The cradle of heaven-human induction idealism: agricultural intensification, environmental consequences and social responses in Han China and Three-Kingdoms Korea

Han China (206 bc–ad 220) witnessed significant population growth, pronounced technological development, intensified agricultural practices and the construction of large-scale hydraulic engineering projects in the Yellow River. These processes coincided with increased frequency and intensity of major floods along the Yellow River. The interactions between flooding and social-technical developments fundamentally reshaped the politics of the Han and stimulated the formation of so-called heaven-human induction idealism. This Confucian environmental ethic gradually became a powerful orthodoxy that shaped political and economic behaviours and society’s perspective on and actions towards utilizing environmental resources and transforming landscapes. Similar processes played out in Three-Kingdoms Korea (ad 300–668). The Korean case exemplifies how, as in China, this idealism was a product of the long-term interplay between state formation and the environment through the development of intensive agriculture

Expression of the long non-coding RNA TCL6 is associated with clinical outcome in pediatric B-cell acute lymphoblastic leukemia

The authors would like to thank the Deutsche José Carreras Leukämie-Stiftung, Inocente Inocente Foundation, the Ministry of Economy of Spain (SAF2015- 67919-R), Consejería de Salud de la Junta de Andalucía (Pl-0245-2017, CS2016- 3), BBVA Foundation, Francisco-Cobos Foundation, Fero Foundation and AECC Foundation for funding Pedro P. Medinas’s lab. Álvaro Andrades is supported by an FPU17/00067 PhD fellowship, Alberto M. Arenas is supported by an FPU17/01258 PhD fellowship, Paola Peinado is supported by a La Caixa Foundation PhD Fellowship (LCF/BQ/DE15/10360019), Isabel F. Coira was supported by a PhD FPI-fellowship (BES-2013-064596), Daniel J. García is supported by a Fundación Benéfica Anticáncer Santa Cándida y San Francisco Javier PhD fellowship and Juan Carlos Álvarez-Pérez is supported by a Marie Sklodowska Curie action (H2020-MSCA-IF-2018). The funding agencies had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript. The authors would also like to thank the Biobanc de l’Hospital Infantil Sant Joan de Déu per a la Investigació, integrated in the Spanish Biobank Network of ISCIII, as well as Asociación Malagueña para la Investigación en Leucemias (AMPILE), for the sample and data procurement

Fibronectin-Containing Extracellular Vesicles Protect Melanocytes against Ultraviolet Radiation-Induced Cytotoxicity.

Skin melanocytes are activated by exposure to UV radiation to secrete melanin-containing melanosomes to protect the skin from UV-induced damage. Despite the continuous renewal of the epidermis, the turnover rate of melanocytes is very slow, and they survive for long periods. However, the mechanisms underlying the survival of melanocytes exposed to UV radiation are not known. Here, we investigated the role of melanocyte-derived extracellular vesicles in melanocyte survival. Network analysis of the melanocyte extracellular vesicle proteome identified the extracellular matrix component fibronectin at a central node, and the release of fibronectin-containing extracellular vesicles was increased after exposure of melanocytes to UVB radiation. Using an anti-fibronectin neutralizing antibody and specific inhibitors of extracellular vesicle secretion, we demonstrated that extracellular vesicles enriched in fibronectin were involved in melanocyte survival after UVB radiation. Furthermore, we observed that in the hyperpigmented lesions of patients with melasma, the extracellular space around melanocytes contained more fibronectin compared with normal skin, suggesting that fibronectin is involved in maintaining melanocytes in pathological conditions. Collectively, our findings suggest that melanocytes secrete fibronectin-containing extracellular vesicles to increase their survival after UVB radiation. These data provide important insight into how constantly stimulated melanocytes can be maintained in pathological conditions such as melasma.1166Ysciescopu

Membrane-Associated Transporter Protein (MATP) Regulates Melanosomal pH and Influences Tyrosinase Activity

The SLC45A2 gene encodes a Membrane-Associated Transporter Protein (MATP). Mutations of this gene cause oculocutaneous albinism type 4 (OCA4). However, the molecular mechanism of its action in melanogenesis has not been elucidated. Here, we discuss the role of MATP in melanin production. The SLC45A2 gene is highly enriched in human melanocytes and melanoma cell lines, and its protein, MATP, is located in melanosomes. The knockdown of MATP using siRNAs reduced melanin content and tyrosinase activity without any morphological change in melanosomes or the expression of melanogenesis-related proteins. Interestingly, the knockdown of MATP significantly lowered the melanosomal pH, as verified through DAMP analysis, suggesting that MATP regulates melanosomal pH and therefore affects tyrosinase activity. Finally, we found that the reduction of tyrosinase activity associated with the knockdown of MATP was readily recovered by copper treatment in the in vitro L-DOPA oxidase activity assay of tyrosinase. Considering that copper is an important element for tyrosinase activity and that its binding to tyrosinase depends on melanosomal pH, MATP may play an important role in regulating tyrosinase activity via controlling melanosomal pH.112820Ysciescopu

Reducing appointment lead-time in an outpatient department of gynecology and obstetrics through discrete-event simulation: A case study

Appointment lead-time is a critical variable in outpatient clinic services. In Gynecology and Obstetrics departments, longer appointment lead times are associated with lower patient satisfaction, the use of more complex healthcare services, development of long-term and severe complications and the increase of fetal, infant and maternal mortality rates. This paper aims to define and evaluate improvement alternatives through the use of Discrete-event simulation (DES). First, input data analysis is performed. Second, the simulation model is created; then, performance metrics are calculated and analyzed. Finally, improvement scenarios are designed and assessed. A case study of a mixed-patient type environment (Perinatology and Gynecobstetrics) in an outpatient department has been explored to verify the effectiveness of the proposed approach. Statistical analysis evidence that appointment lead times could be significantly reduced in both Perinatology and Gynecobstetrics appointments based on the proposed approaches in this paper

Manganese and acute paranoid psychosis: a case report

Contains fulltext : 103167.pdf (publisher's version ) (Open Access)Introduction Manganese regulates many enzymes and is essential for normal development and body function. Chronic manganese intoxication has an insidious and progressive course and usually starts with complaints of headache, fatigue, sleep disturbances, irritability and emotional instability. Later, several organ systems may be affected and, due to neurotoxicity, an atypical parkinsonian syndrome may emerge. With regard to neuropsychiatry, an array of symptoms may develop up to 30 years after intoxication, of which gait and speech abnormalities, cognitive and motor slowing, mood changes and hallucinations are the most common. Psychotic phenomena are rarely reported. Case presentation We describe the case of a 49-year-old Caucasian man working as a welder who was referred to our facility for evaluation of acute paranoid psychotic behavior. Our patient's medical history made no mention of any somatic complaints or psychiatric symptoms, and he had been involved in a professional career as a metalworker. On magnetic resonance imaging scanning of his brain, a bilateral hyperdensity of the globus pallidus, suggestive for manganese intoxication, was found. His manganese serum level was 52 to 97 nmol/L (range: 7 to 20 nmol/L). A diagnosis of organic psychotic disorder due to manganese overexposure was made. His psychotic symptoms disappeared within two weeks of treatment with low-dose risperidone. At three months later, serum manganese was decreased to slightly elevated levels and the magnetic resonance imaging T1 signal intensity was reduced. No signs of Parkinsonism were found and a definite diagnosis of manganese-induced apathy syndrome was made. Conclusion Although neuropsychiatric and neurological symptoms caused by (chronic) manganese exposure have been reported frequently in the past, in the present day the disorder is rarely diagnosed. In this report we stress that manganese intoxication can still occur, in our case in a confined-space welder, and may present clinically with a paranoid psychotic state that necessitates a rapid diagnostic procedure in order to avoid the permanent structural brain damage that may occur with chronic exposure.4 p

New evidence for a massive black hole at the centre of the quiescent galaxy M32

Massive black holes are thought to reside at the centres of many galaxies, where they power quasars and active galactic nuclei. But most galaxies are quiescent, indicating that any central massive black hole present will be starved of fuel and therefore detectable only through its gravitational influence on the motions of the surrounding stars. M32 is a nearby, quiescent elliptical galaxy in which the presence of a black hole has been suspected; however, the limited resolution of the observational data and the restricted classes of models used to interpret this data have made it difficult to rule out alternative explanations, such as models with an anisotropic stellar velocity distribution and no dark mass or models with a central concentration of dark objects (for example, stellar remnants or brown dwarfs). Here we present high-resolution optical HST spectra of M32, which show that the stellar velocities near the centre of this galaxy exceed those inferred from previous ground-based observations. We use a range of general dynamical models to determine a central dark mass concentration of (3.4 +/- 1.6) x 10^6 solar masses, contained within a region only 0.3 pc across. This leaves a massive black hole as the most plausible explanation of the data, thereby strengthening the view that such black holes exist even in quiescent galaxies.Comment: 8 pages, LaTeX, 3 figures; mpeg animation of the stellar motions in M32 available at http://oposite.stsci.edu/pubinfo/Anim.htm

Androgenic and Estrogenic Response of Green Mussel Extracts from Singapore’s Coastal Environment Using a Human Cell-Based Bioassay

In the last decade, evidence of endocrine disruption in biota exposed to environmental pollutants has raised serious concern. Human cell-based bioassays have been developed to evaluate induced androgenic and estrogenic activities of chemical compounds. However, bioassays have been sparsely applied to environmental samples. In this study we present data on sex hormone activities in the green mussel, Perna viridis, in Singapore’s coastal waters. P. viridis is a common bioindicator of marine contamination, and this study is a follow-up to an earlier investigation that reported the presence of sex hormone activities in seawater samples from Singapore’s coastal environment. Specimens were collected from eight locations around the Singapore coastline and analyzed for persistent organic pollutants (POPs) and heavy metals. Tissue extracts were then screened for activities on androgen receptors (ARs) and estrogen receptors (ER-α and ER-β) using a reporter gene bio-assay based on a HeLa human cell line. Mussel extracts alone did not exhibit AR activity, but in the presence of the reference androgenic hormone dihydrotestosterone (DHT), activities were up to 340% higher than those observed for DHT alone. Peak activities were observed in locations adjacent to industrial and shipping activities. Estrogenic activities of the mussel extract both alone and in the presence of reference hormone were positive. Correlations were statistically investigated between sex hormone activities, levels of pollutants in the mussel tissues, and various biological parameters (specimen size, sex ratio, lipid and moisture content). Significant correlations exist between AR activities, in the presence of DHT, and total concentration of POPs (r = 0.725, p < 0.05)

Pan-active imidazolopiperazine antimalarials target the Plasmodium falciparum intracellular secretory pathway.

A promising new compound class for treating human malaria is the imidazolopiperazines (IZP) class. IZP compounds KAF156 (Ganaplacide) and GNF179 are effective against Plasmodium symptomatic asexual blood-stage infections, and are able to prevent transmission and block infection in animal models. But despite the identification of resistance mechanisms in P. falciparum, the mode of action of IZPs remains unknown. To investigate, we here combine in vitro evolution and genome analysis in Saccharomyces cerevisiae with molecular, metabolomic, and chemogenomic methods in P. falciparum. Our findings reveal that IZP-resistant S. cerevisiae clones carry mutations in genes involved in Endoplasmic Reticulum (ER)-based lipid homeostasis and autophagy. In Plasmodium, IZPs inhibit protein trafficking, block the establishment of new permeation pathways, and cause ER expansion. Our data highlight a mechanism for blocking parasite development that is distinct from those of standard compounds used to treat malaria, and demonstrate the potential of IZPs for studying ER-dependent protein processing