Pathophysiological reactivity outlined via algorhythmic networks and etiopathogenetic clusters fits the criteria of graph theory

МЕДИЦИНСКИЕ УЧЕБНЫЕ ЗАВЕДЕНИЯОБРАЗОВАНИЕ МЕДИЦИНСКОЕУЧЕБНЫЙ ПРОЦЕССПРАКТИКО-ОРИЕНТИРОВАННОЕ ОБУЧЕНИЕПРАКТИКО-ОРИЕНТИРОВАННЫЕ ТЕХНОЛОГИИПАТОФИЗИОЛОГИЯ (ДИСЦИПЛИНА

A massive, distant proto-cluster at z=2.47 caught in a phase of rapid formation?

Numerical simulations of cosmological structure formation show that the Universe's most massive clusters, and the galaxies living in those clusters, assemble rapidly at early times (2.5 < z < 4). While more than twenty proto-clusters have been observed at z > 2 based on associations of 5-40 galaxies around rare sources, the observational evidence for rapid cluster formation is weak. Here we report observations of an asymmetric, filamentary structure at z = 2.47 containing seven starbursting, submillimeter-luminous galaxies and five additional AGN within a comoving volume of 15000 Mpc$^{3}$. As the expected lifetime of both the luminous AGN and starburst phase of a galaxy is ~100 Myr, we conclude that these sources were likely triggered in rapid succession by environmental factors, or, alternatively, the duration of these cosmologically rare phenomena is much longer than prior direct measurements suggest. The stellar mass already built up in the structure is $\sim10^{12}M_{\odot}$ and we estimate that the cluster mass will exceed that of the Coma supercluster at $z \sim 0$. The filamentary structure is in line with hierarchical growth simulations which predict that the peak of cluster activity occurs rapidly at z > 2.Comment: 7 pages, 3 figures, 2 tables, accepted in ApJL (small revisions from previous version

Gut Microbiota-Testis Axis: FMT Mitigates High-Fat Diet-Diminished Male Fertility via Improving Systemic and Testicular Metabolome

High-fat diet (HFD)-induced obesity is known to be associated with reduced male fertility and decreased semen quality in humans. HFD-related male infertility is a growing issue worldwide, and it is crucial to overcome this problem to ameliorate the distress of infertile couples. For the first time, we discovered that fecal microbiota transplantation (FMT) of alginate oligosaccharide (AOS)-improved gut microbiota (A10-FMT) ameliorated HFD-decreased semen quality (sperm concentration: 286.1 ± 14.1 versus 217.9 ± 17.4 million/mL; sperm motility: 40.1 ± 0.7% versus 29.0 ± 0.9%), and male fertility (pregnancy rate: 87.4 ± 1.1% versus 70.2 ± 6.1%) by benefiting blood and testicular metabolome. A10-FMT improved HFD-disturbed gut microbiota by increasing gut Bacteroides (colon: 24.9 ± 1.1% versus 8.3 ± 0.6%; cecum: 10.2 ± 0.7% versus 3.6 ± 0.7%) and decreasing Mucispirillum (colon: 0.3 ± 0.1% versus 2.8 ± 0.4%; cecum: 2.3 ± 0.5% versus 6.6 ± 0.7%). A10-FMT benefited gut microbiota to improve liver function by adjusting lipid metabolism to produce n-3 polyunsaturated fatty acids, such as eicosapentaenoic acid (blood: 55.5 ± 18.7 versus 20.3 ± 2.4) and docosahexaenoic acid (testis: 121.2 ± 6.2 versus 89.4 ± 6.7), thus ameliorating HFD-impaired testicular microenvironment to rescue spermatogenesis and increase semen quality and fertility. The findings indicated that AOS-improved gut microbiota may be a promising strategy to treat obesity or metabolic issues-related male infertility in the future

Visual Naming Performance after ATL Resection: Impact of Atypical Language Dominance.

Purpose- To characterize the interaction between language dominance and lateralization of the epileptic focus for pre- and postoperative Boston Naming Test (BNT) performance in patients undergoing anterior temporal lobectomy (ATL). Methods- Analysis of pre- and postoperative BNT scores depending on lateralization of language as measured by the intracarotid amobarbital procedure (IAP) versus lateralization of the temporal lobe epileptic focus. Results- Changes between pre- and postoperative BNT performance depended on epilepsy lateralization (effect size = 0.189) with significant decrease in patients undergoing left ATL. Subgroup analysis in these showed that postoperative decline in BNT scores was significant in patients with atypical (n = 14; p \u3c 0.05), but did not reach statistical significance in patients with left language dominance (n = 36; p = 0.09). Chi-square test revealed a trend of higher proportions of patients experiencing significant postsurgical deterioration in naming performance in atypical (57.1%) as compared to left language dominance (30.6%; p = 0.082). Surgical failure was also associated with greater decline of BNT scores and was more common in atypical than in left language dominant patients (χ2 (1, n = 98) = 4.62, p = 0.032). Age of onset, duration of epilepsy, and seizure frequency had no impact on changes in BNT performance. Conclusion- Atypical language dominance is a predictor of change in visual naming performance after left ATL and may also impact postsurgical seizure control. This should be considered when counseling surgical candidates

Discovery of Massive, Mostly Star-formation Quenched Galaxies with Extremely Large Lyman-alpha Equivalent Widths at z ~ 3

We report a discovery of 6 massive galaxies with both extremely large Lya equivalent width and evolved stellar population at z ~ 3. These MAssive Extremely STrong Lya emitting Objects (MAESTLOs) have been discovered in our large-volume systematic survey for strong Lya emitters (LAEs) with twelve optical intermediate-band data taken with Subaru/Suprime-Cam in the COSMOS field. Based on the SED fitting analysis for these LAEs, it is found that these MAESTLOs have (1) large rest-frame equivalent width of EW_0(Lya) ~ 100--300 A, (2) M_star ~ 10^10.5--10^11.1 M_sun, and (3) relatively low specific star formation rates of SFR/M_star ~ 0.03--1 Gyr^-1. Three of the 6 MAESTLOs have extended Ly$\alpha$ emission with a radius of several kpc although they show very compact morphology in the HST/ACS images, which correspond to the rest-frame UV continuum. Since the MAESTLOs do not show any evidence for AGNs, the observed extended Lya emission is likely to be caused by star formation process including the superwind activity. We suggest that this new class of LAEs, MAESTLOs, provides a missing link from star-forming to passively evolving galaxies at the peak era of the cosmic star-formation history.Comment: Accepted for publication in ApJ Letters on 15th July, 2015. 6 pages including 3 figures and 2 table

Preparation of routine automated synthesis of [11C]choline

Introduction [11C]choline is a very effective PET radiopharma-ceutical for the study of prostate cancer. To support the increasing demand for [11C]choline, several different synthetic approaches have been described in the literature, including different automated production methods using remote-controlled synthesis modules [1–4]. The most popular method uses a C18 Sep-Pak as solid support for methylation and, subsequently, a CM Sep-Pak for purification [2]. We report an optimized method for producing [11C]choline using only one CM Sep-Pak for both reaction and purification as was shown in the literature [4]. For synthesis of [11C]choline we used two modules Tracerlab FXC for preparation of methylation reagent [11C]CH3I and GPF-101 for [11C]choline synthesis. Material and Methods TracerlabFXC GE, GPF-101 Veenstra Instrument, 2-(dimethylamino)-ethanol (DMAE) ABX, Sep-Pak Light Accell Plus CM cation-exchange cartridges Waters used without conditioning, precursor 50 µL of DMAE dissolved in 25 µL of ethanol and loaded on a CM Sep-Pak. Schematic diagram of the automated system for the production of [11C]choline is given below. [11C]CH4 was produced in two standard Nitra target IBA irradiation of mixture 90 % N2/10 % H2 with 15 MeV protons using dual beam. Results and Conclusion [11C]CH4 was prepared in the targets and connected with Tracerlab FXC. [11C]CH3I was pre-pared in a loop in which allowed to react of elemental iodine at a temperature 720 oC. Con-version to [11C]CH3I usually is around 50% uncorrected activity. Activity is within the range 15–18 GBq of [11C]CH3I and time of production 10 min. Synthesis of [11C]choline is based on the reaction DMAE with [11C]CH3I on a Accell Plus CM cation-exchange column which serves both as a support for reaction and for separation of choline from DMAE by ethanol washing. The basic parameters are shown in TABLE 1. Beam current 2X 20 µA Irradiation time 30 min DMAE 50 µl Synthesis time from EOB 25 min Absolute yield without correction 6.6 GBq Radiochemical purity > 99 % Residual DMAE in product < 5 ppm Ethanol < 1000 mg/L pH 4.5–8.5 TABLE 1. Reaction parameters and result of production of [11C]choline syntheses Conclusion We have applied a simple synthesis method for [11C]choline preparation using automated commercial equipments with one column used both for reaction and separation purpose. The main advantage of using one column is lower contamination of the product [11C]choline with DMAE. When for synthesis of [11C]choline two columns C18 for synthesis and CM for separation is used, higher contamination of DMAE can be found in the product due to a release of DMAE from C18 column

BICEP3: a 95 GHz refracting telescope for degree-scale CMB polarization

BICEP3 is a 550 mm-aperture refracting telescope for polarimetry of radiation in the cosmic microwave background at 95 GHz. It adopts the methodology of BICEP1, BICEP2 and the Keck Array experiments - it possesses sufficient resolution to search for signatures of the inflation-induced cosmic gravitational-wave background while utilizing a compact design for ease of construction and to facilitate the characterization and mitigation of systematics. However, BICEP3 represents a significant breakthrough in per-receiver sensitivity, with a focal plane area 5$\times$ larger than a BICEP2/Keck Array receiver and faster optics ($f/1.6$ vs. $f/2.4$). Large-aperture infrared-reflective metal-mesh filters and infrared-absorptive cold alumina filters and lenses were developed and implemented for its optics. The camera consists of 1280 dual-polarization pixels; each is a pair of orthogonal antenna arrays coupled to transition-edge sensor bolometers and read out by multiplexed SQUIDs. Upon deployment at the South Pole during the 2014-15 season, BICEP3 will have survey speed comparable to Keck Array 150 GHz (2013), and will significantly enhance spectral separation of primordial B-mode power from that of possible galactic dust contamination in the BICEP2 observation patch.Comment: 12 pages, 5 figures. Presented at SPIE Astronomical Telescopes and Instrumentation 2014: Millimeter, Submillimeter, and Far-Infrared Detectors and Instrumentation for Astronomy VII. To be published in Proceedings of SPIE Volume 915

Reversible Keap1 inhibitors are preferential pharmacological tools to modulate cellular mitophagy

Mitophagy orchestrates the autophagic degradation of dysfunctional mitochondria preventing their pathological accumulation and contributing to cellular homeostasis. We previously identified a novel chemical tool (hereafter referred to as PMI), which drives mitochondria into autophagy without collapsing their membrane potential (ΔΨm). PMI is an inhibitor of the protein-protein interaction (PPI) between the transcription factor Nrf2 and its negative regulator, Keap1 and is able to up-regulate the expression of autophagy-associated proteins, including p62/SQSTM1. Here we show that PMI promotes mitochondrial respiration, leading to a superoxide-dependent activation of mitophagy. Structurally distinct Keap1-Nrf2 PPI inhibitors promote mitochondrial turnover, while covalent Keap1 modifiers, including sulforaphane (SFN) and dimethyl fumarate (DMF), are unable to induce a similar response. Additionally, we demonstrate that SFN reverses the effects of PMI in co-treated cells by reducing the accumulation of p62 in mitochondria and subsequently limiting their autophagic degradation. This study highlights the unique features of Keap1-Nrf2 PPI inhibitors as inducers of mitophagy and their potential as pharmacological agents for the treatment of pathological conditions characterized by impaired mitochondrial quality control

BICEP2 / Keck Array V: Measurements of B-mode Polarization at Degree Angular Scales and 150 GHz by the Keck Array

The Keck Array is a system of cosmic microwave background (CMB) polarimeters, each similar to the BICEP2 experiment. In this paper we report results from the 2012 and 2013 observing seasons, during which the Keck Array consisted of five receivers all operating in the same (150 GHz) frequency band and observing field as BICEP2. We again find an excess of B-mode power over the lensed-$\Lambda$CDM expectation of $> 5 \sigma$ in the range $30 < \ell < 150$ and confirm that this is not due to systematics using jackknife tests and simulations based on detailed calibration measurements. In map difference and spectral difference tests these new data are shown to be consistent with BICEP2. Finally, we combine the maps from the two experiments to produce final Q and U maps which have a depth of 57 nK deg (3.4 $\mu$K arcmin) over an effective area of 400 deg$^2$ for an equivalent survey weight of 250,000 $\mu$K$^{-2}$. The final BB band powers have noise uncertainty a factor of 2.3 times better than the previous results, and a significance of detection of excess power of $> 6\sigma$.Comment: 13 pages, 9 figure