire called for 86 separate answers about use of resources and drug therapy for different types of AF, including recent-onset AF, paroxysmal AF, and chronic AF of less than 6 months' and more than 3 years' duration. RESULTS Transthoracic echocardiography and thyroid function were requested by more than 90% of physicians; transesophageal echocardiography and catheterization were requested by 10% of physicians. To control ventricular response, digoxin was the overwhelming first-line therapy; calcium channel blockers were favored over beta-blockers for adjunct therapy. To prevent thromboemboli, warfarin sodium was preferred for chronic AF; warfarin or aspirin were equally considered for paroxysmal AF. In considering sinus rhythm, respondents agreed about factors determining whether to revert, the number of drug trials, and the first-line drug choice (quinidine sulfate) but disagreed about second-line antiarrhythmic drugs and whether to hospitalize the patient before initiating drug therapy. CONCLUSIONS Physicians ranging from primary care providers to subspecialists agree on issues of AF management such as heart rate control and anticoagulation. Attitudes vary widely about issues such as antiarrhythmic drugs.
Sexting, Risk Behavior, and Mental Health in Adolescents: An Examination of 2015 Pennsylvania Youth Risk Behavior Survey Data.

BACKGROUND Sexting, the sharing of sexually suggestive photos, may be a gateway behavior to early sexual activity and increase the likelihood of social ostracism. METHODS Youth Risk Behavior Survey (N = 6021) data from 2015 among Pennsylvania 9th-12th grade students were used to examine associations between consensual and nonconsensual sexting and substance use, mental health, neighborhood safety, and demographic variables. RESULTS Almost one-third (29%) of students reported consensual sexting, while 3% reported nonconsensual sexting. Female students were 49% less likely to report consensual sexting (OR = .69, 95% confidence interval [CI]: [0.54, 0.87]); consensual sexting was significantly more likely in students who reported depressive symptoms (OR = 1.39, 95% CI: [1.10, 1.75]), electronic bullying (OR = 1.46, 95% CI: [1.05, 2.04]), suicide attempts (OR = 1.96, 95% CI: [1.22, 3.17]), current tobacco use (OR = 1.99, 95% CI: [1.30, 3.03]), current alcohol use (OR = 4.23, 95% CI: [3.04, 5.89]), ever having sex (OR = 5.21, 95% CI: [3.87, 7.02]), and reported both ever having sex, and current alcohol use (OR = 7.74, 95% CI: [5.37, 11.14]). CONCLUSIONS High school students, particularly men, that report sexting may be more likely to participate in other risk behaviors and experience negative mental health outcomes. Further research should clarify the temporality of links between sexting, cyberbullying, depression, and suicide to inform mental health screening and treatment availability in high schools.
Race-ing solidarity: Asian Americans and support for Black Lives Matter

ABSTRACT What explains support for Black Lives Matter among Asian Americans? This article draws on nationally representative data from the 2016 Collaborative Multiracial Post-Election Survey to examine the contours of Asian American public opinion on Black Lives Matter and the factors that shape them. Examining intragroup and intergroup attitudes across a set of racial, ethnic/national origin, and cross-racial group measures, I show that race-based considerations are significant predictors of Asian American support for Black Lives Matter. Specifically, I find that those who support Black Lives Matter are more likely to perceive linked fate with other Asian Americans and with other non-white groups and to perceive anti-black discrimination in the United States. I argue that, while never a panacea, race-based linked fate beliefs among Asian Americans, both as Asian Americans and with other groups of color, are a viable and imperative part of building cross-racial coalitions and contemporary racial justice movements.
Noradrenergic innervation of monkey prefrontal cortex: A dopamine‐β‐hydroxylase immunohistochemical study

Norepinephrine has been implicated in the regulation of a number of cortical functions, yet relatively little is known about the anatomical organization of noradrenergic axons in the expanded and highly differentiated prefrontal cortex of primates. In this study, the distribution of fibers containing dopamine‐ß‐hydroxylase (DBH), the enzyme that converts dopamine to norepinephrine, was characterized immunohistochemically in the prefrontal cortical regions of Old World cynomolgus monkeys (Macaca fascicularis) and New World squirrel monkeys (Saimiri sciureus). In both species, differences in the density of DBH‐labeled fibers were detected both across and within many prefrontal cytoarchitectonic regions. In cynomolgus monkeys, area 8B had the greatest density of DBH‐immunoreactive fibers; within this region, the medial surface had a greater density of labeled processes than the dorsal surface. Areas 9 and 24 also had a high density of DBH‐labeled fibers, areas 11, 12, 13 and 25 were of intermediate density, and portions of areas 10 and 46 had the lowest density of immunoreactive fibers. Regional differences in the density of DBH‐immunoreactive fibers were also present in squirrel monkey prefrontal cortex.
The topography of primate retina: A study of the human, bushbaby, and new‐ and old‐world monkeys

The distribution of ganglion cells has been studied in the retinas of four primates: the prosimian bushbaby, the New‐World squirrel monkey, the Old‐World crab‐eating cynamolgous monkey, and the human. The sizes of ganglion cell somas were also measured at a number of retinal locations and compared with similar measurements in the cat retina to test for the presence in primates of retinal specializations such as the visual streak, and for gradients in retinal structure, such as that between temporal and nasal retina.
Clear Cell `Sugar' Tumor of the Breast: Another Extrapulmonary Site and Review of the Literature

A group of lesions show morphologic and immunophenotypic evidence of differentiation toward a putative perivascular epithelioid cell. These so-called PEComas include angiomyolipoma, lymphangiomyoma, lymphangioleiomyomatosis, renal capsuloma, clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres, and clear cell “sugar” tumor. PEComas are characterized by strong immunoreactivity with the HMB45 antibody and variable expression of muscle markers. This family of lesions may be composed of a spectrum of cells from epithelioid to spindle cells with clear to granular eosinophilic cytoplasm. One member of this family, composed of epithelioid cells with glycogen-rich clear cytoplasm, is descriptively called a clear cell “sugar” tumor. This tumor, originally described in the lung, is being recognized increasingly in extrapulmonary sites. We report a case of a primary extrapulmonary clear cell “sugar” tumor occurring in the right breast of a 16-year-old girl. The tumor was composed of clear epithelioid cells with abundant glycogen and distinct cell borders. The tumor showed strong immunoreactivity with HMB45 antibody and Melan-A. There was focal vimentin staining. In addition, there was diffuse and strong nuclear staining for progesterone receptor. Antibodies to actins, S-100 protein, cytokeratins (AE1/AE3 and CAM5.2), desmin, and estrogen receptor were negative. The tumor was completely excised, and the patient is well without evidence of disease 9 months postexcision.
Aldehyde Dehydrogenase 1A1 Possesses Stem-Like Properties and Predicts Lung Cancer Patient Outcome

Introduction: Lung cancer contains a small population of cancer stem cells that contribute to its initiation and progression. We investigated the biological function and clinical significance of aldehyde dehydrogenase 1A1 (ALDH1A1) in non–small-cell lung carcinoma (NSCLC). Methods: ALDH1A1 assay or small interfering RNA transfection was employed to isolate ALDH1A1+ cells or knock down ALDH1A1 expression in H2087 cells, respectively. Biological functions of ALDH1A1+ and ALDH1A1 silenced cells were investigated using in vitro and in vivo methods. ALDH1A1 expression was analyzed using immunohistochemistry on tissue microarrays with 179 lung cancer tissues and 26 normal lung tissues. Results: The abilities of clone formation, proliferation, cell growth, and migration were increased in ALDH1A1+ and ALDH1A1 silenced cells. ALDH1A1+ lung cancer cells initiated tumors that resembled the histopathologic characteristics and heterogeneity of the parental lung cancer cells in mice. The silencing of ALDH1A1 expression in H2087 lung cancer cells inhibited cell proliferation and migration significantly. ALDH1A1 was expressed in 42% of normal lung tissues (11 of 26), with strong expression in the basal cells and globular cells of the normal bronchus and weak expression in the alveolar epithelial cells. Compared with normal lung tissues, 45% of NSCLC samples (81 of 179) were read as positive for ALDH1A1. Positive ALDH1A1 expression was correlated with patients’ smoking status (p = 0.022), lymph-node metastasis (p = 0.006), clinical stage (p = 0.004), and a decreased overall survival time (p < 0.001). Positive ALDH1A1 expression in lung cancer tissues was an independent prognostic factor for NSCLC (odds ratio = 5.232, p < 0.001). Conclusion: Elucidating the biological functions of ALDH1A1 could be helpful in studying lung tumorigenesis and for developing new therapeutic approaches.
Quantitative assessment of normal soft-tissue elasticity using shear-wave ultrasound elastography.

OBJECTIVE The aim of this study was to measure the elasticity of various tissues and report it in kilopascals. SUBJECTS AND METHODS The thyroid, submandibular, and parotid glands, masseter and gastrocnemius muscles, supraspinatus and Achilles tendons, renal cortex and pelvis, pancreas, and spleen of 127 healthy volunteers (89 women, 38 men; mean age, 37.72 ± 9.11 years; range, 17-63 years) were evaluated with shear-wave ultrasound elastography. RESULTS The mean elasticity values were determined to be 10.97 ± 3.1 kPa for the thyroid, 10.92 ± 3.1 kPa for the submandibular glands, 10.38 ± 3.5 kPa for the parotid glands, 10.4 ± 3.7 kPa for the masseter muscle, 11.1 ± 4.1 kPa for the gastrocnemius muscle, 31.2 ± 13 kPa for the supraspinatus muscle, 51.5 ± 25.1 kPa for the Achilles tendons, 5.0 ± 2.9 kPa for the renal cortex, 23.6 ± 5.4 kPa for the renal pelvis, 4.8 ± 3 kPa for the pancreas, and 2.9 ± 1.8 kPa for the spleen. CONCLUSION Elasticity values were determined for different tissues with shear-wave ultrasound elastography. Further studies comparing the elasticity values of normal and pathologic tissues are necessary to determine the diagnostic role of this technique.
[Expression of USP9X in Non-small Cell Lung Cancer and Its Clinical Significance].

OBJECTIVE To investigate the expression and clinical significance of ubiquitin-specific protease 9X (USP9X) protein in non-small cell lung cancer (NSCLC). METHODS USP9X proteins were detected in 71 cases of NSCLC and 20 cases of benign pulmonary tissues by immunohistochemical staining. The correlation between USP9X expression and 51 NSCLC clinicopathological parameters as well as survival rates were indicated. RESULTS Higher rate [69. 0% (49/71)] of the expression of USP9X was observed in NSCLC samples, compared with 20. 0% (4/20) in benign pulmonary tissues (P<0. 001). Furthermore, the expression of USP9X proteins was positively associated with both histological types and lymph node metastasis (P<0. 05). The survival analysis showed that the survival rate was lower in patients with positive expressions of USP9X than in patients with negative expressions (P< 0. 05). USP9X expression, together with histological types and TNM stage was an independent predictor for overall survival in the multivariate Cox regression model (P < 0. 05). CONCLUSION Up-regulation of USP9X plays an important role in the invasion and progression of NSCLC and could be considered as a prognostic predictor for NSCLC.
Long-term effects of short-lasting early local inflammatory insult

We examined the long-term effects of a short-lasting (∼24 h) inflammatory insult generated by injections of 0.25% carrageenan (1 μl/g) into the hindpaws of newborn (P0) rat pups. At P60 animals which experienced this early inflammatory insult showed significant alterations in the withdrawal responses to noxious stimulation of the affected paws. Furthermore, in the absence of ongoing inflammation, the withdrawal latencies to heat stimulation and withdrawal thresholds to mechanical stimulation were increased by such experience. In the presence of ongoing CFA-induced inflammation, however, the same early experience decreased these parameters of response to noxious stimulation. These data suggest that early inflammatory insult may differentially affect the aspects of nociceptive circuitry involved in transient pain sensitivity and in inflammation-induced hyperalgesia.