bluuebunny/crossref_metadata_2025_split huggingface dataset:
High Viral Burden Restricts Short-Lived Effector Cell Number at Late Times Postinfection through Increased Natural Regulatory T Cell Expansion
Authors: Amoah Samuel , Holbrook Beth C. , Yammani Rama D. , Alexander-Miller Martha A. 
Published: April 2013

Abstract
Generating and maintaining a robust CD8+ T cell response in the face of high viral burden is vital for host survival. Further, balancing the differentiation of effectors along the memory precursor effector cell pathway versus the short-lived effector cell (SLEC) pathway may be critical in controlling the outcome of virus infection with regard to clearance and establishing protection. Although recent studies have identified several factors that have the capacity to regulate effector CD8+ T cell differentiation—for example, inflammatory cytokines—we are far from a complete understanding of how cells choose the memory precursor effector cell versus SLEC fate following infection. In this study, we have modulated the infectious dose of the poxvirus vaccinia virus as an approach to modulate the environment present during activation and expansion of virus-specific effector cells. Surprisingly, in the face of a high virus burden, the number of SLECs was decreased. This decrease was the result of increased natural regulatory T cells (Tregs) generated by high viral burden, as depletion of these cells restored SLECs. Our data suggest Treg modulation of differentiation occurs via competition for IL-2 during the late expansion period, as opposed to the time of T cell priming. These findings support a novel model wherein modulation of the Treg response as a result of high viral burden regulates late-stage SLEC number.
G Protein–Coupled Receptor Kinase 6 Deficiency Promotes Angiogenesis, Tumor Progression, and Metastasis
Authors: Raghuwanshi Sandeep K. , Smith Nikia , Rivers Elizabeth J. , Thomas Ariel J. , Sutton Natalie , Hu Yuhui , Mukhopadhyay Somnath , Chen Xiaoxin L. , Leung TinChung , Richardson Ricardo M. 
Published: April 2013

Abstract
G protein–coupled receptor kinases (GRKs) phosphorylate the activated form of G protein–coupled receptors leading to receptor desensitization and downregulation. We have recently shown that the chemokine receptor, CXCR2, couples to GRK6 to regulate cellular responses including chemotaxis, angiogenesis, and wound healing. In this study, we investigate the role of GRK6 in tumorigenesis using murine models of human lung cancer. Mice deficient in GRK6 (GRK6−/−) exhibited a significant increase in Lewis lung cancer growth and metastasis relative to control littermates (GRK6+/+). GRK6 deletion had no effect on the expression of proangiogenic chemokine or vascular endothelial growth factor, but upregulated matrix metalloproteinase (MMP)-2 and MMP-9 release, tumor-infiltrating PMNs, and microvessel density. Because β-arrestin-2–deficient (βarr2−/−) mice exhibited increased Lewis lung cancer growth and metastasis similar to that of GRK6−/−, we developed a double GRK6−/−/βarr2−/− mouse model. Surprisingly, GRK6−/−/βarr2−/− mice exhibited faster tumor growth relative to GRK6−/− or βarr2−/− mice. Treatment of the mice with anti-CXCR2 Ab inhibited tumor growth in both GRK6−/− and GRK6−/−/βarr2−/− animals. Altogether, the results indicate that CXCR2 couples to GRK6 to regulate angiogenesis, tumor progression, and metastasis. Deletion of GRK6 increases the activity of the host CXCR2, resulting in greater PMN infiltration and MMP release in the tumor microenvironment, thereby promoting angiogenesis and metastasis. Because GRK6−/−/βarr2−/− showed greater tumor growth relative to GRK6−/− or βarr2−/− mice, the data further suggest that CXCR2 couples to different mechanisms to mediate tumor progression and metastasis.
Control of the STAT6–BCL6 Antagonism by SWAP-70 Determines IgE Production
Authors: Audzevich Tatsiana , Pearce Glen , Breucha Michael , Günal Gamze , Jessberger Rolf 
Published: April 2013

Abstract
Asthma and allergies are major health concerns in which Ig isotype E plays a pivotal role. Ag-bound IgE drives mast cells and basophils into exocytosis, thereby promoting allergic and potentially anaphylactic reactions. The importance of tightly regulated IgE production is underscored by severe immunological conditions in humans with elevated IgE levels. Cytokines direct IgH class-switching to a particular isotype by initiation of germline transcription (GLT) from isotype-specific intronic (I) promoters. The switch to IgE depends on IL-4, which stimulates GLT of the Iε promoter, but is specifically and strongly impaired in Swap-70−/− mice. Although early events in IL-4 signal transduction (i.e., activation of the JAK/STAT6 pathway) do not require SWAP-70, SWAP-70 deficiency results in impaired Iε GLT. The affinity of STAT6 to chromatin is reduced in absence of SWAP-70. Chromatin immunoprecipitation revealed that SWAP-70 binds to Iε and is required for association of STAT6 with Iε. BCL6, known to antagonize STAT6 particularly at Iε, is increased on Iε in absence of SWAP-70. Other promoters bound by BCL6 and STAT6 were found unaffected. We conclude that SWAP-70 controls IgE production through regulation of the antagonistic STAT6 and BCL6 occupancy of Iε. The identification of this mechanism opens new avenues to inhibit allergic reactions triggered by IgE.
Dopamine Receptor D3 Expressed on CD4+ T Cells Favors Neurodegeneration of Dopaminergic Neurons during Parkinson’s Disease
Authors: González Hugo , Contreras Francisco , Prado Carolina , Elgueta Daniela , Franz Dafne , Bernales Sebastián , Pacheco Rodrigo 
Published: April 2013

AbstractEmerging evidence has demonstrated that CD4+ T cells infiltrate into the substantia nigra (SN) in Parkinson's disease (PD) patients and in animal models of PD. SN-infiltrated CD4+ T cells bearing inflammatory phenotypes promote microglial activation and strongly contribute to neurodegeneration of dopaminergic neurons. Importantly, altered expression of dopamine receptor D3 (D3R) in PBLs from PD patients has been correlated with disease severity. Moreover, pharmacological evidence has suggested that D3R is involved in IFN-γ production by human CD4+ T cells. In this study, we examined the role of D3R expressed on CD4+ T cells in neurodegeneration of dopaminergic neurons in the SN using a mouse model of PD. Our results show that D3R-deficient mice are strongly protected against loss of dopaminergic neurons and microglial activation during 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD. Notably, D3R-deficient mice become susceptible to MPTP-induced neurodegeneration and microglial activation upon transfer of wild-type (WT) CD4+ T cells. Furthermore, RAG1 knockout mice, which are devoid of T cells and are resistant to MPTP-induced neurodegeneration, become susceptible to MPTP-induced loss of dopaminergic neurons when reconstituted with WT CD4+ T cells but not when transferred with D3R-deficient CD4+ T cells. In agreement, experiments analyzing activation and differentiation of CD4+ T cells revealed that D3R favors both T cell activation and acquisition of the Th1 inflammatory phenotype. These findings indicate that D3R expressed on CD4+ T cells plays a fundamental role in the physiopathology of MPTP-induced PD in a mouse model.
Phosphatidylinositol 4-Phosphate 5-Kinase α Activation Critically Contributes to CD28-Dependent Signaling Responses
Authors: Muscolini Michela , Camperio Cristina , Capuano Cristina , Caristi Silvana , Piccolella Enza , Galandrini Ricciarda , Tuosto Loretta 
Published: April 2013

Abstract
CD28 is one of the most relevant costimulatory receptors that deliver both TCR-dependent and TCR-independent signals regulating a wide range of signaling pathways crucial for cytokine and chemokine gene expressions, T cell survival, and proliferation. Most of the CD28-dependent signaling functions are initiated by the recruitment and activation of class IA PI3Ks, which catalyze the conversion of phosphatidylinositol 4,5-biphosphate (PIP2) into phosphatidylinositol 3,4,5-triphosphate, thus generating the docking sites for key signaling proteins. Hence, PIP2 is a crucial substrate in driving the PI3K downstream signaling pathways, and PIP2 turnover may be an essential regulatory step to ensure the activation of PI3K following CD28 engagement. Despite some data evidence that CD28 augments TCR-induced turnover of PIP2, its direct role in regulating PIP2 metabolism has never been assessed. In this study, we show that CD28 regulates PIP2 turnover by recruiting and activating phosphatidylinositol 4-phosphate 5-kinases α (PIP5Kα) in human primary CD4+ T lymphocytes. This event leads to the neosynthesis of PIP2 and to its consumption by CD28-activated PI3K. We also evidenced that PIP5Kα activation is required for both CD28 unique signals regulating IL-8 gene expression as well as for CD28/TCR-induced Ca2+ mobilization, NF-AT nuclear translocation, and IL-2 gene transcription. Our findings elucidate a novel mechanism that involves PIP5Kα as a key modulator of CD28 costimulatory signals.
Regulator of Calcineurin 1 Suppresses Inflammation during Respiratory Tract Infections
Authors: Junkins Robert D. , MacNeil Adam J. , Wu Zhengli , McCormick Craig , Lin Tong-Jun 
Published: April 2013

Abstract
Respiratory tract infection with Pseudomonas aeruginosa is a common cause of hospitalization in immune-compromised individuals. However, the molecular mechanisms involved in the immune response to P. aeruginosa lung infection remain incompletely defined. In this study, we demonstrate that the regulator of calcineurin 1 (RCAN1) is a central negative regulator of inflammation in a mouse model of acute bacterial pneumonia using the opportunistic bacterial pathogen P. aeruginosa. RCAN1-deficient mice display greatly increased mortality following P. aeruginosa lung infection despite enhanced neutrophil recruitment and bacterial clearance. This mortality is associated with higher systemic levels of proinflammatory cytokines in RCAN1-deficient animals. These aberrant inflammatory responses coincide with increased transcriptional activity of proinflammatory RCAN1-target proteins NFAT and NF-κB. In addition, we reveal a novel regulatory role for RCAN1 in the ERK/STAT3 pathway both in vitro and in vivo, suggesting that aberrant STAT3 activity may significantly contribute to delayed resolution of inflammatory responses in our model. Together, these findings demonstrate that RCAN1 is a potent negative regulator of inflammation during respiratory tract infections.
Butyrophilin Btn2a2 Inhibits TCR Activation and Phosphatidylinositol 3-Kinase/Akt Pathway Signaling and Induces Foxp3 Expression in T Lymphocytes
Authors: Ammann Johannes U. , Cooke Anne , Trowsdale John 
Published: April 2013

Abstract
The butyrophilin-related protein Btn2a2 was upregulated on murine APC including CD19+ B cells, CD11b+F4/80+ peritoneal macrophages, and CD11c+ bone marrow–derived dendritic cells after activation with LPS or Pam3CysK4, suggesting a role in modulation of T lymphocytes. Consistent with this, binding of mouse Btn2a2-Fc to CD3+ primary mouse T cells stimulated with anti-CD3 and anti-CD28 reduced the number of proliferating cells and entry of cells into the cell cycle. Binding of Btn2a2-Fc to anti-CD3–stimulated T cells inhibited CD3ε, Zap70, and subsequent Erk1/2 activation. It also interfered with activation of the regulatory subunit of PI3K, p85, and activation of Akt in T cells stimulated with both anti-CD3 and anti-CD28. Inhibition of Akt activation by Btn2a2-Fc was, in contrast to inhibition by programmed death ligand-1–Fc, not overcome by anti-CD28 costimulation. Using Foxp3-GFP–transgenic, naive T cells, Btn2a2-Fc induced de novo expression of Foxp3 in a dose-dependent manner, and Btn2a2-Fc–induced CD4+CD25+Foxp3+ T cells had inhibitory properties. The data indicate an important physiological role for Btn2a2 in inhibiting T cell activation and inducing Foxp3+ regulatory T cells.
THE USE OF MONOCLONAL ANTIBODIES IN THE TREATMENT OF AUTOIMMUNE COMPLICATIONS OF CHRONIC LYMPHOCYTIC LEUKEMIA
Authors: Laurenti Luca 
Published: April 2013

Autoimmune cytopenias are a frequent complication in CLL, occuring in approximately 5-10% of the patients. The most common manifestation is autoimmune haemolytic anaemia, followed by immune thrombocytopaenia and only rarely pure red blood cell aplasia or autoimmune granulocytopaenia. Initial treatment is as for the idiopathic autoimmune cytopenias, with most patients responding to conventional corticosteroid therapy. Patients not responding after 4–6 weeks of conventional therapy should be considered for alternative immunosuppression, monoclonal antibody therapy or splenectomy. While randomized trials demonstrating the benefit of rituximab in CLL-related autoimmune diseases are still lacking, there are considerable data in the literature that provide evidence for its effectiveness.The monoclonal antibody alemtuzumab also displays considerable activity against both the malignant disease and the autoimmune complication in patients with CLL, although at the expense of greater toxicity. A number of new monoclonal antibodies, such as ofatumumab, GA-101, lumiliximab, TRU-016, epratuzumab, and galiximab, are currently investigated in CLL and their activity in CLL-related autoimmune cytopenias should be evaluated in future studies.
Comparison of Crack Formation in Retrograde Cavities prepared with Ultrasound, Er, Cr:YSGG Laser or Bur: An ex vivo Study
Authors: Arslan Seda , Bala Oya , Berk Gizem , Kayaoglu Guven 
Published: April 2013

ABSTRACTObjectiveThe aim of this study was to compare the number of crack formation in retrograde cavities after preparation with ultrasound, Er, Cr:YSGG (erbium, chromium:yttrium, scandium, gallium and garnet) laser with different power and frequency settings and bur.Materials and MethodsRoot canals of 60 extracted human maxillary incisors were prepared, the apices were horizontally cut and class I retrograde cavities were prepared using an ultrasonic unit (group 1), Er, Cr:YSGG laser (group 2: 3.5 W, 30 Hz; group 3: 3.5 W, 20 Hz; group 4: 4 W, 30 Hz; group 5: 4 W 20 Hz) or high-speed bur (group 6). Cracks were examined under a stereomicroscope at a magnification of ×20, scored (0 to 3) and classified according to their location (cementum, dentin, canal wall). Scanning electron microscopy analysis was also performed.ResultsGreatest number of cracks was found in the cementum, and least on the canal wall. Ultrasonics followed by bur created the greatest number of crack in the dentin. No significant differences were found when groups 2 and 4, 3 and 5, and 2 and 3 were compared at the 3 regions. A significant difference was found between groups 4 and 5 at the dentin region.ConclusionThe ultrasonic is the most aggressive root-end preparation technique. The most favorable laser setting was the one used in Group 5; and generally it was safer also than the ultrasound and the bur groups.How to cite this articleArslan S, Bala O, Berk G, Kayaoglu G. Comparison of Crack Formation in Retrograde Cavities prepared with Ultrasound, Er, Cr:YSGG Laser or Bur: Anex vivoStudy. J Contemp Dent 2013;3(1):1-6.
Two-Phase Treatment of a Growing Patient with a Skeletal Class II
Authors: Gaikwad Shashank Sharad , Sonawane Manish Suresh , Karandikar Girish Ramchandra , Pawar Priyanka Anil , Shah Shaili Sanjay 
Published: April 2013

ABSTRACTFunctional appliances have been used for many years in the treatment of class II malocclusions. They redirect the growth of mandible bringing about a skeletal change in a growing patient. In case of any remaining dental discrepancy, a fixed appliance is obligatory. This patient was an 11-year-old growing female with a convex profile, receding chin, lower lip trap, class II skeletal and dental relationship, a large overjet and overbite and a high maxillary labial frenum attachment. Treatment started with the Twin-block appliance with an expansion screw to achieve transverse correction, promote growth of the mandible and improve her profile. This was followed by fixed appliance mechanotherapy to align and level the dentition, close spaces and retract the maxillary anteriors. Frenectomy was carried out after space closure.How to cite this articleSonawane MS, Karandikar GR, Gaikwad SS, Pawar PA, Shah SS. Two-Phase Treatment of a Growing Patient with a Skeletal Class II. J Contemp Dent 2013;3(1):40-43.
A Trio Discovery—Cardarelli-Riga-Fede Disease: A Case Report and Review of Literature
Authors: Dixit Uma B , Patil Sonal Dinesh 
Published: April 2013

ABSTRACTThe natal and neonatal teeth have been reported to cause ulceration on the ventral surface of the tongue in neonates and infants. These can be presented with mild to severe ulceration which may affect the child's feeding habits. This appearance was described by Cardarelli, Riga and Fede and hence been termed as Cardarelli-Riga-Fede disease. It is important to diagnose the lesion early and treat it by eliminating the cause of trauma to avoid untoward complications. We present a large Riga-Fede lesion in an infant along with the clinical management. The purpose of this report is to review the literature related to neonatal teeth epidemiology and discuss their possible etiology and treatment.How to cite this articlePatil SD, Dixit UB. A Trio Discovery— Cardarelli-Riga-Fede Disease: A Case Report and Review of Literature. J Contemp Dent 2013;3(1):44-48.
Highly Emissive Chiral Indium‐Based Perovskite Single Crystals for Efficient Optoelectronic Applications
Authors: He Qingqing , Feng Jie , Du Liping , Shen Yueqi , Chen Haoyu , Yan Chi , Kang Shuilong , Wang Hengguang , Yin Yao , Wan Li , Li Youyong , Wang Yong , Fang Yuan , Ning Weihua 
Published: July 2024

AbstractChiral lead halide perovskites have captivated considerable attentions due to their distinctive attributes, such as ferroelectricity, spin‐dependent transport, and chiroptical activity. However, lead toxicity and weak circularly polarized luminescence (CPL) have cast a pall over their practical applications. Here, a series of 0D lead‐free chiral enantiomorphic hybrids, such as (R‐/S‐MBA)3In1‐xSbxCl6 (x = 0–1) is successfully developed. By optimizing the Sb3+ doping concentration to 0.55%, the resultant (R‐/S‐MBA)3In99.45%Sb0.55%Cl6 not only shows a near‐unity quantum yield but also emanates potent CPL, boasting a dissymmetry factor (glum) of 6.3 × 10–3. These efficient CPL activities are intricately tied to the presence of a twisted luminescent cluster [SbCl6]3– induced by structural chirality. The comprehensive results reveal that the emission of the chiral perovskite originated from self‐trapped excitons (STEs) of 5s2 Sb3+ ions. Moreover, (MBA)3In99.45%Sb0.55%Cl6 single crystals also exhibit bright orange emission and UV detector signals. These findings will pave the way for the further investigation in efficient CPL and detectors based on lead‐free chiral optoelectronic materials.
Access to clinical genetic services: An evaluation of patient referral characteristics and identifying barriers in Michigan
Authors: Lemke Lacey N. , Bupp Caleb P. , Niemchick Karen L. 
Published: July 2024

AbstractThe utilization of genetics in medical care has enhanced the utility of precision medicine and hence increased the need for clinical genetic services. These services have reduced the costs and expanded the availability of genetic testing, but their use is limited in certain populations. This study explores the access to clinical genetic services for Michigan patients referred to a genetics clinic on the western side of the state. Factors included the travel distance (miles), wait time for appointment (days from the referral date to the date of first appointment), population demographics, and cultural characteristics. A retrospective record review of all aged patients (n = 568) referred to a genetics clinic in 2018 demonstrated that all patients were insured (100%), of which majority were white‐non‐Hispanic (90.7%), more than half were < 10 years of age at referral (53.3%), and most of them kept their first appointment (93.5%). Our analysis showed that the wait time was associated with referral non‐compliance, p < 0.01. Adjusting for all variables, for each additional day in wait time, patients had 1% increased risk of not seeking clinical genetic services (OR = 1.01, 90% CI [1.01, 1.02]). Policies to encourage genetic service utilization and improve equitable access to precision health are needed. An opportunity exists for strategies that broaden and add diverse populations to those receiving genetic services.
Clustering‐Triggered Emission Mechanism of Sulfur Ester‐Polyacrylamide Aqueous Solution
Authors: Lei Xiaoping , Zhang Yuanchao , Wu Qingfeng , Zhang Xiangxi , Zhou Qing , Li Qi , Yi Lingmin 
Published: July 2024

AbstractMost nonconventional luminogens enjoy good water solubility and biocompatibility, showing unique application prospects in fields like biological imaging. Although clustering‐triggered emission (CTE) mechanisms have been proposed to explain such emissions, it has not been thoroughly elucidated, which limits their development and application. Herein, the photoluminescence properties of polyacrylamide prepared by reversible addition‐fragmentation chain transfer (RAFT) polymerization aqueous solution are utilized to further investigate the effects of changes in concentration, in order to elucidate the emission mechanism through transmission electron microscopy (TEM), small angle X‐ray scattering (SAXS) and theoretical calculation. The results showed that the size distribution, morphology, and distance between the polymer clusters formed in the water solution are successfully correlated with the cluster emission centers. The emission mechanism of nonconventional luminogens solutions is more clearly and intuitively elucidated, which has a promoting effect on the emission and application of this field. It provides a strategy a strategy to clarify the CTE mechanism of nonconventional luminogens solution more clearly.
α‐Halocarbonyls as a Valuable Functionalized Tertiary Alkyl Source
Authors: Nishikata Takashi 
Published: July 2024

AbstractThis review introduces the synthetic organic chemical value of α‐bromocarbonyl compounds with tertiary carbons. This α‐bromocarbonyl compound with a tertiary carbon has been used primarily only as a radical initiator in atom transfer radical polymerization (ATRP) reactions. However, with the recent development of photo‐radical reactions (around 2010), research on the use of α‐bromocarbonyl compounds as tertiary alkyl radical precursors became popular (around 2012). As more examples were reported, α‐bromocarbonyl compounds were studied not only as radicals but also for their applications in organometallic and ionic reactions. That is, α‐bromocarbonyl compounds act as nucleophiles as well as electrophiles. The carbonyl group of α‐bromocarbonyl compounds is also attractive because it allows the skeleton to be converted after the reaction, and it is being applied to total synthesis. In our survey until 2022, α‐bromocarbonyl compounds can be used to perform a full range of reactions necessary for organic synthesis, including multi‐component reactions, cross‐coupling, substitution, cyclization, rearrangement, stereospecific reactions, asymmetric reactions. α‐Bromocarbonyl compounds have created a new trend in tertiary alkylation, which until then had limited reaction patterns in organic synthesis. This review focuses on how α‐bromocarbonyl compounds can be used in synthetic organic chemistry.
Minimally invasive and robotic‐assisted approaches applied to pediatric surgical oncology
Authors: Pachl Max , Lautz Timothy B. , Aldrink Jennifer H. , Abdelhafeez Hafeez , Irtan Sabine 
Published: July 2024

AbstractThe management of pediatric tumors is complex, with surgery, chemotherapy, and radiotherapy being cornerstones in their treatment. Tumor removal is increasingly performed by a minimally invasive approach, which allows for quicker postoperative recovery and less postoperative pain. The goal of this report is to give an overview of minimally invasive surgical approaches for common pediatric tumors, with a focus on technical considerations and postoperative outcomes.