Loss-of-function G6PD variant moderated high-fat diet-induced obesity, adipocyte hypertrophy, and fatty liver in male rats.

Obesity is a major risk factor for liver and cardiovascular diseases. However, obesity-driven mechanisms that contribute to the pathogenesis of multiple organ diseases are still obscure and treatment is inadequate. We hypothesized that increased , glucose-6-phosphate dehydrogenase (G6PD), the key rate-limiting enzyme in the pentose shunt, is critical in evoking metabolic reprogramming in multiple organs and is a significant contributor to the pathogenesis of liver and cardiovascular diseases. G6PD is induced by a carbohydrate-rich diet and insulin. Long-term (8 months) high-fat diet (HFD) feeding increased body weight and elicited metabolic reprogramming in visceral fat, liver, and aorta, of the wild-type rats. In addition, HFD increased inflammatory chemokines in visceral fat. Interestingly, CRISPR-edited loss-of-function Mediterranean G6PD variant (G6PDS188F) rats, which mimic human polymorphism, moderated HFD-induced weight gain and metabolic reprogramming in visceral fat, liver, and aorta. The G6PDS188F variant prevented HFD-induced CCL7 and adipocyte hypertrophy. Furthermore, the G6PDS188F variant increased Magel2 - a gene encoding circadian clock-related protein that suppresses obesity associated with Prader-Willi syndrome - and reduced HFD-induced non-alcoholic fatty liver. Additionally, the G6PDS188F variant reduced aging-induced aortic stiffening. Our findings suggest G6PD is a regulator of HFD-induced obesity, adipocyte hypertrophy, and fatty liver.

Recent updates of eye movement abnormalities in patients with schizophrenia: A scoping review.

AIM: Although eye-tracking technology expands beyond capturing eye data just for the sole purpose of ensuring participants maintain their gaze at the presented fixation cross, gaze technology remains of less importance in clinical research. Recently, impairments in visual information encoding processes indexed by novel gaze metrics have been frequently reported in patients with schizophrenia. This work undertakes a scoping review of research on saccadic dysfunctions and exploratory eye movement deficits among patients with schizophrenia. It gathers promising pieces of evidence of eye movement abnormalities in attention-demanding tasks on the schizophrenia spectrum that have mounted in recent years and their outcomes as potential biological markers. METHODS: The protocol was drafted based on PRISMA for scoping review guidelines. Electronic databases were systematically searched to identify articles published between 2010 and 2020 that examined visual processing in patients with schizophrenia and reported eye movement characteristics as potential biomarkers for this mental illness. RESULTS: The use of modern eye-tracking instrumentation has been reported by numerous neuroscientific studies to successfully and non-invasively improve the detection of visual information processing impairments among the screened population at risk of and identified with schizophrenia. CONCLUSIONS: Eye-tracking technology has the potential to contribute to the process of early intervention and more apparent separation of the diagnostic entities, being put together by the syndrome-based approach to the diagnosis of schizophrenia. However, context-processing paradigms should be conducted and reported in equally accessible publications to build comprehensive models.

Carotid body type I cells engage flavoprotein and Pin1 for oxygen sensing.

Carotid body (CB) type I cells sense the blood Po2 and generate a nervous signal for stimulating ventilation and circulation when blood oxygen levels decline. Three oxygen-sensing enzyme complexes may be used for this purpose: 1) mitochondrial electron transport chain metabolism, 2) heme oxygenase 2 (HO-2)-generating CO, and/or 3) an NAD(P)H oxidase (NOX). We hypothesize that intracellular redox changes are the link between the sensor and nervous signals. To test this hypothesis type I cell autofluorescence of flavoproteins (Fp) and NAD(P)H within the mouse CB ex vivo was recorded as Fp/(Fp+NAD(P)H) redox ratio. CB type I cell redox ratio transiently declined with the onset of hypoxia. Upon reoxygenation, CB type I cells showed a significantly increased redox ratio. As a control organ, the non-oxygen-sensing sympathetic superior cervical ganglion (SCG) showed a continuously reduced redox ratio upon hypoxia. CN-, diphenyleneiodonium, or reactive oxygen species influenced chemoreceptor discharge (CND) with subsequent loss of O2 sensitivity and inhibited hypoxic Fp reduction only in the CB but not in SCG Fp, indicating a specific role of Fp in the oxygen-sensing process. Hypoxia-induced changes in CB type I cell redox ratio affected peptidyl prolyl isomerase Pin1, which is believed to colocalize with the NADPH oxidase subunit p47phox in the cell membrane to trigger the opening of potassium channels. We postulate that hypoxia-induced changes in the Fp-mediated redox ratio of the CB regulate the Pin1/p47phox tandem to alter type I cell potassium channels and therewith CND.

Autophagy induced by ionizing radiation promotes cell death over survival in human colorectal cancer cells.

Autophagy is commonly described as a cell survival mechanism and has been implicated in chemo- and radioresistance of cancer cells. Whether ionizing radiation induced autophagy triggers tumor cell survival or cell death still remains unclear. In this study the autophagy related proteins Beclin1 and ATG7 were tested as potential targets to sensitize colorectal carcinoma cells to ionizing radiation under normoxic, hypoxic and starvation conditions. Colony formation, apoptosis and cell cycle analysis revealed that knockdown of Beclin1 or ATG7 does not enhance radiosensitivity in HCT-116 cells. Furthermore, ATG7 knockdown led to an increased survival fraction under oxygen and glutamine starvation, indicating that ionizing radiation indeed induces autophagy which, however, leads to cell death finally. These results highlight that inhibition of autophagic pathways does not generally increase therapy success but may also lead to an unfavorable outcome especially under amino acid and oxygen restriction.

Initial microbial colonization of enamel in children with different levels of caries activity: An in situ study.

PURPOSE: To investigate patterns of overnight in situ microbial colonization of enamel in children. METHODS: Overall, 29 children (aged 5-9 years) participated in the study. Nine were caries-free with no decayed, missing, or filled teeth (DMFT), 11 were caries-rehabilitated (DMFT ≥ 2, no active carious lesions), and nine were caries-active (DMFT ≥ 2, at least two carious lesions). Bovine enamel samples were fixed on individual upper jaw splints stored overnight in situ. 4',6-diamidino-2-phenylindole (DAPI) combined with Concanavalin A staining was applied for fluorescence microscopic visualization of total adherent bacteria and glucans. Fluorescence in situ hybridization (FISH) was used for distinction of eubacteria, streptococci, and Candida albicans. Salivary samples were investigated for Streptococcus mutans (S. mutans) by using CRT bacteria test and yeasts with Calcofluor white (CFW) staining. RESULTS: With all fluorescence methods, bacteria but not Candida albicans were detected on enamel samples. No statistically significant differences were observed in distribution patterns of the adherent bacteria between the groups. CFW staining indicated fungal structures in saliva samples of all participants. Based on CRT test results, the lowest amount of S. mutans were observed in caries-free children. Thus, initial microbial colonization patterns of enamel in children are not influenced by caries activity. CLINICAL SIGNIFICANCE: Caries activity in children may influence the process of initial bioadhesion and thus distribution patterns of bacterial attachment to the enamel surface. Investigation of in situ biofilm formation might provide valuable insights regarding the varying caries susceptibility in children.

Health effects of cow's milk consumption in infants up to 3 years of age: a systematic review and meta-analysis.

OBJECTIVE: To summarize the best available evidence regarding the short- and long-term health effects of cow's milk intake in healthy, full-term infants up to 3 years of age. DESIGN: We conducted a systematic review and meta-analysis. SETTING: We searched MEDLINE (via PubMed), EMBASE and the Cochrane Library between 1960 and July 2013 and manually reviewed reference lists of pertinent articles. Two researchers independently reviewed abstracts and full-text articles and extracted relevant data. SUBJECTS: We included (randomized/non-randomized) controlled trials and observational studies. RESULTS: We included data from twenty-three studies (one randomized controlled trial, four non-randomized controlled trials, eight case-control studies and ten cohort studies) for the evidence synthesis. Pooled results of four studies revealed a higher risk of Fe-deficiency anaemia for infants consuming cow's milk compared with those consuming follow-on formula (relative risk=3·76; 95 % CI 2·73, 5·19). For type 1 diabetes mellitus, six out of seven case-control studies did not show a difference in the risk of developing this disease based on the age of introduction of cow's milk. We did not find negative associations for other health effects. CONCLUSIONS: Cow's milk consumption in infancy is associated with an increased risk of developing Fe-deficiency anaemia. Limiting cow's milk consumption may be important to ensure an adequate Fe intake for infants and toddlers. High-quality patient information for caregivers is needed on how infants' Fe requirements can be met.

Eye-tracking paradigms for the assessment of mild cognitive impairment: a systematic review.

Mild cognitive impairment (MCI), representing the 'transitional zone' between normal cognition and dementia, has become a novel topic in clinical research. Although early detection is crucial, it remains logistically challenging at the same time. While traditional pen-and-paper tests require in-depth training to ensure standardized administration and accurate interpretation of findings, significant technological advancements are leading to the development of procedures for the early detection of Alzheimer's disease (AD) and facilitating the diagnostic process. Some of the diagnostic protocols, however, show significant limitations that hamper their widespread adoption. Concerns about the social and economic implications of the increasing incidence of AD underline the need for reliable, non-invasive, cost-effective, and timely cognitive scoring methodologies. For instance, modern clinical studies report significant oculomotor impairments among patients with MCI, who perform poorly in visual paired-comparison tasks by ascribing less attentional resources to novel stimuli. To accelerate the Global Action Plan on the Public Health Response to Dementia 2017-2025, this work provides an overview of research on saccadic and exploratory eye-movement deficits among older adults with MCI. The review protocol was drafted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Electronic databases were systematically searched to identify peer-reviewed articles published between 2017 and 2022 that examined visual processing in older adults with MCI and reported gaze parameters as potential biomarkers. Moreover, following the contemporary trend for remote healthcare technologies, we reviewed studies that implemented non-commercial eye-tracking instrumentation in order to detect information processing impairments among the MCI population. Based on the gathered literature, eye-tracking-based paradigms may ameliorate the screening limitations of traditional cognitive assessments and contribute to early AD detection. However, in order to translate the findings pertaining to abnormal gaze behavior into clinical applications, it is imperative to conduct longitudinal investigations in both laboratory-based and ecologically valid settings.

20-Hydroxyeicosatetraenoic acid (20-HETE): Bioactions, receptors, vascular function, cardiometabolic disease and beyond.

Vascular function is dynamically regulated and dependent on a bevy of cell types and factors that work in concert across the vasculature. The vasoactive eicosanoid, 20-Hydroxyeicosatetraenoic acid (20-HETE) is a key player in this system influencing the sensitivity of the vasculature to constrictor stimuli, regulating endothelial function, and influencing the renin angiotensin system (RAS), as well as being a driver of vascular remodeling independent of blood pressure elevations. Several of these bioactions are accomplished through the ligand-receptor pairing between 20-HETE and its high-affinity receptor, GPR75. This 20-HETE axis is at the root of various vascular pathologies and processes including ischemia induced angiogenesis, arteriogenesis, septic shock, hypertension, atherosclerosis, myocardial infarction and cardiometabolic diseases including diabetes and insulin resistance. Pharmacologically, several preclinical tools have been developed to disrupt the 20-HETE axis including 20-HETE synthesis inhibitors (DDMS and HET0016), synthetic 20-HETE agonist analogues (20-5,14-HEDE and 20-5,14-HEDGE) and 20-HETE receptor blockers (AAA and 20-SOLA). Systemic or cell-specific therapeutic targeting of the 20-HETE-GPR75 axis continues to be an invaluable approach as studies examine the molecular underpinnings activated by 20-HETE under various physiological settings. In particular, the development and characterization of 20-HETE receptor blockers look to be a promising new class of compounds that can provide a considerable benefit to patients suffering from these cardiovascular pathologies.

Crucial neuroprotective roles of the metabolite BH4 in dopaminergic neurons.

Dopa-responsive dystonia (DRD) and Parkinson's disease (PD) are movement disorders caused by the dysfunction of nigrostriatal dopaminergic neurons. Identifying druggable pathways and biomarkers for guiding therapies is crucial due to the debilitating nature of these disorders. Recent genetic studies have identified variants of GTP cyclohydrolase-1 (GCH1), the rate-limiting enzyme in tetrahydrobiopterin (BH4) synthesis, as causative for these movement disorders. Here, we show that genetic and pharmacological inhibition of BH4 synthesis in mice and human midbrain-like organoids accurately recapitulates motor, behavioral and biochemical characteristics of these human diseases, with severity of the phenotype correlating with extent of BH4 deficiency. We also show that BH4 deficiency increases sensitivities to several PD-related stressors in mice and PD human cells, resulting in worse behavioral and physiological outcomes. Conversely, genetic and pharmacological augmentation of BH4 protects mice from genetically- and chemically induced PD-related stressors. Importantly, increasing BH4 levels also protects primary cells from PD-affected individuals and human midbrain-like organoids (hMLOs) from these stressors. Mechanistically, BH4 not only serves as an essential cofactor for dopamine synthesis, but also independently regulates tyrosine hydroxylase levels, protects against ferroptosis, scavenges mitochondrial ROS, maintains neuronal excitability and promotes mitochondrial ATP production, thereby enhancing mitochondrial fitness and cellular respiration in multiple preclinical PD animal models, human dopaminergic midbrain-like organoids and primary cells from PD-affected individuals. Our findings pinpoint the BH4 pathway as a key metabolic program at the intersection of multiple protective mechanisms for the health and function of midbrain dopaminergic neurons, identifying it as a potential therapeutic target for PD.

Depletion of HIF-1α by Inducible Cre/loxP Increases the Sensitivity of Cultured Murine Hepatocytes to Ionizing Radiation in Hypoxia.

The transcription factor hypoxia-inducible factor (HIF) is the main oxygen sensor which regulates adaptation to cellular hypoxia. The aim of this study was to establish cultured murine hepatocyte derived cells (mHDC) as an in vitro model and to analyze the role of HIF-1α in apoptosis induction, DNA damage repair and sensitivity to ionizing radiation (IR). We have crossed C57/BL6 mice that bear loxP sites flanking exon 2 of Hif1a with mice which carry tamoxifen-inducible global Cre expression. From the offspring, we have established transduced hepatocyte cultures which are permanently HIF-1α deficient after tamoxifen treatment. We demonstrated that the cells produce albumin, acetylcholine esterase, and the cytokeratins 8 and 18 which functionally characterizes them as hepatocytes. In moderate hypoxia, HIF-1α deficiency increased IR-induced apoptosis and significantly reduced the surviving fraction of mHDC as compared to HIF-1α expressing cells in colony formation assays. Furthermore, HIF-1α knockout cells displayed increased IR-induced DNA damage as demonstrated by increased generation and persistence of γH2AX foci. HIF-1α deficient cells showed delayed DNA repair after IR in hypoxia in neutral comet assays which may indicate that non-homologous end joining (NHEJ) repair capacity was affected. Overall, our data suggest that HIF-1α inactivation increases radiation sensitivity of mHDC cells.

Lucanthone Targets Lysosomes to Perturb Glioma Proliferation, Chemoresistance and Stemness, and Slows Tumor Growth In Vivo.

Glioblastoma is the most common and aggressive primary brain tumor in adults. Median survival time remains at 16-20 months despite multimodal treatment with surgical resection, radiation, temozolomide and tumor-treating fields therapy. After genotoxic stress glioma cells initiate cytoprotective autophagy, which contributes to treatment resistance, limiting the efficacy of these therapies and providing an avenue for glioma recurrence. Antagonism of autophagy steps has recently gained attention as it may enhance the efficacy of classical chemotherapies and newer immune-stimulating therapies. The modulation of autophagy in the clinic is limited by the low potency of common autophagy inhibitors and the inability of newer ones to cross the blood-brain barrier. Herein, we leverage lucanthone, an anti-schistosomal agent which crosses the blood-brain barrier and was recently reported to act as an autophagy inhibitor in breast cancer cells. Our studies show that lucanthone was toxic to glioma cells by inhibiting autophagy. It enhanced anti-glioma temozolomide (TMZ) efficacy at sub-cytotoxic concentrations, and suppressed the growth of stem-like glioma cells and temozolomide-resistant glioma stem cells. In vivo lucanthone slowed tumor growth: reduced numbers of Olig2+ glioma cells, normalized tumor vasculature, and reduced tumor hypoxia. We propose that lucanthone may serve to perturb a mechanism of temozolomide resistance and allow for successful treatment of TMZ-resistant glioblastoma.

Contribution of Eye-Tracking to Study Cognitive Impairments Among Clinical Populations.

In the field of psychology, the merge of decision-theory and neuroscientific methods produces an array of scientifically recognized paradigms. For example, by exploring consumer's eye-movement behavior, researchers aim to deepen the understanding of how patterns of retinal activation are being meaningfully transformed into visual experiences and connected with specific reactions (e.g., purchase). Notably, eye-movements provide knowledge of one's homeostatic balance and gatekeep information that shape decisions. Hence, vision science investigates the quality of observed environments determined under various experimental conditions. Moreover, it answers questions on how human process visual stimuli and use gained information for a successful strategy to achieve certain goals. While capturing cognitive states with the support of the eye-trackers progresses at a relatively fast pace in decision-making research, measuring the visual performance of real-life tasks, which require complex cognitive skills, is tentatively translated into clinical experiments. Nevertheless, the potential of the human eye as a highly valuable source of biomarkers has been underlined. In this article, we aim to draw readers attention to decision-making experimental paradigms supported with eye-tracking technology among clinical populations. Such interdisciplinary approach may become an important component that will (i) help in objectively illustrating patient's models of beliefs and values, (ii) support clinical interventions, and (iii) contribute to health services. It is possible that shortly, eye-movement data from decision-making experiments will grant the scientific community a greater understanding of mechanisms underlining mental states and consumption practices that medical professionals consider as obsessions, disorders or addiction.

Scaling Up a Community-Based Exercise Program for Women in Difficult Life Situations in Germany-The BIG Project as a Case-Study.

Scaling up community-based participatory research (CBPR) remains challenging. This case-study reports on how, and under which conditions, a CBPR project aiming at promoting exercise among socially disadvantaged women (BIG) scaled up at four project sites. As part of BIG, researchers support city administrations in implementing a participatory project to reach socially disadvantaged women for exercise. The case study was conducted in winter 2020 in southern Germany and is based on a co-creative process involving city administrators and researchers. Following Kohl and Cooley's scaling up dimensions, scaling up BIG was investigated at the four sites using a mixed-method approach. Course registrations and offers were analysed, and qualitative interviews (n = 4) with administrative staff members were conducted and analysed using content analysis. The geographical coverage of exercise classes, the addressed groups, and the utilisation of participatory methods by city administrations are described. All four sites managed to scale-up project activities. Three of the four sites reported that further growth of the project was no longer possible due to limited resources. All sites attempted to reach a larger number of, and more diverse, women. One site managed to scale-up the use of participatory methods within the city administration. The following important facilitators for scaling up CBPR projects were reported: advertisements tailored to the needs of the addressed women, utilising participatory approaches, and equipping project coordinators with sufficient resources.

In oxygen-deprived tumor cells ERp57 provides radioprotection and ensures proliferation via c-Myc, PLK1 and the AKT pathway.

The disulfide isomerase ERp57, originally found in the endoplasmic reticulum, is located in multiple cellular compartments, participates in diverse cell functions and interacts with a huge network of binding partners. It was recently suggested as an attractive new target for cancer therapy due to its critical role in tumor cell proliferation. Since a major bottleneck in cancer treatment is the occurrence of hypoxic areas in solid tumors, the role of ERp57 in cell growth was tested under oxygen depletion in the colorectal cancer cell line HCT116. We observed a severe growth inhibition when ERp57 was knocked down in hypoxia (1% O2) as a consequence of downregulated c-Myc, PLK1, PDPK1 (PDK1) and AKT (PKB). Further, irradiation experiments revealed also a radiosensitizing effect of ERp57 depletion under oxygen deprivation. Compared to ERp57, we do not favour PDPK1 as a suitable pharmaceutical target as its efficient knockdown/chemical inhibition did not show an inhibitory effect on proliferation.

Predicted crystal structures of tetramethylsilane and tetramethylgermane and an experimental low-temperature structure of tetramethylsilane.

No crystal structure at ambient pressure is known for tetramethylsilane, Si(CH(3))(4), which is used as a standard in NMR spectroscopy. Possible crystal structures were predicted by global lattice-energy minimizations using force-field methods. The lowest-energy structure corresponds to the high-pressure room-temperature phase (Pa3, Z = 8). Low-temperature crystallization at 100 K resulted in a single crystal, and its crystal structure has been determined. The structure corresponds to the predicted structure with the second lowest energy rank. In X-ray powder analyses this is the only observed phase between 80 and 159 K. For tetramethylgermane, Ge(CH(3))(4), no experimental crystal structure is known. Global lattice-energy minimizations resulted in 47 possible crystal structures within an energy range of 5 kJ mol(-1). The lowest-energy structure was found in Pa3, Z = 8.

Tumor cells rely on the thiol oxidoreductase PDI for PERK signaling in order to survive ER stress.

Upon ER stress cells activate the unfolded protein response through PERK, IRE1 and ATF6. Remarkable effort has been made to delineate the downstream signaling of these three ER stress sensors after activation, but upstream regulation at the ER luminal site still remains mostly undefined. Here we report that the thiol oxidoreductase PDI is mandatory for activation of the PERK pathway in HEK293T as well as in human pancreatic, lung and colon cancer cells. Under ER stress, depletion of PDI selectively abrogated eIF2α phosphorylation, induction of ATF4, CHOP and even BiP. Furthermore, we could demonstrate that PDI prevented degradation of activated PERK by the 26S proteasome and therefore contributes to maintained PERK signaling. As a result of decreased PERK activity, PDI depleted cells showed an increased vulnerability to ER stress induced by chemicals or ionizing radiation in 2D as well as in 3D culture models. We conclude that PDI is an obligatory regulator of the PERK pathway with future therapy implications.

Nutritional composition of the food supply: a comparison of soft drinks and breakfast cereals between three European countries based on labels.

BACKGROUND/OBJECTIVES: Monitoring of processed products at the brand level was implemented in Austria, France and Romania on the basis of the Oqali methodology during the Joint Action on Nutrition and Physical Activity (JANPA) to compare the nutritional quality of the food offering. The objective of this paper is to present the results obtained during this study. SUBJECTS/METHODS: Collected data were those available on product packaging. In total, 2155 soft drinks and 943 breakfast cereals were classified in a standardised list of product families and analysed in a harmonised way. For each product family, mean values for sugar, fat, saturated fat, salt and dietary fibres were compared between countries. Common products across countries were also studied. RESULTS: For all the studied nutrients, significant differences were observed between countries, with a higher sugar content for Romania in regular carbonated and non-carbonated beverages containing fruits, regular lemonades and regular tonics and bitters (together with Austria for tonics), for France in fruit beverages with more than 50% fruit, and for Austria in low-sugar beverages containing tea. For France, higher nutrient contents were also observed for sugar in chocolate-flavoured cereals, filled cereals and cornflakes, and other plain cereals (at a similar level as Romania for cornflakes), and for saturated fats in honey/caramel cereals and crunchy mueslis. These differences were explained by a different food offering in the three countries, but also by differences in nutrient contents for common products. This study also showed high variability of the nutrient content within a product family, suggesting a real potential for product reformulation. CONCLUSIONS: National tools, at the branded products level, are essential to monitor the nutritional quality of the food offering, and to follow up on processed food reformulations.

Zinc regulates the dopamine transporter in a membrane potential and chloride dependent manner.

The dopamine transporter (DAT), a membrane protein specifically expressed by dopaminergic neurons and mediating the action of psychostimulants and dopaminergic neurotoxins, is regulated by Zn(2+) which directly interacts with the protein. Herein, we report a host-cell-specific direction of the Zn(2+) effect on wild type DAT. Whereas low mumolar Zn(2+) decreased dopamine uptake by DAT expressing HEK293 cells, it stimulated uptake by DAT expressing SK-N-MC cells. Inhibition or stimulation was lost in a DAT construct without the binding site for Zn(2+). Also reverse transport was differentially affected by Zn(2+), dependent on whether the DAT was expressed in HEK293 or SK-N-MC cells. Pre-treatment of DAT expressing cells with phorbol-12-myristate-13-acetate, an activator of protein kinase C, attenuated the inhibitory effect of Zn(2+) on uptake in HEK293 cells and increased the stimulatory effect in SK-N-MC cells. Patch-clamp experiments under non-voltage-clamped conditions revealed a significantly higher membrane potential of HEK293 than SK-N-MC cells and a reduced membrane potential after phorbol ester treatment. Lowering chloride in the uptake buffer switched the stimulatory effect of Zn(2+) in SK-N-MC cells to an inhibitory, whereas high potassium depolarization of HEK293 cells switched the inhibitory effect of Zn(2+) to a stimulatory one. This study represents the first evidence that DAT regulation by Zn(2+) is profoundly modulated by the membrane potential and chloride.

SiBr4--prediction and determination of crystal structures.

For SiBr4 no crystal structures have been reported yet. In this work the crystal structures of SiBr4 were predicted by global lattice-energy minimizations using force-field methods. Over an energy range of 5 kJ mol(-1) above the global minimum ten possible structures were found. Two of these structures were experimentally determined from X-ray synchrotron powder diffraction data: The low-temperature beta phase crystallizes in P2(1)/c, the high-temperature alpha phase in Pa3. Temperature-dependant X-ray powder diffraction shows that the phase transition occurs at 168 K.

Electron diffraction, X-ray powder diffraction and pair-distribution-function analyses to determine the crystal structures of Pigment Yellow 213, C23H21N5O9.

The crystal structure of the nanocrystalline alpha phase of Pigment Yellow 213 (P.Y. 213) was solved by a combination of single-crystal electron diffraction and X-ray powder diffraction, despite the poor crystallinity of the material. The molecules form an efficient dense packing, which explains the observed insolubility and weather fastness of the pigment. The pair-distribution function (PDF) of the alpha phase is consistent with the determined crystal structure. The beta phase of P.Y. 213 shows even lower crystal quality, so extracting any structural information directly from the diffraction data is not possible. PDF analysis indicates the beta phase to have a columnar structure with a similar local structure as the alpha phase and a domain size in column direction of approximately 4 nm.