Miracle-dz/UniFAR-FTUs huggingface dataset:
Multi-scale kinetics of a field-directed colloidal phase transition

Polarizable colloids are expected to form crystalline equilibrium phases when exposed to a steady, uniform field. However, when colloids become localized this field-induced phase transition arrests and the suspension persists indefinitely as a kinetically trapped, percolated structure. We anneal such gels formed from magneto-rheological fluids by toggling the field strength at varied frequencies. This processing allows the arrested structure to relax periodically to equilibrium—colloid-rich, cylindrical columns. Two distinct growth regimes are observed: one in which particle domains ripen through diffusive relaxation of the gel, and the other where the system-spanning structure collapses and columnar domains coalesce apparently through field-driven interactions. There is a stark boundary as a function of magnetic field strength and toggle frequency distinguishing the two regimes. These results demonstrate how kinetic barriers to a colloidal phase transition are subverted through measured, periodic variation of driving forces. Such directed assembly may be harnessed to create unique materials from dispersions of colloids.
Tmem100, an ALK1 receptor signaling-dependent gene essential for arterial endothelium differentiation and vascular morphogenesis

Members of the transforming growth factor-β superfamily play essential roles in various aspects of embryonic development and physiological organ function. Among them, bone morphogenetic protein (BMP) 9 and BMP10 regulate embryonic vascular development by activating their endothelial receptor ALK1 (activin receptor-like kinase 1, also called Acvrl1). ALK1-mediated intracellular signaling is implicated in the etiologies of human diseases, but their downstream functional proteins are largely unknown. In this study, we identified Tmem100, a gene encoding a previously uncharacterized intracellular transmembrane protein, to be an embryonic endothelium-enriched gene activated by BMP9 and BMP10 through the ALK1 receptor. Tmem100 null mice showed embryonic lethality due to impaired differentiation of arterial endothelium and defects of vascular morphogenesis, which phenocopied most of the vascular abnormalities observed with the Acvrl1/Alk1 deficiency. The activity of Notch- and Akt-mediated signaling, which is essential for vascular development, was down-regulated in Tmem100 null mice. Cre-mediated deletion of Tmem100 in endothelial cells was sufficient to recapitulate the null phenotypes. These data indicated that TMEM100 may play indispensable roles downstream of BMP9/BMP10-ALK1 signaling during endothelial differentiation and vascular morphogenesis.
Intelligent MnO2 Nanosheets Anchored with Upconversion Nanoprobes for Concurrent pH‐/H2O2‐Responsive UCL Imaging and Oxygen‐Elevated Synergetic Therapy

Dr. W. Fan, Prof. W. Bu, Dr. Q. He, Dr. Z. Cui, Dr. Y. Liu, Prof. J. Shi State Key Laboratory of High Performance Ceramics and Superfi ne Microstructures Shanghai Institute of Ceramics Chinese Academy of Sciences Shanghai 200050 , P. R. China E-mail: wbbu@mail.sic. ac.cn; jlshi@mail.sic. ac.cn Prof. W. Bu Jiangsu Collaborative Innovation Center for Advanced Inorganic Functional Composites Nanjing Tech University Nanjing 210009 , P. R. China Dr. B. Shen Institute of Radiation Medicine Fudan University Shanghai 200032 , P. R. China Dr. X. Zheng Department of Radiation Oncology Shanghai Huadong Hospital Fudan University Shanghai 200040 , P. R. China Dr. K. Zhao Department of Radiology Shanghai Cancer Hospital Fudan University Shanghai 200032 , P. R. China
Classical subjective expected utility

We consider decision makers who know that payoff-relevant observations are generated by a process that belongs to a given class M, as postulated in Wald [Wald A (1950) Statistical Decision Functions (Wiley, New York)]. We incorporate this Waldean piece of objective information within an otherwise subjective setting à la Savage [Savage LJ (1954) The Foundations of Statistics (Wiley, New York)] and show that this leads to a two-stage subjective expected utility model that accounts for both state and model uncertainty.
MiR-494 is regulated by ERK1/2 and modulates TRAIL-induced apoptosis in non–small-cell lung cancer through BIM down-regulation

MicroRNAs (miRNAs) have an important role in the development of chemosensitivity or chemoresistance in different types of cancer. Activation of the ERK1/2 pathway is a major determinant of diverse cellular processes and cancer development and is responsible for the transcription of several important miRNAs. Here we show a link between the ERK1/2 pathway and BIM expression through miR-494. We blocked ERK1/2 nuclear activity through the overexpression of an ERK1/2 natural interactor, the protein PED/PEA15, and we performed a microRNA expression profile. miR-494 was the most down-regulated microRNA after ERK1/2 inactivation. Moreover, we found that miR-494 induced Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) resistance in non–small-cell lung cancer (NSCLC) through the down-modulation of BIM. Elucidation of this undiscovered ERK1/2 pathway that regulates apoptosis and cell proliferation through miR-494 in NSCLC will greatly enhance our understanding of the mechanisms responsible for TRAIL resistance and will provide an additional arm for the development of anticancer therapies.
Biotic interactions modify the effects of oxygen on insect gigantism

Size is one of the most significant and fascinating characteristics of all organisms. Its significance derives from the strong relationships, especially in animals, between body size and many physiological traits and ecological characteristics (1, 2). What makes size fascinating is its extremes. They not only compel wonder at deviation from the average for a given group (3), but also provide insight into the mechanisms underlying size variation (4). Among the insects, the giant forms of the late Paleozoic have perhaps captured most attention. Many species from this period were large by modern standards; an extreme case is a member of the aerial predator group, the Protodonata, with a wingspan of ca. 71 cm (5). Modern dragonflies have wingspans typically one-tenth of the size (6). How such gigantism could have arisen and why these large species subsequently disappeared have long been staples of biology (5, 7). Although several explanations for the rise and fall of insect giants have been proposed, the physiological limits to performance or fitness at a given size and the improvements (constraints) brought by higher (lower) atmospheric oxygen concentration (partial pressures) have garnered most attention (7, 8). In PNAS, the work by Clapham and Karr (9) uses a massive compilation of fossil data to show that biotic interactions, especially predation by birds, are plausibly responsible for a decoupling of size from oxygen concentration from the Early Cretaceous onward. Their findings bring a robust and fresh ecological perspective to the discussion of insect size variation.
Compensatory mechanisms for ameliorating the fundamental trade-off between predator avoidance and foraging

Most organisms face the problem of foraging and maintaining growth while avoiding predators. Typical animal responses to predator exposure include reduced feeding, elevated metabolism, and altered development rate, all of which can be beneficial in the presence of predators but detrimental in their absence. How then do animals balance growth and predator avoidance? In a series of field and greenhouse experiments, we document that the tobacco hornworm caterpillar, Manduca sexta, reduced feeding by 30–40% owing to the risk of predation by stink bugs, but developed more rapidly and gained the same mass as unthreatened caterpillars. Assimilation efficiency, extraction of nitrogen from food, and percent body lipid content all increased during the initial phase (1-3 d) of predation risk, indicating that enhanced nutritional physiology allows caterpillars to compensate when threatened. However, we report physiological costs of predation risk, including altered body composition (decreased glycogen) and reductions in assimilation efficiency later in development. Our findings indicate that hornworm caterpillars use temporally dynamic compensatory mechanisms that ameliorate the trade-off between predator avoidance and growth in the short term, deferring costs to a period when they are less vulnerable to predation.
Structural basis for Zn2+-dependent intercellular adhesion in staphylococcal biofilms

Significance Under adverse environmental conditions, bacteria can form specialized antibiotic-resistant colonies called “biofilms. ” In Staphylococcus epidermidis biofilms, a protein, Aap, links bacterial cells together but does so only in the presence of zinc ions. We have determined the atomic structure of an adhesive portion of Aap bound to zinc. The protein adopts an elongated, flexible fold with zinc ions bridging two protein chains. The mode of assembly indicates that Aap is likely to form twisted rope-like structures between bacterial cells. These data provide clues about regions of the protein that could be targeted to prevent intercellular adhesion in the developing biofilm. Staphylococcal bacteria, including Staphylococcus epidermidis and Staphylococcus aureus, cause chronic biofilm-related infections. The homologous proteins Aap and SasG mediate biofilm formation in S. epidermidis and S. aureus, respectively. The self-association of these proteins in the presence of Zn2+ leads to the formation of extensive adhesive contacts between cells. This study reports the crystal structure of a Zn2+-bound construct from the self-associating region of Aap. Several unusual structural features include elongated β-sheets that are solvent-exposed on both faces and the lack of a canonical hydrophobic core. Zn2+-dependent dimers are observed in three distinct crystal forms, formed via pleomorphic coordination of Zn2+ in trans across the dimer interface. These structures illustrate how a long, flexible surface protein is able to form tight intercellular adhesion sites under adverse environmental conditions.
Arthropods in amber from the Triassic Period

The occurrence of arthropods in amber exclusively from the Cretaceous and Cenozoic is widely regarded to be a result of the production and preservation of large amounts of tree resin beginning ca. 130 million years (Ma) ago. Abundant 230 million-year-old amber from the Late Triassic (Carnian) of northeastern Italy has previously yielded myriad microorganisms, but we report here that it also preserves arthropods some 100 Ma older than the earliest prior records in amber. The Triassic specimens are a nematoceran fly (Diptera) and two disparate species of mites, Triasacarus fedelei gen. et sp. nov., and Ampezzoa triassica gen. et sp. nov. These mites are the oldest definitive fossils of a group, the Eriophyoidea, which includes the gall mites and comprises at least 3,500 Recent species, 97% of which feed on angiosperms and represents one of the most specialized lineages of phytophagous arthropods. Antiquity of the gall mites in much their extant form was unexpected, particularly with the Triassic species already having many of their present-day features (such as only two pairs of legs); further, it establishes conifer feeding as an ancestral trait. Feeding by the fossil mites may have contributed to the formation of the amber droplets, but we find that the abundance of amber during the Carnian (ca. 230 Ma) is globally anomalous for the pre-Cretaceous and may, alternatively, be related to paleoclimate. Further recovery of arthropods in Carnian-aged amber is promising and will have profound implications for understanding the evolution of terrestrial members of the most diverse phylum of organisms.
Metastatic basal cell carcinoma: report of two cases treated with cetuximab

SIR, The article ‘The ultrastructure of acantholysis in pemphigus vulgaris’ by Drs Diercks, Pas and Jonkman confirms prior electron microscopic observations made by multiple investigators in patients with pemphigus and in in vitro and in vivo models of pemphigus acantholysis. These and the article by Diercks et al. show that the initial event in pemphigus acantholysis is the separation of keratinocytes from each other at sites where there are no desmosomes. Desmosomes do not separate from each other until very late in acantholysis, if at all. Often, desmosomes continue to stick so tightly to each other that they are ripped off from acantholytic keratinocytes without coming apart. We have previously summarized these and other observations and their implications. They lead to two important conclusions: (i) acantholysis in pemphigus is not caused by loss of desmosomal adhesion due to autoantibodies blocking the adhesive properties of desmogleins; and (ii) rather, they suggest acantholysis occurs because the cytoskeleton of keratinocytes is disrupted causing these cells to collapse and to shrink more than desmosomes can hold them together. We call this the ‘basal cell shrinkage hypothesis’. Recently published experimental results have further substantiated this hypothesis. We are pleased the observations of Diercks et al. provide further support for it.
EFFECT OF HYPERCHOLESTEROLEMIA AND ISOSORBIDE DINITRATE ADMINISTRATION ON SERUM NITRIC OXIDE AND SOME RELATED BIOCHEMICAL PARAMETERS IN MALE ALBINO RATS

: Isosorbide dinitrate "ISDN" is an organic nitrate that generates nitric oxide "NO" that helps in treatment of the vascular disturbance which results from metabolic hypercholesterolemia. Forty two adult male albino rats weighting 170-190 g were divided randomly into six groups, each of seven rats, as follows: control group (standard diet), coconut oil treated group (0.5 ml daily), cholesterol treated group (400 mg/kg BW dissolved in 0.5 ml coconut oil), ISDN treated group (1.0 mg/kg BW dissolved in 0.5 ml H 2 O), ISDN plus cholesterol treated group (ISDN + cholesterol) for 3 weeks and cholesterol followed with ISDN treated group (cholesterol for 3 weeks then ISDN for 3 weeks) by oral administration. Serum nitric oxide, antioxidant enzymes "superoxide dismutase (SOD) and glutathione peroxidase (GPx)" activities, lipid profile, glucose, uric acid, total protein, albumin and globulin percentage were determined. At the end of the experimental period, coconut oil treated group showed a significant increase in serum of both high density lipoprotein "HDL" and very low density lipoprotein "VLDL" and a significant decrease in serum SOD activity as compared to the control group. Cholesterol treated group showed a significant increase in total cholesterol "TC" and low density lipoprotein "LDL-C" and a significant decrease in NO level, SOD and GPx activity as compared to the control one. ISDN administration showed a significant increase in the triglyceride "TG", VLDL, and NO levels, but exhibited a significant decrease in LDL, albumin and GPx activity compared to control group. The ISDN plus cholesterol group showed a significant increase in LDL-C level and a significant decrease in albumin and GPx activity compared to the control one. The group treated with cholesterol followed with ISDN showed significant increase and decrease in HDL level and SOD activity, respectively compared to the control group. ISDN administration after cholesterol induction helped in the return of most studied parameters to the control values.
MANAGEMENT OF HEPATOCELLULAR JAUNDICE IN AYURVEDA

Hepatocellular jaundice arises because of damage to hepatic cells. Jaundice is a condition in whichyellowness of skin, sclerae, mucous membranes, and excretionsoccurs due to hyperbilirubinemia and deposition of bile pigments. It occurs when the ability of the liver to conjugate normal amounts of bilirubin into bilirubin diglucoronide is significantly reduced by inadequate intracellular transport or enzyme systems. In Ayurveda jaundice is described as kamla roga. Kamala has been described in detail along with its etiology, pathogenesis, symptoms, complications and management also. In Ayurveda kamala roga is divided into two parts and Hepatocellular jaundice is very similar to kosthashrita kamla. A lot of medicines either in form of kvatha , vati , churna or arista has been described during the description of treatment of kamla in Ayurveda. Here a case report of a 17 1/2-Years-male having jaundice with increased prothrombin time is being presented who was treated with Ayurveda effectively.
Global identification of MLL2-targeted loci reveals MLL2’s role in diverse signaling pathways

Myeloid/lymphoid or mixed-lineage leukemia (MLL)-family genes encode histone lysine methyltransferases that play important roles in epigenetic regulation of gene transcription. MLL genes are frequently mutated in human cancers. Unlike MLL1, MLL2 (also known as ALR/MLL4) and its homolog MLL3 are not well-understood. Specifically, little is known regarding the extent of global MLL2 involvement in the regulation of gene expression and the mechanism underlying its alterations in driving tumorigenesis. Here we profile the global loci targeted by MLL2. A combinatorial analysis of the MLL2 binding profile and gene expression in MLL2 wild-type versus MLL2-null isogenic cell lines identified direct transcriptional target genes and revealed the connection of MLL2 to multiple cellular signaling pathways, including the p53 pathway, cAMP-mediated signaling, and cholestasis signaling. In particular, we demonstrate that MLL2 participates in retinoic acid receptor signaling by promoting retinoic acid-responsive gene transcription. Our results present a genome-wide integrative analysis of the MLL2 target loci and suggest potential mechanisms underlying tumorigenesis driven by MLL2 alterations.
DIRECT COST OF TREATMENT OF DIABETES MELLITUS TYPE 2 IN PAKISTAN

Objective: Diabetes is a serious illness. It is a key and growing threat to the health of the global world. The prime concern of this research was to estimate the cost-of-illness of type 2 diabetes in Karachi, a major metropolitan city of Pakistan. This study was performed on the basis a community perspective to calculate the economic burden of diabetes mellitus type 2 in Pakistan. Methods: This study was conducted in all districts of Karachi, the patients were taken from all economic segment of society from low income group, average revenue and high revenue group. A preliminary test questionnaire was used to collect the data directly from patients and in some locations conducted interviews with patients due to lack of understanding and un-educated patients. The total of 885diabetes patients was selected with convenient random sampling. Results: The average direct cost of all these expense bear by diabetic patient in Pakistan is Pak Rupees Rs.5542 per month. The cost range starts from Rs. 650/month to 20000 per month on the basis of patient economic condition and disease state. The average appointment fee of a physician, laboratory test and medicines came to Rs. 700/visit, 400/test, and 1100/visit precisely. The average travel and food spent was Rs.200/visit and 1000/month. Medicine accounted for largest cost followed by consultation with the physician. Conclusion: This is clearly indicated by this study that considerable cost is amounted by diabetes, it is suggested that a huge amount of resources could be prevented by taking care, initial understanding of the disease and a decrease in diabetes co-morbidities and complications through better diabetes mellitus treatment. Very extensive and cost-effective programs should be started to maximize health benefits and to diminish the prevalence of this epidemic.
Growth of Carnobacterium spp. from permafrost under low pressure, temperature, and anoxic atmosphere has implications for Earth microbes on Mars

The ability of terrestrial microorganisms to grow in the near-surface environment of Mars is of importance to the search for life and protection of that planet from forward contamination by human and robotic exploration. Because most water on present-day Mars is frozen in the regolith, permafrosts are considered to be terrestrial analogs of the martian subsurface environment. Six bacterial isolates were obtained from a permafrost borehole in northeastern Siberia capable of growth under conditions of low temperature (0 °C), low pressure (7 mbar), and a CO2-enriched anoxic atmosphere. By 16S ribosomal DNA analysis, all six permafrost isolates were identified as species of the genus Carnobacterium, most closely related to C. inhibens (five isolates) and C. viridans (one isolate). Quantitative growth assays demonstrated that the six permafrost isolates, as well as nine type species of Carnobacterium (C. alterfunditum, C. divergens, C. funditum, C. gallinarum, C. inhibens, C. maltaromaticum, C. mobile, C. pleistocenium, and C. viridans) were all capable of growth under cold, low-pressure, anoxic conditions, thus extending the low-pressure extreme at which life can function.
Hypertension and aldosterone levels in women with early‐onset androgenetic alopecia

Background Few studies have analysed the relationship between androgenetic alopecia (AGA) in women and cardiovascular disease. There is reported to be an elevated prevalence of hypertension among men with AGA, and it has been proposed that both phenomena may be explained by the presence of hyperaldosteronism. However, no data on blood pressure (BP) and aldosterone levels in women with AGA have been published to date.
The association between null mutations in the filaggrin gene and contact sensitization to nickel and other chemicals in the general population

Background It was recently shown that filaggrin gene (FLG) null mutations are positively associated with nickel sensitization. We have hypothesized that histidine‐rich filaggrin proteins in the epidermis chelate nickel ions and prevent their skin penetration and exposure to Langerhans cells. Furthermore, we have proposed that the low degree of genetic predisposition to nickel sensitization found by a Danish twin study was explained by a high prevalence of ear piercing among participants resulting in ‘bypassing’ of the filaggrin proteins.
Laccase detoxification mediates the nutritional alliance between leaf-cutting ants and fungus-garden symbionts

Leaf-cutting ants combine large-scale herbivory with fungus farming to sustain advanced societies. Their stratified colonies are major evolutionary achievements and serious agricultural pests, but the crucial adaptations that allowed this mutualism to become the prime herbivorous component of neotropical ecosystems has remained elusive. Here we show how coevolutionary adaptation of a specific enzyme in the fungal symbiont has helped leaf-cutting ants overcome plant defensive phenolic compounds. We identify nine putative laccase-coding genes in the fungal genome of Leucocoprinus gongylophorus cultivated by the leaf-cutting ant Acromyrmex echinatior. One of these laccases (LgLcc1) is highly expressed in the specialized hyphal tips (gongylidia) that the ants preferentially eat, and we confirm that these ingested laccase molecules pass through the ant guts and remain active when defecated on the leaf pulp that the ants add to their gardens. This accurate deposition ensures that laccase activity is highest where new leaf material enters the fungus garden, but where fungal mycelium is too sparse to produce extracellular enzymes in sufficient quantities to detoxify phenolic compounds. Phylogenetic analysis of LgLcc1 ortholog sequences from symbiotic and free-living fungi revealed significant positive selection in the ancestral lineage that gave rise to the gongylidia-producing symbionts of leaf-cutting ants and their non–leaf-cutting ant sister group. Our results are consistent with fungal preadaptation and subsequent modification of a particular laccase enzyme for the detoxification of secondary plant compounds during the transition to active herbivory in the ancestor of leaf-cutting ants between 8 and 12 Mya.