RESUMEN
The ability to initiate an action quickly when needed and the ability to cancel an impending action are both fundamental to action control. It is often presumed that they are qualitatively distinct processes, yet they have largely been studied in isolation and little is known about how they relate to one another. Comparing previous experimental results shows a similar time course for response initiation and response inhibition. However, the exact time course varies widely depending on experimental conditions, including the frequency of different trial types and the urgency to respond. For example, in the stop-signal task, where both action initiation and action inhibition are involved and could be compared, action inhibition is typically found to be much faster. However, this apparent difference is likely due to there being much greater urgency to inhibit an action than to initiate one in order to avoid failing at the task. This asymmetry in the urgency between action initiation and action inhibition makes it impossible to compare their relative time courses in a single task. Here, we demonstrate that when action initiation and action inhibition are measured separately under conditions that are matched as closely as possible, their speeds are not distinguishable and are positively correlated across participants. Our results raise the possibility that action initiation and action inhibition may not necessarily be qualitatively distinct processes but may instead reflect complementary outcomes of a single decision process determining whether or not to act.NEW & NOTEWORTHY The time courses of initiating an action and canceling an action have largely been studied in isolation, and little is known about their relationship. Here, we show that when measured under comparable conditions the speeds of action initiation and action inhibition are the same. This finding raises the possibility that these two functions may be more closely related than previously assumed, with potentially important implications for their underlying neural basis.
Asunto(s)
Cognición , Desempeño Psicomotor , Humanos , Desempeño Psicomotor/fisiología , Tiempo de Reacción/fisiología , Inhibición PsicológicaRESUMEN
INTRODUCTION: Brigham and Women's Hospital historically used titratable weight-based heparin nomograms with as needed boluses managed by extracorporeal membrane oxygenation specialists to achieve a predetermined goal-activated partial thromboplastin time (aPTT). Due to concern amongst providers that as needed boluses may lead to supratherapeutic aPTT's and subsequent bleeding, new nomograms without as needed boluses were implemented. The purpose of this retrospective observational analysis is to provide a comparison in safety and efficacy between the heparin nomograms with as needed boluses and the new nomograms without boluses. METHODS: Adult patients who were cannulated on extracorporeal membrane oxygenation and initiated on an approved heparin bolus nomogram (January 1, 2018-December 31, 2019) or an approved heparin no-bolus nomogram (October 20, 2020-March 31, 2021) were screened for inclusion. The major endpoint evaluated was the percentage of supratherapeutic aPTTs, defined as an aPTT above the upper limit of the specified nomogram goal, within the first 72 hours. RESULTS: A total of 23 patients were included in the bolus nomogram cohort and 9 patients in the no-bolus nomogram cohort. Within the first 72 hours of initiation, there were 11.5% supratherapeutic aPTTs in the bolus group and 5.1% in the no-bolus group ( P = 0.101). Overall there was 1 bleeding event in the no-bolus group (11.1%) and 7 in the bolus group (30.4%) ( P = 0.26). There were no thromboembolic events in either group. CONCLUSIONS: Overall, there was no difference found in the percentage of supratherapeutic aPTTs within the first 72 hours of heparin initiation between the bolus and no-bolus nomograms.
Asunto(s)
Anticoagulantes , Oxigenación por Membrana Extracorpórea , Heparina , Nomogramas , Humanos , Tiempo de Tromboplastina Parcial , Oxigenación por Membrana Extracorpórea/métodos , Femenino , Heparina/administración & dosificación , Heparina/efectos adversos , Estudios Retrospectivos , Masculino , Persona de Mediana Edad , Anticoagulantes/administración & dosificación , Hemorragia/inducido químicamente , Anciano , AdultoRESUMEN
Cerebral malaria is the deadliest complication that can arise from Plasmodium infection. CD8 T-cell engagement of brain vasculature is a putative mechanism of neuropathology in cerebral malaria. To define contributions of brain endothelial cell major histocompatibility complex (MHC) class I antigen-presentation to CD8 T cells in establishing cerebral malaria pathology, we developed novel H-2Kb LoxP and H-2Db LoxP mice crossed with Cdh5-Cre mice to achieve targeted deletion of discrete class I molecules, specifically from brain endothelium. This strategy allowed us to avoid off-target effects on iron homeostasis and class I-like molecules, which are known to perturb Plasmodium infection. This is the first endothelial-specific ablation of individual class-I molecules enabling us to interrogate these molecular interactions. In these studies, we interrogated human and mouse transcriptomics data to compare antigen presentation capacity during cerebral malaria. Using the Plasmodium berghei ANKA model of experimental cerebral malaria (ECM), we observed that H-2Kb and H-2Db class I molecules regulate distinct patterns of disease onset, CD8 T-cell infiltration, targeted cell death and regional blood-brain barrier disruption. Strikingly, ablation of either molecule from brain endothelial cells resulted in reduced CD8 T-cell activation, attenuated T-cell interaction with brain vasculature, lessened targeted cell death, preserved blood-brain barrier integrity and prevention of ECM and the death of the animal. We were able to show that these events were brain-specific through the use of parabiosis and created the novel technique of dual small animal MRI to simultaneously scan conjoined parabionts during infection. These data demonstrate that interactions of CD8 T cells with discrete MHC class I molecules on brain endothelium differentially regulate development of ECM neuropathology. Therefore, targeting MHC class I interactions therapeutically may hold potential for treatment of cases of severe malaria.
Asunto(s)
Malaria Cerebral , Ratones , Humanos , Animales , Malaria Cerebral/patología , Malaria Cerebral/prevención & control , Células Endoteliales/patología , Encéfalo/patología , Barrera Hematoencefálica/patología , Linfocitos T CD8-positivos , Endotelio/patología , Ratones Endogámicos C57BL , Modelos Animales de EnfermedadRESUMEN
Interdisciplinary teams are on the rise as scientists attempt to address complex environmental issues. While the benefits of team science approaches are clear, researchers often struggle with its implementation, particularly for new team members. The challenges of large projects often weigh on the most vulnerable members of a team: trainees, including undergraduate students, graduate students, and post-doctoral researchers. Trainees on big projects have to navigate their role on the team, with learning project policies, procedures, and goals, all while also training in key scientific tasks such as co-authoring papers. To address these challenges, we created and participated in a project-specific, graduate-level team science course. The purposes of this course were to: (1) introduce students to the goals of the project, (2) build trainees' understanding of how big projects operate, and (3) allow trainees to explore how their research interests dovetailed with the overall project. Additionally, trainees received training regarding: (1) diversity, equity & inclusion, (2) giving and receiving feedback, and (3) effective communication. Onboarding through the team science course cultivated psychological safety and a collaborative student community across disciplines and institutions. Thus, we recommend a team science course for onboarding students to big projects to help students establish the skills necessary for collaborative research. Project-based team science classes can benefit student advancement, enhance the productivity of the project, and accelerate the discovery of solutions to ecological issues by building community, establishing a shared project vocabulary, and building a workforce with collaborative skills to better answer ecological research questions.
RESUMEN
Background: The nervous and immune systems interact in a reciprocal manner, both under physiologic and pathologic conditions. Literature spanning various CNS pathologies including brain tumors, stroke, traumatic brain injury and de-myelinating diseases describes a number of associated systemic immunologic changes, particularly in the T-cell compartment. These immunologic changes include severe T-cell lymphopenia, lymphoid organ contraction, and T-cell sequestration within the bone marrow. Methods: We performed an in-depth systematic review of the literature and discussed pathologies that involve brain insults and systemic immune derangements. Conclusions: In this review, we propose that the same immunologic changes hereafter termed 'systemic immune derangements', are present across CNS pathologies and may represent a novel, systemic mechanism of immune privilege for the CNS. We further demonstrate that systemic immune derangements are transient when associated with isolated insults such as stroke and TBI but persist in the setting of chronic CNS insults such as brain tumors. Systemic immune derangements have vast implications for informed treatment modalities and outcomes of various neurologic pathologies.
RESUMEN
The contribution of circulating verses tissue resident memory T cells (TRMs) to clinical neuropathology is an enduring question due to a lack of mechanistic insights. The prevailing view is TRMs are protective against pathogens in the brain. However, the extent to which antigen-specific TRMs induce neuropathology upon reactivation is understudied. Using the described phenotype of TRMs, we found that brains of naïve mice harbor populations of CD69+ CD103- T cells. Notably, numbers of CD69+ CD103- TRMs rapidly increase following neurological insults of various origins. This TRM expansion precedes infiltration of virus antigen-specific CD8 T cells and is due to proliferation of T cells within the brain. We next evaluated the capacity of antigen-specific TRMs in the brain to induce significant neuroinflammation post virus clearance, including infiltration of inflammatory myeloid cells, activation of T cells in the brain, microglial activation, and significant blood brain barrier disruption. These neuroinflammatory events were induced by TRMs, as depletion of peripheral T cells or blocking T cell trafficking using FTY720 did not change the neuroinflammatory course. Depletion of all CD8 T cells, however, completely abrogated the neuroinflammatory response. Reactivation of antigen-specific TRMs in the brain also induced profound lymphopenia within the blood compartment. We have therefore determined that antigen-specific TRMs can induce significant neuroinflammation, neuropathology, and peripheral immunosuppression. The use of cognate antigen to reactivate CD8 TRMs enables us to isolate the neuropathologic effects induced by this cell type independently of other branches of immunological memory, differentiating this work from studies employing whole pathogen re-challenge. This study also demonstrates the capacity for CD8 TRMs to contribute to pathology associated with neurodegenerative disorders and long-term complications associated with viral infections. Understanding functions of brain TRMs is crucial in investigating their role in neurodegenerative disorders including MS, CNS cancers, and long-term complications associated with viral infections including COVID-19.
Asunto(s)
COVID-19 , Virosis , Ratones , Animales , Células T de Memoria , Enfermedades Neuroinflamatorias , Linfocitos T CD8-positivos , Encéfalo , Memoria InmunológicaRESUMEN
Glioblastoma (GBM) is the most common malignant brain tumor in adults, responsible for approximately 225,000 deaths per year. Despite preclinical successes, most interventions have failed to extend patient survival by more than a few months. Treatment with anti-programmed cell death protein 1 (anti-PD-1) immune checkpoint blockade (ICB) monotherapy has been beneficial for malignant tumors such as melanoma and lung cancers but has yet to be effectively employed in GBM. This study aimed to determine whether supplementing anti-PD-1 ICB with engineered extended half-life IL2, a potent lymphoproliferative cytokine, could improve outcomes. This combination therapy, subsequently referred to as enhanced checkpoint blockade (ECB), delivered intraperitoneally, reliably cures approximately 50% of C57BL/6 mice bearing orthotopic GL261 gliomas and extends median survival of the treated cohort. In the CT2A model, characterized as being resistant to CBI, ECB caused a decrease in CT2A tumor volume in half of measured animals similar to what was observed in GL261-bearing mice, promoting a trending survival increase. ECB generates robust immunologic responses, features of which include secondary lymphoid organ enlargement and increased activation status of both CD4 and CD8 T cells. This immunity is durable, with long-term ECB survivors able to resist GL261 rechallenge. Through employment of depletion strategies, ECB's efficacy was shown to be independent of host MHC class I-restricted antigen presentation but reliant on CD4 T cells. These results demonstrate ECB is efficacious against the GL261 glioma model through an MHC class I-independent mechanism and supporting further investigation into IL2-supplemented ICB therapies for tumors of the central nervous system.
Asunto(s)
Glioblastoma , Glioma , Ratones , Animales , Interleucina-2/farmacología , Interleucina-2/uso terapéutico , Semivida , Ratones Endogámicos C57BL , Glioma/patología , Línea Celular TumoralRESUMEN
Kinetic stability, defined as the rate of protein unfolding, is central to determining the functional lifetime of proteins, both in nature and in wide-ranging medical and biotechnological applications. Further, high kinetic stability is generally correlated with high resistance against chemical and thermal denaturation, as well as proteolytic degradation. Despite its significance, specific mechanisms governing kinetic stability remain largely unknown, and few studies address the rational design of kinetic stability. Here, we describe a method for designing protein kinetic stability that uses protein long-range order, absolute contact order, and simulated free energy barriers of unfolding to quantitatively analyze and predict unfolding kinetics. We analyze two ß-trefoil proteins: hisactophilin, a quasi-three-fold symmetric natural protein with moderate stability, and ThreeFoil, a designed three-fold symmetric protein with extremely high kinetic stability. The quantitative analysis identifies marked differences in long-range interactions across the protein hydrophobic cores that partially account for the differences in kinetic stability. Swapping the core interactions of ThreeFoil into hisactophilin increases kinetic stability with close agreement between predicted and experimentally measured unfolding rates. These results demonstrate the predictive power of readily applied measures of protein topology for altering kinetic stability and recommend core engineering as a tractable target for rationally designing kinetic stability that may be widely applicable.
RESUMEN
The extracellular matrix is a dynamic framework bearing chemical and morphological cues that support many cellular functions, and artificial analogs with well-defined chemistry are of great interest for biomedical applications. Herein, we describe hierarchical, extracellular-matrix-mimetic microgels, termed "superbundles" (SBs) composed of peptide amphiphile (PA) supramolecular nanofiber networks created using flow-focusing microfluidic devices. We explore the effects of altered flow rate ratio and PA concentration on the ability to create SBs and develop design rules for producing SBs with both cationic and anionic PA nanofibers and gelators. We demonstrate the morphological similarities of SBs to decellularized extracellular matrices and showcase their ability to encapsulate and retain proteinaceous cargos with a wide variety of isoelectric points. Finally, we demonstrate that the novel SB morphology does not affect the well-established biocompatibility of PA gels.
Asunto(s)
Nanofibras , Nanofibras/química , Microfluídica , Biomimética , Péptidos/química , Matriz ExtracelularRESUMEN
The suprachiasmatic nucleus (SCN) is composed of functionally distinct subpopulations of GABAergic neurons which form a neural network responsible for synchronizing most physiological and behavioral circadian rhythms in mammals. To date, little is known regarding which aspects of SCN rhythmicity are generated by individual SCN neurons, and which aspects result from neuronal interaction within a network. Here, we utilize in vivo miniaturized microscopy to measure fluorescent GCaMP-reported calcium dynamics in arginine vasopressin (AVP)-expressing neurons in the intact SCN of awake, behaving mice. We report that SCN AVP neurons exhibit periodic, slow calcium waves which we demonstrate, using in vivo electrical recordings, likely reflect burst firing. Further, we observe substantial heterogeneity of function in that AVP neurons exhibit unstable rhythms, and relatively weak rhythmicity at the population level. Network analysis reveals that correlated cellular behavior, or coherence, among neuron pairs also exhibited stochastic rhythms with about 33% of pairs rhythmic at any time. Unlike single-cell variables, coherence exhibited a strong rhythm at the population level with time of maximal coherence among AVP neuronal pairs at CT/ZT 6 and 9, coinciding with the timing of maximal neuronal activity for the SCN as a whole. These results demonstrate robust circadian variation in the coordination between stochastically rhythmic neurons and that interactions between AVP neurons in the SCN may be more influential than single-cell activity in the regulation of circadian rhythms. Furthermore, they demonstrate that cells in this circuit, like those in many other circuits, exhibit profound heterogenicity of function over time and space.
Asunto(s)
Arginina Vasopresina , Ritmo Circadiano , Núcleo Supraquiasmático , Animales , Ratones , Arginina , Ritmo Circadiano/fisiología , Neuronas/metabolismo , Núcleo Supraquiasmático/metabolismoRESUMEN
Self-regulated insulin delivery that mimics native pancreas function has been a long-term goal for diabetes therapies. Two approaches towards this goal are glucose-responsive insulin delivery and islet cell transplantation therapy. Here, biodegradable, partially oxidized alginate carriers for glucose-responsive nanoparticles or islet cells are developed. Material composition and formulation are tuned in each of these contexts to enable glycemic control in diabetic mice. For injectable, glucose-responsive insulin delivery, 0.5 mm 2.5% oxidized alginate microgels facilitate repeat dosing and consistently provide 10 days of glycemic control. For islet cell transplantation, 1.5 mm capsules comprised of a blend of unoxidized and 2.5% oxidized alginate maintain cell viability and glycemic control over a period of more than 2 months while reducing the volume of nondegradable material implanted. These data show the potential of these biodegradable carriers for controlled drug and cell delivery for the treatment of diabetes with limited material accumulation in the event of multiple doses.
Asunto(s)
Diabetes Mellitus Experimental , Trasplante de Islotes Pancreáticos , Islotes Pancreáticos , Ratones , Animales , Diabetes Mellitus Experimental/tratamiento farmacológico , Alginatos , Insulina , Glucosa , GlucemiaRESUMEN
This chapter explores the involvement of the temporal lobes in distinct language functions. The examination of cases of localized damage to the temporal lobes and the resulting pattern of impairment across language tasks and types of errors made can reveal clear neural regions and associated networks essential for word comprehension, semantics, naming, reading, and spelling. Key regions implicated in these functions include left superior temporal gyrus posterior to the temporal pole in word comprehension, bilateral anterior temporal lobes in semantics, left posterior inferior temporal gyrus (pITG) in naming, and left pITG and fusiform cortex in reading and spelling. Results we review provide evidence that the temporal lobes have a critical role in many language tasks. Although various areas and associated white matter tracts work together in supporting language, damage to specific regions of the temporal lobes results in distinct and relatively predictable impairments of language functions.
Asunto(s)
Comprensión , Lóbulo Temporal , Corteza Cerebral , Humanos , Lenguaje , LecturaRESUMEN
Most naming error lesion-symptom mapping (LSM) studies have focused on semantic and/or phonological errors. Anomic individuals also produce unrelated word errors, which may be linked to semantic or modality-independent lexical deficits. To investigate the neural underpinnings of rarely-studied unrelated errors, we conducted LSM analyses in 100 individuals hospitalized with a left hemisphere stroke who completed imaging protocols and language assessments. We used least absolute shrinkage and selection operator regression to capture relationships between naming errors and dysfunctional brain tissue metrics (regional damage or hypoperfusion in vascular territories) in two groups: participants with and without impaired single-word auditory comprehension. Hypoperfusion-particularly within the parietal lobe-was an important error predictor, especially for the unimpaired group. In both groups, higher unrelated error proportions were associated with primarily ventral stream damage, the language route critical for processing meaning. Nonetheless, brain metrics implicated in unrelated errors were distinct from semantic error correlates.
RESUMEN
Introduction: The use of telehealth screening (TS) for diabetic retinopathy (DR) consists of fundus photography in a primary care setting with remote interpretation of images. TS for DR is known to increase screening utilization and reduce vision loss compared with standard in-person conventional diabetic retinal exam (CDRE). Anti-vascular endothelial growth factor intravitreal injections have become standard of care for the treatment of DR, but they are expensive. We investigated whether TS for DR is cost-effective when DR management includes intravitreal injections using national data. Materials and Methods: We compared cost and effectiveness of TS and CDRE using decision-tree analysis and probabilistic sensitivity analysis with Monte Carlo simulation. We considered the disability weight (DW) of vision impairment and 1-year direct medical costs of managing patients based on Medicare allowable rates and clinical trial data. Primary outcomes include incremental costs and incremental effectiveness. Results: The average annual direct cost of eye care was $196 per person for TS and $275 for CDRE. On average, TS saves $78 (28%) compared with CDRE and was cost saving in 88.9% of simulations. The average DW outcome was equivalent in both groups. Discussion: Although this study was limited by a 1-year time horizon, it provides support that TS for DR can reduce costs of DR management despite expensive treatment with anti-VEGF agents. TS for DR is equally effective as CDRE at preserving vision. Conclusions: Annual TS for DR is cost saving and equally effective compared with CDRE given a 1-year time horizon.
Asunto(s)
Diabetes Mellitus , Retinopatía Diabética , Telemedicina , Anciano , Ahorro de Costo , Análisis Costo-Beneficio , Retinopatía Diabética/diagnóstico , Humanos , Tamizaje Masivo/métodos , Medicare , Telemedicina/métodos , Estados UnidosRESUMEN
Glucose-responsive insulin delivery systems have the potential to improve quality of life for individuals with diabetes by improving blood sugar control and limiting the risk of hypoglycemia. However, systems with desirable insulin release kinetics and high loading capacities have proven difficult to achieve. Here, we report the development of electrostatic complexes (ECs) comprised of insulin, a polycation, and glucose oxidase (GOx). Under normoglycemic physiological conditions, insulin carries a slight negative charge and forms a stable EC with the polycation. In hyperglycemia, the encapsulated glucose-sensing enzyme GOx converts glucose to gluconic acid and lowers the pH of the microenvironment, causing insulin to adopt a positive charge. Thus, the electrostatic interactions are disrupted, and insulin is released. Using a model polycation, we conducted molecular dynamics simulations to model these interactions, synthesized ECs with > 50% insulin loading capacity, and determined in vitro release kinetics. We further showed that a single dose of ECs can provide a glycemic profile in streptozotocin-induced diabetic mice that mimics healthy mice over a 9 h period with 2 glucose tolerance tests.
Asunto(s)
Diabetes Mellitus Experimental , Insulina , Animales , Glucemia , Glucosa , Ratones , Polielectrolitos , Calidad de VidaRESUMEN
OBJECTIVE: To understand the prevalence of intrapartum oxytocin use, assess associated perinatal and maternal outcomes, and evaluate the impact of a WHO Safe Childbirth Checklist intervention on oxytocin use at primary-level facilities in Uttar Pradesh, India. DESIGN: Secondary analysis of a cluster-randomised controlled trial. SETTING: Thirty Primary and Community public health facilities in Uttar Pradesh, India from 2014 to 2017. POPULATION: Women admitted to a study facility for childbirth at baseline, 2, 6 or 12 months after intervention initiation. METHODS: The BetterBirth intervention aimed to increase adherence to the WHO Safe Childbirth Checklist. We used Rao-Scott Chi-square tests to compare (1) timing of oxytocin use between study arms and (2) perinatal mortality and resuscitation of infants whose mothers received intrapartum oxytocin versus who did not. MAIN OUTCOME MEASURES: Intrapartum and postpartum oxytocin administration, perinatal mortality, use of neonatal bag and mask. RESULTS: We observed 5484 deliveries. At baseline, intrapartum oxytocin was administered to 78.2% of women. Two months after intervention initiation, intrapartum oxytocin (I) was administered to 32.1% of women compared with 70.6% in the control (C) (P < 0.01); this difference diminished after the end of the intervention (I = 48.2%, C = 74.7%, P = 0.03). Partograph use remained at <1% at all facilities. Resuscitation was performed on 7.5% of infants whose mother received intrapartum oxytocin versus 2.0% who did not (P < 0.0001). CONCLUSIONS: In this setting, intrapartum oxytocin use was high despite limited maternal/fetal monitoring or caesarean capability, and was associated with increased neonatal resuscitation. The BetterBirth intervention was successful at decreasing intrapartum oxytocin use. Ongoing support is needed to sustain these practices. TWEETABLE ABSTRACT: Coaching + WHO Safe Childbirth Checklist reduces intrapartum oxytocin use and need for newborn resuscitation.
Asunto(s)
Lista de Verificación/métodos , Parto Obstétrico/estadística & datos numéricos , Tutoría/métodos , Oxitocina/uso terapéutico , Resucitación/estadística & datos numéricos , Adulto , Lista de Verificación/normas , Análisis por Conglomerados , Parto Obstétrico/normas , Femenino , Adhesión a Directriz/estadística & datos numéricos , Humanos , India , Recién Nacido , Tutoría/normas , Parto/efectos de los fármacos , Mortalidad Perinatal , Embarazo , Mejoramiento de la Calidad , Organización Mundial de la SaludRESUMEN
Systemic inflammation as manifested in sepsis is an excessive, life-threatening inflammatory response to severe bacterial or viral infection or extensive injury. It is also a thrombo-inflammatory condition associated with vascular leakage/hemorrhage and thrombosis that is not effectively treated by current anti-inflammatory or anti-thrombotic drugs. Here, we show that MB2mP6 peptide nanoparticles, targeting the Gα13-mediated integrin "outside-in" signaling in leukocytes and platelets, inhibited both inflammation and thrombosis without causing hemorrhage/vascular leakage. MB2mP6 improved mouse survival when infused immediately or hours after onset of severe sepsis. Furthermore, platelet Gα13 knockout inhibited septic thrombosis whereas leukocyte Gα13 knockout diminished septic inflammation, each moderately improving survival. Dual platelet/leukocyte Gα13 knockout inhibited septic thrombosis and inflammation, further improving survival similar to MB2mP6. These results demonstrate that inflammation and thrombosis independently contribute to poor outcomes and exacerbate each other in systemic inflammation, and reveal a concept of dual anti-inflammatory/anti-thrombotic therapy without exacerbating vascular leakage.
Asunto(s)
Antígenos CD18/antagonistas & inhibidores , Subunidades alfa de la Proteína de Unión al GTP G12-G13/antagonistas & inhibidores , Fragmentos de Péptidos/farmacología , Sepsis/tratamiento farmacológico , Trombosis/tratamiento farmacológico , Animales , Antiinflamatorios , Plaquetas/efectos de los fármacos , Plaquetas/inmunología , Plaquetas/metabolismo , Antígenos CD18/metabolismo , Cloruros/administración & dosificación , Cloruros/toxicidad , Modelos Animales de Enfermedad , Compuestos Férricos/administración & dosificación , Compuestos Férricos/toxicidad , Fibrinolíticos , Subunidades alfa de la Proteína de Unión al GTP G12-G13/metabolismo , Humanos , Leucocitos/efectos de los fármacos , Leucocitos/inmunología , Leucocitos/metabolismo , Macrófagos , Ratones , Ratones Noqueados , Nanopartículas/uso terapéutico , Fragmentos de Péptidos/uso terapéutico , Adhesividad Plaquetaria/efectos de los fármacos , Agregación Plaquetaria/efectos de los fármacos , Cultivo Primario de Células , Unión Proteica/efectos de los fármacos , Sepsis/sangre , Sepsis/complicaciones , Sepsis/inmunología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunología , Células THP-1 , Trombosis/sangre , Trombosis/inducido químicamenteRESUMEN
While individuals value honesty in relationships, disagreements can create discomfort and individuals tend to prefer partners who engage in attitude alignment (i.e., shift their attitude toward agreement when disagreement occurs). In order to maintain smooth interactions, partners may even deceive individuals by concealing their continued disagreement. In a 2 (Attitude Alignment Deception) x 2 (Partner Motivation) between-subjects design, we examined whether individuals would evaluate interaction partners who engaged in deceptive attitude alignment less favorably compared to interaction partners who engaged in honest attitude alignment, and we examined whether partner motivation (relationship- vs. self-oriented) impacted this effect. After a brief in-person discussion about a disagreed upon social issue, participants received written feedback, allegedly from their interaction partners, that their partners engaged in attitude alignment that was either honest (i.e., partner came to agree with the individual) or deceptive (i.e., partner pretended to reach agreement with the individual). Participants also received feedback that their partners actions were motivated by either a relationship-orientation (i.e., to be liked by the individual) or self-orientation (i.e., to be viewed as correct on the issue). Individuals evaluated (e.g., were less attracted to) partners who engaged in deceptive (vs. honest) attitude alignment less favorably, but deceptive partners were evaluated more favorably if their deception was relationship- vs. self-oriented.
Asunto(s)
Decepción , Relaciones Interpersonales , Actitud , Humanos , MotivaciónRESUMEN
To control the population of an invasive species of green crab, we investigated the feasibility of producing a fermented crab condiment. Commercial fermented fish condiments were tested to assess variability in the marketplace and to identify targets for lab-fermented sauces. Finely chopped crab was combined with 100 mg g-1, 200 mg g-1, or 300 mg g-1 NaCl, and spontaneously fermented for up to 120 days. Chromatographic analysis revealed that histamine content was not a safety concern as all treatments were below the current U.S. legal threshold (50 mg 100 mL-1). The majority of microbial and physicochemical properties measured within salt level (proteolytic bacterial population, total volatile basic nitrogen (TVBN), amine nitrogen, water activity, moisture, and biogenic amines) were statistically unchanged between days 60 and 120 of fermentation, suggesting that most of the biochemical changes happened early in the fermentation. While the production of a fermented condiment was successful and could represent an opportunity for the valorization of this invasive species, additional work is needed to accelerate the process and further understand the dynamics of the early fermentation stages.