Miracle-dz/UniFAR-FTUs huggingface dataset:
Insulin Inhibits Cardiac Mesoderm, Not Mesendoderm, Formation During Cardiac Differentiation of Human Pluripotent Stem Cells and Modulation of Canonical Wnt Signaling Can Rescue This Inhibition

The study of the regulatory signaling hierarchies of human heart development is limited by a lack of model systems that can reproduce the precise developmental events that occur during human embryogenesis. The advent of human pluripotent stem cell (hPSC) technology and robust cardiac differentiation methods affords a unique opportunity to monitor the full course of cardiac induction in vitro. Here, we show that stage‐specific activation of insulin signaling strongly inhibited cardiac differentiation during a monolayer‐based differentiation protocol that used transforming growth factor β superfamily ligands to generate cardiomyocytes. However, insulin did not repress cardiomyocyte differentiation in a defined protocol that used small molecule regulators of canonical Wnt signaling. By examining the context of insulin inhibition of cardiomyocyte differentiation, we determined that the inhibitory effects by insulin required Wnt/β‐catenin signaling and that the cardiomyocyte differentiation defect resulting from insulin exposure was rescued by inhibition of Wnt/β‐catenin during the cardiac mesoderm (Nkx2.5+) stage. Thus, insulin and Wnt/β‐catenin signaling pathways, as a network, coordinate to influence hPSC differentiation to cardiomyocytes, with the Wnt/β‐catenin pathway dominant to the insulin pathway. Our study contributes to the understanding of the regulatory hierarchies of human cardiomyocyte differentiation and has implications for modeling human heart development. STEM CELLS2013;31:447–457
Expression of dimeric and tetrameric acetylcholinesterase isoforms on the surface of cultured bovine adrenal chromaffin cells

Acetylcholinesterase is a highly polymorphic enzyme, which can be anchored to the cell surface through several different mechanisms. Dimeric (G2) acetylcholinesterase isoforms are attached by a glycosylphosphatidyl‐inositol (GPI) linkage, whereas tetrameric (G4) forms are linked through a 20 kilodalton hydrophobic subunit. Although cells of haemopoietic origin contain large amounts of G2 GPI‐linked acetylcholinesterase, most tissues express only trace amounts of this isoform. We examined the expression of acetylcholinesterase isoforms in cultured bovine adrenal medullary chromaffin cells. Two major isoforms (G2 and G4) were identified on the cell surface. The G2 isoform, which accounted for approximately half the cell‐surface enzyme activity, was linked to the membrane through a GPI anchor. After treatment with diisopropylfluorophosphate to completely inhibit cellular acetylcholinesterase, the G4 isoform was found to be resynthesised and transported to the cell surface more rapidly than the G2 isoform. As the addition of GPI anchors is known to be a very rapid step, this finding suggested that the G2 and G4 isoforms might be transported to the cell surface by two different mechanisms. This conclusion was supported by results from subcellular fractionation experiments. The ratio of G4/G2 membrane‐bound acetylcholinesterase varied between different subcellular fractions. The membrane‐bound G2 isoform was greatly enriched in a high‐speed “microsomal” fraction. G4 acetylcholinesterase is known to be actively secreted by chromaffin cells in culture. Although the G4 isoform was present on the cell surface, most of the secreted enzyme was derived from an intracellular pool. Thus, it is unlikely that the cell‐surface G4 isoform contributes significantly to the pool of secreted enzyme. Instead, the expression of two different membrane‐bound isoforms may provide a means by which chromaffin cells can target the enzyme to different locations on the cell surface. © 1994 Wiley‐Liss, Inc.
A EuroPrevall review of factors affecting incidence of peanut allergy: priorities for research and policy

Peanuts are extensively cultivated around the world, providing a foodstuff that is both cheap to produce and nutritious. However, allergy to peanuts is of growing global concern, particularly given the severity of peanut‐allergic reactions, which can include anaphalaxis and death. Consequently, it is important to understand the factors related to the prevalence of peanut allergy in order to inform efforts to ameliorate or pre‐empt the condition. In this article we review evidence for the relevance of factors hypothesized to have some association with allergy prevalence, including both genetic and environmental factors. Although our analysis does indicate some empirical support for the importance of a number of factors, the key finding is that there are significant data gaps in the literature that undermine our ability to provide firm conclusions. We highlight these gaps, indicating questions that need to be addressed by future research.
Do females in advertisements reflect adolescents’ ideal female images?

Purpose – The purpose of this study was to investigate how Chinese adolescent girls and boys construct their own ideal female images in response to gendered advertisements based on Arnett’s (1995) theory of self-socialization and Hirschman and Thompson’s (1997) three interpretive strategies. A qualitative interview study was conducted for this purpose. Design/methodology/approach – Altogether, 32 adolescents aged 15-19 living in 16 different provinces in China were recruited for a face-to-face interview. Three advertisements were shown depicting an elegant woman, an urban sophisticated female and a strong woman, and interviewees were asked to describe the appearance, the personality and the work and family life of the female character in each advertisement. They were asked to choose one of them as most closely representing their ideal female image. Findings – The interviewees constructed their ideal female images from the advertisement that best suited their ideal appearance, personality and work and fami.
Evidence of an association between the vasopressin V1b receptor gene (AVPR1B) and childhood-onset mood disorders.

CONTEXT Disturbances in stress hormones have been implicated in mood disorders, in particular in the hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Arginine vasopressin (AVP) plays a crucial role in modulating the HPA axis under stress and does so through a G protein-coupled receptor, vasopressin V1b receptor (AVPR1b). OBJECTIVE To determine if genetic variation in AVPR1B could be contributing to vulnerability to mood disorders. DESIGN We genotyped single nucleotide polymorphisms (SNPs) across the AVPR1B gene in a family-based sample with childhood-onset mood disorders. Six SNPs were genotyped; 2 were novel nonsynonymous polymorphisms, and the other 4 were constituents of a haplotype that was previously shown to be protective against depression. SETTING Twenty-three mental health facilities in Hungary. PARTICIPANTS The sample was composed of 382 Hungarian nuclear families ascertained through affected probands with a diagnosis of childhood-onset mood disorder. MAIN OUTCOME MEASURES Association with childhood-onset mood disorders was tested using the transmission disequilibrium test, which measures the transmission frequency of alleles, or haplotypes, from parents to affected offspring. RESULTS Two of the AVPR1B SNPs showed association individually (Lys65Asn: chi(2) = 7.81, P = . 005; S4: chi(2) = 4.58, P = . 03); of particular interest is Lys65Asn, which causes an amino acid change in an intracellular protein domain. Haplotype analysis demonstrated significant overtransmission of the most frequent haplotype (chi(2)(3) = 22.42, P <. 001). Furthermore, stratifying the sample by sex established that the association was predominantly in affected females, which is consistent with previous observations. CONCLUSIONS We have found evidence to implicate the AVPR1B gene in the etiology of mood disorders, particularly in females. Antagonists of AVPR1b exhibit antidepressant qualities; hence, genetic variation in AVPR1B may have implications in HPA axis dysregulation in mood disorders.
TLR4/MD-2 activation by a synthetic agonist with no similarity to LPS

Significance The Toll-like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD-2) complex recognizes lipopolysaccharide (LPS) on Gram-negative bacteria to induce an innate immune response. Neoseptins, chemically synthesized peptidomimetics that bind and activate the mouse TLR4 (mTLR4)/MD-2 complex independent of LPS, were discovered through unbiased screening and reverse genetic studies, and improved by chemical modification. NMR and X-ray crystallography of the TLR4/MD-2/Neoseptin-3 complex determined the mechanism by which Neoseptin-3 activates mTLR4/MD-2 and triggers myeloid differentiation primary response gene 88- and Toll-interleukin 1 receptor domain-containing adaptor inducing IFN-beta-dependent signaling. Neoseptin-3 binds as a dimer within the hydrophobic pocket of MD-2, contacting residues distinct from those contacted by LPS or lipid A, yet triggering a conformational change very similar to that elicited by LPS or lipid A. Natural peptides might conceivably produce similar effects. Structurally disparate molecules reportedly engage and activate Toll-like receptor (TLR) 4 and other TLRs, yet the interactions that mediate binding and activation by dissimilar ligands remain unknown. We describe Neoseptins, chemically synthesized peptidomimetics that bear no structural similarity to the established TLR4 ligand, lipopolysaccharide (LPS), but productively engage the mouse TLR4 (mTLR4)/myeloid differentiation factor 2 (MD-2) complex. Neoseptin-3 activates mTLR4/MD-2 independently of CD14 and triggers canonical myeloid differentiation primary response gene 88 (MyD88)- and Toll-interleukin 1 receptor (TIR) domain-containing adaptor inducing IFN-beta (TRIF)-dependent signaling. The crystal structure mTLR4/MD-2/Neoseptin-3 at 2.57-Å resolution reveals that Neoseptin-3 binds as an asymmetrical dimer within the hydrophobic pocket of MD-2, inducing an active receptor complex similar to that induced by lipid A. However, Neoseptin-3 and lipid A form dissimilar molecular contacts to achieve receptor activation; hence strong TLR4/MD-2 agonists need not mimic LPS.
Protostoria: teoria e pratica

La ricerca sul periodo che in Italia viene oggi indicato con il termine di protostoria, ovvero sull'eta del bronzo e la prima eta del ferro, si avvale di categorie ben distinte (archeologiche e "storiche") collocandosi di fatto tra le scienze etno-antropologiche e le scienze dell'antichita. Il testo esamina in questa duplice prospettiva gli aspetti essenziali della disciplina, con particolare attenzione ai possibili modelli di organizzazione dei dati e di ricostruzione di societa protostoriche nel loro complesso, attraverso un esame critico delle fonti e delle metodologie della loro utilizzazione. Ampio spazio viene dedicato alla protostoria dell'Italia continentale con riferimento allo sviluppo di comunita socio-politiche.
Serum Zinc, Insulin-like Growth Factor-I and Insulin-like Growth Factor Binding Protein-3 Levels in Children with Type 1 Diabetes Mellitus

BACKGROUND Growth is impaired during the course of diabetes mellitus (DM). Derangement of the growth hormone/insulin-like growth factor (IGF) axis, insulinopenia and zinc deficiency are the possible causative factors of this impairment. Zn supplementation is proven to attenuate hyperglycemia in mice but its use to ameliorate impaired height is still a matter of discussion. OBJECTIVE To investigate serum Zn, IGF-I and IGF binding protein-3 (IGFBP-3) levels and to emphasize the potential beneficial effects of Zn supplementation for the prevention of growth failure in children with type 1 DM (DM1). PATIENTS AND METHODS Twenty-eight patients with DM1 and 15 control children were included in the study. Zn levels were measured by flame atomic absorption spectrophotometry; IGF-I and IGFBP-3 levels were measured by immunoradiometric assay. RESULTS Mean serum Zn levels were significantly lower in diabetic children taken as a whole and as their pubertal subgroup compared to the controls. Mean serum IGF-I and IGFBP-3 levels were significantly lower in both prepubertal and pubertal diabetic groups compared to those of control groups. CONCLUSION From the results of our study, it can be hypothesized that serum Zn levels should be closely monitored during the course of DM1 and supplementation may be given to patients, especially at the time of puberty. This hypothesis needs to be confirmed by further studies.
Application of various iterative reconstruction for quantitative 3D dynamic brain PET studies

Iterative image reconstruction algorithms may suffer from bias in case of poor statistics. The purpose of this study is: (1) to implement various existing and new iterative methods and (2) to evaluate the applicability of these methods for quantitative 3D brain PET studies. Various OSEM and weighted least squares (WLS) algorithms were implemented. WLS and WLS with OSEM start image (OS-EM-WLS) were implemented with and w/o nonnegativity constraints. Accuracy and precision were assessed using phantom and simulations studies. Clinical evaluation was performed for 3 tracers using 9 dynamic brain PET studies including arterial sampling. ROI analysis was performed to evaluate contrast, noise and bias. Simulations were used to generate variance images at various noise levels. Dynamic human brain scans were analysed using parametric Logan plot analysis. Phantom data showed that all methods with nonnegativity constraint showed bias up to a factor 4 in low activity areas. Algorithms that allowed negative values within sinogram and image space provided smallest bias. Simulations showed that WLS w/o constraint, but with an OSEM start image, provided lowest variance amongst all tested reconstruction methods. OS-EM-WLS was more accurate and showed lower variance than other methods tested. Finally, parametric Logan analysis showed that OS-EM-WLS agreed most with FBP. OS-EM-WLS provided most accurate results and is therefore a promising candidate for reconstruction of 3D brain PET studies.
Patterns of differential introgression in a salamander hybrid zone: inferences from genetic data and ecological niche modelling

Hybrid zones have yielded considerable insight into many evolutionary processes, including speciation and the maintenance of species boundaries. Presented here are analyses from a hybrid zone that occurs among three salamanders –Plethodon jordani, Plethodon metcalfi and Plethodon teyahalee– from the southern Appalachian Mountains. Using a novel statistical approach for analysis of non‐clinal, multispecies hybrid zones, we examined spatial patterns of variation at four markers: single‐nucleotide polymorphisms (SNPs) located in the mtDNA ND2 gene and the nuclear DNA ILF3 gene, and the morphological markers of red cheek pigmentation and white flecks. Concordance of the ILF3 marker and both morphological markers across four transects is observed. In three of the four transects, however, the pattern of mtDNA is discordant from all other markers, with a higher representation of P. metcalfi mtDNA in the northern and lower elevation localities than is expected given the ILF3 marker and morphology. To explore whether climate plays a role in the position of the hybrid zone, we created ecological niche models for P. jordani and P. metcalfi. Modelling results suggest that hybrid zone position is not determined by steep gradients in climatic suitability for either species. Instead, the hybrid zone lies in a climatically homogenous region that is broadly suitable for both P. jordani and P. metcalfi. We discuss various selective (natural selection associated with climate) and behavioural processes (sex‐biased dispersal, asymmetric reproductive isolation) that might explain the discordance in the extent to which mtDNA and nuclear DNA and colour‐pattern traits have moved across this hybrid zone.
Root coverage of advanced gingival recession: a comparative study between acellular dermal matrix allograft and subepithelial connective tissue grafts.

BACKGROUND Acellular dermal matrix allograft (ADMA) has successfully been applied as a substitute for free connective tissue grafts (CTG) in various periodontal procedures, including root coverage. The purpose of this study was to clinically compare the efficiency of ADMA and CTG in the treatment of gingival recessions > or = 4 mm. METHODS Seven patients with bilateral recession lesions participated. Fourteen teeth presenting gingival recessions > or = 4 mm were randomly treated with ADMA or CTG covered by coronally advanced flaps. Recession, probing depth, and width of keratinized tissue were measured preoperatively and 12 months postoperatively. Changes in these clinical parameters were calculated within and compared between groups and analyzed statistically. RESULTS Baseline recession, probing depth, and keratinized tissue width were similar for both groups. At 12 months, root coverage gain was 4.57 mm (89.1%) versus 4.29 mm (88.7%) (P = NS), and keratinized tissue gain was 0.86 mm (36%) versus 2.14 mm (107%) (P < 0.05) for ADMA and CTG, respectively. Probing depth remained unchanged (0.22 mm/0 mm), with no difference between the groups. CONCLUSIONS Recession defects may be covered using ADMA or CTG, with no practical difference. However, CTG results in significantly greater gain of keratinized gingiva.
Pregnancy and Interferon-τ Upregulate Gene Expression of Members of the 1-8 Family in the Bovine Uterus1

Abstract The 1-8 family (1-8U, 1-8D, Leu-13/9-27) of interferon (IFN)-inducible genes encodes proteins that are components of multimeric complexes involved with transduction of antiproliferative and homotypic adhesion signals. Human 1-8 family members are highly similar and are regulated by type 1 and type 2 IFNs. Because the bovine uterus is bathed in conceptus-derived IFNτ during early pregnancy, it was hypothesized that members of the 1-8 family were upregulated in the bovine uterus during early pregnancy. Oligonucleotide primers were designed based on human and rat 1-8U and Leu-13 cDNAs and used in reverse transcription polymerase chain reactions to amplify bovine cDNAs from endometrial RNA. The bovine 1-8U cDNA was sequenced, found to be 84% identical to the human 1-8U, and used to screen a bovine endometrial cDNA library to isolate the full-length 1-8U and Leu-13 cDNAs. The inferred amino acid sequences of bovine 1-8U and Leu-13 were 72% and 73% identical to their respective human counterparts. Bovine 1-8U and Leu-13 retain an amino acid motif that is conserved in other 1-8 family members and in some ubiquitin-conjugating enzymes (E2s). This motif is critical for function of E2s in covalently linking ubiquitin to targeted proteins. Northern blotting revealed that bovine endometrial 1-8U and Leu-13 mRNAs were upregulated on Day 15 of pregnancy (P < 0.0001) and continued to accumulate through Day 18 of pregnancy (P < 0.05) when compared with endometrium from nonpregnant cows. The bovine 1-8U and Leu-13 mRNAs were also upregulated (P < 0.05) by IFNτ (25 nM) within 3 h, continued to accumulate through 12 h, and reached a plateau at 12–24 h in cultured bovine endometrial cells. In situ hybridization revealed that mRNAs encoding 1-8 family members were heavily localized to glandular epithelium but also were present to a lesser extent in the luminal epithelium and stroma. The temporal upregulation of 1-8U and Leu-13 mRNAs by pregnancy and IFNτ and tissue distribution of these mRNAs paralleled closely that of the ubiquitin homolog, IFN-stimulated gene product 17. These IFN-induced proteins probably work together to prepare the endometrium for adhesion of the developing conceptus.
Diet and activity pattern of howler monkeys (Alouatta palliata) in Los Tuxtlas, Mexico: effects of habitat fragmentation and implications for conservation

Accelerated deforestation is causing the rapid loss and fragmentation of primary habitat for primates. Although the genus Alouatta is one of the most studied primate taxa under these circumstances, some results are contradictory and responses of howlers to habitat fragmentation are not yet clear. In this paper, we conduct a cross‐study of the available researches on mantled howlers (Alouatta palliata) in forest fragments in Los Tuxtlas, Mexico, to (1) describe the diet and activity pattern of howlers; (2) analyze the similarity in the diet across studies; and (3) relate both fragment size and howler population density with different characteristics of their diet, home range size, and activity pattern. Howlers consumed 181 plant species belonging to 54 families. Ficus was the most important taxa in the howlers' diet, followed by primary species such as Pterocarpus rohrii, Nectandra ambigens, Poulsenia armata, and Brosimum alicastrum. Secondary and non‐secondary light‐demanding plant species, which are representatives of disturbed habitat, contributed with a high percentage of their feeding time. Only 23% of the species consumed were the same across all the studies, suggesting that howlers adapt their diet to the food availability of their respective habitats. Population density is the best predictor of howlers' ecological and behavioral changes in response to forest fragmentation, probably owing to its relationship with food availability. Howlers respond to the increase in population densities by increasing the (1) diversity of food species in the diet; (2) consumption of non‐tree growth forms; and (3) consumption of new plant items. Home range size is also predicted by population density, but fragment size is a better predictor, probably owing to the fact that howler groups can overlap their home ranges. Our results emphasize the importance of conserving the larger fragments and increasing the size of small and medium‐sized ones. Am. J. Primatol. 69:1013–1029, 2007. © 2007 Wiley‐Liss, Inc.
Expression of CD90 on keratinocyte stem/progenitor cells

Background The identification and purification of keratinocyte stem cells (KSCs) that are capable of self‐renewal and maintenance of differentiating cell populations could contribute both to our understanding of the biology of these cells, and to significant clinical applications, such as the culturing of keratinocytes for transplantation to severe burn wounds. Here, we report the detection of CD90+ cells in cultured normal human epidermal keratinocytes and adult skin.
Experimentally induced habitat filtering in marine bacterial communities

We tested the habitat filtering hypothesis by measuring the phylogenetic structure in marine bacterial communities before and after experimentally induced stress. The habitat filtering hypothesis predicts that phylogenetic clustering (mean relatedness) should increase as the environment becomes suitable for only a subset of the original community. We show that community composition and phylogenetic structure were considerably changed with changes in salinity and dissolved organic carbon. Community composition showed no consistent patterns, while the phylogenetic relatedness between species consistently increased with treatment. We have no information about species interactions in our system, but the phylogenetic signal is strong enough to suggest that habitat filtering is the dominant assembly process. Our results support the hypothesis that habitat characteristics and environmental stress can 'filter' a community so that only closely related species can persist. This non-random phylogenetic signal also implies a relationship between ecologically relevant characteristics and species relatedness.