bluuebunny/crossref_metadata_2025_split huggingface dataset:
ERK and p38 MAPK Activities Determine Sensitivity to PI3K/mTOR Inhibition via Regulation of MYC and YAP
Authors: Muranen Taru , Selfors Laura M. , Hwang Julie , Gallegos Lisa L. , Coloff Jonathan L. , Thoreen Carson C. , Kang Seong A. , Sabatini David M. , Mills Gordon B. , Brugge Joan S. 
Published: October 2016

Abstract
Aberrant activation of the PI3K/mTOR pathway is a common feature of many cancers and an attractive target for therapy, but resistance inevitably evolves as is the case for any cancer cell–targeted therapy. In animal tumor models, chronic inhibition of PI3K/mTOR initially inhibits tumor growth, but over time, tumor cells escape inhibition. In this study, we identified a context-dependent mechanism of escape whereby tumor cells upregulated the proto-oncogene transcriptional regulators c-MYC and YAP1. This mechanism was dependent on both constitutive ERK activity as well as inhibition of the stress kinase p38. Inhibition of p38 relieved proliferation arrest and allowed upregulation of MYC and YAP through stabilization of CREB. These data provide new insights into cellular signaling mechanisms that influence resistance to PI3K/mTOR inhibitors. Furthermore, they suggest that therapies that inactivate YAP or MYC or augment p38 activity could enhance the efficacy of PI3K/mTOR inhibitors. Cancer Res; 76(24); 7168–80. ©2016 AACR.
Paleontologia da fácies arenosa do membro Taquaral (Permiano) no Estado de São Paulo: estado da arte e contribuições adicionais
Authors: Chahud Artur , Petri Setembrino 
Published: October 2016

A Formação Irati, Permiano (Cisuraliano) da Bacia do Paraná, destaca-se por importantes características geológicas e paleontológicas. Entre seus fósseis, os crustáceos e répteis Mesosauridae são os mais conhecidos e estudados. Nas fácies arenosas do Membro Taquaral sempre foram citados restos de peixes desarticulados, mas nenhum trabalho foi publicado. Esta lacuna no conhecimento paleontológico foi preenchida com diversas contribuições que serão resumidas neste trabalho. A maior parte dos fósseis são dentes, escamas e partes ósseas indeterminadas de Actinopterygii, porém deve-se aos Chondrichthyes maior diversidade taxonômica, na forma de dentes e espinhos. Os dentes mais abundantes pertencem ao Holocephali Itapyrodus, inicialmente considerado monoespecífico, I. punctatus. Estudos recentes revelaram que diferentes morfotipos identificados como Itapyrodus, podem incluir várias espécies. Os elasmobrânquios são representados por dentes cladodontes, pelo menos três gêneros baseados em espinhos, (Amelacanthus, Sphenacanthus e um indeterminado), uma espécie de Orodontiformes, Orodus ipeunaensis, e Xenacanthiformes, com a espécie Taquaralodus albuquerquei e duas espécies indeterminadas. Outros fósseis também foram registrados; Sarcopterygii (Actinistia, Osteolepiformes), tetrápodes (Temnospondyli), icnofósseis indeterminados e citações de microfósseis (foraminiferos, ostracodes e acritarcas).
Modelo de alojamento do Plúton Cupira, Província Borborema (NE Brasil)
Authors: Miranda Tiago Siqueira de , Mariano Gorki , Correia Paulo de Barros 
Published: October 2016

O Plúton Cupira está localizado no Domínio Sul da Província Borborema, possui área aflorante de aproximadamente 300 km2 e forma ovalada com leve alongamento na direção E-W. Com objetivo de determinar o modelo de alojamento do plúton e os alinhamentos magnético-estruturais, foi realizada a integração inédita de estudos de anisotropia de suscetibilidade magnética (ASM) e magnetometria. Os dados de ASM mostram que a susceptibilidade total apresenta variação de 0,105x10-3 SI a 34,618x10-3 SI, indicando caráter ferromagnético. O grau de anisotropia varia de 1,06 a 1,272 e apresenta correlação positiva com a susceptibilidade total. O parâmetro de forma varia de -0,802 a 0,897, com preponderância de elipsoides oblatos sobre prolatos, refletindo trama magnética planar. A maioria das lineações magnéticas possuem direção NE-SW, com caimentos suaves a fortes para NE e para SW. A foliação magnética varia de NE a NNE, com mergulhos moderados a fortes (30° a 86°). A porção central do corpo tem foliações magnéticas e magmáticas essencialmente concêntricas, com mergulhos fortes para o centro do plúton, associadas à lineações com caimento forte, sugerindo ser a zona de alimentação magmática. Os alinhamentos magnéticos reforçam as direções estruturais evidenciadas pela ASM. Estes dados favorecem a proposição de modelo de alojamento do Plúton Cupira a partir de uma zona de alimentação magmática central, com fluxo do magma distribuído de forma concêntrica, com geometria de intrusão similar a um lopólito.
TULA-2 (T-Cell Ubiquitin Ligand-2) Inhibits the Platelet Fc Receptor for IgG IIA (FcγRIIA) Signaling Pathway and Heparin-Induced Thrombocytopenia in Mice
Authors: Zhou Yuhang , Abraham Shaji , Renna Stephanie , Edelstein Leonard C. , Dangelmaier Carol A. , Tsygankov Alexander Y. , Kunapuli Satya P. , Bray Paul F. , McKenzie Steven E. 
Published: October 2016

Objective—
The objective of this study is to investigate the role of T-cell ubiquitin ligand-2 (TULA-2) in the platelet Fc receptor for IgG IIA (FcγRIIA) pathway and in the pathogenesis of heparin-induced thrombocytopenia (HIT).

Approach and Results—

HIT is a life-threatening thrombotic disease in which IgG antibodies against the heparin–platelet factor 4 complex activate platelets via FcγRIIA. We reported previously differential expression of TULA-2 in human population was linked to FcγRIIA responsiveness. In this study, we investigated the role of TULA-2, a protein phosphatase, in the FcγRIIA pathway and HIT pathogenesis by crossing TULA-2
−
/−
mice with transgenic FcγRIIA
+/+
mice. Ablation of TULA-2 resulted in hyperphosphorylation of spleen tyrosine kinase, linker for the activation of T cells, and phospholipase Cγ2 in platelets via FcγRIIA activation. Platelet integrin activation, granule secretion, phosphatidylserine exposure, and aggregation were also enhanced in TULA-2
−
/−
murine platelets. Compared with wild-type mice, TULA-2
−
/−
mice showed aggravated antibody-mediated thrombocytopenia, augmented thrombin generation, and shortened tail bleeding time. In contrast, there was no significant difference between TULA-2
−
/−
and TULA-2
+/+
platelets in platelet spreading and clot retraction. Of note, heterozygous TULA-2
+/−
mice, whose platelets contained 50% as much protein as the TULA-2
+/+
platelets, showed significantly increased platelet reactivity and more severe thrombocytopenia in vivo compared with TULA-2
+/+
mice.

Conclusions—
Together, the data demonstrate that not only the absence of TULA-2 but also the relative level of TULA-2 expression modulates FcγRIIA-mediated platelet reactivity and HIT in vivo. TULA-2 expression could be a valuable marker for HIT and inhibiting TULA-2 may serve as a potential therapy to reverse the bleeding adverse effect of anticoagulants.
Inhibition of Aberrant MicroRNA-133a Expression in Endothelial Cells by Statin Prevents Endothelial Dysfunction by Targeting GTP Cyclohydrolase 1 in Vivo
Authors: Li Peng , Yin Ya-Ling , Guo Tao , Sun Xue-Ying , Ma Hui , Zhu Mo-Li , Zhao Fan-Rong , Xu Ping , Chen Yuan , Wan Guang-Rui , Jiang Fan , Peng Qi-Sheng , Liu Chao , Liu Li-Ying , Wang Shuang-Xi 
Published: October 2016

Background:
GTP cyclohydrolase 1 (GCH1) deficiency is critical for endothelial nitric oxide synthase uncoupling in endothelial dysfunction. MicroRNAs (miRs) are a class of regulatory RNAs that negatively regulate gene expression. We investigated whether statins prevent endothelial dysfunction via miR-dependent GCH1 upregulation.

Methods:
Endothelial function was assessed by measuring acetylcholine-induced vasorelaxation in the organ chamber. MiR-133a expression was assessed by quantitative reverse transcription polymerase chain reaction and fluorescence in situ hybridization.

Results:
We first demonstrated that GCH1 mRNA is a target of miR-133a. In endothelial cells, miR-133a was robustly induced by cytokines/oxidants and inhibited by lovastatin. Furthermore, lovastatin upregulated GCH1 and tetrahydrobiopterin, and recoupled endothelial nitric oxide synthase in stressed endothelial cells. These actions of lovastatin were abolished by enforced miR-133a expression and were mirrored by a miR-133a antagomir. In mice, hyperlipidemia- or hyperglycemia-induced ectopic miR-133a expression in the vascular endothelium, reduced GCH1 protein and tetrahydrobiopterin levels, and impaired endothelial function, which were reversed by lovastatin or miR-133a antagomir. These beneficial effects of lovastatin in mice were abrogated by in vivo miR-133a overexpression or GCH1 knockdown. In rats, multiple cardiovascular risk factors including hyperglycemia, dyslipidemia, and hyperhomocysteinemia resulted in increased miR-133a vascular expression, reduced GCH1 expression, uncoupled endothelial nitric oxide synthase function, and induced endothelial dysfunction, which were prevented by lovastatin.

Conclusions:
Statin inhibits aberrant miR-133a expression in the vascular endothelium to prevent endothelial dysfunction by targeting GCH1. Therefore, miR-133a represents an important therapeutic target for preventing cardiovascular diseases.
Relationship Between QT Interval and Outcome in Low‐Flow Low‐Gradient Aortic Stenosis With Low Left Ventricular Ejection Fraction
Authors: Dahou Abdellaziz , Toubal Oumhani , Clavel Marie‐Annick , Beaudoin Jonathan , Magne Julien , Mathieu Patrick , Philippon François , Dumesnil Jean G. , Puri Rishi , Ribeiro Henrique B. , Larose Éric , Rodés‐Cabau Josep , Pibarot Philippe 
Published: October 2016

Background

QT
interval has been shown to be associated with cardiovascular events. There is no data regarding the association between
QT
interval and left ventricular (
LV
) function and prognosis in patients with low
LV
ejection fraction (
LVEF
), low‐flow, low‐gradient aortic stenosis (
LF
‐
LG AS
). We aimed to examine the relationship between corrected
QT
interval (
QT
c
) and
LV
function and outcome in these patients.

Methods and Results

Ninety‐three patients (73±10 years; 74% men) with
LF
‐
LG AS
(mean gradient <40 mm Hg and indexed aortic valve area ≤0.6 cm
2
/m
2
) and reduced
LVEF
(≤40%) were prospectively included in this analysis and 63 of them underwent aortic valve replacement within 3 months following inclusion. Prolonged
QT
c
was defined as
QT
c
>450 ms in men and >470 ms in women.
LV
global longitudinal strain was measured by speckle tracking and expressed in absolute value |%|.
QT
c
correlated with the following: global longitudinal strain (
r
=−0.40,
P
=0.005),
LVEF
(
r
=−0.27,
P
=0.02), stroke volume (
r
=−0.35,
P
=0.007), and B‐type natriuretic peptide (
r
=0.45,
P
=0.0006). During a median follow‐up of 2.0 years, 49 patients died. Prolonged
QT
c
was associated with a 2‐fold increase in all‐cause mortality (hazard ratio=2.05;
P
=0.01) and cardiovascular mortality (hazard ratio=1.89;
P
=0.04). In multivariable analysis adjusted for Euro
SCORE
, aortic valve replacement, previous myocardial infarction,
LVEF
, and ß‐blocker medication, prolonged
QT
c
was independently associated with all‐cause mortality (hazard ratio=2.56;
P
=0.008) and cardiovascular mortality (hazard ratio=2.50;
P
=0.02).

Conclusions

In patients with
LF
‐
LG AS
and reduced
LVEF
, longer
QT
c
interval was associated with worse
LV
function and increased risk of death. Assessment of
QT
c
may provide a simple and inexpensive tool to enhance risk stratification in
LF
‐
LG AS
patients.

Clinical Trial Registration

URL
:
https://www.clinicaltrials.gov
. Unique identifier:
NCT
01835028.
Morphological and molecular characterisation of new and known species of Tripyla Bastian, 1865 (Triplonchida: Tripylidae) from northern Iran, with phylogenetic relationships, compendium and identification key
Authors: Asghari Ramezan , Eskandari Ali , Tanha Maafi Zahra , Álvarez-Ortega Sergio , Zhao Zeng Qi 
Published: October 2016

During a nematological survey of the family Tripylidae, two new and two known species of the genusTripyla, namelyT. paraffinissp. n.,T. parafilicaudatasp. n.,T. glomeransandT. setifera, were identified and described from soil samples collected from the rhizosphere of forest trees in northern Iran. Three populations ofT. paraffinissp. n., found in different locations, are described and morphometric data of the type and other populations provided.Tripyla paraffinissp. n. is characterised by its body length of 1.21-1.89 mm, dorsal tooth wedge-shaped and triangular, short outer labial and cephalic sensilla, tail bent ventrad and gradually tapering to the end, horn-shaped spicules bearing a distinct constriction in the middle, and presence of 16-20 ventromedian supplementary papillae.Tripyla parafilicaudatasp. n. is described and illustrated from four different locations. It is characterised by females with a body length of 1.48-1.95 mm, dorsal tooth hook-shaped, vaginal wall with a downward pointing tooth-like projection in the middle, long outer labial and setiform cephalic sensilla, long tail, sausage-shaped spermatozoa, males with horn-shaped spicules and 11-17 ventromedian supplementary papillae.Tripyla glomeransandT. setiferaare new records for the Iranian nematofauna. The results of phylogenetic analyses based on sequences of the partial 18S and D2-D3 expansion segments of 28S rRNA fromT. paraffinissp. n. andT. parafilicaudatasp. n. and other species in the genus clearly support the proposal ofT. paraffinissp. n. andT. parafilicaudatasp. n. as new species, as well as indicating thatTripylashares a more recent common ancestor withTobrilus,Tripylella,Prismatolaimus,Diphtherophoraand two trichodorids,TrichodorusandParatrichodorus. The Tripylidae is placed in a main clade within the Triplonchida.
Херменевтични бележки за библейските псалми
Authors: Койчева [Koĭcheva] Регина [Regina] 
Published: October 2016

Some hermeneutical notes on the biblical Psalms The article examines two difficult to interpret verses from the Book of Psalms. The analysis compares the Hebrew text, the Septuagint, the Old Bulgarian text (along with its Church Sla­vonic version) and the Modern Bulgarian synodical translation of the psalms. The proposed reading is based on linguistic, literary and theological observations. In the first analysed verse (Ps. 4:2), semantic illegibility is interpreted as a result of the implicit presence of a specific Hebraism in the translations. In the other case (Ps. 5:9), verbal expression is highly elliptical because of the preference given to the phonetic structure of the verse in the Hebrew original. Hermeneutyczne uwagi o biblijnych PsalmachArtykuł prezentuje dwie różne interpretacje wersów pochodzących z biblijnej Księgi Psal­mów. Autorka porównuje przekłady Psalmów, pochodzące z tekstu hebrajskiego, Septuaginty, tekstu starobułgarskiego (wraz z jego cerkiewnosłowiańską wersją) oraz z pierwszego nowo­bułgarskiego przekładu synodalnego. Zaproponowane odczytanie uwzględnia perspektywę językoznawczą, literaturoznawczą i teologiczną. W pierwszym analizowanym wersie (Ps 4,2) semantyczna nieczytelność jest interpretowana jako wynik bezpośredniej obecności specy­ficznego hebraizmu w komentowanych przekładach. W innym przypadku (Ps 5,9) ekspresja słowna jest niezwykle eliptyczna z powodu zastosowania obecnej w hebrajskim oryginale fonetycznej struktury wersu.
Biblia w kulturze Rusi polsko-litewskiej w XVI wieku
Authors: Naumow Aleksander 
Published: October 2016

The Bible in the culture of Polish-Lithuanian Rus’ in the sixteenth centuryBeginning in the mid-fourteenth century, the East Slavic citizens of the Polish-Lithuanian Commonwealth (“Ruthenians,” the “Rutheni”) took active part in a process of multicultural inte­gration. The increase of interests in the biblical text that took place in Europe in that period was not without influence on Ruthenians – both those who remained Orthodox and those who became followers of the Reformation. The article discusses two outstanding figures: Matvej Ioannovič Desjatyj (the biblical codex of Vilnius and Supraśl, 1502–1507) and Francisk Skorina (Prague edi­tion of 23 Books of the Slavonic Bible – Bivlija ruska of 1517–1520, the Vilnius edition of Malaja podorožnaja knižka – The little traveller’s book, 1522, and the Apostolos of 1525). The article also examines how the circle of the Ostroh Academy approached the task of preparing a print edition of the Slavonic Bible (1580–1581) and investigates the viewpoint of those who were influenced by Reformation ideas as well as that of those promoting the usage of prosta/rus’ka mova. This biblical production, which is only a part of the literary activity undertaken in Rus’, testifies to the high level of Ruthenian culture in the Polish-Lithuanian state and shows how Ruthenians were able to match their traditional spirituality with the philologia sacra of the Renaissance. Biblia w kulturze Rusi polsko-litewskiej w XVI wiekuOd połowy XIV wieku wschodniosłowiańscy obywatele Rusi polsko-litewskiej brali czynny udział w procesie wielokulturowej integracji. Wzrost zainteresowania tekstem biblijnym w całej Europie wpłynął zarówno na prawosławnych, jak i sprzyjających reformacji. Artykuł koncentruje się na działalności dwóch wybitnych postaci: Mateusza (Macieja) Joannowicza Dziesiątego (Kodeks biblijny z Wilna i Supraśla z lat 1502–1507) i Franciszka Skoryny („Bivlija ruska” – praskie wydanie 23 ksiąg biblijnych w latach 1517–1520, „Malaja podorožnaja knižka”, wydana w Wilnie w 1522 i „Apostoł”, 1525). Omówiono tu również proces przygotowania w kręgu Akademii Ostrogskiej pierwszej drukowanej Biblii cerkiewnosłowiańskiej (1580–1581), ukazując także punkt widzenia zwolenników reformacji na problem tekstu biblijnego, w tym także propagatorów „prostej/ruśkiej mowy”. Ta biblijna produkcja, stanowiąca jedynie część literackiej piśmienniczej aktywności, świadczy o wysokim poziomie ruskiej kultury w państwie polsko-litewskim i pokazuje, w jaki sposób Rusini byli w stanie połączyć tradycyjną duchowość z renesansową philologia sacra.
Небесният симпозиум. Коментарите към Йов 1:6 във византийската и славянската традиция
Authors: Христова-Шомова [Khristova-Shomova] Искра [Iskra] 
Published: October 2016

Celestial symposium: Commentaries to the Book of Job 1:6 in the Byzantine and Slavic traditionsJob 1:6 is one of several places in the Bible where God’s sons (celestial beings) are men­tioned: “One day the sons of God came to present themselves before the Lord, and Satan also came among them.” Numerous commentaries of the Church Fathers were included in the Greek catena to the Book of Job. Some of these were not written specially as commentaries to this passage but are extracts from works commenting the nature of the angels, their place in God’s providence and their role in human life. The author then goes on to discuss the two Slavic translations that were made of the catena. The first one comprises the majority of the texts included in the Greek catena, while the second one contains only two small passages from commentaries of Saint John Chrysostom and Olympiodoros. The article provides a comparison between Slavic texts, which were translated from Greek in the Balkans at the same time: in the late fourteenth or early fifteenth century. Several miniatures from medieval Greek manuscripts, which illustrate the Celestial symposium, are represented at the end of the article. Niebiańskie sympozjum. Komentarze do Księgi Hioba (1, 6) w bizantyńskiej i słowiańskiej tradycjiWerset 1,6 Księgi Hioba jest jednym z wielu miejsc w Biblii, w którym wspomina się synów Bożych: „Zdarzyło się pewnego dnia, gdy synowie Boży udawali się, by stanąć przed Panem, że i szatan też poszedł z nimi”. Ogromna liczba komentarzy Ojców Kościoła do Księgi Hioba została zawarta w greckiej katenie. Niektóre z nich nie zostały napisane jako bezpo­średni komentarz do tego wersetu, lecz są wypisami z prac autorów, komentującymi naturę aniołów, ich miejsce w Bożej opatrzności, a także rolę w życiu ludzkim. Ponadto istniały dwa słowiańskie przekłady kateny. Pierwszy zawierał większość tekstów pochodzących z greckiej kateny, a drugi składał się zaledwie z dwóch passusów, będących wyimkami z komentarzy św. Jana Chryzostoma i Olimpiododrosa.W artykule porównano teksty słowiańskie, które zostały przetłumaczone z języka greckiego na Bałkanach w tym samym czasie: pod koniec wieku XIV lub na początku XV. W artykule przedstawiono również kilka miniatur pochodzących ze średniowiecznych greckich rękopisów, przedstawiających niebiańskie sympozjum.
Неизвестен славянски текст на катена към Псалтира в два ръкописа от Хилендар
Authors: Карачорова [Karachorova] Ивона [Ivona] 
Published: October 2016

An unknown Slavic text of a catena to the Psalter, in two manuscripts from the Hilandar monasteryThis article presents a hitherto unknown catena to the Psalter. It is divided in two parts, placed in two manuscripts: in Manuscript No. 116 (psalms 1 through 76), and in Manuscript No. 117 (the remaining psalms). The catena contains commentaries of more than 15 Byzan­tine authors. The article then goes on to compare the Psalter text accompanying the catena with texts of other editions. It becomes clear that the text of the Hilandar manuscripts is very close to the texts of the Mount Athos edition and of Cyprian’s edition, although it has its own characteristics. The newly found catena is the most voluminous catena translated into a Slavic language. The discovery of the text will lead to new researches into the history of the Slavic Psalter and the Slavic translations of the Bible. Nieznany słowiański tekst kateny do Psałterza w dwóch rękopisach z klasztoru ChilandarArtykuł prezentuje nową i nieznaną dotąd katenę do Psałterza. Podzielona na dwie części znajduje się w dwóch rękopisach: N:116 (do Psalmu 76) i N:117 (od Psalmu 77 do końca). Katena zawiera komentarze pochodzące od ponad piętnastu bizantyńskich autorów. Tekst Psałterza, będący częścią kateny, został porównany z tekstami innych komentatorów. Dzięki temu widać wyraźnie, że tekst z manuskryptów chilandarskich jest bliski tekstom komentowanym na Górze Atos, a także na Cyprze, mimo że posiada swoją własną specyfikę. Nowoodkryta katena jest najbardziej obszernym dokumentem tego typu przełożonym na język słowiański. Jej odkrycie umożliwi nowe badania nad historią słowiańskiego Psałterza i słowiańskich przekładów Biblii.