Miracle-dz/UniFAR-FTUs huggingface dataset:
Circadian cycles are the dominant transcriptional rhythm in the intertidal mussel Mytilus californianus

Residents in the marine intertidal, the zone where terrestrial and marine habitats converge, inhabit an environment that is subject to both the 24-h day and night daily rhythm of the terrestrial earth and also the 12.4-h ebb and flow of the tidal cycle. Here, we investigate the relative contribution of the daily and tidal cycle on the physiology of intertidal mussels, Mytilus californianus, by monitoring rhythms of gene expression in both simulated and natural tidal environments. We report that >40% of the transcriptome exhibits rhythmic gene expression, and that depending on the specific tidal conditions, between 80% and 90% of the rhythmic transcripts follow a circadian expression pattern with a period of 24 to 26 h. Consistent with the dominant effect of the circadian cycle we show that the expression of clock genes oscillates with a 24-h period. Our data indicate that the circadian 24-h cycle is the dominant driver of rhythmic gene expression in this intertidal inhabitant despite the profound environmental and physiological changes associated with aerial exposure during tidal emergence.
SOX4 can redirect TGF-β-mediated SMAD3-transcriptional output in a context-dependent manner to promote tumorigenesis

Abstract Expression of the transcription factor SOX4 is often elevated in human cancers, where it generally correlates with tumor-progression and poor-disease outcome. Reduction of SOX4 expression results in both diminished tumor-incidence and metastasis. In breast cancer, TGF-β-mediated induction of SOX4 has been shown to contribute to epithelial-to-mesenchymal transition (EMT), which controls pro-metastatic events. Here, we identify SMAD3 as a novel, functionally relevant SOX4 interaction partner. Genome-wide analysis showed that SOX4 and SMAD3 co-occupy a large number of genomic loci in a cell-type specific manner. Moreover, SOX4 expression was required for TGF-β-mediated induction of a subset of SMAD3/SOX4-co-bound genes regulating migration and extracellular matrix-associated processes, and correlating with poor-prognosis. These findings identify SOX4 as an important SMAD3 co-factor controlling transcription of pro-metastatic genes and context-dependent shaping of the cellular response to TGF-β. Targeted disruption of the interaction between these factors may have the potential to disrupt pro-oncogenic TGF-β signaling, thereby impairing tumorigenesis.
Population pharmacokinetics of intravenously and orally administered docetaxel with or without co-administration of ritonavir in patients with advanced cancer.

AIM Docetaxel has a low oral bioavailability due to affinity for P-glycoprotein and cytochrome P450 (CYP) 3A4 enzymes. Inhibition of the CYP3A4 enzymes by ritonavir resulted in increased oral bioavailability. The aim of this study was to develop a population pharmacokinetic (PK) model and to evaluate and quantify the influence of ritonavir on the PK of docetaxel. METHODS Data from two clinical trials were included in the data analysis, in which docetaxel (75 mg m(-2) or 100 mg) had been administered intravenously or orally (10 mg or 100 mg) with or without co-administration of oral ritonavir (100 mg). Population modelling was performed using non-linear mixed effects modelling. A three-compartment model was used to describe the i.v. data. PK data after oral administration, with or without co-administration of ritonavir, were incorporated into the model. RESULTS Gut bioavailability of docetaxel increased approximately two-fold from 19 to 39% (CV 13%) with ritonavir co-administration. The hepatic extraction ratio and the elimination rate of docetaxel were best described by estimating the intrinsic clearance. Ritonavir was found to inhibit in a concentration dependent manner the intrinsic clearance of docetaxel, which was described by an inhibition constant of 0.028 microg ml(-1) (CV 36%). A maximum inhibition of docetaxel clearance of more then 90% was reached. CONCLUSIONS A PK model describing both the PK of orally and intravenously administered docetaxel in combination with ritonavir, was successfully developed. Co-administration of ritonavir lead to increased oral absorption and reduced elimination rate of docetaxel.
Self‐Assembly of Graphene Oxide at Interfaces

Due to its amphiphilic property, graphene oxide (GO) can achieve a variety of nanostructures with different morphologies (for example membranes, hydrogel, crumpled particles, hollow spheres, sack‐cargo particles, Pickering emulsions, and so on) by self‐assembly. The self‐assembly is mostly derived from the self‐concentration of GO sheets at various interfaces, including liquid‐air, liquid‐liquid and liquid‐solid interfaces. This paper gives a comprehensive review of these assembly phenomena of GO at the three types of interfaces, the derived interfacial self‐assembly techniques, and the as‐obtained assembled materials and their properties. The interfacial self‐assembly of GO, enabled by its fantastic features including the amphiphilicity, the negatively charged nature, abundant oxygen‐containing groups and two‐dimensional flexibility, is highlighted as an easy and well‐controlled strategy for the design and preparation of functionalized carbon materials, and the use of self‐assembly for uniform hybridization is addressed for preparing hybrid carbon materials with various functions. A number of new exciting and potential applications are also presented for the assembled GO‐based materials. This contribution concludes with some personal perspectives on future challenges before interfacial self‐assembly may become a major strategy for the application‐targeted design and preparation of functionalized carbon materials.
Quantitative assessment of Plasmodium falciparum sexual development reveals potent transmission-blocking activity by methylene blue

Clinical studies and mathematical models predict that, to achieve malaria elimination, combination therapies will need to incorporate drugs that block the transmission of Plasmodium falciparum sexual stage parasites to mosquito vectors. Efforts to measure the activity of existing antimalarials on intraerythrocytic sexual stage gametocytes and identify transmission-blocking agents have, until now, been hindered by a lack of quantitative assays. Here, we report an experimental system using P. falciparum lines that stably express gametocyte-specific GFP-luciferase reporters, which enable the assessment of dose- and time-dependent drug action on gametocyte maturation and transmission. These studies reveal activity of the first-line antimalarial dihydroartemisinin and the partner drugs lumefantrine and pyronaridine against early gametocyte stages, along with moderate inhibition of mature gametocyte transmission to Anopheles mosquitoes. The other partner agents monodesethyl-amodiaquine and piperaquine showed activity only against immature gametocytes. Our data also identify methylene blue as a potent inhibitor of gametocyte development across all stages. This thiazine dye almost fully abolishes P. falciparum transmission to mosquitoes at concentrations readily achievable in humans, highlighting the potential of this chemical class to reduce the spread of malaria.
Antarctic and Southern Ocean influences on Late Pliocene global cooling

The influence of Antarctica and the Southern Ocean on Late Pliocene global climate reconstructions has remained ambiguous due to a lack of well-dated Antarctic-proximal, paleoenvironmental records. Here we present ice sheet, sea-surface temperature, and sea ice reconstructions from the ANDRILL AND-1B sediment core recovered from beneath the Ross Ice Shelf. We provide evidence for a major expansion of an ice sheet in the Ross Sea that began at ∼3.3 Ma, followed by a coastal sea surface temperature cooling of ∼2.5 °C, a stepwise expansion of sea ice, and polynya-style deep mixing in the Ross Sea between 3.3 and 2.5 Ma. The intensification of Antarctic cooling resulted in strengthened westerly winds and invigorated ocean circulation. The associated northward migration of Southern Ocean fronts has been linked with reduced Atlantic Meridional Overturning Circulation by restricting surface water connectivity between the ocean basins, with implications for heat transport to the high latitudes of the North Atlantic. While our results do not exclude low-latitude mechanisms as drivers for Pliocene cooling, they indicate an additional role played by southern high-latitude cooling during development of the bipolar world.
Photosensitive Graphene Transistors

High performance photodetectors play important roles in the development of innovative technologies in many fields, including medicine, display and imaging, military, optical communication, environment monitoring, security check, scientific research and industrial processing control. Graphene, the most fascinating two‐dimensional material, has demonstrated promising applications in various types of photodetectors from terahertz to ultraviolet, due to its ultrahigh carrier mobility and light absorption in broad wavelength range. Graphene field effect transistors are recognized as a type of excellent transducers for photodetection thanks to the inherent amplification function of the transistors, the feasibility of miniaturization and the unique properties of graphene. In this review, we will introduce the applications of graphene transistors as photodetectors in different wavelength ranges including terahertz, infrared, visible, and ultraviolet, focusing on the device design, physics and photosensitive performance. Since the device properties are closely related to the quality of graphene, the devices based on graphene prepared with different methods will be addressed separately with a view to demonstrating more clearly their advantages and shortcomings in practical applications. It is expected that highly sensitive photodetectors based on graphene transistors will find important applications in many emerging areas especially flexible, wearable, printable or transparent electronics and high frequency communications.
Dysregulation of Kruppel-like factor 4 during brain development leads to hydrocephalus in mice

Kruppel-like factor 4 (KLF4) is involved in self-renewal of embryonic stem cells and reprogramming of somatic cells to pluripotency. However, its role in lineage-committed stem cells remains largely unknown. Here, we show that KLF4 is expressed in neural stem cells (NSCs) and is down-regulated during neuronal differentiation. Unexpectedly, enhanced expression of KLF4 reduces self-renewal of cultured NSCs and inhibits proliferation of subventricular neural precursors in transgenic mice. Mice with increased KLF4 in NSCs and NSCs-derived ependymal cells developed hydrocephalus-like characteristics, including enlarged ventricles, thinned cortex, agenesis of the corpus callosum, and significantly reduced subcommissural organ. These characteristics were accompanied by elevation of GFAP expression and astrocyte hypertrophy. The ventricular cilia, vital for cerebrospinal fluid flow, are also disrupted in the mutant mice. These results indicate that down-regulation of KLF4 is critical for neural development and its dysregulation may lead to hydrocephalus.
Role of ribosome assembly in Escherichia coli ribosomal RNA degradation

Abstract DEAD-Box proteins (DBPs) constitute a prominent class of RNA remodeling factors that play a role in virtually all aspects of RNA metabolism. To better define their cellular functions, deletions in the genes encoding each of the Escherichia coli DBPs were combined with mutations in genes encoding different Ribonucleases (RNases). Significantly, double-deletion strains lacking Ribonuclease R (RNase R) and either the DeaD or SrmB DBP were found to display growth defects and an enhanced accumulation of ribosomal RNA (rRNA) fragments. As RNase R is known to play a key role in removing rRNA degradation products, these observations initially suggested that these two DBPs could be directly involved in the same process. However, additional investigations indicated that DeaD and SrmB-dependent rRNA breakdown is caused by delays in ribosome assembly that increase the exposure of nascent RNAs to endonucleolytic cleavage. Consistent with this notion, mutations in factors known to be important for ribosome assembly also resulted in enhanced rRNA breakdown. Additionally, significant levels of rRNA breakdown products could be visualized in growing cells even in the absence of assembly defects. These findings reveal a hitherto unappreciated mechanism of rRNA degradation under conditions of both normal and abnormal ribosome assembly.
Fiber‐Based Wearable Electronics: A Review of Materials, Fabrication, Devices, and Applications

Fiber‐based structures are highly desirable for wearable electronics that are expected to be light‐weight, long‐lasting, flexible, and conformable. Many fibrous structures have been manufactured by well‐established lost‐effective textile processing technologies, normally at ambient conditions. The advancement of nanotechnology has made it feasible to build electronic devices directly on the surface or inside of single fibers, which have typical thickness of several to tens microns. However, imparting electronic functions to porous, highly deformable and three‐dimensional fiber assemblies and maintaining them during wear represent great challenges from both views of fundamental understanding and practical implementation. This article attempts to critically review the current state‐of‐arts with respect to materials, fabrication techniques, and structural design of devices as well as applications of the fiber‐based wearable electronic products. In addition, this review elaborates the performance requirements of the fiber‐based wearable electronic products, especially regarding the correlation among materials, fiber/textile structures and electronic as well as mechanical functionalities of fiber‐based electronic devices. Finally, discussions will be presented regarding to limitations of current materials, fabrication techniques, devices concerning manufacturability and performance as well as scientific understanding that must be improved prior to their wide adoption.
Resultados das tenorrafias em flexores dos dedos da mão, na zona II, submetidos a movimentação precoce passiva assistida

Avaliamos os resultados de 50 dedos das maos, de 29 pacientes, com lesao dos tendoes flexores, na zona II, submetidos a tenorrafia e a "movimentacao precoce passiva assistida" pos-operatoria. Quanto a tecnica cirurgica, utilizou-se a incisao em ziguezague, abertura da bainha e ponto de Kessler modificado com reforco do epitendao. O inicio da movimentacao precoce ocorreu entre o 2o e o 8o dia por meio de exercicios passivos realizados por terapeutas da mao. Os pacientes foram avaliados apos seguimento de, no minimo, seis meses. Obtivemos 72 por cento de resultados satisfatorios (excelentes e bons) quando avaliados pelo metodo TAM da FISCM e 58 por cento, quando avaliados pelo metodo de Strickland. Nao houve nenhum caso de rotura no sitio da sutura, ou qualquer complicacao com o metodo. (AU)
Community differentiation and kinship among Europe’s first farmers

Community differentiation is a fundamental topic of the social sciences, and its prehistoric origins in Europe are typically assumed to lie among the complex, densely populated societies that developed millennia after their Neolithic predecessors. Here we present the earliest, statistically significant evidence for such differentiation among the first farmers of Neolithic Europe. By using strontium isotopic data from more than 300 early Neolithic human skeletons, we find significantly less variance in geographic signatures among males than we find among females, and less variance among burials with ground stone adzes than burials without such adzes. From this, in context with other available evidence, we infer differential land use in early Neolithic central Europe within a patrilocal kinship system.
Kax and kol: Collapse and resilience in lowland Maya civilization

Episodes of population loss and cultural change, including the famous Classic Collapse, punctuated the long course of Maya civilization. In many cases, these downturns in the fortunes of individual sites and entire regions included significant environmental components such as droughts or anthropogenic environmental degradation. Some afflicted areas remained depopulated for long periods, whereas others recovered more quickly. We examine the dynamics of growth and decline in several areas in the Maya Lowlands in terms of both environmental and cultural resilience and with a focus on downturns that occurred in the Terminal Preclassic (second century Common Era) and Terminal Classic (9th and 10th centuries CE) periods. This examination of available data indicates that the elevated interior areas of the Yucatán Peninsula were more susceptible to system collapse and less suitable for resilient recovery than adjacent lower-lying areas.
Breakfast consumption in UK schoolchildren and provision of school breakfast clubs

Summary Breakfast is known to confer benefits for children, including improvement in nutrient and weight status as well as cognitive performance. Reliable UK-specific data regarding breakfast consumption patterns in schoolchildren and the provision of breakfast clubs in schools are limited, but are required to inform academics and policy makers alike. The aim of this study was to establish patterns in breakfast consumption in UK schoolchildren and to assess the current provision of breakfast clubs in England. Data were gathered by Childwise in June–July 2011. The large population representative sample included a total of 65 schools (38 primary and 27 secondary), from which 3311 children aged 5–15 years were surveyed at school regarding their breakfast consumption. Data regarding school breakfast club provision were collected from 2087 teachers via the National Foundation for Educational Research omnibus. The results indicated that 86% of children ate something before school (whether at home, on the way to school or at a school breakfast club). Of the remaining 14% of breakfast skippers, a third reported not eating anything until lunch time. The extent of breakfast skipping was higher in girls than boys, and higher in secondary than primary school pupils. Breakfast skipping also varied by UK region, such that the highest levels were evident in Scotland and the North West of England, and the lowest in the East of England. Within secondary schools, breakfast skipping was higher in schools from urban areas and areas of high deprivation. Of the 86% of children who did eat breakfast, 4% reported consuming it at a school breakfast club and a further 4% on the way to school. In contrast, 56% of schools in England were found to be operating a breakfast club at the time of survey, with greater availability at primary compared with secondary school. Overall, the findings suggest that breakfast skipping remains a considerable problem in UK schoolchildren, particularly in adolescents.
Natural disasters and population mobility in Bangladesh

The consequences of environmental change for human migration have gained increasing attention in the context of climate change and recent large-scale natural disasters, but as yet relatively few large-scale and quantitative studies have addressed this issue. We investigate the consequences of climate-related natural disasters for long-term population mobility in rural Bangladesh, a region particularly vulnerable to environmental change, using longitudinal survey data from 1,700 households spanning a 15-y period. Multivariate event history models are used to estimate the effects of flooding and crop failures on local population mobility and long-distance migration while controlling for a large set of potential confounders at various scales. The results indicate that flooding has modest effects on mobility that are most visible at moderate intensities and for women and the poor. However, crop failures unrelated to flooding have strong effects on mobility in which households that are not directly affected but live in severely affected areas are the most likely to move. These results point toward an alternate paradigm of disaster-induced mobility that recognizes the significant barriers to migration for vulnerable households as well their substantial local adaptive capacity.
Pharmacokinetics of linagliptin in subjects with hepatic impairment.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Linagliptin is an oral, highly selective dipeptidyl peptidase-4 (DPP-4) inhibitor that was approved in the United States, Europe and elsewhere in 2011 for the treatment of type 2 diabetes mellitus. • The elimination of linagliptin is primarily non-renal. Therefore, a potential effect of hepatic impairment on the elimination of linagliptin may have important implications for dosing recommendations. WHAT THIS STUDY ADDS • This study shows that mild, moderate or severe hepatic impairment did not result in an increase in linagliptin exposure after single and multiple dosing as compared with normal hepatic function. • No linagliptin dose adjustment is required in patients with any degree of hepatic impairment. AIM To investigate whether hepatic impairment affects linagliptin pharmacokinetics, pharmacodynamics and tolerability. METHOD This open label, parallel group, single centre study enrolled patients with mild (n= 8), moderate (n= 9) or severe (n= 8) hepatic impairment and healthy subjects (n= 8). Groups were matched with regard to age, weight and gender. Primary endpoints were linagliptin exposure following 5 mg linagliptin once daily for 7 days in patients with mild and moderate hepatic impairment vs. healthy subjects or after a single 5 mg dose for patients with severe hepatic impairment vs. healthy subjects. RESULTS In mild hepatic impairment, steady-state linagliptin exposure was slightly lower than in healthy subjects [AUC(τ,ss) geometric mean ratio (GMR) 75.5%, 90% confidence interval (CI) 61.6%, 92.5%, and C(max,ss) GMR 64.4%, 90% CI 43.2%, 96.0%]. Exposure also tended to be lower in moderate hepatic impairment (AUC(τ,ss) GMR 85.5%, 90% CI 70.2%, 104.2% and C(max,ss) GMR 92.3%, 90% CI 62.8%, 135.6%). After a single dose, AUC(0,24 h) in patients with severe hepatic impairment was similar to that in healthy subjects (GMR 100.4%, 90% CI 75.0%, 134.3%) and C(max) was lower (GMR 77.0%, 90% CI 44.9%, 132.3%). Accumulation based on AUC or C(max) and renal excretion of unchanged linagliptin (≤ 7%) were comparable across groups. Median plasma DPP-4 inhibition was similar in healthy subjects (91%), and patients with mild (90%) and moderate (89%) hepatic impairment at steady-state trough concentrations, and in patients with severe hepatic impairment 24 h after a single dose (84%). Linagliptin was well tolerated. CONCLUSION Mild, moderate or severe hepatic impairment did not result in an increase in linagliptin exposure after single and multiple dosing compared with normal hepatic function. Dose adjustment with linagliptin is not required in patients with hepatic impairment.