bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Protective Role for Human IL-10–Expressing CD4+ T Cells in Colitis
Authors: Ranatunga Dilini C. , Ramakrishnan Amritha , Uprety Priyanka , Wang Fengying , Zhang Hao , Margolick Joseph B. , Brayton Cory , Bream Jay H. 
Published: July 2012

Abstract
IL-10 is an immunoregulatory cytokine expressed by numerous cell types. Studies in mice confirm that different IL-10–expressing cell subsets contribute differentially to disease phenotypes. However, little is known about the relationship between cell- or tissue-specific IL-10 expression and disease susceptibility in humans. In this study, we used the previously described human (h)IL10BAC transgenic model to examine the role of hIL-10 in maintaining intestinal homeostasis. Genomically controlled hIL-10 expression rescued Il10−/− mice from Helicobacter-induced colitis and was associated with control of proinflammatory cytokine expression and Th17 cell accumulation in gut tissues. Resistance to colitis was associated with an accumulation of hIL-10–expressing CD4+Foxp3+ regulatory T cells specifically within the lamina propria but not other secondary lymphoid tissues. Cotransfer of CD4+CD45RBlo cells from Il10−/−/hIL10BAC mice rescued Rag1−/− mice from colitis, further suggesting that CD4+ T cells represent a protective source of hIL-10 in the colon. In concordance with an enhanced capacity to express IL-10, CD4+CD44+ T cells isolated from the lamina propria exhibited lower levels of the repressive histone mark H3K27Me3 and higher levels of the permissive histone mark acetylated histone H3 in both the human and mouse IL10 locus compared with the spleen. These results provide experimental evidence verifying the importance of T cell-derived hIL-10 expression in controlling inflammation within the colonic mucosa. We also provide molecular evidence suggesting the tissue microenvironment influences IL-10 expression patterns and chromatin structure in the human (and mouse) IL10 locus.
Chronic Alcohol Consumption Impairs Distribution and Compromises Circulation of B Cells in B16BL6 Melanoma-Bearing Mice
Authors: Zhang Hui , Zhu Zhaohui , Meadows Gary G. 
Published: July 2012

Abstract
Accumulating research indicates that B cells are involved in anti-tumor immunity. Chronic alcohol consumption is associated with decreased survival of cancer patients. The effect of alcohol consumption on B cells in tumor-bearing hosts is unknown. Results in melanoma-bearing mice showed that chronic alcohol consumption did not alter the percentage and number of B cells in bone marrow, spleen, and lymph nodes but dramatically decreased B cells in the peripheral blood. Alcohol consumption did not alter the development of B cells in the bone marrow and did not affect follicular B cells in the spleen; however, it increased T1 B cells and decreased marginal zone B cells in the spleen. Alcohol consumption also decreased mature B cells in the blood. It did not alter the chemotactic capacity of plasma to facilitate migration of splenocytes or the chemotactic response of splenocytes to CXCL13 and CCL21. However, the response of splenocytes to sphingosine-1-phosphate was impaired in alcohol-consuming, melanoma-bearing mice. The expression of sphingosine-1-phosphate receptor-1 (S1PR1) and sphingosine-1-phosphate lyase-1 (SPL1) in splenocytes was downregulated. Taken together, these results indicate that chronic alcohol consumption decreases peripheral blood B cells by compromising B cell egress from the spleen. The downregulation of S1PR1 and SPL1 expression in alcohol-consuming, melanoma-bearing mice could be associated with compromised egress of B cells from the spleen.
Transcription Factor Zinc Finger and BTB Domain 1 Is Essential for Lymphocyte Development
Authors: Punwani Divya , Simon Karen , Choi Youngnim , Dutra Amalia , Gonzalez-Espinosa Diana , Pak Evgenia , Naradikian Martin , Song Chang-Hwa , Zhang Jenny , Bodine David M. , Puck Jennifer M. 
Published: July 2012

Abstract
Absent T lymphocytes were unexpectedly found in homozygotes of a transgenic mouse from an unrelated project. T cell development did not progress beyond double-negative stage 1 thymocytes, resulting in a hypocellular, vestigial thymus. B cells were present, but NK cell number and B cell isotype switching were reduced. Transplantation of wild-type hematopoietic cells corrected the defect, which was traced to a deletion involving five contiguous genes at the transgene insertion site on chromosome 12C3. Complementation using bacterial artificial chromosome transgenesis implicated zinc finger BTB-POZ domain protein 1 (Zbtb1) in the immunodeficiency, confirming its role in T cell development and suggesting involvement in B and NK cell differentiation. Targeted disruption of Zbtb1 recapitulated the T−B+NK− SCID phenotype of the original transgenic animal. Knockouts for Zbtb1 had expanded populations of bone marrow hematopoietic stem cells and also multipotent and early lymphoid lineages, suggesting a differentiation bottleneck for common lymphoid progenitors. Expression of mRNA encoding Zbtb1, a predicted transcription repressor, was greatest in hematopoietic stem cells, thymocytes, and pre-B cells, highlighting its essential role in lymphoid development.
The Peptide-Receptive Transition State of MHC Class I Molecules: Insight from Structure and Molecular Dynamics
Authors: Mage Michael G. , Dolan Michael A. , Wang Rui , Boyd Lisa F. , Revilleza Maria Jamela , Robinson Howard , Natarajan Kannan , Myers Nancy B. , Hansen Ted H. , Margulies David H. 
Published: July 2012

Abstract
MHC class I (MHC-I) proteins of the adaptive immune system require antigenic peptides for maintenance of mature conformation and immune function via specific recognition by MHC-I–restricted CD8+ T lymphocytes. New MHC-I molecules in the endoplasmic reticulum are held by chaperones in a peptide-receptive (PR) transition state pending release by tightly binding peptides. In this study, we show, by crystallographic, docking, and molecular dynamics methods, dramatic movement of a hinged unit containing a conserved 310 helix that flips from an exposed “open” position in the PR transition state to a “closed” position with buried hydrophobic side chains in the peptide-loaded mature molecule. Crystallography of hinged unit residues 46–53 of murine H-2Ld MHC-I H chain, complexed with mAb 64-3-7, demonstrates solvent exposure of these residues in the PR conformation. Docking and molecular dynamics predict how this segment moves to help form the A and B pockets crucial for the tight peptide binding needed for stability of the mature peptide-loaded conformation, chaperone dissociation, and Ag presentation.
Cutting Edge: Cell-Extrinsic Immune Regulation by CTLA-4 Expressed on Conventional T Cells
Authors: Wang Chun Jing , Kenefeck Rupert , Wardzinski Lukasz , Attridge Kesley , Manzotti Claire , Schmidt Emily M. , Qureshi Omar S. , Sansom David M. , Walker Lucy S. K. 
Published: July 2012

Abstract
The CTLA-4 pathway is a key regulator of T cell activation and a critical failsafe against autoimmunity. Although early models postulated that CTLA-4 transduced a negative signal, in vivo evidence suggests that CTLA-4 functions in a cell-extrinsic manner. That multiple cell-intrinsic mechanisms have been attributed to CTLA-4, yet its function in vivo appears to be cell-extrinsic, has been an ongoing paradox in the field. Although CTLA-4 expressed on conventional T cells (Tconv) can mediate inhibitory function, it is unclear why this fails to manifest as an intrinsic effect. In this study, we show that Tconv-expressed CTLA-4 can function in a cell-extrinsic manner in vivo. CTLA-4+/+ T cells, from DO11/rag−/− mice that lack regulatory T cells, were able to regulate the response of CTLA-4−/− T cells in cotransfer experiments. This observation provides a potential resolution to the above paradox and suggests CTLA-4 function on both Tconv and regulatory T cells can be achieved through cell-extrinsic mechanisms.
Cutting Edge: In the Absence of TGF-β Signaling in T Cells, Fewer CD103+ Regulatory T Cells Develop, but Exuberant IFN-γ Production Renders Mice More Susceptible to Helminth Infection
Authors: Reynolds Lisa A. , Maizels Rick M. 
Published: July 2012

Abstract
Multiple factors control susceptibility of C57BL/6 mice to infection with the helminth Heligmosomoides polygyrus, including TGF-β signaling, which inhibits immunity in vivo. However, mice expressing a T cell-specific dominant-negative TGF-β receptor II (TGF-βRII DN) show dampened Th2 immunity and diminished resistance to infection. Interestingly, H. polygyrus-infected TGF-βRII DN mice show greater frequencies of CD4+Foxp3+Helios+ Tregs than infected wild-type mice, but levels of CD103 are greatly reduced on both these cells and on the CD4+Foxp3+Helios– population. Although Th9 and Th17 levels are comparable between infected TGF-βRII DN and wild-type mice, the former develop exaggerated CD4+ and CD8+ T cell IFN-γ responses. Increased susceptibility conferred by TGF-βRII DN expression was lost in IFN-γ–deficient mice, although they remained unable to completely clear infection. Hence, overexpression of IFN-γ negatively modulates immunity, and the presence of Helios+ Tregs may maintain susceptibility on the C57BL/6 background.
NLRP1-Dependent Pyroptosis Leads to Acute Lung Injury and Morbidity in Mice
Authors: Kovarova Martina , Hesker Pamela R. , Jania Leigh , Nguyen MyTrang , Snouwaert John N. , Xiang Zhidan , Lommatzsch Stephen E. , Huang Max T. , Ting Jenny P.-Y. , Koller Beverly H. 
Published: July 2012

Abstract
Acute inflammation in response to both exogenous and endogenous danger signals can lead to the assembly of cytoplasmic inflammasomes that stimulate the activation of caspase-1. Subsequently, caspase-1 facilitates the maturation and release of cytokines and also, under some circumstances, the induction of cell death by pyroptosis. Using a mouse line lacking expression of NLRP1, we show that assembly of this inflammasome in cells is triggered by a toxin from anthrax and that it initiates caspase-1 activation and release of IL-1β. Furthermore, NLRP1 inflammasome activation also leads to cell death, which escalates over 3 d following exposure to the toxin and culminates in acute lung injury and death of the mice. We show that these events are not dependent on production of IL-1β by the inflammasome but are dependent on caspase-1 expression. In contrast, muramyl dipeptide-mediated inflammasome formation is not dependent on NLRP1 but NLRP3. Taken together, our findings show that assembly of the NLRP1 inflammasome is sufficient to initiate pyroptosis, which subsequently leads to a self-amplifying cascade of cell injury within the lung from which the lung cannot recover, eventually resulting in catastrophic consequences for the organism.
Intraoperative Assessment of Medial Rectus Pulley Location in Strabismus
Authors: Thouvenin Dominique , Norbert Olivier 
Published: July 2012

Purpose. Extraocular muscle (EOM) pulleys are important in eye movement physiology and may play a role in the outcome of strabismus surgery. Few studies have evaluated “normal” position of EOM pulleys. We sought to assess intraoperatively medial rectus (MR) pulley location and variations in a prospective observational case series. Methods. A total of 194 consecutive patients with all types of strabismus aged 2 to 64 years had primary surgery on MR. We conducted 357 measures of the distance between scleral insertion of MR and anterior part of the pulley. We compared results to preoperative angle of deviation, age, refraction, and position of eyes under anesthesia. Results. Median location of the anterior part of the MR's pulley is 12.03 mm from scleral insertion, varying from 8 to 15 mm. There is a strong relation with refraction (p=0.005) and with preoperative angle of deviation (p=0.00002) and deviation under anesthesia (p=0.0001). The MR's pulley tends to be more anterior in hyperopic cases and esotropias, and posterior in myopias and exotropias. Conclusions. Our study shows physiologic variations of MR's pulley position with evidence of an adaptation to biometric parameters of the globe, represented by refraction state of the eyes in our study. Elsewhere, strabismus leads to an independent variation of MR's pulley location evaluated relatively to muscle's scleral insertion, but probably not if evaluated relatively to the orbit. We discuss consequences on ocular motility and surgery of these variations. They may explain some unexpected effects of strabismus surgery. Further studies are needed to ascertain their real impact.
Repeated Injection of Botulinum Toxin a in Patients with Neurogenic Bladder: Our Experience
Authors: Cantoro Ubaldo , Minardi Daniele , Lacetera Vito , Conti Alessandro , Catanzariti Francesco , Muzzonigro Giovanni 
Published: July 2012

Background In literature, the majority of data about treatment with botulinum toxin A are based on the results of a single treatment. We evaluate the safety and effectiveness in the medium term of the use of botulinum toxin type A in patients with neurogenic bladder, taking into consideration the clinical and urodynamic parameters, particularly in cases with repeated injections. Methods 25 patients were divided into 2 groups: a first group of patients with detrusor overactivity, and a second with overactive sphincter. We performed 20–30 injections (Dysport), at a dose ranging between 500 and 1000 U. The first group was treated with infiltration in the detrusor and in the detrusor and trigone. The second group received injections in the perisphinteric zone, and in the perisphinteric zone and bladder neck. Of the 25 patients, 12 received a retreatment: the first group of patients kept a daily voiding diary to record the number of bladder emptying, incontinence episodes, nycturia and urgency of urination. The urodynamic parameters and symptoms pre-treatment and 4 months after the treatment were compared in both groups. Results In the first group there were significant changes in the cystometric capacity, maximum detrusor pressure, and in the post-void residual urine 4 months after treatment. These patients were satisfied with the treatment because of the improvement of incontinence and episodes of urgency. In 9 out of 15 retreated patients, the therapeutic results were similar to the first treatment. The second group reported significant improvements in maximum urinary flow rate, post-void residual urine and maximum detrusor pressure. 3 out of 10 patients were retreated even in this group; the new therapeutic results were similar to the first treatment. Conclusions Our results in 25 patients with neurogenic bladder showed a concordance with the literature data. The treatment of detrusor and sphincter neurogenic overactivity with botulinum toxin A is effective and safe. Also in the 12 patients with repeated injection treatment, it has been proven safe and effective.
Energy Efficiency Policy Puzzles
Authors: Brennan Timothy J. 
Published: July 2012

Promoting energy efficiency (EE) has become a leading policy response to greenhouse gas emissions, energy dependence, and the cost of new generators and transmission lines. Such policies present numerous puzzles. Electricity prices below marginal production costs could warrant EE policies if EE and energy are substitutes, but they will not be substitutes if the energy price is sufficiently high. Using EE savings to meet renewable energy requirements can dramatically increase the marginal cost of electricity. Rejecting “rationality” of consumer energy choices raises doubts regarding cost-benefit analysis when demand curves may not reveal willingness to pay. Decoupling to guarantee constant profit regardless of use contradicts findings that incentive-based mechanisms outperform cost-of-service regulation. Regulators may implement EE policies to exercise buyer-side market power against generators, increasing consumer welfare but reducing overall economic performance. Encouraging utilities to take over potentially competitive EE contradicts policies to separate competitive from monopoly enterprises. http://dx.doi.org/10.5547/01956574.34.2.1
Changes in the Operational Efficiency of National Oil Companies
Authors: Hartley Peter R. , Medlock Kenneth B. 
Published: July 2012

Using data on 61 oil companies from 2001-09, we examine the evolution of revenue efficiency of National Oil Companies (NOCs) and shareholder-owned oil companies (SOCs). We find that NOCs generally are less efficient than SOCs, but their efficiency increased faster over the last decade. We also find evidence that partial privatizations increase operational efficiency, and (weaker) evidence that mergers and acquisitions during the decade tended to increase the efficiency of the merging firms. Finally, we find evidence that much of the inefficiency of NOCs is consistent with the hypothesis that government ownership leads to different firm objectives. http://dx.doi.org/10.5547/01956574.34.2.2
Regional Trade Agreements, Emissions Bubbles, and Carbon Tariff Harmonization
Authors: Dissou Yazid , Siddiqui Muhammad Shahid 
Published: July 2012

In the context of sub-global participation in greenhouse gas mitigation efforts, this paper investigates the effectiveness of a Canada-U.S. emissions bubble under their existing regional trade agreement. It also explores the potential economic impact of carbon tariff harmonization through the implementation of a common Canada-U.S. external border tariff adjustment as a mean to address competitiveness issues. Using a multi-region, multi-sector computable general equilibrium model, the paper finds that the creation of an emission bubble between the two countries could improve efficiency. The findings also suggest that a carbon tariff harmonization policy could give rise to distributional issues among Annex I regions and could fail to mitigate the negative competitiveness impacts of carbon abatement policies. http://dx.doi.org/10.5547/01956574.34.2.3
Current policies in Europe and South Asia do not prevent veterinary use of drugs toxic to vultures
Authors: Cook Sophie E. , Green Rhys E. , Lieberherr Eva , Bowden Christopher G. R. , Chaudhry Muhammed Jamshed Iqbal , Alam A. B. M. Sarowar , Bharathidasan S. , Prakash Vibhu , Ghoshal Abhishek , Margalida Antoni , Shobrak Mohammed , Thapa Ishana 
Published: June 2024

Abstract

Population declines of vultures of the genus Gyps in the Indian Subcontinent in the 1990s and 2000s were among the most rapid global population declines recorded for any bird species.

Multiple lines of evidence identified veterinary treatment of cattle with the non‐steroidal anti‐inflammatory drug (NSAID) diclofenac as the principal cause of the vulture population crash. Diclofenac causes kidney failure and death within a few days of a vulture scavenging the carcass of a recently treated cow.

Despite coordinated regulatory action by governments to ban veterinary diclofenac in South Asia, enforcement has been incomplete in many areas. Progress in preventing the veterinary use of other NSAIDs now also known to be vulture‐toxic has been slow. A mosaic of inconsistent licensing processes currently exists across South Asian vulture range states, leading to issues with successful policy implementation, legitimacy and effectiveness.

At present, mandatory safety testing to ensure NSAIDs already in use or proposed for use are vulture‐safe is not part of drug licensing procedures in any vulture range state.

In 2021, Bangladesh became the first country to ban a vulture‐toxic NSAID, in addition to diclofenac, by banning veterinary use of ketoprofen. In 2023, India became the second country to take this step when the government announced a ban on veterinary aceclofenac and ketoprofen. This government action in India may have been triggered by a recent legal challenge.

Despite its veterinary use now being banned in South Asian and the Middle Eastern countries, diclofenac has been authorised for sale since 2013 as a veterinary drug in Spain, even though Spain holds 90% of the vulture population of Europe. The European Commission's decision to leave the authorisation of this drug to Member States is at odds with a central pillar of environmental law in the European Union (EU): the precautionary principle. Furthermore, this approach is not consistent with the stringent standards and burden of proof applied to the licensing of EU plant protection products.

Solution. A solution to this lack of protection of Gyps vulture populations is for regulatory regimes for veterinary NSAIDs to be augmented.
Study to evaluate the effect of Tangshen Fang combined with guideline‐directed medical treatment on the quality of life and clinical outcomes in patients with diabetic nephropathy: A clinical trial on constructing a novel paradigm of integrated traditional Chinese and Western medicine in the treatment of diabetic nephropathy
Authors: Jin Xian , Wang Yanmei , Li Ping , Wu Lili , Wang Na , Duan Jun , Jiang Qinyu , Li Yangxi , Yin Zhuo , Wu Xi'ai , Chen Xiaoping 
Published: June 2024

AbstractBackgroundDiabetic kidney disease (DKD) is one of the most common microvascular complications of diabetes mellitus and has become the primary cause of end‐stage renal disease in China. In patients with severe renal insufficiency, Western medical treatments often yield unsatisfactory results. Preliminary studies have indicated that the Chinese herbal formula Tangshen Fang improves estimated glomerular filtration rate (eGFR) in patients with DKD.Methods/designThis is a multicenter, randomized, open‐label, controlled clinical trial. DKD patients with eGFR levels between 25 and 75 mL/min (1.73 m2) and urinary albumin‐to‐creatinine ratio (UACR) ≥ 30 mg/g, or eGFR level between 25 and 60 mL/min (1.73 m2) and UACR <30 mg will be included. A total of 144 participants will be randomly allocated to the treatment group (Tangshen Fang plus standard Western medicine with or without other traditional Chinese medicine [TCM]) and the control group (standard Western medicine with or without other TCM) at a 1:1 ration. The study duration will be 24 weeks and the follow‐up period will be extended to 96 weeks. The primary endpoint will be the change in eGFR from baseline to week 24. Secondary endpoints will include changes in UACR, body weight, waist circumference, blood pressure, lipid levels, fasting plasma glucose, glycosylated hemoglobin A1c (HbA1c), and improvement in TCM symptoms and quality of life. Adverse events will also be evaluated.DiscussionThis study will provide evidence of the effectiveness and safety of Tangshen Fang in treating patients with DKD. It will also form the clinical pathway and expert consensus on integrating traditional Chinese and Western medicine for DKD and provide clinical evidence for the rational use of hospital preparations of Tangshen Fang.Trial registrationChinese Clinical Trials Registry, ChiCTR2300069269. Registered March 10, 2023.