56 research outputs found
Using Transcranial Alternating Current Stimulation (tACS) to Improve Romantic Relationships Can Be a Promising Approach
The romantic relationship refers to the specific relationship in which partners are dependent upon each other to obtain satisfactory outcomes and facilitate the pursuit of their most important needs and goals. Satisfying romantic relationships is a strong predictor of better psychological well-being, better physical health, and longer life expectancy. However, romantic relationships are not all smooth-sailing and lovers are often confronted with a variety of unavoidable issues that constantly challenge the stability of their romantic relationships. Dissatisfying romantic relationships are harmful and even destructive. Dyads of lovers engage in a variety of efforts to protect and maintain their romantic relationships based on qualitative research methods including theories- and psychological consultation-based approaches. Unfortunately, those existing approaches do not seem to effectively improve romantic relationships. Thus, it is necessary to seek an efficient approach regulating dyads of lovers in romantic relationships simultaneously. Transcranial alternating current stimulation (tACS) with advantages over existing approaches satisfies this purpose. We discuss the practicability of tACS in detail, as well as why and how tACS can be utilized to improve romantic relationships. In summary, this review firstly introduced the concept of romantic relationship and the necessity of enhancing it. Then, it discussed methods to improve romantic relationships including some existing approaches. This review next discussed the practicability of using tACS to improve romantic relationships. Finally, it shone a spotlight on potential future directions for researches aiming to improve romantic relationships
Low-Theta Electroencephalography Coherence Predicts Cigarette Craving in Nicotine Addiction
Addicts are often vulnerable to drug use in the presence of drug cues, which elicit significant drug cue reactivity. Mounting neuroimaging evidence suggests an association between functional magnetic resonance imaging connectivity networks and smoking cue reactivity; however, there is still little understanding of the electroencephalography (EEG) coherence basis of smoking cue reactivity. We therefore designed two independent experiments wherein nicotine-dependent smokers performed a smoking cue reactivity task during EEG recording. Experiment I showed that a low-theta EEG coherence network occurring 400–600 ms after onset during long-range (mainly between frontal and parieto-occipital) scalp regions, which was involved in smoking cue reactivity. Moreover, the average coherence of this network was significantly correlated with participants’ level of cigarette craving. In experiment II, we tested an independent group of smokers and demonstrated that the low-theta coherence network significantly predicted changes in individuals’ cigarette craving. Thus, the low-theta EEG coherence in smokers’ brains might be a biomarker of smoking cue reactivity and can predict addiction behavior
Neuroimaging Studies Reveal the Subtle Difference Among Social Network Size Measurements and Shed Light on New Directions
Social network size is a key feature when we explore the constructions of human social networks. Despite the disparate understanding of individuals’ social networks, researchers have reached a consensus that human’s social networks are hierarchically organized with different layers, which represent emotional bonds and interaction frequency. Social brain hypothesis emphasizes the significance of complex and demanding social interaction environments and assumes that the cognitive constraints may have an impact on the social network size. This paper reviews neuroimaging studies on social networks that explored the connection between individuals’ social network size and neural mechanisms and finds that Social Network Index (SNI) and Social Network Questionnaires (SNQs) are the mostly-adopted measurements of one’s social network size. The two assessments have subtle difference in essence as they measure the different sublayers of one’s social network. The former measures the relatively outer sub-layer of one’s stable social relationship, similar to the sympathy group, while the latter assesses the innermost layer—the core of one’s social network, often referred to as support clique. This subtle difference is also corroborated by neuroimaging studies, as SNI-measured social network size is largely correlated with the amygdala, while SNQ-assessed social network size is closely related to both the amygdala and the orbitofrontal cortex. The two brain regions respond to disparate degrees of social closeness, respectively. Finally, it proposes a careful choice among the measurements for specific purposes and some new approaches to assess individuals’ social network size
A Renal Cell Carcinoma with Biallelic Somatic TSC2 Mutation: Clinical Study and Literature Review.
OBJECTIVES: To elucidate the effect of the biallelic somatic TSC2 mutations, identified in one adolescent patient, in renal cell carcinoma (RCC).
METHODS: Mutation analyses, immunohistochemistry and real-time polymerase chain reaction (PCR) were conducted.
RESULTS: Two novel somatic mutations of TSC2 in unilateral and solitary RCC samples from a 14-year-old female were identified. The pathological features suggest the tumor as a clear-cell renal cell carcinoma. In addition, immunohistochemistry revealed elevated levels of phosphorylated S6K1. Results from in vitro cellular experiments suggest that the mutant TSC2 proteins were quickly degraded and they failed to repress the phosphorylation of S6K1 and STAT3, which leads to constitutive activation of mTORC1 pathway and ultimately cause the development of RCC.
CONCLUSIONS: Detecting TSC2 mutation in patients with early RCC onset would be beneficial and mTOR inhibitor could be a therapeutic option for TSC2 mutation-induced RCC
Safety evaluation of employing temporal interference transcranial alternating current stimulation in human studies
Temporal interference transcranial alternating current stimulation (TI-tACS) is a new technique of noninvasive brain stimulation. Previous studies have shown the effectiveness of TI-tACS in stimulating brain areas in a selective manner. However, its safety in modulating human brain neurons is still untested. In this study, 38 healthy adults were recruited to undergo a series of neurological and neuropsychological measurements regarding safety concerns before and after active (2 mA, 20/70 Hz, 30 min) or sham (0 mA, 0 Hz, 30 min) TI-tACS. The neurological and neuropsychological measurements included electroencephalography (EEG), serum neuron-specific enolase (NSE), the Montreal Cognitive Assessment (MoCA), the Purdue Pegboard Test (PPT), an abbreviated version of the California Computerized Assessment Package (A-CalCAP), a revised version of the Visual Analog Mood Scale (VAMS-R), a self-assessment scale (SAS), and a questionnaire about adverse effects (AEs). We found no significant difference between the measurements of the active and sham TI-tACS groups. Meanwhile, no serious or intolerable adverse effects were reported or observed in the active stimulation group of 19 participants. These results support that TI-tACS is safe and tolerable in terms of neurological and neuropsychological functions and adverse effects for use in human brain stimulation studies under typical transcranial electric stimulation (TES) conditions (2 mA, 20/70 Hz, 30 min)
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Release of gp120 Restraints Leads to an Entry-Competent Intermediate State of the HIV-1 Envelope Glycoproteins
ABSTRACT Primary human immunodeficiency virus (HIV-1) envelope glycoprotein (Env) trimers [(gp120/gp41)3] typically exist in a metastable closed conformation (state 1). Binding the CD4 receptor triggers Env to undergo extensive conformational changes to mediate virus entry. We identified specific gp120 residues that restrain Env in state 1. Alteration of these restraining residues destabilized state 1, allowing Env to populate a functional conformation (state 2) intermediate between state 1 and the full CD4-bound state (state 3). Increased state 2 occupancy was associated with lower energy barriers between the states. State 2 was an obligate intermediate for all transitions between state 1 and state 3. State 2-enriched Envs required lower CD4 concentrations to trigger virus entry and more efficiently infected cells expressing low levels of CD4. These Envs were resistant to several broadly neutralizing antibodies and small-molecule inhibitors. Thus, state 2 is an Env conformation on the virus entry pathway; sampling state 2 increases the adaptability of HIV-1 to different host cell receptor levels and immune environments. Our results provide new insights into the conformational regulation of HIV-1 entry
Rejection of Unfair Offers Can Be Driven by Negative Emotions, Evidence from Modified Ultimatum Games with Anonymity
The rejection of unfair offers can be affected by both negative emotions (e.g. anger and moral disgust) and deliberate cognitive processing of behavioral consequences (e.g. concerns of maintaining social fairness and protecting personal reputation). However, whether negative emotions are sufficient to motivate this behavior is still controversial. With modified ultimatum games, a recent study (Yamagishi T, et al. (2009) Proc Natl Acad Sci USA 106∶11520–11523) found that people reject unfair offers even when this behavior increases inequity, and even when they could not communicate to the proposers. Yamagishi suggested that rejection of unfair offers could occurr without people’s concerning of maintaining social fairness, and could be driven by negative emotions. However, as anonymity was not sufficiently guaranteed in Yamagishi’s study, the rejection rates in their experiments may have been influenced by people’s concerns of protecting personal reputation (reputational concerns) in addition to negative emotions; thus, it was unclear whether the rejection was driven by negative emotions, or by reputational concerns, or both. In the present study, with specific methods to ensure anonymity, the effect of reputational concerns was successfully ruled out. We found that in a private situation in which rejection could not be driven by reputational concerns, the rejection rates of unfair offers were significantly larger than zero, and in public situations in which rejection rates could be influenced by both negative emotions and reputational concerns, rejection rates were significantly higher than that in the private situation. These results, together with Yamagishi’s findings, provided more complete evidence suggesting (a) that the rejection of unfair offers can be driven by negative emotions and (b) that deliberate cognitive processing of the consequences of the behavior can increase the rejection rate, which may benefit social cooperation
ALKYNYL AMINOISOQUINOLINES, NOVEL FLT3 KINASE INHIBITORS WITH POTENT ACTIVITY AGAINST ACUTE MYELOID LEUKEMIA
Acute myeloid leukemia (AML) is a type of blood cancer. If not properly treated, this subclass of leukemia can progress quickly, and be fatal after a few months. Aberrantly expressed FMS (Feline McDonough Sarcoma)-like tyrosine kinase (FLT3) is observed in approximately 30% of AML patients, so it is a promising molecular target for AML. Midostaurin (commercial name, Rydapt) was the first approved FDA drug for AML that targets FLT3. However, Midostaurin, is not a single agent drug and is only effective when used in combination with other cytotoxic drugs. Therefore, there is a need for FLT3 inhibitors that are effective as a single agent.
In Chapter 2, the synthesis of a series of amidine-acetylene-isoquinoline-3-amines is described. Amidine-acetylene-isoquinoline-3-amine compounds have the potential to serve new FLT3 inhibitors with inhibition IC50 values in the nanomolar region against wild type FLT3, FLT3-ITD (internal tandem duplications) and FLT3-D835Y (a tyrosine kinase domain mutant, commonly found in AML patients).
Amidine drugs are generally not orally bioavailable, the synthesis of amide-acetylene-isoquinoline-3-amines, our second generation FLT3 inhibitors are described in Chapters 3 and 4. The amide-acetylene-isoquinolines inhibit FLT3-driven AML cell lines with single digit nanomolar IC50 values and are either comparable to or better than most FLT3 inhibitors reported to date
Miniaturized whole-cell bacterial bioreporter assay for identification of quorum sensing interfering compounds
The continuing emergence and spread of antibiotic-resistant bacteria is worrisome and new strategies to curb bacterial infections are being sought. The interference of bacterial quorum sensing (QS) signaling has been suggested as a prospective antivirulence strategy. The AI-2 QS system is present in multiple bacterial species and has been shown to be correlated with pathogenicity. To facilitate the discovery of novel compounds interfering with AI-2 QS, we established a high-throughput setup of whole-cell bioreporter assay, which can be performed in either 96- or 384-well format. Agonistic or antagonistic activities of the test compounds against Escherichia coli LsrB-type AI-2 QS system are monitored by measuring the level of beta-galactosidase expression. A control strain expressing beta-galactosidase in quorum sensing-independent manner is included into the assay for false-positive detection.Peer reviewe
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