Regulation Of Circuitry Research Articles

Distinct Associations of BMI and Fatty Acids With DNA Methylation in Fasting and Postprandial States in Men.

We have previously shown that blood global DNA methylation (DNAm) differs between postprandial state (PS) and fasting state (FS) and is associated with BMI and polyunsaturated fatty acid (PUFA) (negatively and positively, respectively) in 12 metabolically healthy adult Mexican men (AMM cohort) equally distributed among conventional BMI classes. Here, we detailed those associations at CpG dinucleotide level by exploiting the Infinium methylation EPIC array (Illumina). We sought differentially methylated CpG (dmCpG) that were (1) associated with BMI (BMI-dmCpG) and/or fatty acids (FA) (FA-dmCpG) in FS or PS and (2) different across FS and PS within a BMI class. BMI-dmCpG and FA-dmCpG were more numerous in FS compared to PS and largely prandial state-specific. For saturated and monounsaturated FA, dmCpG overlap was higher across than within the respective saturation group. Several BMI- and FA-dmCpG mapped to genes involved in metabolic disease and in some cases matched published experimental data sets. Notably, SETDB1 and MTHFS promoter dmCpG could explain the previously observed associations between global DNAm, PUFA content, and BMI in FS. Surprisingly, overlap between BMI-dmCpG and FA-dmCpG was limited and the respective dmCpG were differentially distributed across functional genomic elements. BMI-dmCpG showed the highest overlap with dmCpG of the saturated FA palmitate, monounsaturated C20:1 and PUFA C20:2. Of these, selected promoter BMI-dmCpG showed opposite associations with palmitate compared to C20:1 and C20:2. As for the comparison between FS and PS within BMI classes, dmCpG were strikingly more abundant and variably methylated in overweight relative to normoweight or obese subjects (∼70–139-fold, respectively). Overweight-associated dmCpG-hosting genes were significantly enriched in targets for E47, SREBP1, and RREB1 transcription factors, which are known players in obesity and lipid homeostasis, but none overlapped with BMI-dmCpG. We show for the first time that the association of BMI and FA with methylation of disease-related genes is distinct in FS and PS and that limited overlap exists between BMI- and FA-dmCpG within and across prandial states. Our study also identifies a transcriptional regulation circuitry in overweight that might contribute to adaptation to that condition or to transition to obesity. Further work is necessary to define the pathophysiological implications of these findings.

COLOR CONTROL OF THE DEVICE WITH LED TAPE ON THE VALUE OF TEMPERATURE AND HUMIDITY OF AIR

The work is devoted to the development of a lighting device with control of the color of the LED strip depending on the value of temperature and humidity. To develop a prototype of a lighting installation, an A-Star 32U4 Micro microcontroller (analogue of Arduino Micro), 2 pieces of RGB tape of 5 and 10 cm each, a DHT11 temperature and humidity sensor, connecting wires, a case were purchased. The A-Star 32U4 Micro microcontroller used in the proposed setup is a universal programmable module based on the ATmega32U4 AVR microcontroller from Microchip (formerly Atmel), which has 32KB flash memory, 2.5KB RAM, and builtin USB functionality. A voltage regulator and power selection circuitry allows the board to be powered from either USB or an external 5.5V to 15V supply, while a resettable PTC fuse on the USB VBUS power supply and reverse protection on the VIN help protect it from accidental damage. In the course of the work, studies were carried out on the operation of the installation under normal conditions and at low and high temperatures.

White matter microstructure of the neural emotion regulation circuitry in mild traumatic brain injury.

Emotion regulation is related to recovery after mild traumatic brain injury (mTBI). This longitudinal tractography study examined white matter tracts subserving emotion regulation across the spectrum of mTBI, with a focus on persistent symptoms. Four groups were examined: (a) symptomatic (n = 33) and (b) asymptomatic (n = 20) patients with uncomplicated mTBI (i.e., no lesions on computed tomography [CT]), (c) patients with CT‐lesions in the frontal areas (n = 14), and (d) healthy controls (HC) (n = 20). Diffusion and conventional MRI were performed approximately 1‐ and 3‐months post‐injury. Whole‐brain deterministic tractography followed by region of interest analyses was used to identify forceps minor (FM), uncinate fasciculus (UF), and cingulum bundle as tracts of interest. An adjusted version of the ExploreDTI Atlas Based Tractography method was used to obtain reliable tracts for every subject. Mean fractional anisotropy (FA), mean, radial and axial diffusivity (MD, RD, AD), and number of streamlines were studied per tract. Linear mixed models showed lower FA, and higher MD, and RD of the right UF in asymptomatic patients with uncomplicated mTBI relative to symptomatic patients and HC. Diffusion alterations were most pronounced in the group with frontal lesions on CT, particularly in the FM and UF; these effects increased over time. Within the group of patients with uncomplicated mTBI, there were no associations of diffusion measures with the number of symptoms nor with lesions on conventional MRI. In conclusion, mTBI can cause microstructural changes in emotion regulation tracts, however, no explanation was found for the presence of symptoms.

Predicting Neuroimaging Biomarkers for Antidepressant Selection in Early Treatment of Depression.

Due to the biological heterogeneity, 60%-70% of patients with major depressive disorder (MDD) do not respond to or achieve remission from first-line antidepressants. Predicting neuroimaging biomarkers for early antidepressant treatment could guide initial antidepressant therapy. To assess for neuroimaging biomarkers for antidepressant selection in early antidepressant treatment. Prospective. A total of 85 MDD patients from the major site and 33 MDD patients from an out-of-sample test site. A 3.0 T, T1-weighted imaging using a magnetization-prepared rapid acquisition gradient-echo sequence and diffusion tensor imaging (DTI) using an echo-planar sequence. Baseline DTI data of patients who achieved early improvement after 2-weeks of antidepressant treatment (selective serotonin reuptake inhibitors [SSRI] or serotonin-norepinephrine reuptake inhibitors [SNRI]) were analyzed. An ensemble model was constructed using data from the major site and then applied to assess the early response of patients at the out-of-sample test site. Support vector machine combined with leave-one-out cross-validation were applied to construct the whole model from individual base models from different brain regions. Discriminative biomarkers were evaluated by calculating the changes in sensitivity and specificity obtained when removing a single base model from the whole model, the base model being removed changing in each run. Training performance over MDD patients at the major site achieved 75% accuracy while performance with accuracy of 70% was achieved in the out-of-sample test site. Assessing sensitivity and specificity changes following the removal of single base models from the prominent model highlighted the functions of two neural circuitries: SSRI-related emotion regulation circuitry, centered on the hippocampus (sensitivity changes: 10%) and amygdala (sensitivity changes: 11%); and SNRI-related emotion and reward circuitry, centered on the putamen (specificity changes: 8%) and orbital part of superior frontal gyrus (specificity changes: 12%). These findings support future research on clinical antidepressant selection for MDD. 1 TECHNICAL EFFICACY: Stage 2.

Multifaceted Chromatin Structure and Transcription Changes in Plant Stress Response.

Sessile plants are exposed throughout their existence to environmental abiotic and biotic stress factors, such as cold, heat, salinity, drought, dehydration, submergence, waterlogging, and pathogen infection. Chromatin organization affects genome stability, and its dynamics are crucial in plant stress responses. Chromatin dynamics are epigenetically regulated and are required for stress-induced transcriptional regulation or reprogramming. Epigenetic regulators facilitate the phenotypic plasticity of development and the survival and reproduction of plants in unfavorable environments, and they are highly diversified, including histone and DNA modifiers, histone variants, chromatin remodelers, and regulatory non-coding RNAs. They contribute to chromatin modifications, remodeling and dynamics, and constitute a multilayered and multifaceted circuitry for sophisticated and robust epigenetic regulation of plant stress responses. However, this complicated epigenetic regulatory circuitry creates challenges for elucidating the common or differential roles of chromatin modifications for transcriptional regulation or reprogramming in different plant stress responses. Particularly, interacting chromatin modifications and heritable stress memories are difficult to identify in the aspect of chromatin-based epigenetic regulation of transcriptional reprogramming and memory. Therefore, this review discusses the recent updates from the three perspectives—stress specificity or dependence of transcriptional reprogramming, the interplay of chromatin modifications, and transcriptional stress memory in plants. This helps solidify our knowledge on chromatin-based transcriptional reprogramming for plant stress response and memory.

Phosphorylation on PstP Regulates Cell Wall Metabolism and Antibiotic Tolerance in Mycobacterium smegmatis.

Mycobacterium tuberculosis and its relatives, like many bacteria, have dynamic cell walls that respond to environmental stresses. Modulation of cell wall metabolism in stress is thought to be responsible for decreased permeability and increased tolerance to antibiotics. The signaling systems that control cell wall metabolism under stress, however, are poorly understood. Here, we examine the cell wall regulatory function of a key cell wall regulator, the serine/threonine phosphatase PstP, in the model organism Mycobacterium smegmatis We show that the peptidoglycan regulator CwlM is a substrate of PstP. We find that a phosphomimetic mutation, pstP T171E, slows growth, misregulates both mycolic acid and peptidoglycan metabolism in different conditions, and interferes with antibiotic tolerance. These data suggest that phosphorylation on PstP affects its activity against various substrates and is important in the transition between growth and stasis.IMPORTANCE Regulation of cell wall assembly is essential for bacterial survival and contributes to pathogenesis and antibiotic tolerance in mycobacteria, including pathogens such as Mycobacterium tuberculosis However, little is known about how the cell wall is regulated in stress. We describe a pathway of cell wall modulation in Mycobacterium smegmatis through the only essential Ser/Thr phosphatase, PstP. We showed that phosphorylation on PstP is important in regulating peptidoglycan metabolism in the transition to stasis and mycolic acid metabolism in growth. This regulation also affects antibiotic tolerance in growth and stasis. This work helps us to better understand the phosphorylation-mediated cell wall regulation circuitry in Mycobacteria.

Voltage and Frequency Controller for PMSG-Based Small-Hydro Power Generation

This paper deals with the implementation of voltage and frequency controller (VFC) of a small-hydro system using permanent magnet synchronous generator (PMSG) supplying power to isolated loads in remote areas. An improved second-order generalized integrator control technique is presented for controlling voltage source converter (VSC) of VFC. A circuitry for voltage and frequency regulation across a 230 V, 50 Hz, 3.7 kW PMSG feeding three-phase consumer loads is presented in this work. The VSC is used for regulating voltage constant at the generator terminals and also to ensure balanced stator currents, stabilized DC link voltage and current harmonics mitigation at linear/nonlinear and balanced/unbalanced loading conditions. The VFC is used for maintaining frequency intact by supplying excess power in the dump load. This system is modelled and simulated in MATLAB/Simulink environment. Simulated and experimental results demonstrate that the generated voltage and frequency are regulated under dynamic changes in consumer loads.

Exploring valence bias as a metric for frontoamygdalar connectivity and depressive symptoms in childhood.

Negativity bias is a core feature of depression that is associated with dysfunctional frontoamygdalar connectivity; this pathway is associated with emotion regulation and sensitive to neurobiological change during puberty. We used a valence bias task (ratings of emotional ambiguity) as a potential early indicator of depression risk and differences in frontoamygdalar connectivity. Previous work using this task demonstrated that children normatively have a negative bias that attenuates with maturation. Here, we test the hypothesis that persistence of this negativity bias as maturation ensues may reveal differences in emotion regulation development, and may be associated with increased risk for depression. In children aged 6-13years, we tested the moderating role of puberty on relationships between valence bias, depressive symptoms, and frontoamygdalar connectivity. A negative bias was associated with increased depressive symptoms for those at more advanced pubertal stages (within this sample) and less regulatory frontoamygdalar connectivity, whereas a more positive bias was associated with more regulatory connectivity patterns. These data suggest that with maturation, individual differences in positivity biases and associated emotion regulation circuitry confer a differential risk for depression. Longitudinal work is necessary to determine the directionality of these effects and explore the influence of early life events.

Diverse Mechanisms and Circuitry for Global Regulation by the RNA-Binding Protein CsrA.

The carbon storage regulator (Csr) or repressor of stationary phase metabolites (Rsm) system of Gammaproteobacteria is among the most complex and best-studied posttranscriptional regulatory systems. Based on a small RNA-binding protein, CsrA and homologs, it controls metabolism, physiology, and bacterial lifestyle decisions by regulating gene expression on a vast scale. Binding of CsrA to sequences containing conserved GGA motifs in mRNAs can regulate translation, RNA stability, riboswitch function, and transcript elongation. CsrA governs the expression of dozens of transcription factors and other regulators, further expanding its influence on cellular physiology, and these factors can participate in feedback to the Csr system. Expression of csrA itself is subject to autoregulation via translational inhibition and indirect transcriptional activation. CsrA activity is controlled by small noncoding RNAs (sRNAs), CsrB and CsrC in Escherichia coli, which contain multiple high affinity CsrA binding sites that compete with those of mRNA targets. Transcription of CsrB/C is induced by certain nutrient limitations, cellular stresses, and metabolites, while these RNAs are targeted for degradation by the presence of a preferred carbon source. Consistent with these findings, CsrA tends to activate pathways and processes that are associated with robust growth and repress stationary phase metabolism and stress responses. Regulatory loops between Csr components affect the signaling dynamics of the Csr system. Recently, systems-based approaches have greatly expanded our understanding of the roles played by CsrA, while reinforcing the notion that much remains to be learned about the Csr system.

Involvement of brainstem noradrenergic system in cutaneous heat loss during exercise

The involvement of brainstem noradrenergic system in thermoregulation during exercise was evaluated by assessing the neuronal activation of A1, A2, locus coeruleus (LC) during exercise. Male Wistar rats weighing 280−330 g were used in the present study. Ninety minutes after exercise bout until fatigue, animals were anaesthesiated and brain removed and processed immunohistochemically for Fos protein and tyrosine hydroxylase in A1, A2 and LC and for Fos in POA subregions. Core and tail temperature were recorded during all running period by telemetry system. Heat storage rate (HSR, cal.min−1), maximum tail vasoconstriction (°C) and vasodilatation threshold (°C) were calculated and correlated with Fos expression in all nuclei studied. Fos expression in LC correlated inversely with maximum tail skin vasoconstriction (r = −0.787, p < 0.03) and HSR (r = −0.834, p < 0.02) and positively to time to fatigue (r = 0.862, p < 0.01). A1 nucleus showed an inverse correlation with tail skin vasodilatation threshold (r = −0.861, p < 0.01). Fos expression in LC correlated inversely with Fos expression in the median (MnPO, r = −0.909, p < 0.01) and medial preoptic nucleus (MPOM, r = −0.942, p < 0.05). Our results bring further evidences that noradrenergic neurons from LC and A1 nuclei are involved in cutaneous heat loss mechanisms during exercise. LC nucleus probably modulates the sympathetic tonus of tail artery and integrates the central network LC / POA that could represent an important circuitry of temperature regulation during exercise. Also, noradrenergic neurons from A1 nucleus could be involved in cutaneous heat loss during exercise by modulating of vasodilatation threshold.

Amygdala Circuitry During Neurofeedback Training and Symptoms' Change in Adolescents With Varying Depression.

Typical adolescents have increased limbic engagement unchecked by regulatory medial prefrontal cortex (PFC) activity as well as heightened self-focus. The resulting emotion dysregulation and self-focused rumination make adolescents more susceptible to depression and suicide attempts. Heightened self-focus converges with mental illness among depressed adolescents, who deploy exaggerated attention to negative self-relevant stimuli and neglect positive ones as part of depression’s phenomenology. This results in rigid negative self-representations during an identity formative period with potential lifetime repercussions. Current empirically supported treatments fail to allay recurrent depression. Evidence-based interventions for illnesses linked to suicide ideation and attempts (e.g., depression) underperform across the lifespan. This could be because current treatments are not successful in altering pervasive negative self-representations and affect dysregulation, which is known to be a risk factor of chronic depression. This study departs from the premise that increasing positive self-processing might be protective against chronic depression particularly during adolescence. The present research is a novel investigation of neurofeedback as a potential treatment alternative for adolescent depression. To enhance positive self-processing, we used the happy self-face as a cue to initiate neurofeedback from the bilateral amygdala and hippocampus and adolescents attempted to upregulate that limbic activity through the recall of positive autobiographical memories. We identified limbic functional circuitry engaged during neurofeedback and links to short-term symptoms’ change in depression and rumination. We found that depressed youth showed greater right amygdala to right frontocortical connectivity and lower left amygdala to right frontocortical connectivity compared to healthy controls during neurofeedback vs. control conditions. Depressed youth also showed significant symptom reduction. Connectivity between the right amygdala and frontocortical regions was positively correlated with rumination and depression change, but connectivity between frontocortical regions and the left amygdala was negatively correlated with depression change. The results suggest that depressed youth might engage implicit emotion regulation circuitry while healthy youth recruit explicit emotion regulation circuits during neurofeedback. Our findings support a compensatory approach (i.e., target the right amygdala) during future neurofeedback interventions in depressed youth. Future work ought to include a placebo condition or group.

Pyruvate kinase M2 in lung APCs regulates Alternaria-induced airway inflammation

Sensitivity to allergenic fungi (Alternaria alternata) is associated with acute, severe asthma attacks. Antigen presenting cells (APCs) in the lung sense environmental perturbations that induce cellular stress and metabolic changes and are critical for allergic airway inflammation. However, the mechanisms underlying such environmental sensing by APCs in the lung remains unclear. Here we show that acute Alternaria challenge rapidly induces neutrophil accumulation in airways, and alter expressions of Pyruvate Kinase (PKM2) and hypoxia-inducible factor -1α (Hif-1α) that correlates with proinflammatory mediator release. Blockade of IL33 signaling in vivo led to reduce oxidative stress and glycolysis in lung APCs. Lung-specific ablation of CD11c+ cells abrogates Alternaria-induced neutrophil accumulation and inflammation. Furthermore, administration of Alternaria into the airways stimulated APCs and elevate the expression of Glut-1. Mechanistically, we establish that PKM2 is a critical modulator of lung APC activation in Alternaria-induced acute inflammation. Allosteric activation of PKM2 by a small molecule ML265 or siRNA-mediated knock down correlated negatively with glycolysis and activation of APCs. These results collectively demonstrates that PKM2-mediated glycolytic reprogramming by fungal allergen Alternaria influences lung APC activation, thereby promotes acute airway inflammation. Our data support a model in which Alternaria sensitization in airways induce a circuitry of glycolysis and PKM2 regulation that confers an acute activation of APCs in the lung, whose targeting might represent a strategy for asthma treatment.

Trait Anxiety Mediated by Amygdala Serotonin Transporter in the Common Marmoset.

High trait anxiety is associated with altered activity across emotion regulation circuitry and a higher risk of developing anxiety disorders and depression. This circuitry is extensively modulated by serotonin. Here, to understand why some people may be more vulnerable to developing affective disorders, we investigated whether serotonin-related gene expression across the brain's emotion regulation circuitry may underlie individual differences in trait anxiety using the common marmoset (Callithrix jacchus, mixed sexes) as a model. First, we assessed the association of region-specific expression of the serotonin transporter (SLC6A4) and serotonin receptor (HTR1A, HTR2A, HTR2C) genes with anxiety-like behavior; and second, we investigated their causal role in two key features of the high trait anxious phenotype: high responsivity to anxiety-provoking stimuli and an exaggerated conditioned threat response. While the expression of the serotonin receptors did not show a significant relationship with anxiety-like behavior in any of the targeted brain regions, serotonin transporter expression, specifically within the right ventrolateral prefrontal cortex (vlPFC) and most strongly in the right amygdala, was associated positively with anxiety-like behavior. The causal relationship between amygdala serotonin levels and an animal's sensitivity to threat was confirmed via direct amygdala infusions of a selective serotonin reuptake inhibitor (SSRI), citalopram. Both anxiety-like behaviors, and conditioned threat-induced responses were reduced by the blockade of serotonin reuptake in the amygdala. Together, these findings provide evidence that high amygdala serotonin transporter expression contributes to the high trait anxious phenotype and suggest that reduction of threat reactivity by SSRIs may be mediated by their actions in the amygdala.SIGNIFICANCE STATEMENT Findings here contribute to our understanding of how the serotonin system underlies an individual's expression of threat-elicited negative emotions such as anxiety and fear within nonhuman primates. Exploration of serotonergic gene expression across brain regions implicated in emotion regulation revealed that serotonin transporter gene expression in the ventrolateral prefrontal cortex (vlPFC) and most strongly in the amygdala, but none of the serotonin receptor genes, were predictive of interindividual differences in anxiety-like behavior. Targeting of amygdala serotonin reuptake with selective serotonin reuptake inhibitors (SSRIs) confirmed the causal relationship between amygdala serotonin transporter and an animal's sensitivity to threat by reversing expression of two key features of the high trait-like anxiety phenotype: high responsivity to anxiety-provoking uncertain threat and responsivity to certain conditioned threat.

Neighborhood Disadvantage Moderates the Association Between Age and Amygdala Resting State Functional Connectivity

Converging evidence suggests that early life adversity precipitates altered maturation of emotion regulation neurocircuitry, which may underlie increased psychiatric risk in adversity-exposed individuals. However, it is unknown whether neighborhood poverty, a more protracted form of adversity, has a similar effect on emotion regulation circuitry.

Targeting Emotion Regulation Circuitry With a Psychobehavioral Intervention to Reduce Hopelessness in Bipolar Disorder

Hopelessness is an important behavioral construct that is a robust predictor of suicide. The identification and targeting of brain circuitry underlying hopelessness may therefore help in preventing suicide, yet, such study is rare. This study examined hopelessness in bipolar disorder (BD), which carries one of the highest risks for suicide. Using magnetic resonance imaging (MRI) data, we investigated (a) regional and connectome-based patterns of brain circuitry dysfunction that underlie hopelessness, and (b) aspects of the circuitry that change in association with reductions in hopelessness following a 12-week psychobehavioral intervention, Brain Emotion Circuitry Targeted SelfMonitoring and Regulation Therapy for Emotion Regulation (BE-SMART-ER).

Transcranial Photobiomodulation: A Simulation-Based Light Dosimetry Study Across Lifespan

While some brain disorders are typical of senescence and others are more prevalent in youth, many occur at any age across the lifespan. Therapeutic interventions are often dosed differently depending on age; a proper understanding of how transcranial near-infrared light should be dosed at different ages is lacking. In line with our prior work that refers to affective disorders (e.g. major depressive disorder) and dysfunction in the emotion regulation circuitry, this work addresses this point by accurate light modeling across the lifespan.

Elucidating Multimodal Neural Marker Predictors of Future Vulnerability to Mood Disorders Across Infancy, Childhood and Adolescence

In ongoing studies, using multimodal neuroimaging, we are examining prefrontal cortical-striatal-amygdala emotional regulation circuitry in infants, and youth at familial risk for mood disorders, to identify neural predictors of future risk for these disorders from infancy to adolescence.

Neural Subtypes of Euthymic Bipolar I Disorder Characterized by Emotion Regulation Circuitry

BackgroundCurrent diagnostic strategy for bipolar disorders relies on symptomological classification. Yet, responses to both pharmacological and psychotherapeutic treatments vary widely, suggesting that underlying neuropathological differences are not well defined by current nosology. Classifying patients with bipolar disorder based on emotion regulation network (ERN) activation may account for some of the heterogeneity within the disorder. MethodsEuthymic participants diagnosed with bipolar I disorder (n = 86) and healthy subjects (n = 80) underwent functional magnetic resonance imaging scans while engaged in emotional reappraisal of negative stimuli. After determining average regional activations in key network regions, we applied agglomerative hierarchical clustering to identify subtypes of bipolar disorder. Next, we examined relations among neural subtypes, demographic variables, and mood symptoms. ResultsAnalyses revealed two primary neural subtypes of euthymic bipolar I disorder participants. The first subtype, ERN cluster 1, was characterized by increased amygdala activation and slightly increased ventrolateral prefrontal and subgenual cingulate activation, whereas ERN cluster 2 was defined by decreased amygdala activation with wider-spread prefrontal activation. Cluster 1 was associated with a higher number of hospitalizations for depression (odds ratio = 1.30, 95% confidence interval = 1.02–1.64) and later onset of manic episodes (odds ratio = 1.06, 95% confidence interval = 1.00–21.13) than cluster 2. ERN clusters of healthy subjects differed from bipolar disorder clusters and were defined by differential activation of the prefrontal cortex. ERN clusters of healthy subjects, which differed from bipolar disorder clusters, were defined by differential activation of the prefrontal cortex. ConclusionsEmotion regulation circuitry can distinguish neurobiological subtypes of bipolar disorder in the euthymic state. These subtypes, which are differentially associated with indices of illness severity and subsyndromal affective symptoms, may help to inform relapse risk and more personalized treatment approaches.

MYC's Fine Line Between B Cell Development and Malignancy.

The transcription factor MYC is transiently expressed during B lymphocyte development, and its correct modulation is essential in defined developmental transitions. Although temporary downregulation of MYC is essential at specific points, basal levels of expression are maintained, and its protein levels are not completely silenced until the B cell becomes fully differentiated into a plasma cell or a memory B cell. MYC has been described as a proto-oncogene that is closely involved in many cancers, including leukemia and lymphoma. Aberrant expression of MYC protein in these hematological malignancies results in an uncontrolled rate of proliferation and, thereby, a blockade of the differentiation process. MYC is not activated by mutations in the coding sequence, and, as reviewed here, its overexpression in leukemia and lymphoma is mainly caused by gene amplification, chromosomal translocations, and aberrant regulation of its transcription. This review provides a thorough overview of the role of MYC in the developmental steps of B cells, and of how it performs its essential function in an oncogenic context, highlighting the importance of appropriate MYC regulation circuitry.

Structural and Functional Connectivity of the Anterior Cingulate Cortex in Patients With Borderline Personality Disorder.

BackgroundEmerging evidences supported the hypothesis that emotional dysregulation results from aberrant connectivity within the fronto-limbic neural networks in patients with borderline personality disorder (BPD). Considering its important role in emotional regulation, the anterior cingulate cortex (ACC) has not yet been fully explored in BPD patients. Therefore, using the seed-based resting state functional connectivity (rsFC) and probabilistic fiber tracking, we aimed to explore the alterations of functional and structural connectivity (SC) of the ACC in patients with BPD.MethodsA cohort of 50 unmedicated, young BPD patients and 54 sex-, age-, and education-matched healthy controls (HCs) completed psychological tests and underwent rs-fMRI and diffuse tensor imaging (DTI) scanning. Rs-FC analysis and probabilistic fiber tracking were used to plot SC and FC of the ACC.ResultsWith the left ACC selected as a seed, BPD patients exhibited increased rsFC and abnormal SC with the right middle frontal gyrus (MFG), and decreased rsFC with the left middle temporal gyrus (MTG), compared with HCs. Additionally, negative cognitive emotion regulation and depressive symptoms both correlated negatively with the rsFC of the left ACC in BPD patients.ConclusionAbnormal SC and FC of the ACC underlie the deficient emotional regulation circuitry in BPD patients. Such alterations may be important biomarkers of BPD and thus could point to potential BPD treatment targets.