bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diminished supraspinal pain modulation in patients with mild traumatic brain injury
Authors: Leung Albert , Shukla Shivshil , Yang Eric , Canlas Bryan , Kadokana Mawj , Heald Jason , Davani Ariea , Song David , Lin Lisa , Polston Greg , Tsai Alice , Lee Roland 
Published: August 2016

Background Chronic pain conditions are highly prevalent in patients with mild traumatic brain injury. Supraspinal diffuse axonal injury is known to dissociate brain functional connectivity in these patients. The effect of this dissociated state on supraspinal pain network is largely unknown. A functional magnetic resonance imaging study was conducted to compare the supraspinal pain network in patients with mild traumatic brain injury to the gender and age-matched healthy controls with the hypothesis that the functional connectivities of the medial prefrontal cortices, a supraspinal pain modulatory region to other pain-related sensory discriminatory and affective regions in the mild traumatic brain injury subjects are significantly reduced in comparison to healthy controls. Results The mild traumatic brain injury group ( N = 15) demonstrated significantly ( P < 0.01, cluster threshold > 150 voxels) less activities in the thalamus, pons, anterior cingulate cortex, insula, dorsolateral prefrontal cortex, and medial prefrontal cortices than the healthy control group ( N = 15). Granger Causality Analyses (GCA) indicated while the left medial prefrontal cortices of the healthy control group cast a noticeable degree of outward (to affect) causality inference to multiple pain processing related regions, this outward inference pattern was not observed in the mild traumatic brain injury group. On the other hand, only patients’ bilateral anterior cingulate cortex received multiple inward (to be affected) causality inferences from regions including the primary and secondary somatosensory cortices and the inferior parietal lobe. Resting state functional connectivity analyses indicated that the medial prefrontal cortices of the mild traumatic brain injury group demonstrated a significantly ( P < 0.01, F = 3.6, cluster size > 150 voxels) higher degree of functional connectivity to the inferior parietal lobe, premotor and secondary somatosensory cortex than the controls. Conversely, the anterior cingulate cortex of the healthy group demonstrated significantly ( P < 0.01, F = 3.84, cluster size > 150 voxels) less degree of functional connectivities to the inferior parietal lobe and secondary somatosensory cortex than their mild traumatic brain injury counterparts. Conclusions In short, the current study demonstrates that patients with mild traumatic brain injury and headaches appear to have an altered state of supraspinal modulatory and affective functions related to pain perception.
Is size an essential criterion to define tumefactive plaque? MR features and clinical correlation in multiple sclerosis
Authors: Patriarca Lucia , Torlone Silvia , Ferrari Fabiana , Di Carmine Caterina , Totaro Rocco , di Cesare Ernesto , Splendiani Alessandra 
Published: August 2016

Tumefactive multiple sclerosis is an inflammatory demyelinating disease of the central nervous system. It has recently been described as a rare subtype of multiple sclerosis (MS) characterised by the appearance of solitary or multiple space-occupying lesions associated with imaging characteristics mimicking neoplasm. Atypical features include plaque size >2 cm with mass effect, oedema, and/or ring enhancement on magnetic resonance (MR) images. This study is a retrospective review designed to evaluate the prevalence of tumefactive plaques in a selected population of 440 MS patients referred to our MS centre in Southern Italy between 2005 and 2014. We analysed the radiographic features of lesions ranging in size from 0.5 to 2 cm to establish whether smaller plaques with MR characteristics similar to tumefactive plaques present different symptoms, disease evolution and prognosis. We also aimed to ascertain if MR features suggestive of biological aggressiveness could be useful prognostic criteria for a correct diagnosis of the disease and subsequent treatment. Our data suggest that lesions 0.5–2 cm and >2 cm have similar MR features and clinical evolution.
Estimation of the prevalence of intraductal papillary mucinous neoplasm of the pancreas in the French population through patients waiting for liver transplantation
Authors: Laurent Lucie , Vullierme Marie‐Pierre , Rebours Vinciane , Maire Frédérique , Hentic Olivia , Francoz Claire , Durand François , Ruszniewski Philippe , Lévy Philippe 
Published: August 2016

Background and aimsSome studies have explored the prevalence of pancreatic cystic lesions (PCLs). Only one study based on magnetic resonance imaging (MRI) report examination focused specifically on intraductal papillary mucinous neoplasm (IPMN) in a European general population. The aim of this study was to evaluate the prevalence of IPMN in a population of patients who had MRI for a non‐pancreatic disease.MethodsWe conducted a retrospective, single‐center study. All consecutive patients placed on the French liver transplant waiting list who had MRI for a non‐pancreatic disease before liver transplantation between 2009 and 2013 were included. Only diagnoses consistent with IPMN were retained (cyst(s) clearly communicating with the main pancreatic duct).ResultsAmong 315 patients on the national waiting list, 212 patients had an MRI. PCLs with ductal communication were diagnosed in 14 patients (6.6%; six women, eight men, median age 62 years (45–70)). Liver disease was caused by a virus in seven cases, alcohol in three cases, other in four cases (multiple causes possible). Four patients had hepatocellular carcinoma. No patient had clinical or radiological sign of chronic pancreatitis. The median diameter of the largest cystic lesion was 14 mm (7–22). The number of PCLs was one (n  = 4), two (n  = 2), four (n  = 3), five (n  = 2), > 5 (n  = 3), respectively. There was no worrisome or main pancreatic duct involvement.ConclusionsPrevalence of pancreatic cystic lesions consistent with the diagnosis of IPMN was 6.6% in French patients waiting for liver transplantation. These results underscore that IPMN can be considered as a public health problem and justify a screening.
A machine learning strategy for predicting localization of post-translational modification sites in protein-protein interacting regions
Authors: Saethang Thammakorn , Payne D. Michael , Avihingsanon Yingyos , Pisitkun Trairak 
Published: August 2016

Abstract
Background
One very important functional domain of proteins is the protein-protein interacting region (PPIR), which forms the binding interface between interacting polypeptide chains. Post-translational modifications (PTMs) that occur in the PPIR can either interfere with or facilitate the interaction between proteins. The ability to predict whether sites of protein modifications are inside or outside of PPIRs would be useful in further elucidating the regulatory mechanisms by which modifications of specific proteins regulate their cellular functions.

Results
Using two of the comprehensive databases for protein-protein interaction and protein modification site data (PDB and PhosphoSitePlus, respectively), we created new databases that map PTMs to their locations inside or outside of PPIRs. The mapped PTMs represented only 5 % of all known PTMs. Thus, in order to predict localization within or outside of PPIRs for the vast majority of PTMs, a machine learning strategy was used to generate predictive models from these mapped databases. For the three mapped PTM databases which had sufficient numbers of modification sites for generating models (acetylation, phosphorylation, and ubiquitylation), the resulting models yielded high overall predictive performance as judged by a combined performance score (CPS). Among the multiple properties of amino acids that were used in the classification tasks, hydrophobicity was found to contribute substantially to the performance of the final predictive models. Compared to the other classifiers we also evaluated, the SVM provided the best performance overall.

Conclusions
These models are the first to predict whether PTMs are located inside or outside of PPIRs, as demonstrated by their high predictive performance. The models and data presented here should be useful in prioritizing both known and newly identified PTMs for further studies to determine the functional relationship between specific PTMs and protein-protein interactions. The implemented R package is available online (http://sysbio.chula.ac.th/PtmPPIR).
Characterization of FRM-36143 as a new γ-secretase modulator for the potential treatment of familial Alzheimer’s disease
Authors: Blain Jean-François , Bursavich Matthew G. , Freeman Emily A. , Hrdlicka Lori A. , Hodgdon Hilliary E. , Chen Ting , Costa Don E. , Harrison Bryce A. , Kapadnis Sudarshan , Murphy Deirdre A. , Nolan Scott , Tu Zhiming , Tang Cuyue , Burnett Duane A. , Patzke Holger , Koenig Gerhard 
Published: August 2016

Abstract
Background
Familial Alzheimer’s disease (FAD) is caused by mutations in the amyloid precursor protein (APP) or presenilin (PS). Most PS mutations, which account for the majority of FAD cases, lead to an increased ratio of longer to shorter forms of the amyloid beta (Aβ) peptide. The therapeutic rationale of γ-secretase modulators (GSMs) for Alzheimer’s disease is based on this genetic evidence as well as on enzyme kinetics measurements showing changes in the processivity of the γ-secretase complex. This analysis suggests that GSMs could potentially offset some of the effects of PS mutations on APP processing, thereby addressing the root cause of early onset FAD. Unfortunately, the field has generated few, if any, molecules with good central nervous system (CNS) drug-like properties to enable proof-of-mechanism studies.

Method
We characterized the novel GSM FRM-36143 using multiple cellular assays to determine its in vitro potency and off-target activity as well as its potential to reverse the effect of PS mutations. We also tested its efficacy in vivo in wild-type mice and rats.

Results
FRM-36143 has much improved CNS drug-like properties compared to published GSMs. It has an in vitro EC50 for Aβ42 of 35 nM in H4 cells, can reduce Aβ42 to 58 % of the baseline in rat cerebrospinal fluid, and also increases the non-amyloidogenic peptides Aβ37 and Aβ38. It does not inhibit Notch processing, nor does it inhibit 24-dehydrocholesterol reductase (DHCR24) activity. Most interestingly, it can reverse the effects of presenilin mutations on APP processing in vitro.

Conclusions
FRM-36143 possesses all the characteristics of a GSM in terms of Aβ modulation Because FRM-36143 was able to reverse the effect of PS mutations, we suggest that targeting patients with this genetic defect would be the best approach at testing the efficacy of a GSM in the clinic. While the amyloid hypothesis is still being tested with β-site APP-cleaving enzyme inhibitors and monoclonal antibodies in sporadic AD, we believe it is not a hypothesis for FAD. Since GSMs can correct the molecular defect caused by PS mutations, they have the promise to provide benefits to the patients when treated early enough in the course of the disease.
The ACVR1 R206H mutation found in fibrodysplasia ossificans progressiva increases human induced pluripotent stem cell-derived endothelial cell formation and collagen production through BMP-mediated SMAD1/5/8 signaling
Authors: Barruet Emilie , Morales Blanca M. , Lwin Wint , White Mark P. , Theodoris Christina V. , Kim Hannah , Urrutia Ashley , Wong Sarah Anne , Srivastava Deepak , Hsiao Edward C. 
Published: August 2016

Abstract
Background
The Activin A and bone morphogenetic protein (BMP) pathways are critical regulators of the immune system and of bone formation. Inappropriate activation of these pathways, as in conditions of congenital heterotopic ossification, are thought to activate an osteogenic program in endothelial cells. However, if and how this occurs in human endothelial cells remains unclear.

Methods
We used a new directed differentiation protocol to create human induced pluripotent stem cell (hiPSC)-derived endothelial cells (iECs) from patients with fibrodysplasia ossificans progressiva (FOP), a congenital disease of heterotopic ossification caused by an activating R206H mutation in the Activin A type I receptor (ACVR1). This strategy allowed the direct assay of the cell-autonomous effects of ACVR1 R206H in the endogenous locus without the use of transgenic expression. These cells were challenged with BMP or Activin A ligand, and tested for their ability to activate osteogenesis, extracellular matrix production, and differential downstream signaling in the BMP/Activin A pathways.

Results
We found that FOP iECs could form in conditions with low or absent BMP4. These conditions are not normally permissive in control cells. FOP iECs cultured in mineralization media showed increased alkaline phosphatase staining, suggesting formation of immature osteoblasts, but failed to show mature osteoblastic features. However, FOP iECs expressed more fibroblastic genes and Collagen 1/2 compared to control iECs, suggesting a mechanism for the tissue fibrosis seen in early heterotopic lesions. Finally, FOP iECs showed increased SMAD1/5/8 signaling upon BMP4 stimulation. Contrary to FOP hiPSCs, FOP iECs did not show a significant increase in SMAD1/5/8 phosphorylation upon Activin A stimulation, suggesting that the ACVR1 R206H mutation has a cell type-specific effect. In addition, we found that the expression of ACVR1 and type II receptors were different in hiPSCs and iECs, which could explain the cell type-specific SMAD signaling.

Conclusions
Our results suggest that the ACVR1 R206H mutation may not directly increase the formation of mature chondrogenic or osteogenic cells by FOP iECs. Our results also show that BMP can induce endothelial cell dysfunction, increase expression of fibrogenic matrix proteins, and cause differential downstream signaling of the ACVR1 R206H mutation. This iPSC model provides new insight into how human endothelial cells may contribute to the pathogenesis of heterotopic ossification.
Vitamin D machinery and metabolism in porcine adipose-derived mesenchymal stem cells
Authors: Valle Yovani Llamas , Almalki Sami G. , Agrawal Devendra K. 
Published: August 2016

Abstract
Background
Vitamin D, a hormone once thought to have a role limited to calcium homeostasis and bone mineralization, has pleiotropic effects on different types of cells. Vitamin D receptors are reported in vascular smooth muscle cells, endothelial cells, and cardiomyocytes. Adipose-derived MSCs (ADMSCs) are multipotent cells with the capacity to differentiate into cells of different lineages. To our knowledge, the presence of vitamin D machinery on porcine ADMSCs has not yet been examined. In this study, we investigated the presence of vitamin D machinery and metabolism in ADMSCs by analyzing the expression levels of vitamin D receptor (VDR), vitamin D metabolizing enzymes (CYP24A1 and CYP27B1) after in vitro stimulation with active vitamin D, calcitriol.

Methods and results
ADMSCs isolated from porcine adipose tissue were characterized by positive staining for ADMSC markers, CD44, CD73, and CD90, and negative staining for macrophage marker CD11b and hematopoietic stem cell markers CD34 and CD45, and trilineage differentiation to osteocytes, chondrocytes, and adipocytes. No cytotoxicity was observed when MSCs were stimulated with 0.1–10 nM calcitriol. The ADMSCs were analyzed for mRNA and protein expression of CYP24A1, CYP27B1, and VDR by immunostaining, qPCR, and ELISA. A significant increase (p <0.01) in the mRNA expression of CYP24A1, CYP27B1, and VDR was observed after stimulation of ADMSCs with calcitriol (10 nM). The in vitro time-dependent effect of calcitriol (10 nM) on the components of vitamin D machinery in cultured MSCs was determined by qPCR. The VDR and CYP27B1 expression peaked at 3 h and CYP24A1 at 24 h, respectively. The in vitro biosynthesis of 1, 25(OH)2D3 by ADMSCs was analyzed by ELISA and Western blot. The levels of the active form of vitamin D were significantly decreased once the CYP enzymes were inhibited (p <0.01), demonstrating the ability of ADMSCs to convert inactive vitamin D into active vitamin D for cellular action.

Conclusions
Porcine ADMSCs possess vitamin D hydrolases and VDR to metabolize and respond to vitamin D. Hence, in vivo circulating 25-hydroxy vitamin D levels may have a significant role in regulating the differentiation of ADMSCs into different lineages, which might assist in stem cell-based therapy.
The genome of the largest bony fish, ocean sunfish (Mola mola), provides insights into its fast growth rate
Authors: Pan Hailin , Yu Hao , Ravi Vydianathan , Li Cai , Lee Alison P , Lian Michelle M , Tay Boon-Hui , Brenner Sydney , Wang Jian , Yang Huanming , Zhang Guojie , Venkatesh Byrappa 
Published: August 2016

Abstract

Background
The ocean sunfish (Mola mola), which can grow up to a length of 2.7 m and weigh 2.3 tons, is the world's largest bony fish. It has an extremely fast growth rate and its endoskeleton is mainly composed of cartilage. Another unique feature of the sunfish is its lack of a caudal fin, which is replaced by a broad and stiff lobe that results in the characteristic truncated appearance of the fish.

Results
To gain insights into the genomic basis of these phenotypic traits, we sequenced the sunfish genome and performed a comparative analysis with other teleost genomes. Several sunfish genes involved in the growth hormone and insulin-like growth factor 1 (GH/IGF1) axis signalling pathway were found to be under positive selection or accelerated evolution, which might explain its fast growth rate and large body size. A number of genes associated with the extracellular matrix, some of which are involved in the regulation of bone and cartilage development, have also undergone positive selection or accelerated evolution. A comparison of the sunfish genome with that of the pufferfish (fugu), which has a caudal fin, revealed that the sunfish contains more homeobox (Hox) genes although both genomes contain seven Hox clusters. Thus, caudal fin loss in sunfish is not associated with the loss of a specific Hox gene.

Conclusions
Our analyses provide insights into the molecular basis of the fast growth rate and large size of the ocean sunfish. The high-quality genome assembly generated in this study should facilitate further studies of this ‘natural mutant'.
Tackling a long‐standing problem: Typification of Orthotrichum crispum, Ulota crispula and Ulota intermedia (Bryopsida: Orthotrichaceae)
Authors: Caparrós Rut , Garilleti Ricardo , Price Michelle J. , Mazimpaka Vicente , Lara Francisco 
Published: August 2016

AbstractPrevious taxonomic studies on the Holarctic species of Ulota, including both morphological and molecular approaches, distinguished Ulota crispa, U. crispula and U. intermedia as separate taxa worthy of recognition at the specific level, instead of belonging to a single, highly variable species (U. crispa). Available original material for these three names has been studied and in several cases these are heterogeneous, containing two or even three of these closely related species. We discuss the nomenclatural history of each species and the extant original specimens from which lectotypes for Orthotrichum crispum, Ulota crispula and U. intermedia are designated.
Lectotypification of the Linnaean name Salsola sativa (Amaranthaceae s.l.)
Authors: Iamonico Duilio 
Published: August 2016

AbstractThe typification of the name Salsola sativa (Amaranthaceae) is discussed. An illustration of Antoine de Jussieu's Kali Hispanicum, supinum, annuum, Sedi foliis brevibus from 1719 is designated as the lectotype.
Untangling a vine and its parasite: Host specificity of Philippine Rafflesia (Rafflesiaceae)
Authors: Pelser Pieter B. , Nickrent Daniel L. , Barcelona Julie F. 
Published: August 2016

AbstractRafflesia species are endo‐holoparasites of Tetrastigma (Vitaceae) vines. Despite receiving considerable attention because of their rarity, enormous flowers, and fascinating parasitic life style, surprisingly little is known about their host specificity and host preference. This lack of information prevents a better understanding of the evolution of the host‐parasite associations and host‐focused conservation management of these threatened plants. This study is the first comprehensive analysis of host specificity and preference in Rafflesia. A total of 180 host plants of 11 out of 13 species of Philippine Rafflesia as well as non‐parasitized Tetrastigma plants from most areas where Rafflesia species have been found were included in our study. Morphological data and nuclear and plastid DNA sequence phylogenies were used to identify and distinguish Tetrastigma lineages. Our studies provide support for previous claims that Tetrastigma species are the exclusive hosts of Rafflesia. A total of eight lineages of Philippine Tetrastigma were identified of which six are hosts of Rafflesia. Most of these Tetrastigma lineages are hosts of multiple Rafflesia species. In addition, four Rafflesia species parasitize multiple Tetrastigma lineages. The finding that Tetrastigma lineages and Rafflesia species that are relatively common are involved in multiple host‐parasite associations suggests that these Rafflesia species are less host‐specific than previous studies indicated. However, because some sympatric Tetrastigma species are not among the observed host species, we tentatively conclude that Philippine Rafflesia show at least some degree of host specificity. Host phylogenies suggest that cospeciation might not have occurred in the diversification of Philippine Rafflesia and Tetrastigma.
Correlations between hemoglobin, serum ferritin, and soluble transferrin receptor levels in children aged 6-59 months
Authors: Tri Kusumastuti Fajar Diah , Sutaryo Sutaryo , Mulatsih Sri 
Published: August 2016

Background Early detection of iron deficiency is important in young children to prevent iron deficiency anemia, which may cause permanent neurocognitive development disorders. Hemoglobin level is an insensitive tool for detecting iron deficiency without anemia, while serum ferritin levels may be influenced by infection and inflammation. However, soluble transferrin receptor (sTfR) is a sensitive marker for detecting iron deficiency, yet not widely used in daily practice.Objective To assess for correlations between hemoglobin, serum ferritin, and soluble transferrin receptor levels in children aged 6-59 months.Methods We performed a cross-sectional study in the Yogyakarta and Bantul Districts involving 85 children aged 6-59 months who visited integrated health posts (posyandu) and who met the inclusion criteria. Subjects were chosen by cluster random sampling. Blood specimens were collected to examine hemoglobin, serum ferritin, and sTfR levels.Results Spearman’s correlation test revealed weak negative correlations between hemoglobin and serum ferritin levels, as well as between hemoglobin and sTfR levels, with coefficient correlations of r = -0.220, (P=0.043) and r = -0.317, (P=0.003), respectively. There was no correlation between serum ferritin and sTfR levels (r = -0.033; P=0.767).Conclusion Hemoglobin levels has weak negative correlations with serum ferritin and sTfR, but serum ferritin does not correlate with sTfR. [Paediatr Indones. 2014;54:122-6.]