Miracle-dz/UniFAR-FTUs huggingface dataset:
Shuffling peptides to create T‐cell epitopes: does the immune system play cards?

For a long time, immunologists have believed that classical CD4+ and CD8+ T cells recognize peptides (referred to as epitopes), derived from protein antigens presented by MHC/HLA class I or II. Over the past 10–15 years, it has become clear that epitopes recognized by CD8+, and more recently CD4+ T cells, can be formed by protein splicing. Here, we review the discovery of spliced epitopes recognized by tumor‐specific human CD8+ T cells. We discuss how these epitopes are formed and some of the unusual variants that have been reported. Now, over a decade since the first report, evidence is emerging that spliced CD8+ T‐cell epitopes are much more common, and potentially much more important, than previously imagined. Recent work has shown that epitopes recognized by CD4+ T cells can also be formed by protein splicing. We discuss the recent discovery of spliced CD4+ T‐cell epitopes and their potential role as targets of autoimmune T‐cell responses. Finally, we highlight some of the new questions raised from our growing appreciation of T‐cell epitopes formed by peptide splicing.
Waypoints on a Journey of Discovery: Mental Models in Human-Environment Interactions

Although the broad concept of mental models is gaining currency as a way to explore the link between how people think and interact with their world, this concept is limited by a theoretical and practical understanding of how it can be applied in the study of human-environment relationships. Tools and processes are needed to be able to elicit and analyze mental models. Because mental models are not directly observable, it is also important to understand how the application of any tools and processes affects what is measured. Equally important are the needs to be clear on the intent of the elicitation and to design the methods and choose the settings accordingly. Through this special edition, we explore how mental models are elicited using two approaches applied in two case-study regions. We analyze two approaches used in the Crocodile River catchment of South Africa: a graphically based approach, i.e., actors, resources, dynamics, and interactions (ARDI); and an interview- or text-based approach, i.e., consensus analysis (CA). A further experiment in the Rhone Delta (Camargue), France, enabled us to test a cross- over between these two methods using ARDI methodology to collect data and CA to analyse it. Here, we compare and explore the limitations and challenges in applying these two methods in context and conclude that they have much to offer when used singly or in combination. We first develop a conceptual framework as a synthesis of key social and cognitive psychology literature. We then use this framework to guide the enquiry into the key lessons emerging from the comparative application of these approaches to eliciting mental models in the two case regions. We identify key gaps in our knowledge and suggest important research questions that remain to be addressed.
Effects of dopaminergic treatment on striatal dopamine turnover in de novo Parkinson disease

Objective: To evaluate the effects of levodopa and the dopamine D2 agonist cabergoline on striatal dopamine turnover estimated as the inverse of the effective dopamine distribution volume ratio (EDVR) measured by 18F-dopa PET in de novo Parkinson disease (PD). Methods: Single-center, parallel-group, randomized, observer-blinded study of cabergoline (3 mg/day) and levodopa (300 mg/day) over 12 weeks in patients with de novo PD. Primary efficacy measure was the change of the side-to-side averaged putaminal EDVR comparing baseline and end-of-maintenance period. Results: Thirty-five out of 39 randomized patients were assigned to the primary efficacy analysis (cabergoline, n = 17; levodopa, n = 18). At the end of treatment period, mean EDVRs were significantly lower compared to baseline solely in the levodopa group (relative change −1.0 ± 13.0% in cabergoline [p = 0.525 when compared to baseline], −8.3 ± 11.8% in levodopa group [p = 0.006]) with a nonsignificant trend between groups (mean relative difference: 7.3% (95% confidence interval −1.2% to 15.8%; p = 0.091). There was significant clinical improvement in both groups at 12 weeks compared to baseline, but no significant differences between groups in clinical and PET secondary outcome measures. Both pharmacologic treatments and PET scanning were well-tolerated and safe. Conclusion: Putaminal dopamine turnover is increased by levodopa treatment in de novo PD. The nonsignificant trend toward a larger influence by levodopa compared to cabergoline is supported by ancillary statistical analyses. This augmentation of early compensatory events by levodopa might contribute not only to its symptomatic effects, but also to its induction of motor complications.
Unrelated chromosomal anomalies found in patients with suspected 22q11.2 deletion

Screening for 22q11.2 deletions has not an easy approach due to the wide variability of their associated phenotype. Many clinical features overlap with those of other known syndromes and reported loci. Patients referred to exclude a 22q11.2 deletion are usually tested with a locus‐specific FISH probe, with 10% positive cases depending on the selection criteria, but patients testing negative for FISH at 22q11.2 may have other chromosomal aberrations in routine cytogenetic analysis. We tested 819 patients suspected of having a 22q11.2 deletion. Eighty‐eight patients (10.7%) were positive for 22q11.2 deletion, whereas 30 patients (3.7%) showed other chromosomal abnormalities involving deletions and duplications, derivative chromosomes, marker chromosomes, apparently balanced and unbalanced translocations and sex chromosome aneuploidies. Of these alterations, 28 did not involve region 22q11 and most had not been associated with 22q11.2 deletion phenotype before. We discuss the similarity of DiGeorge/velocardiofacial syndrome with other known clinical entities and suggest correlations between the new loci and the observed clinical features. The frequency of unrelated chromosomal anomalies reported in this study and in other previous reports highlights the importance of conventional cytogenetic analysis as an initial genome‐wide screening tool in all referred patients, and provides useful data to optimize diagnostic and screening protocols according to the most frequent chromosomal findings. © 2008 Wiley‐Liss, Inc.
Diabetic nephropathy among type 2 diabetes mellitus patients in Dr. Cipto Mangunkusumo Hospital

Diabetic nephropathy has been known as one of the most serious long-term complications of diabetes mellitus (DM), which could lead to end-stage kidney failure. However, data showing the presence of diabetic nephropathy among ambulatory type 2 diabetic patients is currently not available. This cross-sectional study was conducted to find the prevalence of diabetic nephropathy among non-hospitalized type 2 diabetic patients, who came for the first time to the Metabolic and Endocrinology Clinic, Dr. Cipto Mangunkusumo Hospital, Jakarta. From December 2001 to June 2002, 100 new type 2 diabetic patients were included in the study. Forty-two of them were men and the mean age was 54 ± 9.6 years. Overt nephropathy (macroalbuminuria) was found in 11% of patients, while incipient nephropathy (microalbuminuria) was 26%, and the rest were normal (normoalbuminuria). Duration of illness of more than 5 years was significantly correlated with the degree of albuminuria. However, there is no significant correlation between the degree of albuminuria and other risk factors, i.e. patient’s age, dyslipidemia, hypertension, obesity, HbA1c level. All patients with overt nephropathy had creatinine clearance test below 75 ml/ min. (mean 45.3 mL/min), significantly lower than patients with micro- or normoalbuminuria (p=0.01). Retinopathy was found in 10 out of 11 (90%) patients with overt nephropathy. Multivariate analysis showed that the duration of illness and retinopathy was significantly correlated with the presence of diabetic nephropathy (p< 0.05). We concluded that the prevalence of diabetic nephropathy (i.e. overt nephropathy with retinopathy) among non-hospitalized type 2 diabetic patients was 10%. The duration of illness was an important risk factor for the development of this complication. (Med J Indones 2004; 13: 161-5) Keywords: diabetic nephropathy, chronic kidney disease, diabetic retinopathy, albuminuria, ambulatory type 2 diabetic patients
Tower of London versus Real Life Analogue Planning in Schizophrenia with Disorganization and Psychomotor Poverty Symptoms

Abstract Neuropsychological models propose qualitatively distinct planning impairments in the psychomotor poverty and disorganization syndromes in schizophrenia. It was proposed that poor plan initiation in psychomotor poverty would lead to longer initial planning times, while poor plan execution in disorganization would lead to greater inefficiency. Participants with psychomotor poverty (n = 30) and disorganization (n = 29) symptoms were contrasted with healthy controls (n = 28) to elucidate distinct planning impairments. Planning was compared in the Tower of London task versus real life analogue performance in the form of a board-game style diary planning task. The specificity of planning impairments was investigated by controlling for current IQ. The disorganization group demonstrated inefficient planning across both tasks, with poor performance on the Tower of London but not on the real life analogue task remaining after intelligence levels were taken into account. Initial planning times did not differ between groups. Previous associations between poor planning and symptoms may have been driven by poor planning with disorganization symptoms and associated lower order impairments in executive function or the semantic system. Targeting these impairments in people with disorganization symptoms may lead to a greater chance of success in promoting generalization to the real world. (JINS, 2011, 17, 474–484)
Self-ligating RNA sequences on the antigenome of human hepatitis delta virus

A 179-base fragment of RNA from the 1,679-base antigenome of hepatitis delta virus can not only self-cleave but, when the ends of the resultant fragments are brought into apposition by base pairing to another RNA, also self-ligate. Thus, processing events needed for genome replication in vivo may be strictly RNA mediated.
Aspects of the crustal structure of the western Mojave Desert, California, from seismic reflection and gravity data

Seismic and gravity data taken along line 1 of the 1982 Consortium for Continental Reflection Profiling (COCORP) Mojave Desert Survey (N-S profile, ∼30 km long) have been used to characterize the upper crust north of the San Andreas fault in the western Mojave block of southern California. Consortium for Continental Reflection Profiling seismic reflection data were reprocessed to emphasize the upper 5 seconds (two-way travel time). The resultant common depth point (CDP) sections provided starting models for generating a refined geologic cross-section using a combination of ray tracing (forward modeling) and gravity interpretation. The forward modeling was used to validate the existence of faults and constrain their dips. The gravity data were used to refine the overall model, particularly in poor data areas on the CDP sections. Gravity data, taken along three nearby profiles parallel to primary line of section, were also used to determine the structural trend. Results from the first two seconds indicate the presence of a series of ENE striking reverse faults beneath the late Tertiary and Quaternary sedimentary cover of the western Mojave. The faults dip northward and offset the sediment-basement interface. The largest such feature has an apparent throw of ∼1.8 km and exhibits a subtle scarp at the Earth's surface suggesting Holocene displacement. The orientation of these faults, although not an instantaneous representation of the present-day stress field, is consistent with NNW compression across the western Mojave block and WNW striking San Andreas fault, as determined from nearby focal mechanisms and in situ stress measurements. The faults also appear to be closing small sedimentary basins in the Mojave block, which may have formed during an earlier extensional phase, similar to what is happening on a much larger scale in the Los Angeles basin to the south of the San Andreas fault. Reflections between 2 and 5 s, coupled with the local geology and gravity modeling, are consistent with the presence of the Pelona/Rand schist in the subsurface beneath the western Mojave. The upper surface of the schist (i.e., Vincent/Rand thrust equivalent) rises southward toward the San Andreas fault where it is displaced vertically (up to the south) at least 5 km along the E-W trending Hitchbrook fault, such that the schist crops out between the Hitchbrook and subparallel San Andreas to the south. The same structure may exist beneath the Tehachapi mountains, with the roles of the Hitchbrook and San Andreas faults played by the north and south branches of the Garlock fault, respectively. The rising or arching of the basement toward the San Andreas fault (and toward the Garlock) is not only reflected in the geology and topography local to these faults in many places but is also generally observed on seismic reflection profiles in the vicinity of these faults in the western Mojave. Furthermore, the arching is also consistent with a strong component of fault normal compression.
On the Correlation between Iranian EFL Learners' Shyness Level and their Attitudes toward Language Learning

The current probe was after pinpointing the would-be correlation between learners' shyness and their language learning attitudes. The participants of the study were a total of 104 male and female institute EFL learners and the means of data collection were two ready-made questionnaires, one for gauging the learners' shyness and the other for tapping data regarding their language learning attitudes. The data thus collected were then analyzed through running Pearson Product Moment Correlation, independent samples t-test, and Eta Test. The results gained pointed toward lack of a significant correlation between the participants' shyness and the subscales of attitudes toward language learning. Moreover, no significant relationship was reported to be at work between gender of participants and their language learning attitudes. Nonetheless, with regard to learners' shyness, gender difference was found to play a part. Keywords: ambiguity tolerance, attitudes toward language learning, ego-permeability, inhibition, Iranian EFL learners, risk-taking, self-image, shyness
A comparison of diabetic foot ulcer outcomes using negative pressure wound therapy versus historical standard of care

Diabetic foot ulcers (DFUs) are a leading cause of morbidity and hospitalisation among patients with diabetes. We analysed claims data for Medicare part B diabetic foot ulcer patients treated with Negative Pressure Wound Therapy at home (N = 1135) and diabetic foot ulcer patients from a published meta‐analysis of randomised controlled wet‐to‐moist therapy. The expected costs of care for the two treatments were also compared. A significantly greater proportion of wounds treated with NPWT achieved a successful treatment endpoint compared with wet‐to‐moist therapy at both 12 weeks (39·5% versus 23·9%; P < 0·001) and 20 weeks (46·3% versus 32·8%; P < 0·001). NPWT‐treated patients reached a successful wound treatment endpoint more rapidly, and the benefit was apparent in all wound sizes. Expected 20‐week treatment costs for NPWT were similar to those for wet‐to‐moist therapy if one nursing visit per day for the latter is assumed but 42% less if two nursing visits per day are made. Thus, NPWT may improve the proportion of DFUs that attain a successful wound treatment endpoint and decrease resource utilisation by a given health care system compared with standard wet‐to‐moist therapy.
Suppression of in Vivo β-Amyloid Peptide Toxicity by Overexpression of the HSP-16.2 Small Chaperone Protein*

Expression of the human β-amyloid peptide (Aβ) in a transgenic Caenorhabditis elegans Alzheimer disease model leads to the induction of HSP-16 proteins, a family of small heat shock-inducible proteins homologous to vertebrate αB crystallin. These proteins also co-localize and co-immunoprecipitate with Aβ in this model (Fonte, V., Kapulkin, V., Taft, A., Fluet, A., Friedman, D., and Link, C. D. (2002) Proc. Natl. Acad. Sci. U. S. A. 99, 9439–9444). To investigate the molecular basis and biological function of this interaction between HSP-16 and Aβ, we generated transgenic C. elegans animals with high level, constitutive expression of HSP-16.2. We find that constitutive expression of wild type, but not mutant, HSP-16.2 partially suppresses Aβ toxicity. Wild type Aβ-(1–42), but not Aβ single chain dimer, was observed to become sequestered in HSP-16.2-containing inclusions, indicating a conformation-dependent interaction between HSP-16.2 and Aβ in vivo. Constitutive expression of HSP-16.2 could reduce amyloid fibril formation, but it did not reduce the overall accumulation of Aβ peptide or alter the pattern of the predominant oligomeric species. Studies with recombinant HSP-16.2 demonstrated that HSP-16.2 can bind directly to Aβ in vitro, with a preferential affinity for oligomeric Aβ species. This interaction between Aβ and HSP-16.2 also influences the formation of Aβ oligomers in in vitro assays. These studies are consistent with a model in which small chaperone proteins reduce Aβ toxicity by interacting directly with the Aβ peptide and altering its oligomerization pathways, thereby reducing the formation of a minor toxic species.
Characterization of Mannheimia haemolytica in beef calves via nasopharyngeal culture and pulsed-field gel electrophoresis

Mannheimia haemolytica is a major bacterial component of bovine respiratory disease (BRD); unfortunately, very little is known about M. haemolytica transmission dynamics among cattle. Identifying potential variation in M. haemolytica populations over time and induction of nasopharyngeal colonization and subsequent shedding are 2 areas where knowledge is lacking. In our study, 2 separate loads of 20 mixed-origin, male calves were purchased through an order buyer on different dates. Deep nasopharyngeal cultures (NPC) were performed on all calves on arrival and, if M. haemolytica–negative, a second screening culture was obtained. Calves that were negative on 2 initial NPCs (NEG; n = 4) were subsequently challenged with a previously isolated field strain of M. haemolytica in both the upper and lower respiratory tract, individually housed, and then monitored for M. haemolytica shedding via NPCs at 0.5, 1, 3, 5, 7, and 9 days postchallenge. Naturally M. haemolytica–positive calves (2 per load) were kept for additional daily cultures (POS; n = 4). Individual calf M. haemolytica status for both the POS and NEG groups was inconsistent between study days. Additionally, pulsed-field gel electrophoresis performed on isolates from the positive cultures showed that the NEG calves did not shed the M. haemolytica challenge strain, but rather 2 distinct clusters of M. haemolytica were shared among POS and NEG calves regardless of their initial status. Although sample sizes were small, these findings illustrate how variable the results of a single nasopharyngeal swab can be and the challenges of using an individual culture to truly represent animal M. haemolytica status.
Two- to Five-Year Followup of Arthroscopic Bankart Reconstruction Using a Suture Anchor Technique

This is a retrospective review of 27 patients (27 shoul ders) with recurrent anterior instability who underwent arthroscopic Bankart reconstruction with a suture an chor technique between 1990 and 1993. Average length of followup was 40 months (range, 26 to 64). The average Bankart rating score was 88 (range, 45 to 100) with 70% good-to-excellent results and 30% fair- to-poor results. The average University of California (Los Angeles) shoulder function score was 32 (range, 27 to 35). The average loss of external rotation in abduction was 1°. Eight patients (30%) failed the pro cedure and had recurrent anterior shoulder instability; seven of these had repeat traumatic events. A Pearson chi-square analysis of multiple variables was per formed to determine which variables correlated with a successful result. A higher success rate was obtained if the patient had five or fewer dislocations before surgical reconstruction. This technique should be lim ited to patients not returning to contact sports, or in whom the improved cosmetic result or increased post operative external rotation of the arthroscopic proce dure are valued.
Selective Distribution of a High-Affinity Plasminogen-Binding Site among Group A Streptococci Associated with Impetigo

ABSTRACT Group A streptococci can be classified according to their tendency to cause either impetigo, pharyngitis, or both types of infection. Genotypic markers for tissue site preference lie within emmgenes, which encode fibrillar surface proteins that play a key role in virulence. emm gene products (M and M-like proteins) display an extensive array of binding activities for tissue and plasma proteins of the human host. In a previous study, a high-affinity binding site for human plasmin(ogen) was mapped to theemm53 gene product. In this report, a structurally similar plasminogen-binding domain is found to be widely and selectively distributed among group A streptococci harboring the emmgene marker for the skin as the preferred tissue site for infection. The findings are highly suggestive of a central role for bacterial modulation of host plasmin(ogen) during localized infection at the epidermis.
Seminal plasma induces inflammation and enhances HIV-1 replication in human cervical tissue explants

The most immediate and evident effect of mucosal exposure to semen in vivo is a local release of proinflammatory mediators accompanied by an influx of leukocytes into the female genital mucosa (FGM). The implication of such response in HIV-1 transmission has never been addressed due to limitations of currently available experimental models. Using human tissue explants from the uterine cervix, we developed a system of mucosal exposure to seminal plasma (SP) that supports HIV-1 replication. Treatment of ectocervical explants with SP resulted in the upregulation of inflammatory and growth factors, including IL-6, TNF, CCL5, CCL20, CXCL1, and CXCL8, and IL1A, CSF2, IL7, PTGS2, as evaluated by measuring protein levels in explant conditioned medium (ECM) and gene expression in tissue. SP treatment was also associated with increased recruitment of monocytes and neutrophils, as observed upon incubation of peripheral blood leukocytes with ECM in a transwell system. To evaluate the impact of the SP-mediated response on local susceptibility to HIV-1, we infected ectocervical explants with the CCR5-tropic variant HIV-1BaL either in the presence of SP, or after explant pre-incubation with SP. In both experimental settings SP enhanced virus replication as evaluated by HIV-1 p24gag released in explant culture medium over time, as well as by HIV-1 DNA quantification in explants infected in the presence of SP. These results suggest that a sustained inflammatory response elicited by SP soon after coitus may promote HIV-1 transmission to the FGM. Nevertheless, ectocervical tissue explants did not support the replication of transmitted/founder HIV-1 molecular clones, regardless of SP treatment. Our system offers experimental and analytical advantages over traditional models of HIV-1 transmission for the study of SP immunoregulatory effect on the FGM, and may provide a useful platform to ultimately identify new determinants of HIV-1 infection at this site.