Cocaine-induced neuron subtype mitochondrial dynamics through Egr3 transcriptional regulation.

Mitochondrial function is required for brain energy homeostasis and neuroadaptation. Recent studies demonstrate that cocaine affects mitochondrial dynamics and morphological characteristics within the nucleus accumbens (NAc). Further, mitochondria are differentially regulated by cocaine in dopamine receptor-1 containing medium spiny neurons (D1-MSNs) vs dopamine receptor-2 (D2)-MSNs. However, there is little understanding into cocaine-induced transcriptional mechanisms and their role in regulating mitochondrial processes. Here, we demonstrate that cocaine enhances binding of the transcription factor, early growth response factor 3 (Egr3), to nuclear genes involved in mitochondrial function and dynamics. Moreover, cocaine exposure regulates mRNA of these mitochondria-associated nuclear genes in both contingent or noncontingent cocaine administration and in both rodent models and human postmortem tissue. Interestingly, several mitochondrial nuclear genes showed distinct profiles of expression in D1-MSNs vs D2-MSNs, with cocaine exposure generally increasing mitochondrial-associated nuclear gene expression in D1-MSNs vs suppression in D2-MSNs. Further, blunting Egr3 expression in D1-MSNs blocks cocaine-enhancement of the mitochondrial-associated transcriptional coactivator, peroxisome proliferator-activated receptor gamma coactivator (PGC1α), and the mitochondrial fission molecule, dynamin related protein 1 (Drp1). Finally, reduction of D1-MSN Egr3 expression attenuates cocaine-induced enhancement of small-sized mitochondria, causally demonstrating that Egr3 regulates mitochondrial morphological adaptations. Collectively, these studies demonstrate cocaine exposure impacts mitochondrial dynamics and morphology by Egr3 transcriptional regulation of mitochondria-related nuclear gene transcripts; indicating roles for these molecular mechanisms in neuronal function and plasticity occurring with cocaine exposure.

The Atomic-Level Structure of Cementitious Calcium Aluminate Silicate Hydrate.

Despite use of blended cements containing significant amounts of aluminum for over 30 years, the structural nature of aluminum in the main hydration product, calcium aluminate silicate hydrate (C-A-S-H), remains elusive. Using first-principles calculations, we predict that aluminum is incorporated into the bridging sites of the linear silicate chains and that at high Ca:Si and H2O ratios, the stable coordination number of aluminum is six. Specifically, we predict that silicate-bridging [AlO2(OH)4]5- complexes are favored, stabilized by hydroxyl ligands and charge balancing calcium ions in the interlayer space. This structure is then confirmed experimentally by one- and two-dimensional dynamic nuclear polarization enhanced 27Al and 29Si solid-state NMR experiments. We notably assign a narrow 27Al NMR signal at 5 ppm to the silicate-bridging [AlO2(OH)4]5- sites and show that this signal correlates to 29Si NMR signals from silicates in C-A-S-H, conflicting with its conventional assignment to a "third aluminate hydrate" (TAH) phase. We therefore conclude that TAH does not exist. This resolves a long-standing dilemma about the location and nature of the six-fold-coordinated aluminum observed by 27Al NMR in C-A-S-H samples.

Zinner syndrome: an unusual cause of bladder outflow obstruction.

Zinner syndrome is a rare condition comprising a triad of unilateral renal agenesis, ipsilateral seminal vesicle obstruction and ipsilateral ejaculatory duct obstruction. The mutual embryological origins of the seminal vesicle and the ureteral bud result in both anomalous genital and urinary tracts. We present the case of a 39-year-old patient where the initial presentation of this condition was bladder outflow obstruction. In this paper, we discuss the embryological origin of this condition, the range of imaging tools used to diagnose Zinner syndrome and the inherent benefits and shortcomings of each modality.

Recreational ketamine: from pleasure to pain.

Ketamine has become increasingly recognized as a drug of recreational use. Individuals using significant amounts have developed symptoms including a small painful bladder, ureteric obstruction, papillary necrosis and hepatic dysfunction. The present paper examines the current literature on the relationship between ketamine use and these symptoms. Our own clinical experience and the data available clarify the causal relationship, and further data help to elucidate the mechanism of damage. On the basis of continued work and development with patients who are ketamine users we suggest an assessment and treatment regime that includes cessation of ketamine use and adequate analgesia to overcome symptoms. In conclusion, it is important for medical practitioners who encounter patients with these symptoms to ask about recreational drug use. Ketamine remains a safe and effective drug to use under appropriate medical supervision. Patients identified as suffering from this syndrome will need to be referred to a urological unit with an interest in the treatment of the condition.