NECAB2 is an endosomal protein important for striatal function.

Synaptic signaling depends on ATP generated by mitochondria. Dysfunctional mitochondria shift the redox balance towards a more oxidative environment. Due to extensive connectivity, the striatum is especially vulnerable to mitochondrial dysfunction.

Bax inhibitor-1 deficiency leads to obesity by increasing Ca-dependent insulin secretion.

Transmembrane BAX inhibitor motif containing 6 (TMBIM6), also known as Bax inhibitor-1, is an evolutionarily conserved protein involved in endoplasmic reticulum (ER) function. TMBIM6 is an ER Ca leak channel and its deficiency enhances susceptibility to ER stress due to inhibition of the ER stress sensor IRE1α. It was previously shown that TMBIM6 overexpression improves glucose metabolism and that TMBIM6 knockout mice develop obesity.

Dimethyl Fumarate Induces Glutathione Recycling by Upregulation of Glutathione Reductase.

Neuronal degeneration in multiple sclerosis has been linked to oxidative stress. Dimethyl fumarate (DMF) is an effective oral therapeutic option shown to reduce disease activity and progression in patients with relapsing-remitting multiple sclerosis. DMF activates the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) leading to increased synthesis of the major cellular antioxidant glutathione (GSH) and prominent neuroprotection .

TOX3 regulates neural progenitor identity.

The human genomic locus for the transcription factor TOX3 has been implicated in susceptibility to restless legs syndrome and breast cancer in genome-wide association studies, but the physiological role of TOX3 remains largely unknown. We found Tox3 to be predominantly expressed in the developing mouse brain with a peak at embryonic day E14 where it co-localizes with the neural stem and progenitor markers Nestin and Sox2 in radial glia of the ventricular zone and intermediate progenitors of the subventricular zone. Tox3 is also expressed in neural progenitor cells obtained from the ganglionic eminence of E15 mice that express Nestin, and it specifically binds the Nestin promoter in chromatin immunoprecipitation assays.

BAX inhibitor-1 is a Ca(2+) channel critically important for immune cell function and survival.

The endoplasmic reticulum (ER) serves as the major intracellular Ca(2+) store and has a role in the synthesis and folding of proteins. BAX (BCL2-associated X protein) inhibitor-1 (BI-1) is a Ca(2+) leak channel also implicated in the response against protein misfolding, thereby connecting the Ca(2+) store and protein-folding functions of the ER. We found that BI-1-deficient mice suffer from leukopenia and erythrocytosis, have an increased number of splenic marginal zone B cells and higher abundance and nuclear translocation of NF-κB (nuclear factor-κ light-chain enhancer of activated B cells) proteins, correlating with increased cytosolic and ER Ca(2+) levels.

The transmembrane Bax inhibitor motif (TMBIM) containing protein family: Tissue expression, intracellular localization and effects on the ER CA²⁺-filling state.

Bax inhibitor-1 (BI-1) is an evolutionarily conserved pH-dependent Ca²⁺ leak channel in the endoplasmic reticulum and the founding member of a family of six highly hydrophobic mammalian proteins named transmembrane BAX inhibitor motif containing (TMBIM) 1-6 with BI-1 being TMBIM6. Here we compared the structure, subcellular localization, tissue expression and the effect on the cellular Ca²⁺ homeostasis of all family members side by side. We found that all TMBIM proteins possess the di-aspartyl pH sensor responsible for pH sensing identified in TMBIM6 and its bacterial homologue BsYetJ.

Estimating the activity of transcription factors by the effect on their target genes.

Motivation: Understanding regulation of transcription is central for elucidating cellular regulation. Several statistical and mechanistic models have come up the last couple of years explaining gene transcription levels using information of potential transcriptional regulators as transcription factors (TFs) and information from epigenetic modifications. The activity of TFs is often inferred by their transcription levels, promoter binding and epigenetic effects.

Protein kinase inhibitor β enhances the constitutive activity of G-protein-coupled zinc receptor GPR39.

GPR39 is a G-protein-coupled zinc receptor that protects against diverse effectors of cell death. Its protective activity is mediated via constitutive activation of Gα13 and the RhoA pathway, leading to increased SRE (serum-response element)-dependent transcription; the zinc-dependent immediate activation of GPR39 involves Gq-mediated increases in cytosolic Ca2+ and Gs coupling leading to increased cAMP levels. We used the cytosolic and soluble C-terminus of GPR39 in a Y2H (yeast-2-hybrid) screen for interacting proteins, thus identifying PKIB (protein kinase A inhibitor β).

Expression of genes encoding the calcium signalosome in cellular and transgenic models of Huntington's disease.

Huntington's disease (HD) is a hereditary neurodegenerative disease caused by the expansion of a polyglutamine stretch in the huntingtin (HTT) protein and characterized by dysregulated calcium homeostasis. We investigated whether these disturbances are correlated with changes in the mRNA level of the genes that encode proteins involved in calcium homeostasis and signaling (i.e.

Mitochondrial function and energy metabolism in neuronal HT22 cells resistant to oxidative stress.

Background And Purpose: The hippocampal cell line HT22 is an excellent model for studying the consequences of endogenous oxidative stress. Extracellular glutamate depletes cellular glutathione by blocking the glutamate/cystine antiporter system xc-. Glutathione depletion induces a well-defined programme of cell death characterized by an increase in reactive oxygen species and mitochondrial dysfunction.

Endo- and exopolygalacturonases of Ralstonia solanacearum are inhibited by polygalacturonase-inhibiting protein (PGIP) activity in tomato stem extracts.

Polygalacturonases (PGs) of wild-type and non-virulent phenotype conversion mutant (PC) strains of Ralstonia solanacearum were compared by investigating their activities and their inhibition by polygalacturonase-inhibiting proteins (PGIPs) from tomato stems. In cultures of wild-type strain ToUdk2, slimy (s), retarded slimy (rs) and non-slimy (ns) colonies appeared. The conversion of the 's' into the 'rs' colony form coincided with the beginning of PG production.

The effects of training in time-limited dynamic psychotherapy: changes in therapeutic outcome.

The present study explored the effects on therapeutic outcomes of training therapists in brief manualized therapy. As part of the Vanderbilt II project, each of 16 therapists (8 psychiatrists and 8 clinical psychologists) treated 2 moderately disturbed adult patients using his or her customary short-term treatment methods; they then received a year of training in a manualized form of brief dynamic therapy, Time-Limited Dynamic Psychotherapy (TLDP); finally, they administered TLDP to 2 additional patients. It was hypothesized that training would result in improved outcomes generally and that differentially greater improvement would be seen in patients commonly considered less suitable for brief dynamic therapy.

Effects of training in time-limited dynamic psychotherapy: mediators of therapists' responses to training.

Sixteen therapists were enrolled in a year-long manualized training program as part of the Vanderbilt II study of time-limited dynamic psychotherapy (TLDP). The training program successfully changed therapists' interventions in line with prescriptions of the TLDP manual, but some unanticipated changes ran counter to the intent of the training, including increased negative interpersonal transactions as indicated by process measures such as the Structural Analysis of Social Behavior (SASB). We examined therapist variables, patient variables, and training variables that appeared to mediate therapist responses to the training program.

Effects of training in time-limited dynamic psychotherapy: changes in therapist behavior.

Sixteen therapists participated in a year-long manualized training program as part of the Vanderbilt II study of time-limited dynamic psychotherapy. Changes in therapist behavior were measured with the Vanderbilt Therapeutic Strategies Scale (an adherence measure), the Vanderbilt Psychotherapy Process Scale (VPPS), and interpersonal process codings using the Structural Analysis of Social Behavior (SASB). The training program successfully changed therapists' technical interventions in line with the manualized protocol.

Patient and therapist introject, interpersonal process, and differential psychotherapy outcome.

The Structural Analysis of Social Behavior (SASB; Benjamin, 1974, 1982, 1984) system was used to study the interpersonal process between patient and therapist in the 3rd session of 14 therapeutic dyads. Dyads were grouped into good and poor outcomes cases (n = 7) on the basis of the amount of change in the patients' introject as measured by the INTREX Introject Questionnaire (Benjamin, 1983). Strong support was found for the following hypotheses based on interpersonal theory, linking therapists' introject state, interpersonal process in therapy, and outcome: (a) Poor outcome cases (no introject change) were typified by interpersonal behaviors by the therapist that confirmed a negative patient introject; (b) the number of therapists' statements that were subtly hostile and controlling was highly correlated with the number of self-blaming statements by the patients; (c) therapists with disaffiliative introjects tended to engage in a much higher level of problematic interpersonal processes that have been associated with poor outcome.

Converging evidence for identification of recurrent relationship themes: comparison of two methods.

The therapeutic process is complex, and researchers and clinicians alike search for organizing principles or underlying structures that will reduce this complexity and thereby augment the efficacy of their respective endeavors. As other papers in this issue indicate, one such organizing principle is the concept of a recurring relationship theme that can be identified in the patient's descriptions of current and past relationships, as well as observed in the patient's interaction with the therapist. This concept has its origins in Freud's discovery of the transference phenomenon (1912), wherein the patient reenacts early relationships with significant others in the relationship with the analyst, and in Sullivan's interpersonal theory of psychiatry, with its central tenet that "personality is the relatively enduring pattern of recurrent interpersonal situations which characterize a human life" (1953, pp.