Miracle-dz/UniFAR-FTUs huggingface dataset:
The suprachiasmatic nucleus balances sympathetic and parasympathetic output to peripheral organs through separate preautonomic neurons

Opposing parasympathetic and sympathetic signals determine the autonomic output of the brain to the body and the change in balance over the sleep‐wake cycle. The suprachiasmatic nucleus (SCN) organizes the activity/inactivity cycle and the behaviors that go along with it, but it is unclear how the hypothalamus, in particular the SCN, with its high daytime electrical activity, influences this differentiated autonomic balance. In a first series of experiments, we visualized hypothalamic pre‐sympathetic neurons by injecting the retrograde tracer Fluoro‐Gold into the thoracic sympathetic nuclei of the spinal cord. Pre‐parasympathetic neurons were revealed by injection of the retrograde trans‐synaptic tracer pseudorabies virus (PRV) into the liver and by sympathetic liver denervation, forcing the virus to infect via the vagus nerve only. This approach revealed separate pre‐sympathetic and pre‐parasympathetic neurons in the brainstem and hypothalamus. Next, selective retrograde tracing with two unique reporter PRV strains, one injected into the adrenal and the other into the sympathetic denervated liver, demonstrated that there are two separate populations of pre‐sympathetic and pre‐parasympathetic neurons within the paraventricular nucleus of the hypothalamus. Interestingly, this segregation persists into the SCN, where, as a result, the day‐night balance in autonomic function of the organs is affected by specialized pre‐sympathetic or pre‐parasympathetic SCN neurons. These separate preautonomic SCN neurons provide the anatomical basis for the circadian‐driven regulation of the parasympathetic and sympathetic autonomic output. J. Comp. Neurol. 464:36–48, 2003. © 2003 Wiley‐Liss, Inc.
Etk/Bmx as a Tumor Necrosis Factor Receptor Type 2-Specific Kinase: Role in Endothelial Cell Migration and Angiogenesis

ABSTRACT Tumor necrosis factor (TNF) is a cytokine that mediates many pathophysiologial processes, including angiogenesis. However, the molecular signaling involved in TNF-induced angiogenesis has not been determined. In this study, we examined the role of Etk/Bmx, an endothelial/epithelial tyrosine kinase involved in cell adhesion, migration, and survival in TNF-induced angiogenesis. We show that TNF activates Etk specifically through TNF receptor type 2 (TNFR2) as demonstrated by studies using a specific agonist to TNFR2 and TNFR2-deficient cells. Etk forms a preexisting complex with TNFR2 in a ligand-independent manner, and the association is through multiple domains (pleckstrin homology domain, TEC homology domain, and SH2 domain) of Etk and the C-terminal domain of TNFR2. The C-terminal 16-amino-acid residues of TNFR2 are critical for Etk association and activation, and this Etk-binding and activating motif in TNFR2 is not overlapped with the TNFR-associated factor type 2 (TRAF2)-binding sequence. Thus, TRAF2 is not involved in TNF-induced Etk activation, suggesting a novel mechanism for Etk activation by cytokine receptors. Moreover, a constitutively active form of Etk enhanced, whereas a dominant-negative Etk blocked, TNF-induced endothelial cell migration and tube formation. While most TNF actions have been attributed to TNFR1, our studies demonstrate that Etk is a TNFR2-specific kinase involved in TNF-induced angiogenic events.
Influence of liver pathology on markers of postmortem brain tissue quality.

BACKGROUND Postmortem brain tissue provides an important resource to investigate various brain disorders, including those resulting from the effects of alcohol abuse. Unlike the traditionally recognized confounders to tissue quality (e.g., coma, hypoxia), our understanding of the effects of liver disease is incomplete. The aim of this study was to determine the effects of liver pathology, and in particular cirrhosis resulting in hepatic encephalopathy (HE), on 2 postmortem brain tissue quality markers, brain pH and RNA integrity. METHODS We measured tissue quality markers in a cohort of alcohol abuse and control cases collected by the NSW Tissue Resource Centre. Cerebellar tissue was used to evaluate both brain pH and RNA quality (as indicated by the RNA integrity number: RIN). A histological assessment was performed on each case to exclude coexisting pathologies (e.g., cerebrovascular disease, hypoxic encephalopathy, neurodegenerative disease) and to assess the presence or absence of HE. Autopsy reports were reviewed for liver pathology and toxicology. RESULTS Analysis revealed that cases of alcohol abuse had a lower mean (±SD) brain pH, 6.46 (±0.3) as compared with the control mean 6.64 (±0.2). The mean RIN for the alcohol abuse group was 6.97 (±1.3) and controls 7.66 (±0.5). The severity of liver pathology affected both brain pH (p < 0.0001) and RIN (p < 0.0001). The comparison between cirrhotic cases highlighted increased degradation of RNA in cases with cirrhosis resulting in HE (p = 0.0095). A similar effect was seen on brain pH (p = 0.0019). CONCLUSIONS The results show that the presence of cirrhosis and, more so, HE reduces the pH and RIN of postmortem brain tissue.
Autoantibodies in gluten ataxia recognize a novel neuronal transglutaminase

Gluten sensitivity typically presents as celiac disease, a chronic, autoimmune‐mediated, small‐intestinal disorder. Neurological disorders occur with a frequency of up to 10% in these patients. However, neurological dysfunction can also be the sole presenting feature of gluten sensitivity. Development of autoimmunity directed toward different members of the transglutaminase gene family could offer an explanation for the diversity in manifestations of gluten sensitivity. We have identified a novel neuronal transglutaminase isozyme and investigated whether this enzyme is the target of the immune response in patients with neurological dysfunction.
Emphysema: diagnosis, classification, quantification and treatment planning

Radiol Bras. 2013 Jan/Fev;46(1):IX In this volume of Radiologia Brasileira, our readers can find an interesting paper from Koenigkam-Santos et al. The study from the department of Prof. Kauczor and Prof. Heussel describes the results of their research on the pre-operative assessment of the completeness of the lung fissures and pre and post operative quantification of lung volumes and emphysema in a group of patients submitted to endobronchial valves (EBV) implantation for palliative treatment of emphysema. Their results report that EBV implantation benefit is most likely in patients who have complete interlobar fissures and develop lobar atelectasis. This study confirms previous data concerning the validity of pulmonary fissure integrity and response to non-pharmacological treatment of emphysema. The confirmation of these data is particularly important because recent studies have reported that in some non-pharmacological treatment of emphysema the pulmonary fissure integrity has a minor influence. Their study is a good example of the practical application of years of dedication to the understanding and testing of new modalities in the imaging analysis of chronic obstructive pulmonary disease. The paper also reflects the current trend on imaging studies, which has been moving from a purely anatomical interpretation to a combined anatomical and functional assessment of lung diseases. Prof. Nestor Müller first introduced the concept of quantifying emphysema using CT densitometry. This process is known as density mask, in which the lung areas with density or attenuation values below a chosen threshold are masked by a solid color, so the observer can promptly identify the areas of abnormal lung density or emphysema. In 1995, Prof. Gevenois and his group suggested the threshold set at –950 HU for the quantification of emphysema, which is the most frequently used threshold. With the advent of the helical scanning, it was possible to calculate the actual volume (cm), rather than area (cm) and Prof. Kauczor’s paper from 1998, introduced volumetric CT quantification of emphysema. These techniques have provided increasingly early diagnosis and monitoring of these patients.
Outcomes of One-Step Incomplete and Complete Excavation in Primary Teeth: A 24-Month Randomized Controlled Trial

Aim: To compare 24-month pulp health outcomes of partial caries removal (PCR) and total caries removal (TCR) with composite restoration in primary molars. Methods: 48 children aged 3-8 years with at least one molar with a deep carious lesion were included. 120 teeth were randomized to control (TCR; n = 54; 69% class II) and test (PCR; n = 66; 63% class II) groups. Total absence of carious tissue was confirmed using a blunt-tipped probe in the TCR group. For PCR, excavation was stopped when hardened, dried dentin with a leathery consistency was achieved. Pulpotomy was performed in cases of pulp exposure. Results: Pulp exposure occurred in 2 and 27.5% of teeth treated with PCR and TCR, respectively (p < 0.01). The operative time was significantly higher for TCR than PCR. Success rates were 92 and 96% in the PCR and TCR groups, respectively (p = 0.34). The success rate tended to be lower in occlusoproximal (92%) than in occlusal (100%) lesions (p = 0.08). Conclusion: The clinical and radiographic success rates of PCR and TCR in primary teeth with deep carious lesions were high and did not differ significantly, indicating that PCR is a reliable minimally invasive approach in primary teeth and that the retention of carious dentin does not interfere with pulp vitality. Moreover, PCR provided other clinically relevant advantages over TCR, especially lower incidence of pulp exposure and lower operative time.
CLINICAL PRESENTATION AND DISEASE COURSE OF USHER SYNDROME BECAUSE OF MUTATIONS IN MYO7A OR USH2A

Purpose: To evaluate differences in the visual phenotype and natural history of Usher syndrome caused by mutations in MYO7A or USH2A, the most commonly affected genes of Usher syndrome Type I (USH1) and Type II (USH2), respectively. Methods: Eighty-eight patients with a clinical diagnosis of USH1 (26 patients) or USH2 (62 patients) were retrospectively evaluated. Of these, 48 patients had 2 disease-causing mutations in MYO7A (10 USH1 patients), USH2A (33 USH2 patients), and other USH (5 patients) genes. Clinical investigation included best-corrected visual acuity, Goldmann visual field, fundus photography, electroretinography, and audiologic and vestibular assessments. Longitudinal analysis was performed over a median follow-up time of 3.5 years. Results: Patients carrying mutations in MYO7A had a younger age of onset of hearing and visual impairments than those carrying mutations in USH2A, leading to an earlier diagnosis of the disease in the former patients. Longitudinal analysis showed that visual acuity and visual field decreased more rapidly in subjects carrying MYO7A mutations than in those carrying USH2A mutations (mean annual exponential rates of decline of 3.92 vs. 3.44% and of 8.52 vs. 4.97%, respectively), and the former patients reached legal blindness on average 15 years earlier than the latter. Conclusion: The current study confirmed a more severe progression of the retinal disease in USH1 patients rather than in USH2 patients. Furthermore, most visual symptoms (i.e., night blindness, visual acuity worsening) occurred at an earlier age in USH1 patients carrying mutations in MYO7A.
Diverse Enzymatic Specificities of Digestive Proteases, 'Intestains', Enable Colorado Potato Beetle Larvae to Counteract the Potato Defence Mechanism

Abstract In response to insect attack, high levels of proteinase inhibitors are synthesised in potato leaves. This can cause inefficient protein digestion in insects, leading to reduced growth, delayed development and lower fecundity. It has been suggested that Colorado potato beetle overcomes this defence mechanism by inducing the production of a set of cysteine proteases that are resistant to potato proteinase inhibitors. Experiments with gut extracts showed that these proteases have unusual inhibition profiles as they are not inhibited by most of the cystatins but are strongly inhibited by thyropins. In this study we have isolated three cysteine proteases from adapted guts of Colorado potato beetle larvae, named intestains 1, 2 and 3, the first cysteine proteases known to be involved in extracellular protein digestion. The N-terminal sequences suggest their classification into the papain family. Intestains differ in substrate specificities and inhibitory profiles. Their substrate specificities suggest that intestains 1 and 2 are general digestive enzymes, while intestain 3 has a more specific function. The inhibitory profile of intestain 1 is similar to that of proteases of the papain family. However, the K1 values for the interaction of intestain 2 with the same set of inhibitors are several hundred fold higher, which would enable the enzyme to circumvent the potato defence mechanism characterised by high concentrations of protease inhibitors in attacked potato leaves. A further, different strategy of the Colorado potato beetle to avoid potato defence is exhibited by intestain 3, which is able to cleave off the N-terminus of model cystatin and thus inactivate the inhibitor. These results suggest that the Colorado potato beetle combines different strategies to counteract plant defence mechanisms.
Social, cultural and political factors in the design of HIV programmes with Papuan highland communities

The Indonesian province of Papua faces a growing HIV epidemic, particularly amongst remote highland Papuans, such as the Western Dani. The specific, challenging political and sociocultural context of Papuan highland communities greatly influences the transmission of HIV. Different initiatives have struggled to meet the sexual and reproductive health needs of Papuan communities and of minority ethnic communities and the challenges they pose. The prolonged cultural tensions between Papuan and Indonesian communities are a major barrier to effective dialogue between the Indonesian state and its minority ethnic communities, the absence of which only exacerbates the epidemic. Tackling HIV in Papua requires responses that are both culturally and politically sensitive, in direct challenge to existing development paradigms.
International consensus on nomenclature and classification of atrial fibrillation: A collaborative project of the Working Group on Arrhythmias and the Working Group of Cardiac Pacing of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology.

Atrial fibrillation (AF) has in recent years been the subject of intense investigation in terms of obtaining a better understanding of its mechanism and improving its management. Despite the advances made, AF remains a challenge for the clinician, and it is uncertain whether these theoretical advances have resulted in a significant improvement in the way the vast majority of patients are managed in general practice. Several reasons may account for this situation. One possible reason is incomplete knowledge of the complex mechanism of this common arrhythmia. Another possible reason is the heterogeneous clinical presentation of the arrhythmia. Still, the numerous publications and clinical trials devoted to AF have dealt with this arrhythmia as if it were a single entity. Furthermore, the abundant terminology used to characterize various subsets of AF and the absence of consistency in the definitions have added to the difficulty in communication.1 Consequently, it has become difficult to compare the results of pharmacologic or nonpharmacologic therapies because different classifications have been used, and the difficulty in characterizing the patient population has not allowed easy or appropriate comparison. The Working Group of Arrhythmia of the European Society of Cardiology (WGA-ESC) and the North American Society of Pacing and Electrophysiology (NASPE) have recognized the need to create a Study Group in an attempt to achieve a consensus on the terminology and classification of AF. This document reports the conclusions reached by this Study Group during a meeting held on June, 13, 2000, and completed by the members soon thereafter. The definitions and classification resulting from this consen-
Dysplasia Should Not Be Ignored in Lichenoid Mucositis

Oral lichen planus is categorized as a potentially malignant condition by the World Health Organization; however, some argue that only lichen planus with dysplasia have malignant potential. Many pathologists call lichen planus with dysplasia “dysplasia with lichenoid mucositis (LM)” or “LM with dysplasia. ” Previous research has shown that certain high-risk patterns of loss of heterozygosity (LOH) in dysplastic lesions are associated with significantly increased cancer risk. However, LM without dysplasia lacks such molecular patterns, supporting the hypothesis that LM, by itself, is not potentially malignant and that only those with dysplasia have malignant potential. To further investigate the premalignant nature of LM with dysplasia, this study compared the rate of malignant progression of dysplasia with LM with that of dysplasia without LM. Patients from a population-based prospective cohort study with >10 y of follow-up were analyzed. Study eligibility included a histological diagnosis of a primary low-grade dysplasia with or without LM. A total of 446 lesions in 446 patients met the selection criteria; 373 (84%) were classified as dysplasia without LM, while 73 (16%) were classified as dysplasia with LM. Demographic and habit information, clinical information, and outcome (progression) were compared between the 2 groups. Forty-nine of 373 cases of dysplasia (13%) progressed compared to 8% (6/73) of dysplasia with LM. However, the difference was not statistically different (P = 0.24). The 3- and 5-y rate of progression did not differ between the groups (6.7% and 12.5% for dysplasia without LM and 2.9% and 6.6% for those with LM; P = 0.36). Progression was associated with nonsmoking, location at a high-risk site, and diagnosis of moderate dysplasia regardless of whether LM was present or not. Dysplasia with or without LM had similar cancer risk, and dysplasia should not be discounted in the presence of LM.
Supply chain network modeling in a golf club industry via fuzzy linear programming approach

This paper addresses a supply chain network planning problem faced by a company that manages a golf club supply chain. The supply chain network is considered for the production of several products through an assembly of three modules supplied by different suppliers. A linear programming model is proposed to describe the problem, where multiple components can be assembled within a planning horizon of one to twelve months. The model involves the supply of various components from a set of suppliers and allocation of assembled products to customers. In real world problems practical situations are often not well-defined and thus can not be described precisely. Therefore this model is transformed into the fuzzy models with flexibility in the objective function, in the market demand, and in the available capacity of resources. The main objective is to construct a procurement-assembly plan enabling it to minimize its costs while satisfying the customers’ demand over a given planning horizon in such a way as to hedge against uncertainty. Finally, the proposed model is tested using a case of supply chain from the golf club industry. Sensitivity analyses are also conducted on various parameters to gain insight into the proposed model. Numerical case demonstrates that the proposed fuzzy model can provide a better and more flexible way of representing the problem for the considered industry.
Preparations of recombinant HIV‐1 p66 antigen to improve the specificity of immune complex transfer enzyme immunoassay of antibody IgG to HIV‐1 reverse transcriptase

Recombinant HIV‐1 p66 (rp66, a subunit of reverse transcriptase (RT), a heterodimer of p66 and p51) was produced in Escherichia coli in three different ways. First, rp66 was produced as a part of the fusion protein of lacZ protein and HIV‐1 pol protein consisting of three components: protease (p10), RT (p51/p66), and integrase (p31), and was released from the fusion protein by the protease (pol–rp66). Second, rp66 with Ser–Ser at the N‐terminus was produced as a fusion protein with maltose‐binding protein containing a factor Xa site between the two proteins (MBP–Ser–Ser–rp66) and was released from the fusion protein by factor Xa (Ser–Ser–rp66). Third, rp66 with Met–Gly at the N‐terminus was produced in transformed cells (Met–Gly–rp66). The recombinant proteins were purified from sonic extracts of transformed cells by ammonium sulfate fractionation and various column chromatographies. MBP–Ser–Ser–rp66 and Met–Gly–rp66 were readily purified in sufficient amounts for labeling with 2,4‐dinitrophenyl groups and β‐D‐galactosidase from E. coli, but pol–rp66 and Ser–Ser–rp66 were not for enzyme‐labeling. Ser–Ser–rp66 was not only polymerized but also degraded to considerable extents. The purified preparations were labeled with 2,4‐dinitrophenyl groups and β‐D‐galactosidase and were tested in immune complex transfer enzyme immunoassay of antibody IgG to HIV‐1 RT using serum samples from 600 HIV‐1 seronegative and 30 HIV‐1 seropositive subjects. Among various combined uses of the two labeled preparations, the uses of 2,4‐dinitrophenylated MBP–Ser–Ser–rp66 and pol–rp66 with β‐D‐galactosidase‐labeled Met–Gly–rp66 showed the highest (99.8%) and the second highest (99.5%) specificities, which were higher than that with the labeled preparations used in the previous study (98.0%). J. Clin. Lab. Anal. 14:169–179, 2000. © 2000 Wiley‐Liss, Inc.
Access of emotional information to visual awareness in patients with major depressive disorder

Background According to cognitive theories of depression, negative biases affect most cognitive processes including perception. Such depressive perception may result not only from biased cognitive appraisal but also from automatic processing biases that influence the access of sensory information to awareness. Method Twenty patients with major depressive disorder (MDD) and 20 healthy control participants underwent behavioural testing with a variant of binocular rivalry, continuous flash suppression (CFS), to investigate the potency of emotional visual stimuli to gain access to awareness. While a neutral, fearful, happy or sad emotional face was presented to one eye, high-contrast dynamic patterns were presented to the other eye, resulting in initial suppression of the face from awareness. Participants indicated the location of the face with a key press as soon as it became visible. The modulation of suppression time by emotional expression was taken as an index of unconscious emotion processing. Results We found a significant difference in the emotional modulation of suppression time between MDD patients and controls. This difference was due to relatively shorter suppression of sad faces and, to a lesser degree, to longer suppression of happy faces in MDD. Suppression time modulation by sad expression correlated with change in self-reported severity of depression after 4 weeks. Conclusions Our finding of preferential access to awareness for mood-congruent stimuli supports the notion that depressive perception may be related to altered sensory information processing even at automatic processing stages. Such perceptual biases towards mood-congruent information may reinforce depressed mood and contribute to negative cognitive biases.