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1.
J Neurosci ; 42(50): 9426-9434, 2022 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-36332978

RESUMO

Motivation is a powerful driver of learning and memory. Functional MRI studies show that interactions among the dopaminergic midbrain substantia nigra/ventral tegmental area (SN/VTA), hippocampus, and nucleus accumbens (NAc) are critical for motivated memory encoding. However, it is not known whether these effects are transient and purely functional, or whether individual differences in the structure of this circuit underlie motivated memory encoding. To quantify individual differences in structure, diffusion-weighted MRI and probabilistic tractography were used to quantify SN/VTA-striatum and SN/VTA-hippocampus pathways associated with motivated memory encoding in humans. Male and female participants completed a motivated source memory paradigm. During encoding, words were randomly assigned to one of three conditions, reward ($1.00), control ($0.00), or punishment (-$1.00). During retrieval, participants were asked to retrieve item and source information of the previously studied words and were rewarded or penalized according to their performance. Source memory for words assigned to both reward and punishment conditions was greater than those for control words, but there were no differences in item memory based on value. Anatomically, probabilistic tractography results revealed a heterogeneous, topological arrangement of the SN/VTA. Tract density measures of SN/VTA-hippocampus pathways were positively correlated with individual differences in reward-and-punishment-modulated memory performance, whereas density of SN/VTA-striatum pathways showed no association. This novel finding suggests that pathways emerging from the human SV/VTA are anatomically separable and functionally heterogeneous. Individual differences in structural connectivity of the dopaminergic hippocampus-VTA loop are selectively associated with motivated memory encoding.SIGNIFICANCE STATEMENT Functional MRI studies show that interactions among the SN/VTA, hippocampus, and NAc are critical for motivated memory encoding. This has led to competing theories that posit either SN/VTA-NAc reward prediction errors or SN/VTA-hippocampus signals underlie motivated memory encoding. Additionally, it is not known whether these effects are transient and purely functional or whether individual differences in the structure of these circuits underlie motivated memory encoding. Using diffusion-weighted MRI and probabilistic tractography, we show that tract density measures of SN/VTA-hippocampus pathways are positively correlated with motivated memory performance, whereas density of SN/VTA-striatum pathways show no association. This finding suggests that anatomic individual differences of the dopaminergic hippocampus-VTA loop are selectively associated with motivated memory encoding.


Assuntos
Hipocampo , Área Tegmentar Ventral , Feminino , Humanos , Masculino , Dopamina/metabolismo , Hipocampo/metabolismo , Imageamento por Ressonância Magnética , Mesencéfalo/diagnóstico por imagem , Mesencéfalo/metabolismo , Recompensa , Substância Negra/diagnóstico por imagem , Substância Negra/metabolismo , Área Tegmentar Ventral/diagnóstico por imagem , Área Tegmentar Ventral/metabolismo
2.
Cogn Affect Behav Neurosci ; 23(4): 1014-1058, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37081225

RESUMO

The current set of studies examined the relationship among working memory capacity, attention control, fluid intelligence, and pupillary correlates of tonic arousal regulation and phasic responsiveness in a combined sample of more than 1,000 participants in two different age ranges (young adults and adolescents). Each study was designed to test predictions made by two recent theories regarding the role of the locus coeruleus-norepinephrine (LC-NE) system in determining individual differences in cognitive ability. The first theory, proposed by Unsworth and Robison (2017a), posits two important individual differences: the moment-to-moment regulation of tonic arousal, and the phasic responsiveness of the system to goal-relevant stimuli. The second theory, proposed by Tsukahara and Engle (2021a), argues that people with higher cognitive abilities have greater functional connectivity between the LC-NE system and cortical networks at rest. These two theories are not mutually exclusive, but they make different predictions. Overall, we found no evidence consistent with a resting-state theory. However, phasic responsiveness was consistently correlated with working memory capacity, attention control, and fluid intelligence, supporting a prediction made by Unsworth and Robison (2017a). Tonic arousal regulation was not correlated with working memory or fluid intelligence and was inconsistently correlated with attention control, which offers only partial support for Unsworth and Robison's (2017a) second prediction.


Assuntos
Memória de Curto Prazo , Norepinefrina , Humanos , Adolescente , Memória de Curto Prazo/fisiologia , Norepinefrina/fisiologia , Locus Cerúleo/fisiologia , Atenção/fisiologia , Inteligência
3.
Cancer ; 128 Suppl 4: 883-891, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-35133658

RESUMO

Multicancer screening is a promising approach to improving the detection of preclinical disease, but current technologies have limited ability to identify precursor or early stage lesions, and approaches for developing the evidentiary chain are unclear. Frameworks to enable development and evaluation from discovery through evidence of clinical effectiveness are discussed.


Assuntos
Detecção Precoce de Câncer , Neoplasias , Humanos , Programas de Rastreamento , Neoplasias/diagnóstico
4.
Int Rev Psychiatry ; 34(3-4): 171-199, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36151836

RESUMO

Sexual orientation is a key determinant of the identity of human beings. It has also been seen as a social determinant of health. People whose sexual orientation is non-heterosexual or sexual minorities or sexually diverse are included in the broad umbrella term LGBT (Lesbian, Gay, Bisexual, and Transgender) which is a commonly used acronym in activism, social policy, and subsequently cultural literature. For this reason, this Commission focuses primarily on sexual orientation i.e. lesbian, gay and bisexual (LGB) groups. We have used terms non-heterosexual, sexual minorities or sexual variation interchangeably. We have not considered asexual individuals as research in the field is too limited. We are cognisant of the fact that topics relating to mental health and sexual orientation discussed in this Commission will intersect with other issues of personal, cultural and social identity, and will thus be relevant to individuals including many transgender individuals. The inclusion of mental health issues relevant to gender-diverse individuals as well as gender identity is important and deserves its own separate detailed discussion. The exact number of sexually diverse individuals in a population is often difficult to estimate but is likely to be somewhere around 5% of the population. Rates of various psychiatry disorders and suicidal ideation and acts of suicide in LGB populations are higher than general population and these have been attributed to minority stress hypothesis. Elimination of inequality in law can lead to reduction in psychiatric morbidity in these groups. However, these are all diverse groups but even within each group there is diversity and each individual has a distinct and unique experiences, upbringing, responses to their own sexual orientation, and generating varying responses from families, peers and friends as well as communities (including healthcare professionals). The mental healthcare needs of sexual minority individuals vary and these variations must be taken into account in design, development and delivery of healthcare and policies. Improving access to services will help engagement and outcomes and also reduce stigma. The commission recommends that there is no role for so-called conversion therapies and other recommendations are made for clinicians, researchers and policymakers.


Assuntos
Saúde Mental , Minorias Sexuais e de Gênero , Feminino , Identidade de Gênero , Humanos , Masculino , Comportamento Sexual , Ideação Suicida
5.
Psychol Res ; 86(3): 808-822, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33978805

RESUMO

Binaural beats have been used as a way of modifying cognition via auditory stimulation. A recent meta-analysis suggests that binaural beat stimulation can have a positive effect on attention (Garcia-Argibay et al., Psychologische Forschung 83:1124-1136, 2019a, Psychological Research Psychologische Forschung 83:357-372, 2019b), with the sample-weighted average effect size being about .58. This is an intriguing and potentially useful finding, both theoretically and practically. In this study, we focus on sustained attention. We delivered beta-frequency (16 Hz) binaural beat stimulation during a sustained attention task. In "Experiment 1", reaction times were faster under beat stimulation than control stimulation in a between-subjects design. However, the effect was modest in magnitude, and model comparisons using Bayes Factors were indiscriminate between including and excluding the effect from the model. We followed this initial experiment with two concurrently administered follow-up experiments. In "Experiment 2", we added thought probes to measure any changes in task engagement associated with binaural beat stimulation. "Experiment 2" revealed a different effect from "Experiment 1": participants in the binaural beat condition exhibited a shallower vigilance decrement. However, the beat stimulation did not affect the thought probes responses. Combining data across the two experiments indicated rather strong evidence against the hypothesis that beta-frequency binaural beats can augment sustained attention, either via a general speeding of responding or a mitigation of the vigilance decrement. Finally, in "Experiment 3", we investigated whether pupillary measures of arousal and/or task engagement would be affected by binaural beat stimulation. There was no evidence for such effects. Overall, we did not observe any consistent evidence that binaural beat stimulation can augment sustained attention or its subjective and physiological correlates.


Assuntos
Nível de Alerta , Atenção , Estimulação Acústica , Nível de Alerta/fisiologia , Atenção/fisiologia , Teorema de Bayes , Humanos , Tempo de Reação/fisiologia
6.
Mem Cognit ; 50(4): 751-764, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34713420

RESUMO

The current study leveraged experimental and individual differences methodology to examine whether false memories across different list-learning tasks arise from a common cause. Participants completed multiple false memory (associative and conjunction lure), working memory (operation and reading span), and source monitoring (verbal and picture) tasks. Memory discriminability in the associative and conjunction tasks loaded onto a single (general) factor and were unaffected by warnings provided at encoding. Consistent with previous research, source-monitoring ability fully mediated the relation between working memory and false memories. Moreover, individuals with higher source monitoring-ability were better able to recall contextual information from encoding to correctly reject lures. These results suggest that there are stable individual differences in false remembering across tasks. The commonality across tasks may be due, at least in part, to the ability to effectively use disqualifying monitoring processes.


Assuntos
Individualidade , Reconhecimento Psicológico , Humanos , Memória de Curto Prazo , Rememoração Mental
7.
Neuroimage ; 206: 116296, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31648002

RESUMO

The prioritized encoding and retrieval of valuable information is an essential aspect of human memory. We used electroencephalography (EEG) to determine which of two hypothesized processes underlies the influence of reward value on episodic memory. One hypothesis is that value engages prefrontal executive control processes, so that valuable stimuli engage an elaborative rehearsal strategy that benefits memory. A second hypothesis is that value acts through the reward-related midbrain dopamine system to modulate synaptic plasticity in hippocampal and cortical efferents, thereby benefiting memory encoding. We used a value-directed recognition memory (VDR) paradigm in which participants encoded words assigned different point values and aimed to maximize the point value of subsequently recognized words. Subjective states of recollection (i.e., "remember") and familiarity (i.e., "know") were assessed at retrieval. Words assigned higher values at study were recognized more effectively than words assigned lower values, due to increased "remember" responses but no difference in "know" responses. Greater value was also associated with larger amplitudes of an EEG component at retrieval that indexes recollection (parietal old/new component), but had no relationship with a component that indexes familiarity (FN400 component). During encoding, we assessed a late frontal positivity (frontal slow wave, FSW) that has been related to elaborative rehearsal strategies and an early parietal component (P3) thought to index dopamine driven attention allocation. Our findings indicate that the effect of value on recognition memory is primarily driven by the dopamine-driven reward valuation system (P3) with no discernible effect on rehearsal processes (FSW).


Assuntos
Córtex Cerebral/fisiologia , Eletroencefalografia , Potenciais Evocados/fisiologia , Neuroimagem Funcional , Rememoração Mental/fisiologia , Reconhecimento Psicológico/fisiologia , Recompensa , Adulto , Potenciais Evocados P300/fisiologia , Humanos , Adulto Jovem
8.
Radiographics ; 38(5): 1516-1535, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30207937

RESUMO

Spinal hematomas are a frequent indication for radiologic evaluation and can be a diagnostic dilemma for many radiologists and surgeons. There are four types of spinal hematomas: epidural, subdural, subarachnoid, and intramedullary (spinal cord) hematomas. Because they differ by their location in relationship to the meningeal membranes and spinal cord, unique radiologic appearances can be recognized to distinguish these types of spinal hemorrhage. Anatomic knowledge of the spinal compartments is essential to the radiologist for confident imaging diagnosis of spinal hematomas and to specify correct locations. MRI is the modality of choice to diagnose the location of the hematoma, characterize important features such as age of the hemorrhage, and detect associated injury or disease. Each type of spinal hematoma has imaging patterns and characteristics that distinguish it from the others, as these specific spinal compartments displace and affect the adjacent anatomic structures. Early detection and accurate localization of spinal hematomas is critical for the surgeon to address the proper treatment and surgical decompression, when necessary, as neurologic deficits may otherwise become permanent. Online supplemental material is available for this article. ©RSNA, 2018.


Assuntos
Hematoma/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Doenças da Medula Espinal/diagnóstico por imagem , Diagnóstico Diferencial , Hematoma/terapia , Humanos , Doenças da Medula Espinal/terapia
9.
Conscious Cogn ; 62: 21-33, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29723709

RESUMO

Understanding and resolving complex problems is of vital importance in daily life. Problems can be defined by the limitations they place on the problem solver. Multiply-constrained problems are traditionally examined with the compound remote associates task (CRAT). Performance on the CRAT is partially dependent on an individual's working memory capacity (WMC). These findings suggest that executive processes are critical for problem solving and that there are reliable individual differences in multiply-constrained problem solving abilities. The goals of the current study are to replicate and further elucidate the relation between WMC and CRAT performance. To achieve these goals, we manipulated preexposure to CRAT solutions and measured WMC with complex-span tasks. In Experiment 1, we report evidence that preexposure to CRAT solutions improved problem solving accuracy, WMC was correlated with problem solving accuracy, and that WMC did not moderate the effect of preexposure on problem solving accuracy. In Experiment 2, we preexposed participants to correct and incorrect solutions. We replicated Experiment 1 and found that WMC moderates the effect of exposure to CRAT solutions such that high WMC participants benefit more from preexposure to correct solutions than low WMC (although low WMC participants have preexposure benefits as well). Broadly, these results are consistent with theories of working memory and problem solving that suggest a mediating role of attention control processes.


Assuntos
Individualidade , Resolução de Problemas , Humanos , Memória de Curto Prazo , Tempo de Reação
10.
Memory ; 26(8): 1159-1168, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29415613

RESUMO

Output monitoring refers to memory for one's previously completed actions. In the context of prospective memory (PM) (e.g., remembering to take medication), failures of output monitoring can result in repetitions and omissions of planned actions (e.g., over- or under-medication). To be successful in output monitoring paradigms, participants must flexibly control attention to detect PM cues as well as engage controlled retrieval of previous actions whenever a particular cue is encountered. The current study examined individual differences in output monitoring abilities in a group of younger adults differing in attention control (AC) and episodic memory (EM) abilities. The results showed that AC ability uniquely predicted successful cue detection on the first presentation, whereas EM ability uniquely predicted successful output monitoring on the second presentation. The current study highlights the importance of examining external correlates of PM abilities and contributes to the growing body of research on individual differences in PM.


Assuntos
Atenção/fisiologia , Sinais (Psicologia) , Individualidade , Memória Episódica , Adolescente , Adulto , Cognição/fisiologia , Feminino , Humanos , Masculino , Rememoração Mental/fisiologia , Testes Neuropsicológicos , Reconhecimento Psicológico/fisiologia , Priming de Repetição/fisiologia , Adulto Jovem
11.
Memory ; 26(10): 1450-1459, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29962319

RESUMO

Prospective memory refers to the planning, retention, retrieval, and execution of intentions for future behaviours and it is integral to the enterprise of daily living. Although prospective memory relies upon retrospective memory and executive processes often disrupted by pain, limited research has explored the influence of acute or chronic pain on the ability to complete prospective memory tasks. In the present study we investigated the influence of acute pain on prospective memory tasks that varied in their demands on executive processes (i.e., non-focal versus focal prospective memory cues). Complex-span working memory tasks were also administered to examine whether individual differences in working memory capacity moderated any negative impact of pain on prospective memory. Acute pain significantly impaired prospective memory performance in conditions that encouraged non-focal strategic processing of prospective memory cues, but not in conditions that encouraged more spontaneous focal processing. Individual differences in working memory capacity did not moderate the effect of acute pain on non-focal prospective memory. These findings provide new insights into prospective memory dysfunction created by painful experiences.


Assuntos
Dor Aguda/psicologia , Sinais (Psicologia) , Memória Episódica , Adulto , Feminino , Humanos , Intenção , Masculino , Memória de Curto Prazo , Resolução de Problemas , Estudos Retrospectivos , Adulto Jovem
12.
Environ Sci Technol ; 51(23): 13592-13602, 2017 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-29148733

RESUMO

The Neuse River, North Carolina, U.S., exemplifies a typical de facto potable reuse scenario, where drinking water sources are located downstream of treated wastewater effluent discharges. The study results imply that planned potable water reuse, whether in an indirect or direct potable reuse scenario, might provide better control over water quality than the status quo conditions. Using fluorescence excitation-emission matrix (EEM) measurements, anthropogenic influence of a wastewater treatment plant (WWTP) discharge was observed in samples near the location of drinking water treatment plant (WTP) intakes, eight or more miles downstream of the WWTP, implying that anthropogenic compounds were not fully removed or degraded by natural processes in this reach of the river. PARAllel FACtor (PARAFAC) analysis supported a two-component model of humic-like and nonhumic-like dissolved organic matter (DOM). A nonmodeled anthropogenic feature was also indicated. Significantly, the quenched fluorescence of humic-like DOM (static and/or dynamic quenching) by nonhumic-like DOM-previously demonstrated for probe molecules but first reported here in a natural/anthropogenic-influenced system-offers exciting insight into studies of humic/nonhumic interactions with important implications for pollutant fate and transport, sensing applications, and water treatment. A molecular spectroscopic explanation for dual fluorescing peaks in amino acids and humic substances is postulated.


Assuntos
Rios , Águas Residuárias , Abastecimento de Água , Análise Fatorial , Substâncias Húmicas , North Carolina , Espectrometria de Fluorescência , Estados Unidos , Poluentes Químicos da Água , Qualidade da Água
13.
Neurocrit Care ; 27(3): 334-340, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28660341

RESUMO

BACKGROUND: Prothrombin complex concentrates (PCCs) have become the first-line therapy for warfarin reversal in the setting of central nervous system (CNS) hemorrhage. Randomized, controlled studies comparing agents for warfarin reversal excluded patients with international normalized ratio (INR) <2, yet INR values of 1.6-1.9 are also associated with poor outcomes. METHODS: We retrospectively reviewed our use of a low-dose (15 units/kg) strategy of 4-factor PCC (4F-PCC) on warfarin reversal (INR 1.6-1.9) in the setting of both traumatic and spontaneous intracranial bleeding. RESULTS: A total of 21/134 (15.7%) patients with either spontaneous or traumatic intracranial hemorrhage presented with an INR value of 1.6-1.9. Nine patients (43%) presented with traumatic bleeding and 12 (57%) with spontaneous bleeding. The median (IQR) presenting INR was 1.8 (1.7, 1.9) which decreased to 1.3 (1.2, 1.3) following the administration of low-dose 4F-PCC (median dose = 1062 units; 15.2 units/kg). A total of 19/20 (95%) patients achieved a goal INR value of ≤1.5 on the first check following dosing and 17/20 (85%) achieved an INR value ≤1.3. One patient did not have follow-up INR testing due to withdrawal of life support. No patient experienced hematoma expansion within 48 h of 4F-PCC, and there were no thromboembolic events within 72 h of administration. CONCLUSIONS: The administration of low dose (15 units/kg) of 4F-PCC for urgent warfarin reversal in the setting of CNS hemorrhage was effective in correcting the INR in patients presenting with INR values of 1.6-1.9. Further assessment of low-dose PCC for urgent reversal of modest INR elevation is warranted.


Assuntos
Anticoagulantes/efeitos adversos , Fatores de Coagulação Sanguínea/farmacologia , Hemorragia Intracraniana Traumática/tratamento farmacológico , Hemorragias Intracranianas/tratamento farmacológico , Avaliação de Resultados em Cuidados de Saúde , Varfarina/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Fatores de Coagulação Sanguínea/administração & dosagem , Feminino , Humanos , Coeficiente Internacional Normatizado , Hemorragias Intracranianas/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
14.
J Mol Evol ; 82(4-5): 183-98, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26961431

RESUMO

Na/K-ATPase is a key plasma membrane enzyme involved in cell signaling, volume regulation, and maintenance of electrochemical gradients. The α-subunit, central to these functions, belongs to a large family of P-type ATPases. Differences in transmembrane (TM) helix topology, sequence homology, helix-helix contacts, cell signaling, and protein domains of Na/K-ATPase α-subunit were compared in fungi (Beauveria), unicellular organisms (Paramecia), primitive multicellular organisms (Hydra), and vertebrates (Xenopus, Homo sapiens), and correlated with evolution of physiological functions in the α-subunit. All α-subunits are of similar length, with groupings of four and six helices in the N- and C-terminal regions, respectively. Minimal homology was seen for protein domain patterns in Paramecium and Hydra, with high correlation between Hydra and vertebrates. Paramecium α-subunits display extensive disorder, with minimal helix contacts. Increases in helix contacts in Hydra approached vertebrates. Protein motifs known to be associated with membrane lipid rafts and cell signaling reveal significant positional shifts between Paramecium and Hydra vulgaris, indicating that regional membrane fluidity changes occur during evolution. Putative steroid binding sites overlapping TM-3 occurred in all species. Sites associated with G-protein-receptor stimulation occur both in vertebrates and amphibia but not in Hydra or Paramecia. The C-terminus moiety "KETYY," necessary for the Na(+) activation of pump phosphorylation, is not present in unicellular species indicating the absence of classical Na(+)/K(+)-pumps. The basic protein topology evolved earliest, followed by increases in protein domains and ordered helical arrays, correlated with appearance of α-subunit regions known to involve cell signaling, membrane recycling, and ion channel formation.


Assuntos
Evolução Molecular , ATPase Trocadora de Sódio-Potássio/genética , Sequência de Aminoácidos , Animais , Sítios de Ligação , Evolução Biológica , Membrana Celular/metabolismo , Humanos , Dados de Sequência Molecular , Conformação Proteica em alfa-Hélice/fisiologia , Sódio/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo
15.
Biochem Biophys Res Commun ; 477(4): 834-840, 2016 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-27369077

RESUMO

The steroid hormone, vitamin D3, regulates gene transcription via at least two receptors and initiates putative rapid response systems at the plasma membrane. The vitamin D receptor (VDR) binds vitamin D3 and a second receptor, importin-4, imports the VDR-vitamin D3 complex into the nucleus via nuclear pores. Here we present evidence that the Homo sapiens VDR homodimer contains two transmembrane (TM) helices ((327)E - D(342)), two TM "half-helix" ((264)K N(276)), one or more large channels, and 16 cholesterol binding (CRAC/CARC) domains. The importin-4 monomer exhibits 3 pore-lining regions ((226)E - L(251); (768)V - G(783); (876)S - A(891)) and 16 CRAC/CARC domains. The MEMSAT algorithm indicates that VDR and importin-4 may not be restricted to cytoplasm and nucleus. VDR homodimer TM helix-topology predicts insertion into the plasma membrane, with two 84 residue C-terminal regions being extracellular. Similarly, MEMSAT predicts importin-4 insertion into the plasma membrane with 226 residue extracellular N-terminal regions and 96 residue C-terminal extracellular loops; with the pore-lining regions contributing gated Ca(2+) channels. The PoreWalker algorithm indicates that, of the 427 residues in each VDR monomer, 91 line the largest channel, including two vitamin D3 binding sites and residues from both the TM helix and "half-helix". Cholesterol-binding domains also extend into the channel within the ligand binding region. Programmed changes in bound cholesterol may regulate both membrane Ca(2+) response systems and vitamin D3 uptake as well as receptor internalization by the endomembrane system culminating in uptake of the vitamin D3-VDR-importin-4 complex into the nucleus.


Assuntos
Cálcio/química , Membrana Celular/química , Núcleo Celular/química , Colecalciferol/química , Receptores de Calcitriol/química , Receptores de Calcitriol/ultraestrutura , Cálcio/metabolismo , Sinalização do Cálcio/fisiologia , Membrana Celular/metabolismo , Núcleo Celular/metabolismo , Colecalciferol/metabolismo , Simulação por Computador , Modelos Químicos , Modelos Moleculares , Conformação Proteica , Receptores de Calcitriol/metabolismo , Relação Estrutura-Atividade
16.
J Surg Res ; 206(2): 398-404, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27884335

RESUMO

BACKGROUND: Ventilator-associated pneumonia (VAP) is a common cause of infectious morbidity and mortality in the intensive care unit (ICU). The type of stress-ulcer prophylaxis (SUP) given to ventilated patients may, in part, be responsible. We observed an increase in VAP as ventilator bundle compliance increased and a decrease in VAP when bundle compliance decreased. We reasoned that SUP which raises gastric pH such as proton-pump inhibitors (PPIs) and histamine II (H2) receptor antagonists as opposed to SUP which does not raise pH such as sucralfate (S) may be responsible and also may alter the causative bacteria. MATERIALS AND METHODS: This is a single-center retrospective cohort analysis of all intubated, adult surgical patients admitted to the surgical ICU between January and June during the 3-y period 2012-2014. Demographics, APACHE II, Injury Severity Score, VAP occurrence, culprit bacteria, ventilator days, and ICU days were recorded based on the type of SUP given. RESULTS: There were 45 instances of VAP in the 504 study patients, 33 in the PPI/H2 group, and 12 in the S group (P < 0.01). VAP per 1000 ventilator days were 10.2 for PPI/H2 and 3.7 for S (P < 0.01). Culprit bacteria were mostly Pseudomonas, gram-negative bacilli, and methicillin-resistant Staphylococcus aureus in PPI/H2 patients (n = 29) compared with oropharyngeal flora in S patients (n = 6; P < 0.001). CONCLUSIONS: There was a substantial difference in VAP occurrence and in the culprit bacteria between S and PPI/H2 treated patients due perhaps to gastric alkalization.


Assuntos
Antiulcerosos/efeitos adversos , Cuidados Críticos/métodos , Antagonistas dos Receptores H2 da Histamina/efeitos adversos , Úlcera Péptica/prevenção & controle , Pneumonia Associada à Ventilação Mecânica/prevenção & controle , Inibidores da Bomba de Prótons/efeitos adversos , Sucralfato/uso terapêutico , Adulto , Idoso , Antiulcerosos/uso terapêutico , Feminino , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/complicações , Pneumonia Associada à Ventilação Mecânica/etiologia , Pneumonia Associada à Ventilação Mecânica/microbiologia , Inibidores da Bomba de Prótons/uso terapêutico , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
17.
Biochim Biophys Acta ; 1838(11): 2838-51, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25037006

RESUMO

Cytochrome c oxidase (CcO) is the terminal enzyme in the electron transfer chain. CcO catalyzes a four electron reduction of O2 to water at a catalytic site formed by high-spin heme (a3) and copper atoms (CuB). While it is recognized that proton movement is coupled to oxygen reduction, the proton channel(s) have not been well defined. Using computational methods developed to study protein topology, membrane channels and 3D packing arrangements within transmembrane (TM) helix arrays, we find that subunit-1 (COX-1), subunit-2 (COX-2) and subunit-3 (COX-3) contribute 139, 46 and 25 residues, respectively, to channel formation between the mitochondrial matrix and intermembrane space. Nine of 12 TM helices in COX-1, both helices in COX-2 and 5 of the 6 TM helices in COX-3 are pore-lining regions (possible channel formers). Heme a3 and the CuB sites (as well as the CuA center of COX-2) are located within the channel that includes TM-6, TM-7, TM-10 and TM-11 of COX-1 and are associated with multiple cholesterol and caveolin-binding (CB) motifs. Sequence analysis identifies five CB motifs within COX-1, two within COX-2 and four within COX-3; each caveolin containing a pore-lining helix C-terminal to a TM helix-turn-helix. Channel formation involves interaction between multiple pore-lining regions within protein subunits and/or dimers. PoreWalker analysis lends support to the D-channel model of proton translocation. Under physiological conditions, caveolins may introduce channel formers juxtaposed to those in COX-1, COX-2 and COX-3, which together with cholesterol may form channel(s) essential for proton translocation through the inner mitochondrial membrane.

18.
Biochem Biophys Res Commun ; 459(1): 36-41, 2015 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-25701780

RESUMO

The extracellular Ca(2+) sensing receptor (CaSR) belongs to Class C G-protein-coupled receptors (GPCRs) which include receptors for amino acids, γ-aminobutyric acid and glutamate neurotransmitters. CaSR has been described as having an extended sequence containing a Ca(2+) binding pocket within an extracellular amino (N)-terminal domain, called a Venus Fly Trap (VFT) module. CaSR is thought to consist of three domains: 1) a Ca(2+-)sensory domain, 2) a region containing 7 transmembrane (TM) helices, and 3) a carboxy (C)-terminal tail. We find that SPOCTOPUS (a combination of hidden Markov models and artificial neural networks) predicts that Homo sapiens CaSR contains two additional TM helices ((190)D - G(210); (262)S-E(282)), with the second TM helix containing a pore-lining region ((265)K - I(280)). This predicts that the putative Ca(2+) sensory domain is within an extracellular loop, N-terminal to the highly conserved heptahelical bundle. This loop contains both the cysteine-rich domain ((537)V - C(598)) and a 14 residue "linker" sequence ((599)I - F(612)) thought to support signal transmission to the heptahelical bundle. Thus domain 1 may contain a 189 residue N-terminal extracellular region followed successively by TM-1, a short intracellular loop, TM-2 and a 329 residue extracellular loop; rather than the proposed 620 residue VFT module based on crystallography of the N-terminal region of mGluR1. Since the topologies of the two proteins differ, the published CaSR VFT model is questionable. CaSR also contains multiple caveolin-binding motifs and cholesterol-binding (CRAC/CARC) domains, facilitating localization to plasma membrane lipid rafts. Ion sensing may involve combination of pore-lining regions from CaSR dimers and CaSR-bound caveolins to form ion channels capable of monitoring ionized Ca(2+) levels.


Assuntos
Receptores de Detecção de Cálcio/química , Receptores de Detecção de Cálcio/metabolismo , Motivos de Aminoácidos , Sequência de Aminoácidos , Sítios de Ligação , Caveolinas/metabolismo , Membrana Celular/química , Membrana Celular/metabolismo , Colesterol/metabolismo , Humanos , Interações Hidrofóbicas e Hidrofílicas , Dados de Sequência Molecular , Multimerização Proteica , Estrutura Terciária de Proteína , Receptores de Glutamato Metabotrópico/química , Receptores de Glutamato Metabotrópico/metabolismo
19.
Psychol Sci ; 26(9): 1368-76, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26187247

RESUMO

Trust is a critical aspect of social interaction. One might predict that individuals trust religious out-groups less than religious in-groups, and that costly signals performed by members of religious in-groups increase trust while costly signals performed by members of religious out-groups decrease trust. We examined how Christian participants perceived the trustworthiness of Muslim and Christian individuals who did or did not engage in religious costly signaling. Religious costly signaling, operationalized as giving to religious charities (Experiments 1 and 2) or adhering to religious dietary restrictions (Experiment 3), increased self-reported trust, regardless of target religious affiliation. Furthermore, when estimating the likelihood that trustworthy versus untrustworthy targets engaged in costly signaling, participants made systematic judgments that showed that costly signaling is associated with trust for both Muslim and Christian targets (Experiment 4). These results are novel in their suggestion that costly signals of religious commitment can increase trust both within and, crucially, across religious-group lines.


Assuntos
Julgamento , Religião e Psicologia , Religião , Confiança , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Percepção , Análise de Regressão , Adulto Jovem
20.
Birth Defects Res B Dev Reprod Toxicol ; 104(1): 35-51, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25707689

RESUMO

BACKGROUND: 2-Hydroxy-4-methoxybenzophenone (HMB) is an ultraviolet (UV) absorbing compound used in many cosmetic products as a UV-protecting agent and in plastics for preventing UV-induced photodecomposition. HMB has been detected in over 95% of randomly collected human urine samples from adults and from premature infants, and it may have estrogenic potential. METHODS: To determine the effects of maternal and lactational exposure to HMB on development and reproductive organs of offspring, time-mated female Harlan Sprague-Dawley rats were dosed with 0, 1000, 3000, 10,000, 25,000, or 50,000 ppm HMB (seven to eight per group) added to chow from gestation day 6 until weaning on postnatal day (PND) 23. RESULTS AND CONCLUSION: Exposure to HMB was associated with reduced body and organ weights in female and male offspring. No significant differences were observed in the number of implantation sites/litter, mean resorptions/litter, % litters with resorptions, number and weights of live fetuses, or sex ratios between the control and HMB dose groups. Normalized anogenital distance in male pups at PND 23 was decreased in the highest dose group. Spermatocyte development was impaired in testes of male offspring in the highest dose group. In females, follicular development was delayed in the highest dose group. However, by evaluating levels of the compound in rat serum, the doses at which adverse events occurred are much higher than usual human exposure levels. Thus, exposure to less than 10,000 ppm HMB does not appear to be associated with adverse effects on the reproductive system in rats.


Assuntos
Benzofenonas/toxicidade , Desenvolvimento Embrionário/efeitos dos fármacos , Lactação/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/patologia , Reprodução/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Peso Corporal/efeitos dos fármacos , Contagem de Células , Feminino , Masculino , Tamanho do Órgão/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Ratos Sprague-Dawley , Túbulos Seminíferos/efeitos dos fármacos , Túbulos Seminíferos/patologia , Espermatócitos/efeitos dos fármacos , Espermatócitos/patologia , Testosterona/sangue
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