Genomic and Proteomic Analysis of the Impact of Mitotic Quiescence on the Engraftment of Human CD34+ Cells

It is well established that in adults, long-term repopulating hematopoietic stem cells (HSC) are mitotically quiescent cells that reside in specialized bone marrow (BM) niches that maintain the dormancy of HSC. Our laboratory demonstrated that the engraftment potential of human HSC (CD34+ cells) from BM and mobilized peripheral blood (MPB) is restricted to cells in the G0 phase of cell cycle but that in the case of umbilical cord blood (UCB) -derived CD34+ cells, cell cycle status is not a determining factor in the ability of these cells to engraft and sustain hematopoiesis. We used this distinct in vivo behavior of CD34+ cells from these tissues to identify genes associated with the engraftment potential of human HSC. CD34+ cells from BM, MPB, and UCB were fractionated into G0 and G1 phases of cell cycle and subjected in parallel to microarray and proteomic analyses. A total of 484 target genes were identified to be associated with engraftment potential of HSC. System biology modeling indicated that the top four signaling pathways associated with these genes are Integrin signaling, p53 signaling, cytotoxic T lymphocyte-mediated apoptosis, and Myc mediated apoptosis signaling. Our data suggest that a continuum of functions of hematopoietic cells directly associated with cell cycle progression may play a major role in governing the engraftment potential of stem cells. While proteomic analysis identified a total of 646 proteins in analyzed samples, a very limited overlap between genomic and proteomic data was observed. These data provide a new insight into the genetic control of engraftment of human HSC from distinct tissues and suggest that mitotic quiescence may not be the requisite characteristic of engrafting stem cells, but instead may be the physiologic status conducive to the expression of genetic elements favoring engraftment

The Bank of Standardized Stimuli (BOSS), a New Set of 480 Normative Photos of Objects to Be Used as Visual Stimuli in Cognitive Research

There are currently stimuli with published norms available to study several psychological aspects of language and visual cognitions. Norms represent valuable information that can be used as experimental variables or systematically controlled to limit their potential influence on another experimental manipulation. The present work proposes 480 photo stimuli that have been normalized for name, category, familiarity, visual complexity, object agreement, viewpoint agreement, and manipulability. Stimuli are also available in grayscale, blurred, scrambled, and line-drawn version. This set of objects, the Bank Of Standardized Stimuli (BOSS), was created specifically to meet the needs of scientists in cognition, vision and psycholinguistics who work with photo stimuli

Comparative morphology of the forewing base articulationin Sternorrhyncha compared with a representative of Fulgoromorpha (Insecta, Hemiptera)

The forewing articulation of single species from each of the four subgroups of Sternorrhyncha (Aleyrodomorpha, Aphidomorpha, Coccomorpha, Psyllomorpha) was examined by optical and scanning electron microscopy. The species were compared with a species of Cixiidae (Fulgoromorpha), as an outgroup of Sternorrhyncha. We present the results of a comparative analysis of the forewing articulation in these five groups, propose a standardized terminology and compare our findings with those previously reported. The wing base of all examined species is composed of the following structures: anterior and posterior notal wing process, first, second, and third axillary sclerites, tegula, and axillary cord. The number of elements included in the wing base and the surrounding area is the greatest in Cacopsylla mali, the most complicated species from Sternorrhyncha. Based on the shape of axillary sclerites and the number of elements forming the wing base environment, Orthezia urticae (Coccomorpha) and Cixius nervosus (Fulgoromorpha) are the most similar. Among Sternorrhyncha, the most similar axillaries are those of Aphis fabae and Orthezia urticae, which is congruent with existing classifications. In this paper we show that the four groups from Sternorrhyncha exhibit their own distinct wing base morphology

Skeletal Morphology of Opius dissitus and Biosteres carbonarius (Hymenoptera: Braconidae), with a Discussion of Terminology

The Braconidae, a family of parasitic wasps, constitute a major taxonomic challenge with an estimated diversity of 40,000 to 120,000 species worldwide, only 18,000 of which have been described to date. The skeletal morphology of braconids is still not adequately understood and the terminology is partly idiosyncratic, despite the fact that anatomical features form the basis for most taxonomic work on the group. To help address this problem, we describe the external skeletal morphology of Opius dissitus Muesebeck 1963 and Biosteres carbonarius Nees 1834, two diverse representatives of one of the least known and most diverse braconid subfamilies, the Opiinae. We review the terminology used to describe skeletal features in the Ichneumonoidea in general and the Opiinae in particular, and identify a list of recommend terms, which are linked to the online Hymenoptera Anatomy Ontology. The morphology of the studied species is illustrated with SEM-micrographs, photos and line drawings. Based on the examined species, we discuss intraspecific and interspecific morphological variation in the Opiinae and point out character complexes that merit further study

Clinical emergence of neurometastatic merkel cell carcinoma: a surgical case series and literature review

Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine neoplasm of possible viral origin and is known for its aggressive behavior. The incidence of MCC has increased in the last 15 years. Merkel cell carcinoma has the potential to metastasize, but rarely involves the central nervous system. Herein, we report three consecutive surgical cases of MCC presenting at a single institution within 1 year. We used intracavitary BCNU wafers (Gliadel®) in two cases. Pathological features, including CK20 positivity, consistent with MCC, were present in all cases. We found 33 published cases of MCC with CNS involvement. We suggest that the incidence of neurometastatic MCC may be increasing, parallel to the increasing incidence of primary MCC. We propose a role for intracavitary BCNU wafers in the treatment of intra-axial neurometastatic MCC

Direct effects of diazepam on emotional processing in healthy volunteers

RATIONALE: Pharmacological agents used in the treatment of anxiety have been reported to decrease threat relevant processing in patients and healthy controls, suggesting a potentially relevant mechanism of action. However, the effects of the anxiolytic diazepam have typically been examined at sedative doses, which do not allow the direct actions on emotional processing to be fully separated from global effects of the drug on cognition and alertness. OBJECTIVES: The aim of this study was to investigate the effect of a lower, but still clinically effective, dose of diazepam on emotional processing in healthy volunteers. MATERIALS AND METHODS: Twenty-four participants were randomised to receive a single dose of diazepam (5 mg) or placebo. Sixty minutes later, participants completed a battery of psychological tests, including measures of non-emotional cognitive performance (reaction time and sustained attention) and emotional processing (affective modulation of the startle reflex, attentional dot probe, facial expression recognition, and emotional memory). Mood and subjective experience were also measured. RESULTS: Diazepam significantly modulated attentional vigilance to masked emotional faces and significantly decreased overall startle reactivity. Diazepam did not significantly affect mood, alertness, response times, facial expression recognition, or sustained attention. CONCLUSIONS: At non-sedating doses, diazepam produces effects on attentional vigilance and startle responsivity that are consistent with its anxiolytic action. This may be an underlying mechanism through which benzodiazepines exert their therapeutic effects in clinical anxiety

Increasing Protein at the Expense of Carbohydrate in the Diet Down-Regulates Glucose Utilization as Glucose Sparing Effect in Rats

High protein (HP) diet could serve as a good strategy against obesity, provoking the changes in energy metabolic pathways. However, those modifications differ during a dietary adaptation. To better understand the mechanisms involved in effect of high protein diet (HP) on limiting adiposity in rats we studied in parallel the gene expression of enzymes involved in protein and energy metabolism and the profiles of nutrients oxidation. Eighty male Wistar rats were fed a normal protein diet (NP, 14% of protein) for one week, then either maintained on NP diet or assigned to a HP diet (50% of protein) for 1, 3, 6 and 14 days. mRNA levels of genes involved in carbohydrate and lipid metabolism were measured in liver, adipose tissues, kidney and muscles by real time PCR. Energy expenditure (EE) and substrate oxidation were measured by indirect calorimetry. Liver glycogen and plasma glucose and hormones were assayed. In liver, HP feeding 1) decreased mRNA encoding glycolysis enzymes (GK, L-PK) and lipogenesis enzymes(ACC, FAS), 2) increased mRNA encoding gluconeogenesis enzymes (PEPCK), 3) first lowered, then restored mRNA encoding glycogen synthesis enzyme (GS), 4) did not change mRNA encoding β-oxidation enzymes (CPT1, ACOX1, βHAD). Few changes were seen in other organs. In parallel, indirect calorimetry confirmed that following HP feeding, glucose oxidation was reduced and fat oxidation was stable, except during the 1st day of adaptation where lipid oxidation was increased. Finally, this study showed that plasma insulin was lowered and hepatic glucose uptake was decreased. Taken together, these results demonstrate that following HP feeding, CHO utilization was increased above the increase in carbohydrate intake while lipogenesis was decreased thus giving a potential explanation for the fat lowering effect of HP diets

The 2016 Feb 19 outburst of comet 67P/CG: an ESA Rosetta multi-instrument study

On 2016 Feb 19, nine Rosetta instruments serendipitously observed an outburst of gas and dust from the nucleus of comet 67P/Churyumov-Gerasimenko. Among these instruments were cameras and spectrometers ranging from UV over visible to microwave wavelengths, in situ gas, dust and plasma instruments, and one dust collector. At 09:40 a dust cloud developed at the edge of an image in the shadowed region of the nucleus. Over the next two hours the instruments recorded a signature of the outburst that significantly exceeded the background. The enhancement ranged from 50 per cent of the neutral gas density at Rosetta to factors >100 of the brightness of the coma near the nucleus. Dust related phenomena (dust counts or brightness due to illuminated dust) showed the strongest enhancements (factors >10). However, even the electron density at Rosetta increased by a factor 3 and consequently the spacecraft potential changed from ∼−16 V to −20 V during the outburst. A clear sequence of events was observed at the distance of Rosetta (34 km from the nucleus): within 15 min the Star Tracker camera detected fast particles (∼25 m s−1) while 100 μm radius particles were detected by the GIADA dust instrument ∼1 h later at a speed of 6 m s−1. The slowest were individual mm to cm sized grains observed by the OSIRIS cameras. Although the outburst originated just outside the FOV of the instruments, the source region and the magnitude of the outburst could be determined

OGLE-2017-BLG-0406: Spitzer microlens parallax reveals Saturn-mass planet orbiting M-dwarf host in the inner galactic disk

Funding: Work by Y.H. was supported by JSPS KAKENHI Grant Number 17J02146. DPB, AB, and CR were supported by NASA through grant NASA-80NSSC18K0274. Work by N.K. is supported by JSPS KAKENHI Grant Number JP18J00897. Work by AG was supported by AST-1516842 from the US NSF and by JPL grant 1500811. AG received support from the European Research Council under the European Unions Seventh Framework Programme (FP 7) ERC Grant Agreement n.[321035]. Work by C.H. was supported by the grants of the National Research Foundation of Korea (2017R1A4A1015178 and 2019R1A2C2085965). YT acknowledges the support of DFG priority program SPP 1992 ”Exploring the Diversity of Extrasolar Planets” (WA 1047/11-1).We report the discovery and analysis of the planetary microlensing event OGLE-2017-BLG-0406, which was observed both from the ground and by the Spitzer satellite in a solar orbit. At high magnification, the anomaly in the light curve was densely observed by ground-based-survey and follow-up groups, and it was found to be explained by a planetary lens with a planet/host mass ratio of q = 7.0 x 10-4 from the light-curve modeling. The ground-only and Spitzer-"only" data each provide very strong one-dimensional (1-D) constraints on the 2-D microlens parallax vector πE. When combined, these yield a precise measurement of πE, and so of the masses of the host Mhost = 0.56 ± 0.07 M⊙ and planet Mplanet = 0.41 ± 0.05 MJup. The system lies at a distance DL = 5.2 ± 0.5 kpc from the Sun toward the Galactic bulge, and the host is more likely to be a disk population star according to the kinematics of the lens. The projected separation of the planet from the host is a⊥ = 3.5 ± 0.3 au, i.e., just over twice the snow line. The Galactic-disk kinematics are established in part from a precise measurement of the source proper motion based on OGLE-IV data. By contrast, the Gaia proper-motion measurement of the source suffers from a catastrophic 10σ error.PostprintPeer reviewe