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Rabies virus (RABV) transmitted by the common vampire bat (

BackgroundThe global pandemic of COVID-19 and the social distancing efforts implemented worldwide to limit its spread have disrupted the economy, increased food insecurity, and mental health problems.ObjectivesThe aim of this study was to determine the association between food insecurity and mental health outcomes (stress, depression, and anxiety) in Peruvian households during the COVID-19 pandemic.Materials and methodsA cross-sectional investigation was conducted with 525 participants of both sexes (68% women), over 18 years of age and from the three geographic regions of Peru: Coast (54.9%), Highlands (28.4%), and Jungle (16.8%). The data were collected during the year 2021, between July 6 and September 22 through a self-administered online survey designed to assess socio-demographic, socioeconomic, food insecurity, and mental health outcomes (depression, anxiety, and stress).ResultsThe majority of households (71.4%) experienced some degree of food insecurity. Mild food insecurity was the most frequent, affecting 49.1%, followed by moderate 15.4%, and severe 6.9%. Regarding mental health outcomes, 24.8% manifested depression, 26.7% anxiety, and 15.3% stress. With respect to the association between the level of food insecurity and anxiety, this was highly significant (p < 0.01). Households with mild, moderate and severe food insecurity are 2.04, 4.5, and 10.44 times, respectively, more likely to have moderate-severe anxiety. On the other hand, the mild food insecurity was not associated with moderate-severe depression. In contrast, households with moderate and severe food insecurity are 2.8 and 5.7 times, respectively, more likely to have moderate-severe depression. Finally, households with moderate food insecurity are 5.9 times more likely to have moderate-severe stress, and households with severe food insecurity are 8.5 times more likely to have moderate-severe stress, both having a highly significant association (p < 0.01).ConclusionIn conclusion, during the second wave of the COVID-19 pandemic in Peru, household food insecurity was independently associated with worse mental health outcomes. Monitoring of both food insecurity and mental health will be important as the COVID-19 pandemic continues.

Following surgical removal of one kidney, the other enlarges and increases its function. The mechanism for the sensing of this change and the growth is incompletely understood but begins within days and compensatory renal hypertrophy (CRH) is the dominant contributor to the growth. In many individuals undergoing nephrectomy for cancer or kidney donation this produces a substantial and helpful increase in renal function. Two main mechanisms have been proposed, one in which increased activity by the remaining kidney leads to hypertrophy, the second in which there is release of a kidney specific factor in response to a unilateral nephrectomy that initiates CRH. Whilst multiple growth factors and pathways such as the mTORC pathway have been implicated in experimental studies, their roles and the precise mechanism of CRH are not defined. Unrestrained hypoxia inducible factor activation in renal cancer promotes growth and may play an important role in driving CRH.

Vampire bat transmitted rabies (VBR) is a continuing burden to public health and agricultural sectors in Latin America, despite decades-long efforts to control the disease by culling bat populations. Culling has been shown to disperse bats, leading to an increased spread of rabies. Thus, non-lethal strategies to control VBR, such as vaccination, are desired. Here, we evaluated the safety and efficacy of a viral-vectored recombinant mosaic glycoprotein rabies vaccine candidate (RCN-MoG) in vampire bats (Desmodus rotundus) of unknown history of rabies exposure captured in México and transported to the United States. Vaccination with RCN-MoG was demonstrated to be safe, even in pregnant females, as no evidence of lesions or adverse effects were observed. We detected rabies neutralizing antibodies in 28% (8/29) of seronegative bats post-vaccination. Survival proportions of adult bats after rabies virus (RABV) challenge ranged from 55–100% and were not significantly different among treatments, pre- or post-vaccination serostatus, and route of vaccination, while eight pups (1–2.5 months of age) used as naïve controls all succumbed to challenge (P

BackgroundTo test the antimicrobial potential of clove essential oil that has been less investigated on antimicrobial-resistant organisms (extended-spectrum β-lactamase-ESBL-producingEscherichia coli),we collected 135 ESBL-producingEscherichia colistrains given thatE. coliis the major organism increasingly isolated as a cause of complicated urinary and gastrointestinal tract infections, which remains an important cause of therapy failure with antibiotics for the medical sector. Then, in this study, we evaluated the relationship between the antibacterial potential activity ofSyzygium aromaticumessential oil (EOSA) and the expression of antibiotic-resistant genes (SHV-2, TEM-20) in plasmidic DNA on ESBL-producingE. coliusing RT-PCR technique.ResultsEOSA was obtained by hydrodistillation. Using Kirby-Baüer method, we found that EOSA presented a smaller media (mean = 15.59 mm) in comparison with chloramphenicol (mean = 17.73 mm). Thus, there were significant differences (p ConclusionsPlant essential oils and their active ingredients have potentially high bioactivity against a different target (membranes, cytoplasm, genetic material). In this research, EOSA might become an important adjuvant against urinary and gastrointestinal diseases caused by ESBL-producingE. coli.

Se presenta el diseño, implementación y operación de un módulo didáctico desarrollado con la finalidad de obtener una adecuada capacitación en el manejo de los Sistemas Fototérmicos y Fotovoltaicos. Al verificar el desempeño del equipo, se observaron sus capacidades tales como: Sistema de captación fototérmica con circulación natural y forzada, almacenamiento de líquido, suministro y distribución de tubería. Se incluye el Sistema de captación fotovoltaica trabajando paralelamente con la distribución de energía requerida para un sistema de bombeo y contribuir en el funcionamiento del sistema utilizando lámparas de halógeno para prácticas dentro del laboratorio. Al poner el sistema a disposición de la comunidad académica de la institución, se mejoró el proceso de enseñanza aprendizaje, facilitando la labor del docente e incrementando la motivación del estudiante a adquirir conocimientos en este tema. Basándose en la idea de trabajar con un sistema fototérmico de aplicaciones prácticas con el suministro de energía fotovoltaica, con los sistemas de simulación a uno real.

We report mortality events in a group of 123 common vampire bats (Desmodus rotundus) captured in México and housed for a rabies vaccine efficacy study in Madison, Wisconsin. Bat mortalities occurred in México and Wisconsin, but rabies cases reported herein are only those that occurred after arrival in Madison (n = 15). Bats were confirmed positive for rabies virus (RABV) by the direct fluorescent antibody test. In accordance with previous reports, we observed long incubation periods (more than 100 days), variability in clinical signs prior to death, excretion of virus in saliva, and changes in rabies neutralizing antibody (rVNA) titers post-infection. We observed that the furious form of rabies (aggression, hyper-salivation, and hyper-excitability) manifested in three bats, which has not been reported in vampire bat studies since 1936. RABV was detected in saliva of 5/9 bats, 2−5 days prior to death, but was not detected in four of those bats that had been vaccinated shortly after exposure. Bats from different capture sites were involved in two separate outbreaks, and phylogenetic analysis revealed differences in the glycoprotein gene sequences of RABV isolated from each event, indicating that two different lineages were circulating separately during capture at each site.

Ektacytometry techniques quantifies red blood cells (RBCs) deformability by measuring the elongation of suspended RBCs subjected to shear stress. Raw shear stress elongation plots are difficult to understand, thus most research papers apply data reduction methods characterizing the relationship between curve fitting. Our approach works with the naturally generated photometrically recorded time series of the diffraction pattern of several million of RBCs subjected to shear stress, and applies nonlinear quantifiers to study the fluctuations of these elongations. The development of new quantitative methods is crucial for restricting the subjectivity in the study of the cells behavior, mainly if they are capable of analyze at the same time biological and mechanical aspects of the cells in flowing conditions and compare their dynamics. A patented optical system called Erythrocyte Rheometer was used to evaluate viscoelastic properties of erythrocytes by Ektacytometry. To analyze cell dynamics we used the technique of Time Delay Coordinates, False Nearest Neighbors, the forecasting procedure proposed by Sugihara and May, and Hurst exponent. The results have expressive meaning on comparing healthy samples with parasite treated samples, suggesting that apparent noise associated with deterministic chaos can be used not only to distinguish but also to characterize biological and mechanical aspects of cells at the same time in flowing conditions.

In recent years, interest for petrochemical processes has been increasing, especially in refinement area. However, the high variability in the dynamic characteristics present in the atmospheric distillation column poses a challenge to obtain quality products. To improve distillates quality in spite of the changes in the input crude oil composition, this paper details a new design of a control strategy in a conventional crude oil distillation plant defined using formal interaction analysis tools. The process dynamic and its control are simulated on Aspen HYSYS® dynamic environment under real operating conditions. The simulation results are compared against a typical control strategy commonly used in crude oil atmospheric distillation columns.

En este documento se presenta el diseño, implementación y operación de un módulo didáctico desarrollado con la finalidad de obtener una adecuada capacitación en el aprendizaje de los Sistemas Solares Fotovoltaicos. Al verificar el desempeño del equipo, se observaron sus capacidades tales como: potencia de suministro, medición de parámetros eléctricos utilizando puntos de prueba distribuidos en el panel de monitoreo, posibilidad de expansión de capacidad mediante la interconexión con módulos de características similares. Al poner el sistema a disposición de la comunidad académica de la institución, se mejoró el proceso de enseñanza aprendizaje, facilitando la labor del docente e incrementando la motivación del estudiante a adquirir conocimientos en este tema. Basándose en la idea de pasar de trabajar con celdas solares de aplicaciones de laboratorio a un sistema fotovoltaico de aplicaciones prácticas en el suministro de energía eléctrica, y de los sistemas de simulación a uno

International audience; In the past few decades great effort has been devoted to the study of water confined in hydrophobic geometries at the nanoscale (tubes and slit pores) due to the multiple technological applications of such systems, ranging from drug delivery to water desalination devices. To our knowledge, neither numerical/theoretical nor experimental approaches have so far reached a consensual understanding of structural and transport properties of water under these conditions. In this work, we present molecular dynamics simulations of TIP4P/2005 water under different nanoconfinements (slit pores or nanotubes, with two degrees of hydrophobicity) within a wide temperature range. It has been found that water is more structured near the less hydrophobic walls, independently of the confining geometries. Meanwhile, we observe an enhanced diffusion coefficient of water in both hydrophobic nanotubes. Finally, we propose a confined Stokes–Einstein relation to obtain the viscosity from diffusivity, whose result strongly differs from the Green–Kubo expression that has been used in previous works. While viscosity computed with the Green–Kubo formula (applied for anisotropic and confined systems) strongly differs from that of the bulk, viscosity computed with the confined Stokes–Einstein relation is not so much affected by the confinement, independently of its geometry. We discuss the shortcomings of both approaches, which could explain this discrepancy.

Resumen Definicion El termino cardio-oncologia hace referencia a una monitorizacion y estratificacion de riesgo durante todas las etapas del cancer, con el objetivo de minimizar o eliminar las complicaciones cardiovasculares, asi como las interrupciones precoces de tratamientos potencialmente curativos. Objetivos Estos objetivos solo pueden conseguirse con un enfoque multidisciplinar. El desarrollo de protocolos locales de monitorizacion que adapten las recomendaciones generales a los medios disponibles en cada centro es un paso critico en el manejo de la cardiotoxicidad. Protocolo de prevencion y diagnostico A continuacion se resume el protocolo de prevencion y diagnostico precoz de la miocardiopatia secundaria a tratamientos oncologicos de la unidad de Cardio-Oncologia del Hospital Universitario La Paz.

SUMMARY Efficient Ca2+ flux induced during cognate T cell activation requires signaling the T cell receptor (TCR) and unidentified G-protein-coupled receptors (GPCRs). T cells express the neurokinin-1 receptor (NK1R), a GPCR that mediates Ca2+ flux in excitable and non-excitable cells. However, the role of the NK1R in TCR signaling remains unknown. We show that the NK1R and its agonists, the neuropeptides substance P and hemokinin-1, co-localize within the immune synapse during cognate activation of T cells. Simultaneous TCR and NK1R stimulation is necessary for efficient Ca2+ flux and Ca2+-dependent signaling that sustains the survival of activated T cells and helper 1 (Th1) and Th17 bias. In a model of contact dermatitis, mice with T cells deficient in NK1R or its agonists exhibit impaired cellular immunity, due to high mortality of activated T cells. We demonstrate an effect of the NK1R in T cells that is relevant for immunotherapies based on pro-inflammatory neuropeptides and its receptors., Graphical Abstract, In Brief The neurokinin 1 receptor (NK1R) induces Ca2+ flux in excitable cells. Here, Morelli et al. show that NK1R signaling in T cells promotes optimal Ca2+ flux triggered by TCR stimulation, which is necessary to sustain T cell survival and the efficient Th1- and Th17-based immunity that is relevant for immunotherapies based on pro-inflammatory neuropeptides.

Objetivo: Medir la Calidad de Vida en el trabajo (CVT) y sus factores asociados en profesores de colegios públicos de Concepción, Chile. Método: Investigación cuantitativa, transversal, descriptiva. Muestra: 92 profesores. Instrumentos: Se empleó CVT-GOHISALO para evaluar CVT (Alpha de Cronbach 0.952) y un cuestionario biosociodemográfico diseñado por el primer autor. El procesamiento de datos se realizó con SPPS, empleándose Rho-Spearman, Rho-Pearson, ANOVA y pruebas no-paramétricas. Se contó con las autorizaciones de los comités de ética involucrados, así como de la Dirección de Administración de Educación Municipal de Concepción (DAEM), y con el consentimiento informado de los participantes. Resultados: Promedio CVT global: 215.8 (DE=43.3), que indica nivel medio de CVT. Promedios CVT por dimensiones: Soporte institucional para el trabajo (SIT)=44.6 (DE=10.2), Seguridad en el trabajo (ST)=30 (DE=11.7), Integración al puesto de trabajo (IPT)=33.4 (DE=6.1), Satisfacción por el trabajo (SPT)=34.9 (DE=6.8), Bienestar logrado a través del trabajo (BAT)=36.6 (DE=5.7), Desarrollo personal (DP)=23.3 (DE=6.4) y Administración del tiempo libre (ATL)=12.7 (DE=4.2). Clasificación CVT por dimensiones: SIT: nivel alto; ST, IPT, SPT y DP: nivel medio; BAT y ATL: nivel bajo. Anova para prexistencia de trastorno en salud mental y CVT global, dimensiones SIT, ST, IPT, SPT, BAT, DP y ATL con valor p=0.000; p=0.000; p=0.017; p=0.005; p=0.000; p=0.001 y p=0.046 respectivamente. Conclusiones: Los maestros se encuentran medianamente satisfechos con su CVT; existe asociación entre prexistencia de trastornos en salud mental y baja percepción de CVT. Es fundamental que enfermería vele por adecuadas condiciones laborales de profesores y alumnos con el fin de asegurar una CVT satisfactoria así como mejorar la calidad de la educación impartida.

En este trabajo se realizo una modelizacion fisicomatematica del proceso de coagulacion enzimatica utilizando elsistema constituido por micelas de caseina bovina y un pool enzimatico obtenido a partir de Bacillus sp. P7aislado de Piaractus mesopotamicus. La modelizacion consistio en la realizacion de disenos factorialescompletos considerando el efecto de la temperatura, del pH y de la relacion enzima/sustrato sobre el tiempo decoagulacion, la dimension fractal y la velocidad inicial del proceso de coagulacion. Palabras clave: modelizacion fisicomatematica, micelas de caseina, proteasa bacteriana. In this paper it is shown a physicomathematical modeling of enzymatic coagulation process of casein micelles.The enzymatic pool was obtained from Bacillus sp. P7 which was isolated from Piaractus mesopotamicus.Modelling was achieved by complete design of experiments considering the effect of temperature, pH and ratioenzyme:sustrate on time of coagulation, fractal dimention and initial velocity of the coagulation process. Keywords: physicomathematical modeling, casein micelles, bacterial protease.

A detailed study of the benthic foraminiferal assemblages at the Bajocian Global Stratotype Section and Point (GSSP— Murtinheira section, Lusitanian Basin, western Portugal) presented herein increases the correlation potential of this relevant global geological time reference. The recorded assemblages are relatively abundant and diverse, and are composed of wellpreserved taxa typical of the Boreal Realm. The most abundant suborders are Lagenina and Spirillinina. Representatives of the Suborder Textulariina are also abundant in some assemblages, while those of the suborders Robertinina and Rotaliina are scarce. Lenticulina specimens are the most abundant in all assemblages, but at the specific level, there are differences between Aalenian and Bajocian assemblages, with Lenticulina muensteri being most abundant in the former and Spirillina orbicula in the latter. Two biozones, based on calcareous foraminifers, have been established and calibrated to the standard ammonite zonation: 1) the Lenticulina quenstedti Zone, ranging from the upper part of the Gigantea Subzone, Bradfordensis Biozone, upper Aalenian, to the lower part of the Discites Biozone, lower Bajocian, and 2) the Ramulina spandeli Zone, beginning at the top of the preceeding zone and having an undefined upper boundary. In addition, 11 bioevents are defined on first occurrences, last occurrences, changes in abundances of some taxa, or changes in assemblage diversity. After a severe impoverishment at the Aalenian–Bajocian transition, an important foraminiferal turnover takes place in the early Bajocian, where some Lower Jurassic and Aalenian forms are replaced by typical Middle Jurassic taxa

Successful engraftment of organ transplants has traditionally relied on preventing the activation of recipient (host) T cells. Once T-cell activation has occurred, however, stalling the rejection process becomes increasingly difficult, leading to graft failure. Here we demonstrate that graft-infiltrating, recipient (host) dendritic cells (DCs) play a key role in driving the rejection of transplanted organs by activated (effector) T cells. We show that donor DCs that accompany heart or kidney grafts are rapidly replaced by recipient DCs. The DCs originate from non-classical monocytes and form stable, cognate interactions with effector T cells in the graft. Eliminating recipient DCs reduces the proliferation and survival of graft-infiltrating T cells and abrogates ongoing rejection or rejection mediated by transferred effector T cells. Therefore, host DCs that infiltrate transplanted organs sustain the alloimmune response after T-cell activation has already occurred. Targeting these cells provides a means for preventing or treating rejection., Blocking T cell activation in organ transplantation is important to prevent rejection. Here the authors show that unconventional monocyte-derived host dendritic cells enter allogeneic grafts to amplify the T cell response outside lymph nodes.

The immune response against transplanted allografts is one of the most potent reactions mounted by the immune system. The acute rejection response has been attributed to donor dendritic cells (DCs), which migrate to recipient lymphoid tissues and directly activate alloreactive T cells against donor MHC molecules. Here, using a murine heart transplant model, we determined that only a small number of donor DCs reach lymphoid tissues and investigated how this limited population of donor DCs efficiently initiates the alloreactive T cell response that causes acute rejection. In our mouse model, efficient passage of donor MHC molecules to recipient conventional DCs (cDCs) was dependent on the transfer of extracellular vesicles (EVs) from donor DCs that migrated from the graft to lymphoid tissues. These EVs shared characteristics with exosomes and were internalized or remained attached to the recipient cDCs. Recipient cDCs that acquired exosomes became activated and triggered full activation of alloreactive T cells. Depletion of recipient cDCs after cardiac transplantation drastically decreased presentation of donor MHC molecules to directly alloreactive T cells and delayed graft rejection in mice. These findings support a key role for transfer of donor EVs in the generation of allograft-targeting immune responses and suggest that interrupting this process has potential to dampen the immune response to allografts.

T-cell receptor (TCR)-signaling triggers intracellular Ca2+ increase required for NFAT1/2-mediated IL-2 secretion. This pathway is necessary for thymocyte maturation and survival of activated T cells in secondary lymphoid organs (SLOs). In T cells, cellular Ca2+ levels are regulated by TCR- and G-protein coupled receptor (GPCR)-signaling via the PLCγ and PLCβ subunits, respectively. Nevertheless, the GPCR(s) involved in this phenomenon has not been identified. The neurokinin-1 receptor (NK1R) is a GPCR that induces Ca2+ flux in neurons, and NK1R-signaling by the neuropetides substance P (SP) and hemokinin 1 (HK1) promotes T-cell immunity. We studied the role of NK1R-signaling in T-cell development in the thymus and after T-cell priming in SLOs. By Imagestream, we found that the NK1R and its ligands localize at the site of dendritic cell (DC)-T cell contact. Following CD3-signaling, the NK1R was required for optimal Ca2+flux and NFAT-mediated IL-2 secretion in T cells, effects that were abrogated in NK1RKO or SP/HK1double KO T cells. In the thymus, absence of NK1R resulted in decreased maturation and survival of TCR+ double positive CD4 CD8, single positive CD4, and single positive CD8thymocytes. In SLOs, the NK1R was required for survival of Ag-activated CD4 Th1 and CD8 T cells. In vivo, in a skin model of Th1-DTH induced in NK1RKO T-cell or HK-1/SPdouble KOT-cell bone marrow chimeras, 73±5% of activated CD4 and CD8 T cells died during priming in skin-draining SLOs, and the remaining T cells died in the skin following elicitation. We conclude that the NK1R cooperates with the TCR to increase intracellular Ca2+ necessary for thymocyte maturation and survival of activated T cells in SLOs. NIH R01 AR068249 and AR071277 to ATL and LDF.

In the article by Lv et al. [1][1] published in the Journal of the American Society of Nephrology , the authors describe enhanced urinary exosomal release in experimental models of acute and chronic renal injury. They also describe increased exosomal release in patients with IgA nephropathy and a

BACKGROUND: Electroconvulsive therapy (ECT) is a most effective treatment for patients with major affective disorders. The influence of anesthetic drugs on seizure "adequacy" or on treatment success has not been systematically investigated. METHODS: A bispectral EEG index score (BIS) was used to identify the depth of anesthesia during ECT. Our study included 22 major depressive episode (MDE) patients expanding to 219 ECTs (05/05-01/06) with no limitations of concurrent medication. RESULTS: Fourteen out of the 22 patients showed full remission. Individual number of ECT sessions needed to reach full remission correlated negatively with mean pre-ECT BIS values (p=0.001). Additionally, using a repeated measurement regression analysis significant correlations were found for pre-ECT BIS versus motor response time, seizure concordance, ictal coherence and peak heart rate. CONCLUSION: The results of our study suggest BIS-levels as a predictor of faster ECT response. Controlling BIS-levels before stimulation may have an additional effect on treatment success.

A new cyclophane-type crown ether endowed with two exTTF units forms supramolecular ensembles with different dibenzylammonium salts with a binding constant of K a ∼50 M −1 determined by 1 H NMR and fluorescence experiments. Cyclic voltammetry studies show the existence of electronic interaction between the exTTF units due to the flexible nature of the crown ether chains.

We confirmed safety and immunogenicity of mass-produced vaccine baits carrying an experimental, commercial-source plague vaccine (RCN-F1/V307) expressing Yersinia pestis V and F1 antigens. Forty-five juvenile black-tailed prairie dogs (Cynomys ludovicianus) were randomly divided into three treatment groups (n=15 animals/group). Animals in the first group received one standard-dose vaccine bait (5×107 plaque-forming units [pfu]; STD). The second group received a lower-dose bait (1×107 pfu; LOW). In the third group, five animals received two standard-dose baits and 10 were left untreated but in contact. Two vaccine-treated and one untreated prairie dogs died during the study, but laboratory analyses ruled out vaccine involvement. Overall, 17 of 33 (52%; 95% confidence interval for binomial proportion [bCI] 34−69%) prairie dogs receiving vaccine-laden bait showed a positive anti-V antibody response on at least one sampling occasion after bait consumption, and eight (24%; bCI 11–42%) showed sustained...

The idea that donor dendritic cells (DCs) from the graft present donor MHC Ag to naïve T cells has been challenged. Evidence suggests that donor DCs are undetectable or found are low numbers in graft-draining lymphoid organs. Thus, the aim of our study is to elucidate how donor MHC molecules are recognized so efficiently by recipient naïve T cells. Results After transplantation of CD45.2 BALB/c hearts in CD45.1 B6 mice, very few donor DCs were detected in the spleen, and no donor DCs were found in lymph nodes draining BALB/c skin grafted in B6 mice. In both cases, donor intact MHC molecules were detected by electron microscopy on exosomes attached to recipient conventional DCs in graft-draining lymphoid organs. The transferred MHC Ag induced proliferation and differentiation of CD8 T cells against the BALB/c H2Ld Ag. Cultures of BALB/c DCs with B6 DCs with inhibitors of exosome release (Rab27a siRNA) confirmed that passage of BALB/c MHC occurred via exosomes. Importantly, transfer of exosomes released by donor DCs (unlike other types of vesicles) promoted maturation of recipient DCs. By high resolution confocal microscopy, BALB/c DCs, engineered to release RFP+ exosomes and injected in CD11c-YFP B6 mice, transferred RFP+ exosomes to recipient YFP+ DCs in lymph nodes and spleen. Accordingly, depletion of recipient DCs in CD11c-DTR B6 recipients prevented presentation of donor intact MHC Ag to T cells and delayed heart allograft rejection. Conclusion Our results elucidate the ultrastructural basis of the still elusive semi-direct pathway of allorecognition, by demonstrating that donor exosomes (released by the graft or donor migrating DCs) cross-dress recipient APCs and promote the potent T-cell allosensitization seen in transplantation.

Initiation of cellular immunity relies on T cell activation by Ag-presenting dendritic cells (DCs). By signaling via the neurokinin-1 receptor (NK1R), the neuropeptides hemokinin-1 (HK-1) and substance P (SP) potentiate cellular immunity by mechanisms not fully elucidated. Although SP is mainly secreted by sensory nerves, it is also synthesized and released by T cells. Here, we investigated the role of NK1R and autocrine SP and HK-1 on T cell activation. Using Imagestream flow cytometry (Amnis) to visualize couplets of OVA loaded WT or SP/HK1double KO DCs and responder OT-II CD4 T cells, we observed that the NK1R, SP and HK-1 colocalize with phalloidin at the site of DC-T cell contact. Following CD3/CD28 activation in vitro, we demonstrate that T cells express the full-length NK1R, and that NK1R signaling induces Ca2 flux, activation of calcineurin, NFAT1/2 and NFκB, which results in IL-2 secretion and survival of CD4 and CD8 T cells. These effects were abrogated in NK1RKO orSP/HK1double KO T cells, or by soluble NK1R antagonists. Addition of exogenous SP or HK-1 to CD3/CD28 activated WT T cells did not increase IL-2 secretion indicating that autocrine SP and HK1 released at the DC-T cell synapse suffice to promote T cell survival. In a model of skin DTH in NK1RKO or HK-1/SPdouble KOT cell chimeras, 73 ± 5% of activated (CD44high) CD4 and CD8 T cells die in the draining lymph nodes after priming, and 79%± 7% of the remaining T cells recruited to the skin die in situ following elicitation. In summary, NK1R signaling by autocrine SP and HK1 at the DC-T cell synapse is necessary for the survival of activated T cells and the development of potent cellular immunity.

Of 20 blood samples from nilgais from Mexico, five were polymerase chain reaction-positive for Babesia bigemina and one for Babesia bovis. Positive samples had the expected 170 (B. bigemina) and 291 (B. bovis) base pairs and were identical to Gen- Bank B. bigemina accession S45366 and B. bovis M38218.

A detailed study carried out on 37 well preserved benthic foraminiferal assemblages sampled throughout the upper Toarcian-middle Aalenian in two well calibrated sections representing different facies within the Lusitanian Basin (Portugal) - the Maria Pares and the Zambujal de Alcaria sections - allows interpreting the past environmental conditions. Several mathematical indexes related to diversity, which enable establishing the particular conditions to which the assemblages were submitted, were applied. All the studied assemblages are characteristic of the Jurassic carbonate platforms of the Boreal Realm, in which the genus Lenticulina usually dominates. The suborder Lagenina is the most abundant, but taking the second more abundant suborder into account, the comparison between coeval sections in the Lusitanian Basin allows the recognition of a regional gradient ranging from the distal part of the platform (Murtinheira) towards the transitional and proximal parts of the shelf (sections of Maria Pares and Zambujal de Alcaria respectively). The relative abundance values, as well as the obtained data from the diversity indexes indicate that the studied assemblages are relatively abundant and diverse, reflecting general appropriate paleoenvironmental conditions for their development. The detailed analysis of the data allows the identification in both sections of three different episodes, traducing particular environmental conditions: unstable (Mactra Subzone-lower part of the Opalinum Subzone), favorable and stable (lower part of the Opalinum Subzone-upper part of the Comptum Subzone), and unfavorable (upper part of the Comptum Subzone-lower Bradfordensis Subzone). These data are consistent with previous results obtained in the sections of Murtinheira and São Gião, located in the Northern Lusitanian Basin and corresponding to the distal and transitional parts of the platform respectively, and they aimed at contributing to a better understanding of the paleoecological conditions prevailing within the Lusitanian Basin during the Early-Middle Jurassic times.

The prognosis for fit patients with mantle cell lymphoma has improved with intensive strategies. Currently, the role of maintenance/consolidation approaches is being tested as relapses continue to appear. In this trial we evaluated the feasibility, safety and efficacy of rituximab-hyperCVAD alternating with rituximab-methotrexate-cytarabine followed by consolidation with 90Y-ibritumomab tiuxetan. Patients received six cycles followed by a single dose of 90Y-ibritumomab tiuxetan. Thirty patients were enrolled; their median age was 59 years. Twenty-four patients finished the induction treatment, 23 achieved complete remission (77%, 95% confidence interval 60–93) and one patient had progressive disease (3%). Eighteen patients (60%), all in complete remission, received consolidation therapy. In the intent-to-treat population, failure-free, progression-free and overall survival rates at 4 years were 40% (95% confidence interval 20.4–59.6), 52% (95% confidence interval 32.4–71.6) and 81% (95% confidence interval 67.28–94.72), respectively. For patients who received consolidation, failure-free and overall survival rates were 55% (95% confidence interval 31.48–78.52) and 87% (95% confidence interval 70–100), respectively. Hematologic toxicity was significant during induction and responsible for one death (3.3%). After consolidation, grade 3–4 neutropenia and thrombocytopenia were observed in 72% and 83% of patients, with a median duration of 5 and 12 weeks, respectively. Six (20%) patients died, three due to secondary malignancies (myelodysplastic syndrome and bladder and rectum carcinomas). In conclusion, in our experience, rituximab-hyperCVAD alternated with rituximab-methotrexate-cytarabine and followed by consolidation with 90Y-ibritumomab tiuxetan was efficacious although less feasible than expected. The unacceptable toxicity observed, especially secondary malignancies, advise against the use of this strategy. Trial registration: clinical.gov identifier: NCT2005-004400-37

Substance-P and hemokinin-1 are proinflammatory neuropeptides with potential to promote type 1 immunity through agonistic binding to neurokinin-1 receptor (NK1R). Dendritic cells (DCs) are professional antigen-presenting cells that initiate and regulate the outcome of innate and adaptive immune responses. Immunostimulatory DCs are highly desired for the development of positive immunization techniques. DCs express functional NK1R; however, regardless of their potential DC-stimulatory function, the ability of NK1R agonists to promote immunostimulatory DCs remains unexplored. Here, we demonstrate that NK1R signaling activates therapeutic DCs capable of biasing type 1 immunity by inhibition of interleukin-10 (IL-10) synthesis and secretion, without affecting their low levels of IL-12 production. The potent type 1 effector immune response observed following cutaneous administration of NK1R-signaled DCs required their homing in skin-draining lymph nodes (sDLNs) where they induced inflammation and licensed endogenous-conventional sDLN-resident and -recruited inflammatory DCs to secrete IL-12. Our data demonstrate that NK1R signaling promotes immunostimulatory DCs, and provide relevant insight into the mechanisms used by neuromediators to regulate innate and adaptive immune responses.

Se trata de un varon de 56 anos, fumador de 20 cigarrillos/dia, con antecedentes de hipertension arterial en tratamiento con losartan y criterios de enfermedad pulmonar obstructiva cronica, en tratamiento ocasional con s 2 agonistas y esteroides sistemicos e inhalados, que acude a Urgencias por fiebre, dolor toracico de caracteristicas pleuriticas, tos y expectoracion mucopurulenta. En la exploracion destaca taquipnea, hipoventilacion en base pulmonar izquierda, con roncus dispersos y discreta hepatoesplenomegalia. En los analisis presenta 42 x 109/l leucocitos, hemoglobina (Hb) 11,2 g/dl y 108 x 109/l plaquetas, con discreta elevacion de lacticodeshidrogenasa (LDH) y ligera hipoxemia, sin otras alteraciones significativas. En la radiografia de torax presenta imagen de consolidacion en lingula, compatible con neumonia. A su ingreso se inicia tratamiento antibiotico con ceftriaxona, precisando ademas la administracion de broncodilatadores y esteroides, con recuperacion clinica progresiva. A pesar de ello, a las 3 semanas de su ingreso en los analisis persiste leucocitosis (48 x 109/l leucocitos), Hb 10,7 g/dl y 102 x 109/l plaquetas. La leucocitosis se confirma en los analisis realizados 6 meses despues, no recibiendo en ese momento tratamiento con s 2 agonistas o esteroides. Pasados 12 meses del ingreso la cifra de leucocitos es de 82 x 109/l y en la exploracion persiste hepatoesplenomegalia.