Pancreatic islet β-cells are factories for insulin production; however, ectopic expression of insulin also is well recognized. The gallbladder is a next-door neighbor to the developing pancreas. ...Here, we wanted to understand if gallbladders contain functional insulin-producing cells.
We compared developing and adult mouse as well as human gallbladder epithelial cells and islets using immunohistochemistry, flow cytometry, enzyme-linked immunosorbent assays, RNA sequencing, real-time polymerase chain reaction, chromatin immunoprecipitation, and functional studies.
We show that the epithelial lining of developing, as well as adult, mouse and human gallbladders naturally contain interspersed cells that retain the capacity to actively transcribe, translate, package, and release insulin. We show that human gallbladders also contain functional insulin-secreting cells with the potential to naturally respond to glucose in vitro and in situ. Notably, in a non-obese diabetic (NOD) mouse model of type 1 diabetes, we observed that insulin-producing cells in the gallbladder are not targeted by autoimmune cells. Interestingly, in human gallbladders, insulin splice variants are absent, although insulin splice forms are observed in human islets.
In summary, our biochemical, transcriptomic, and functional data in mouse and human gallbladder epithelial cells collectively show the evolutionary and developmental similarities between gallbladder and the pancreas that allow gallbladder epithelial cells to continue insulin production in adult life. Understanding the mechanisms regulating insulin transcription and translation in gallbladder epithelial cells would help guide future studies in type 1 diabetes therapy.
Massively parallel DNA sequencing technologies provide an unprecedented ability to screen entire genomes for genetic changes associated with tumour progression. Here we describe the genomic analyses ...of four DNA samples from an African-American patient with basal-like breast cancer: peripheral blood, the primary tumour, a brain metastasis and a xenograft derived from the primary tumour. The metastasis contained two de novo mutations and a large deletion not present in the primary tumour, and was significantly enriched for 20 shared mutations. The xenograft retained all primary tumour mutations and displayed a mutation enrichment pattern that resembled the metastasis. Two overlapping large deletions, encompassing CTNNA1, were present in all three tumour samples. The differential mutation frequencies and structural variation patterns in metastasis and xenograft compared with the primary tumour indicate that secondary tumours may arise from a minority of cells within the primary tumour.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background Outcomes of neoadjuvant systemic therapy versus an upfront operation for clinical, stage III pancreatic adenocarcinoma remain poorly defined. Our aim was to compare survival among patients ...receiving neoadjuvant chemotherapy versus surgery-first with an intention-to-treat analysis. Methods The National Cancer Data Base was reviewed from 2002–2011 for patients with clinical, stage III adenocarcinoma of the head or body of the pancreas. Patients were categorized as neoadjuvant or surgery-first. The intention-to-treat analysis included all neoadjuvant therapy patients in whom a potentially curative operation was planned and all surgery-first patients for whom adjuvant therapy was recommended. Intention-to-treat overall survival was compared by Kaplan-Meier and Cox proportional hazards multivariable regression. Results A total of 593 patients were identified: 377 (63.6%) in the neoadjuvant cohort, wherein 104 (27.6%) experienced preoperative attrition, and 216 (36.4%) in the surgery-first cohort, of whom 30 (13.9%) failed to receive intended adjuvant chemotherapy. Intention-to-treat Kaplan-Meier analysis demonstrated superior survival for neoadjuvant compared to surgery-first (median overall survival 20.7 months vs 13.7 months, log rank P < .001). Intention-to-treat multivariable regression analysis revealed a decreased mortality hazard (hazard ratio = 0.68, 95% confidence interval 0.53–0.86, P = .0012) for neoadjuvant compared to surgery-first. Conclusion Despite preoperative attrition, neoadjuvant therapy in clinical, stage III pancreatic cancer patients is associated with improved overall survival when compared to patients receiving surgery-first.
PAD4 has been strongly implicated in the pathogenesis of autoimmune, cardiovascular and oncological diseases through clinical genetics and gene disruption in mice. New selective PAD4 inhibitors ...binding a calcium-deficient form of the PAD4 enzyme have validated the critical enzymatic role of human and mouse PAD4 in both histone citrullination and neutrophil extracellular trap formation for, to our knowledge, the first time. The therapeutic potential of PAD4 inhibitors can now be explored.
Abstract Background Worsening renal function in heart failure may be related to increased venous congestion, decreased cardiac output, or both. Diuretics are universally used in acute decompensated ...heart failure, but they may be ineffective and may lead to azotemia. We aimed to compare the decongestive properties of a urine output–guided diuretic adjustment and standard therapy for the management of cardiorenal syndrome in acute decompensated heart failure. Methods and Results Data were pooled from subjects randomized to the stepwise pharmacologic care algorithm (SPCA) in the CARRESS-HF trial and those who developed cardiorenal syndrome (rise in creatinine >0.3 mg/dL) in the DOSE-AHF and ROSE-AHF trials. Patients treated with SPCA (n = 94) were compared with patients treated with standard decongestive therapy (SDT) that included intravenous loop diuretic use (DOSE-AHF and ROSE-AHF; n = 107) at the time of cardiorenal syndrome and followed for net fluid balance, weight loss, and changing renal function. The SPCA group had higher degrees of jugular venous pressure ( P < .0001) at the time of cardiorenal syndrome. The group that received SPCA had more weight change (−3.4 ± 5.2 lb) and more net fluid loss (1.705 ± 1.417 L) after 24 hours than the SDT group (−0.8 ± 3.4 lb and 0.892 ± 1.395 L, respectively; P < .001 for both) with a slight improvement in renal function (creatinine change −0.1 ± 0.3 vs 0.0 ± 0.3 mg/dL, respectively; P = .03). Conclusions Compared with SDT, patients who received an intensification of medication therapy for treating persisting congestion had greater net fluid and weight loss without being associated with renal compromise.
We report the discovery of KELT-20b, a hot Jupiter transiting a early A star, HD 185603, with an orbital period of days. Archival and follow-up photometry, Gaia parallax, radial velocities, Doppler ...tomography, and AO imaging were used to confirm the planetary nature of KELT-20b and characterize the system. From global modeling we infer that KELT-20 is a rapidly rotating ( ) A2V star with an effective temperature of K, mass of , radius of , surface gravity of , and age of . The planetary companion has a radius of , a semimajor axis of au, and a linear ephemeris of . We place a upper limit of on the mass of the planet. Doppler tomographic measurements indicate that the planetary orbit normal is well aligned with the projected spin axis of the star ( ). The inclination of the star is constrained to , implying a three-dimensional spin-orbit alignment of . KELT-20b receives an insolation flux of , implying an equilibrium temperature of of ∼2250 K, assuming zero albedo and complete heat redistribution. Due to the high stellar , KELT-20b also receives an ultraviolet (wavelength nm) insolation flux of , possibly indicating significant atmospheric ablation. Together with WASP-33, Kepler-13 A, HAT-P-57, KELT-17, and KELT-9, KELT-20 is the sixth A star host of a transiting giant planet, and the third-brightest host (in V) of a transiting planet.
Three experiments are reported in which we investigate whether the recently reported interactions between central cues (e.g., arrows) and reflexive attention are attributable to the overlearned ...spatial properties of certain central cues. In all three experiments, a nonpredictive cue with arbitrary spatial properties (a colour patch) is presented prior to a detection target in the left or right visual field. Reaction times to detect targets are compared before and after a training session in which participants are trained to associate each colour patch with left and right space, either via a target detection task in which colour predicts target location 100% of the time (Experiments 1 and 3), or via a left/right motor movement as a function of colour (Experiments 2 and 3). In the first two experiments, a small but highly significant training effect is observed. Participants are approximately 10 ms faster to detect targets at congruent locations relative to incongruent locations after training relative to before training, despite the fact that cue colour was nonpredictive during the test sessions. In Experiment 3, the length of the training session is increased and the magnitude of the training effect also increases as a result. Implications for the interaction between central cues and reflexive attention, as well as premotor theory of attention, are discussed.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Malaria and irrigated crops, Accra, Ghana Klinkenberg, Eveline; McCall, P J; Hastings, Ian M ...
Emerging infectious diseases,
08/2005, Letnik:
11, Številka:
8
Journal Article
Recenzirano
Odprti dostop
We investigated the prevalence of malaria and associated risk factors in children living in urban Ghana. Malaria prevalence was associated with low hemoglobin concentration, low socioeconomic status, ...and higher age. Our findings indicate that African urban poor are seriously affected by malaria and that irrigated agriculture may increase this risk.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Pseudomonas aeruginosa is an important cause of pulmonary infection in cystic fibrosis (CF). Its correct identification ensures effective patient management and infection control strategies. However, ...little is known about how often CF sputum isolates are falsely identified as P. aeruginosa. We used P. aeruginosa-specific duplex real-time PCR assays to determine if 2,267 P. aeruginosa sputum isolates from 561 CF patients were correctly identified by 17 Australian clinical microbiology laboratories. Misidentified isolates underwent further phenotypic tests, amplified rRNA gene restriction analysis, and partial 16S rRNA gene sequence analysis. Participating laboratories were surveyed on how they identified P. aeruginosa from CF sputum. Overall, 2,214 (97.7%) isolates from 531 (94.7%) CF patients were correctly identified as P. aeruginosa. Further testing with the API 20NE kit correctly identified only 34 (59%) of the misidentified isolates. Twelve (40%) patients had previously grown the misidentified species in their sputum. Achromobacter xylosoxidans (n = 21), Stenotrophomonas maltophilia (n = 15), and Inquilinus limosus (n = 4) were the species most commonly misidentified as P. aeruginosa. Overall, there were very low rates of P. aeruginosa misidentification among isolates from a broad cross section of Australian CF patients. Additional improvements are possible by undertaking a culture history review, noting colonial morphology, and performing stringent oxidase, DNase, and colistin susceptibility testing for all presumptive P. aeruginosa isolates. Isolates exhibiting atypical phenotypic features should be evaluated further by additional phenotypic or genotypic identification techniques.
Fipronil, a relatively new insecticide more recently developed than organophosphates and pyrethroids, has been detected in surface water draining from agricultural and urban-developed areas. This ...insecticide is primarily lost through subsurface and surface drainage from terrestrial areas where it has been applied. Invasive aquatic plants often need to be managed in these receiving water bodies to prevent loss of recreational and functional values (e.g., drainage), especially in subtropical and tropical areas. One insect of particular interest is the chironomid midge Cricotopus lebetis Sublette, which may be a useful augmentative biocontrol agent for the invasive aquatic weed Hydrilla verticillata L.f. Royale. Exposure of aquatic organisms, especially insects, to fipronil may significantly impact nontarget populations. These studies investigated the sensitivity of C. lebetis to fipronil exposures ranging from 24 to 96 h. The LC
50
observed for each exposure interval was 7.26 μg/L (24 h), 2.61 μg/L (48 h), 1.78 μg/L (72 h), and 1.06 μg/L (96 h). The LC
90
values observed were 47.18 μg/L (24 h), 9.55 μg/L (48 h), 6.45 μg/L (72 h), and 4.81 μg/L (96 h). Behavioral changes were seen at all fipronil concentration levels, where larvae exited the plant and exhibited abnormal behavior, such as restricted movement and lack of feeding. Results indicate that acute lethality occurred at environmentally relevant concentrations of fipronil.
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