Radiative decay of a massive particle and the non-thermal process in primordial nucleosynthesis

We consider the effects on big bang nucleosynthesis (BBN) of the radiative decay of a long-lived massive particle. If high-energy photons are emitted after the BBN epoch ($t \sim 1 - 10^3$ sec), they may change the abundances of the light elements through photodissociation processes, which may result in a significant discrepancy between standard BBN and observation. Taking into account recent observational and theoretical developments in this field, we revise our previous study constraining the abundance of the radiatively-decaying particles. In particular, on the theoretical side, it was recently claimed that the non-thermal production of $^6$Li, which is caused by the photodissociation of \hefour, most severely constrains the abundance of the radiatively-decaying particle. We will see, however, it is premature to emphasize the importance of the non-thermal production of $^6$Li because (i) the theoretical computation of the $^6$Li abundance has large uncertainty due to the lack of the precise understanding of the $^6$Li production cross section, and (ii) the observational data of $^6$Li abundance has large errors.Comment: 15 pages, using REVTeX and 3 postscript figure

Elevated serum homocysteine levels have differential gender-specific associations with motor and cognitive states in Parkinson’s disease

Background: Studies attempting to elucidate an association between homocysteine and symptom progression in Parkinson’s disease (PD) have had largely discrepant findings. This study aimed to investigate elevated serum homocysteine levels and symptom progression in a cohort of PD patients. Methods: Serum homocysteine, folate, and vitamin B12 levels were measured in 205 people with PD and 78 age-matched healthy controls. People with Parkinson’s disease underwent a battery of clinical assessments to evaluate symptom severity, including motor (MDS-UPDRS) and cognitive (ACE-R) assessments. Multivariate generalized linear models were created, controlling for confounding variables, and were used to determine whether serum markers are associated with various symptom outcome measures. Results; People with Parkinson’s disease displayed significantly elevated homocysteine levels (p\u3c0.001), but not folate or vitamin B12 levels, when compared to healthy controls. A significant positive correlation between homocysteine and MDS-UPDRS III score was identified in males with Parkinson’s disease (rs=0.319, p\u3c0.001), but not in females, whereas a significant negative correlation between homocysteine levels and total ACE-R score was observed in females with Parkinson’s disease (rs=−0.449, p\u3c0.001), but not in males. Multivariate general linear models confirmed that homocysteine was significantly predictive of MDS-UPDRSIII score in male patients (p = 0.004) and predictive of total ACE-R score in female patients (p = 0.021). Conclusion: Elevated serum homocysteine levels are associated with a greater motor impairment in males with Parkinson’s disease and poorer cognitive performance in females with Parkinson’s disease. Our gender specific findings may help to explain previous discrepancies in the literature surrounding the utility of homocysteine as a biomarker in PD

Black Girls Speak STEM: Counterstories of Informal and Formal Learning Experiences

This study presents the interpretations and perceptions of Black girls who participated in I AM STEM – a community-based informal science, technology, engineering, and mathematics (STEM) program. Using narrative inquiry, participants generated detailed accounts of their informal and formal STEM learning experiences. Critical race methodology informed this research to portray the dynamic and complex experiences of girls of color, whose stories have historically been silenced and misrepresented. The data sources for this qualitative study included individual interviews, student reflection journals, samples of student work, and researcher memos, which were triangulated to produce six robust counterstories. Excerpts of the counterstories are presented in this article. The major findings of this research revealed that I AM STEM ignited an interest in STEM learning through field trips and direct engagement in scientific phenomena that allowed the girls to become agentic in continuing their engagement in STEM activities throughout the year. This call to awaken the voices of Black girls to speak casts light on their experiences and challenges as STEM learners ⎯ from their perspectives. The findings confirm that when credence and counterspaces are given to Black girls, they are poised to reveal their luster toward STEM learning. This study provided a space for Black girls to reflect on their STEM learning experiences, formulate new understandings, and make connections between the informal and formal learning environments within the context of their everyday lives, thus offering a more holistic approach to STEM learning that occurs across settings and over a lifetime

Late Replicating Domains Are Highly Recombining in Females but Have Low Male Recombination Rates: Implications for Isochore Evolution

In mammals sequences that are either late replicating or highly recombining have high rates of evolution at putatively neutral sites. As early replicating domains and highly recombining domains both tend to be GC rich we a priori expect these two variables to covary. If so, the relative contribution of either of these variables to the local neutral substitution rate might have been wrongly estimated owing to covariance with the other. Against our expectations, we find that sex-averaged recombination rates show little or no correlation with replication timing, suggesting that they are independent determinants of substitution rates. However, this result masks significant sex-specific complexity: late replicating domains tend to have high recombination rates in females but low recombination rates in males. That these trends are antagonistic explains why sex-averaged recombination is not correlated with replication timing. This unexpected result has several important implications. First, although both male and female recombination rates covary significantly with intronic substitution rates, the magnitude of this correlation is moderately underestimated for male recombination and slightly overestimated for female recombination, owing to covariance with replicating timing. Second, the result could explain why male recombination is strongly correlated with GC content but female recombination is not. If to explain the correlation between GC content and replication timing we suppose that late replication forces reduced GC content, then GC promotion by biased gene conversion during female recombination is partly countered by the antagonistic effect of later replicating sequence tending increase AT content. Indeed, the strength of the correlation between female recombination rate and local GC content is more than doubled by control for replication timing. Our results underpin the need to consider sex-specific recombination rates and potential covariates in analysis of GC content and rates of evolution

Organizational Heterogeneity of Vertebrate Genomes

Genomes of higher eukaryotes are mosaics of segments with various structural, functional, and evolutionary properties. The availability of whole-genome sequences allows the investigation of their structure as “texts” using different statistical and computational methods. One such method, referred to as Compositional Spectra (CS) analysis, is based on scoring the occurrences of fixed-length oligonucleotides (k-mers) in the target DNA sequence. CS analysis allows generating species- or region-specific characteristics of the genome, regardless of their length and the presence of coding DNA. In this study, we consider the heterogeneity of vertebrate genomes as a joint effect of regional variation in sequence organization superimposed on the differences in nucleotide composition. We estimated compositional and organizational heterogeneity of genome and chromosome sequences separately and found that both heterogeneity types vary widely among genomes as well as among chromosomes in all investigated taxonomic groups. The high correspondence of heterogeneity scores obtained on three genome fractions, coding, repetitive, and the remaining part of the noncoding DNA (the genome dark matter - GDM) allows the assumption that CS-heterogeneity may have functional relevance to genome regulation. Of special interest for such interpretation is the fact that natural GDM sequences display the highest deviation from the corresponding reshuffled sequences

CHFR Protein Expression Predicts Outcomes to Taxane-Based First Line Therapy in Metastatic NSCLC

Abstract Purpose: Currently, there is no clinically validated test for the prediction of response to tubulin-targeting agents in non–small cell lung cancer (NSCLC). Here, we investigated the significance of nuclear expression of the mitotic checkpoint gene checkpoint with forkhead and ringfinger domains (CHFR) as predictor of response and overall survival with taxane-based first-line chemotherapy in advanced stage NSCLC. Methods: We studied a cohort of 41 patients (median age 63 years) with advanced NSCLC treated at the Atlanta VAMC between 1999 and 2010. CHFR expression by immunohistochemistry (score 0–4) was correlated with clinical outcome using chi-square test and Cox proportional models. A cutoff score of “3” was determined by receiver operator characteristics analysis for “low” CHFR expression. Results were validated in an additional 20 patients who received taxane-based chemotherapy at Emory University Hospital and the Atlanta VAMC. Results: High expression (score = 4) of CHFR is strongly associated with adverse outcomes: the risk for progressive disease after first-line chemotherapy with carboplatin–paclitaxel was 52% in patients with CHFR-high versus only 19% in those with CHFR-low tumors (P = 0.033). Median overall survival was strongly correlated with CHFR expression status (CHFR low: 9.9 months; CHFR high: 6.2 months; P = 0.002). After multivariate adjustment, reduced CHFR expression remained a powerful predictor of improved overall survival (HR = 0.24; 95% CI, 0.1–0.58%; P = 0.002). In the validation set, low CHFR expression was associated with higher likelihood of clinical benefit (P = 0.03) and improved overall survival (P = 0.038). Conclusions: CHFR expression is a novel predictive marker of response and overall survival in NSCLC patients treated with taxane-containing chemotherapy. Clin Cancer Res; 19(6); 1603–11. ©2013 AACR.</jats:p

A Gene Catalogue of the Euchromatic Male-Specific Region of the Horse Y Chromosome: Comparison with Human and Other Mammals

Studies of the Y chromosome in primates, rodents and carnivores provide compelling evidence that the male specific region of Y (MSY) contains functional genes, many of which have specialized roles in spermatogenesis and male-fertility. Little similarity, however, has been found between the gene content and sequence of MSY in different species. This hinders the discovery of species-specific male fertility genes and limits our understanding about MSY evolution in mammals. Here, a detailed MSY gene catalogue was developed for the horse – an odd-toed ungulate. Using direct cDNA selection from horse testis, and sequence analysis of Y-specific BAC clones, 37 horse MSY genes/transcripts were identified. The genes were mapped to the MSY BAC contig map, characterized for copy number, analyzed for transcriptional profiles by RT-PCR, examined for the presence of ORFs, and compared to other mammalian orthologs. We demonstrate that the horse MSY harbors 20 X-degenerate genes with known orthologs in other eutherian species. The remaining 17 genes are acquired or novel and have so far been identified only in the horse or donkey Y chromosomes. Notably, 3 transcripts were found in the heterochromatic part of the Y. We show that despite substantial differences between the sequence, gene content and organization of horse and other mammalian Y chromosomes, the functions of MSY genes are predominantly related to testis and spermatogenesis. Altogether, 10 multicopy genes with testis-specific expression were identified in the horse MSY, and considered likely candidate genes for stallion fertility. The findings establish an important foundation for the study of Y-linked genetic factors governing fertility in stallions, and improve our knowledge about the evolutionary processes that have shaped Y chromosomes in different mammalian lineages

Updated Nucleosynthesis Constraints on Unstable Relic Particles

We revisit the upper limits on the abundance of unstable massive relic particles provided by the success of Big-Bang Nucleosynthesis calculations. We use the cosmic microwave background data to constrain the baryon-to-photon ratio, and incorporate an extensively updated compilation of cross sections into a new calculation of the network of reactions induced by electromagnetic showers that create and destroy the light elements deuterium, he3, he4, li6 and li7. We derive analytic approximations that complement and check the full numerical calculations. Considerations of the abundances of he4 and li6 exclude exceptional regions of parameter space that would otherwise have been permitted by deuterium alone. We illustrate our results by applying them to massive gravitinos. If they weigh ~100 GeV, their primordial abundance should have been below about 10^{-13} of the total entropy. This would imply an upper limit on the reheating temperature of a few times 10^7 GeV, which could be a potential difficulty for some models of inflation. We discuss possible ways of evading this problem.Comment: 40 pages LaTeX, 18 eps figure