Search

Volunteer‐based roadkill monitoring schemes, including road carcass sampling, can represent considerable advances with respect to classical methods employed in conservation biology. We studied the genetic diversity, structure, and dynamics of the European polecat (Mustela putorius) across the Iberian Peninsula. We used samples of road carcasses collected by volunteers because this carnivore is an elusive species otherwise difficult to monitor with standard field protocols. We gathered 238 samples obtained from 2004 to 2022 from 13 different areas (8–31 samples/area). Using microsatellite loci, we identified 4 genetic units with gene flow among 3 of them in the Iberian Peninsula. The genetic variability was steadily low in 1 of the areas (Girona) for all the parameters evaluated. This area is also genetically isolated from the other studied areas. The inbreeding coefficient was significant in the north‐ and south‐Iberia units, and we did not detect a bottleneck signature in any of the 4 genetic units. Future conservation actions should consider the genetic dissimilarity among detected units and elucidate the ecological factors that have led to the observed genetic patterns. [ABSTRACT FROM AUTHOR]

The article in the journal "Allergy" discusses the assessment of sIgE to rLep d 2 for detecting Lepidoglyphus destructor sensitization in patients with respiratory allergies. The study found a high correlation between sIgE to rLep d 2 and L. destructor, with good sensitivity (71.64%) and excellent specificity (96.43%). However, the diagnostic value of rLep d 2 compared to skin prick tests and specific IgE tests for L. destructor allergies is minimal. The authors recommend using sIgE against Lep d 2 cautiously in diagnosing L. destructor allergies and suggest further research on its diagnostic utility. [Extracted from the article]

The human NQO1 (hNQO1) is a flavin adenine nucleotide (FAD)‐dependent oxidoreductase that catalyzes the two‐electron reduction of quinones to hydroquinones, being essential for the antioxidant defense system, stabilization of tumor suppressors, and activation of quinone‐based chemotherapeutics. Moreover, it is overexpressed in several tumors, which makes it an attractive cancer drug target. To decipher new structural insights into the flavin reductive half‐reaction of the catalytic mechanism of hNQO1, we have carried serial crystallography experiments at new ID29 beamline of the ESRF to determine, to the best of our knowledge, the first structure of the hNQO1 in complex with NADH. We have also performed molecular dynamics simulations of free hNQO1 and in complex with NADH. This is the first structural evidence that the hNQO1 functional cooperativity is driven by structural communication between the active sites through long‐range propagation of cooperative effects across the hNQO1 structure. Both structural results and MD simulations have supported that the binding of NADH significantly decreases protein dynamics and stabilizes hNQO1 especially at the dimer core and interface. Altogether, these results pave the way for future time‐resolved studies, both at x‐ray free‐electron lasers and synchrotrons, of the dynamics of hNQO1 upon binding to NADH as well as during the FAD cofactor reductive half‐reaction. This knowledge will allow us to reveal unprecedented structural information of the relevance of the dynamics during the catalytic function of hNQO1. [ABSTRACT FROM AUTHOR]

A large conformational heterogeneity of human NAD(P)H:quinone oxidoreductase 1 (NQO1), a flavoprotein associated with various human diseases, has been observed to occur in the catalytic site of the enzyme. Here, we report the X‐ray structure of NQO1 with phenylmethylsulfonyl fluoride (PMSF) at 1.6 Å resolution. Activity assays confirmed that, despite being covalently bound to the Tyr128 residue at the catalytic site, PMSF did not abolish NQO1 activity. This may indicate that the PMSF molecule does not reduce the high flexibility of Tyr128, thus allowing NADH and DCPIP substrates to bind to the enzyme. Our results show that targeting Tyr128, a key residue in NQO1 function, with small covalently bound molecules could possibly not be a good drug discovery strategy to inhibit this enzyme. [ABSTRACT FROM AUTHOR]

Summary: Cardiovascular disease (CVD) involves the second cause of death in low‐risk myelodysplastic syndrome (MDS) population. Prospective study to characterise the CVD and to identify predictors for the combined event (CE) cardiovascular event and/or all‐cause mortality in transfusion dependent low‐risk MDS patients. Thirty‐one patients underwent a cardiac assessment including biomarkers and cardiac magnetic resonance (cMR) with parametric sequences (T1, T2 and T2* mapping) and myocardial deformation by feature tracking (FT) and were analysed for clonal hematopoiesis of indeterminate potential mutations. Cardiac assessment revealed high prevalence of unknown structural heart disease (51% cMR pathological findings). After 2·2 [0·44] years follow‐up, 35·5% of patients suffered the CE: 16% death, 29% cardiovascular event. At multivariate analysis elevated NT‐proBNP ≥ 486pg/ml (HR 96·7; 95%‐CI 1·135–8243; P = 0·044), reduced native T1 time < 983ms (HR 44·8; 95%‐CI 1·235–1623; P = 0·038) and higher left ventricular global longitudinal strain (LV‐GLS) (HR 0·4; 95%‐CI 0·196–0·973; P = 0·043) showed an independent prognostic value. These variables, together with the myocardial T2* time < 20ms, showed an additive prognostic value (Log Rank: 12·4; P = 0·001). In conclusion, low‐risk MDS patients frequently suffer CVD. NT‐proBNP value, native T1 relaxation time and longitudinal strain by FT are independent predictors of poor cardiovascular prognosis, thus, their determination would identify high‐risk patients who could benefit from a cardiac treatment and follow‐up. [ABSTRACT FROM AUTHOR]

The increase in successful adaptations of serial crystallography at synchrotron radiation sources continues. To date, the number of serial synchrotron crystallography (SSX) experiments has grown exponentially, with over 40 experiments reported so far. In this work, we report the first SSX experiments with viscous jets conducted at ALBA beamline BL13-XALOC. Small crystals (15-30 µm) of five soluble proteins (lysozyme, proteinase K, phycocyanin, insulin and α-spectrin-SH3 domain) were suspended in lipidic cubic phase (LCP) and delivered to the X-ray beam with a high-viscosity injector developed at Arizona State University. Complete data sets were collected from all proteins and their high-resolution structures determined. The high quality of the diffraction data collected from all five samples, and the lack of specific radiation damage in the structures obtained in this study, confirm that the current capabilities at the beamline enables atomic resolution determination of protein structures from microcrystals as small as 15 µm using viscous jets at room temperature. Thus, BL13-XALOC can provide a feasible alternative to X-ray free-electron lasers when determining snapshots of macromolecular structures. [ABSTRACT FROM AUTHOR]

Purpose: The disc‐fovea angle (DFA) is used as a relevant indicator of ocular torsion change in cyclovertical strabismus. However, interpretation of the variation in time must differentiate whether a real change has occurred or if the disparity is due to random measurement error. The aim of the study was to obtain the minimal detectable change (MDC) of the DFA. It represents the minimal variation between two measurements that may be considered a real ocular torsion change. Methods: A prospective cross‐sectional study was conducted in San Carlos Clinical Hospital of Madrid, Spain. Sixty healthy right eyes from 60 patients (31 men and 29 women) were recruited. Three digital fundus photographs were obtained, and between measurements, the patient moved their head away from the head support and then returned. Two observers quantified the DFA with software designed with MATLAB. Test‐retest and interrater reliability were calculated. Results: Mean participant age was 56.1 years (SD 16.6, range 25–85). Mean DFA was 8.1° (SD 3.5, range 1.3–18.5). Test‐retest reliability for Observer 1 (Ob1), Observer 2 (Ob2) and interrater reliability were excellent (ICC 0.80, 0.83 and 0.95, respectively). Precision was 2.9° (Ob1) and 3.0° (Ob2), and the MDC95 was 4.1° (Ob1) and 4.2° (Ob2). Bland‐Altman analysis revealed an absence of bias and a homoscedastic distribution of the differences. Conclusions: The MDC of the DFA in fundus photography was 4°, which represents the minimal change that may be considered a real change in ocular torsion. This result may improve the interpretation of ocular torsion changes in surgery and clinical scenarios. [ABSTRACT FROM AUTHOR]

Tisagenlecleucel (tisa‐cel) is a second‐generation autologous CD19‐targeted chimeric antigen receptor (CAR) T‐cell therapy approved for relapsed/refractory (R/R) large B‐cell lymphoma (LBCL). The approval was based on the results of phase II JULIET trial, with a best overall response rate (ORR) and complete response (CR) rate in infused patients of 52% and 40%, respectively. We report outcomes with tisa‐cel in the standard‐of‐care (SOC) setting for R/R LBCL. Data from all patients with R/R LBCL who underwent leukapheresis from December 2018 until June 2020 with the intent to receive SOC tisa‐cel were retrospectively collected at 10 Spanish institutions. Toxicities were graded according to ASTCT criteria and responses were assessed as per Lugano 2014 classification. Of 91 patients who underwent leukapheresis, 75 (82%) received tisa‐cel therapy. Grade 3 or higher cytokine release syndrome and neurotoxicity occurred in 5% and 1%, respectively; non‐relapse mortality was 4%. Among the infused patients, best ORR and CR were 60% and 32%, respectively, with a median duration of response of 8.9 months. With a median follow‐up of 14.1 months from CAR T‐cell infusion, median progression‐free survival and overall survival were 3 months and 10.7 months, respectively. At 12 months, patients in CR at first disease evaluation had a PFS of 87% and OS of 93%. Patients with an elevated lactate dehydrogenase showed a shorter PFS and OS on multivariate analysis. Treatment with tisa‐cel for patients with relapsed/refractory LBCL in a European SOC setting showed a manageable safety profile and durable complete responses. [ABSTRACT FROM AUTHOR]

μNS is a 70 kDa major nonstructural protein of avian reoviruses, which cause significant economic losses in the poultry industry. They replicate inside viral factories in host cells, and the μNS protein has been suggested to be the minimal viral factor required for factory formation. Thus, determining the structure of μNS is of great importance for understanding its role in viral infection. In the study presented here, a fragment consisting of residues 448–605 of μNS was expressed as an EGFP fusion protein in Sf9 insect cells. EGFP‐μNS(448–605) crystallization in Sf9 cells was monitored and verified by several imaging techniques. Cells infected with the EGFP‐μNS(448–605) baculovirus formed rod‐shaped microcrystals (5–15 µm in length) which were reconstituted in high‐viscosity media (LCP and agarose) and investigated by serial femtosecond X‐ray diffraction using viscous jets at an X‐ray free‐electron laser (XFEL). The crystals diffracted to 4.5 Å resolution. A total of 4227 diffraction snapshots were successfully indexed into a hexagonal lattice with unit‐cell parameters a = 109.29, b = 110.29, c = 324.97 Å. The final data set was merged and refined to 7.0 Å resolution. Preliminary electron‐density maps were obtained. While more diffraction data are required to solve the structure of μNS(448–605), the current experimental strategy, which couples high‐viscosity crystal delivery at an XFEL with in cellulo crystallization, paves the way towards structure determination of the μNS protein. [ABSTRACT FROM AUTHOR]

Aims: Current guidelines recommend sacubitril/valsartan for patients with heart failure and reduced left ventricular ejection fraction (LVEF), but there is lack of evidence of its efficacy and safety in cancer therapy‐related cardiac dysfunction (CTRCD). Our aim was to analyse the potential benefit of sacubitril/valsartan in patients with CTRCD. Methods and results: We performed a retrospective multicentre registry (HF‐COH) in six Spanish hospitals with cardio‐oncology clinics including all patients treated with sacubitril/valsartan. Demographic and clinical characteristics and laboratory and echocardiographic data were collected. Median follow‐up was 4.6 [1; 11] months. Sixty‐seven patients were included (median age was 63 ± 14 years; 64% were female, 87% had at least one cardiovascular risk factor). Median time from anti‐cancer therapy to CTRD was 41 [10; 141] months. Breast cancer (45%) and lymphoma (39%) were the most frequent neoplasm, 31% had metastatic disease, and all patients were treated with combination antitumor therapy (70% with anthracyclines). Thirty‐nine per cent of patients had received thoracic radiotherapy. Baseline median LVEF was 33 [27; 37], and 21% had atrial fibrillation. Eighty‐five per cent were on beta‐blocker therapy and 76% on mineralocorticoid receptor antagonists; 90% of the patients were symptomatic NYHA functional class ≥II. Maximal sacubitril/valsartan titration dose was achieved in 8% of patients (50 mg b.i.d.: 60%; 100 mg b.i.d.: 32%). Sacubitril/valsartan was discontinued in four patients (6%). Baseline N‐terminal pro‐B‐type natriuretic peptide levels (1552 pg/mL [692; 3624] vs. 776 [339; 1458]), functional class (2.2 ± 0.6 vs. 1.6 ± 0.6), and LVEF (33% [27; 37] vs. 42 [35; 50]) improved at the end of follow‐up (all P values ≤0.01). No significant statistical differences were found in creatinine (0.9 mg/dL [0.7; 1.1] vs. 0.9 [0.7; 1.1]; P = 0.055) or potassium serum levels (4.5 mg/dL [4.1; 4.8] vs. 4.5 [4.2; 4.8]; P = 0.5). Clinical, echocardiographic, and biochemical improvements were found regardless of the achieved sacubitril–valsartan dose (low or medium/high doses). Conclusions: Our experience suggests that sacubitril/valsartan is well tolerated and improves echocardiographic functional and structural parameters, N‐terminal pro‐B‐type natriuretic peptide levels, and symptomatic status in patients with CTRCD. [ABSTRACT FROM AUTHOR]

Background: The anecdotic evidence of the benefits from biologic agents for psoriasis is extensive. However, data on the efficacy of biologic agents for pustular psoriasis are limited. Methods: To update the data on the efficacy and safety of biologic agents for the management of pustular psoriasis. A systematic review of published data regarding biologic therapies on PubMED database, used in the management of pustular psoriasis from 2012 was undertaken. Results: A total of 209 articles were identified, and 43 articles were selected for inclusion. TNF‐α inhibitors were used in 205 patients, and 86 patients received ustekinumab, secukinumab, brodalumab, ixekizumab and IL‐1 inhibitors. Overall response was favorable for most modalities. No serious adverse events were reported. Inconsistent measures of treatment response and study variability limited the overall evaluation of data. Conclusions: Infliximab and ustekinumab have the most evidence of efficacy and safety for the treatment of pustular psoriasis. Recent evidence supports the use of IL‐17 antagonists. Prospective controlled and comparative trials are needed to further explore the efficacy and safety of biologic agents in order to establish objective recommendations for the management of this challenging condition. [ABSTRACT FROM AUTHOR]

Objective: Angioimmunoblastic T‐cell lymphoma (AITL) is frequently associated with autoimmune cytopenia (AIC). Whether such patients have a particular phenotype and require particular management is unclear. Method: Angioimmunoblastic T‐cell lymphoma patients from the multicentric database of the Lymphoma Study Association presenting with AIC during disease course were included and matched to AITL patients without AIC (1/5 ratio). Results: At diagnosis, AIC patients (n = 28) had more spleen and bone marrow involvement (54% vs 19% and 71% vs 34%, P < 0.001), Epstein‐Barr virus replication (89% vs 39%, P < 0.001), gamma globulin titers (median 23 vs 15 g/L, P = 0.002), and proliferating B cells and plasmablasts in biopsies, as compared to control patients (n = 136). The 28 AIC patients had 41 episodes of AIC, diagnosed concomitantly with AITL in 23 (82%) cases. After a median follow‐up of 24 months (range 3‐155), 10 patients relapsed, all associated with AITL relapse. Conclusion: Our results provide new insight into AIC associated with AITL by highlighting the significant interplay between AITL and B‐cell activation leading to subsequent autoimmunity. [ABSTRACT FROM AUTHOR]

Aims We aimed to define the clinicopathological characteristics of 29 primary sinonasal diffuse large B cell lymphoma ( DLBCLsn) in a series of 240 cases of DLBCL not otherwise specified [ DLBCLall ( NOS)], including DLBCLsn training set ( n = 11) and validation set ( n = 18), and DLBCLnon-sn ( n = 211). Methods and results In the training set, 82% had a non-germinal center B-cell-like (Hans' Classifier) (non- GCB) phenotype and 18% were Epstein-Barr virus-encoded small RNAs ( EBER)+. The genomic profile showed gains(+) of 1q21.3q31.2 (55%), 10q24.1 (46%), 11q14.1 (46%) and 18q12.1q23 (46%); losses(−) of 6q26q27 (55%) and 9p21.3 (64%); and copy number neutral loss of heterozygosity (LOH) (acquired uniparental disomy, UPD) at 6p25.3p21.31 (36%). This profile is comparable to DLBCLNOS ( GSE11318, n = 203.) and closer to non- GCB/activated B-cell-like subtype ( ABC). Nevertheless, +1q31, −9p21.3 and −10q11.1q26.2 were more characteristic of DLBCLsn ( P < 0.001). Array results were verified successfully by fluorescence in situ hybridization ( FISH) on +1q21.3 ( CKS1B), −6q26 ( PARK2), +8q24.21 ( MYC), −9p21.3 ( MTAP, CDKN2A/B), −17p13.1 ( TP53) and +18q21.33 ( BCL2) with 82-91% agreement. Minimal common regions included biologically relevant genes of MNDA (+1q23.1), RGS1 and RGS13 (+1q31.2), FOXP1 (+3p13), PRDM1 (BLIMP1) and PARK2 (−6q21q26) , MYC ( +8q24.21), CDKN2A (−9p21.3), PTEN (−10q23.31), MDM2 (+12q15), TP53 (−17p13.1) and BCL2 (+18q21.33). Correlation between DNA copy number and protein immunohistochemistry was confirmed for RGS1, RGS13, FOXP1, PARK2 and BCL2. The microenvironment had high infiltration of M2-like tumour associated macrophages ( TAMs) and CD8+T lymphocytes that associated with higher genomic instability. The DLBCLsn validation set confirmed the clinicopathological characteristics, all FISH loci and immunohistochemistry ( IHC) for RGS1. RGS1, one of the most frequently altered genes, was analysed by IHC in DLBCLall and high RGS1 expression associated with non- GCB, EBER+ and unfavourable overall survival (hazard ratio = 1.794; P = 0.016). Conclusions DLBCLsn has a characteristic genomic profile. High RGS1 IHC expression associates with poor overall survival in DLBCLall ( NOS). [ABSTRACT FROM AUTHOR]

Interactions of proline-rich motifs with SH3 domains are present in signal transduction and other important cell processes. Analysis of structural and thermodynamic data suggest a relevant role of water molecules in these protein-protein interactions. To determine whether or not the SH3 domain of the Fyn tyrosine kinase shows the same behaviour, the crystal structures of its complexes with two high-affinity synthetic peptides, VSL12 and APP12, which are class I and II peptides, respectively, have been solved. In the class I complexes two water molecules were found at the binding interface that were not present in the class II complexes. The structures suggest a role of these water molecules in facilitating conformational changes in the SH3 domain to allow the binding of the class I or II peptides. In the third binding pocket these changes modify the cation-π and salt-bridge interactions that determine the affinity of the binding. Comparison of the water molecules involved in the binding of the peptides with previous reported hydration spots suggests a different pattern for the SH3 domains of the Src tyrosine kinase family. [ABSTRACT FROM AUTHOR]

Despite their differential cell tropisms, HIV-1 and HCV dramatically influence disease progression in coinfected patients. Macrophages are important target cells of HIV-1. We hypothesized that secreted HCV core protein might modulate HIV-1 replication. We demonstrate that HCV core significantly enhances HIV-1 replication in human macrophages by upregulating TNF-α and IL-6 via TLR2-, JNK-, and MEK1/2-dependent pathways. Furthermore, we show that TNF-α and IL-6 secreted from HCV core-treated macrophages reactivates monocytic U1 cells latently infected with HIV-1. Our studies reveal a previously unrecognized role of HCV core by enhancing HIV-1 infection in macrophages. [ABSTRACT FROM AUTHOR]

BACKGROUND There is a need to examine the impact of anaerobic reactor type and wastewater strength on anaerobic-aerobic two-stage biological systems for temperate wastewater treatment An expanded granular sludge blanket reactor and an anaerobic membrane bioreactor for crude wastewater treatment with downstream aerobic biological treatment were studied together with increasing the organic concentration by fortifying the crude wastewater with primary sludge. RESULTS A chemical oxygen demand and ammonia compliant effluent was produced from the anaerobic-aerobic two-stage process. Due to the enhanced organics removal achieved by the membrane, a lower denitrification rate, kd, was recorded for the anaerobic membrane bioreactor effluent treatment. However, the residual organic carbon in the anaerobic effluents from both the expanded granular sludge blanket reactor and the anaerobic membrane bioreactor treating crude wastewater was not of sufficient quality to support denitrification. Complete nitrification was achieved during downstream treatment of the fortified effluent. In addition, fortification increased kd to values analogous to exogenous carbon substrates. CONCLUSIONS It is postulated that fortification currently presents the most sustainable strategy for anaerobic-aerobic two-stage biological systems due to a combination of enhanced methane production and denitrification. © 2013 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

B-phycoerythrin from the red alga Porphyridium cruentum was crystallized using the technique of capillary counter-diffusion. Crystals belonging to the space group R3 with almost identical unit cell constants and diffracting to 1.85 and 1.70 Å were obtained at pH values of 5 and 8, respectively. The most important difference between structures is the presence of the residue His88α in two different conformations at pH 8. This residue is placed next to the chromophore phycoerythrobilin PEB82α and the new conformation results in the relocation of the hydrogen-bond network and hydration around PEB82α, which probably contributes to the observed pH dependence of the optical spectrum associated with this chromophore. Comparison with the structures of B-phycoerythrin from other red algae shows differences in the conformation of the A-ring of the chromophore PEB139α. This conformational difference in B-phycoerythrin from P. cruentum enables the formation of several hydrogen bonds that connect PEB139α with the chromophore PEB158β at the (αβ)3 hexamer association interface. The possible influence of these structural differences on the optical spectrum and the ability of the protein to perform energy transfer are discussed, with the two pH-dependent conformations of His88α and PEB82α being proposed as representing critical structural features that are correlated with the pH dependence of the optical spectrum and transient optical states during energy transfer. Database Structural data have been deposited in the Protein Data Bank under accession numbers and . Structured digital abstract B-phycoerythrin beta and B-phycoerythrin alpha bind by x-ray crystallography (View interaction) [ABSTRACT FROM AUTHOR]

The hepatitis C virus nonstructural 5A (NS5A) protein is a large zinc-binding phosphoprotein that plays an important role in viral RNA replication and is involved in altering signal transduction pathways in the host cell. This protein interacts with Fyn tyrosine kinase in vivo and regulates its kinase activity. The 1.5 Å resolution crystal structure of a complex between the SH3 domain of the Fyn tyrosine kinase and the C-terminal proline-rich motif of the NS5A-derived peptide APPIPPPRRKR has been solved. Crystals were obtained in the presence of ZnCl2 and belonged to the tetragonal space group P41212. The asymmetric unit is composed of four SH3 domains and two NS5A peptide molecules; only three of the domain molecules contain a bound peptide, while the fourth molecule seems to correspond to a free form of the domain. Additionally, two of the SH3 domains are bound to the same peptide chain and form a ternary complex. The proline-rich motif present in the NS5A protein seems to be important for RNA replication and virus assembly, and the promiscuous interaction of the Fyn SH3 domain with the NS5A C-terminal proline-rich peptide found in this crystallographic structure may be important in the virus infection cycle. [ABSTRACT FROM AUTHOR]

The -phenylalanine oxidase IL4I1 inhibits T-cell proliferation in vitro through HO production, and is highly expressed in tumor-associated macrophages. IL4I1 is also detected by immunohistochemistry in neoplastic cells from several B-cell lymphomas and some non-lymphoid tumors. To evaluate IL4I1's effect on tumor growth, we developed a mouse melanoma model constitutively coexpressing IL4I1 and the GP33 epitope. After GP33 vaccination, tumors developed more frequently in mice injected with IL4I1-expressing cells in comparison with mice receiving control cells. Tumor escape was preceded by a rapid diminution of IFN-γ-producing cytotoxic antitumor CD8 T cells. Moreover, tumor incidence was already increased when only 20% of the injected cells expressed IL4I1. The minimal IL4I1 activities leading to tumor escape were close to those detected in human melanoma and mesothelioma. Thus, we demonstrate the immunosuppressive functions of IL4I1 in vivo and suggest that IL4I1 facilitates human tumor growth by inhibiting the CD8 antitumor T-cell response. [ABSTRACT FROM AUTHOR]

MΦ and DC are key elements in the control of tissue homeostasis and response to insult. In this work, we demonstrate that MΦ and DC are the major producers of the phenylalanine catabolizing enzyme IL-4-induced gene 1 (IL4I1) under inflammatory conditions. IL4I1 was first described in B cells, which indeed can produce IL4I1 in vitro, although at much lower levels. In vivo, IL4I1 is highly expressed by MΦ and DC of Th1 granulomas (sarcoidosis, tuberculosis) but poorly detected in Th2 granulomas (schistosomiasis). In vitro, expression of the enzyme is induced in mononuclear phagocytes by various pro-inflammatory stimuli through the activation of the transcription factors NF-κB and/or STAT1. B cells also express IL4I1 in response to NF-κB-activating stimuli such as CD40L; however, in contrast to myeloid cells, B cells are insensitive to IFN-γ but respond to stimulation of the IL-4/STAT6 axis. As we show that the expression of IL4I1 by a monocytic cell line inhibits T-cell proliferation and production of IFN-γ and inflammatory cytokines, we propose that IL4I1 participates in the downregulation of Th1 inflammation in vivo. [ABSTRACT FROM AUTHOR]

The α-spectrin SH3 domain (Spc-SH3) is a small modular domain which has been broadly used as a model protein in folding studies and these studies have sometimes been supported by structural information obtained from the coordinates of Spc-SH3 mutants. The structure of B5/D48G, a multiple mutant designed to improve the hydrophobic core and as a consequence the protein stability, has been solved at 1 Å resolution. The crystals belonged to the orthorhombic space group P212121, with unit-cell parameters a = 24.79, b = 37.23, c = 62.95 Å. This mutant also bears a D48G substitution in the distal loop and this mutation has also been reported to increase the stability of the protein by itself. The structure of the B5/D48G mutant shows a highly packed hydrophobic core and a more ordered distal loop compared with previous Spc-SH3 structures. [ABSTRACT FROM AUTHOR]

BACKGROUND:: Previous studies have shown that 4.6 μg of nicotine administered to the hippocampus can deteriorate learning acquisition in alcohol-drinking rats. The aim of the present study was to research whether this nicotine dose can alter the alcohol withdrawal syndrome and whether the two neurosteroids, allopregnanolone (AlloP) and pregnenolone sulfate (PregS), at doses previously reported as anxiolytic and promnesic, respectively, can modulate these effects.METHODS:: We used a free-choice drinking procedure that involved providing the rats with an alcoholic solution (10% ethanol) at an early age. Alcohol and control rats were assigned randomly to six groups that received two consecutive intrahippocampal (dorsal CA1) injections once per week during three consecutive weeks after one hour of ethanol drinking. The first injection was nicotine (4.6 μg, 20 mM) or saline and the second injection was PregS (5 ng, 24 μM), AlloP (0.2 μg, 1.26 μM) or saline. Blood alcohol concentrations were assessed one week before the withdrawal testing. Locomotor activity and audiogenic seizures were tested during withdrawal after 110 days of voluntary ethanol consumption. Rats were injected immediately before the withdrawal testing.RESULTS:: AlloP induced a decrease in horizontal and vertical activities, suggesting that the dose tested has sedative effects. AlloP reversed the seizures induced by ethanol withdrawal and also the spontaneous audiogenic seizures induced by the acoustic stimulation in control rats. Moreover, AlloP decreased other alcohol withdrawal signs, such as tail stiffening and body rigidity. Intrahippocampal administration of nicotine or PregS, at the doses tested, did not effectively modify the expression of audiogenic seizures induced by alcohol withdrawal.CONCLUSIONS:: These results show that hippocampal GABAergic activity and AlloP have an important role in preventing convulsive behavior. The results also highlight the therapeutic potential of AlloP for reducing the alcohol withdrawal syndrome. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses a retrospective study on the hemophagocytic syndrome (HPS) cases on allogeneic hematopoietic stem cell transplantation (HCT) patients from 15 European Group for Blood and Marrow Transplantation (EBMT) centers.

Focuses on the urticaria reaction due to trimebutine confirmed by patch and oral provocation test. Treatment of the patient with intramuscular corticosteroid; Diagnosis of a type IV hypersensitivity reaction to trimebustine; Publication of literature on contact allergic dermatitis caused by trimebutine.

The article discusses about a case study where dermatitis due to Edding 3000 was caused to a patient. A 28-year-old woman presented with skin lesions on her right thigh 4 hours after liposuction. It was the fifth liposuction that the patient had undergone. International GmbH, Germany was used to outline the area at each liposuction. Epicutaneous tests were carried out with the suspected agent the permanent marker, Edding 3000 in three different colors blue, red and black. The incidence of allergic reactions to colophony has increased to such an extent that in most countries it has become one of the 10 most important sensitizations'.

Reports a case of rhinoconjunctivitis and asthma in a housewife who referred respiratory symptoms during exposure to vapors released by boiling rice. Suspected immunoglobulin E (IgE)-mediated hypersensitivity; Confirmation of the presence of one allergen in the vapors by in vivo and in vitro studies.

Reports on the case of hypersensitivity pneumonitis induced by exposure to corn flour. Symptoms of hypersensitivity pneumonitis; Contamination of corn by the presence of microbes.

Reports on a case of a 72-year-old woman who was admitted for evaluation of recurrent, non-pruritic, edematous attacks occurring on the face, lips and uvula. Detection ofimmunoglobulin A through serum immunoelectrophoresis; Results of a chest radiograph; Bronchofiberscope test.