Construction of an active humidity regulation setup for NMR/MRI-Observation and simulation of the controlled evaporation of sessile water droplets.

Controlling and improving processes like for example the production of organic semiconductors via printing depends on understanding the interplay of wetting and evaporation of complex fluids. Therefore, examination of the time dependent composition of complex fluid droplets during wetting or evaporation is of interest. The evaporation rate of sessile droplets containing largely water depends on the vapor pressures of the individual components and on the humidity (or partial pressure) of the surrounding gas phase. Hence, for a complete picture of an evaporation process and the comparability of the results of different measurements, it is essential to measure and control the humidity and temperature in the measurement compartment. Accordingly, climate chambers are available in different scales to fit a variety of techniques like contact angle goniometry to obtain results in a controlled atmosphere. We recently reported the application of MRI (Magnetic Resonance Imaging) and spatially resolved NMR (Nuclear Magnetic Resonance) spectroscopy for the examination of the evaporation of sessile droplets on surfaces in 10 mm NMR tubes. These are considered to be closed compartments. Here, we present an apparatus to a) measure and b) control the relative humidity within the sample compartment of the NMR setup by introducing preconditioned gas into the NMR tube. We monitored the evaporation of water droplets using RARE images and compared the volume decay with a) a simple diffusive evaporation model and b) with detailed FEM (finite element numerical model) simulations using COMSOL for validation. We find three evaporation regimes depending on the flow rate as well as on the distance of the gas outlet and the evaporating droplet. In one of the sample configurations tested the evaporation takes place in such a way that it can be described with the help of the simple diffusive model without convection. Thus, the presented approach opens comparative measurements with other methods as well as the observation of droplet evaporation in very dry or very humid environments with and without the influence of convection. Finally, using PRESS spectra, it is shown that the evaporation rate of water from a water/DMSO droplet can be controlled. This shows how the setup presented here can be used to study the evaporation of droplets of more complex mixtures.

MRI and localised NMR spectroscopy of sessile droplets on hydrophilic, hydrophobic and superhydrophobic surfaces - Examination of the chemical composition during evaporation.

Evaporation of droplets is a process important in many different areas of science, technology and also everyday life. The understanding of droplet evaporation of homogeneous and heterogeneous substance mixtures is important, for example, to explain the formation of coffee stains or to optimize the results in offset printing. For a detailed understanding of the evaporation of complex mixtures from structured surfaces, such as inks used in offset printing, a time-resolved analysis of the droplet composition is essential. Measurement of (local) concentrations may deepen the understanding of wetting phenomena and their connection with transport phenomena. Therefore, we demonstrate in this paper that magnetic resonance methods can be used to (a) image sessile droplets on structured surfaces and (b) investigate their composition in a time-resolved manner. First it is shown that water droplets on superhydrophobic, hydrophobic and hydrophilic surfaces, despite the large liquid/gas interface, can be imaged well and without interfering artefacts using RARE. Further, the signals are examined in localised PRESS NMR spectra with respect to line shape and quantifiability. Finally, it is demonstrated that non-localised NMR spectra can be used to track the droplet composition during evaporation.

Cloud-based simulation studies in R - A tutorial on using doRedis with Amazon spot fleets.

Simulation studies are helpful in testing novel statistical methods. From a computational perspective, they constitute embarrassingly parallel tasks. We describe parallelization techniques in the programming language R that can be used on Amazon's cloud-based infrastructure. After a short conceptual overview of the parallelization techniques in R, we provide a hands-on tutorial on how the doRedis package in conjunction with the Redis server can be used on Amazon Web Services, specifically running spot fleets. The tutorial proceeds in seven steps, ie, (1) starting up an EC2 instance, (2) installing a Redis server, (3) using doRedis with a local worker, (4) using doRedis with a remote worker, (5) setting up instances that automatically fetch tasks from a specific master, (6) using spot-fleets, and (7) shutting down the instances. As a basic example, we show how these techniques can be used to assess the effects of heteroscedasticity on the equal-variance t-test. Furthermore, we address several advanced issues, such as multiple conditions, cost-management, and chunking.

Identification of CASZ1 NES reveals potential mechanisms for loss of CASZ1 tumor suppressor activity in neuroblastoma.

As a transcription factor, localization to the nucleus and the recruitment of cofactors to regulate gene transcription is essential. Nuclear localization and nucleosome remodeling and histone deacetylase (NuRD) complex binding are required for the zinc-finger transcription factor CASZ1 to function as a neuroblastoma (NB) tumor suppressor. However, the critical amino acids (AAs) that are required for CASZ1 interaction with NuRD complex and the regulation of CASZ1 subcellular localization have not been characterized. Through alanine scanning, immunofluorescence cell staining and co-immunoprecipitation, we define a critical region at the CASZ1 N terminus (AAs 23-40) that mediates the CASZ1b nuclear localization and NuRD interaction. Furthermore, we identified a nuclear export signal (NES) at the N terminus (AAs 176-192) that contributes to CASZ1 nuclear-cytoplasmic shuttling in a chromosomal maintenance 1-dependent manner. An analysis of CASZ1 protein expression in a primary NB tissue microarray shows that high nuclear CASZ1 staining is detected in tumor samples from NB patients with good prognosis. In contrast, cytoplasmic-restricted CASZ1 staining or low nuclear CASZ1 staining is found in tumor samples from patients with poor prognosis. These findings provide insight into mechanisms by which CASZ1 regulates transcription, and suggests that regulation of CASZ1 subcellular localization may impact its function in normal development and pathologic conditions such as NB tumorigenesis.

Prevalence of medication errors in admitted patients at the Philippine General Hospital

@#<p style="text-align: justify;"><strong>BACKGROUND:</strong> Medication errors are preventable events that can cause or lead to inappropriate drug use. Knowing the prevalence and types of errors can help us institute corrective measures and avoid adverse drug events.<br /><strong>OBJECTIVE:</strong> This study determined the prevalence of medication errors and its specific types in the four main service wards of a tertiary government training medical center.<br /><strong>METHODS:</strong> This is a retrospective, descriptive chart review study. From the master list of admissions, systematic sampling was done to retrieve the required number of charts. Relevant pages such as order sheets, nurses' notes, therapeutic sheets were photographed. For prolonged admissions, only the first 7 days were reviewed. Each chart was evaluated by two people who then met and agreed on the errors identified.<br /><strong>RESULTS:</strong> The overall prevalence of medication errors is 97.8%. Pediatrics had the most (63.3/chart), followed by Medicine, OB-Gynecology, and Surgery (7.3/chart). The most common type of errors identified were prescribing, followed by compliance, then administration errors.<br /><strong>CONCLUSION:</strong> Medication errors are present in the four main wards in our hospital. We recommend orientation of all incoming first year residents on proper ordering and prescribing of drugs, as well as a prospective observational study to determine true prevalence of all types of medication errors.</p>

Prevalence of medication errors in admitted patients at the Philippine General Hospital

BACKGROUND: Medication errors are preventable events that can cause or lead to inappropriate drug use. Knowing the prevalence and types of errors can help us institute corrective measures and avoid adverse drug events.OBJECTIVE: This study determined the prevalence of medication errors and its specific types in the four main service wards of a tertiary government training medical center.METHODS: This is a retrospective, descriptive chart review study. From the master list of admissions, systematic sampling was done to retrieve the required number of charts. Relevant pages such as order sheets, nurses' notes, therapeutic sheets were photographed. For prolonged admissions, only the first 7 days were reviewed. Each chart was evaluated by two people who then met and agreed on the errors identified.RESULTS: The overall prevalence of medication errors is 97.8%. Pediatrics had the most (63.3/chart), followed by Medicine, OB-Gynecology, and Surgery (7.3/chart). The most common type of errors identified were prescribing, followed by compliance, then administration errors.CONCLUSION: Medication errors are present in the four main wards in our hospital. We recommend orientation of all incoming first year residents on proper ordering and prescribing of drugs, as well as a prospective observational study to determine true prevalence of all types of medication errors.

Still shimming or already measuring?--Quantitative reaction monitoring for small molecules on the sub minute timescale by NMR.

In order to enable monitoring of rapidly occurring reactions Wagner et al. recently presented a simple scheme for 1D NMR experiments with continuous data acquisition, without inter-scan delays, using a spatially-selective and frequency-shifted excitation approach (Wagner et al., 2013). This scheme allows acquisition of proton spectra with temporal resolutions on the millisecond timescale. Such high temporal resolutions are desired in the case of reaction monitoring using stopped flow setups. In regular (1)H NMR-spectra without spatial selection the line width increases for a given shim setting with changes in sample volume, susceptibility, convection and temperature or concentration gradients due to the disturbance of magnetic field homogeneity. Concerning reaction monitoring this is unfortunate as shimming prior to acquisition becomes necessary to obtain narrow signals after injection of a reactant into an NMR sample. Even automatic shim routines may last up to minutes. Thus fast reactions can hardly be monitored online without large hardware dead times in a single stopped flow experiment. This problem is reduced in the spatially-selective and frequency-shifted continuous NMR experiment as magnetic field inhomogeneties are less pronounced and negative effects on the obtained line shapes are reduced as pointed out by Bax and Freeman (1980) [2] and demonstrated by Wagner et al. (2013). Here we present the utilization of this technique for observation of reactions in small molecule systems in which chemical conversion and longitudinal relaxation occur on the same timescale. By means of the alkaline ethyl acetate hydrolysis, a stoichiometric reaction, we show advantages of spatially-selective excitation on both temporal resolution and line shapes in stopped flow experiments. Results are compared to data obtained by non-selective small angle excitation experiments.

Molecular weight and molar substitution are more important in HES-induced renal impairment than concentration after hemorrhagic and septic shock.

BACKGROUND: Clinical studies have raised concerns about the safety of 6% hydroxyethylstarch (HES) 130/0.42, but the pathomechanisms of this renal impairment remain unknown. To evaluate the effects of different HES concentrations, molar substitutions and molecular weights in HES-induced renal impairment, we used a porcine two-hit model that combined haemorrhagic and septic shock. METHODS: We conducted a prospective, randomised, double-blinded, controlled study in a university animal laboratory. Thirty anaesthetised and ventilated pigs were randomised to receive volume replacement therapy using 6% HES130/0.42, 6% HES200/0.5, 10% HES130/0.42 or 10% HES200/0.5, all dissolved in 0.9% NaCl rather than 0.9% NaCl alone. First, we bled the animals until they reached half of their baseline mean arterial pressure (MAP) for 45 minutes followed by fluid resuscitation. As a second hit, sepsis was induced using an Escherichia coli-laden clot 6 hours after haemorrhagic shock. Volume resuscitation started with a delay of two hours and a central venous pressure goal of 12 mmHg. RESULTS: At the end of the study, the groups showed no difference in cardiac output or MAP, but the volume balance (mL/kg BW) was significantly higher in the 0.9% NaCl group (346±90; P≤0.05) than in the other groups (6% HES130, 125±26; 6% HES200, 105±15; 10% HES130, 114±17; 10% HES200, 96±23). Creatinine clearance (mL/min) was significantly lower in the 6% HES200 (26±33) and 10% HES200 (15±18) groups compared to the 0.9% NaCl group (104±46; P≤0.05) but not in the HES 130 formulations (6% HES130: 64±51; 10% HES130: 58±38) at the end of the study. CONCLUSION: In this porcine two-hit shock model, treatment with 0.9% NaCl, HES 130/0.42 or HES 200/0.5 led to a similar maintenance of haemodynamic values. Despite this similar maintenance of the haemodynamic values, volume replacement with 6% and 10% HES 200/0.5 led to an accumulation of HES, higher colloid osmotic pressure and significantly reduced renal function after haemorrhagic and septic shock. These facts support the presumption that not the concentration but the degree of substitution and the molecular weight play a decisive role in HES-induced renal impairment.

"Perfecting" pure shift HSQC: full homodecoupling for accurate and precise determination of heteronuclear couplings.

Fully homodecoupled HSQC spectra can be obtained through the use of a new pulse sequence element, "perfectBIRD". By way of illustration, we show that perfectBIRD decoupling allows one-bond residual dipolar couplings (RDCs), which provide important NMR restraints for structure elucidation, to be measured with outstanding precision, even in methylene groups.

[Testing the comparability of free-field and HDA200 headphone measurements for the Freiburg speech test]. / Überprüfung der Vergleichbarkeit von Freifeld- und HDA200-Kopfhörermessungen für den Freiburger Sprachtest.

BACKGROUND: In clinical practice, the standardized Freiburg speech test is presented via headphones as well as via loudspeakers. To achieve comparable results with both presentation modes, the headphone measurements are equated to the free-field situation. The free-field correction is determined by subjective loudness balance measurements and realized by a free-field equalizer network and a broadband frequency correction value during headphone calibration. Using the Freiburg speech test, this study tested the comparability of free-field and HDA200 headphone measurements. PATIENTS AND METHODS: In 15 normal hearing subjects, the Freiburg speech intelligibility test was performed using both loudspeakers and HDA200 headphones. RESULTS: The 50% speech reception threshold measured using HDA200 headphones was on average 5.1 dB lower than for loudspeakers and lay below the standardized reference values. CONCLUSION: The desired comparability to free-field measurements could not be shown for the HDA200 headphones. The improved intelligibility via HDA200 is probably caused by the fact that the calibration correction factor of 4 dB is too high. This should be checked by the PTB.

[Application of new speech intelligibility tests in silence for the assessment of acquired hearing losses]. / Der Einsatz neuer Testverfahren zur Erfassung des Sprachverstehens in Ruhe bei der Begutachtung erworbener Schwerhörigkeiten.

BACKGROUND: Previous studies comparing the Freiburg speech tests (FST) currently used in Germany to assess the severity of hearing loss with two modern speech intelligibility tests [the Göttingen sentence test (GöSa) and the monosyllabic rhyme test devised by von Wallenberg and Kollmeier (WaKo)] have indicated that a replacement of the old procedure would be possible. The current study investigates the consequences of the modern test procedures for the estimation of reduction in earning capacity resulting from hearing loss, and considers the optimal presentation levels for the WaKo test. METHODS: The FST, GöSa, and WaKo speech intelligibility tests were performed on 29 volunteers with a hearing impairment. All tests were conducted in silence. The presentation levels for the Freiburg monosyllabic test were 60, 80, and for some participants also 100 dB SPL. The WaKo test was carried out once at 45, 65, and 85 dB SPL (a reduction of 15 dB relative to the FST) and again at 40, 60 and 80 dB SPL (reduction of 20 dB relative to the FST). RESULTS: A consideration across all presentation levels revealed that the best correlation match between the two monosyllabic tests was achieved at a 20-dB reduction in presentation level for the WaKo test relative to the FST. On average, the application of modern procedures and the different options for level reduction had only a minor effect on the quantitative assessment of reduction in earning capacity.

Stimulation of gastric slow waves with manual acupuncture at acupuncture points ST36 and PC6--a randomized single blind controlled trial.

BACKGROUND: To investigate the effects of stimulated and non-stimulated manual acupuncture at ST36 and PC6 on gastric myoelectrical activity and autonomic function. METHODS: A total of 65 healthy volunteers were randomly assigned to a 1: 1: 2 ratio to receive either 15 min of verum acupuncture (VA) with stimulation followed by 15 min of VA without stimulation (nsVA), or 15 min of nsVA followed by 15 min of VA with stimulation (sVA), or 30 min of sham acupuncture (SA). Measures of autonomic function included electrogastrogram, electrocardiogram, impedance cardiography and assessment of blood pressure, breathing frequency, and electrodermal activity. Outcome parameters were compared between VA and SA, and between sVA and nsVA. The percentage of regular gastric slow waves (normogastria) was defined as the primary outcome. KEY RESULTS: The percentage of normogastria was not significantly different between VA and SA. Differences in secondary outcomes such as power spectrum of gastric slow waves and heart rate variability parameters were pronounced in the comparison of sVA and nsVA. During sVA, the percentage of normogastria was lower (P = 0.005), the percentage of bradygastria was higher (P = 0.003) and power ratio was higher (P < 0.001), systolic blood pressure was lower (P = 0.039) and RMSSD was higher (P < 0.001) as compared with nsVA. CONCLUSIONS & INFERENCES: Our study suggests that manual stimulation of acupuncture needles at ST36 and PC6 affects gastric myoelectrical as well as cardiac activities in healthy volunteers. The effect of stimulation in acupuncture deserves further investigation.

[Göttingen sentence in noise for different audiogram classes]. / Göttinger Satztest im Störgeräusch für verschiedene Gruppen von Schwerhörigkeit.

BACKGROUND: In addition to the standardized Freiburg sentence test in silence validated speech tests in noise are available. They are mainly used to test the benefit of hearing systems in everyday-life situations. In diagnostics tests in noise can also give additional information of the patients' hearing impairment. The determined speech reception threshold (SRT) depends on the degree of hearing loss and the used speech and noise test material. Aim of this study was to analyze the results of the Göttingen sentence test in noise in relation to different audiogram classes. MATERIAL AND METHODS: The Göttingen sentence test in stationary noise (65 dB) was performed for 135 patients with different degrees of hearing losses. Based on the air-conducted threshold all ears were categorized to an audiogram class by an automated procedure. RESULTS: For the mild hearing losses the results of the Göttingen sentence test increased with increasing pure-tone-average (PTA) and the values are smaller than 0 dB SNR with a small standard deviation (± 1-2 dB SNR). For the moderate hearing losses values of 5 dB SNR with a standard deviation of 6 dB SNR were achieved on average. Patients with a high hearing loss achieved values higher than 20 dB SNR. CONCLUSION: For the mild hearing losses the results were located in a small range. However, they can give important information about the patient's hearing impairment mainly appears in a noisy environment. With increasing hearing loss also the reduced hearing in silence affects the results achieved with the Göttingen sentence test in noise. Therefore the hearing in silence has to be taken into account at the interpretation of the results.

Hyponatremia and cerebral edema associated with radioiodine therapy for papillary thyroid carcinoma / Journal of the ASEAN Federation of Endocrine Societies

Among the serious complications associated with radioiodine therapy (RAI) for thyroid cancer, cerebral edema is uncommon and has been reported previously in cases of swelling of brain metastases. This case is of a patient with papillary thyroid carcinoma who complained of nausea and vomiting after RAI and was then found unconscious the next day. Laboratory results showed electrolyte imbalances including hyponatremia and cranial imaging only revealed cerebral edema, and she regained consciousness after sodium correction. The etiology of the cerebral edema here is likely multifactorial - due to hyponatremia from hypothyroidism, aggravated by vomiting, copious water intake and a low sodium diet.

[Hearing loss determination and assessment of the reduction in earning capacity taking speech discrimination tests in noise into account]. / Hörverlustbestimmung und MdE-Abschätzung unter Einbezug von Sprachverständlichkeitsmessungen im Störgeräusch.

BACKGROUND: In Germany the guideline for the hearing loss quantification and the resulting assessment of the reduction in earning capacity is the Königsteiner Merkblatt (KM). The quantification depends on the results of the tone and speech audiogram in silence. However, speech discrimination tests in noise may provide additional information about the impairment of the ENT patients. Especially, the impairment of persons with a slight hearing loss, characterized by high-frequency hearing loss, in noisy environment can not be indicated by the measurement in silence, which is proposed in the KM. METHODS UND PATIENTS: The Göttingen sentence test in noise was applied as a supplement to the routine ENT procedures of the medical estimate in 135 test persons. Based on these measurement results a table for the percentage hearing loss in noise is defined. Furthermore, an integration of the hearing loss in noise in the assessment of the reduction in earning capacity is proposed in addition to the hearing loss in silence. RESULTS: Using the newly introduced hearing loss for speech in noise, a suitable assessment for persons with a slight hearing loss is achieved. By integrating it into the assessment procedure additionally to the hearing loss in silence, the hearing impairment of all patients can be rated depending on their speech test results in silence and in noise. In comparison to the results obtained by the KM, the new procedure does not lead to higher values for the proposed reduction in earning capacity in general, but instead seems to be equally suitable for all groups of patients.

CASZ1, a candidate tumor-suppressor gene, suppresses neuroblastoma tumor growth through reprogramming gene expression.

Neuroblastoma (NB) is a common childhood malignant tumor of the neural crest-derived sympathetic nervous system. In NB the frequent loss of heterozygosity (LOH) on chromosome 1p raises the possibility that this region contains tumor-suppressor genes whose inactivation contributes to tumorigenesis. The human homolog of the Drosophila neural fate determination gene CASZ1, a zinc-finger transcription factor, maps to chromosome 1p36.22, a region implicated in NB tumorigenesis. Quantitative real-time PCR analysis showed that low-CASZ1 expression is significantly correlated with increased age (≥18 months), Children's Oncology Group high-risk classification, 1p LOH and MYCN amplification (all P<0.0002) and decreased survival probability (P=0.0009). CASZ1 was more highly expressed in NB with a differentiated histopathology (P<0.0001). Retinoids and epigenetic modification agents associated with regulation of differentiation induced CASZ1 expression. Expression profiling analysis revealed that CASZ1 regulates the expression of genes involved in regulation of cell growth and developmental processes. Specific restoration of CASZ1 in NB cells induced cell differentiation, enhanced cell adhesion, inhibited migration and suppressed tumorigenicity. These data are consistent with CASZ1 being a critical modulator of neural cell development, and that somatically acquired disruption of normal CASZ1 expression contributes to the malignant phenotype of human NB.

The MYCN oncogene is a direct target of miR-34a.

Loss of 1p36 heterozygosity commonly occurs with MYCN amplification in neuroblastoma tumors, and both are associated with an aggressive phenotype. Database searches identified five microRNAs that map to the commonly deleted region of 1p36 and we hypothesized that the loss of one or more of these microRNAs contributes to the malignant phenotype of MYCN-amplified tumors. By bioinformatic analysis, we identified that three out of the five microRNAs target MYCN and of these miR-34a caused the most significant suppression of cell growth through increased apoptosis and decreased DNA synthesis in neuroblastoma cell lines with MYCN amplification. Quantitative RT-PCR showed that neuroblastoma tumors with 1p36 loss expressed lower level of miR-34a than those with normal copies of 1p36. Furthermore, we demonstrated that MYCN is a direct target of miR-34a. Finally, using a series of mRNA expression profiling experiments, we identified other potential direct targets of miR-34a, and pathway analysis demonstrated that miR-34a suppresses cell-cycle genes and induces several neural-related genes. This study demonstrates one important regulatory role of miR-34a in cell growth and MYCN suppression in neuroblastoma.

Downregulation of Bim by brain-derived neurotrophic factor activation of TrkB protects neuroblastoma cells from paclitaxel but not etoposide or cisplatin-induced cell death.

Chemoresistance and increased expression of TrkB and brain-derived neurotrophic factor (BDNF) are biomarkers of poor prognosis in tumors from patients with neuroblastoma (NB). Previously, we found BDNF activation of TrkB through PI3K/Akt protects NB from etoposide/cisplatin-induced cell death. In this study, the role of Bim, a proapoptotic protein, was investigated. Bim was involved in paclitaxel but not etoposide or cisplatin-induced cell death in NB cells. Pharmacological and genetic studies showed that BDNF-induced decreases in Bim were regulated by MAPK and not PI3K/Akt pathway. Both MAPK and PI3K pathways were involved in BDNF protection of NB cells from paclitaxel-induced cell death, while PI3K predominantly mediated BDNF protection of NB cells from etoposide or cisplatin-induced cell death. These data indicate that different chemotherapeutic drugs induce distinct death pathways and growth factors utilize different signal transduction pathways to modulate the effects of chemotherapy on cells.

Antineoplastic effects of rosiglitazone and PPARgamma transactivation in neuroblastoma cells.

Neuroblastoma (NB) is the most common extracranial solid tumour in infants. Unfortunately, most children present with advanced disease and have a poor prognosis. In the present study, we evaluated the role of the peroxisome proliferator-activated receptor gamma (PPARgamma) agonist rosiglitazone (RGZ) in two NB cell lines (SK-N-AS and SH-SY5Y), which express PPARgamma. Rosiglitazone decreased cell proliferation and viability to a greater extent in SK-N-AS than in SH-SY5Y. Furthermore, 20 microM RGZ significantly inhibited cell adhesion, invasiveness and apoptosis in SK-N-AS, but not in SH-SY5Y. Because of the different response of SK-N-AS and SH-SY5Y cells to RGZ, the function of PPARgamma as a transcriptional activator was assessed. Noticeably, transient transcription experiments with a PPARgamma responsive element showed that RGZ induced a three-fold increase of the reporter activity in SK-N-AS, whereas no effect was observed in SH-SY5Y. The different PPARgamma activity may be likely due to the markedly lower amount of phopshorylated (i.e. inactive) protein observed in SK-N-AS. To our knowledge, this is the first demonstration that the differential response of NB cells to RGZ may be related to differences in PPARgamma transactivation. This finding indicates that PPARgamma activity may be useful to select those patients, for whom PPARgamma agonists may have a beneficial therapeutic effect.

The OSBP-related proteins (ORPs): global sterol sensors for co-ordination of cellular lipid metabolism, membrane trafficking and signalling processes?

Protein families related to OSBP (oxysterol-binding protein) are present in eukaryotes from yeast to human. The functions of the ORPs (OSBP-related proteins) have remained largely enigmatic. Even though they have been implicated in the function of ERJs (endoplasmic reticulum junctions), it is evident that any single model for their mechanism of action is insufficient. The existing evidence points in many different directions, such as integration of sterol and sphingomyelin metabolism, regulation of neutral lipid metabolism, control of signalling cascades, regulation of secretory vesicle generation, and function in the microtubule-based motility of endo/lysosomes. Some of these functions could involve ERJ and non-vesicular transport of lipids, but this is unlikely to be the unifying feature. We believe, rather, that the common denominator for ORP function is acting as sterol sensors that relay information to a spectrum of cellular processes.