bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered mRNP granule dynamics in FTLD pathogenesis
Authors: Bowden Hilary A. , Dormann Dorothee 
Published: March 2016

AbstractIn neurons, RNA‐binding proteins (RBPs) play a key role in post‐transcriptional gene regulation, for example alternative splicing, mRNA localization in neurites and local translation upon synaptic stimulation. There is increasing evidence that defective or mislocalized RBPs – and consequently altered mRNA processing – lead to neuronal dysfunction and cause neurodegeneration, including frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Cytosolic RBP aggregates containing TAR DNA‐binding protein of 43 kDa (TDP‐43) or fused in sarcoma (FUS) are a common hallmark of both disorders. There is mounting evidence that translationally silent mRNP granules, such as stress granules or transport granules, play an important role in the formation of these RBP aggregates. These granules are thought to be ‘catalytic convertors’ of RBP aggregation by providing a high local concentration of RBPs. As recently shown in vitro, RBPs that contain a so‐called low‐complexity domain start to ‘solidify’ and eventually aggregate at high protein concentrations. The same may happen in mRNP granules in vivo, leading to ‘solidified’ granules that lose their dynamic properties and ability to fulfill their physiological functions. This may result in a disturbed stress response, altered mRNA transport and local translation, and formation of pathological TDP‐43 or FUS aggregates, all of which may contribute to neuronal dysfunction and neurodegeneration. Here, we discuss the general functional properties of these mRNP granules, how their dynamics may be disrupted in frontotemporal lobar degeneration/amyotrophic lateral sclerosis, for example by loss or gain of function of TDP‐43 and FUS, and how this may contribute to the development of RBP aggregates and neurotoxicity.
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In this review, we discuss how dynamic mRNP granules, such as stress granules or neuronal transport granules, may be converted into pathological aggregates containing misfolded RNA‐binding proteins (RBPs), such as TDP‐43 and FUS. Abnormal interactions between low‐complexity domains in RBPs may cause dynamic mRNP granules to solidify and become dysfunctional. This may result in a disturbed stress response, altered mRNA transport and local translation, as well as RBP aggregation, all of which may contribute to neuronal dysfunction and neurodegeneration.This article is part of the Frontotemporal Dementia special issue.
Exocytosis in non‐neuronal cells
Authors: Thorn Peter , Zorec Robert , Rettig Jens , Keating Damien J. 
Published: March 2016

AbstractExocytosis is the process by which stored neurotransmitters and hormones are released via the fusion of secretory vesicles with the plasma membrane. It is a dynamic, rapid and spatially restricted process involving multiple steps including vesicle trafficking, tethering, docking, priming and fusion. For many years great steps have been undertaken in our understanding of how exocytosis occurs in different cell types, with significant focus being placed on synaptic release and neurotransmission. However, this process of exocytosis is an essential component of cell signalling throughout the body and underpins a diverse array of essential physiological pathways. Many similarities exist between different cell types with regard to key aspects of the exocytosis pathway, such as the need for Ca2+ to trigger it or the involvement of members of the N‐ethyl maleimide‐sensitive fusion protein attachment protein receptor protein families. However, it is also equally clear that non‐neuronal cells have acquired highly specialized mechanisms to control the release of their own unique chemical messengers. This review will focus on several important non‐neuronal cell types and discuss what we know about the mechanisms they use to control exocytosis and how their specialized output is relevant to the physiological role of each individual cell type. These include enteroendocrine cells, pancreatic β cells, astrocytes, lactotrophs and cytotoxic T lymphocytes.
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Non‐neuronal cells have acquired highly specialized mechanisms to control the release of unique chemical messengers, such as polarised fusion of insulin granules in pancreatic β cells targeted towards the vasculature (top). This review discusses mechanisms used in several important non‐neuronal cell types to control exocytosis, and the relevance of intermediate vesicle fusion pore states (bottom) and their specialized output to the physiological role of each cell type. These include enteroendocrine cells, pancreatic β cells, astrocytes, lactotrophs and cytotoxic T lymphocytes.This article is part of a mini review series on Chromaffin cells (ISCCB Meeting, 2015).
Cranial biomechanics, bite force and function of the endocranial sinuses in Diprotodon optatum, the largest known marsupial
Authors: Sharp Alana C. , Rich Thomas H. 
Published: March 2016

AbstractThe giant extinct marsupial Diprotodon optatum has unusual skull morphology for an animal of its size, consisting of very thin bone and large cranial sinuses that occupy most of the internal cranial space. The function of these sinuses is unknown as there are no living marsupial analogues. The finite element method was applied to identify areas of high and low stress, and estimate the bite force of Diprotodon to test hypotheses on the function of the extensive cranial sinuses. Detailed three‐dimensional models of the cranium, mandible and jaw adductor muscles were produced. In addition, manipulations to the Diprotodon cranial model were performed to investigate changes in skull and sinus structure, including a model with no sinuses (sinuses ‘filled’ with bone) and a model with a midsagittal crest. Results indicate that the cranial sinuses in Diprotodon significantly lighten the skull while still providing structural support, a high bite force and low stress, indicating the cranium may have been able to withstand higher loads than those generated during feeding. Data from this study support the hypothesis that pneumatisation is driven by biomechanical loads and occurs in areas of low stress. The presence of sinuses is likely to be a byproduct of the separation of the outer surface of the skull from the braincase due to the demands of soft tissue including the brain and the large jaw adductor musculature, especially the temporalis. In very large species, such as Diprotodon, this separation is more pronounced, resulting in extensive cranial sinuses due to a relatively small brain compared with the size of the skull.
Correlation of serum fructosamine and recurrent pregnancy loss: Case–control study
Authors: Romero Stephanie T. , Sharshiner Rita , Stoddard Gregory J. , Ware Branch D. , Silver Robert M. 
Published: March 2016

AbstractAimPre‐gestational diabetes is associated with an elevated risk of pregnancy loss, but it is unclear whether subclinical glucose intolerance is associated with pregnancy loss, especially recurrent pregnancy loss (RPL). The aim of this study was therefore to compare maternal serum fructosamine (a marker of glycemic control) in patients with and without RPL.MethodsA case–control study was carried out of 117 women with unexplained RPL, defined as two or more pregnancy losses with no more than one live birth, and 117 age‐matched controls with at least one full‐term uncomplicated pregnancy and no more than one pregnancy loss. No RPL patients or controls had a clinical diagnosis of pre‐gestational or gestational diabetes. Maternal serum was analyzed for fructosamine on quantitative spectrophotometry.ResultsMean body mass index (BMI) of RPL patients was 26.0 ± 6.4 kg/m2 compared with 26.6 ± 5.8 kg/m2 (P = 0.40). Fructosamine was higher in women with RPL (224.1 ± 28.79 μmol/mL) compared with controls (188.9 ± 19.3 μmol/mL, P < 0.001). This difference persisted when RPL patients and controls were stratified by BMI. The proportion of women with elevated fructosamine considered diagnostic of diabetes (>285 μmol/L) was similar in RPL patients and controls.ConclusionThe RPL patients and controls had a similar proportion of women with elevated fructosamine considered diagnostic of diabetes. Serum fructosamine was increased in women with RPL compared with controls. Thus, subclinical glucose intolerance may be associated with an increased risk of RPL. These data support further investigation into the mechanisms of RPL associated with glucose intolerance, but do not support testing for subclinical glucose intolerance in women with RPL.
Brain Volume Loss During the First Year of Interferon‐Beta Treatment in Multiple Sclerosis: Baseline Inflammation and Regional Brain Volume Dynamics
Authors: Vidal‐Jordana Angela , Sastre‐Garriga Jaume , Pérez‐Miralles Francisco , Pareto Deborah , Rio Jordi , Auger Cristina , Tintoré Mar , Rovira Alex , Montalban Xavier 
Published: March 2016

ABSTRACTOBJECTIVEA pseudoatrophy effect, mostly affecting white matter, can be observed in patients with multiple sclerosis (MS) early on natalizumab therapy. We aimed to investigate whether a similar pattern could be found after interferon‐beta treatment onset.METHODSFrom a prospective, ongoing cohort, 123 patients treated with interferon‐beta were included. A brain MRI was performed at baseline (3 months prior) and 12 months after therapy onset in all patients. SPM8 software was used for volumetric analysis. Brain parenchymal, gray and white matter volumes at baseline and follow‐up were obtained, allowing calculation of percentage of volume changes (BVc, GMVc, and WMVc, respectively). Descriptive statistics and linear regression models were performed.RESULTSEighty‐four patients were analyzed (39 patients were excluded mostly due to incomplete MRI protocol or segmentation errors); baseline mean age was 33.6 years (SD 8.7), median disease duration was 2.8 years (.3‐14), and median EDSS was 1.5 (0‐6). Forty‐nine patients (58.3%) had baseline gadolinium‐enhancing (Gd+) lesions with a median number of 1 (0‐18). The regression analysis (adjusted by the number of Gd+ at follow‐up MRI, age, disease duration, and baseline EDSS) showed that a higher baseline number of Gd+ lesions was predictive of larger decreases in BVc and WMVc (P = .013 and P = .003, respectively) but not GMVc (P = .777).CONCLUSIONConcurrent inflammation has an impact on brain volume measurements (especially white matter) during the first year of interferon‐beta therapy, and should be taken into account when interpreting early brain volume changes on therapy.
Effects of monensin and essential oils on immunological, haematological and biochemical parameters of cows during the transition period
Authors: Drong C. , Meyer U. , von Soosten D. , Frahm J. , Rehage J. , Schirrmeier H. , Beer M. , Dänicke S. 
Published: March 2016

SummaryUsing a model to generate experimental groups with different manifestations of post‐partum (p.p.) fat mobilization and ketogenesis, the effects of a dietary and a medical intervention on biochemical and haematological parameters, antibody titre, leucocytes subsets and function of transition cows were examined. In total, 60 German Holstein cows were allocated 6 weeks antepartum (a.p.) to 3 high‐body condition score (BCS) groups (BCS 3.95) and 1 low‐BCS group (LC, BCS 2.77). High‐BCS cows received a monensin controlled‐release capsule (HC/MO) or a blend of essential oils (HC/EO) or formed a control group (HC). Parameters were evaluated in 3 periods (day (d) −42 until calving, 1 until 14 days in milk (DIM), 15 until 56 DIM).Over the course of trial, various parameters were influenced by period with greatest variability next to calving. White blood cell count was higher in the HC (8.42 × 103/μl) and HC/EO (8.38 × 103/μl) groups than in the HC/MO group (6.81 × 103/μl) considering the whole trial. Supplementation of monensin decreased aspartate aminotransferase in comparison with the HC group similar to LC treatment. Bilirubin concentration was nearly doubled in all high‐BCS cows in period 2. In period 3, essential oils increased γ‐glutamyltransferase (80.4 Units/l) in comparison with all other groups and glutamine dehydrogenase (61 Units/l) in comparison with the LC (19 Units/l) and the HC/MO group (18 Units/l).Results suggest that parameters were generally characterized by a high variability around calving. Based on biochemical characteristics, it appeared that the HC cows seemed to have compromised hepatocyte integrity when compared to the LC cows. From the immune parameters investigated, the BVDV antibody response was more pronounced in HC/MO compared to HC/EO.
Temperature‐dependent phagotrophy and phototrophy in a mixotrophic chrysophyte
Authors: Princiotta Sarah DeVaul , Smith Brian T. , Sanders Robert W. 
Published: March 2016

The roles of temperature and light on grazing and photosynthesis were examined for Dinobryon sociale, a common freshwater mixotrophic alga. Photosynthetic rate was determined for D. sociale adapted to temperatures of 8, 12, 16, and 20°C under photosynthetically active radiation light irradiances of 25, 66, and 130 μmol photons · m−2 · s−1, with concurrent measurement of bacterial ingestion at all temperatures under medium and high light (66 and 130 μmol photons · m−2 · s−1). Rates of ingestion and photosynthesis increased with temperature to a maximum at 16°C under the two higher light regimes, and declined at 20°C. Although both light and temperature had a marked effect on photosynthesis, there was no significant difference in bacterivory at medium and high irradiances at any given temperature. At the lowest light condition (25 μmol photons · m−2 · s−1), photosynthesis remained low and relatively stable at all temperatures. D. sociale acquired the majority of carbon from photosynthesis, although the low photosynthetic rate without a concurrent decline in feeding rate at 8°C suggested 20%–30% of the carbon budget could be attributed to bacterivory at low temperatures. Grazing experiments in nutrient‐modified media revealed that this mixotroph had increased ingestion rates when either dissolved nitrogen or phosphorus was decreased. This work increases our understanding of environmental effects on mixotrophic nutrition. Although the influence of abiotic factors on phagotrophy and phototrophy in pure heterotrophs and phototrophs has been well studied, much less is known for mixotrophic organisms.
Impact of smoking on experimental gingivitis. A clinical, microbiological and immunological prospective study
Authors: Peruzzo D. C. , Gimenes J. H. , Taiete T. , Casarin R. C. V. , Feres M. , Sallum E. A. , Casati M. Z. , Kantovitz K. R. , Nociti F. H. 
Published: March 2016

ObjectiveThe present study assessed the effect of smoking on clinical, microbiological and immunological parameters in an experimental gingivitis model.Material and MethodsTwenty‐four healthy dental students were divided into two groups: smokers (n = 10); and nonsmokers (n = 14). Stents were used to prevent biofilm removal during brushing. Visible plaque index (VPI) and gingival bleeding index (GBI) were determined 5‐ on day ‐7 (running phase), baseline, 21 d (experimental gingivitis) and 28 d (resolution phase). Supragingival biofilm and gingival crevicular fluid were collected and assayed by checkerboard DNA–DNA hybridization and a multiplex analysis, respectively. Intragroup comparison was performed by Friedman and Dunn's multiple comparison tests, whereas the Mann–Whitney U‐test was applied for intergroup analyses.ResultsCessation of oral hygiene resulted in a significant increase in VPI, GBI and gingival crevicular fluid volume in both groups, which returned to baseline levels 7 d after oral hygiene was resumed. Smokers presented lower GBI than did nonsmokers (p < 0.05) at day 21. Smokers had higher total bacterial counts and higher proportions of red‐ and orange complex bacteria, as well as lower proportions of Actinomyces spp., and of purple‐ and yellow‐complex bacteria (p < 0.05). Furthermore, the levels of key immune‐regulatory cytokines, including interleukin (IL)‐8, IL‐17 and interferon‐γ, were higher in smokers than in nonsmokers (p < 0.05).ConclusionSmokers and nonsmokers developed gingival inflammation after supragingival biofilm accumulation, but smokers had less bleeding, higher proportions of periodontal pathogens and distinct host‐response patterns during the course of experimental gingivitis.
Therapeutic outcome of 6198 interferon‐naïve Egyptian patients with chronic hepatitis C: a real‐life experience and lessons to be learned in DAAs’ era
Authors: Zayed N. , Gamal Eldeen H. , Elmakhzangy H. , Seif M. , El‐Akel W. , Awad T. , Esmat G. , Mabrouk M. 
Published: March 2016

SummaryAntiviral therapy for HCV infection has been validated in randomized controlled clinical trials, but its value in the real world is less well studied. There is relatively little data on real‐world responses to interferon‐based therapies for patients with genotype 4 infection. We aimed to examine experience with large‐scale access to antiviral therapy in chronic HCV in a real‐life clinical setting in Egypt. Detailed pretreatment data of 6198 IFN‐naïve chronic HCV patients who had received PEG‐IFN/RBV therapy at Cairo‐Fatemic Hospital, Egypt, between 2009 and 2012 were obtained from the HCV database. At week 12, 95.7% of patients had undetectable HCV RNA, and by week 24 and 48, breakthrough was 6% and 4%, respectively. However, 43.7% of patients discontinued treatment prematurely, and intent to treat end of treatment response was 44.6% (79.3% per protocol). Sustai‐ned response data were available from only 1281 patients and was 84.9%. Haematological abnormalities were comparable in patients who did or did not comply with therapy. This is the first real‐world, large‐scale experience of antiviral therapy in chronic HCV in Egypt. Suboptimal response in HCV predominantly genotype 4 was mainly driven by noncompliance as well as gaps in the healthcare system leading to treatment discontinuation. These results need to be considered in the era of all oral antiviral regimes.
Should surveillance for liver cancer be modified in hepatitis C patients after treatment‐related cirrhosis regression?
Authors: D'Ambrosio Roberta , Colombo Massimo 
Published: March 2016

AbstractSurveillance of hepatocellular carcinoma (HCC) with abdominal ultrasound (US) is recommended for patients with advanced liver fibrosis because of hepatitis C virus (HCV) infections who achieve a sustained virological response (SVR) to antiviral therapy. HCC, in fact, may still develop following SVR as a consequence of long‐standing carcinogenic activity of either HCV or hepatic fibrosis, whereas HCC risk in non‐viraemic patients may also be driven by cofactors like alcohol abuse or diabetes. This explains the debate on whether surveillance for HCC should be continued in patients with documented cirrhosis regression following a SVR too. While regression of cirrhosis was documented to occur in a majority of patients with compensated cirrhosis 5 years after an SVR to interferon, it should be noted that this clinical benefit could be the consequence of treating a selected population with well‐compensated liver disease who in fact were interferon able. This may not be the case for most real‐life patients with advanced cirrhosis receiving direct antivirals, in whom liver fibrosis may have reached a point of no‐return thus potentially preventing the recovery of a normal liver architecture following SVR. Both invasive and non‐invasive tools have suboptimal diagnostic accuracy for fibrosis regression in non‐viraemic patients, and this prompts to follow international societies’ recommendation to perform surveillance in patients with advanced liver fibrosis achieving a SVR, independently on liver histology outcome.
Anthropogenic impacts on nitrogen fixation rates between restored and natural Mediterranean salt marshes
Authors: Moseman‐Valtierra Serena , Levin Lisa A. , Martin Rose M. 
Published: March 2016

AbstractTo test the effects of site and successional stage on nitrogen fixation rates in salt marshes of the Venice Lagoon, Italy, acetylene reduction assays were performed with Salicornia veneta‐ and Spartina townsendii‐vegetated sediments from three restored (6–14 years) and two natural marshes. Average nitrogen fixation (acetylene reduction) rates ranged from 31 to 343 μmol C2H4·m−2·h−1 among all marshes, with the greatest average rates being from one natural marsh (Tezze Fonde). These high rates are up to six times greater than those reported from Southern California Spartina marshes of similar Mediterranean climate, but substantially lower than those found in moister climates of the Atlantic US coast. Nitrogen fixation rates did not consistently vary between natural and restored marshes within a site (Fossei Est, Tezze Fonde, Cenesa) but were negatively related to assayed plant biomass within the acetylene reduction samples collected among all marshes. Highest nitrogen fixation rates were found at Tezze Fonde, the location closest to the city of Venice, in both natural and restored marshes, suggesting possible site‐specific impacts of anthropogenic stress on marsh succession.
Case of intermittent claudication as a result of cervical myelopathy presenting with ankle clonus induced by the gait loading test
Authors: Sawamura Masanori , Murata Oki , Ogawa Masafumi 
Published: March 2016

AbstractSpinal lesions can cause intermittent claudication. A 67‐year‐old man was referred to our department with a 3‐year history of progressive intermittent claudication. Spinal magnetic resonance imaging showed only moderate cervical canal stenosis, but not severe lumbar canal stenosis, which could cause intermittent claudication. The gait loading test reproduced tightness and weakness in the lower extremities, as well as an induced pyramidal tract sign that included Achilles tendon hyperreflexia and right ankle clonus. He was therefore diagnosed with spinal intermittent claudication. Two weeks later, sudden lower limb paralysis with urinary retention appeared without a traumatic event. After cervical spine surgery, the intermittent claudication disappeared. Spinal claudication is rare, and a relatively unknown symptom. As such, it is therefore a diagnostic challenge. Here, we highlight the importance of a full clinical report and the usefulness of the gait loading test for determining the clinical diagnosis.
Imaginatively‐Colored Perception: Walton on Pictorial Experience
Authors: Chasid Alon 
Published: March 2016

AbstractThis paper develops Kendall Walton's account of pictorial experience. Walton argues that the key feature of that experience is that it is imaginatively‐penetrated experience. I argue that this idea, as put forward by Walton, has various shortcomings. After discussing these limitations, I suggest, on the basis of a more general phenomenon of cognitive penetration, a refinement of Walton's account. I then show how the revised account explains various features of pictorial experience. Specifically, I show that, given the manner in which imaginings influence perceptual experience, Walton can dispense with the thesis that pictorial experience is twofold.
Transactive Memory Reconstructed: Rethinking Wegner's Research Program
Authors: Huebner Bryce 
Published: March 2016

AbstractIn this paper, I argue that recent research on episodic memory supports a limited defense of the phenomena that Daniel Wegner has termed transactive memory. Building on psychological and neurological research, targeting both individual and shared memory, I argue that individuals can collaboratively work to construct shared episodic memories. In some cases, this yields memories that are distributed across multiple individuals instead of being housed in individual brains.