bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of c.2268dup and detection of two novel alterations, c.670_672del and c.1186C>T, in theTPOgene in a cohort of Malaysian–Chinese with thyroid dyshormonogenesis
Authors: Lee Ching Chin , Harun Fatimah , Jalaludin Muhammad Yazid , Heh Choon Han , Othman Rozana , Junit Sarni Mat 
Published: January 2015

ObjectivesThe c.2268dup mutation in the thyroid peroxidase (TPO) gene is the most commonTPOalteration reported in Taiwanese patients with thyroid dyshormonogenesis. The ancestors of these patients are believed to originate from the southern province of China. Our previous study showed that this mutation leads to reduced abundance of the TPO protein and loss of TPO enzyme activity in a Malaysian–Chinese family with goitrous hypothyroidism. The aim of our study was to provide further data on the incidence of the c.2268dup mutation in a cohort of Malaysian–Chinese and its possible phenotypic effects.SettingCohort study.ParticipantsTwelve biologically unrelated Malaysian–Chinese patients with congenital hypothyroidism were recruited in this study. All patients showed high thyrotropin and low free thyroxine levels at the time of diagnosis with proven presence of a thyroid gland.Primary outcome measureScreening of the c.2268dup mutation in theTPOgene in all patients was carried out using a PCR–direct DNA sequencing method.Secondary outcome measureFurther screening for mutations in other exonic regions of theTPOgene was carried out if the patient was a carrier of the c.2268dup mutation.ResultsThe c.2268dup mutation was detected in 4 of the 12 patients. Apart from the c.2268dup and a previously documented mutation (c.2647C>T), two novelTPOalterations, c.670_672del and c.1186C>T, were also detected in our patients. In silico analyses predicted that the novel alterations affect the structure/function of the TPO protein.ConclusionsThe c.2268dup mutation was detected in approximately one-third of the Malaysian–Chinese patients with thyroid dyshormonogenesis. The detection of the novel c.670_672del and c.1186C>T alterations expand the mutation spectrum ofTPOassociated with thyroid dyshormonogenesis.
Objectively measured physical activity and vitamin D status in older people from Germany
Authors: Klenk Jochen , Rapp Kilian , Denkinger Michael , Nagel Gabriele , Nikolaus Thorsten , Peter Richard , Boehm Bernhard O , Koenig Wolfgang , Rothenbacher Dietrich ,   and the ActiFE Study Group
Published: January 2015

BackgroundTo analyse the seasonal relationship of objectively measured physical activity with vitamin D status in older persons from Southern Germany (latitude: 48.4°N).MethodsPhysical activity was assessed in 1193 community-dwelling individuals aged ≥65 years (58% men) over 1 week using a thigh-worn accelerometer. Furthermore, the 25-hydroxyvitamin D (25(OH)D) level was measured. Least-square means of 25(OH)D serum levels were calculated for quartiles of average daily walking duration stratified by season and adjusted for gender, age and body mass index. Participants with prescribed vitamin D supplements were excluded.ResultsStatistically significant linear associations between quartiles of walking duration with 25(OH)D serum levels were observed in all seasons but not in summer. Differences in 25(OH)D serum levels between the first and the last quartile were 3.42 ng/mL (p=0.002) in winter, 2.80 ng/mL (p=0.009) in spring, and 3.60 ng/mL (p<0.001) in the fall. The proportion of vitamin D insufficiency (<20 ng/mL) even in the highest quartile of walking duration was 45.3% in winter, 73.7% in spring, 17.4% in summer and 16.5% in the fall.ConclusionsAlthough a positive dose–response relationship was seen between walking duration and the 25(OH)D serum level for most seasons, vitamin D insufficiency was still very prevalent even in high-active persons during all seasons.
PEST Domain Mutations in Notch Receptors Comprise an Oncogenic Driver Segment in Triple-Negative Breast Cancer Sensitive to a γ-Secretase Inhibitor
Authors: Wang Kai , Zhang Qin , Li Danan , Ching Keith , Zhang Cathy , Zheng Xianxian , Ozeck Mark , Shi Stephanie , Li Xiaorong , Wang Hui , Rejto Paul , Christensen James , Olson Peter 
Published: January 2015

Abstract
Purpose: To identify and characterize novel, activating mutations in Notch receptors in breast cancer and to determine response to the gamma secretase inhibitor (GSI) PF-03084014.
Experimental Design: We used several computational approaches, including novel algorithms, to analyze next-generation sequencing data and related omic datasets from The Cancer Genome Atlas (TCGA) breast cancer cohort. Patient-derived xenograft (PDX) models were sequenced, and Notch-mutant models were treated with PF-03084014. Gene-expression and functional analyses were performed to study the mechanism of activation through mutation and inhibition by PF-03084014.
Results: We identified mutations within and upstream of the PEST domains of NOTCH1, NOTCH2, and NOTCH3 in the TCGA dataset. Mutations occurred via several genetic mechanisms and compromised the function of the PEST domain, a negative regulatory domain commonly mutated in other cancers. Focal amplifications of NOTCH2 and NOTCH3 were also observed, as were heterodimerization or extracellular domain mutations at lower incidence. Mutations and amplifications often activated the Notch pathway as evidenced by increased expression of canonical Notch target genes, and functional mutations were significantly enriched in the triple-negative breast cancer subtype (TNBC). PDX models were also identified that harbored PEST domain mutations, and these models were highly sensitive to PF-03084014.
Conclusions: This work suggests that Notch-altered breast cancer constitutes a bona fide oncogenic driver segment with the most common alteration being PEST domain mutations present in multiple Notch receptors. Importantly, functional studies suggest that this newly identified class can be targeted with Notch inhibitors, including GSIs. Clin Cancer Res; 21(6); 1487–96. ©2015 AACR.
Lysine Demethylase KDM4A Associates with Translation Machinery and Regulates Protein Synthesis
Authors: Van Rechem Capucine , Black Joshua C. , Boukhali Myriam , Aryee Martin J. , Gräslund Susanne , Haas Wilhelm , Benes Cyril H. , Whetstine Johnathan R. 
Published: January 2015

Abstract
Chromatin-modifying enzymes are predominantly nuclear; however, these factors are also localized to the cytoplasm, and very little is known about their role in this compartment. In this report, we reveal a non–chromatin-linked role for the lysine-specific demethylase KDM4A. We demonstrate that KDM4A interacts with the translation initiation complex and affects the distribution of translation initiation factors within polysome fractions. Furthermore, KDM4A depletion reduced protein synthesis and enhanced the protein synthesis suppression observed with mTOR inhibitors, which paralleled an increased sensitivity to these drugs. Finally, we demonstrate that JIB-04, a JmjC demethylase inhibitor, suppresses translation initiation and enhances mTOR inhibitor sensitivity. These data highlight an unexpected cytoplasmic role for KDM4A in regulating protein synthesis and suggest novel potential therapeutic applications for this class of enzyme.
Significance: This report documents an unexpected cytoplasmic role for the lysine demethylase KDM4A. We demonstrate that KDM4A interacts with the translation initiation machinery, regulates protein synthesis and, upon coinhibition with mTOR inhibitors, enhances the translation suppression and cell sensitivity to these therapeutics. Cancer Discov; 5(3); 255–63. ©2015 AACR.
See related commentary by Rothbart et al., p. 228
See related article by Van Rechem et al., p. 245
This article is highlighted in the In This Issue feature, p. 213
Ethanol and Normobaric Oxygen
Authors: Geng Xiaokun , Elmadhoun Omar , Peng Changya , Ji Xunming , Hafeez Adam , Liu Zongjian , Du Huishan , Rafols Jose A. , Ding Yuchuan 
Published: January 2015

Background and Purpose—
Ischemic stroke induces metabolic disarray. A central regulatory site, pyruvate dehydrogeanse complex (PDHC) sits at the cross-roads of 2 fundamental metabolic pathways: aerobic and anaerobic. In this study, we combined ethanol (EtOH) and normobaric oxygen (NBO) to develop a novel treatment to modulate PDHC and its regulatory proteins, namely pyruvate dehydrogenase phosphatase and pyruvate dehydrogenase kinase, leading to improved metabolism and reduced oxidative damage.

Methods—
Sprague–Dawley rats were subjected to transient (2, 3, or 4 hours) middle cerebral artery occlusion followed by 3- or 24-hour reperfusion, or permanent (28 hours) middle cerebral artery occlusion without reperfusion. At 2 hours after the onset of ischemia, rats received either an intraperitoneal injection of saline, 1 dose of EtOH (1.5 g/kg) for 2- and 3-hour middle cerebral artery occlusion, 2 doses of EtOH (1.5 g/kg followed by 1.0 g/kg in 2 hours) in 4 hours or permanent middle cerebral artery occlusion, and EtOH+95% NBO (at 2 hours after the onset of ischemia for 6 hours) in permanent stroke. Infarct volumes and neurological deficits were examined. Oxidative metabolism and stress were determined by measuring ADP/ATP ratio and reactive oxygen species levels. Protein levels of PDHC, pyruvate dehydrogenase kinase, and pyruvate dehydrogenase phosphatase were assessed.

Results—
EtOH induced dose-dependent neuroprotection in transient ischemia. Compared to EtOH or NBO alone, NBO+EtOH produced the best outcomes in permanent ischemia. These therapies improved brain oxidative metabolism by decreasing ADP/ATP ratios and reactive oxygen species levels, in association with significantly raised levels of PDHC and pyruvate dehydrogenase phosphatase, as well as decreased pyruvate dehydrogenase kinase.

Conclusions—
Both EtOH and EtOH+NBO treatments conferred neuroprotection in severe stroke by affecting brain metabolism. The treatment may modulate the damaging cascade of metabolic events by bringing the PDHC activity back to normal metabolic levels.
Między brakiem a nadmiarem. Z Ireną Grudzińską-Gross rozmawia Joanna Tokarska-Bakir
Authors: Tokarska-Bakir Joanna , Grudzińska-Gross Irena 
Published: January 2015

Between overabundance and scarcity. Joanna Tokarska-Bakir in an interview with Irena Grudzińska GrossThis conversation with Irena Grudzińska-Gross starts a series of interviews in “Studia Litteraria et Historica”, which motto is the title of the essay of Jan Stanisław Bystroń “On subjects I was advised not to pursue”. Among these subjects that Irena Grudzińska-Gross names are: war, family history, women. Grudzińska-Gross tells also about the reactions to “Złote Żniwa” - a book that she wrote together with Jan Tomasz Gross, and about academic work of people of Eastern Europe living in the United States. One part of the interview concerns also a “collective hypnosis”, that Americans underwent after the 9/11 World Trade Center Attack and the price, that Susan Sontag had to pay for being critical about American militarism. Między brakiem a nadmiarem. Z Ireną Grudzińską-Gross rozmawia Joanna Tokarska-BakirRozmowa z Ireną Grudzińską-Gross otwiera cykl wywiadów “Studia Litteraria et Historica”, których mottem jest tytuł eseju Jana Stanisława Bystronia: “Tematy, które mi odradzano”. Wśród “odradzanych” tematów, które wymienia Irena Grudzińska-Gross są między innymi: wojna, historia rodzinna, kobiety. Grudzińska-Gross opowiada także o reakcjach na książkę “Złote żniwa”, którą napisała wraz z Janem Tomaszem Grossem oraz o pracy akademickiej osób z Europy Wschodniej w Stanach Zjednoczonych. Część rozmowy dotyczy także “zbiorowej hipnozy”, której ulegli mieszkańcy USA po ataku 11 września 2001 na World Trade Center i ceny, jaką musiała zapłacić Susan Sontag za krytykę amerykańskiego militaryzmu.
Go native. Debaty o książce Timothy Snydera
Authors: Tokarska-Bakir Joanna 
Published: January 2015

Go native. Debates on a book by Timothy Snyder This article debates the content of the latest issue of “Contemporary European History” from 2012 (vol. 21, no. 2) dedicated to Timothy Snyder’s book Bloodlands. The debate includes contributions by: Mark Mazower (Columbia University), Dan Diner (Hebrew University/Simon-Dubnow-Institute Leipzig), Thomas Kühne (Clark University) and Jörg Baberowski (Humboldt University). Timothy Snyder reacts to their comments in an extensive essay.
Fałszywy znak równości
Authors: Zuroff Efraim 
Published: January 2015

The equivalency canardEfraim Zuroff's text, originally published in Haaretz magazine, is a review of Timothy Snyder's Bloodlands. Snyder distinguishes six main mass murders commited by Nazi Germany and Soviet Union during the period of the Third Reich's existence. In Zuroff's opinion there are some significant differences between these tragedies. Dubious comparisons proposed by Snyder made the Holocaust most affected. Describing the Shoah as one of the six equally horryfying mass murders, the author ignores its ideological roots. Roots that sentenced to death all Jews - regardless of their political views, religious practicies or the level of identification with Jewish community. Moreover Snyder takes no notice of the georaphical scope of the Holocaust. He also does not notice the fact, that the Nazis effectively managed to make so many Europeans their accomplices, who actively supported the Shoah. Fałszywy znak równościTekst Efraima Zuroffa, który pierwotnie ukazał się w piśmie Haaretz, to recenzja książki Skrwawione ziemie Timothy Snydera. Snyder wyróżnia sześć głównych masowych mordów popełnionych przez Niemcy i Związek Radziecki w okresie, który odpowiada istnieniu Trzeciej Rzeszy. Istnieją jednak, zdaniem Zuroffa, znaczące różnice między tymi tragediami. Na wątpliwych porównaniach, które proponuje Snyder, najbardziej „ucierpiał” Holokaust. Opisując Shoah jako jeden z sześciu równie straszliwych, masowych mordów, autor pomija jego ideologiczne korzenie, które sprawiały, że na śmierć skazany był każdy bez wyjątku Żyd, niezależnie od jego poglądów politycznych, praktyk religijnych czy stopnia identyfikacji z żydowską wspólnotą. Ponadto Snyder ignoruje ogromny zasięg geograficzny Holokaustu. Nie zauważa także skuteczności, z jaką naziści potrafili uczynić swoimi wspólnikami tak wielu Europejczyków, którzy w konsekwencji aktywnie wspomagali Shoah.
Opowieść o nieuwikłanych ziemiach
Authors: Kozłowski Michał 
Published: January 2015

Narrative of untangled lands Timothy Snyder’s Bloodlands is an extremely ambitious project not only of historiography but also, we dare say, of historiosophy. Snyder seeks originality in shaping both the geography and the narrative of what he considers to be the central occurrence of contemporary history – mass killings of the Nazi regime and Stalinist Russia. He claims that in order to comprehend the logic of the killings we need to put emphasis on the (intentional and unintentional) collusion (interaction) of the two regimes. I believe that this interpretation is trivial if we take its weak interpretation, and wrong if we want to understand it in a strong way. Snyder is widely praised for adopting or giving justice to the Central European (namely Polish) perception of the WWII, but in doing it he gladly succumbs to its lacunas and deliberate misinterpretations. He not only downgrades the importance of the Shoah but also downplays the role of Eastern European anti-Semitism and its interaction with the Nazi “messianic” anti-judaismus as the key factor in successful execution of the Final Solution.
Ex silentio. O wierszu „Todtnauberg” Paula Celana
Authors: Tokarska-Bakir Joanna 
Published: January 2015

Ex silentio. On Paul Celan’s Poem “Todtnauberg”This paper contests the interpretative framework proposed by Hans Georg Gadamer and Cezary Wodziński in their interpretations of certain poems by Paul Celan. The point of contention lies in the understanding of the relationship between biography and poem. The author analyses the “concept of discretion,” which excludes Celan’s Jewish identity from the analysis of his poetry, and proposes her own reading of both his poem Todtnauberg and anti-volkist interpretation Hüttenfenster. The background consists of the polemic about the famous meeting of Paul Celan and Martin Heidegger in August 1, 1967 in Todtnauberg.
Zapożyczenia z mowy żydowskiej w narracji antysemickiej
Authors: Cała Alina 
Published: January 2015

Loanwords from Jewish speech in an anti-Semitic narrative Anti-Semites used a particular form of narrative that changed over time. Beginning with the 1880s the language of anti-Semitic propaganda adopted an increasingly aggressive tone. In the interwar period, on top of aggression, insinuations, lies or stereotypical simplifications already known from previous publications, anti-Semites more and more often turned to mockery, whose aim was to humiliate and depreciate Jews as well as their culture by means of sneering. The author of the article analyses a particular form of mockery which employed loanwords from the Yiddish language or was stylised as the Yiddish language itself. Such a phenomenon is illustrated with an example of feature articles published in “Myśl narodowa” weekly, a body of the nationalist political movement National Democracy targeted at intelligentsia and issued between 1921 and 1939 in Warsaw. The roots of this stylistic device go back to the vaudevilles staged in cafés in the late 19thcentury, which included satirical monologues of Jewish protagonists speaking a distinct Polish language filled with linguistic mistakes and Yiddishisms.
Age-Dependent Healing Potential of Anterior Cruciate Ligament Remnant-Derived Cells
Authors: Nakano Naoki , Matsumoto Tomoyuki , Takayama Koji , Matsushita Takehiko , Araki Daisuke , Uefuji Atsuo , Nagai Kanto , Zhang Shurong , Inokuchi Takao , Nishida Kyohei , Kuroda Ryosuke , Kurosaka Masahiro 
Published: January 2015

Background: The anterior cruciate ligament (ACL) does not heal spontaneously after injury, and ACL patients of different ages respond differently to treatment. Although ACL-derived CD34-positive cells contribute to bone-tendon healing after ACL reconstruction, the relationship between the healing potential of ACL-derived cells and a patient’s age is unknown. Hypothesis: ACL-derived cells from young patients will have a greater effect on the maturation of bone-tendon integration in an immunodeficient rat model of ACL reconstruction compared with cells derived from older patients. Study Design: Controlled laboratory study. Methods: Sixty 10-week-old female immunodeficient rats underwent ACL reconstruction (using the autologous flexor digitorum longus tendon as a graft) followed by intracapsular administration of ACL-derived cells from patients aged 10 to 19 years (younger group) or patients aged 30 to 39 years (older group), or they were given phosphate-buffered saline (PBS; PBS group). Histologic, radiographic, and biomechanical examinations were performed 2 to 8 weeks after surgery. In addition, intrinsic and human cell–derived angiogenesis and osteogenesis were examined by immunohistochemistry. Results: In the younger group, histologic assessment demonstrated early bone-tendon healing, which induced endochondral ossification-like integration. Micro–computed tomography showed a statistically significant reduction in the area of tibial bone tunnel in the younger group (week 4, 20.0% ± 11.2% reduction; week 8, 25.7% ± 5.6% reduction) compared with the older group (week 4, 1.8% ± 3.0% reduction; week 8, 4.0% ± 5.9% reduction) and the PBS group (week 4, –0.5% ± 3.2% reduction; week 8, 3.3% ± 5.2% reduction) (week 4, P < .05; week 8, P < .01). Failure loads during tensile testing demonstrated a significantly higher ultimate load to failure in the younger group (17.52 ± 4.01 N) compared with the older (8.05 ± 2.91 N) and PBS (7.01 ± 3.16 N) groups ( P < .05), and isolectin B4 and rat osteocalcin immunostaining indicated enhanced intrinsic angiogenesis and osteogenesis in the younger group. There was no statistically significant difference in the results of radiographic and biomechanical examinations between the older and PBS groups. Double immunohistochemistry for human-specific endothelial cell and osteoblast markers demonstrated a greater ability of differentiation into endothelial cells and osteoblasts in the younger group. Conclusion: ACL-derived cells from younger patients enhanced early bone-tendon healing in an immunodeficient rat model of ACL reconstruction. Clinical Relevance: Surgeons should consider a patient’s age when performing ACL reconstruction with remnant preservation or ruptured tissue incorporation, as this can predict healing ability.
The Biomechanical Function of the Anterolateral Ligament of the Knee
Authors: Parsons Erin M. , Gee Albert O. , Spiekerman Charles , Cavanagh Peter R. 
Published: January 2015

Background: Recent anatomic investigations of the lateral structures of the knee have identified a new ligament, called the anterolateral ligament (ALL). To date, the anterolateral ligament has not been biomechanically tested to determine its function. Hypothesis: The ALL of the knee will resist internal rotation at high angles of flexion but will not resist anterior drawer forces. Study Design: Controlled laboratory study. Methods: Eleven cadaveric knees were subjected to 134 N of anterior drawer at flexion angles between 0° and 90° and separately to 5 N·m of internal rotation at the same flexion angles. The in situ forces of the ALL, anterior cruciate ligament (ACL), and lateral collateral ligament (LCL) were determined by the principle of superposition. Results: The contribution of the ALL during internal rotation increased significantly with increasing flexion, whereas that of the ACL decreased significantly. At knee flexion angles greater than 30°, the contribution of the ALL exceeded that of the ACL. During anterior drawer, the forces in the ALL were significantly less than the forces in the ACL at all flexion angles ( P < .001). The forces in the LCL were significantly less than those in either the ACL or the ALL at all flexion angles for both anterior drawer and internal rotation ( P < .001). Conclusion: The ALL is an important stabilizer of internal rotation at flexion angles greater than 35°; however, it is minimally loaded during anterior drawer at all flexion angles. The ACL is the primary resister during anterior drawer at all flexion angles and during internal rotation at flexion angles less than 35°. Clinical Relevance: Damage to the ALL of the knee could result in knee instability at high angles of flexion. It is possible that a positive pivot-shift sign may be observed in some patients with an intact ACL but with damage to the ALL. This work may have implications for extra-articular reconstruction in patients with chronic anterolateral instability.
Bistability and pH Hysteresis of Graphene Oxide Solution in Circle Acid–Base Titration
Authors: Zhuang Qiang , Liu Heguang , Li Tiehu , Zhao Tingkai 
Published: January 2015

Abstract
Although the dispersion of graphene oxide in solution has been well studied, there still exists mysteries. Here the graphene oxide was synthesized by the modified Hummers method. By the circle acid–base titration, we reported a bistable and pH hysteretic behavior of the graphene oxide in aqueous solution. To interpret the phenomena, a varying pKa mechanism based on the self-assembly of graphene oxide sheets in the circle titration is proposed.