bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Rapid Subcortical Amygdala Route for Faces Irrespective of Spatial Frequency and Emotion
Authors: McFadyen Jessica , Mermillod Martial , Mattingley Jason B. , Halász Veronika , Garrido Marta I. 
Published: March 2017

There is significant controversy over the existence and function of a direct subcortical visual pathway to the amygdala. It is thought that this pathway rapidly transmits low spatial frequency information to the amygdala independently of the cortex, and yet the directionality of this function has never been determined. We used magnetoencephalography to measure neural activity while human participants discriminated the gender of neutral and fearful faces filtered for low or high spatial frequencies. We applied dynamic causal modeling to demonstrate that the most likely underlying neural network consisted of a pulvinar-amygdala connection that was uninfluenced by spatial frequency or emotion, and a cortical-amygdala connection that conveyed high spatial frequencies. Crucially, data-driven neural simulations revealed a clear temporal advantage of the subcortical connection over the cortical connection in influencing amygdala activity. Thus, our findings support the existence of a rapid subcortical pathway that is nonselective in terms of the spatial frequency or emotional content of faces. We propose that that the “coarseness” of the subcortical route may be better reframed as “generalized.”SIGNIFICANCE STATEMENTThe human amygdala coordinates how we respond to biologically relevant stimuli, such as threat or reward. It has been postulated that the amygdala first receives visual input via a rapid subcortical route that conveys “coarse” information, namely, low spatial frequencies. For the first time, the present paper provides direction-specific evidence from computational modeling that the subcortical route plays a generalized role in visual processing by rapidly transmitting raw, unfiltered information directly to the amygdala. This calls into question a widely held assumption across human and animal research that fear responses are produced faster by low spatial frequencies. Our proposed mechanism suggests organisms quickly generate fear responses to a wide range of visual properties, heavily implicating future research on anxiety-prevention strategies.
Self‐organized developmental patterning and differentiation in cerebral organoids
Authors: Renner Magdalena , Lancaster Madeline A , Bian Shan , Choi Heejin , Ku Taeyun , Peer Angela , Chung Kwanghun , Knoblich Juergen A 
Published: March 2017

AbstractCerebral organoids recapitulate human brain development at a considerable level of detail, even in the absence of externally added signaling factors. The patterning events driving this self‐organization are currently unknown. Here, we examine the developmental and differentiative capacity of cerebral organoids. Focusing on forebrain regions, we demonstrate the presence of a variety of discrete ventral and dorsal regions. Clearing and subsequent 3D reconstruction of entire organoids reveal that many of these regions are interconnected, suggesting that the entire range of dorso‐ventral identities can be generated within continuous neuroepithelia. Consistent with this, we demonstrate the presence of forebrain organizing centers that express secreted growth factors, which may be involved in dorso‐ventral patterning within organoids. Furthermore, we demonstrate the timed generation of neurons with mature morphologies, as well as the subsequent generation of astrocytes and oligodendrocytes. Our work provides the methodology and quality criteria for phenotypic analysis of brain organoids and shows that the spatial and temporal patterning events governing human brain development can be recapitulated in vitro.
Mitochondrial chaperone HSP‐60 regulates anti‐bacterial immunity via p38 MAP kinase signaling
Authors: Jeong Dae‐Eun , Lee Dongyeop , Hwang Sun‐Young , Lee Yujin , Lee Jee‐Eun , Seo Mihwa , Hwang Wooseon , Seo Keunhee , Hwang Ara B , Artan Murat , Son Heehwa G , Jo Jay‐Hyun , Baek Haeshim , Oh Young Min , Ryu Youngjae , Kim Hyung‐Jun , Ha Chang Man , Yoo Joo‐Yeon , Lee Seung‐Jae V 
Published: March 2017

AbstractMitochondria play key roles in cellular immunity. How mitochondria contribute to organismal immunity remains poorly understood. Here, we show that HSP‐60/HSPD1, a major mitochondrial chaperone, boosts anti‐bacterial immunity through the up‐regulation of p38 MAP kinase signaling. We first identify 16 evolutionarily conserved mitochondrial components that affect the immunity of Caenorhabditis elegans against pathogenic Pseudomonas aeruginosa (PA14). Among them, the mitochondrial chaperone HSP‐60 is necessary and sufficient to increase resistance to PA14. We show that HSP‐60 in the intestine and neurons is crucial for the resistance to PA14. We then find that p38 MAP kinase signaling, an evolutionarily conserved anti‐bacterial immune pathway, is down‐regulated by genetic inhibition of hsp‐60, and up‐regulated by increased expression of hsp‐60. Overexpression of HSPD1, the mammalian ortholog of hsp‐60, increases p38 MAP kinase activity in human cells, suggesting an evolutionarily conserved mechanism. Further, cytosol‐localized HSP‐60 physically binds and stabilizes SEK‐1/MAP kinase kinase 3, which in turn up‐regulates p38 MAP kinase and increases immunity. Our study suggests that mitochondrial chaperones protect host eukaryotes from pathogenic bacteria by up‐regulating cytosolic p38 MAPK signaling.
ER–mitochondria contacts control surface glycan expression and sensitivity to killer lymphocytes in glioma stem‐like cells
Authors: Bassoy Esen Yonca , Kasahara Atsuko , Chiusolo Valentina , Jacquemin Guillaume , Boydell Emma , Zamorano Sebastian , Riccadonna Cristina , Pellegatta Serena , Hulo Nicolas , Dutoit Valérie , Derouazi Madiha , Dietrich Pierre Yves , Walker Paul R , Martinvalet Denis 
Published: March 2017

AbstractGlioblastoma is a highly heterogeneous aggressive primary brain tumor, with the glioma stem‐like cells (GSC) being more sensitive to cytotoxic lymphocyte‐mediated killing than glioma differentiated cells (GDC). However, the mechanism behind this higher sensitivity is unclear. Here, we found that the mitochondrial morphology of GSCs modulates the ER–mitochondria contacts that regulate the surface expression of sialylated glycans and their recognition by cytotoxic T lymphocytes and natural killer cells. GSCs displayed diminished ER–mitochondria contacts compared to GDCs. Forced ER–mitochondria contacts in GSCs increased their cell surface expression of sialylated glycans and reduced their susceptibility to cytotoxic lymphocytes. Therefore, mitochondrial morphology and dynamism dictate the ER–mitochondria contacts in order to regulate the surface expression of certain glycans and thus play a role in GSC recognition and elimination by immune effector cells. Targeting the mitochondrial morphology, dynamism, and contacts with the ER could be an innovative strategy to deplete the cancer stem cell compartment to successfully treat glioblastoma.
MTCL1 plays an essential role in maintaining Purkinje neuron axon initial segment
Authors: Satake Tomoko , Yamashita Kazunari , Hayashi Kenji , Miyatake Satoko , Tamura‐Nakano Miwa , Doi Hiroshi , Furuta Yasuhide , Shioi Go , Miura Eriko , Takeo Yukari H , Yoshida Kunihiro , Yahikozawa Hiroyuki , Matsumoto Naomichi , Yuzaki Michisuke , Suzuki Atsushi 
Published: March 2017

AbstractThe axon initial segment (AIS) is a specialized domain essential for neuronal function, the formation of which begins with localization of an ankyrin‐G (AnkG) scaffold. However, the mechanism directing and maintaining AnkG localization is largely unknown. In this study, we demonstrate that in vivo knockdown of microtubule cross‐linking factor 1 (MTCL1) in cerebellar Purkinje cells causes loss of axonal polarity coupled with AnkG mislocalization. MTCL1 lacking MT‐stabilizing activity failed to restore these defects, and stable MT bundles spanning the AIS were disorganized in knockdown cells. Interestingly, during early postnatal development, colocalization of MTCL1 with these stable MT bundles was observed prominently in the axon hillock and proximal axon. These results indicate that MTCL1‐mediated formation of stable MT bundles is crucial for maintenance of AnkG localization. We also demonstrate that Mtcl1 gene disruption results in abnormal motor coordination with Purkinje cell degeneration, and provide evidence suggesting possible involvement of MTCL1 dysfunction in the pathogenesis of spinocerebellar ataxia.
Increased osteoclastogenesis in patients with vertebral fractures following discontinuation of denosumab treatment
Authors: Anastasilakis Athanasios D , Yavropoulou Maria P , Makras Polyzois , Sakellariou Grigorios T , Papadopoulou Fotini , Gerou Spyridon , Papapoulos Socrates E 
Published: March 2017

Objective
To test the hypothesis that rebound of bone remodeling is responsible for clinical vertebral fractures reported in a few patients with osteoporosis after cessation of denosumab treatment.

Design
In this case-control study we compared clinical and biochemical characteristics of postmenopausal women with clinical vertebral fractures 8–16 months after the last injection of denosumab (Dmab/Fx+, n = 5) with those of treatment-naïve women with such fractures (Fx+, n = 5). In addition, 5 women who discontinued denosumab treatment but did not sustain vertebral fractures 18–20 months after the last injection were studied (Dmab/Fx−, n = 5).

Methods
We measured serum microRNAs, gene expression of mRNAs of factors regulating formation and activity of osteoclasts and biochemical markers of bone and mineral metabolism. In Dmab/Fx+ and Fx+ women, blood was taken 4–8 weeks after the fracture.

Results
Compared to Fx+ women, Dmab/Fx+ women had higher serum P1NP and CTx levels, and significantly lower serum miR-503 and miR-222-2 that downregulate osteoclastogenesis and osteoclast activity, and higher RANK (13-fold) and CTSK (2.6-fold) mRNA. The respective values of Dmab/Fx− women were in the same direction as those of Dmab/Fx+ women but of a lesser magnitude.

Conclusions
Bone fragility in women with clinical vertebral fractures after stopping denosumab therapy is pathophysiologically different from that of treatment-naïve women with osteoporosis and clinical vertebral fractures and it is associated with upregulation of markers of osteoclast formation and activity. The small number of women with this rare event studied is a limitation.
Determinant of Mudharabah Financing: A Study at Indonesian Islamic Rural Banking
Authors: Amelia Erika , Hardini Eva Fauziah 
Published: March 2017

This study aims to determine the variables that affect the financing in the Islamic rural banking in Indonesia. The data used in this study is a monthly time series data that is from June 2009 until June 2015 in the monthly financial statements Islamic Banking Statistics published by Bank Indonesia. The analytical method used in this research is multiple linear regressions. The results of data analysis showed that the variables simultaneously deposit fund, capital adequacy ratio, inflation, exchange rate and the level of revenue sharing significantly influence the composition of financing. Partially deposit funds and the exchange rate significant positive effect, while capital adequacy ratio had a negative effect. Variable inflation and the level of revenue sharing do not significantly influence the composition of financing. This result implies that Islamic rural banking should increase the deposit funds to increase the mudaraba financing.DOI: 10.15408/etk.v16i1.4638
Clinical Benefit in Response to Palbociclib Treatment in Refractory Uterine Leiomyosarcomas with a Common CDKN2A Alteration
Authors: Elvin Julia A. , Gay Laurie M. , Ort Rita , Shuluk Joseph , Long Jennifer , Shelley Lauren , Lee Ronald , Chalmers Zachary R. , Frampton Garrett M. , Ali Siraj M. , Schrock Alexa B. , Miller Vincent A. , Stephens Philip J. , Ross Jeffrey S. , Frank Richard 
Published: March 2017

Abstract

Background
Uterine leiomyosarcoma (uLMS) responds poorly to conventional chemotherapeutic agents, and personalized therapies have yet to be systematically explored. Comprehensive genomic profiling (CGP) can identify therapeutic targets and provide insight into the biology of this highly aggressive tumor. We report a case of uLMS treated with the CGP-matched therapy palbociclib, a CDK4/6 inhibitor, with sustained clinical benefit in this rare and deadly malignancy.

Materials and Methods
This study analyzed 279 clinically advanced/recurrent uLMS samples. Median patient age was 54 years (range, 23–83 years). DNA was extracted from 40 µm of formalin-fixed, paraffin-embedded sections, and CGP was performed on hybridization-captured, adaptor ligation-based libraries for up to 405 cancer-related genes plus introns from up to 31 genes frequently rearranged in cancer. Sequencing data were analyzed for base pair substitutions, insertions/deletions, copy number alterations, and rearrangements.

Results
CGP shows that 97.1% of uLMS harbor at least one alteration, and approximately 57% harbor alterations in one or more therapeutically targetable pathways. CDKN2A mutations that inactivate p16INK4a were identified in 11% of uLMS. We report the first demonstration of clinical benefit in response to palbociclib treatment for a uLMS patient with a CDKN2A mutation, resulting in disease stabilization and significant symptom reduction.

Conclusion
A patient with uLMS harboring a CDKN2A mutation experienced clinical benefit from treatment with palbociclib, and genomic analysis of 279 uLMS samples revealed that 19% of patients had mutations affecting the cyclin-dependent kinase (CDK) pathway. These observations provide a rationale for a clinical trial investigating treatment with CDK pathway inhibitors for uLMS harboring relevant genomic alterations.
Adsorption characteristics of ciprofloxacin on the schorl: kinetics, thermodynamics, effect of metal ion and mechanisms
Authors: Yin Danyang , Xu Zhengwen , Shi Jing , Shen Lili , He Zexiang 
Published: March 2017

Abstract
In this study, schorl was used as an effective adsorbent for ciprofloxacin removal from wastewater. The adsorption performance, mechanism and effect of metal ion on sorption were investigated. Adsorption capacity reached a maximum (8.49 mg/g) when the pH value was 5.5. The pseudo-second-order kinetic model and Freundlich model could better describe the experimental data. The negative ΔH (–22.96 KJ/mol) value showed that the adsorption process was exothermic. The results also indicated physical adsorption existed on the adsorption process, which was in agreement with the analysis of X-ray diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy. The desorption rate could reach 94%, which suggested that schorl had a good desorption and regeneration performance. Coexisting ions, such as Cu2+ and Al3+, could obviously inhibit adsorption, and the inhibition from Al3+ was significantly higher than that from Cu2+. However, the additional Zn2+ could slightly promote the adsorption.
Variation in wood physical properties within stems of Guazuma crinita, a timber tree species in the Peruvian Amazon
Authors: Tuisima-Coral Lady L. , Odicio-Guevara Joel E. , Weber John C. , Lluncor-Mendoza David , Lojka Bohdan 
Published: March 2017

An understanding of wood physical properties and the interrelationships that govern them is required for efficient utilization of timber tree species. Guazuma crinita is a fast-growing timber tree of agroforestry systems in the Peruvian Amazon. The aim of this study was to assess variation in wood physical properties within the G. crinita stem. Wood samples were obtained from the base, middle and top of the stem of 12 randomly selected eight-year-old trees from six provenances in order to determine wood moisture content, density, specific gravity, radial, tangential and volumetric shrinkage and the coefficient of anisotropy. Pearson correlations between physical properties were also determined. The highest basic density was 459 kg/m3 from Tournavista provenance. Mean basic density and specific gravity were 430 kg/m3 and 0.45 respectively. There was statistically significant variation (p ≤ 0.05), due to stem level within the trees. The moderate values of density and anisotropy coefficient (1.56) suggest that G. crinita is a stable wood; these are important advantages in terms of costs of the processes of transport and transformation. Given the variation found in the limited tree samples of this study, we recommend further analysis with larger samples from different provenances and planting zones.Variación de las propiedades físicas en troncos de Guazuma crinita, una especie maderable en el Amazonas Peruano El entendimiento de las propiedades físicas de la madera y de las interrelaciones que las gobiernan es necesario para el uso eficiente de las especies maderables. Guazuma crinita es una especie arbórea de rápido crecimiento en sistemas agroforestales del Amazonas peruano. El objetivo de este estudio fue determinar la variación de las propiedades físicas de la madera en el fuste de árboles G. crinita. Las muestras de madera fueron obtenidas de la base, parte media y parte superior del tronco de 12 árboles de ocho años de edad aleatoriamente seleccionados, de seis lugares de procedencia. Con ellas se determinó: contenido de humedad, densidad, densidad relativa, contracciones radial, tangencial y volumétrica y coeficiente de anisotropía; se determinaron también las correlaciones de Pearson entre las propiedades físicas. La densidad básica mayor fue 459 kg/m3, de la procedencia de Tournavista. Las densidades básica y relativa promedio fueron 430 kg/m3 y 0.45, respectivamente. Se encontró variación estadísticamente significativa (p ≤ 0.05) entre alturas en el fuste. La madera moderadamente densa y el coeficiente de anisotropía (1.56) sugieren que G. Crinita es una madera estable, lo que representa importantes ventajas en términos de costos por transporte y proceso de transformación. Debido a la variación encontrada en las limitadas muestras de árboles de este estudio, se recomienda la realización de más análisis con mayores muestras y de diferentes sitios y plantaciones.
Assessment of Pancreas Safety in the Development Program of Once-Weekly GLP-1 Receptor Agonist Dulaglutide
Authors: Nauck Michael A. , Frossard Jean-Louis , Barkin Jamie S. , Anglin Greg , Hensley Ingrid E. , Harper Kristine D. , Milicevic Zvonko 
Published: March 2017

OBJECTIVE
To assess the risk of acute pancreatitis during treatment with glucagon-like peptide 1 receptor agonist dulaglutide, placebo, and active comparators across phase 2/3 dulaglutide trials.

RESEARCH DESIGN AND METHODS
A total of 6,005 patients with type 2 diabetes participated (dulaglutide group N = 4,006 [dose range 0.1–3.0 mg]; active comparator group [metformin, sitagliptin, exenatide twice daily, insulin glargine] N = 1,541; placebo group N = 703; 245 placebo-treated patients subsequently received dulaglutide or sitagliptin and were also included in these groups) for up to 104 weeks. The following events were adjudicated: investigator-reported pancreatitis, adverse events (AEs) of severe or serious abdominal pain of unknown etiology, and confirmed asymptomatic increases in pancreatic enzymes ≥3× the upper limit of normal range.

RESULTS
Overall, 203 events from 151 patients underwent adjudication (dulaglutide group n = 108; comparator group including placebo n = 43). Acute pancreatitis was confirmed by adjudication in seven patients (dulaglutide n = 3, placebo n = 1, sitagliptin n = 3). Exposure-adjusted incidence rates were as follows: dulaglutide group 0.85 patients/1,000 patient-years, placebo group 3.52 patients/1,000 patient-years, sitagliptin group 4.71 patients/1,000 patient-years. No events of pancreatitis were confirmed by adjudication in patients treated with exenatide twice daily, metformin, or glargine. Increases in median values of lipase and pancreatic amylase within the normal range were observed with all treatments except glargine. These changes were not associated with AEs.

CONCLUSIONS
The exposure-adjusted incidence rate of acute pancreatitis in dulaglutide-treated patients was similar to the rates with placebo, with few reported cases during the entire program.
APLICACIÓN DE NUEVAS TECNOLOGÍAS AL ESTUDIO DE POSICIONES DE LA GUERRA CIVIL ESPAÑOLA EN PINTO (MADRID)
Authors: Crespo Fraguas Ángela , Díaz Moreno Miguel Ángel , Farjas Abadía Mercedes , Martínez-Pardo Gil Guillermo , Alfonso Carbajosa Esther , Ruiz Serrano Carlos 
Published: March 2017

Los trabajos de prospección llevados a cabo en el término municipal de Pinto (Madrid) han permitido localizar diferentes enclaves con restos arqueológicos re- lacionados con las operaciones militares realizadas en torno a la capital durante la Guerra Civil Española (1936-1939). Para su identificación y documentación se recurrió al uso de GPS durante las batidas de prospección así como a fotografías aéreas de diferentes periodos que ayudaron en el proceso. En colaboración con investigadores de la Universidad Politécnica de Madrid se aplicaron en una de las zonas de mayor relevancia, el yacimiento de “Los Yesares”, diversas técni- cas con el objetivo de conseguir una representación espacial lo más completa posible. Estas técnicas incluyeron levantamientos topográficos para realizar car- tografias a diferentes escalas, la captación de imágenes mediante vuelos UAV (Unmanned Aerial Vehicle) y el uso de escáneres terrestres para la obtención de representaciones 3D.
EL USO DE FOTOGRAMETRÍA DE BAJO COSTE EN LA CREACIÓN DE NUBES DE PUNTOS APLICADA A LA ARQUEOLOGÍA COMERCIAL
Authors: Hernández Cordero Moisés 
Published: March 2017

El Láser Escáner y la Fotogrametría han sido recientemente incorporados a nuevos proyectos en el marco de trabajo del equipo de Geomática de Museum of London Archaeology (MOLA). La intención es adaptar nuevas formas de medición a la Arqueología de la Arquitectura y la Arqueología de campo, para poder ampliar los servicios que se ofrecen en el mercado de dichas disciplinas.En la presente comunicación se quiere mostrar el uso de estos métodos aplicados a distintos ambientes de trabajo, para así reforzar la idea del uso del Láser Escáner y de la Fotogrametría como alternativa –especialmente cuando el registro arqueológico ha desaparecido- en la captura de datos estratigráficos, edificios y objetos. El uso conjunto de dichos métodos puede ayudar a completar o mejorar el empleo de otras técnicas utilizadas (GPS y estación total) facilitando así un mejor resultado final que, además, puede ser rectificado con posterioridad.Finalmente, abordaremos la cuestión acerca del uso real de estas técnicas en la arqueología comercial llevadas a cabo por el equipo de Geomática de MOLA. Se pretenden exponer con ello las distintas posibilidades existentes de uso de esta técnica con uno de los distintos softwares disponibles (Agisoft Photoscan), los problemas surgidos en su empleo, así como las posibles aplicaciones de las mismas a la arqueología de investigación.