bluuebunny/crossref_metadata_2025_split huggingface dataset:
Noncore RAG1 Regions Promote Vβ Rearrangements and αβ T Cell Development by Overcoming Inherent Inefficiency of Vβ Recombination Signal Sequences
Authors: Horowitz Julie E. , Bassing Craig H. 
Published: January 2014

Abstract
The RAG proteins are comprised of core endonuclease domains and noncore regions that modulate endonuclease activity. Mutation or deletion of noncore RAG regions in humans causes immunodeficiency and altered TCR repertoire, and mice expressing core but not full-length Rag1 (Rag1C/C) or Rag2 (Rag2C/C) exhibit lymphopenia, reflecting impaired V(D)J recombination and lymphocyte development. Rag1C/C mice display reduced D-to-J and V-to-DJ rearrangements of TCRβ and IgH loci, whereas Rag2C/C mice show decreased V-to-DJ rearrangements and altered Vβ/VH repertoire. Because Vβs/VHs only recombine to DJ complexes, the Rag1C/C phenotype could reflect roles for noncore RAG1 regions in promoting recombination during only the D-to-J step or during both steps. In this study, we demonstrate that a preassembled TCRβ gene, but not a preassembled DβJβ complex or the prosurvival BCL2 protein, completely rescues αβ T cell development in Rag1C/C mice. We find that Rag1C/C mice exhibit altered Vβ utilization in Vβ-to-DJβ rearrangements, increased usage of 3′Jα gene segments in Vα-to-Jα rearrangements, and abnormal changes in Vβ repertoire during αβ TCR selection. Inefficient Vβ/VH recombination signal sequences (RSSs) have been hypothesized to cause impaired V-to-DJ recombination on the background of a defective recombinase as in core-Rag mice. We show that replacement of the Vβ14 RSS with a more efficient RSS increases Vβ14 recombination and rescues αβ T cell development in Rag1C/C mice. Our data indicate that noncore RAG1 regions establish a diverse TCR repertoire by overcoming Vβ RSS inefficiency to promote Vβ recombination and αβ T cell development, and by modulating TCRβ and TCRα gene segment utilization.
Posttranscriptional Modulation of Cytokine Production in T Cells for the Regulation of Excessive Inflammation by TFL
Authors: Minagawa Kentaro , Wakahashi Kanako , Kawano Hiroki , Nishikawa Shinichiro , Fukui Chie , Kawano Yuko , Asada Noboru , Sato Mari , Sada Akiko , Katayama Yoshio , Matsui Toshimitsu 
Published: January 2014

Abstract
Posttranscriptional machinery regulates inflammation and is associated with autoimmunity as well as tumorigenesis in collaboration with transcription factors. We previously identified the tumor suppressor gene transformed follicular lymphoma (TFL) on 6q25 in a patient with follicular lymphoma, which transformed into diffuse large B cell lymphoma. TFL families have a common RNase domain that governs macrophage-mediated inflammation. In human peripheral blood, TFL is dominantly expressed at the glycine- and tryptophan-rich cytoplasmic processing bodies of T lymphocytes, and it is persistently upregulated in activated T cells. To address its physiological role, we established TFL−/− mice in which TFL−/− lymphocytes proliferated more rapidly than TFL+/+ upon stimulation with inappropriate cytokine secretion, including IL-2, IL-6, and IL-10. Moreover, TFL inhibited the synthesis of cytokines such as IL-2, IL-6, IL-10, TNF-α, and IL-17a by 3′ untranslated region RNA degradation. Experimental autoimmune encephalitis induced in TFL−/− mice demonstrated persistent severe paralysis. CNS-infiltrated CD4+ T cells in TFL−/− mice contained a higher proportion of Th17 cells than did those in TFL+/+ mice during the resolution phase, and IL-17a mRNA levels were markedly increased in TFL−/− cells. These results suggest that TFL may play an important role in attenuating local inflammation by suppressing the infiltration of Th17 cells in the CNS during the resolution phase of experimental autoimmune encephalitis. TFL is a novel gradual and persistent posttranscriptional regulator, and the TFL-driven attenuation of excessive inflammation could contribute to recovery from T cell–mediated autoimmune diseases.
Enforced Expression of Gata3 in T Cells and Group 2 Innate Lymphoid Cells Increases Susceptibility to Allergic Airway Inflammation in Mice
Authors: KleinJan Alex , Klein Wolterink Roel G. J. , Levani Yelvi , de Bruijn Marjolein J. W. , Hoogsteden Henk C. , van Nimwegen Menno , Hendriks Rudi W. 
Published: January 2014

Abstract
Airway inflammation in allergic asthma reflects a threshold response of the innate immune system, including group 2 innate lymphoid cells (ILC2), followed by an adaptive Th2 cell–mediated response. Transcription factor Gata3 is essential for differentiation of both Th2 cells and ILC2. We investigated the effects of enforced Gata3 expression in T cells and ILC2 on the susceptibility of mice to allergic airway inflammation (AAI). We used CD2-Gata3 transgenic (Tg) mice with enforced Gata3 expression driven by the CD2 promoter, which is active both in T cells and during ILC2 development. CD2-Gata3 Tg mice and wild-type (WT) littermates were analyzed in mild models of AAI without adjuvants. Whereas OVA allergen exposure did not induce inflammation in WT controls, CD2-Gata3 Tg mice showed clear AAI and enhanced levels of IL-5 and IL-13 in bronchoalveolar lavage. Likewise, in house dust mite–driven asthma, CD2-Gata3 Tg mice were significantly more susceptible to AAI than WT littermates, whereby both ILC2 and Th2 cells were important cellular sources of IL-5 and IL-13 in bronchoalveolar lavage and lung tissue. Compared with WT littermates, CD2-Gata3 Tg mice contained increased numbers of ILC2, which expressed high levels of IL-33R and contributed significantly to early production of IL-4, IL-5, and IL-13. CD2-Gata3 Tg mice also had a unique population of IL-33–responsive non-B/non-T lymphoid cells expressing IFN-γ. Enforced Gata3 expression is therefore sufficient to enhance Th2 and ILC2 activity, and leads to increased susceptibility to AAI after mild exposure to inhaled harmless Ags that otherwise induce Ag tolerance.
Fetal Intervention Increases Maternal T Cell Awareness of the Foreign Conceptus and Can Lead to Immune-Mediated Fetal Demise
Authors: Wegorzewska Marta , Nijagal Amar , Wong Charissa M. , Le Tom , Lescano Ninnia , Tang Qizhi , MacKenzie Tippi C. 
Published: January 2014

AbstractFetal interventions to diagnose and treat congenital anomalies are growing in popularity but often lead to preterm labor. The possible contribution of the maternal adaptive immune system to postsurgical pregnancy complications has not been explored. We recently showed that fetal intervention in mice increases maternal T cell trafficking into the fetus and hypothesized that this process also may lead to increased maternal T cell recognition of the foreign conceptus and subsequent breakdown in maternal–fetal tolerance. In this study, we show that fetal intervention in mice results in accumulation of maternal T cells in the uterus and that these activated cells can produce effector cytokines. In adoptive transfer experiments, maternal T cells specific for a fetal alloantigen proliferate after fetal intervention, escape apoptosis, and become enriched compared with endogenous T cells in the uterus and uterine-draining lymph nodes. Finally, we demonstrate that such activation and accumulation can have a functional consequence: in utero transplantation of hematopoietic cells carrying the fetal alloantigen leads to enhanced demise of semiallogeneic fetuses within a litter. We further show that maternal T cells are necessary for this phenomenon. These results suggest that fetal intervention enhances maternal T cell recognition of the fetus and that T cell activation may be a culprit in postsurgical pregnancy complications. Our results have clinical implications for understanding and preventing complications associated with fetal surgery such as preterm labor.
Resident Duty Hours in the Outpatient Electronic Health Record Era: Inaccuracies and Implications
Authors: Gilleland Meghan , Komis Katherine , Chawla Sonya , Fernandez Stephen , Fishman Mary , Adams Michael 
Published: January 2014

Abstract

Background
The Accreditation Council for Graduate Medical Education expects resident duty hours to be monitored, yet no previous studies have examined the effect of after-hours electronic health record (EHR) use on resident hours or burnout.

Objective
We assessed internal medicine residents' perceived and actual time spent on after-hours outpatient EHR use and calculated increased duty hours if after-hours EHR use were included; we also assessed its effect on resident burnout.

Methods
We retrospectively aggregated time spent logged on to the outpatient EHR for residents in a general internal medicine clinic for 13 weeks in 2011. Residents completed a survey on EHR use, which was correlated with objectively recorded data on EHR usage. We compared actual and self-reported EHR time and identified violations that would be generated if these hours were included in reported duty hours. We also correlated resident after-hours EHR use with responses to an internally developed burnout survey.

Results
The 44 residents in this study overestimated time spent on the ambulatory EHR (they spent 3.03 hours/week on after-hours use compared with a recorded 1.20 hours/week). In total, 190 duty hour violations (mean duration of violation  =  37 minutes) would have been generated if after-hours EHR usage were included in residents' reported duty hours.

Conclusions
Resident estimates of EHR use by residents were not accurate; including after-hours EHR use would increase the number of reported duty hour violations. There was no association between after-hours EHR use and resident burnout.
Performance of Residents Serving as Clinical Teachers: A Student-Based Assessment
Authors: Owolabi Mayowa O. , Afolabi Adefemi O. , Omigbodun Akinyinka O. 
Published: January 2014

Abstract

Background
Little is known about the competences of residents as clinical teachers in African health care institutions.

Objective
We evaluated the clinical teaching skills of internal medicine residents from the perspective of medical students in a tertiary teaching institution in Africa.

Methods
We used the augmented Stanford Faculty Development Program Questionnaire, which has evidence of validity and reliability. To avoid a Hawthorne effect, students completed the questionnaire anonymously and confidentially after clinical teaching sessions by residents. A minimum score of 4 on a scale of 1 to 5 was defined a priori as possession of good clinical teaching skills.

Results
Sixty-four medical students assessed all 20 internal medicine residents in the Department of Medicine, University of Ibadan. Mean performance scores for the domains ranged from 3.07 to 3.66. Residents performed best in creating a good learning climate and worst in the promotion of understanding and retention. Sex of the resident, duration of residency, and rank had no significant impact (.09 &lt; P &lt; .94) on their teaching skills.

Conclusions
Consistent with other observations in the literature, residents' clinical teaching skills were suboptimal, particularly in their ability to promote understanding and retention. To enhance these skills, we recommend the integration of appropriately tailored programs to teach pedagogic skills programs in residency training.
Death and Disability in a Younge Phase Community
Authors: Spence Michael W. , Williams Lana J. , Wheeler Sandra M. 
Published: January 2014

AbstractRoffelsen is an early Younge phase mortuary component in southwestern Ontario. The single burial feature is a pit containing the articulated skeletons of seven successively buried individuals, ranging in age from a few months to late middle age. All had been stripped of soft tissues, except for the connecting tissues that maintained their articulation. Most also had a disk cut from the cranium and a hole drilled near bregma. All but the infant display various forms of developmental failure of the outer and middle ear and the petrous portion of the temporal bone. The pit was apparently the burial facility for an extended family with significant hearing impairments. This disability may have limited their interaction with neighboring communities, perhaps even playing a role in their eventual disappearance as a separate community.
Concerning the Atlatl and the Bow: Further Observations Regarding Arrow and Dart Points in the Archaeological Record
Authors: Walde Dale 
Published: January 2014

AbstractHildebrandt and King (2012) propose a new method for distinguishing between archaeologically obtained atlatl darts and arrow points, suggesting their dart-arrow index identifies specimens more accurately than previously developed multivariate approaches. They assert that use of their index supports conclusions that the bow was a superior technology and replaced the atlatl quickly. I use their index, as well as Shott’s (1997) equations, to analyze southern Saskatchewan archaeological point specimens. My results suggest that the proposed dart-arrow index performs poorly for Canadian Plains specimens and that atlatl and bow technology coexisted for an extended period of time.
Darts, Arrows, and Archaeologists: Distinguishing Dart and Arrow Points in the Archaeological Record
Authors: Erlandson Jon M. , Watts Jack L. , Jew Nicholas P. 
Published: January 2014

AbstractUsing several methods to distinguish dart and arrow points, archaeologists have suggested that the bow and arrow appeared in various parts of the world between ˜65,000 and 1,000 years ago. Hildebrandt and King (2012) proposed a dart-arrow index (DAI) to help differentiate dart and arrow points, rejecting claims that the bow and arrow was introduced to western North America prior to the Late Holocene. We used the DAI and other methods to evaluate ˜11,700-year-old projectile points from Santa Rosa Island, obtaining mean values below the threshold for darts, comparable to several North American arrow point types. We have no direct evidence that these small points were used on darts, arrows, or hand-thrown spears, but faunal associations suggest that they may have served as harpoon tips used on atlatl darts to capture birds, fish, and marine mammals. The DAI and other methods for discriminating between dart and arrow points are based almost exclusively on ethnographic and archaeological specimens from interior regions. Our analysis suggests that such methods should not be applied universally, especially in coastal or other aquatic settings, and that archaeologists should continue to critically assess the antiquity of the bow and arrow and the function of projectile points worldwide.
Pre-Clovis Lithic Technology at the Debra L. Friedkin Site, Texas: Comparisons to Clovis through Site-Level Behavior, Technological Trait-List, and Cladistic Analyses
Authors: Jennings Thomas A. , Waters Michael R. 
Published: January 2014

AbstractHumans first left Siberia and colonized the Americas perhaps around 16,000 years ago, and the Clovis archaeological complex in North America has traditionally been linked to this migratory pulse. Archaeologists searching for evidence of Clovis technological antecedents have focused their attention on the Beringian and Siberian archaeological records. Growing evidence for the pre-Clovis occupation of North America provides a possible alternative source for the origins of Clovis. In this paper, we present new data on the pre-Clovis lithic assemblage from the Debra L. Friedkin site, Texas, and compare Clovis and pre-Clovis lithic technological signatures. We show that while Clovis and pre-Clovis share some important technological traits, they also differ in important ways. We conclude that the pre-Clovis assemblage from Debra L. Friedkin cannot be called “Clovis,” but it could represent a technological antecedent of Clovis.
Eye of the Needle: Cold Stress, Clothing, and Sewing Technology During the Younger Dryas Cold Event in North America
Authors: Osbora Alan J. 
Published: January 2014

AbstractThis paper examines the possible underlying systemic contexts) for spurred flake gravers and eyed bone needles recovered from Paleoindian sites in North America. The idea that spurred flake gravers and eyed bone needles were closely associated is not new. Archaeologists in both Eurasia and North America have also proposed that eyed bone and ivory needles were used for manufacturing tailored skin clothing. It is suggested here that spurred flake gravers and eyed bone needles may, in fact, be the material correlates of critical non-subsistence related work carried out by women to meet the challenges of very severe winters and cold stress of the Younger Dryas Cold Event (YDCE) between 12,900–11,600 cal. B.P. It is argued here that such expediently produced flake implements and curated sewing technology including eyed needles ultimately reflect the significant ecological bottlenecks) posed by the YDCE for Paleoindian populations. Metric attributes of both spurred flake gravers and eyed bone needles, their spatial co-occurrence in archaeological contexts, and their temporal co-occurrence within the YDCE lend empirical support for this causal argument.
Grand Challenges for Archaeology
Authors: Kintigh Keith W. , Altschul Jeffrey H. , Beaudry Mary C. , Drennan Robert D. , Kinzig Ann P. , Kohler Timothy A. , Limp W. Fredrick , Maschner Herbert D. G. , Michener William K. , Pauketat Timothy R. , Peregrine Peter , Sabloff Jeremy A. , Wilkinson Tony J. , Wright Henry T. , Zeder Melinda A. 
Published: January 2014

AbstractThis article represents a systematic effort to answer the question, What are archaeology’s most important scientific challenges? Starting with a crowd-sourced query directed broadly to the professional community of archaeologists, the authors augmented, prioritized, and refined the responses during a two-day workshop focused specifically on this question. The resulting 25 “grand challenges” focus on dynamic cultural processes and the operation of coupled human and natural systems. We organize these challenges into five topics: (1) emergence, communities, and complexity; (2) resilience, persistence, transformation, and collapse; (3) movement, mobility, and migration; (4) cognition, behavior, and identity; and (5) human-environment interactions. A discussion and a brief list of references accompany each question. An important goal in identifying these challenges is to inform decisions on infrastructure investments for archaeology. Our premise is that the highest priority investments should enable us to address the most important questions. Addressing many of these challenges will require both sophisticated modeling and large-scale synthetic research that are only now becoming possible. Although new archaeological fieldwork will be essential, the greatest pay off will derive from investments that provide sophisticated research access to the explosion in systematically collected archaeological data that has occurred over the last several decades.
Evaluating Cahokian Contact and Mississippian Identity Politics in the Late Prehistoric Central Illinois River Valley
Authors: Bardolph Dana N. 
Published: January 2014

AbstractThis paper employs a practice-based framework for investigating early Mississippian period culture contact and identity negotiation in the Central Illinois River Valley (CIRV) through the lens offoodways. The Evelandphase (A.D. 1100–1200) was a setting of significant cultural change as a result of the movement of Cahokian people, objects, and ideas into the region. Recent analysis of excavated materials from the Lamb site in the southern portion of the CIRV affords a closer look at this historical process. Using ceramic and pit feature data, I assess Cahokian influence on traditional Late Woodlandera culinary practices. I conclude that although local residents were actively adopting some aspects of Mississippian culture (including Cahokia potting traditions), they retained traditional Late Woodland organizational practices of cooking, serving, and storing food. By placing the organization offoodways at the center of this study, this paper illuminates another dimension of Cahokian contact in the region.
Ritual Change and the Distant: Mesoamerican Iconography, Scarlet Macaws, and Great Kivas in the Mimbres Region of Southwestern New Mexico
Authors: Gilman Patricia A. , Thompson Marc , Wyckoff Kristina C. 
Published: January 2014

AbstractThe Mimbres Classic period (A .D. 1000–1130) in southwestern New Mexico was marked by dramatic and complex changes. The use of Great Kivas ended, and macaws and Mesoamerican-inspired iconography appeared. We argue that these events were systematically related and signify observable changes in Mimbres ritual economy. The presence of macaws, images of macaws, and representations of characters and motifs from the Hero Twins saga suggest that ideology accompanied macaws north from the Gulf Coast of Mexico. We recognize and discuss episodes and icons from the saga painted on Mimbres black-on-white bowls and propose that the macaws and narrative reached the Mimbres region through direct acquisition rather than down-the-line trade. This research has significant implications for the importance of long distance travel to faraway places and interaction with distant peoples, Mesoamerican-southwestern United States relationships, changing religious practices in non-hierarchical societies, and the adoption of extrinsic elements into local settings.
Les professionnels de la surveillance financière. Le malentendu comme condition de possibilité1
Authors: Amicelle2 Anthony 
Published: January 2014

Le suivi de la piste financière fait aujourd’hui partie des pratiques instituées en matière de police et de renseignement. Située à l’interface de la finance et de la sécurité, la lutte contre le blanchiment de capitaux et le financement du terrorisme repose sur les relations de coopération tissées entre deux groupes d’acteurs aux motivations et aux savoir-faire différents. La notion floue d’« argent sale » est en effet le point de rencontre d’une constellation d’intérêts et de deux logiques d’action propres aux forces de l’ordre et aux opérateurs du système financier. Analysant le dispositif anti-blanchiment au Royaume-Uni, le présent article met en lumière l’articulation fragile de ces deux logiques d’action autour d’un malentendu sur le sens donné à la lutte contre l’« argent sale ». Loin de constituer un obstacle à l’élaboration et à l’opérationnalisation d’une politique spécifique, le malentendu est ici sa condition même de possibilité. Méprises et divergences d’interprétation sur le « problème » à traiter et les objectifs à poursuivre contribuent paradoxalement à la formation du bataillon bigarré des professionnels de la surveillance financière.
Equatorial signatures of the Pacific Meridional Modes: Dependence on mean climate state
Authors: Zhang Honghai , Deser Clara , Clement Amy , Tomas Robert 
Published: January 2014

AbstractExtratropical atmospheric variability can impact tropical climate in the Pacific sector via the Pacific Meridional Modes (PMMs). The South PMM (SPMM) has a larger equatorial signature than the North PMM (NPMM) for the same amount of extratropical variability. Here we explain this interhemispheric asymmetry using an atmospheric general circulation model coupled to a slab ocean model. By imposing an anomalous interhemispheric heating gradient, we strengthen the northeasterly trades and weaken the southeasterly trades, shifting the Intertropical Convergence Zone south of the equator. As a result, the SPMM no longer influences the equatorial region while the NPMM shows strengthened linkages to the central‐western equatorial Pacific. By demonstrating that background winds determine the propagation of the wind‐evaporation‐sea surface temperature feedback fundamental for the PMMs, we conclude that the interhemispheric asymmetry between the PMMs is largely attributed to the asymmetric mean trades in the Pacific. The results have implications for both paleoclimate studies and model development.