Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulating Adipogenesis*

The raison d’etre of the adipocyte is to store energy (in the form of triacylglycerol) for use during periods of caloric insufficiency. Adipocytes first appear late in fetal development preparatory to postnatal life when a substantial energy reserve is needed to survive periods of fasting. Considerable progress has been made during the past few years in our understanding of the adipocyte differentiation program. This review will focus on the roles of the CAAT/enhancer binding protein (C/EBP) and peroxisome proliferator-activated receptor (PPAR) families of transcription factors in the differentiation program. The reader is referred to other recent reviews (1–3) for references too numerous to include in this Minireview. Our understanding of adipocyte differentiation derives largely from studies with preadipose cell lines in culture, notably the C3H10T1/2 and NIH 3T3 fibroblastic cell lines and the 3T3-L1 and 3T3-F442A preadipocyte lines (1). Treatment of multipotent C3H10T1/2 cells with 5-azacytidine gives rise to cells committed to the myogenic, adipogenic, or chondrogenic lineages. This is consistent with the view that the adipose lineage arises from the same multipotent stem cell population of mesodermal origin that gives rise to the muscle and cartilage lineages (1). When appropriately induced with hormonal agents (e.g. glucocorticoid, insulin-like growth factor-1, and cyclic AMP or factors that mimic these agents) committed preadipocytes differentiate into adipocytes in culture. A large body of evidence shows that differentiation of 3T3 preadipocytes faithfully mimics the in vivo process giving rise to cells that possess virtually all of the biochemical and morphological characteristics of adipocytes (2). Following hormonal induction, confluent preadipocytes undergo mitotic clonal expansion, become growth arrested, and then coordinately express adipocyte gene products (1). Several transcription factors have been identified, which act cooperatively and sequentially to trigger the terminal differentiation program (3–5). These include members of the C/EBP and PPAR families. The sequence of expression of certain of these transcription factors during differentiation is outlined in Fig. 1. It should be noted that these patterns differ somewhat depending upon the differentiation protocol and preadipocyte cell line employed, e.g. 3T3-L1 versus 3T3-F442A versus NIH 3T3 cells.
CFHTLenS: higher order galaxy–mass correlations probed by galaxy–galaxy–galaxy lensing

We present the first direct measurement of the galaxy–matter bispectrum as a function of galaxy luminosity, stellar mass and type of spectral energy distribution (SED). Our analysis uses a galaxy–galaxy–galaxy lensing technique (G3L), on angular scales between 9 arcsec and 50 arcmin, to quantify (i) the excess surface mass density around galaxy pairs (excess mass hereafter) and (ii) the excess shear–shear correlations around single galaxies, both of which yield a measure of two types of galaxy–matter bispectra. We apply our method to the state-of-the-art Canada–France–Hawaii Telescope Lensing Survey (CFHTLenS), spanning 154 square degrees. This survey allows us to detect a significant change of the bispectra with lens properties. Measurements for lens populations with distinct redshift distributions become comparable by a newly devised normalization technique. That will also aid future comparisons to other surveys or simulations. A significant dependence of the normalized G3L statistics on luminosity within −23 ≤ Mr ≤ −18 and stellar mass within 5 × 10^9 M_⊙ ≤ M* ≤ 2 × 10^(11) M_⊙ is found (h = 0.73). Both bispectra exhibit a stronger signal for more luminous lenses or those with higher stellar mass (up to a factor of 2–3). This is accompanied by a steeper equilateral bispectrum for more luminous or higher stellar mass lenses for the excess mass. Importantly, we find the excess mass to be very sensitive to galaxy type as recently predicted with semi-analytic galaxy models: luminous (M_r < −21) late-type galaxies show no detectable signal, while all excess mass detected for luminous galaxies seems to be associated with early-type galaxies. We also present the first observational constraints on third-order stochastic galaxy biasing parameters.
Single-Folded Leaky-Wave Antennas for Automotive Radars at 77 GHz

Low-cost multilayer antennas are proposed for the next-generation automotive radar systems at millimeter waves. The antennas consist of a multilayer pillbox leaky-wave antenna structure where the feeding (integrated horn) and radiating parts are connected by a quasi-optical system made by an integrated parabola and several coupling slots (pillbox transition). In addition, a scanning capability is obtained by displacing the feeding part in the focal plane of the pillbox transition. Three prototypes with different feed locations have been manufactured and tested. The antenna stack-up consists of two Rogers 5880 substrates piled up by a diffusion bonding process. The integrated horn and pillbox transition are synthesized by perfect vertical metallic walls and closely spaced metallic pins, respectively. The E- and H-plane radiation patterns measured in the 74-78-GHz band show an average half-power beamwidth of about 11.5° and 5.5°, respectively, and sidelobe levels better than -15 dB up to a scan angle of 18°. The measured gains are about 24 dB around 77 GHz, resulting in a total efficiency higher than 50%.
APOL1, α-thalassemia, and BCL11A variants as a genetic risk profile for progression of chronic kidney disease in sickle cell anemia

Sickle cell anemia (SCA) is caused by a mutation in the β-globin gene that results in hemoglobin polymerization and affects approximately 1 in 500 African Americans and 25 million people worldwide. Chronic kidney disease (CKD) is observed in up to 58% of adults, and is associated with a 3-fold increased risk for early mortality in SCA. Multiple genetic modifiers of clinical complications in SCA have been reported, and combining these genetic factors into a risk profile may strengthen the predictive value as compared to the individual factors alone. Homozygosity or compound heterozygosity for APOL1 G1/G2 (G1=S342G/I384M substitutions, G2=N388/Y389 deletions) is observed in 10-15% of African Americans, and is the strongest genetic association for CKD in African Americans in general. APOL1 G1/G2 is also associated with proteinuria and albumin-
Persistent high job demands and reactivity to mental stress predict future ambulatory blood pressure

Objective To test the hypothesis that work stress (persistent high job demands over 1 year) in combination with high reactivity to mental stress predict ambulatory blood pressure. Design Assessment of cardiovascular responses to standardized behavioural tasks, job demands, and ambulatory blood pressure over a working day and evening after 12 months. Participants We studied 81 school teachers (26 men, 55 women), 36 of whom experienced persistent high job demands over 1 year, while 45 reported lower job demands. Methods Participants were divided on the basis of high and low job demands, and high and low systolic pressure reactions to an uncontrollable stress task. Blood pressure and concurrent physical activity were monitored using ambulatory apparatus from 0900 to 2230 h on a working day. Results Cardiovascular stress reactivity was associated with waist/hip ratio. Systolic and diastolic pressure during the working day were greater in high job demand participants who were stress reactive than in other groups, after adjustment for age, baseline blood pressure, body mass index and negative affectivity. The difference was not accounted for by variations in physical activity. Conclusions Cardiovascular stress reactivity and sustained psychosocial stress may act in concert to increase cardiovascular risk in susceptible individuals.
Wnt/β‐catenin signaling is critical for dedifferentiation of aged epidermal cells in vivo and in vitro

Aged epidermal cells have the capacity to dedifferentiate into stem cell‐like cells. However, the signals that regulate the dedifferentiation of aged epidermal cells remain unclear. Here, we provide evidence that Wnt/β‐catenin is critical for aged epidermal cell dedifferentiation in vivo and in vitro. Some aged epidermal cells in human ultrathin epidermal sheets lacking basal stem cells transplanted onto wounds dedifferentiated into stem cell‐like cells that were positive for CK19 and β1 integrin but negative for CK10. In addition, Wnt/β‐catenin pathway was activated during this process. There was increased expression of Wnt‐1, Wnt‐4, Wnt‐7a, β‐catenin, cyclin D1, and c‐myc. Secreted frizzled‐related protein 1, a Wnt/β‐catenin pathway inhibitor, blocked dedifferentiation in vivo. Then, the activator, a highly specific glycogen synthase kinase (GSK)‐3β inhibitor, of Wnt/β‐catenin pathway was added to the culture medium of aged epidermal cells. Surprisingly, we found that the activator induced higher expression of CK19, β1 integrin, Oct4, and Nanog proteins. The induced aged epidermal cells exhibited high colony‐forming efficiency, long‐term proliferative potential and could regenerate a skin equivalent (as do epidermal stem cells). These results suggested that activation of Wnt/β‐catenin pathway induced the dedifferentiation of aged epidermal cells, which suggest a new approach to generate epidermal stem cell‐like cells.
Data-driven Topological Filtering based on Orthogonal Minimal Spanning Trees: Application to Multi-Group MEG Resting-State Connectivity

In the present study a novel data-driven topological filtering technique is introduced to derive the backbone of functional brain networks relying on orthogonal minimal spanning trees (OMST). The method aims to identify the essential functional connections to ensure optimal information flow via the objective criterion of global efficiency minus the cost of surviving connections. The OMST technique was applied to multichannel, resting-state neuromagnetic recordings from four groups of participants: healthy adults (n=50), adults who have suffered mild traumatic brain injury (n=30), typically developing children (n=27), and reading-disabled children (n=25). Weighted interactions between network nodes (sensors) were computed using an integrated approach of dominant intrinsic coupling modes based on two alternative metrics (symbolic mutual information and phase lag index), resulting in excellent discrimination of individual cases according to their group membership. Classification results using OMST-derived functional networks were clearly superior to results using either relative power spectrum features or functional networks derived through the conventional minimal spanning trees algorithm.
NEW WORLD NINE-PRIMARIED OSCINE RELATIONSHIPS: CONSTRUCTING A MITOCHONDRIAL DNA FRAMEWORK

Abstract Historically, a paucity of comparative morphological characters has led to much debate regarding relationships within and among the major lineages of New World nine-primaried oscines. More recently, DNA-DNA hybridization studies have provided novel and testable hypotheses of relationships, although no consensus has been reached. For 40 songbird taxa, we obtained 1,929 base pairs (bp) of DNA sequence from the mitochondrial cytochrome-b (894 bp) and NADH dehydrogenase subunit 2 (1,035 bp) genes. Phylogenetic analyses confirm the monophyly of this assemblage as traditionally defined. The lineages delineated historically on morphological grounds are retained; finches (Fringillinae) are sister to a well-supported clade (Emberizinae) containing blackbirds (Icterini), sparrows (Emberizini), wood-warblers (Parulini), tanagers (Thraupini), and cardinal-grosbeaks (Cardinalini). However, each tribe individually is either paraphyletic or polyphyletic with respect to most recent songbird classifications. Our results suggest that Euphonia is not a tanager but perhaps represents a derived form of cardueline finch. Piranga, traditionally considered a typical tanager, is a cardinaline in all of our analyses. Calcarius falls outside the sparrow lineage in all of our analyses, but its true affinities remain unclear. Elements of four different AOU families are represented in our clade Thraupini. The inclusion of several “tanager-finches” (Haplospiza, Diglossa, Tiaris, Volatinia, Sporophila) and a nectarivore (Coereba) in this clade is consistent with findings from other molecular phylogenies in suggesting that convergence in feeding specializations among some lineages has confounded traditional morphological classifications. We obtained a novel arrangement of relationships among tribes in our “best” topology; Cardinalini is sister to the rest of the Emberizinae assemblage (as defined by Sibley and Ahlquist [1990]), and Thraupini is sister to a clade containing Icterini, Emberizini, and Parulini. Despite nearly 2,000 bp of sequence for each taxon, and a high degree of stability across most weighting schemes and analytical methods, most nodes lack strong bootstrap support. The ND2 gene provided higher resolution than did cytochrome b, but combining genes provided the most highly supported and resolved topology. We consider the phylogeny a working hypothesis to be used as a guide for further studies within the nine-primaried oscine assemblage.
Molecular basis for recognition of methylated and specific DNA sequences by the zinc finger protein Kaiso

Methylation of CpG dinucleotides in DNA is a common epigenetic modification in eukaryotes that plays a central role in maintenance of genome stability, gene silencing, genomic imprinting, development, and disease. Kaiso, a bifunctional Cys2His2 zinc finger protein implicated in tumor-cell proliferation, binds to both methylated CpG (mCpG) sites and a specific nonmethylated DNA motif (TCCTGCNA) and represses transcription by recruiting chromatin remodeling corepression machinery to target genes. Here we report structures of the Kaiso zinc finger DNA-binding domain in complex with its nonmethylated, sequence-specific DNA target (KBS) and with a symmetrically methylated DNA sequence derived from the promoter region of E-cadherin. Recognition of specific bases in the major groove of the core KBS and mCpG sites is accomplished through both classical and methyl CH···O hydrogen-bonding interactions with residues in the first two zinc fingers, whereas residues in the C-terminal extension following the third zinc finger bind in the opposing minor groove and are required for high-affinity binding. The C-terminal region is disordered in the free protein and adopts an ordered structure upon binding to DNA. The structures of these Kaiso complexes provide insights into the mechanism by which a zinc finger protein can recognize mCpG sites as well as a specific, nonmethylated regulatory DNA sequence.
5 Rural Institutions and Imperfect Agricultural Markets in Africa: Experiences from Producer Marketing Groups in Kenya

Many Sub-Saharan African countries have liberalized their economies and developed poverty reduction strategies aimed at opening up new market-led opportunities for economic recovery and accelerated growth. The outcomes of these policy reforms have, however, been quite mixed (Winter-Nelson and Temu 2002; Dorward and Kydd 2004; Fafchamps 2004). Many smallholder farmers continue to engage in subsistence agriculture and are therefore unable to benefit from liberalized markets. Structural problems of poor infrastructure (Kydd and Dorward 2004; Dorward et al. 2005) and lack of market-enabling institutions (World Bank 2002, 2003) continue to characterize the subsector, contributing to high transaction costs, coordination failure, and pervasive market imperfections. Moreover, partial implementation of reforms and policy reversals in terms of increasing the use of discretionary trade policy instruments by the state or parastatal marketing boards have tended to mute the positive effects of liberalization (Jayne et al. 2002; Jayne, Chapoto, and Shiferaw 2009). Although the opportunities afforded by liberalization have not been fully exploited, the expectation that removing or rationalizing state marketing boards would open opportunities for the private sector to take over these functions has not been fully realized in many areas. This is mainly because of underdeveloped infrastructure and missing institutions that support the proper functioning of markets. The private-sector traders are unlikely to offer input and output marketing services to smallholder producers in such less favored areas, where market infrastructure or enabling institutions are weak or missing. Lack of such infrastructure and institutions diminishes the incentives for the private sector to invest in agribusiness development and the provision of marketing functions, especially for food staples and other low-value grains produced in these areas. However, avenues exist in market institutions that make use of collective action to complement government and private-sector responses for enhanced coordination in rural commodity markets. This is because the individual marketing of produce may not make economic sense due to small quantities, large spatial distances from input and output markets, and the associated high transportation costs, all characteristics of small-scale production in Sub-Saharan Africa. 5 Rural Institutions and Imperfect Agricultural Markets in Africa: Experiences from Producer Marketing Groups in Kenya
Protein partners of dynamin-1 in the retina

Abstract Dynamin proteins are involved in vesicle generation, providing mechanical force to excise newly formed vesicles from membranes of cellular compartments. In the brain, dynamin-1, dynamin-2, and dynamin-3 have been well studied; however, their function in the retina remains elusive. A retina-specific splice variant of dynamin-1 interacts with the photoreceptor-specific protein Tubby-like protein 1 (Tulp1), which when mutated causes an early onset form of autosomal recessive retinitis pigmentosa. Here, we investigated the role of the dynamins in the retina, using immunohistochemistry to localize dynamin-1, dynamin-2, and dynamin-3 and immunoprecipitation followed by mass spectrometry to explore dynamin-1 interacting proteins in mouse retina. Dynamin-2 is primarily confined to the inner segment compartment of photoreceptors, suggesting a role in outer segment protein transport. Dynamin-3 is present in the terminals of photoreceptors and dendrites of second-order neurons but is most pronounced in the inner plexiform layer where second-order neurons relay signals from photoreceptors. Dynamin-1 appears to be the dominant isoform in the retina and is present throughout the retina and in multiple compartments of the photoreceptor cell. This suggests that it may function in multiple cellular pathways. Surprisingly, dynamin-1 expression and localization did not appear to be disrupted in tulp1−/− mice. Immunoprecipitation experiments reveal that dynamin-1 associates primarily with proteins involved in cytoskeletal-based membrane dynamics. This finding is confirmed by western blot analysis. Results further implicate dynamin-1 in vesicular protein transport processes relevant to synaptic and post-Golgi pathways and indicate a possible role in photoreceptor stability.
Regulation by Rho family GTPases of IL–1 receptor induced signaling: C3‐like chimeric toxin and Clostridium difficile toxin B inhibit signaling pathways involved in IL‐2 gene expression

In this study the participation of Rho family GTPases in the regulation of IL‐1‐activated protein kinase cascades controlling IL‐2 synthesis was investigated in murine EL‐4 thymoma cells. The recombinant C3‐like chimeric toxin, which consists of the C3 toxin of Clostridium limosum and the N‐terminal part of Clostridium botulinum C2 toxin (C2IN‐C3) interacting with the C2II binding subunit to facilitate uptake into cells, and selectively inactivates Rho A by ADP‐ribosylation, prevented IL‐1‐stimulated activation of Jun‐NH2‐terminal‐kinases (JNK) and p38 mitogen‐activated‐protein kinases (MAPK). UDP‐monoglucosylation and concomitant inactivation of Rho A and of Rac‐2 by Clostridium difficile toxin B also inhibited IL‐1‐induced activation of JNK and p38 MAPK, but additionally inhibited activation of the extracellular‐regulated‐kinase pathway and DNA binding of the transcription factor NFκB. Accordingly, pre‐treatment of cells with C2IN‐C3 fusion toxin only decreased IL‐1‐stimulated IL‐2 synthesis by 50%, while in C. difficile toxin B‐treated cells IL‐1‐induced IL‐2 secretion was reduced by 90%. These results imply that together with Rho A an additional member of the Rho family G proteins, i.e. Rac‐2, is critically involved as an upstream regulator in IL‐1‐induced activation of different MAPK, stress‐activated protein kinases, and in NFκB activation controlling IL‐2 gene expression in response to IL‐1, acting in close proximity to the IL‐1‐receptor complex.
Simulation of a Single Streamer Traveling Along Two Counterpropagating Helium Jets in Ambient Air

Variation of the structure of one guided streamer moving along two counterpropagating helium jets is studied by means of numerical simulation. It is shown, in agreement with experimental results, that, due to variation of the gas composition along the streamer path, the radial intensity profile changes during streamer propagation. Its form, being initially, just after emerging from the first tube, an annular one, changes to a spherical one far from the tube, in the middle of the gap, and returns again to an annular one when approaching the second tube.
Survival results of neoadjuvant chemotherapy for advanced squamous cell carcinoma of the head and neck.

BACKGROUND We carried out an open, randomized multi-center clinical trial for advanced head and neck cancer between April 1991 and December 1992. In this report, we update the results and analyze the 5-year survival results. METHODS Thirty-two patients with previously untreated stage III and IV resectable squamous cell carcinoma of the oral cavity and pharynx were entered into the study. The PEM regimen consisted of cisplatin 60 mg/m2 2 h infusion on day 1, etoposide 40 mg/m2 1 h infusion on days 1, 2 and 3 and mitomycin-C 7 mg/m2 i.v. bolus on day 1. RESULTS Among the 32 patients entered into this trial, eight were disqualified from the analysis. Of the remaining 24 patients, 13 were given neoadjuvant chemotherapy (NAC) and 11 underwent surgery alone. Among the 13 patients who received NAC, four achieved a complete response (31%) and three a partial response (23%), with an overall response rate of 54%. Myelosuppression was a major side effect. Thrombocytopenia and anemia were dose-limiting toxicities. Other adverse reactions, including mucositis, were all mild and transient. The overall 5-year survival after NAC and without NAC were 83 and 62%, respectively. The survival difference was not statistically significant (p = 0.33). CONCLUSIONS NAC does not appear to play a role in the treatment of cancer of the oral cavity and pharynx with our PEM regimen. However, the degree of toxicity was limited in our trial and therefore attempts to increase the dosage and/or revise the administration schedule for cancer of the pharynx and T1 to T3 tumor disease appear warranted.