Latent TGF-beta binding protein-1 plays an important role in craniofacial development

Objective: This study aims to replicate the phenotype of Ltbp1 knockout mice in zebrafish, and to address the function of LTBP1 in craniofacial development. Methods: Whole mount in situ hybridization (WISH) of ltbp1 was performed at critical periods of zebrafish craniofacial development to explore the spatial-temporal expression pattern. Furthermore, we generated morpholino based knockdown model of ltbp1 to study the craniofacial phenotype. Results: WISH of ltbp1 was mainly detected in the mandibular jaw region, brain trunk, and internal organs such as pancreas and gallbladder. And ltbp1 colocalized with both sox9a and ckma in mandibular region. Morpholino based knockdown of ltbp1 results in severe jaw malformation. Alcian blue staining revealed severe deformity of Meckel's cartilage along with the absence of ceratobranchial. Three-dimension measurements of ltbp1 morphants jaws showed decrease in both mandible length and width and increase in open mouth distance. Expression of cartilage marker sox9a and muscle marker ckma was decreased in ltbp1 morphants. Conclusions: Our experiments found that ltbp1 was expressed in zebrafish mandibular jaw cartilages and the surrounding muscles. The ltbp1 knockdown zebrafish exhibited phenotypes consistent with Ltbp1 knockout mice. And loss of ltbp1 function lead to significant mandibular jaw defects and affect both jaw cartilages and surrounding muscles

Precise Orbit and Clock Products of Galileo, BDS and QZSS from MGEX Since 2018: Comparison and PPP Validation

In recent years, the development of new constellations including Galileo, BeiDou Navigation Satellite System (BDS) and Quasi-Zenith Satellite System (QZSS) have undergone dramatic changes. Since January 2018, about 30 satellites of the new constellations have been launched and most of the new satellites have been included in the precise orbit and clock products provided by the Multi Global Navigation Satellite System (Multi-GNSS) Experiment (MGEX). Meanwhile, critical issues including antenna parameters, yaw-attitude models and solar radiation pressure models have been continuously refined for these new constellations and updated into precise MGEX orbit determination and precise clock estimation solutions. In this context, MGEX products since 2018 are herein assessed by orbit and clock comparisons among individual analysis centers (ACs), satellite laser ranging (SLR) validation and precise point positioning (PPP) solutions. Orbit comparisons showed 3D agreements of 3–5 cm for Galileo, 8–9 cm for BDS-2 inclined geosynchronous orbit (IGSO), 12–18 cm for BDS-2 medium earth orbit (MEO) satellites, 24 cm for BDS-3 MEO and 11–16 cm for QZSS IGSO satellites. SLR validations demonstrated an orbit accuracy of about 3–4 cm for Galileo and BDS-2 MEO, 5–6 cm for BDS-2 IGSO, 4–6 cm for BDS-3 MEO and 5–10 cm for QZSS IGSO satellites. Clock products from different ACs generally had a consistency of 0.1–0.3 ns for Galileo, 0.2–0.5 ns for BDS IGSO/MEO and 0.2–0.4 ns for QZSS satellites. The positioning errors of kinematic PPP in Galileo-only mode were about 17–19 mm in the north, 13–16 mm in the east and 74–81 mm in the up direction, respectively. As for BDS-only PPP, positioning accuracies of about 14, 14 and 49 mm could be achieved in kinematic mode with products from Wuhan University applied

Wip1-dependent modulation of macrophage migration and phagocytosis

Macrophage accumulation within the vascular wall is a hallmark of atherosclerosis. Controlling macrophage conversion into foam cells remains a major challenge for treatment of atherosclerotic diseases. Here, we show that Wip1, a member of the PP2C family of Ser/Thr protein phosphatases, modulates macrophage migration and phagocytosis associated with atherosclerotic plaque formation. Wip1 deficiency increases migratory and phagocytic activities of the macrophage under stress conditions. Enhanced migration of Wip1-/- macrophages is mediated by Rac1-GTPase and PI3K/AKT signalling pathways. Elevated phagocytic ability of Wip1-/- macrophages is linked to CD36 plasma membrane recruitment that is regulated by AMPK activity. Our study identifies Wip1 as an intrinsic negative regulator of macrophage chemotaxis. We propose that Wip1-dependent control of macrophage function may provide avenues for preventing or eliminating plaque formation in atherosclerosis

Susceptibilities of Yersinia pestis to Twelve Antimicrobial Agents in China

Streptomycin is the preferred choice for therapy of plague in China and other countries. However, Yersinia pestis exhibiting plasmid-mediated antimicrobial agent–resistant traits had been reported in Madagascar. In this study, we evaluated the susceptibility of traditional or newer antimicrobial agents used for treatment and/or prophylaxis of plague. Following Clinical and Laboratory Standards Institute (CLSI) recommendations, the susceptibility of 12 antimicrobial agents was evaluated by the agar microdilution method in 1,012 strains of Y. pestis isolated from 1943 to 2017 in 12 natural plague foci in China. One clinical Y. pestis isolate (S19960127) was found to be highly resistant to streptomycin, while the strain was still sensitive to other 11 antibiotics, that is, ciprofloxacin, ofloxacin, kanamycin, chloramphenicol, ampicillin, ceftriaxone, cefuroxime, trimethoprim-sulfamethoxazole, tetracycline, spectinomycin and moxifloxacin. The remaining 1,011 Y. pestis strains in this study demonstrated susceptibility to the above-mentioned 12 antimicrobial agents. Antimicrobial sensitivity surveillance of Y. pestis isolates, including dynamic monitoring of streptomycin resistance during various clinical plague treatments, should be carried out routinely

A Novel Escherichia coli O157:H7 Clone Causing a Major Hemolytic Uremic Syndrome Outbreak in China

An Escherichia coli O157:H7 outbreak in China in 1999 caused 177 deaths due to hemolytic uremic syndrome. Sixteen outbreak associated isolates were found to belong to a new clone, sequence type 96 (ST96), based on multilocus sequence typing of 15 housekeeping genes. Whole genome sequencing of an outbreak isolate, Xuzhou21, showed that the isolate is phylogenetically closely related to the Japan 1996 outbreak isolate Sakai, both of which share the most recent common ancestor with the US outbreak isolate EDL933. The levels of IL-6 and IL-8 of peripheral blood mononuclear cells induced by Xuzhou21 and Sakai were significantly higher than that induced by EDL933. Xuzhou21 also induced a significantly higher level of IL-8 than Sakai while both induced similar levels of IL-6. The expression level of Shiga toxin 2 in Xuzhou21 induced by mitomycin C was 68.6 times of that under non-inducing conditions, twice of that induced in Sakai (32.7 times) and 15 times higher than that induced in EDL933 (4.5 times). Our study shows that ST96 is a novel clone and provided significant new insights into the evolution of virulence of E. coli O157:H7

Isolation and Characterization of Cytotoxic, Aggregative Citrobacter freundii

Citrobacter freundii is an infrequent but established cause of diarrhea in humans. However, little is known of its genetic diversity and potential for virulence. We analyzed 26 isolates, including 12 from human diarrheal patients, 2 from human fecal samples of unknown diarrheal status, and 12 from animals, insects, and other sources. Pulsed field gel electrophoresis using XbaI allowed us to divide the 26 isolates into 20 pulse types, while multi-locus sequence typing using 7 housekeeping genes allowed us to divide the 26 isolates into 6 sequence types (STs) with the majority belonging to 4 STs. We analyzed adhesion and cytotoxicity to HEp-2 cells in these 26 strains. All were found to adhere to HEp-2 cells. One strain, CF74, which had been isolated from a goat, showed the strongest aggregative adhesion pattern. Lactate dehydrogenase (LDH) released from HEp-2 cells was evaluated as a measure of cytotoxicity, averaging 7.46%. Strain CF74 induced the highest level of LDH, 24.3%, and caused >50% cell rounding, detachment, and death. We named strain CF74 “cytotoxic and aggregative C. freundii.” Genome sequencing of CF74 revealed that it had acquired 7 genomic islands, including 2 fimbriae islands and a type VI secretion system island, all of which are potential virulence factors. Our results show that aggregative adherence and cytotoxicity play an important role in the pathogenesis of C. freundii

La expresión de la causatividad en español y en chino : en la interfaz léxico-sintáctica

La causativitat, un concepte que es repeteix en diferents llengües, sempre ha estat un punt d'interès per a la lingüística generativa, que ha intentat analitzar la forma en què aquesta s'expressa en les diferents llengües. El present treball té com a objecte d'estudi els verbs causatius i les construccions causatives de l'espanyol i del xinès, amb la finalitat d'indagar en les seves distribucions i les seves propietats, així com de descriure i resumir els punts tant convergents com divergents entre les dues llengües, als quals intentem donar explicacions des del punt de vista de l'estructura argumental. Al mateix temps, també es fa una aproximació a les qüestions més discutides de la causativitat a la interfície lèxico-sintàctica. El treball es porta a terme des d'una perspectiva neoconstruccionista, amb el patró d'anàlisi basat en la teoria de l'estructura argumental de Hale i Keyser (1993) i Mateu (2002), la Morfologia Distribuïda proposta per Halle i Marantz (1993), el tractament de la v petita de Cuervo (2003), la Hipòtesi del nucli Veu de Kratzer (1996) i la teoria del nucli Aplicatiu de Pylkkänen (2002). Amb l'anàlisi que presentem, es conclou que les dues llengües tenen divergències importants en l'expressió de la causativitat. D'una banda, en la distribució, la manera més freqüent de l'espanyol correspon als verbs morfològics, mentre que en xinès els verbs compostos constitueixen la forma més recurrent. Això es deu a la diferència tipològica entre les dues llengües: l'espanyol, com a llengua flexiva, té la derivació com un procediment important en la formació de paraules; en canvi, el xinès, sent una llengua aïllant, es caracteritza per tenir nombroses paraules compostes. D'altra banda, en l'estructura, les construccions causatives de l'espanyol presenten més variants, mentre que l'ordre de paraules de les construccions causatives del xinès és més fix. La raó és que en el cas de l'espanyol el verb causatiu hacer i el verb en infinitiu poden formar un predicat complex, però en el cas del xinès el verb subordinat pertany a una predicació completa. O, millor dit, la mida de l'estructura del predicat subordinat difereix entre les dues llengües: el de l'espanyol és Sv i el de l'xinès és SComp. Això també confirma la natura sintètica de l'espanyol i la analiticitat del xinès, ja que una característica d'aquest darrer consisteix que els nuclis funcionals són massa febles com per desencadenar desplaçaments; per exemple, el verb causatiu shi no pot desencadenar el desplaçament del verb subordinat.La causatividad, un concepto que se repite en diferentes lenguas, siempre ha sido un punto de interés para la lingüística generativa, que ha intentado analizar la forma en que esta se expresa en las distintas lenguas. El presente trabajo tiene como objeto de estudio los verbos causativos y las construcciones causativas del español y del chino, con la finalidad de indagar en sus distribuciones y sus propiedades, así como de describir y resumir los puntos tanto convergentes como divergentes entre las dos lenguas, a los cuales intentamos dar explicaciones desde el punto de vista de la estructura argumental. Al mismo tiempo, también se hace una aproximación a las cuestiones más discutidas de la causatividad en la interfaz léxico-sintáctica. El trabajo se lleva a cabo desde una perspectiva neoconstruccionista, con el patrón de análisis basado en la teoría de estructura argumental de Hale y Keyser (1993) y Mateu (2002), la Morfología Distribuida propuesta por Halle y Marantz (1993), el tratamiento de la v pequeña de Cuervo (2003), la Hipótesis del núcleo Voz de Kratzer (1996) y la teoría del núcleo Aplicativo de Pylkkänen (2002). Con el análisis del trabajo concluimos que las dos lenguas tienen divergencias importantes en la expresión de la causatividad. Por un lado, en la distribución, la manera más abundante del español corresponde a los verbos morfológicos, mientras que en chino los verbos compuestos constituyen la forma más recurrente. Esto se debe a la diferencia tipológica entre las dos lenguas: el español, como una lengua flexiva, tiene la derivación como un procedimiento importante en la formación de palabras; en cambio, el chino, siendo una lengua aislante, se caracteriza por tener numerosas palabras compuestas. Por otra parte, en la estructura, las construcciones causativas del español presentan más variantes, mientras que el orden de palabras de las construcciones causativas del chino es más fijo. La razón reside en que en el caso del español el verbo causativo hacer y el verbo en infinitivo pueden formar un predicado complejo, pero en el caso del chino el verbo subordinado pertenece a una predicación completa. O, mejor dicho, el tamaño de la estructura del predicado subordinado difiere entre las dos lenguas, consideramos que el del español es Sv y el del chino es SComp. Esto también confirma la sinteticidad del español y la analiticidad del chino, puesto que una característica del último consiste en que los núcleos funcionales son débiles como para desencadenar desplazamientos, por ejemplo, el verbo causativo shi no puede desencadenar el desplazamiento del verbo subordinado.The causation, a concept that is repeated in different languages, has always been a point of interest for generative linguistics, which has tried to analyze the way in which it is expressed in different languages. The object of this study is to analyze the causative verbs and the causative constructions of Spanish and Chinese, in order to investigate their distributions and properties, as well as to describe and summarize both the convergent and divergent points between the two languages, to which we try to give explanations from the point of view of the argument structure. At the same time, an approach is also made to the most controversial questions of causation at the lexical-syntactic interface. The work is carried out from a neoconstructionist perspective, with the analysis pattern based on the semantic-relational structure theory of Hale and Keyser (1993) and Mateu (2002), the Distributed Morphology proposed by Halle and Marantz (1993), the treatment of the little v of Cuervo (2003), the Kratzer's Voice Hypothesis (1996) and the theory of Applicative proposed by Pylkkänen (2002). With the analysis of the work we conclude that the two languages have important divergences in the expression of causation. On the one hand, in the distribution, the most abundant form of Spanish corresponds to morphological verbs, while in Chinese compound verbs are the most recurrent form. This is due to the typological difference between the two languages: Spanish, as an inflectional language, has derivation as an important procedure in word formation; instead, Chinese, being an isolating language, is characterized by having numerous compound words. On the other hand, in the structure, the causative constructions in Spanish present more variants, while the word order of the causative constructions in Chinese is more fixed. The reason is that in the case of Spanish the causative verb hacer and the infinitive verb can form a complex predicate, but in the case of Chinese the subordinate verb belongs to a complete predication. Or rather, the size of the subordinate predicate structure differs between the two languages, we consider that of Spanish is vP and that of Chinese is CP. This also confirms the syntheticity of Spanish and the analyticity of Chinese, since a characteristic of the latter is that the functional heads are not strong enough to trigger displacements, for example, the causative verb shi cannot trigger the displacement of the subordinate verb

La expresión de la causatividad en español y en chino: en la interfaz léxico-sintáctica

La causativitat, un concepte que es repeteix en diferents llengües, sempre ha estat un punt d’interès per a la lingüística generativa, que ha intentat analitzar la forma en què aquesta s’expressa en les diferents llengües. El present treball té com a objecte d’estudi els verbs causatius i les construccions causatives de l’espanyol i del xinès, amb la finalitat d’indagar en les seves distribucions i les seves propietats, així com de descriure i resumir els punts tant convergents com divergents entre les dues llengües, als quals intentem donar explicacions des del punt de vista de l’estructura argumental. Al mateix temps, també es fa una aproximació a les qüestions més discutides de la causativitat a la interfície lèxico-sintàctica. El treball es porta a terme des d’una perspectiva neoconstruccionista, amb el patró d’anàlisi basat en la teoria de l’estructura argumental de Hale i Keyser (1993) i Mateu (2002), la Morfologia Distribuïda proposta per Halle i Marantz (1993), el tractament de la v petita de Cuervo (2003), la Hipòtesi del nucli Veu de Kratzer (1996) i la teoria del nucli Aplicatiu de Pylkkänen (2002). Amb l’anàlisi que presentem, es conclou que les dues llengües tenen divergències importants en l’expressió de la causativitat. D’una banda, en la distribució, la manera més freqüent de l’espanyol correspon als verbs morfològics, mentre que en xinès els verbs compostos constitueixen la forma més recurrent. Això es deu a la diferència tipològica entre les dues llengües: l’espanyol, com a llengua flexiva, té la derivació com un procediment important en la formació de paraules; en canvi, el xinès, sent una llengua aïllant, es caracteritza per tenir nombroses paraules compostes. D’altra banda, en l’estructura, les construccions causatives de l’espanyol presenten més variants, mentre que l’ordre de paraules de les construccions causatives del xinès és més fix. La raó és que en el cas de l’espanyol el verb causatiu hacer i el verb en infinitiu poden formar un predicat complex, però en el cas del xinès el verb subordinat pertany a una predicació completa. O, millor dit, la mida de l’estructura del predicat subordinat difereix entre les dues llengües: el de l’espanyol és Sv i el de l’xinès és SComp. Això també confirma la natura sintètica de l’espanyol i la analiticitat del xinès, ja que una característica d’aquest darrer consisteix que els nuclis funcionals són massa febles com per desencadenar desplaçaments; per exemple, el verb causatiu shi no pot desencadenar el desplaçament del verb subordinat.La causatividad, un concepto que se repite en diferentes lenguas, siempre ha sido un punto de interés para la lingüística generativa, que ha intentado analizar la forma en que esta se expresa en las distintas lenguas. El presente trabajo tiene como objeto de estudio los verbos causativos y las construcciones causativas del español y del chino, con la finalidad de indagar en sus distribuciones y sus propiedades, así como de describir y resumir los puntos tanto convergentes como divergentes entre las dos lenguas, a los cuales intentamos dar explicaciones desde el punto de vista de la estructura argumental. Al mismo tiempo, también se hace una aproximación a las cuestiones más discutidas de la causatividad en la interfaz léxico-sintáctica. El trabajo se lleva a cabo desde una perspectiva neoconstruccionista, con el patrón de análisis basado en la teoría de estructura argumental de Hale y Keyser (1993) y Mateu (2002), la Morfología Distribuida propuesta por Halle y Marantz (1993), el tratamiento de la v pequeña de Cuervo (2003), la Hipótesis del núcleo Voz de Kratzer (1996) y la teoría del núcleo Aplicativo de Pylkkänen (2002). Con el análisis del trabajo concluimos que las dos lenguas tienen divergencias importantes en la expresión de la causatividad. Por un lado, en la distribución, la manera más abundante del español corresponde a los verbos morfológicos, mientras que en chino los verbos compuestos constituyen la forma más recurrente. Esto se debe a la diferencia tipológica entre las dos lenguas: el español, como una lengua flexiva, tiene la derivación como un procedimiento importante en la formación de palabras; en cambio, el chino, siendo una lengua aislante, se caracteriza por tener numerosas palabras compuestas. Por otra parte, en la estructura, las construcciones causativas del español presentan más variantes, mientras que el orden de palabras de las construcciones causativas del chino es más fijo. La razón reside en que en el caso del español el verbo causativo hacer y el verbo en infinitivo pueden formar un predicado complejo, pero en el caso del chino el verbo subordinado pertenece a una predicación completa. O, mejor dicho, el tamaño de la estructura del predicado subordinado difiere entre las dos lenguas, consideramos que el del español es Sv y el del chino es SComp. Esto también confirma la sinteticidad del español y la analiticidad del chino, puesto que una característica del último consiste en que los núcleos funcionales son débiles como para desencadenar desplazamientos, por ejemplo, el verbo causativo shi no puede desencadenar el desplazamiento del verbo subordinado.The causation, a concept that is repeated in different languages, has always been a point of interest for generative linguistics, which has tried to analyze the way in which it is expressed in different languages. The object of this study is to analyze the causative verbs and the causative constructions of Spanish and Chinese, in order to investigate their distributions and properties, as well as to describe and summarize both the convergent and divergent points between the two languages, to which we try to give explanations from the point of view of the argument structure. At the same time, an approach is also made to the most controversial questions of causation at the lexical-syntactic interface. The work is carried out from a neoconstructionist perspective, with the analysis pattern based on the semantic-relational structure theory of Hale and Keyser (1993) and Mateu (2002), the Distributed Morphology proposed by Halle and Marantz (1993), the treatment of the little v of Cuervo (2003), the Kratzer’s Voice Hypothesis (1996) and the theory of Applicative proposed by Pylkkänen (2002). With the analysis of the work we conclude that the two languages have important divergences in the expression of causation. On the one hand, in the distribution, the most abundant form of Spanish corresponds to morphological verbs, while in Chinese compound verbs are the most recurrent form. This is due to the typological difference between the two languages: Spanish, as an inflectional language, has derivation as an important procedure in word formation; instead, Chinese, being an isolating language, is characterized by having numerous compound words. On the other hand, in the structure, the causative constructions in Spanish present more variants, while the word order of the causative constructions in Chinese is more fixed. The reason is that in the case of Spanish the causative verb hacer and the infinitive verb can form a complex predicate, but in the case of Chinese the subordinate verb belongs to a complete predication. Or rather, the size of the subordinate predicate structure differs between the two languages, we consider that of Spanish is vP and that of Chinese is CP. This also confirms the syntheticity of Spanish and the analyticity of Chinese, since a characteristic of the latter is that the functional heads are not strong enough to trigger displacements, for example, the causative verb shi cannot trigger the displacement of the subordinate verb.Universitat Autònoma de Barcelona. Programa de Doctorat en Filologia Espanyol

Identification and Evaluation of the Polycentric Urban Structure: An Empirical Analysis Based on Multi-Source Big Data Fusion

Identifying and evaluating polycentric urban spatial structure is essential for understanding and optimizing current urban development. In order to accurately identify the urban centers of the Guangdong–Hong Kong–Macao Greater Bay Area (GBA), this study firstly fused nighttime light data, POI data, and population migration data based on wavelet transform, then identified the polycentric spatial structure of the GBA by carrying out cluster and outlier analysis, and evaluated the level of different urban centers byconducting geographical weighted regression analysis. Using data fusion, we identified 4579.81 km² of the urban poly-center area in the GBA, with an identification accuracy of 93.22%. Although the number and spatial extent of the identified urban poly-centers are consistent with the GBA development plan outline, the poly-center level evaluation results are inconsistent with the development plan, which shows there are great differences in actual development levels among different cities in the GBA. By identifying and grading the polycentric spatial structure of the GBA, this study accurately analyzed the current spatial distribution and could provide policy implications for the GBA’s future development and planning