Biology subjects

Song, A.

Publications and source records attributed to Song, A..

42 records · Page 3Linked to original sources

bioRxiv2019

Measuring Robustness of Brain Networks in Autism Spectrum Disorder with Ricci Curvature

Ricci curvature is a method for measuring the robustness of networks. In this work, we use Ricci curvature to measure robustness of brain networks affected by autism spectrum disorder (ASD). Subjects with ASD are given a stem cell infusion and are imaged with diffusion MRI before and after the infusion. By using Ricci curvature to measure changes in robustness, we quantify both local and global changes in the brain networks correlated with the infusion. Our results find changes in regions associated with ASD that were not detected via traditional brain network analysis.

neuroscience↗

bioRxiv2019

High-resolution and high-accuracy topographic and transcriptional maps of the nucleosome barrier

Nucleosomes represent mechanical and energetic barriers that RNA Polymerase II (Pol II) must overcome during transcription. A high-resolution description of the barrier topography, its modulation by epigenetic modifications, and their effects on Pol II nucleosome crossing dynamics, is still missing. Here, we obtain topographic and transcriptional (Pol II residence time) maps of canonical, H2A.Z, and monoubiquitinated H2B (uH2B) nucleosomes at near base-pair resolution and accuracy. Pol II crossing dynamics are complex, displaying pauses at specific loci, backtracking, and nucleosome hopping between wrapped states. While H2A.Z widens the barrier, uH2B heightens it, and both modifications greatly lengthen Pol II crossing time. Using the dwell times of Pol II at each nucleosomal position we extract the energetics of the barrier. The orthogonal barrier modifications of H2A.Z and uH2B, and their effects on Pol II dynamics rationalize their observed enrichment in +1 nucleosomes and suggest a mechanism for selective control of gene expression.\n\nHighlightsO_LIA single-molecule unzipping assay mimics DNA unwinding by Pol II and maps the topography of human canonical, H2A.Z and uH2B nucleosome barriers at high resolution\nC_LIO_LIReal-time dynamics and full molecular trajectories of Pol II crossing the nucleosomal barrier reveal the transcriptional landscape of the barrier at high accuracy\nC_LIO_LIH2A.Z enhances the width and uH2B the height of the barrier\nC_LIO_LIA unified mechanical model links position-dependent dwell times of Pol II on the nucleosome with energetics of the barrier\nC_LI

biophysics↗

bioRxiv2019

HIV-MALARIA CO-INFECTION AND ITS DETERMINANTS AMONG PATIENTS ATTENDING ANTIRETROVIRAL TREATMENT CLINIC IN ZARIA, NORTH-WESTERN NIGERIA

IntroductionMalaria and HIV are two important global public health problems. Together, they cause more than two million deaths each year. In sub-Saharan Africa alone, more than 29 million people are living with HIV/AIDS and about 70% of population is at risk to malaria infection. Nigeria accounts for about a quarter of the global malaria cases and tenth of the global HIV cases. Recent theories suggested possibilities of high occurrence of HIV-malaria co-infection wherever there is geographical overlap of the two diseases. We therefore conducted this study to determine the prevalence of HIV-malaria co-infection and its determinants in a malaria endemic setting.\n\nMethodsWe conducted a cross-sectional study. Two hundred and sixty-two clients attending antiretroviral treatment (ART) clinic in Zaria, Kaduna State were enrolled between February and April 2018 using systematic sampling technique. Questionnaires were administered to collect information on respondents personal characteristics as well as their knowledge, perception and practices on malaria prevention. Venous blood samples were collected and analyzed for malaria parasite, viral load, CD4, and FBC using Giemsa stained light microscopy, COBAS TaqMan equipment, BD FACS flow cytometer, and Sysmex haematology analyser respectively. Descriptive and inferential statistics were performed, predictors of HIV-malaria co-infection were ascertained at multivariate analysis.\n\nResultsMedian age of the respondents was 33 years, 52% were females, 65% were married, 65% were employed, 57% lived in urban residence, and 34% had tertiary education. The prevalence of malaria co-infection among HIV patients was found to be 22.9%. Significant risk factors for the co-infection were high HIV viral load (aOR= 3.30, C.I = 1.15-9.45), being co-infected with TB (aOR= 5.60, C.I = 1.34-23.33), poor knowledge of malaria infection (aOR= 3.12, C.I = 1.27-7.72) and poor practice of malaria prevention (aOR= 13.30, C.I = 4.88-36.23).\n\nConclusionThe level of occurrence of malaria among HIV infected patients in this setting calls for attention. We recommended that health education on malaria should be a priority in malaria control programme; the programmes for control of HIV, malaria and TB should collaborate to ensure integrated service delivery and that people living with HIV/AIDS should be given special consideration for malaria prevention.

epidemiology↗

bioRxiv2019

Unique structural features of the mitochondrial AAA+ protease AFG3L2 reveal the molecular basis for activity in health and disease

Mitochondrial AAA+ quality control proteases regulate diverse aspects of mitochondrial biology through specialized protein degradation, but the underlying molecular mechanisms that define the diverse activities of these enzymes remain poorly defined. The mitochondrial AAA+ protease AFG3L2 is of particular interest, as genetic mutations localized throughout AFG3L2 are linked to diverse neurodegenerative disorders. However, a lack of structural data has limited our understanding of how mutations impact enzymatic activity. Here, we used cryo-EM to determine a substrate-bound structure of the catalytic core of human AFG3L2. This structure identifies multiple specialized structural features within AFG3L2 that integrate with conserved structural motifs required for hand-over-hand ATP-dependent substrate translocation to engage, unfold and degrade targeted proteins. Mapping disease-relevant AFG3L2 mutations onto our structure demonstrates that many of these mutations localize to these unique structural features of AFG3L2 and distinctly influence its activity and stability. Our results provide a molecular basis for neurological phenotypes associated with different AFG3L2 mutations, and establish a structural framework to understand how different members of the AAA+ superfamily achieve specialized, diverse biological functions.

molecular biology↗

bioRxiv2018

Efficient transposon mutagenesis mediated by an IPTG-controlled conditional suicide plasmid

BackgroundTransposon mutagenesis is highly valuable for bacterial genetic and genomic studies. The transposons are usually delivered into host cells through conjugation or electroporation of a suicide plasmid. However, many bacterial species cannot be efficiently conjugated or transformed for transposon saturation mutagenesis. For this reason, temperature-sensitive (ts) plasmids have also been developed for transposon mutagenesis, but prolonged incubation at high temperatures to induce ts plasmid loss can be harmful to the hosts and lead to enrichment of mutants with adaptive genetic changes. In addition, the ts phenotype of a plasmid is often strain- or species-specific, as it may become non-ts or suicidal in different bacterial species.\n\nResultsWe have engineered several conditional suicide plasmids that have a broad host range and whose loss is IPTG-controlled. One construct, which has the highest stability in the absence of IPTG induction, was then used as a curable vector to deliver hyperactive miniTn5 transposons for insertional mutagenesis. Our analyses show that these new tools can be used for efficient and regulatable transposon mutagenesis in Escherichia coli, Acinetobacter baylyi and Pseudomonas aeruginosa. In P. aeruginosa PAO1, we have used this method to generate a Tn5 insertion library with an estimated diversity of ~108, which is ~2 logs larger than the best transposon insertional library of PAO1 and related Pseudomonas strains previously reported.\n\nConclusionWe have developed a number of IPTG-controlled conditional suicide plasmids. By exploiting one of them for transposon delivery, a highly efficient and broadly useful mutagenesis system has been developed. As the assay condition is mild, we believe that our methodology will have broad applications in microbiology research.

microbiology↗

bioRxiv2018

Conformational ensemble of the human TRPV3 ion channel

Transient receptor potential vanilloid channel 3 (TRPV3), a member of the thermosensitive TRP (thermoTRPV) channels, is activated by warm temperatures and serves as a key regulator of normal skin physiology through the release of pro-inflammatory messengers. Mutations in trpv3 have been identified as the cause of the congenital skin disorder, Olmsted syndrome. Unlike other members of the thermoTRPV channel family, TRPV3 sensitizes upon repeated simulation, yet a lack of structural information about the channel precludes a molecular-level understanding of TRPV3 sensitization and gating. Here, we present the cryo-electron microscopy structures of apo and sensitized human TRPV3, as well as several structures of TRPV3 in the presence of the common thermoTRPV agonist 2-aminoethoxydiphenyl borate (2-APB). Our results show -to-{pi}-helix transitions in the S6 during sensitization, and suggest a critical role for the S4-S5 linker {pi}-helix during ligand gating.

biochemistry↗