Struggling to Breathe: COVID-19, Protest, and the LIS Response

The purpose of this article is to provide a follow up to “Libraries on the Frontlines: Neutrality and Social Justice,” which was published in 2017. It addresses institutional responses to protests and uprising in the spring and summer of 2020 after the deaths of Ahmaud Arbery, Breonna Taylor, and George Floyd—all of which occurred in the context of the global COVID-19 pandemic. The article expands the previous call for libraries to take a stand for Black Lives. We describe the events of 2020 (a global pandemic, multiple murders of unarmed Black people, and the consequent global protests) and responses from within library and information science, from our perspectives as women of color faculty and library professionals. We comment on how libraries are responding to current events, as well as the possibilities for panethnic solidarity. We also consider specifically how libraries and other institutions are responding to the racial uprisings through statements on social media and call for concrete action to ensure that their organizations and information practices are actively antiracist. In so doing, we update the claims and expand the appeals we made in 2017—that Black Lives Matter and that librarianship must not remain neutral

Patient-specific iPSC-derived cellular models of LGMDR1

Limb-girdle muscular dystrophy recessive 1 (LGMDR1) represents one of the most common types of LGMD in the population, where patients develop a progressive muscle degeneration. The disease is caused by mutations in calpain 3 gene, with over 500 mutations reported to date. However, the molecular events that lead to muscle wasting are not clear, nor the reasons for the great clinical variability among patients, and this has so far hindered the development of effective therapies. Here we generate human induced pluripotent stem cells (iPSCs) from skin fibroblasts of 2 healthy controls and 4 LGMDR1 patients with different mutations. The generated lines were able to differentiate into myogenic progenitors and myotubes in vitro and in vivo, upon a transient PAX7 overexpressing protocol. Thus, we have generated myogenic cellular models of LGMDR1 that harbor different CAPN3 mutations within a human genetic background, and which do not derive from muscular biopsies. These models will allow us to investigate disease mechanisms and test therapies. Despite the variability found among iPSC lines that was unrelated to CAPN3 mutations, we found that patient-derived myogenic progenitors and myotubes express lower levels of DMD, which codes a key protein in satellite cell regulation and myotube maturation

Struggling to Breathe: COVID-19, Protest, and the LIS Response

The purpose of this article is to provide a follow up to “Libraries on the Frontlines: Neutrality and Social Justice,” which was published in 2017. It addresses institutional responses to protests and uprising in the spring and summer of 2020 after the deaths of Ahmaud Arbery, Breonna Taylor, and George Floyd—all of which occurred in the context of the global COVID-19 pandemic. The article expands the previous call for libraries to take a stand for Black Lives. We describe the events of 2020 (a global pandemic, multiple murders of unarmed Black people, and the consequent global protests) and responses from within library and information science, from our perspectives as women of color faculty and library professionals. We comment on how libraries are responding to current events, as well as the possibilities for panethnic solidarity. We also consider specifically how libraries and other institutions are responding to the racial uprisings through statements on social media and call for concrete action to ensure that their organizations and information practices are actively antiracist. In so doing, we update the claims and expand the appeals we made in 2017—that Black Lives Matter and that librarianship must not remain neutral

Cross Section Limits for the 208^{208}Pb(86^{86}Kr,n)293^{293}118 Reaction

In April-May, 2001, the previously reported experiment to synthesize element 118 using the $^{208}$Pb($^{86}$Kr,n)$^{293}$118 reaction was repeated. No events corresponding to the synthesis of element 118 were observed with a total beam dose of 2.6 x 10$^{18}$ ions. The simple upper limit cross sections (1 event) were 0.9 and 0.6 pb for evaporation residue magnetic rigidities of 2.00 $T m$ and 2.12 $T m$, respectively. A more detailed cross section calculation, accounting for an assumed narrow excitation function, the energy loss of the beam in traversing the target and the uncertainty in the magnetic rigidity of the Z=118 recoils is also presented. Re-analysis of the primary data files from the 1999 experiment showed the reported element 118 events are not in the original data. The current results put constraints on the production cross section for synthesis of very heavy nuclei in cold fusion reactions.Comment: 7 pages, 2 figures. Submitted to EPJ

Advanced cell-based modeling of the royal disease: characterization of the mutated F9 mRNA

Essentials The Royal disease (RD) is a form of hemophilia B predicted to be caused by a splicing mutation. We generated an iPSC-based model of the disease allowing mechanistic studies at the RNA level. F9 mRNA analysis in iPSC-derived hepatocyte-like cells showed the predicted abnormal splicing. Mutated F9 mRNA level was very low but we also found traces of wild type transcripts. SUMMARY: Background The royal disease is a form of hemophilia B (HB) that affected many descendants of Queen Victoria in the 19th and 20th centuries. It was found to be caused by the mutation F9 c.278-3A>G. Objective To generate a physiological cell model of the disease and to study F9 expression at the RNA level. Methods Using fibroblasts from skin biopsies of a previously identified hemophilic patient bearing the F9 c.278-3A>G mutation and his mother, we generated induced pluripotent stem cells (iPSCs). Both the patient's and mother's iPSCs were differentiated into hepatocyte-like cells (HLCs) and their F9 mRNA was analyzed using next-generation sequencing (NGS). Results and Conclusion We demonstrated the previously predicted aberrant splicing of the F9 transcript as a result of an intronic nucleotide substitution leading to a frameshift and the generation of a premature termination codon (PTC). The F9 mRNA level in the patient's HLCs was significantly reduced compared with that of his mother, suggesting that mutated transcripts undergo nonsense-mediated decay (NMD), a cellular mechanism that degrades PTC-containing mRNAs. We also detected small proportions of correctly spliced transcripts in the patient's HLCs, which, combined with genetic variability in splicing and NMD machineries, could partially explain some clinical variability among affected members of the European royal families who had lifespans above the average. This work allowed the demonstration of the pathologic consequences of an intronic mutation in the F9 gene and represents the first bona fide cellular model of HB allowing the study of rare mutations at the RNA level

EVIDENCE OF PRIMARY EVENTS IN 20Ne, 22Ne FRAGMENTATION FROM COINCIDENCE MEASUREMENTS IN 20, 22Ne + 93Nb REACTION AT 30 MeV/A

Evidence that primary ejectiles formation strongly depends on the projectile structure is given by comparison of 20Ne + 93Nb and 22Ne + 93Nb reactions at 30 MeV/A. Pick-up, stripping, break-up mechanism are identified using light particles-projectile fragments coïncidence measurements

Whole-genome sequencing for an enhanced understanding of genetic variation among South Africans

The Southern African Human Genome Programme is a national initiative that aspires to unlock the unique genetic character of southern African populations for a better understanding of human genetic diversity. In this pilot study the Southern African Human Genome Programme characterizes the genomes of 24 individuals (8 Coloured and 16 black southeastern Bantu-speakers) using deep whole-genome sequencing. A total of ~16 million unique variants are identified. Despite the shallow time depth since divergence between the two main southeastern Bantu-speaking groups (Nguni and Sotho-Tswana), principal component analysis and structure analysis reveal significant (p < 10−6) differentiation, and FST analysis identifies regions with high divergence. The Coloured individuals show evidence of varying proportions of admixture with Khoesan, Bantu-speakers, Europeans, and populations from the Indian sub-continent. Whole-genome sequencing data reveal extensive genomic diversity, increasing our understanding of the complex and region-specific history of African populations and highlighting its potential impact on biomedical research and genetic susceptibility to disease

Modelos de Regressão para Dados de Contagem

Neste trabalho analisam-se os principais modelos de regressão para dados de contagem, na perspectiva habitual de especificação, estimação e avaliação. Após a descrição detalhada dos modelos tradicionais, Poisson e Binomial Negativo, explora-se pormenorizadamente o Poisson Generalizado, um modelo recentemente introduzido nesta área. Os três modelos são depois adaptados a casos em que a amostra recolhida é truncada em zero. De seguida, abordam-se alguns testes de especificação, começando-se por avaliar o modelo de Poisson face às duas alternativas referidas. Para tal, deduzem-se testes score, os quais provam que, para determinadas parametrizações, os modelos Binomial Negativo e Poisson Generalizado constituem alternativas localmente equivalentes. De modo a testar a adequabilidade destes últimos modelos, consideram-se ainda diversos testes de hipóteses não encaixadas, para alguns dos quais é realizado um estudo de simulação de Monte Carlo com o objectivo de examinar o seu comportamento quando aplicados a modelos truncados. Os resultados obtidos mostram que o desempenho dos testes é satisfatório, embora alguns deles sejam claramente afectados pelo nível de sobredispersão e pelo grau de truncagem admitidos

Worldwide distribution of NAT2 diversity: Implications for NAT2 evolutionary history

<p>Abstract</p> <p>Background</p> <p>The N-acetyltransferase 2 (<it>NAT2</it>) gene plays a crucial role in the metabolism of many drugs and xenobiotics. As it represents a likely target of population-specific selection pressures, we fully sequenced the <it>NAT2 </it>coding region in 97 Mandenka individuals from Senegal, and compared these sequences to extant data on other African populations. The Mandenka data were further included in a worldwide dataset composed of 41 published population samples (6,727 individuals) from four continental regions that were adequately genotyped for all common <it>NAT2 </it>variants so as to provide further insights into the worldwide haplotype diversity and population structure at <it>NAT2</it>.</p> <p>Results</p> <p>The sequencing analysis of the <it>NAT2 </it>gene in the Mandenka sample revealed twelve polymorphic sites in the coding exon (two of which are newly identified mutations, C345T and C638T), defining 16 haplotypes. High diversity and no molecular signal of departure from neutrality were observed in this West African sample. On the basis of the worldwide genotyping survey dataset, we found a strong genetic structure differentiating East Asians from both Europeans and sub-Saharan Africans. This pattern could result from region- or population-specific selective pressures acting at this locus, as further suggested in the HapMap data by extremely high values of <it>F</it>_STfor a few SNPs positions in the <it>NAT2 </it>coding exon (T341C, C481T and A803G) in comparison to the empirical distribution of <it>F</it>_STvalues accross the whole 400-kb region of the <it>NAT </it>gene family.</p> <p>Conclusion</p> <p>Patterns of sequence variation at <it>NAT2 </it>are consistent with selective neutrality in all sub-Saharan African populations investigated, whereas the high level of population differentiation between Europeans and East Asians inferred from SNPs could suggest population-specific selective pressures acting at this locus, probably caused by differences in diet or exposure to other environmental signals.</p