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The European Union (EU) presented its new trade strategy in early 2021. This article assesses whether the strategy constitutes a path-altering development in EU trade policy. Drawing on concepts from Historical Institutionalism the article assesses the presence and influence of the permissive and productive conditions necessary for a critical juncture, meaning a path-altering policy development, to occur. The permissive conditions refer to the external environment, while the productive conditions are internal, referring to ideational (cognitive and normative) and instrumental developments. We find that although the EU responded instrumentally to changes in the international trading system, and a loosening of the liberal international order, the new trade strategy was not accompanied by a complete ideational change. The EU's normative outlook was little changed in 2021. The conclusion discusses how subsequent changes in the international environment and trade instruments may affect EU trade policy, and whether, over a longer time-period, the new strategy may nonetheless be identified as the start of a critical juncture. [ABSTRACT FROM AUTHOR]

Abstract Gamma-ray bursts (GRBs) are exceptionally bright electromagnetic events occurring daily on the sky. The prompt emission is dominated by X-/ γ -rays. Since their discovery over 50 years ago, GRBs are primarily studied through spectral and temporal measurements. The properties of the emission jets and underlying processes are not well understood. A promising way forward is the development of missions capable of characterising the linear polarisation of the high-energy emission. For this reason, the SPHiNX mission has been developed for a small-satellite platform. The polarisation properties of incident high-energy radiation (50–600 keV) are determined by reconstructing Compton scattering interactions in a segmented array of plastic and Gd 3 Al 2 Ga 3 O 12 (Ce) (GAGG(Ce)) scintillators. During a two-year mission, ∼ 200 GRBs will be observed, with ∼ 50 yielding measurements where the polarisation fraction is determined with a relative error ≤ 10%. This is a significant improvement compared to contemporary missions. This performance, combined with the ability to reconstruct GRB localisation and spectral properties, will allow discrimination between leading classes of emission models. [ABSTRACT FROM AUTHOR]

In this paper we prove a KAM theorem for small-amplitude solutions of the non linear beam equation on the d-dimensional torus where $${G(x,u)=u^4+ O(u^5)}$$ . Namely, we show that, for generic m, many of the small amplitude invariant finite dimensional tori of the linear equation $${(*)_{G=0}}$$ , written as the system persist as invariant tori of the nonlinear equation $${(*)}$$ , re-written similarly. The persisted tori are filled in with time-quasiperiodic solutions of $${(*)}$$ . If $${d\ge2}$$ , then not all the persisted tori are linearly stable, and we construct explicit examples of partially hyperbolic invariant tori. The unstable invariant tori, situated in the vicinity of the origin, create around them some local instabilities, in agreement with the popular belief in the nonlinear physics that small-amplitude solutions of space-multidimensional Hamiltonian PDEs behave in a chaotic way. [ABSTRACT FROM AUTHOR]

The progression of diabetes is accompanied by increasing demand to the beta-cells to produce and secrete more insulin, requiring complex beta-cell adaptations. Functionally active and ubiquitous non-coding RNAs (nc RNAs) have the capacity to take part in such adaptations as they have been shown to be key regulatory molecules in various biological processes. In the pancreatic islets, the function of nc RNAs and their contribution to disease development is beginning to be understood. Here, we review the different classes of nc RNAs, such as long non-coding RNAs (lnc RNAs) and micro RNAs (mi RNAs), and their potential contribution to insulin secretion. A special focus will be on mi RNAs and their regulatory function in beta-cell physiology and insulin exocytosis. As important players in gene regulation, nc RNAs have huge potential in opening innovative therapeutic avenues against diabetes and associated complications. [ABSTRACT FROM AUTHOR]

Objective: The incretin hormone GIP (glucose-dependent insulinotropic polypeptide) promotes pancreatic β-cell function by potentiating insulin secretion and β-cell proliferation. Recently, a combined analysis of several genome-wide association studies (Meta-analysis of Glucose and Insulin-Related Traits Consortium [MAGIC]) showed association to postprandial insulin at the GIP receptor (GIPR) locus. Here we explored mechanisms that could explain the protective effects of GIP on islet function.Research Design and Methods: Associations of GIPR rs10423928 with metabolic and anthropometric phenotypes in both nondiabetic (N = 53,730) and type 2 diabetic individuals (N = 2,731) were explored by combining data from 11 studies. Insulin secretion was measured both in vivo in nondiabetic subjects and in vitro in islets from cadaver donors. Insulin secretion was also measured in response to exogenous GIP. The in vitro measurements included protein and gene expression as well as measurements of β-cell viability and proliferation.Results: The A allele of GIPR rs10423928 was associated with impaired glucose- and GIP-stimulated insulin secretion and a decrease in BMI, lean body mass, and waist circumference. The decrease in BMI almost completely neutralized the effect of impaired insulin secretion on risk of type 2 diabetes. Expression of GIPR mRNA was decreased in human islets from carriers of the A allele or patients with type 2 diabetes. GIP stimulated osteopontin (OPN) mRNA and protein expression. OPN expression was lower in carriers of the A allele. Both GIP and OPN prevented cytokine-induced reduction in cell viability (apoptosis). In addition, OPN stimulated cell proliferation in insulin-secreting cells.Conclusions: These findings support β-cell proliferative and antiapoptotic roles for GIP in addition to its action as an incretin hormone. Identification of a link between GIP and OPN may shed new light on the role of GIP in preservation of functional β-cell mass in humans. [ABSTRACT FROM AUTHOR]

Summary: In this study, the secretion rate and IgA, albumin and lactoferrin concentrations in minor labial and buccal gland saliva were investigated in individuals with hyposalivation due to primary Sjögren''s syndrome (pSS; 10 subjects) or head and neck radiation therapy (RT; 10 subjects) and in their matched controls. Whole saliva was similarly examined. The minor gland saliva flow was measured using the Periotron® method. IgA, albumin and lactoferrin concentrations were analysed by ELISA techniques. A general finding was that the flow rate and protein concentrations were lower in labial than in buccal gland saliva. In both hyposalivation groups, the labial minor gland saliva secretion rate was lowered compared to their respective controls. The buccal gland saliva flow rate was significantly reduced in the RT group only. IgA and albumin concentrations were not different from the controls in the labial secretions. The concentration of lactoferrin was increased in the RT group. In buccal saliva, the concentrations of all proteins examined but pSS IgA, were increased compared to the controls. Reduced flow rate and increased protein concentrations were seen for whole saliva where the lactoferrin concentration was higher in RT than in pSS subjects. Thus, our findings suggested that minor gland saliva flow rate and protein concentrations are affected in RT and pSS subjects and to highest extent in the former. [Copyright &y& Elsevier]

Bacteria-binding components and the ability to mediate bacterial adhesion to the tooth surface have been thoroughly studied in major salivary gland secretions. Our knowledge on the bacteria binding activity in minor gland saliva is, however, limited. In this study, proteins were examined in parallel in minor (palatal, buccal and labial) and major (parotid and submandibular/sublingual) salivary gland secretions in one subject using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. The adherence of early colonizing Actinomyces naeslundii to pellicles formed from the secretions on hydroxyapatite beads was also examined. Amylase, IgA, proline-rich proteins and the high-molecular-weight glycoproteins, agglutinins, were detected in all saliva tested. Carbohydrate-reactive antibodies recognized the low-molecular weight mucin, MUC 7 in submandibular/sublingual saliva only. A. naeslundii strain 12104 adhered to all pellicles and especially to the buccal gland saliva pellicles. Strain LY7 adhered in highest numbers to the submandibular/sublingual saliva pellicles. It also bound in considerable numbers to parotid and palatal saliva pellicles but not to the ones formed from buccal and labial gland saliva. Our findings indicate that several bacteria-binding components are secreted in both minor and major gland saliva. The adherence-promoting ability of the various gland secretions differs, however. [Copyright &y& Elsevier]

Many women undergo hormone replacement therapy in order to relieve menopausal and postmenopausal symptoms. Oral discomfort is common among these symptoms and studies have shown that the stimulated whole saliva flow rate is increased after combined oestradiol and progesterone replacement therapy. There is, however, no data regarding the effect of other oestrogens or of oestrogen alone on whole and minor gland saliva. In the present study, the flow rate from minor salivary glands (buccal, labial and palatal) and the secretion rate and buffer capacity of whole saliva was examined in 18 postmenopausal women (61–76 years) prior to, and during 1 year of a low potency oestrogen (oestriol) use. The ability of whole saliva to aggregate and mediate bacterial adherence as well as subjective feelings of dry mouth was also examined. For comparison, the same variables were examined in nine peri- and postmenopausal, non-medicated women (reference group, 53–61 years). During hormone treatment, the labial saliva flow was significantly increased and the complaints of dry mouth reduced. Increased stimulated whole saliva flow was seen in both the hormone and reference groups. This was also true for the stimulated whole saliva buffer capacity, which was increased parallel to the flow rate. The secretion rates were generally lower in the hormone group compared to the reference group throughout the study period. Except for stimulated whole saliva, statistical analysis at baseline revealed no age-related reduction of the saliva flow rates. The ability of whole saliva to mediate aggregation of Actinomyces næslundii was significantly decreased after hormone treatment. Thus, the present findings indicate that a low dose oestrogen (oestriol) may affect the flow rate of labial salivary glands and the bacterial aggregation activity of whole saliva. [Copyright &y& Elsevier]

The article presents information on the process of exocytosis, which is the mechanism by which a vesicle inside the cell fuses with the plasma membrane to release its contents into the extra cellular environment. It mentions that the process is a necessary part of neurotransmitter release from the pre-synaptic side into the synaptic cleft. It also mentions that the exocytotic machinery and its components play crucial roles in neurotransmission and hormone release.

An editorial is presented, in which the author discusses need of considering gender issues in science-related debates. it mentions unfair discrimination by the scientific system against women. it also mentions need of gender equality policies aim to dismantle gender-related differences. It mentions social and cultural backgrounds of women that contributes to their career in success.

Aim: MicroRNAs (miRNAs) regulate β‐cell function, and β‐cell mitochondria and insulin secretion are perturbed in diabetes. We aimed to identify key miRNAs regulating β‐cell mitochondrial metabolism and novel β‐cell miRNA‐mitochondrial pathways. Methods: TargetScan (http://www.targetscan.org/) was used to predict if 16 miRNAs implicated in β‐cell function target 27 cis‐eGenes implicated in mitochondrial activity. The expression of candidate miRNAs and insulin secretion after 24 and 1 h pre‐incubation in 2.8, 11.1‐ and 16.7‐mM glucose was measured in clonal INS‐1 832/13 β‐cells. MiR‐29 silenced INS‐1 832/13 cells were assessed for insulin secretion (glucose, pyruvate, and K+), target cis‐eGene expression (Ndufv3 and Ndufa10 components of mitochondrial complex I (CI)), OXPHOS (CI‐V) protein expression, and mitochondrial OXPHOS respiration/activity. The expression of differentially expressed miR‐29 miRNAs was evaluated in Goto‐Kakizaki (GK) rat, db/db mouse and type 2 diabetic (T2D) human islets, as well as NMRI mouse islets cultured under glucolipotoxic conditions. Results: MiR‐29, miR‐15 and miR‐124 were predicted to regulate ~20 cis‐eGenes, while miR‐29 alone was predicted to regulate ≥12 of these in rat and human species. MiR‐29 expression and insulin secretion were reduced in INS‐1 832/13 cells after 24 h in elevated glucose. MiR‐29 knockdown increased all tested insulin secretory responses, Nudfv3, Ndufa10, complex I and II expression, and cellular mitochondrial OXPHOS. MiR‐29 expression was reduced in db/db islets but increased in GK rat and T2D human islets. Conclusion: We conclude miR‐29 is a key miRNA in regulating β‐cell mitochondrial metabolism and insulin secretion via underlying miR‐29‐OXPHOS complex pathways. Furthermore, we infer reduced miR‐29 expression compensatorily enhances insulin secretion under glucotoxicity. [ABSTRACT FROM AUTHOR]

In this article, the editor discusses article "3,5-diiodothyronine (3,5-T2) reduces blood glucose independently of insulin sensitization in obese mice" by S. da Silva Teixeira and others in the issue. It mentions impact of thyroid hormones on the glucose uptake into adipose muscle tissue reducing blood glucose levels. It adds benefit of thyroid hormone mimic 3,5-T2 in obese individual with type 2 diabetes.

The article discusses research on the role of transient receptor potential vanilloid I (TRPV1) in regulating erythropoietin-induced activation of endothelial nitric oxide synthase. It references a study by Y.-B. Yu and colleagues published in the issue. It also mentions the stimulus of the TRPV1 channels.

The author focuses on a study "Long-term oral melatonin administration reduces ethanol-induced increases in duodenal mucosal permeability and motility in rats" by researcher A. Sommansson and others, appeared in a 2014 issue of the periodical. The study discusses the impacts of alcohol consumption to develop gastrointestinal disorders. The study also highlights the role of circulating hormone melatonin in regulation of body fat mass, insulin secretion and glucose metabolism.

An introduction is presented in which the editor discusses an article about the effect of the progesterone metabolite allopregnanolone in male Wistar rats that was published in the 2013 issue.

Candesartan is a new angiotensin II type 1 (AT 1 ) receptor blocker that produces more effective 24-h blood pressure lowering than losartan in hypertensive patients. In in vitro tissue preparations, candesartan displays insurmountable antagonism of the responses to angiotensin II. Both irbesartan and EXP-3174, the active metabolite of losartan, have also previously been described in some studies as insurmountable AT 1 -receptor blockers, whereas losartan exhibits surmountable blockade of the AT 1 -receptor. We compared the properties of candesartan, irbesartan, losartan and EXP-3174 in isolated vascular preparations of rat portal vein and rabbit aortic strips. The concentrations of the different AT 1 -receptor antagonists that were effective in these in vitro preparations were also correlated to the non-protein bound plasma concentrations obtained in clinical use. Preparations of the rabbit aorta and the rat portal vein were dissected, mounted on a force-displacement transducer and submerged in oxygenated Krebs' buffer at 37°C. The vessel strips were pre-stretched to a passive force of 5 and 20 mN for portal vein and aorta, respectively. The response to angiotensin II, measured as the mean force development in response to increasing concentrations of angiotensin II, was recorded in the absence and presence of candesartan, 0.003-10 nmol/l, irbesartan, 1-100 nmol/l, losartan, 1-100 nmol/l, and EXP-3174, 0.01-10 nmol/l, for a period of 90 min. In rabbit aortic strips, candesartan caused a non-parallel shift and suppression of the angiotensin II concentration-response curve, with complete suppression of the response to angiotensin II at a dose of candesartan of 1 nmol/l. In contrast, irbesartan, losartan and EXP-3174 all caused a parallel shift of the concentration-response curve. No suppression of the angiotensin II response was seen with losartan, while its active metabolite caused saturable suppression of the maximal response at higher concentrations. For irbesartan, some degree of suppression of the maximal response could not be excluded at the highest concentration studied. Similar concentration-response curves were obtained in rat portal vein. Data on protein binding for the different AT 1 -receptor blockers are variable in the literature. Plasma protein binding for the different AT 1 -receptor blockers was determined (in triplicate) by liquid chromatography with fluorescence detection after equilibrium dialysis (6 h) of cold drug at a concentration of 1500 nmol/l. Protein binding was high (see Table) and, for candesartan, losartan and its active metabolite EXP-3174, in accordance with previously reported levels. For irbesartan, a large discrepancy in protein binding between previously reported and the present experimental data, obtained from two different non-associated laboratories, was found. The higher plasma protein binding for irbesartan found in the present study may explain why high doses of irbesartan seem to be needed for clinical efficacy. It appears unlikely that losartan exerts any significant inhibitory effect at therapeutic plasma levels, and the main AT 1 -blocking effect observed after oral losartan is probably exerted by EXP-3174. It is concluded that AT 1 -receptor blockers differ in their ability to inhibit angiotensin II-mediated vascular contraction, and that the antagonistic characteristics are similar in vessel preparations of different origins and with different degrees of AT 1 -receptor reserve. [ABSTRACT FROM PUBLISHER]

Spectra measured by incoherent scatter radars are formed predominantly by scattering of the incident signal off ion-acoustic and Langmuir waves in the ionosphere. Occasionally, the upshifted and/or downshifted lines produced by the ion-acoustic waves are enhanced well above thermal levels and referred to as naturally enhanced ion-acoustic lines. In this paper, we study another kind of enhancement, which is spectrally uniform over the whole ion-line, i.e. the upand downshifted shoulder and the spectral valley in between. Based on observations made with the EISCAT Svalbard radar (ESR) facility, we investigate the transient and spectrally uniform power enhancements, which can be explained by ionacoustic solitary waves. We use a theory of nonlinear waves in a magnetized plasma to determine the properties of such waves and evaluate their effects on scattered signals measured by ESR.We suggest a new mechanism that can explain backscattered power enhancements by one order of magnitude above the thermal level and show that it is consistent with observations. [ABSTRACT FROM AUTHOR]

Cystic fibrosis-related diabetes (CFRD) is a common complication for patients with cystic fibrosis (CF), a disease caused by mutations in the cysti c fibrosis transmembrane conductance regulator (CFTR). The cause of CFRD is unclear, but a commonly observed reduction in first-phase insulin secretion suggests defects at t he beta cell level. Here we aimed to examine alpha and beta cell function in the Cftrtm1EUR/F508del mouse model (C57BL/6J), which carries the most common human mutation in CFTR, the F508del mutation. CFTR expression, beta cell mass, insulin granule dist ribution, hormone secretion and single cell capacitance changes were evaluated us ing islets (or beta cells) from F508del mice and age-matched wild type (WT) mice aged 7-10 weeks. Granular pH was measured with DND-189 fluorescence. Serum glucose, insuli n and glucagon levels were measured in vivo, and glucose tolerance was assessed using IPGTT. We show increased secretion of proinsulin and concomitant reduced secretion of C-peptide in islets from F508del mice compared to WT mice. Exocytosis and number of docked granules was reduced. We confirmed reduced granular pH by CFTR s timulation. We detected decreased pancreatic beta cell area, but unchanged beta cell number. Moreover, the F508del mutation caused failure to suppress gluca gon secretion leading to hyperglucagonemia. In conclusion, F508del mice have beta cel l defects resulting in (1) reduced number of docked insulin granules and reduced exocy tosis and (2) potential defective proinsulin cleavage and secretion of immature insulin . These observations provide insight into the functional role of CFTR in pancreatic islets and contribute to increased understanding of the pathogenesis of CFRD. [ABSTRACT FROM AUTHOR]

This paper reviews recent progress toward understanding the dynamics of the middle atmosphere in the framework of the Atmospheric Dynamics Research InfraStructure in Europe (ARISE) initiative. The middle atmosphere, integrating the stratosphere and mesosphere, is a crucial region which influences tropospheric weather and climate. Enhancing the understanding of middle atmosphere dynamics requires improved measurement of the propagation and breaking of planetary and gravity waves originating in the lowest levels of the atmosphere. Inter-comparison studies have shown large discrepancies between observations and models, especially during unresolved disturbances such as sudden stratospheric warmings for which model accuracy is poorer due to a lack of observational constraints. Correctly predicting the variability of the middle atmosphere can lead to improvements in tropospheric weather forecasts on timescales of weeks to season. The ARISE project integrates different station networks providing observations from ground to the lower thermosphere, including the infrasound system developed for the Comprehensive Nuclear-Test-Ban Treaty verification, the Lidar Network for the Detection of Atmospheric Composition Change, complementary meteor radars, wind radiometers, ionospheric sounders and satellites. This paper presents several examples which show how multi-instrument observations can provide a better description of the vertical dynamics structure of the middle atmosphere, especially during large disturbances such as gravity waves activity and stratospheric warming events. The paper then demonstrates the interest of ARISE data in data assimilation for weather forecasting and re-analyzes the determination of dynamics evolution with climate change and the monitoring of atmospheric extreme events which have an atmospheric signature, such as thunderstorms or volcanic eruptions. [ABSTRACT FROM AUTHOR]

Impaired beta-cell function is key to the development of type 2 diabetes. Cocaine- and amphetamine-regulated transcript (CART) is an islet peptide with insulinotropic and glucagonostatic properties. Here we studied the role of endogenous CART in beta-cell function. CART silencing in INS-1 (832/13) beta-cells reduced insulin secretion and production, ATP levels and beta-cell exocytosis. This was substantiated by reduced expression of several exocytosis genes, as well as reduced expression of genes important for insulin secretion and processing. In addition, CART silencing reduced the expression of a network of transcription factors essential for beta-cell function. Moreover, in RNAseq data from human islet donors, CARTPT expression levels correlated with insulin, exocytosis genes and key beta-cell transcription factors. Thus, endogenous beta-cell CART regulates insulin expression and secretion in INS-1 (832/13) cells, via actions on the exocytotic machinery and a network of beta-cell transcription factors. We conclude that CART is important for maintaining the beta-cell phenotype. [ABSTRACT FROM AUTHOR]

Aim MiR-375 has been implicated in insulin secretion and exocytosis through incompletely understood mechanisms. Here we aimed to investigate the role of miR-375 in the regulation of voltage-gated Na+ channel properties and glucose-stimulated insulin secretion in insulin-secreting cells. Methods MiR-375 was overexpressed using double-stranded mature miR-375 in INS-1 832/13 cells ( OE375) or downregulated using locked nucleic acid ( LNA)-based anti-miR against miR-375 ( LNA375). Insulin secretion was determined using RIA. Exocytosis and ion channel properties were measured using the patch-clamp technique in INS-1 832/13 cells and beta-cells from miR-375 KO mice. Gene expression was analysed by RT- qPCR, and protein levels were determined by Western blot. Results Voltage-gated Na+ channels were found to be regulated by miR-375. In INS-1 832/13 cells, steady-state inactivation of the voltage-gated Na+ channels was shifted by approx. 6 mV to a more negative membrane potential upon down-regulation of miR-375. In the miR-375 KO mouse, voltage-gated Na+ channel inactivation was instead shifted by approx. 14 mV to a more positive membrane potential. Potential targets differed among species and expression of suggested targets Scn3a and Scn3b in INS-1 832/13 cells was only slightly moderated by miR-375. Modulation of miR-375 levels in INS-1-832/13 cells did not significantly affect insulin release. However, Ca2+ dependent exocytosis was significantly reduced in OE375 cells. Conclusion We conclude that voltage-gated Na+ channels are regulated by miR-375 in insulin-secreting cells, and validate that the exocytotic machinery is controlled by miR-375 also in INS-1 832/13 cells. Altogether we suggest miR-375 to be involved in a complex multifaceted network controlling insulin secretion and its different components. [ABSTRACT FROM AUTHOR]

We present two cases of incoherent-scatter ion line enhancements in conjunction with auroral arcs drifting through the radar beam. The up- and downshifted ion line shoulders as well as the spectral region between them are enhanced equally and simultaneously. The power enhancements are one order of magnitude above the thermal level and are concentrated in less than 15 km wide altitude ranges at the ionospheric F region peak. The auroral arc passages are preceded by significantly enhanced ion temperatures in the E region, assumed to be caused by transient electric fields associated with velocity shears. We use a Hall MHD model of velocity shears perpendicular to the geomagnetic field and show that a Kelvin–Helmholtz instability will grow for the two presented cases. [ABSTRACT FROM AUTHOR]

The Cassini Radio and Plasma Wave Science (RPWS) Langmuir probe (LP) sensor observed the cold plasma environment around Titan during the first two flybys. The data show that conditions in Saturn's magnetosphere affect the structure and dynamics deep in the ionosphere of Titan. The maximum measured ionospheric electron number density reached 3800 per cubic centimeter near closest approach, and a complex chemistry was indicated. The electron temperature profiles are consistent with electron heat conduction from the hotter Titan wake. The ionospheric escape flux was estimated to be 10[sup 25] ions per second. [ABSTRACT FROM AUTHOR]

alpha-Cells were identified in preparations of dispersed mouse islets by immunofluorescence microscopy. A high fraction of alpha-cells correlated with a small cell size measured as the average cell diameter (10 microm) and whole-cell capacitance (<4 pF). The alpha-cells generated action potentials at a low frequency (1 Hz) in the absence of glucose. These action potentials were reversibly inhibited by elevation of the glucose concentration to 20 mmol/l. The action potentials originated from a membrane potential more negative than -50 mV, had a maximal upstroke velocity of 5 V/s, and peaked at +1 mV. Voltage-clamp experiments revealed the ionic conductances underlying the generation of action potentials. alpha-Cells are equipped with a delayed tetraethyl-ammonium-blockable outward current (activating at voltages above -20 mV), a large tetrodotoxin-sensitive Na+ current (above -30 mV; peak current 200 pA at +10 mV), and a small Ca2+ current (above -50 mV; peak current 30 pA at +10 mV). The latter flowed through omega-conotoxin GVIA (25%)- and nifedipine-sensitive (50%) Ca(2+)-channels. Mouse alpha-cells contained, on average, 7,300 granules, which undergo Ca(2+)-induced exocytosis when the alpha-cell is depolarized. Three functional subsets of granules were identified, and the size of the immediately releasable pool was estimated as 80 granules, or 1% of the total granule number. The maximal rate of exocytosis (1.5 pF/s) was observed 21 ms after the onset of the voltage-clamp depolarization, which is precisely the duration of Ca(2+)-influx during an action potential. Our results suggest that the secretory machinery of the alpha-cell is optimized for maximal efficiency in the use of Ca2+ for exocytosis. [ABSTRACT FROM AUTHOR]

The prevalence of macrophotographically documented sialadenitis in the palatal mucosa of 184 probands, aged 23 yr or older, was studied in the Koster Health project. A total of 75 (mean age 58.9) revealed inflammatory changes around the duct orifices of the palatal glands. In 10, biopsies were performed for histomorphologic analyses to confirm the diagnosis of sialadenitis. Statistics with matched pairs showed a significantly higher ratio of tobacco use among individuals with sialadenitis than among those with clinically unchanged palatal gland orifices. A relationship between the use of diuretics and sialadenitis was also statistically significant. It can be concluded that tobacco use and diuretics may induce inflammatory changes in the palatal glands and that macrophotography of the palatal mucosa may serve as a valuable, non-invasive method for scoring sialadenitis. [ABSTRACT FROM AUTHOR]

Here we show that scratch family transcriptional repressor 1 (SCRT1), a zinc finger transcriptional regulator, is a novel regulator of beta cell function. SCRT1 was found to be expressed in beta cells in rodent and human islets. In human islets, expression of SCRT1 correlated with insulin secretion capacity and the expression of the insulin (INS) gene. Furthermore, SCRT1 mRNA expression was lower in beta cells from T2D patients. siRNA-mediated Scrt1 silencing in INS-1832/13 cells, mouse- and human islets resulted in impaired glucose-stimulated insulin secretion and decreased expression of the insulin gene. This is most likely due to binding of SCRT1 to E-boxes of the Ins1 gene as shown with ChIP. Scrt1 silencing also reduced the expression of several key beta cell transcription factors. Moreover, Scrt1 mRNA expression was reduced by glucose and SCRT1 protein was found to translocate between the nucleus and the cytosol in a glucose-dependent fashion in INS-1832/13 cells as well as in a rodent model of T2D. SCRT1 was also regulated by a GSK3β-dependent SCRT1-serine phosphorylation. Taken together, SCRT1 is a novel beta cell transcription factor that regulates insulin secretion and is affected in T2D. • SCRT1 is a novel constituent of human pancreatic beta cells. • SCRT1 has insulin regulatory properties and binds to insulin-E-boxes. • SCRT1 mRNA expression and intracellular localization is regulated by glucose. • SCRT1 expression is altered in T2D patients and an experimental model of T2D. [ABSTRACT FROM AUTHOR]

The MP SAP-c v3 was designed to estimate the volume of menstrual bleeding through self-report, using pictograms of sanitary pads and tampons. The majority (90.0%) of women preferred the MP SAP-c v3 over the AH method for measuring HMB, with 76.7% considering the AH method to be "unhygienic" or "disgusting" and 36.7% considering the MP SAP-c v3 to be "easier". [Extracted from the article]