bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shoulder Strength and Physical Activity Predictors of Shoulder Pain in People With Paraplegia From Spinal Injury: Prospective Cohort Study
Authors: Mulroy Sara J. , Hatchett Patricia , Eberly Valerie J. , Lighthall Haubert Lisa , Conners Sandy , Requejo Philip S. 
Published: February 2015

Background
Shoulder joint pain is a frequent secondary complaint for people following spinal cord injury (SCI).

Objective
The purpose of this study was to determine predictors of shoulder joint pain in people with paraplegia.

Methods/Design
A 3-year longitudinal study was conducted. Participants were people with paraplegia who used a manual wheelchair for at least 50% of their mobility and were asymptomatic for shoulder pain at study entry. Participants were classified as having developed shoulder pain if they experienced an increase of ≥10 points on the Wheelchair User's Shoulder Pain Index in the 3-year follow-up period. Measurements of maximal isometric shoulder torques were collected at study entry (baseline), 18 months, and 3 years. Daily activity was measured using a wheelchair odometer, and self-reported daily transfer and raise frequency data were collected by telephone every 6 weeks.

Results
Two hundred twenty-three participants were enrolled in the study; 39.8% developed shoulder pain over the 3-year follow-up period. Demographic variables and higher activity levels were not associated with shoulder pain onset. Baseline maximal isometric torque (normalized by body weight) in all shoulder muscle groups was 10% to 15% lower in participants who developed shoulder pain compared with those who remained pain-free. Lower shoulder adduction torque was a significant predictor of shoulder pain development (log-likelihood test=11.38), but the model explained only 7.5% of shoulder pain onset and consequently is of limited clinical utility.

Limitations
Time since SCI varied widely among participants, and transfer and raise activity was measured by participant recall.

Conclusions
Participants who developed shoulder pain had decreased muscle strength, particularly in the shoulder adductors, and lower levels of physical activity prior to the onset of shoulder pain. Neither factor was a strong predictor of shoulder pain onset.
Échecs économiques et dérive du pragmatisme juridique : l'expérience anglaise du droit de la faillite
Authors: Armstrong Mark Anthony , Cerfontaine Alexandrine 
Published: February 2015

Economic Failure and Legal Pragmatism : The English Experience of Insolvency Law.
An examination of the political economy immediately preceding the passage of the Insolvency Act 1986 reveals that the major reform had little hope of reversing the rise in the companies failing. Accordingly, when a new reform is proposed, it is legitimate to question its methodology, the precise relationship between law and economies and an approach espousing predominantly a private law framework.
Range‐wide population genetics and variation in morph ratio in style‐dimorphic Narcissus papyraceus
Authors: Simón‐Porcar Violeta I. , Picó F. Xavier , Arroyo Juan 
Published: February 2015

• Premise of the study: Theoretical models state that natural selection and mating patterns account for floral morph ratio in style‐polymorphic plants. However, the demographic history of populations can also influence variation in morph ratios. If so, we hypothesize an association between the morph ratios and the genetic structure across populations.• Methods: We used nuclear microsatellites to assess genetic variation and structure in populations of Narcissus papyraceus, a style‐dimorphic plant whose floral morph ratios (L‐morph to S‐morph) gradually vary throughout its distribution range in the southwestern Mediterranean Basin. We implemented analyses to relate the genetic features of populations with their morph ratios.• Key results: We found greater frequencies of the S‐morph in central populations and declining frequencies toward the periphery. This geographic pattern was not associated with the genetic structure of populations. Instead, we found two distinct genetic groups, mainly separated by the Strait of Gibraltar, with a mixture of morph ratios within each one. Overall, there was a weak genetic structure. Genetic diversity was greater in central and southern dimorphic populations than in northern L‐monomorphic populations.• Conclusions: Altogether, our results do not support the hypothesis that the demographic history of populations can account for the observed geographical pattern of morph ratios in N. papyraceus. We suggest that adaptive processes shown in previous studies in the species are the main determinant of the existing variation in the morph composition of populations.
Buprenorphine Decreases the CCL2-Mediated Chemotactic Response of Monocytes
Authors: Carvallo Loreto , Lopez Lillie , Che Fa-Yun , Lim Jihyeon , Eugenin Eliseo A. , Williams Dionna W. , Nieves Edward , Calderon Tina M. , Madrid-Aliste Carlos , Fiser Andras , Weiss Louis , Angeletti Ruth Hogue , Berman Joan W. 
Published: February 2015

Abstract
Despite successful combined antiretroviral therapy, ∼60% of HIV-infected people exhibit HIV-associated neurocognitive disorders (HAND). CCL2 is elevated in the CNS of infected people with HAND and mediates monocyte influx into the CNS, which is critical in neuroAIDS. Many HIV-infected opiate abusers have increased neuroinflammation that may augment HAND. Buprenorphine is used to treat opiate addiction. However, there are few studies that examine its impact on HIV neuropathogenesis. We show that buprenorphine reduces the chemotactic phenotype of monocytes. Buprenorphine decreases the formation of membrane projections in response to CCL2. It also decreases CCL2-induced chemotaxis and mediates a delay in reinsertion of the CCL2 receptor, CCR2, into the cell membrane after CCL2-mediated receptor internalization, suggesting a mechanism of action of buprenorphine. Signaling pathways in CCL2-induced migration include increased phosphorylation of p38 MAPK and of the junctional protein JAM-A. We show that buprenorphine decreases these phosphorylations in CCL2-treated monocytes. Using DAMGO, CTAP, and Nor-BNI, we demonstrate that the effect of buprenorphine on CCL2 signaling is opioid receptor mediated. To identify additional potential mechanisms by which buprenorphine inhibits CCL2-induced monocyte migration, we performed proteomic analyses to characterize additional proteins in monocytes whose phosphorylation after CCL2 treatment was inhibited by buprenorphine. Leukosialin and S100A9 were identified and had not been shown previously to be involved in monocyte migration. We propose that buprenorphine limits CCL2-mediated monocyte transmigration into the CNS, thereby reducing neuroinflammation characteristic of HAND. Our findings underscore the use of buprenorphine as a therapeutic for neuroinflammation as well as for addiction.
Predominant Development of Mature and Functional Human NK Cells in a Novel Human IL-2–Producing Transgenic NOG Mouse
Authors: Katano Ikumi , Takahashi Takeshi , Ito Ryoji , Kamisako Tsutomu , Mizusawa Takuma , Ka Yuyo , Ogura Tomoyuki , Suemizu Hiroshi , Kawakami Yutaka , Ito Mamoru 
Published: February 2015

Abstract
We generated a severe immunodeficient NOD/Shi-scid-IL-2Rγnull (NOG) mouse substrain expressing the transgenic human IL-2 gene (NOG–IL-2 Tg). Upon transfer of human cord blood–derived hematopoietic stem cells (HSCs), CD3−CD56highCD16+/− cells developed unexpectedly, predominantly in the NOG–IL-2 Tg (hu-HSC NOG–IL-2 Tg). These cells expressed various NK receptors, including NKp30, NKp44, NKp46, NKG2D, and CD94, as well as a diverse set of killer cell Ig-like receptor molecules at levels comparable to normal human NK cells from the peripheral blood, which is evidence of their maturity. They produced levels of granzyme A as high as in human peripheral blood–derived NK cells, and a considerable amount of perforin protein was detected in the plasma. Human NK cells in hu-HSC NOG–IL-2 Tg produced IFN-γ upon stimulation, and IL-2, IL-15, or IL-12 treatment augmented the in vitro cytotoxicity. Inoculation of K562 leukemia cells into hu-HSC NOG–IL-2 Tg caused complete rejection of the tumor cells, whereas inoculation into hu-HSC NOG fully reconstituted with human B, T, and some NK cells did not. Moreover, when a CCR4+ Hodgkin’s lymphoma cell line was inoculated s.c. into hu-HSC NOG–IL-2 Tg, the tumor growth was significantly suppressed by treatment with a therapeutic humanized anti-CCR4 Ab (mogamulizumab), suggesting that the human NK cells in the mice exerted active Ab-dependent cellular cytotoxicity in vivo. Taken together, these data suggest that the new NOG–IL-2 Tg strain is a unique model that can be used to investigate the biological and pathological functions of human NK cells in vivo.
Macrophage Migration Inhibitory Factor–CXCR4 Is the Dominant Chemotactic Axis in Human Mesenchymal Stem Cell Recruitment to Tumors
Authors: Lourenco Sofia , Teixeira Vitor H. , Kalber Tammy , Jose Ricardo J. , Floto R. Andres , Janes Sam M. 
Published: February 2015

Abstract
Mesenchymal stromal cells (MSCs) are inherently tumor homing and can be isolated, expanded, and transduced, making them viable candidates for cell therapy. This tumor tropism has been used to deliver anticancer therapies to various tumor models. In this study, we sought to discover which molecules are the key effectors of human MSC tumor homing in vitro and using an in vivo murine model. In this study, we discover a novel role for macrophage migration inhibitory factor (MIF) as the key director of MSC migration and infiltration toward tumor cells. We have shown this major role for MIF using in vitro migration and invasion assays, in presence of different receptor inhibitors and achieving a drastic decrease in both processes using MIF inhibitor. Additionally, we demonstrate physical interaction between MIF and three receptors: CXCR2, CXCR4, and CD74. CXCR4 is the dominant receptor used by MIF in the homing tumor context, although some signaling is observed through CXCR2. We demonstrate downstream activation of the MAPK pathway necessary for tumor homing. Importantly, we show that knockdown of either CXCR4 or MIF abrogates MSC homing to tumors in an in vivo pulmonary metastasis model, confirming the in vitro two-dimensional and three-dimensional assays. This improved understanding of MSC tumor tropism will further enable development of novel cellular therapies for cancers.
Alcohol-Induced miR-27a Regulates Differentiation and M2 Macrophage Polarization of Normal Human Monocytes
Authors: Saha Banishree , Bruneau Johanna C. , Kodys Karen , Szabo Gyongyi 
Published: February 2015

Abstract
Alcohol abuse is a leading cause of liver disease characterized by liver inflammation, fatty liver, alcoholic hepatitis, or liver cirrhosis. Immunomodulatory effects of alcohol on monocytes and macrophages contribute to alcoholic liver disease. Alcohol use, an independent risk factor for progression of hepatitis C virus (HCV) infection–mediated liver disease, impairs host defense and alters cytokine production and monocyte/macrophage activation. We hypothesized that alcohol and HCV have synergistic effects on the phenotype and function of monocytes. Our data show that acute alcohol binge drinking in healthy volunteers results in increased frequency of CD16+ and CD68+ and M2-type (CD206+, dendritic cell [DC]-SIGN+–expressing and IL-10–secreting) circulating CD14+ monocytes. Expression of HCV-induced CD68 and M2 markers (CD206 and DC-SIGN) in normal monocytes was further enhanced in the presence of alcohol. The levels of microRNA (miR)-27a was significantly upregulated in monocytes cultured in the presence of alcohol or alcohol and HCV as compared with HCV alone. The functional role of miR-27a in macrophage polarization was demonstrated by transfecting monocytes with an miR-27a inhibitor that resulted in reduced alcohol- and HCV- mediated monocyte activation (CD14 and CD68 expression), polarization (CD206 and DC-SIGN expression), and IL-10 secretion. Overexpression of miR-27a in monocytes enhanced IL-10 secretion via activation of the ERK signaling pathway. We found that miR-27a promoted ERK phosphorylation by downregulating the expression of ERK inhibitor sprouty2 in monocytes. Thus, we identified that sprouty2 is a target of miR-27a in human monocytes. In summary, our study demonstrates the regulatory role of miR-27a in alcohol-induced monocyte activation and polarization.
Extracellular Vesicles Derived from Gram-Negative Bacteria, such asEscherichia coli, Induce Emphysema Mainly via IL-17A–Mediated Neutrophilic Inflammation
Authors: Kim You-Sun , Lee Won-Hee , Choi Eun-Jeong , Choi Jun-Pyo , Heo Young Joo , Gho Yong Song , Jee Young-Koo , Oh Yeon-Mok , Kim Yoon-Keun 
Published: February 2015

AbstractRecent evidence indicates that Gram-negative bacteria–derived extracellular vesicles (EVs) in indoor dust can evoke neutrophilic pulmonary inflammation, which is a key pathology of chronic obstructive pulmonary disease (COPD). Escherichia coli is a ubiquitous bacterium present in indoor dust and secretes nanometer-sized vesicles into the extracellular milieu. In the current study, we evaluated the role of E. coli–derived EVs on the development of COPD, such as emphysema. E. coli EVs were prepared by sequential ultrafiltration and ultracentrifugation. COPD phenotypes and immune responses were evaluated in C57BL/6 wild-type (WT), IFN-γ–deficient, or IL-17A–deficient mice after airway exposure to E. coli EVs. The present study showed that indoor dust from a bed mattress harbors E. coli EVs. Airway exposure to E. coli EVs increased the production of proinflammatory cytokines, such as TNF-α and IL-6. In addition, the repeated inhalation of E. coli EVs for 4 wk induced neutrophilic inflammation and emphysema, which are associated with enhanced elastase activity. Emphysema and elastase activity enhanced by E. coli EVs were reversed by the absence of IFN-γ or IL-17A genes. In addition, during the early period, lung inflammation is dependent on IL-17A and TNF-α, but not on IFN-γ, and also on TLR4. Moreover, the production of IFN-γ is eliminated by the absence of IL-17A, whereas IL-17A production is not abolished by IFN-γ absence. Taken together, the present data suggest that E. coli–derived EVs induce IL-17A–dependent neutrophilic inflammation and thereby emphysema, possibly via upregulation of elastase activity.
Repression of Ccr9 Transcription in Mouse T Lymphocyte Progenitors by the Notch Signaling Pathway
Authors: Krishnamoorthy Veena , Carr Tiffany , de Pooter Renee F. , Akinola Emanuelle Olumide , Gounari Fotini , Kee Barbara L. 
Published: February 2015

Abstract
The chemokine receptor CCR9 controls the immigration of multipotent hematopoietic progenitor cells into the thymus to sustain T cell development. Postimmigration, thymocytes downregulate CCR9 and migrate toward the subcapsular zone where they recombine their TCR β-chain and γ-chain gene loci. CCR9 is subsequently upregulated and participates in the localization of thymocytes during their selection for self-tolerant receptor specificities. Although the dynamic regulation of CCR9 is essential for early T cell development, the mechanisms controlling CCR9 expression have not been determined. In this article, we show that key regulators of T cell development, Notch1 and the E protein transcription factors E2A and HEB, coordinately control the expression of Ccr9. E2A and HEB bind at two putative enhancers upstream of Ccr9 and positively regulate CCR9 expression at multiple stages of T cell development. In contrast, the canonical Notch signaling pathway prevents the recruitment of p300 to the putative Ccr9 enhancers, resulting in decreased acetylation of histone H3 and a failure to recruit RNA polymerase II to the Ccr9 promoter. Although Notch signaling modestly modulates the binding of E proteins to one of the two Ccr9 enhancers, we found that Notch signaling represses Ccr9 in T cell lymphoma lines in which Ccr9 transcription is independent of E protein function. Our data support the hypothesis that activation of Notch1 has a dominant-negative effect on Ccr9 transcription and that Notch1 and E proteins control the dynamic expression of Ccr9 during T cell development.
Ultraviolet Radiation Signaling through TLR4/MyD88 Constrains DNA Repair and Plays a Role in Cutaneous Immunosuppression
Authors: Harberts Erin , Zhou Hua , Fishelevich Rita , Liu Juan , Gaspari Anthony A. 
Published: February 2015

Abstract
UV radiation (UVR) induces DNA damage, leading to the accumulation of mutations in epidermal keratinocytes and immunosuppression, which contribute to the development of nonmelanoma skin cancer. We reported previously that the TLR4–MyD88 signaling axis is necessary for UV-induced apoptosis. In the dinitrofluorobenzene contact hypersensitivity model, UV-irradiated MyD88-deficient (MyD88−/−) C57BL/6 mice had intact ear swelling, exaggerated inflammation, and higher levels of dinitrofluorobenzene-specific IgG2a compared with wild-type (WT) mice. Even with normal UV-induced, dendritic cell migration, DNA damage in the local lymph nodes was less pronounced in MyD88−/− mice compared with WT mice. Cultured, UV-irradiated WT APCs showed cleavage (inactivation) of the DNA damage–recognition molecule PARP, whereas PARP persisted in MyD88−/− and TLR4−/− APCs. Epidermal DNA from in vivo UV-irradiated MyD88−/− mice had an increased resolution rate of cyclobutane pyrimidine dimers. Both in vitro treatment of MyD88−/− APCs with and intradermal in vivo injections of PARP inhibitor, PJ-34, caused WT-level cyclobutane pyrimidine dimer repair. Lymphoblasts deficient in DNA repair (derived from a xeroderma pigmentosum group A patient) failed to augment DNA repair after MyD88 knockdown after UVR, in contrast to lymphoblasts from a healthy control. These data suggest that interference with the TLR4/MyD88 pathway may be a useful tool in promoting DNA repair and maintaining immune responses following UVR-induced damage.
Liver-Resident CD103+ Dendritic Cells Prime Antiviral CD8+ T Cells In Situ
Authors: Krueger Peter D. , Kim Taeg S. , Sung Sun-Sang J. , Braciale Thomas J. , Hahn Young S. 
Published: February 2015

Abstract
The liver maintains a tolerogenic environment to avoid unwarranted activation of its resident immune cells upon continuous exposure to food and bacterially derived Ags. However, in response to hepatotropic viral infection, the liver’s ability to switch from a hyporesponsive to a proinflammatory environment is mediated by select sentinels within the parenchyma. To determine the contribution of hepatic dendritic cells (DCs) in the activation of naive CD8+ T cells, we first characterized resident DC subsets in the murine liver. Liver DCs exhibit unique properties, including the expression of CD8α (traditionally lymphoid tissue specific), CD11b, and CD103 markers. In both the steady-state and following viral infection, liver CD103+ DCs express high levels of MHC class II, CD80, and CD86 and contribute to the high number of activated CD8+ T cells. Importantly, viral infection in the Batf3−/− mouse, which lacks CD8α+ and CD103+ DCs in the liver, results in a 3-fold reduction in the proliferative response of Ag-specific CD8+ T cells. Limiting DC migration out of the liver does not significantly alter CD8+ T cell responsiveness, indicating that CD103+ DCs initiate the induction of CD8+ T cell responses in situ. Collectively, these data suggest that liver-resident CD103+ DCs are highly immunogenic in response to hepatotropic viral infection and serve as a major APC to support the local CD8+ T cell response. It also implies that CD103+ DCs present a promising cellular target for vaccination strategies to resolve chronic liver infections.
Canonical Wnt Signaling in Dendritic Cells Regulates Th1/Th17 Responses and Suppresses Autoimmune Neuroinflammation
Authors: Suryawanshi Amol , Manoharan Indumathi , Hong Yuan , Swafford Daniel , Majumdar Tanmay , Taketo M. Mark , Manicassamy Balaji , Koni Pandelakis A. , Thangaraju Muthusamy , Sun Zuoming , Mellor Andrew L. , Munn David H. , Manicassamy Santhakumar 
Published: February 2015

Abstract
Breakdown in immunological tolerance to self-Ags or uncontrolled inflammation results in autoimmune disorders. Dendritic cells (DCs) play an important role in regulating the balance between inflammatory and regulatory responses in the periphery. However, factors in the tissue microenvironment and the signaling networks critical for programming DCs to control chronic inflammation and promote tolerance are unknown. In this study, we show that wnt ligand-mediated activation of β-catenin signaling in DCs is critical for promoting tolerance and limiting neuroinflammation. DC-specific deletion of key upstream (lipoprotein receptor-related protein [LRP]5/6) or downstream (β-catenin) mediators of canonical wnt signaling in mice exacerbated experimental autoimmune encephalomyelitis pathology. Mechanistically, loss of LRP5/6-β-catenin–mediated signaling in DCs led to an increased Th1/Th17 cell differentiation but reduced regulatory T cell response. This was due to increased production of proinflammatory cytokines and decreased production of anti-inflammatory cytokines such as IL-10 and IL-27 by DCs lacking LRP5/6-β-catenin signaling. Consistent with these findings, pharmacological activation of canonical wnt/β-catenin signaling delayed experimental autoimmune encephalomyelitis onset and diminished CNS pathology. Thus, the activation of canonical wnt signaling in DCs limits effector T cell responses and represents a potential therapeutic approach to control autoimmune neuroinflammation.
Rare Loss-of-Function Mutation in Complement Component C3 Provides Insight into Molecular and Pathophysiological Determinants of Complement Activity
Authors: Sfyroera Georgia , Ricklin Daniel , Reis Edimara S. , Chen Hui , Wu Emilia L. , Kaznessis Yiannis N. , Ekdahl Kristina N. , Nilsson Bo , Lambris John D. 
Published: February 2015

Abstract
The plasma protein C3 is a central element in the activation and effector functions of the complement system. A hereditary dysfunction of C3 that prevents complement activation via the alternative pathway (AP) was described previously in a Swedish family, but its genetic cause and molecular consequences have remained elusive. In this study, we provide these missing links by pinpointing the dysfunction to a point mutation in the β-chain of C3 (c.1180T &gt; C; p.Met373Thr). In the patient’s plasma, AP activity was completely abolished and could only be reconstituted with the addition of normal C3. The M373T mutation was localized to the macroglobulin domain 4 of C3, which contains a binding site for the complement inhibitor compstatin and is considered critical for the interaction of C3 with the AP C3 convertase. Structural analyses suggested that the mutation disturbs the integrity of macroglobulin domain 4 and induces conformational changes that propagate into adjacent regions. Indeed, C3 M373T showed an altered binding pattern for compstatin and surface-bound C3b, and the presence of Thr373 in either the C3 substrate or convertase-affiliated C3b impaired C3 activation and opsonization. In contrast to known gain-of-function mutations in C3, patients affected by this loss-of-function mutation did not develop familial disease, but rather showed diverse and mostly episodic symptoms. Our study therefore reveals the molecular mechanism of a relevant loss-of-function mutation in C3 and provides insight into the function of the C3 convertase, the differential involvement of C3 activity in clinical conditions, and some potential implications of therapeutic complement inhibition.
Ultrasound Imaging of Thyroid Gland
Authors: Kamble Rajesh C , Joshi Alpana N , Mestry Pravin , Shah Mohit 
Published: February 2015

ABSTRACT

How to cite this article
Kamble RC, Joshi AN, Mestry P, Shah M. Ultrasound Imaging of Thyroid Gland. Int J Otorhinolaryngol Clin 2014;6(1):35-46.