Genetic and Epigenetic Interactions in in vivo and in vitro Reprogramming

In cancer pathogenesis and induced pluripotent stem: iPS) cell production, an essential step for reprogramming is acquisition of self-renewal. In hematopoietic cells, HOX genes are partially responsible for self-renewal, and HOX gene dysregulation commonly occurs in acute myeloid leukemia: AML). HOX dysregulation is seen in AML with translocations involving HOX genes themselves: e.g. NUP98-HOXA9) and with other disease-initiating translocations: e.g. MLL translocations and inv(16)). However, HOX genes are also highly expressed in many AML samples without translocations; the mechanism that causes dysregulation in these cases is unknown. Whole genome sequencing of 45 de novo AML genomes showed that recurrent mutations in the HOX gene clusters are not responsible for the phenotype. Expression array data from 190 AML cases revealed that while translocations have unique HOX expression patterns, most AML cases predominantly express HOXA5, A9, A10, B2, B3, and MEIS1 in a canonical, highly coordinated pattern that is virtually identical to that found in normal human CD34 cells. HOX gene dysregulation in these cases may therefore represent the persistence of a normal, stem cell-specific HOX gene expression pattern that is probably required for self-renewal, and captured by mutations that initiate leukemia in hematopoietic stem cells. In vitro reprogramming induces self-renewal with overexpression of a cocktail of transcription factors, often in the form of integrating viruses, which have raised concerns about the genomic integrity of iPS lines. We performed whole genome sequencing of 10 murine iPS lines produced in 3 independent experiments. We found an average of 414 somatic nucleotide variants: SNVs) per iPS clone, with variant allele frequencies suggesting that the mutations occurred at or before reprogramming. In one experiment, four independent iPS clones contained 164 identical variants: 6 protein-coding SNVs, 157 non-coding SNVs and 1 structural variant) that were also found in rare parental cells, suggesting that these rare cells were extraordinarily fit for reprogramming. Our data suggest that most of the mutations detected in iPS cells occurred prior to reprogramming and are simply captured by cloning; however, some preexisting mutations provide an advantage for reprogramming, and may provide novel insights into the genetic underpinnings of this process

Examining educational motivational factors in men of color community college students at a 2-year community college in Southern California

The purpose of this study was to investigate which of the 7 motivational factors measured in the Student Motivations for Attending University-Revised (SMAU) survey developed by Phinney, Dennis, and Osorio (2006)—career/personal, humanitarian, prove worth, default, expectation, encouragement, and help family—if any, contribute to African-American male and Latino male community college completion/graduation at a 2-year community college in Southern California and transfer to 4-year universities. This study employed a survey design and the target population included MOC that were enrolled in a community college in Southern California. This study used a quantitative, correlational method to measure men of color (MOC) students’ perceptions of persistence, academic success, and motivational factors related to enrollment and persistence at a community college in Southern California. The participants were selected through non-probability sampling in a non-controlled setting utilizing the target population from a community college in the South Bay area of Southern California. The population of African-American and Latino males is steadily rising, thus increasing the prevalence of these 2 ethnic groups at 2-year community colleges. An extensive literature review demonstrated that both male African- American and Latino community college students are the most prominent groups by ethnicity and gender, yet both groups are the least likely to graduate and transfer to 4-year universities. After reviewing the literature regarding MOC in postsecondary education and considering the findings from this study, the foremost leading motivational factor for male African-American and Latino community college students to enroll and persist in college is their desire and priority to help improve the condition of their family’s financial status. The second highest rated motivational factor for MOC to enroll and persist in community college is based on their career/personal goals and pursuits. The least motivational factor promoting academic success for these 2 male racial/ethnic groups included feeling pressured by friends and feelings that they had no other alternatives

Effects of Amino Acid Supplementation of Reduced Crude Protein (RCP) Diets on the Performance and Carcass Quality of Growing-Finishing Swine

Barrows and gilts (215/gender) were used to test the effects of synthetic AA supplementation of reduced CP diets on the growth performance and quality characteristics of the LM and the fatty acid composition of the LM and s.c. jowl fat from growing-finishing swine. Pigs were blocked by BW within gender, and allocated randomly to pens (6 pigs/pen) which were then assigned randomly within each block and gender to either corn-SBM diets 1) that were devoid of synthetic lysine (Ctrl); 2) with reduced CP diets where lysine was added to all diets (RCP1); 3) with reduced CP where lysine, threonine, and tryptophan were added to all diets (RCP2); 4) with where lysine, threonine, and tryptophan were added to all diets (RCP3); or 5) with reduced CP diets where lysine, threonine, tryptophan, and isoleucine was added to all diets (RCP4). During finisher phase 3, 10 mg/kg of ractopamine was included in all diets. A subsample of whole pork loins was processed into chops for data collection. Another subsample from the whole pork loin and the s.c. fat from each jowl was freeze dried for fatty acid determination. Gilts had a greater (P = 0.02) (lightness) L* value and drip loss than barrows, but the ultimate pH, marbling, and intramuscular fat (IMF) of the LM were greater (P \u3c 0.04) for barrows than gilts. Color measurements were not affected (P \u3e 0.06) by the RCP diets, with the exception of redness (a*) which increased (P = 0.01) with decreasing CP levels. There were greater (P \u3c 0.001) proportions of SFA in the LM of barrows than the LM from gilts. However, gilts had an increase in PUFA content with decreasing levels of CP in the diet and barrows had a decrease in PUFA content of the LM (P = 0.056). Barrows had greater (P = 0.008) SFA and less (P \u3c 0.001) PUFA content in the jowl fat than gilts. The results point toward the reduced CP diets improving fresh pork quality, especially IMF. Also, pork lean and jowl fat were altered in their fatty acid composition by the reducing dietary CP

The Intermediate Mass Black Hole Candidate in the Center of NGC 404: New Evidence from Radio Continuum Observations

We present the results of deep, high-resolution, 5 GHz Expanded Very Large Array (EVLA) observations of the nearby, dwarf lenticular galaxy and intermediate mass black hole candidate (M ~4.5 x 10^5 M_sun), NGC 404. For the first time, radio emission at frequencies above 1.4 GHz has been detected in this galaxy. We found a modestly resolved source in the NGC 404 nucleus with a total radio luminosity of 7.6 +/- 0.7 x 10^17 W/Hz at 5 GHz and a spectral index from 5 to 7.45 GHz of alpha = -0.88 +/- 0.30. NGC 404 is only the third central intermediate mass black hole candidate detected in the radio regime with subarcsecond resolution. The position of the radio source is consistent with the optical center of the galaxy and the location of a known, hard X-ray point source (Lx ~1.2 x 10^37 erg/s). The faint radio and X-ray emission could conceivably be produced by an X-ray binary, star formation, a supernova remnant or a low-luminosity AGN powered by an intermediate mass black hole. In light of our new EVLA observations, we find that the most likely scenario is an accreting intermediate mass black hole, with other explanations incompatible with the observed X-ray and/or radio luminosities or statistically unlikely.Comment: Accepted for publication to Ap

Characterization of dentine to assess bond strength of dental composites

This study was performed to develop alternating dentine adhesion models that could help in the evaluation of a self-bonding dental composite. For this purpose dentine from human and ivory was characterized chemically and microscopically before and after acid etching using Raman and SEM. Mechanical properties of dentine were determined using 3 point bend test. Composite bonding to dentine, with and without use of acid pre-treatment and/or the adhesive, were assessed using a shear bond test. Furthermore, micro gap formation after restoration of 3 mm diameter cavities in dentine was assessed by SEM. Initial hydroxyapatite level in ivory was half that in human dentine. Surface hydroxyapatites decreased by approximately half with every 23 s of acid etch. The human dentine strength (56 MPa) was approximately double that of ivory, while the modulus was almost comparable to that of ivory. With adhesive use, average shear bond strengths were 30 and 26 MPa with and without acid etching. With no adhesive, average bond strength was 6 MPa for conventional composites. This, however, increased to 14 MPa with a commercial flowable "self-bonding" composite or upon addition of low levels of an acidic monomer to the experimental composite. The acidic monomer additionally reduced micro-gap formation with the experimental composite. Improved bonding and mechanical properties should reduce composite failures due to recurrent caries or fracture respectively

Not Enough Cooks in the Kitchen: Balancing Quality and Speed in Services

Do you find it hard to envision the future when you are struggling to keep up with the present? A reality in many libraries is high demand but limited resources. In this session, participants will develop a menu of current services offered in their position or department. After group discussions on criteria for evaluating services and shortening workflows, participants will eliminate one service and/or shorten its prep time in order to add a forward thinking service

Metabotropic Glutamate Receptors as Novel Therapeutic Targets on Visceral Sensory Pathways

Metabotropic glutamate receptors (mGluR) have a diverse range of structures and molecular coupling mechanisms. There are eight mGluR subtypes divided into three major groups. Group I (mGluR1 and 5) is excitatory; groups II (mGluR2 and 3) and III (mGluR 4, 6, and 7) are inhibitory. All mGluR are found in the mammalian nervous system but some are absent from sensory neurons. The focus here is on mGluR in sensory pathways from the viscera, where they have been explored as therapeutic targets. Group I mGluR are activated by endogenous glutamate or constitutively active without agonist. Constitutive activity can be exploited by inverse agonists to reduce neuronal excitability without synaptic input. This is promising for reducing activation of nociceptive afferents and pain using mGluR5 negative allosteric modulators. Many inhibitory mGluR are also expressed in visceral afferents, many of which markedly reduce excitability. Their role in visceral pain remains to be determined, but they have shown promise in inhibition of the triggering of gastro-esophageal reflux, via an action on mechanosensory gastric afferents. The extent of reflux inhibition is limited, however, and may not reach a clinically useful level. On the other hand, negative modulation of mGluR5 has very potent actions on reflux inhibition, which has produced the most likely candidates so far as therapeutic drugs. These act probably outside the central nervous system, and may therefore provide a generous therapeutic window. There are many unanswered questions about mGluR along visceral afferent pathways, the answers to which may reveal many more therapeutic candidates

Metastable Innershell Molecular State (MIMS)

We propose that the existence of Metastable Innershell Molecular State (MIMS) was experimentally discovered by Bae et al. in hypervelocity (v>100km/s) impact of nanoparticles. The decay of MIMS resulted in the observed intense soft x-rays in the range of 75 - 100 eV in agreement with Winterberg's recent prediction.Comment: Submitted to Physics Letters