Mushroom body-specific profiling of gene expression identifies regulators of long-term memory in Drosophila

Memory formation is achieved by genetically tightly controlled molecular pathways that result in a change of synaptic strength and synapse organization. While for short- term memory traces rapidly acting biochemical pathways are in place, the formation of long-lasting memories requires changes in the transcriptional program of a cell. Although many genes involved in learning and memory formation have been identified, little is known about the genetic mechanisms required for changing the transcriptional program during different phases of long-term memory formation. With Drosophila melanogaster as a model system we profiled transcriptomic changes in the mushroom body, a memory center in the fly brain, at distinct time intervals during long- term memory formation using the targeted DamID technique. We describe the gene expression profiles during these phases and tested 33 selected candidate genes for deficits in long-term memory formation using RNAi knockdown. We identified 10 genes that enhance or decrease memory when knocked-down in the mushroom body. For vajk-1 and hacd1, the two strongest hits, we gained further support for their crucial role in learning and forgetting. These findings show that profiling gene expression changes in specific cell-types harboring memory traces provides a powerful entry point to identify new genes involved in learning and memory. The presented transcriptomic data may further be used as resource to study genes acting at different memory phases

Dialectical Behavior Therapy for Adult Attention Deficit Hyperactivity Disorder: A Narrative Review

Due to the multifaceted psychosocial problems of adults with ADHD and the low level of functionality in different areas such as education, work and family life, the search for psychotherapeutic treatment other than pharmacological approaches has increased in the last decade. This study aims to evaluate the clinical contributions of Dialectical Behavioral Therapy (DBT)-based interventions and the controlled studies in which DBT were tested. This study is a qualitative narrative review. This review included the controlled studies reached by searching the DDT and Adult ADHD as keywords in Medline, Pubmed, Science Direct and EBSCO Psychology & Behavioral Sciences Collection databases until 2021. A total of 12 research articles and 1 short report were identified, but only 9 studies met the inclusion criteria and controlled study conditions. In all studies, it was seen that the skills training mode of DBT was used or adapted. Although the results of the studies reviewed in this review are not consistent, DBT Skills Training shows promise in controlling ADHD symptoms and increasing other psychosocial skills of adults. However, there is a need for more controlled studies on the effectiveness of DBT Skills Training in different experimental research designs

Mediating Roles of Emotion Regulation Difficulties and Rejection Sensitivity in the Relation Between Romantic Attachment and Couple Adjustment

Bağlanma kuramına göre gelişimin erken dönemindeki ilişkiler çerçevesinde hem duygu düzenlemeye ilişkin beceriler kazanılmakta hem de reddedilmeye karşı duyarlı bir örüntü gelişebilmektedir. Erken dönemdeki bu deneyimler aynı zamanda yetişkinlik dönemindeki bağlanma stilleri için de belirleyici bir etkiye sahiptir. Çiftler arasındaki uyumun şekillenmesinde ve sürdürülmesinde bağlanmanın önemli etkileri bulunmaktadır. Bu çalışma çift uyumunu belirleyebileceği düşünülen bu değişkenlerin etkisini incelemeyi amaçlamıştır. Çalışmanın bir diğer hedefi reddedilme hassasiyetinin ve duygu düzenlemenin aracılık etkilerinin incelenmesidir. Örneklem, İstanbul ilinde yaşayan 346 evli bireyden oluşmaktadır (Nkadın = 173, Nerkek = 173). Yol analizine ilişkin bulgular, romantik bağlanmanın kaçınma boyutunun ve duygu düzenleme güçlüğünün çift uyumunu negatif yönde yordadığını göstermektedir. Aracılık analizinin bulguları bağlanma kaygısındaki artışın duygu düzenleme güçlüğünü artırdığını ve bunun da çiftlerin arasındaki uyumu azalttığını göstermektedir. Duygu düzenleme güçlüğü, kaygılı bağlanma örüntüsü ile çift uyumu arasındaki ilişkide tam aracı etki göstermektedir. Bağlanmanın kaygı ve kaçınma boyutlarının reddedilme hassasiyetini artırdığı fakat reddedilme hassasiyetinin çift uyumu üzerinde doğrudan veya dolaylı bir etkisinin olmadığı görülmektedir. Sonuç olarak, çalışmanın bulguları bağlanma kuramını desteklemekte ve erken dönem oluşan yapıların yetişkinlikte romantik ilişkileri etkilemeye devam ettiğini göstermektedir. Bulgulardan hareketle, duyguları düzenlemeye yönelik terapötik müdahalelerin evli bireylerin ilişki kalitesine olumlu katkı sağlaması beklenmektedir.According to the attachment theory, relationships in early developmental stages provide a basis for emotion regulation skills and a pattern for rejection sensitivity. These early experiences also create a tendency for specific attachment styles in adulthood. Attachment shapes and maintains adjustment between couples. The current study aimed to examine the relationship between attachment, emotion regulation, and rejection sensitivity, which are thought to determine couple adjustment. Another aim was to investigate the mediating effects of rejection sensitivity and emotion dysregulation. The participants consist of 346 married individuals living in the city of Istanbul (Nfemale = 173, Nmale = 173). Findings regarding the path analysis show that the avoidance dimension of romantic attachment and the difficulty in emotion regulation negatively predicted the dyadic adjustment. The findings of the mediation analysis revealed an increase in attachment anxiety amplified the difficulty in emotion regulation and that decreased adjustment between the couples. Emotion regulation difficulty fully mediated the relationship between anxious attachment pattern and couple adjustment. Anxiety and avoidance dimensions of attachment were associated with increases in rejection sensitivity. However, rejection sensitivity did not have a direct or indirect effect on couple adjustment. In conclusion, the findings showed early structures continued to influence romantic relationships in adulthood. Based on the findings, therapeutic interventions to regulate emotions were expected to contribute positively relationship quality of couples

Regulators of Long-Term Memory Revealed by Mushroom Body-Specific Gene Expression Profiling in Drosophila melanogaster

Memory formation is achieved by genetically tightly controlled molecular pathways that result in a change of synaptic strength and synapse organization. While for short- term memory traces, rapidly acting biochemical pathways are in place, the formation of long-lasting memories requires changes in the transcriptional program of a cell. Although many genes involved in learning and memory formation have been identified, little is known about the genetic mechanisms required for changing the transcriptional program during different phases of long-term memory (LTM) formation. With Drosophila melanogaster as a model system, we profiled transcriptomic changes in the mushroom body—a memory center in the fly brain—at distinct time intervals during appetitive olfactory LTM formation using the targeted DamID technique. We describe the gene expression profiles during these phases and tested 33 selected candidate genes for deficits in LTM formation using RNAi knockdown. We identified 10 genes that enhance or decrease memory when knocked-down in the mushroom body. For vajk-1 and hacd1—the two strongest hits—we gained further support for their crucial role in appetitive learning and forgetting. These findings show that profiling gene expression changes in specific cell-types harboring memory traces provides a powerful entry point to identify new genes involved in learning and memory. The presented transcriptomic data may further be used as resource to study genes acting at different memory phases

Effectiveness of dialectical behavior therapy-online group skills training during the pandemic: A pilot study

Dialectical Behavior Therapy (DBT) was developed by Linehan for clients with borderline personality disorder. It is based on behaviorist approach, Zen Buddhism, and dialectical philosophy. There are four components: individual session, group skills training, telephone coaching, and consultation team. DBT group skill training consists of four modules in total, including mindfulness, interpersonal effectiveness, stress tolerance, and emotion regulation skills. Many studies have been conducted on the effectiveness of DBT and DBT group skills training. In this study, the effectiveness of 8-week DBT group skill training in university students on depression, anxiety, and stress levels during the pandemic was investigated. In addition, the improvements in emotion regulation, mindfulness, and interpersonal effectiveness skills were observed. A total of 17 women, who were undergraduate students between the ages of 18-24, participated in the study. An online self-evaluation form was sent to the participants and feedback was given to the applicants by phone call. Sociodemographic Information Form, the Five Facet Mindfulness Questionnaire-Short Form, Difficulties in Emotion Regulation Scale-Brief Form, Interpersonal Competence Questionnaire-Short Form, and Depression Anxiety Stress Scale were sent online to the selected participants before participating in the group skill training, after the 4th session, and at the end of the 8th week. According to the results, DBT group skill training was found to be helpful in reducing depression, anxiety, and stress levels. In addition, an increase was observed in emotion regulation and interpersonal competence skills

Ionotropic GABA and glycine receptor subunit composition in human pluripotent stem cell-derived excitatory cortical neurones

We have assessed, using whole-cell patch-clamp recording and RNA-sequencing (RNA-seq), the properties and composition of GABA(A) receptors (GABA(A)Rs) and strychnine-sensitive glycine receptors (GlyRs) expressed by excitatory cortical neurons derived from human embryonic stem cells (hECNs). The agonists GABA and muscimol gave EC(50) values of 278 μm and 182 μm, respectively, and the presence of a GABA(A)R population displaying low agonist potencies is supported by strong RNA-seq signals for α2 and α3 subunits. GABA(A)R-mediated currents, evoked by EC(50) concentrations of GABA, were blocked by bicuculline and picrotoxin with IC(50) values of 2.7 and 5.1 μm, respectively. hECN GABA(A)Rs are predominantly γ subunit-containing as assessed by the sensitivity of GABA-evoked currents to diazepam and insensitivity to Zn(2+), together with the weak direct agonist action of gaboxadol; RNA-seq indicated a predominant expression of the γ2 subunit. Potentiation of GABA-evoked currents by propofol and etomidate and the lack of inhibition of currents by salicylidine salycylhydrazide (SCS) indicate expression of the β2 or β3 subunit, with RNA-seq analysis indicating strong expression of β3 in hECN GABA(A)Rs. Taken together our data support the notion that hECN GABA(A)Rs have an α2/3β3γ2 subunit composition – a composition that also predominates in immature rodent cortex. GlyRs expressed by hECNs were activated by glycine with an EC(50) of 167 μm. Glycine-evoked (500 μm) currents were blocked by strychnine (IC(50) = 630 nm) and picrotoxin (IC(50) = 197 μm), where the latter is suggestive of a population of heteromeric receptors. RNA-seq indicates GlyRs are likely to be composed of α2 and β subunits

Efficient derivation of NPCs, spinal motor neurons and midbrain dopaminergic neurons from hESCs at 3% oxygen

This protocol has been designed to generate neural precursor cells (NPCs) from human embryonic stem cells (hESCs) using a physiological oxygen (O(2)) level of 3% and chemically defined conditions. The first stage involves suspension culture of hESC colonies at 3% O(2), where they acquire a neuroepithelial identity over two weeks. This timescale is comparable to that at 20% O(2), but survival is enhanced. Sequential application of retinoic acid (RA) and purmorphamine (PM), from day 14 to 28, directs differentiation towards spinal motor neurons. Alternatively, addition of FGF-8 and PM generates midbrain dopaminergic neurons. OLIG2 induction in motor neuron precursors is 2-fold greater than at 20% O(2), whereas EN1 is 5-fold enhanced. 3% NPCs can be differentiated into all three neural lineages, and such cultures can be maintained long-term in the absence of neurotrophins. The ability to generate defined cell types at 3% O(2) should represent a significant advance for in vitro disease modelling and potentially cell-based therapies

2D versus 3D human induced pluripotent stem cell-derived cultures for neurodegenerative disease modelling

Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS), affect millions of people every year and so far, there are no therapeutic cures available. Even though animal and histological models have been of great aid in understanding disease mechanisms and identifying possible therapeutic strategies, in order to find disease-modifying solutions there is still a critical need for systems that can provide more predictive and physiologically relevant results. One possible avenue is the development of patient-derived models, e.g. by reprogramming patient somatic cells into human induced pluripotent stem cells (hiPSCs), which can then be differentiated into any cell type for modelling. These systems contain key genetic information from the donors, and therefore have enormous potential as tools in the investigation of pathological mechanisms underlying disease phenotype, and progression, as well as in drug testing platforms. hiPSCs have been widely cultured in 2D systems, but in order to mimic human brain complexity, 3D models have been proposed as a more advanced alternative. This review will focus on the use of patient-derived hiPSCs to model AD, PD, HD and ALS. In brief, we will cover the available stem cells, types of 2D and 3D culture systems, existing models for neurodegenerative diseases, obstacles to model these diseases in vitro, and current perspectives in the field

Calibration of the CMS hadron calorimeters using proton-proton collision data at √s = 13 TeV

Methods are presented for calibrating the hadron calorimeter system of the CMS detector at the LHC. The hadron calorimeters of the CMS experiment are sampling calorimeters of brass and scintillator, and are in the form of one central detector and two endcaps. These calorimeters cover pseudorapidities |η| < 3 and are positioned inside the solenoidal magnet. An outer calorimeter, outside the magnet coil, covers |η| < 1.26, and a steel and quartz-fiber Cherenkov forward calorimeter extends the coverage to |η| < 5.19. The initial calibration of the calorimeters was based on results from test beams, augmented with the use of radioactive sources and lasers. The calibration was improved substantially using proton-proton collision data collected at √s = 7, 8, and 13 TeV, as well as cosmic ray muon data collected during the periods when the LHC beams were not present. The present calibration is performed using the 13 TeV data collected during 2016 corresponding to an integrated luminosity of 35.9 fb⁻¹. The intercalibration of channels exploits the approximate uniformity of energy collection over the azimuthal angle. The absolute energy scale of the central and endcap calorimeters is set using isolated charged hadrons. The energy scale for the electromagnetic portion of the forward calorimeters is set using Z→ ee data. The energy scale of the outer calorimeters has been determined with test beam data and is confirmed through data with high transverse momentum jets. In this paper, we present the details of the calibration methods and accuracy