bluuebunny/crossref_metadata_2025 huggingface dataset:
Tranquilización rápida: nuevos enfoques en el tratamiento de urgencias de las perturbaciones del comportamiento
Authors: De Fruyt Jürgen , Demyttenaerea Koen
Published: May 2020

Las urgencias psiquiátricas se acompañan a menudo por perturbaciones del comportamiento que interfieren la evaluación normal y requieren intervención inmediata. Se han utilizado regímenes de tratamiento farmacológico diferentes para este propósito. La mayoría de estos regímenes se basan en la práctica clínica común y tienen una base probatoria limitada. Hace poco, una publicación importante de expertos en el campo de la psiquiatría de urgencias ha cubierto este asunto y se ha extendido el arsenal terapéutico con los antipsicóticos atípicos. Sin embargo, diferentes limitaciones metodológicas obstaculizan todavía la investigación: una definición poco clara del estado agitado y la meta terapéutica, la medición idiosincrasica y el pequeño tamaño de las muestras. La perspectiva del paciente y la interacción entre el entorno asistencial de urgencias y el regimen de tratamiento requieren también más atención. Todos estos aspectos importantes, pero olvidados a menudo, se cubren en una revisión selectiva de las publicaciones.
Estudio de seguimiento de 67 pacientes con primer episodio de esquizofrenia y su participación en actividades religiosas
Authors: Huguelet P. , Binyet-Vogel S. , González C. , Favre S. , McQuillan A.
Published: May 2020

Estudiamos durante 5 años las características de la práctica religiosa en una cohorte de 67 pacientes esquizofrénicos de primera admisión. Treinta por ciento de estos pacientes participaban en actividades religiosas, con una religión establecida o en un grupo marginal. En su mayoría, eran mujeres que tenían una buena adaptación psicosocial premórbida y no tendían al abuso de sustancias. El quinto año, su adaptación social había mejorado. Cumplían su tratamiento ambulatorio tanto como los demás pacientes. Sin embargo, cuando se controlaron las características en la inclusión, se mostró una evolución similar entre el grupo de pacientes practicantes y el de los no practicantes. Puede que la actividad religiosa no sea por sí misma la causa de esta evolución favorable, ya que es probable que sólo los pacientes que tienen menos síntomas y están relativamente bien adaptados puedan participar realmente en un movimiento religiose El hecho de que muchos pacientes esquizofrénicos encuentren en las actividades religiosas una ocupación y relaciones sociales que no encontrarían en otra parte debería animar a la comunidad psiquiátrica a escoger como objetivo sus metas ocupacionales.
Un estudio de la prevalencia anual de la esquizofrenia en la Isla Reunión
Authors: Jay M. , Gorwood P. , Feingold J. , Leboyer M.
Published: May 2020

La revisión de las comparaciones geográficas de la prevalencia de los trastornos esquizofrénicos encontróuna diferencia de rango de diez veces entre grupos geográficos contiguos, con bolsas de prevalencia alta y baja. Realizamos un estudio de la prevalencia anual de la esquizofrenia en un área limitada de la Isla Reunión en el Océano Indico y analizamos la variabilidad de la prevalencia en regiones contiguas de esta área. Encontramos una de las prevalencias anuales de esquizofrenia corregidas con respecto a la edad (más de 15 años) más altas que se han comunicado (14,9 por mil). Se observaron grandes discrepancias en la distribución de las tasas de prevalencia de la esquizofrenia entre las cinco ciudades analizadas. Tiene interés que cuando se observaba una prevalencia más alta, ésta se encontraba muy correlacionada con un aumento del porcentaje de los casos familiares (r = 0,989, gl = 3, P = 0,0014). La presencia de un efecto de fundador, descrito a menudo en grupos aislados geográficamente, podría explicar la alta tasa de prevalencia y la heterogeneidad entre ciudades observada en nuestra muestra.
Agomelatina: un fármaco nuevo con acción antidepresiva que afecta a los sistemas melatonérgico y serotonérgico
Authors: San Luis , Arranz Belen
Published: May 2020

La observavión clínica de que los trastornos depresivos a menudo se asocian con desincronización de los ritmos internos ha reforzado la idea de que recuperar los ritmos circadianos normales puede tener algún potencial antidepresivo. Agomelatina, un naftaleno análogo de melatonina, es a la vez agonista de los receptores humanos melatonérgicos MT1 y MT2 y antagonista de los receptores de serotonina 5-HT2C. Agomelatina combina la actividad sincronizadora (zeitgeber en alemán, sincronizador del sistema circadiano) con su capacidad de aumentar la neurotransmisión (aumenta las concentraciones de dopamina y noradrenalina en la corteza frontal). Se ha demostrado la eficacia de agomelatina en el tratamiento de la depresión en tres estudios a corto plazo, aleatorios y controlados por placebo. Estos estudios demostraron que agomelatina es eficaz en el trastorno depresivo mayor en una dosis estándar de 25 mg/día, con la posibilidad de aumentar la dosis a 50 mg/día en pacientes con mejoría insuficiente. El número de efectos adversos durante el período de tratamiento fue similar al del placebo. Cuatro estudios han demostrado el efecto positivo de agomelatina sobre la continuidad y la calidad del sueño y el acortamiento de la latencia del sueño. A pesar de que estos datos son prometedores, son necesarios otros estudios para examinar la eficacia de agomelatina durante un período de tratamiento más largo.
Validación de la Escala Informatizada de Riesgo de Suicidio, un instrumento de red neural de retropropagación (CSRS-BP)
Authors: Modai I. , Ritsner M. , Kurs R. , Mendel S. , Ponizovsky A.
Published: May 2020

Antecedentes:

Los intentos de suicidio médicamente graves se han reconocido como el predictor más importante de suicidio. Recientemente se ha encontrado que la Escala Informatizada de Riesgo de Suicidio basada en redes neurales de retropropagación (CSRS-BP) es eficaz en la detección de historias clínicas de pacientes que realizaron intentos de suicidio médicamente graves (ISMG).

Objetivos:

Validar la CSRS-BP: 1) utilizándola con pacientes en lugar de con historias clínicas; 2) comparando la capacidad de psiquiatras expertos para detectar ISMG utilizando la lista de la CSRS, y 3) comparando los resultados del Estimador de Riesgo para el Suicidio (RES) y la Escala de autoevaluación de Riesgo de Suicidio (SRS) con la CSRS-BP.

Métodos:

Profesionales clínicos diagnosticaron a 250 pacientes psiquiátricos hospitalizados (35 con ISMG y 215 sin ISMG) utilizando la SCID del DSM IV. Tres psiquiatras expertos cumplimentaron la lista de la CSRS y el RES para cada paciente, y los pacientes rellenaron la escala de evaluación de autoinforme SRS. La CSRS-BP se pasó en máquina para cada paciente. Otros cinco psiquiatras expertos evaluaron las listas de la CSRS y estimaron la probabilidad de ISMG para cada paciente. Se hicieron comparaciones de las tasas de sensibilidad y especificidad entre la CSRS-BP, las escalas de evaluación y los expertos.

Resultados:

Inicialmente, la CSRS-BP, el RES, la SRS y los expertos obtuvieron malos resultados. Aunque las tasas de sensibilidad y especificidad mejoraron significativamente (de dos a cuatro veces) después de la inclusión de información con respecto al número de intentos previos de suicidio en el conjunto de datos de entrada, los resultados todavía no eran significativos.

Conclusiones:

La CSRS-BP, que tuvo mucho éxito en la detección de historias clínicas de pacientes con ISMG, no detectó a los pacientes con ISMG en entrevistas cara a cara. La información con respecto a los intentos de suicidio anteriores es un predictor importante de ISMG, pero es insuficiente para su detección en los pacientes individuales. La tasa de detección de la SRS y la escala RES fue también mala y, por tanto, no pudieron identificar a los pacientes con ISMG o utilizarse para validar la CSRS-BP.
Monoterapia de modafinilo en la depresión
Authors: Kaufman K. R. , Menza M. A. , Fitzsimmons A.
Published: May 2020

Los trastornos afectivos refractarios requieren a menudo una polifarmacia rational: antidepresivos de más de una clase, antidepresivos con anticonvulsives y antidepresivos con aumento (litio, tiroides y psicoestimulantes). Mientras que los psicoestimulantes (metilfenidato, dextroanfetamina y pemolina de magnesio) se utilizan por lo general en pacientes comprometidos médicamente [8], para la depresión refractaria [2, 11] o para los trastornos por déficit de atención [5], estos agentes se deberían considerar para el tratamiento en monoterapia de la depresión cuando un paciente no ha tenido éxito en los ensayos terapéuticos antidepresivos, tiene efectos secundarios inaceptables ante los antidepresivos habituales, incluso con respuestas positivas, o no está dispuesto a recibir modalidades de tratamiento diferentes por temor a los efectos adversos potenciales.
Inhibición prepulso y “propensión a la psicosis” en individuos sanos: un estudio de RMf
Authors: Kumari Veena , Antonova Elena , Geyer Mark A.
Published: May 2020

Objetivo.

La inhibición prepulso (IPP) de la respuesta de sobresalto es un índice eficaz de la regulación sensitivomotora que puede demostrarse de forma segura tanto en personas como en animales. Los pacientes con esquizofrenia, los familiares de primer grado de pacientes con esquizofrenia, los pacientes con trastorno de personalidad esquizotípica y los individuos sanos que tienen puntuaciones altas en las medidas psicométricas de propensión a la psicosis tienen una IPP reducida. Este estudio analizó las asociaciones entre las diferencias individuales en la “propensión a la psicosis” y la actividad cerebral durante un paradigma de inhibición prepulso táctil con el que previamente se había demostrado activación en los controles y falta de activación en pacientes con esquizofrenia en el estriado, tálamo, ínsula, hipocampo y regiones temporales, frontal inferior y parietal inferior.

Métodos.

Catorce hombres diestros sanos se sometieron a pruebas psicofisiológicas y de resonancia funcional magnética (RMf) durante un paradigma de IPP táctil de 15 minutos aplicando estímulos táctiles de pulso (soplos de aire de 30 psi durante 40 ms) y prepulso (soplos de aire de 6 psi durante 20 ms aplicados 30 ms o 120 ms antes del pulso). Las diferencias individuales en “la propensión a la psicosis” se evaluaron con la escala de Psicoticismo del Cuestionario de Personalidad de Eysenck Revisado (EPQ-R).

Resultados.

La propensión elevada a la psicosis se asoció con una IPP más baja y menor actividad en la circunvolución frontal inferior, en la ínsula hacia el putamen y el tálamo, en la circunvolución parahipocámpica y en la región parietal inferior y temporal media. Ninguna actividad regional se correlacionó positivamente con la propensión a la psicosis.

Conclusiones.

Estas observaciones amplían las conclusiones extraídas previamente en personas con esquizofrenia con elevada propensión a la psicosis, lo que confirma las teorías del continuum de la psicosis con implicaciones para entender los déficit neurales relacionados con el rasgo en la esquizofrenia.
¡Feliz cumpleaños, neurolépticos! Cincuenta años después: la locura de la duda
Authors: Stip E.
Published: May 2020

Dado que celebramos el quicuagésimo cumpleaños de la introducción de los neurolépticos en psiquiatría, el autor propone echar un vistazo a algunos resultados relacionados con la práctica terapéutica. Después de una breve revisión cronológica de las publicaciones de las prácticas clínicas y los modelos teóricos que han controlado el tratamiento farmacológico de la esquizofrenia, el autor presenta una revisión crítica de cuatro meta-análisis. Desde el informe inicial de Delay, Deniker y Harl, la historia de los neurolépticos comprende varios períodos. En 1963 se propuso la teoría hiperdopaminérgica de la psicosis. Otro período comenzó con los modelos basados principalmente en la hipótesis del bloqueo relativo de los receptores de serotonina/dopamina. Más recientemente, un nuevo marco para comprender el efecto diferencial de los antipsicóticos se relaciona con la modulación apropiada (por ejemplo, la disociación rápida) del receptor D2 solo. El concepto de atipicidad se ha convertido en una nueva perspectiva para la investigación y para comercializar nuevos compuestos. Sin embargo, después de 50 años de fármacos neurolépticos, ¿podemos responder a las simples preguntas siguientes?: ¿Son los neurolépticos eficaces en el tratamiento de la esquizofrenia? ¿Hay diferencias entre los neurolépticos atípicos y los convencionales? ¿Cuál es la eficacia y la seguridad de los nuevos medicamentos antipsicóticos comparado con la eficacia y la seguridad de la clozapina? En realidad, las respuestas que los meta-análisis dan a estas simples preguntas deberían provocar en nosotros una gran humildad. Si deseamos basar la psiquiatría en la medicina basada en la evidencia, corremos un riesgo real al mirar más de cerca a lo que durante mucho tiempo se han considerado hechos. Cada psiquiatra debe continuar siendo crítico, escético y (no excesivamente) optimista y aprender para integrar los aspectos positivos de nuestra base creciente de conocimientos.
¿Afecta el contacto telefónico con los pacientes en el año posterior a un intento de suicido a la asistencia al tratamiento y la evolución? Un estudio controlado distribuido al azar
Authors: Cedereke M. , Monti K. , Öjehagen A.
Published: May 2020

La ambivalencia hacia el tratamiento y el comportamiento suicida repetido son problemas muy conocidos en las personas que intentan suicidarse. Se realizó un estudio controlado distribuido al azar para investigar la influencia de los contactos telefónicos repetidos en la asistencia al tratamiento, la repetición del comportamiento suicida y la salud mental el año posterior a un intento de suicidio.

Sujetos y métodos:

Un mes después de su intento de suicido se distribuyó al azar a 216 pacientes a ser objeto de dos intervenciones telefónicas además del tratamiento habitual o a la ausencia de esta intervención durante el año posterior. Las intervenciones incluían apoyo motivacional para asistir al tratamiento, permanecer en él, o ambas cosas. Un mes y de nuevo 12 meses después se utilizaron las medidas siguientes: IGG (SCL-90), GAF y SSI.

Resultados:

En el seguimiento, la asistencia al tratamiento fue alta y no difería entre los grupos distribuidos al azar. Entre los que tuvieron un contacto de tratamiento inicial distinto al psiquiátrico, más pacientes en el grupo de intervención tenían este contacto en el seguimiento. Los grupos distribuidos al azar no difirieron en la repetición de los intentos de suicidio durante el seguimiento o en la mejoría en el IGG (SCL-90), la GAF y el SSI. En los individuos sin tratamiento inicial, el grupo de intervención mejoró más en algunas dimensiones de síntomas psicológicos (SCL-90).

Conclusión:

Las intervenciones telefónicas parecen tener un efecto en los pacientes que cuando intentaron suicidarse tenían un tratamiento distinto al psiquiátrico y en los que no tenían tratamiento.
Un caso clínico de terapia cognitiva informal de las ideas delirantes por un cuidador: ¿un nuevo paradigma de tratamiento?
Authors: George Sanju , Bandopadhay Sumithra , Cowan Colin
Published: May 2020

La terapia cognitiva se ha utilizado de manera efectiva en el tratamiento de síntomas psicóticos como las ideas delirantes y las alucinaciones. La mayor parte del trabajo en esta área se ha centrado sólo en el paciente. Describimos a un paciente con esquizofrenia cuyas ideas delirantes tuvieron un buen tratamiento por su madre utilizando principios de terapia cognitiva informal. Los cuidadores primarios podrían involucrarse más como “co-terapeutas” en el tratamiento cognitivo de los síntomas psicóticos en algunos pacientes. Trabajos futuros tienen que explorar la efectividad y viabilidad de informatión de terapia cognitiva más estructurada para los cuidadores (como co-terapeutas) de pacientes con psicosis.
Combs, cages, and thickets: Níall McLaughlin and an architecture of line
Authors: Carr Andrew
Published: May 2020

Repeating linear elements organised into arrays and lattices are commonly manifest in the work of Niall McLaughlin Architects. This paper describes a series of projects which explore the use of this ‘architecture of line’ in the work of the practice. Organised by formal development, rather than chronology, it identifies sequences that evolve from a two dimensional handling of line, as combs, to a thickened three dimensional handling that produces cat’s cradles, cages, naves, thickets and forests. The work of other architects, including Aalto Aalto, Kengo Kuma, Sverre Fehn, Peter Zumthor, Rudolf Schwarz and Karl Friedrich Schinkel, alongside the influence of Gottfried Semper’s writings, are placed within and alongside these sequences revealing common approaches and individual differences. Developed simultaneously through writing and drawing, the latter have been used to isolate elements of line within each architectural work, helping to understand their use and allowing a comparison to be made between McLaughlin’s work and the wider critical framework of other architect’s work. His particular spatial and temporal handling of line is revealed as a meteorological, environmental and poetic mediator between inner and outer worlds.
White Protectionism in America
Authors: Smith Rogers M. , King Desmond
Published: May 2020

Critics charge President Donald Trump with racism, but he insists he opposes bigotry and is an American nationalist, not a white nationalist. We use analysis of Trump’s campaign rhetoric, his administration’s policies, and their reception to assess these rival claims. In his campaign, Trump narrated American identity as a tale of lost greatness in which a once-unblemished America gave way to globalist elites who have victimized many Americans, particularly traditionalist, predominantly white Christian Americans. His policies have systematically expanded protections for such Americans and sought to increase their share of the American electorate and citizenry, while reducing or eliminating initiatives designed to assist and increase the numbers of non-white, non-Christian American voters and citizens. The evidence thus shows that although Trump does not explicitly endorse white nationalism, his rhetoric and policies articulate not a consistent race-blind nationalism, but a vision of white protectionism.
Mesopause Airglow Disturbances Driven by Nonlinear Infrasonic Acoustic Waves Generated by Large Earthquakes
Authors: Inchin P. A. , Snively J. B. , Williamson A. , Melgar D. , Aguilar Guerrero J. , Zettergren M. D.
Published: May 2020

Near‐epicentral mesopause airglow perturbations, driven by infrasonic acoustic waves (AWs) during a nighttime analog of the 2011 M9.1 Tohoku‐Oki earthquake, are simulated through the direct numerical computation of the 3D nonlinear Navier‐Stokes equations. Surface dynamics from a forward seismic wave propagation simulation, initialized with a kinematic slip model and performed with the SPECFEM3D_GLOBE model, are used to excite AWs into the atmosphere from ground level. Simulated mesopause airglow perturbations include steep oscillations and persistent nonlinear depletions up to 50% and 70% from the background state, respectively, for the hydroxyl OH(3,1) and oxygen O(1S) 557.7‐nm emissions. Results suggest that AWs excited near a large earthquake's epicenter may be strong enough to drive fluctuations in mesopause airglow, some which may persist after the AWs have passed, that could be readily detectable with ground‐ and/or satellite‐based imagers. Synthetic data demonstrate that future airglow observations may be used for the characterization of earthquake mechanisms and surface seismic waves propagation, potentially complementing tsunami early‐warning systems based on total electron content (TEC) observations.
Effusion Rate Evolution During Small‐Volume Basaltic Eruptions: Insights From Numerical Modeling
Authors: Aravena A. , Cioni R. , Coppola D. , de' Michieli Vitturi M. , Neri A. , Pistolesi M. , Ripepe M.
Published: May 2020

The temporal evolution of effusion rate is the main controlling factor of lava spreading and emplacement conditions. Therefore, it represents the most relevant parameter for characterizing the dynamics of effusive eruptions and thus for assessing the volcanic hazard associated with this type of volcanism. Since the effusion rate curves can provide important insights into the properties of the magma feeding system, several efforts have been performed for their classification and interpretation. Here, a recently published numerical model is employed for studying the effects of magma source and feeding dike properties on the main characteristics (e.g., duration, erupted mass, and effusion rate trend) of small‐volume effusive eruptions, in the absence of syn‐eruptive magma injection from deeper storages. We show that the total erupted mass is mainly controlled by magma reservoir conditions (i.e., dimensions and overpressure) prior to the eruption, whereas conduit processes along with reservoir properties can significantly affect mean effusion rate, and thus, they dramatically influence eruption duration. Simulations reproduce a wide variety of effusion rate trends, whose occurrence is controlled by the complex competition between conduit enlargement and overpressure decrease due to magma withdrawal. These effusion rate curves were classified in four groups, which were associated with the different types described in the literature. Results agree with the traditional explanation of effusion rate curves and provide new insights for interpreting them, highlighting the importance of magma reservoir size, initial overpressure, and initial width of the feeding dike in controlling the nature of the resulting effusion rate curve.
Impacts of Suspended Clay Particle Deposition on Sand‐Bed Morphodynamics
Authors: Dallmann J. , Phillips C. B. , Teitelbaum Y. , Sund N. , Schumer R. , Arnon S. , Packman A. I.
Published: May 2020

Fine particles (0.1–100 microns) are ubiquitous within the water column. Observations on the interactions between suspended fine particles and sediment beds remain limited, reducing our ability to understand the interactions and feedbacks between fine particles, morphodynamics, and hyporheic flow. We performed laboratory experiments to explore changes in bedform morphodynamics and hyporheic flow following the progressive addition of kaolinite clay to the water column above a mobile sand bed. We characterized these interactions by taking high‐frequency time series measurements of bed topography and freestream clay concentration combined with solute injections and bed sediment cores to characterize subsurface properties. Deposition of initially suspended clay resulted in a decrease of bedform height, celerity, and sediment flux by 14%, 22%, and 29% when 1000 g was accumulated within the bed (equal to clay/sand mass ratio of 0.4% in the bed). The hyporheic exchange flux decreased by almost a factor of 2 for all clay additions, regardless of the amount of clay eventually deposited in the bed. Post experiment sediment cores showed clay accumulation within and below the mobile layer of the bedforms, with the peak concentration occurring at the most frequent bedform scour depth. These results demonstrate the tight coupling between bed sediment morphodynamics, fine particle (clay) deposition, and hyporheic exchange. Suspended and bed load transport rates are diminished by the transfer of suspended load to the sediment via hyporheic exchange. This coupling should be considered when estimating sediment transport rates.
What It’s Like to Social Distance at Sea
Authors: Duncombe Jenessa
Published: May 2020

A skeleton crew braves the first research cruise since the pandemic began.
Phase Transition of Enstatite‐Ferrosilite Solid Solutions at High Pressure and High Temperature: Constraints on Metastable Orthopyroxene in Cold Subduction
Authors: Xu Jingui , Fan Dawei , Zhang Dongzhou , Guo Xinzhuan , Zhou Wenge , Dera Przemyslaw K.
Published: May 2020

(Mg, Fe)SiO3 orthopyroxene is an abundant mineral of oceanic subducting slabs. In‐situ high‐pressure and high‐temperature single‐crystal X‐ray diffraction has been used to investigate the phase transition of orthopyroxene across the enstatite‐ferrosilite (En‐Fs) join (En70Fs30, En55Fs45, En44Fs56 and Fs100) up to 24.3 GPa and 800 K, simulating conditions within the coldest part of a subduction zone consisting of an old and rapidly subducting slab. Instead of the orthopyroxene → high‐pressure clinopyroxene transition, the α‐opx → β‐opx and β‐opx → γ‐opx phase transition are observed at 7.2–15.3 and 11.6–21.1 GPa (depending on the Fs content), respectively. This study indicates that the pressure‐induced phase transition of (Mg, Fe)SiO3 orthopyroxene under relatively low temperature (<800 K) could be different than those occurring under relatively high temperature (>800 K). Additionally, the α‐opx → β‐opx → γ‐opx phase transition could exist within the center of the extremely cold slabs (like Tonga), where such low temperature persists to ~600‐km depth.
Thank You to Our 2019 Reviewers
Authors: Manighetti Isabelle , ten Brink Uri , Abercrombie Rachel , Ben‐Zion Yehuda , Bernabé Yves , Bostock Michael , Parman Stephen W. , Revil André , Savage Martha , Schmitt Doug , Tregoning Paul
Published: May 2020

Key Point

Thank you to the reviewers of articles submitted to Solid Earth
SIRT7 activates p53 by enhancing PCAF-mediated MDM2 degradation to arrest the cell cycle
Authors: Lu Ya-Fei , Xu Xiao-Peng , Lu Xiao-Peng , Zhu Qian , Liu Ge , Bao Yan-Tao , Wen He , Li Ying-Lu , Gu Wei , Zhu Wei-Guo
Published: May 2020

Sirtuin 7 (SIRT7), an NAD+-dependent deacetylase, plays vital roles in energy sensing, but the underlying mechanisms of action remain less clear. Here, we report that SIRT7 is required for p53-dependent cell-cycle arrest during glucose deprivation. We show that SIRT7 directly interacts with p300/CBP-associated factor (PCAF) and the affinity for this interaction increases during glucose deprivation. Upon binding, SIRT7 deacetylates PCAF at lysine 720 (K720), which augments PCAF binding to murine double minute (MDM2), the p53 E3 ubiquitin ligase, leading to accelerated MDM2 degradation. This effect results in upregulated expression of the cell-cycle inhibitor, p21Waf1/Cip1, which further leads to cell-cycle arrest and decreased cell viability. These data highlight the importance of the SIRT7–PCAF interaction in regulating p53 activity and cell-cycle progression during conditions of glucose deprivation. This axis may represent a new avenue to design effective therapeutics based on tumor starvation.
Carbidopa suppresses prostate cancer via aryl hydrocarbon receptor-mediated ubiquitination and degradation of androgen receptor
Authors: Chen Zhiwei , Cai Aimin , Zheng Hailun , Huang Huirong , Sun Rui , Cui Xiao , Ye Weijian , Yao Qing , Chen Ruijie , Kou Longfa
Published: May 2020

Carbidopa, a peripheral decarboxylase inhibitor used with L-DOPA to treat Parkinson’s disease, has attracted significant interest in recent years for its anticancer effect. Increasing evidence reveals that Carbidopa can inhibit cancer cell growth and induce apoptosis through aryl hydrocarbon receptor (AHR) in some cancers. However, the antitumor effect of Carbidopa in prostate cancer (PCa) is not fully understood. Androgen receptor (AR) plays a central role in PCa, even in advanced “castrate-resistant” disease. In the present study, we report that Carbidopa suppresses the growth of PCa by downregulating the protein expression of AR. Carbidopa inhibits proliferation and migration of LNCaP cells and promotes apoptosis, but has no effect on the AR-independent prostate cell line DU145. Carbidopa increases ubiquitination of AR in LNCaP cells. Several studies have shown that AHR can act as an E3 ubiquitin ligase and promote the proteasomal degradation of AR. Quantitative RT-PCR, immunofluorescence staining and immunoblotting assay demonstrate that AHR is induced and activated by Carbidopa, and the co-immunoprecipitation assay shows that AR interacts with AHR, firmly confirming that Carbidopa decreases AR protein level though AHR-induced proteasomal degradation. In addition, Carbidopa suppresses PCa growth in vivo when xenografted into immunocompromised mice. Carbidopa treatment increases AHR protein level and decreases AR protein level in tumor tissues. Taken together, our study implicates Carbidopa for the first time in effective suppression of prostate cancer via a mechanism, involving AHR-mediated proteasomal degradation of AR.
Extracellular vesicle-mediated transfer of miR-21-5p from mesenchymal stromal cells to neurons alleviates early brain injury to improve cognitive function via the PTEN/Akt pathway after subarachnoid hemorrhage
Authors: Gao Xiao , Xiong Ye , Li Qizhao , Han Min , Shan Dezhi , Yang Guozheng , Zhang Shouji , Xin Danqing , Zhao Rongrong , Wang Zhen , Xue Hao , Li Gang
Published: May 2020

Patients with subarachnoid hemorrhage (SAH) often suffer from cognitive function impairments even when they have received proper treatment, such as the clipping or coiling of aneurysms, and this causes problems with returning to work and burdens the family. Increasing attention has been paid to mesenchymal stem cell (MSC)-derived extracellular vesicle (MSC-EV) as promising therapeutic vesicles for stroke management. In this study, we explored the potential role of MSC-EV in a rat model of SAH. We observed that MSC-EV ameliorated early brain injury (EBI) after SAH by reducing the apoptosis of neurons and that SAH induced an increase in the expression level of miR-21 in the prefrontal cortex and hippocampus. In addition, using miRNA profiling and CSF sequencing data from the exRNA Atlas, we demonstrated that EV-derived miR-21 protected neurons from apoptosis and alleviated SAH-induced cognitive dysfunction. The neuroprotective role of MSC-EV was abrogated by miR-21 knockdown or the administration of MK2206, a PTEN/Akt inhibitor. Overall, our results suggest that MSC-EV promotes neuronal survival and alleviates EBI after SAH through transferring miR-21 to recipient neurons.
Long noncoding RNA lncARSR confers resistance to Adriamycin and promotes osteosarcoma progression
Authors: Shen Peng , Cheng Yanfeng
Published: May 2020

One of the significant challenges for chemotherapy is the appearance of resistance to compounds. Although several signaling pathways have been implicated in the development of Adriamycin (ADM) resistance, mechanisms involved in ADM-resistant osteosarcoma progression remain unknown. The present study attempted to illustrate the role of long noncoding RNA ARSR (lncARSR) in the development of adapted ADM resistance. We found lncARSR overexpressed in the Adriamycin-resistant cell lines U2OS/ADM and MG63/ADM, accompanied with acquired multidrug resistance against to paclitaxel and cisplatin. Overexpression of lncARSR triggered rhodamine 123 efflux and survival, as well as the migration of Adriamycin-resistant cells. Inversely, the depletion of lncARSR promoted rhodamine 123 retention and apoptosis, while reducing the motility of ADM-resistant cells. Further investigation revealed that the upregulation of lncARSR enhanced multidrug resistance-associated protein-1 (MRP1), apoptosis inhibitor Survivin, and matrix metalloproteinase-2 (MMP2) through activating AKT. The reduction of lncARSR overcame the resistance to ADM in U2OS/ADM mouse model. The current study gained novel evidence for understanding the mechanisms underlying adaptive ADM resistance and provided rationales to improve clinical outcomes of refractory osteosarcoma.
Elevated microRNA-125b inhibits cytotrophoblast invasion and impairs endothelial cell function in preeclampsia
Authors: Li Qinghua , Han Yangyang , Xu Peng , Yin Lingxuan , Si Yanru , Zhang Cuijuan , Meng Yuhan , Feng Weiguo , Pan Zhifang , Gao Zhiqin , Li Jie , Yang Weiwei
Published: May 2020

Preeclampsia (PE) is a life-threatening disorder of human pregnancy affecting 5–8% of all pregnancies. Currently, PE remains an elusive complicated and heterogenous medical condition with no early marker or symptoms is recognized for this serious pregnancy complications. Here, we profiled the plasma miRNA expression patterns associated with preeclampsia and found 16 miRNAs were deregulated (p < 0.01) in patients who later developed PE. Circulating hsa-miR-125b was aberrantly upregulated in early pregnancy and significantly reduced after delivery in preeclampsia. We then investigated the underlying molecular mechanisms between miR-125b and PE in vitro. We found that upregulated miR-125b can target KCNA1 to inhibit trophoblast invasion in human trophoblast cells. Moreover, overexpression of miR-125b in HUVECs impaired endothelial cell function through GPC1. The findings indicated that upregulated miR-125b leads to impaired placentation, and an increased risk of preeclampsia, Our studies provide novel insights into the underlying mechanisms on the association of miR-125b in early pregnancy and risk of PE, miR-125b might be a more specific predictive marker and a safe therapeutic target for treating patients with PE.
Community-level signatures of ecological succession in natural bacterial communities
Authors: Pascual-García Alberto , Bell Thomas
Published: May 2020

A central goal in microbial ecology is to simplify the extraordinary biodiversity that inhabits natural environments into ecologically coherent units. We profiled (16S rRNA sequencing)  > 700 semi-aquatic bacterial communities while measuring their functional capacity when grown in laboratory conditions. This approach allowed us to investigate the relationship between composition and function excluding confounding environmental factors. Simulated data allowed us to reject the hypothesis that stochastic processes were responsible for community assembly, suggesting that niche effects prevailed. Consistent with this idea we identified six distinct community classes that contained samples collected from distant locations. Structural equation models showed there was a functional signature associated with each community class. We obtained a more mechanistic understanding of the classes using metagenomic predictions (PiCRUST). This approach allowed us to show that the classes contained distinct genetic repertoires reflecting community-level ecological strategies. The ecological strategies resemble the classical distinction between r- and K-strategists, suggesting that bacterial community assembly may be explained by simple ecological mechanisms.
Deep brain stimulation-guided optogenetic rescue of parkinsonian symptoms
Authors: Valverde Sébastien , Vandecasteele Marie , Piette Charlotte , Derousseaux Willy , Gangarossa Giuseppe , Aristieta Arbelaiz Asier , Touboul Jonathan , Degos Bertrand , Venance Laurent
Published: May 2020

Deep brain stimulation (DBS) of the subthalamic nucleus is a symptomatic treatment of Parkinson’s disease but benefits only to a minority of patients due to stringent eligibility criteria. To investigate new targets for less invasive therapies, we aimed at elucidating key mechanisms supporting deep brain stimulation efficiency. Here, using in vivo electrophysiology, optogenetics, behavioral tasks and mathematical modeling, we found that subthalamic stimulation normalizes pathological hyperactivity of motor cortex pyramidal cells, while concurrently activating somatostatin and inhibiting parvalbumin interneurons. In vivo opto-activation of cortical somatostatin interneurons alleviates motor symptoms in a parkinsonian mouse model. A computational model highlights that a decrease in pyramidal neuron activity induced by DBS or by a stimulation of cortical somatostatin interneurons can restore information processing capabilities. Overall, these results demonstrate that activation of cortical somatostatin interneurons may constitute a less invasive alternative than subthalamic stimulation.
BAF60a deficiency uncouples chromatin accessibility and cold sensitivity from white fat browning
Authors: Liu Tongyu , Mi Lin , Xiong Jing , Orchard Peter , Yu Qi , Yu Lei , Zhao Xu-Yun , Meng Zhuo-Xian , Parker Stephen C. J. , Lin Jiandie D. , Li Siming
Published: May 2020

Brown and beige fat share a remarkably similar transcriptional program that supports fuel oxidation and thermogenesis. The chromatin-remodeling machinery that governs genome accessibility and renders adipocytes poised for thermogenic activation remains elusive. Here we show that BAF60a, a subunit of the SWI/SNF chromatin-remodeling complexes, serves an indispensable role in cold-induced thermogenesis in brown fat. BAF60a maintains chromatin accessibility at PPARγ and EBF2 binding sites for key thermogenic genes. Surprisingly, fat-specific BAF60a inactivation triggers more pronounced cold-induced browning of inguinal white adipose tissue that is linked to induction of MC2R, a receptor for the pituitary hormone ACTH. Elevated MC2R expression sensitizes adipocytes and BAF60a-deficient adipose tissue to thermogenic activation in response to ACTH stimulation. These observations reveal an unexpected dichotomous role of BAF60a-mediated chromatin remodeling in transcriptional control of brown and beige gene programs and illustrate a pituitary-adipose signaling axis in the control of thermogenesis.
LITESEC-T3SS - Light-controlled protein delivery into eukaryotic cells with high spatial and temporal resolution
Authors: Lindner Florian , Milne-Davies Bailey , Langenfeld Katja , Stiewe Thorsten , Diepold Andreas
Published: May 2020

Many bacteria employ a type III secretion system (T3SS) injectisome to translocate proteins into eukaryotic host cells. Although the T3SS can efficiently export heterologous cargo proteins, a lack of target cell specificity currently limits its application in biotechnology and healthcare. In this study, we exploit the dynamic nature of the T3SS to govern its activity. Using optogenetic interaction switches to control the availability of the dynamic cytosolic T3SS component SctQ, T3SS-dependent effector secretion can be regulated by light. The resulting system, LITESEC-T3SS (Light-induced translocation of effectors through sequestration of endogenous components of the T3SS), allows rapid, specific, and reversible activation or deactivation of the T3SS upon illumination. We demonstrate the light-regulated translocation of heterologous reporter proteins, and induction of apoptosis in cultured eukaryotic cells. LITESEC-T3SS constitutes a new method to control protein secretion and translocation into eukaryotic host cells with unparalleled spatial and temporal resolution.
Efficient training of ANN potentials by including atomic forces via Taylor expansion and application to water and a transition-metal oxide
Authors: Cooper April M. , Kästner Johannes , Urban Alexander , Artrith Nongnuch
Published: May 2020

Artificial neural network (ANN) potentials enable the efficient large-scale atomistic modeling of complex materials with near first-principles accuracy. For molecular dynamics simulations, accurate energies and interatomic forces are a prerequisite, but training ANN potentials simultaneously on energies and forces from electronic structure calculations is computationally demanding. Here, we introduce an efficient alternative method for the training of ANN potentials on energy and force information, based on an extrapolation of the total energy via a Taylor expansion. By translating the force information to approximate energies, the quadratic scaling with the number of atoms exhibited by conventional force-training methods can be avoided, which enables the training on reference datasets containing complex atomic structures. We demonstrate for different materials systems, clusters of water molecules, bulk liquid water, and a lithium transition-metal oxide that the proposed force-training approach provides substantial improvements over schemes that train on energies only. Including force information for training reduces the size of the reference datasets required for ANN potential construction, increases the transferability of the potential, and generally improves the force prediction accuracy. For a set of water clusters, the Taylor-expansion approach achieves around 50% of the force error improvement compared to the explicit training on all force components, at a much smaller computational cost. The alternative force-training approach thus simplifies the construction of general ANN potentials for the prediction of accurate energies and interatomic forces for diverse types of materials, as demonstrated here for water and a transition-metal oxide.
Biomimetic Coating-free Superomniphobicity
Authors: Das Ratul , Ahmad Zain , Nauruzbayeva Jamilya , Mishra Himanshu
Published: May 2020

Superomniphobic surfaces, which repel droplets of  polar and apolar liquids, are used for reducing frictional drag, packaging electronics and foods, and separation processes, among other applications. These surfaces exploit perfluorocarbons that are expensive, vulnurable to physical damage, and have a long persistence in the environment. Thus, new approaches for achieving superomniphobicity from common materials are desirable. In this context, microtextures comprising “mushroom-shaped” doubly reentrant pillars (DRPs) have been shown to repel drops of polar and apolar liquids in air irrespective of the surface make-up. However, it was recently demonstrated that DRPs get instantaneously infiltrated by the same liquids on submersion because while they can robustly prevent liquid imbibition from the top, they are vulnerable to lateral imbibition. Here, we remedy this weakness through bio-inspiration derived from cuticles of Dicyrtomina ornata, soil-dwelling bugs, that contain cuboidal secondary granules with mushroom-shaped caps on each face. Towards a proof-of-concept demonstration, we created a perimeter of biomimicking pillars around arrays of DRPs using a two-photon polymerization technique; another variation of this design with a short wall passing below the side caps was investigated. The resulting gas-entrapping microtextured surfaces (GEMS) robustly entrap air on submersion in wetting liquids, while also exhibiting superomniphobicity in air. To our knowledge, this is the first-ever microtexture that confers upon intrinsically wetting materials the ability to simultaneously exhibit superomniphobicity in air and robust entrapment of air on submersion. These findings should advance the rational design of coating-free surfaces that exhibit ultra-repellence (or superomniphobicity) towards liquids.
Bone-like structure by modified freeze casting
Authors: Singh Gurdev , Soundarapandian S.
Published: May 2020

Freeze casting has emerged as one of the most promising manufacturing methods to fabricate porous scaffolds in recent years. This is due to various reasons which include a wide range of materials which can be used in this process, easiness of the process, etc. One of the major objectives of this work was to fabricate bone-like structure by using a modified freeze casting process. In this work, Hydroxyapatite and Tricalcium phosphate scaffolds with bone-like structure were fabricated by understanding and utilizing the basic physics of freeze casting. Thermal conductivity of the base plate is a crucial factor for obtaining controlled pore and porosity distribution in a porous scaffold. It was found that designing the base plate with variable thermal conductivity has led to the formation of bone-like structure. Porous scaffolds were quantitatively analyzed for pore size and porosity distribution at center and circumference. Porosity at circumference was observed to be approximately dropped by 55%, a similar trend was seen for pore size. Therefore, it was significant evidence that modified freeze casting has capable in fabricating bone-like structures with ease and good control. This will open many new applications of porous scaffolds in biomedical, energy devices, chemical catalyst and many more.
Saturn’s near-equatorial ionospheric conductivities from in situ measurements
Authors: Shebanits O. , Hadid L. Z. , Cao H. , Morooka M. W. , Hunt G. J. , Dougherty M. K. , Wahlund J.-E. , Waite J. H. , Müller-Wodarg I.
Published: May 2020

Cassini’s Grand Finale orbits provided for the first time in-situ measurements of Saturn’s topside ionosphere. We present the Pedersen and Hall conductivities of the top near-equatorial dayside ionosphere, derived from the in-situ measurements by the Cassini Radio and Wave Plasma Science Langmuir Probe, the Ion and Neutral Mass Spectrometer and the fluxgate magnetometer. The Pedersen and Hall conductivities are constrained to at least 10−5–10−4 S/m at (or close to) the ionospheric peak, a factor 10–100 higher than estimated previously. We show that this is due to the presence of dusty plasma in the near-equatorial ionosphere. We also show the conductive ionospheric region to be extensive, with thickness of 300–800 km. Furthermore, our results suggest a temporal variation (decrease) of the plasma densities, mean ion masses and consequently the conductivities from orbit 288 to 292.
Optical Absorption Exhibits Pseudo-Direct Band Gap of Wurtzite Gallium Phosphide
Authors: da Silva Bruno C. , Couto Odilon D. D. , Obata Hélio T. , de Lima Mauricio M. , Bonani Fábio D. , de Oliveira Caio E. , Sipahi Guilherme M. , Iikawa Fernando , Cotta Mônica A.
Published: May 2020

Definitive evidence for the direct band gap predicted for Wurtzite Gallium Phosphide (WZ GaP) nanowires has remained elusive due to the lack of strong band-to-band luminescence in these materials. In order to circumvent this problem, we successfully obtained large volume WZ GaP structures grown by nanoparticle-crawling assisted Vapor-Liquid-Solid method. With these structures, we were able to observe bound exciton recombination at 2.14 eV with FHWM of approximately 1 meV. In addition, we have measured the optical absorption edges using photoluminescence excitation spectroscopy. Our results show a 10 K band gap at 2.19 eV and indicate a weak oscillator strength for the lowest energy band-to-band absorption edge, which is a characteristic feature of a pseudo-direct band gap semiconductor. Furthermore, the valence band splitting energies are estimated as 110 meV and 30 meV for the three highest bands. Electronic band structure calculations using the HSE06 hybrid density functional agree qualitatively with the valence band splitting energies.
Intermittent hypoxia modulates redox homeostasis, lipid metabolism associated inflammatory processes and redox post-translational modifications: Benefits at high altitude
Authors: Gangwar Anamika , Paul Subhojit , Ahmad Yasmin , Bhargava Kalpana
Published: May 2020

Intermittent hypoxia, initially associated with adverse effects of sleep apnea, has now metamorphosed into a module for improved sports performance. The regimen followed for improved sports performance is milder intermittent hypoxic training (IHT) as compared to chronic and severe intermittent hypoxia observed in sleep apnea. Although several studies have indicated the mechanism and enough data on physiological parameters altered by IH is available, proteome perturbations remain largely unknown. Altitude induced hypobaric hypoxia is known to require acclimatization as it causes systemic redox stress and inflammation in humans. In the present study, a short IHT regimen consisting of previously reported physiologically beneficial FIO2 levels of 13.5% and 12% was administered to human subjects. These subjects were then airlifted to altitude of 3500 m and their plasma proteome along with associated redox parameters were analyzed on days 4 and 7 of high altitude stay. We observed that redox stress and associated post-translational modifications, perturbed lipid metabolism and inflammatory signaling were induced by IHT exposure at Baseline. However, this caused activation of antioxidants, energy homeostasis mechanisms and anti-inflammatory responses during subsequent high-altitude exposure. Thus, we propose IHT as a beneficial non-pharmacological intervention that benefits individuals venturing to high altitude areas.