Measuring Influence on Twitter

A survey took in MAT 1372 about students\u27 opinions on Twitter showed that most of them assumed that if a Twitter account has more followers, it will receive more likes or replies. However, accounts can buy followers, and followers do not necessarily mean engagement. In this paper, we used Twitter because it is a significant player in social media, but we can measure influence without using Twitter\u27s follower count. We took a reference from Meeyoung Cha\u27s article The Million Follower Fallacy, which has demonstrated that the Twitter follower count is a meaningless metric in determining influence. To measure influence, a new metric was developed, which is what we called The User Ratio

Molecular pathways driving omeprazole nephrotoxicity

Omeprazole, a proton pump inhibitor used to treat peptic ulcer and gastroesophageal reflux disease, has been associated to chronic kidney disease and acute interstitial nephritis. However, whether omeprazole is toxic to renal cells is unknown. Omeprazole has a lethal effect over some cancer cells, and cell death is a key process in kidney disease. Thus, we evaluated the potential lethal effect of omeprazole over tubular cells. Omeprazole induced dose-dependent cell death in human and murine proximal tubular cell lines and in human primary proximal tubular cell cultures. Increased cell death was observed at the high concentrations used in cancer cell studies and also at lower concentrations similar to those in peptic ulcer patient serum. Cell death induced by omeprazole had features of necrosis such as annexin V/7-AAD staining, LDH release, vacuolization and irregular chromatin condensation. Weak activation of caspase-3 was observed but inhibitors of caspases (zVAD), necroptosis (Necrostatin-1) or ferroptosis (Ferrostatin-1) did not prevent omeprazole-induced death. However, omeprazole promoted a strong oxidative stress response affecting mitochondria and lysosomes and the antioxidant N-acetyl-cysteine reduced oxidative stress and cell death. By contrast, iron overload increased cell death. An adaptive increase in the antiapoptotic protein BclxL failed to protect cells. In mice, parenteral omeprazole increased tubular cell death and the expression of NGAL and HO-1, markers of renal injury and oxidative stress, respectively. In conclusion, omeprazole nephrotoxicity may be related to induction of oxidative stress and renal tubular cell deathSupported by FIS CP12/03262, CP14/00133, PI16/02057, PI16/ 01900, PI18/01366, PI19/00588, PI19/00815, DTS18/00032, ERAPerMed-JTC2018 (KIDNEY ATTACK AC18/00064 and PERSTIGAN AC18/00071, ISCIII-RETIC REDinREN RD016/0009 FEDER funds, Sociedad Española de Nefrología, Fundacion Renal Iñigo Álvarez de Toledo (FRIAT), ISCIII Miguel Servet (ABS, MDS-N), ISCIII Sara Borrell (JMM-M), Comunidad de Madrid CIFRA2 B2017/BMD-3686 (MF-B and DM-S

Filtration efficiency of air conditioner filters and face masks to limit exposure to aerosolized algal toxins

Harmful algal blooms (HABs) can generate toxins that can be aerosolized and negatively impact human health through inhalation. HABs are often found in waterways near residences, therefore, aerosolized HAB toxins can potentially affect both indoor and outdoor air quality. Given that HABs are predicted to increase worldwide, effective mitigation strategies are needed to prevent the inhalation of aerosolized HAB toxins. In this work, we characterized both the particle filtration efficiency using particle sizing instruments as well as the mass concentration of different congeners of aerosolized microcystin (MC) toxins that penetrate through commercially available face masks and air conditioner (AC) filters. Particles were generated from cultures of the toxin-producing cyanobacteria Microcystis aeruginosa. Hydrophobic congeners of microcystin including MC-LF and MC-LW were enriched in aerosols compared to water, with MC-LR being the most abundant, which has implications for the toxicity of inhalable particles generated from HAB-contaminated waters. Particle transmission efficiencies and toxin filtration efficiencies scaled with the manufacturer-provided filter performance ratings. Up to 80% of small, microcystin-containing aerosols were transmitted through AC filters with low filter performance ratings. In contrast, both face masks as well as AC filters with high filter performance ratings efficiently removed toxin-containing particles to below limits of quantification. Our findings suggest that face masks and commercially available AC filters with high filtration efficiency ratings are suitable mitigation strategies to avoid indoor and outdoor air exposure to aerosolized HAB toxins. This work also has relevance for reducing airborne exposure to other HAB toxins, non-HAB toxins, pathogens, and viruses, including SARS-CoV-2, the virus responsible for the COVID-19 pandemic

Effect of ABCB1 and ABCC3 Polymorphisms on Osteosarcoma Survival after Chemotherapy: A Pharmacogenetic Study

Standard treatment for osteosarcoma patients consists of a combination of cisplatin, adriamycin, and methotrexate before surgical resection of the primary tumour, followed by postoperative chemotherapy including vincristine and cyclophosphamide. Unfortunately, many patients still relapse or suffer adverse events. We examined whether common germline polymorphisms in chemotherapeutic transporter and metabolic pathway genes of the drugs used in standard osteosarcoma treatment may predict treatment response. METHODOLOGY/PRINCIPAL FINDINGS: In this study we screened 102 osteosarcoma patients for 346 Single Nucleotide Polymorphisms (SNPs) and 2 Copy Number Variants (CNVs) in 24 genes involved in the metabolism or transport of cisplatin, adriamycin, methotrexate, vincristine, and cyclophosphamide. We studied the association of the genotypes with tumour response and overall survival. We found that four SNPs in two ATP-binding cassette genes were significantly associated with overall survival: rs4148416 in ABCC3 (per-allele HR = 8.14, 95%CI = 2.73-20.2, p-value = 5.1x10(-)(5)), and three SNPs in ABCB1, rs4148737 (per-allele HR = 3.66, 95%CI = 1.85-6.11, p-value = 6.9x10(-)(5)), rs1128503 and rs10276036 (r(2) = 1, per-allele HR = 0.24, 95%CI = 0.11-0.47 p-value = 7.9x10(-)(5)). Associations with these SNPs remained statistically significant after correction for multiple testing (all corrected p-values [permutation test] </= 0.03). CONCLUSIONS: Our findings suggest that these polymorphisms may affect osteosarcoma treatment efficacy. If these associations are independently validated, these variants could be used as genetic predictors of clinical outcome in the treatment of osteosarcoma, helping in the design of individualized therapy

Ram pressure feeding super-massive black holes

When supermassive black holes at the center of galaxies accrete matter (usually gas), they give rise to highly energetic phenomena named Active Galactic Nuclei (AGN). A number of physical processes have been proposed to account for the funneling of gas towards the galaxy centers to feed the AGN. There are also several physical processes that can strip gas from a galaxy, and one of them is ram pressure stripping in galaxy clusters due to the hot and dense gas filling the space between galaxies. We report the discovery of a strong connection between severe ram pressure stripping and the presence of AGN activity. Searching in galaxy clusters at low redshift, we have selected the most extreme examples of jellyfish galaxies, which are galaxies with long tentacles of material extending for dozens of kpc beyond the galaxy disk. Using the MUSE spectrograph on the ESO Very Large Telescope, we find that 6 out of the 7 galaxies of this sample host a central AGN, and two of them also have galactic-scale AGN ionization cones. The high incidence of AGN among the most striking jellyfishes may be due to ram pressure causing gas to flow towards the center and triggering the AGN activity, or to an enhancement of the stripping caused by AGN energy injection, or both. Our analysis of the galaxy position and velocity relative to the cluster strongly supports the first hypothesis, and puts forward ram pressure as another, yet unforeseen, possible mechanism for feeding the central supermassive black hole with gas.Comment: published in Nature, Vol.548, Number 7667, pag.30

The missing link: Bordetella petrii is endowed with both the metabolic versatility of environmental bacteria and virulence traits of pathogenic Bordetellae

Gross R, Guzman CA, Sebaihia M, et al. The missing link: Bordetella petrii is endowed with both the metabolic versatility of environmental bacteria and virulence traits of pathogenic Bordetellae. BMC Genomics. 2008;9(1): 449.Background: Bordetella petrii is the only environmental species hitherto found among the otherwise host-restricted and pathogenic members of the genus Bordetella. Phylogenetically, it connects the pathogenic Bordetellae and environmental bacteria of the genera Achromobacter and Alcaligenes, which are opportunistic pathogens. B. petrii strains have been isolated from very different environmental niches, including river sediment, polluted soil, marine sponges and a grass root. Recently, clinical isolates associated with bone degenerative disease or cystic fibrosis have also been described. Results: In this manuscript we present the results of the analysis of the completely annotated genome sequence of the B. petrii strain DSMZ12804. B. petrii has a mosaic genome of 5,287,950 bp harboring numerous mobile genetic elements, including seven large genomic islands. Four of them are highly related to the clc element of Pseudomonas knackmussii B13, which encodes genes involved in the degradation of aromatics. Though being an environmental isolate, the sequenced B. petrii strain also encodes proteins related to virulence factors of the pathogenic Bordetellae, including the filamentous hemagglutinin, which is a major colonization factor of B. pertussis, and the master virulence regulator BvgAS. However, it lacks all known toxins of the pathogenic Bordetellae. Conclusion: The genomic analysis suggests that B. petrii represents an evolutionary link between free-living environmental bacteria and the host-restricted obligate pathogenic Bordetellae. Its remarkable metabolic versatility may enable B. petrii to thrive in very different ecological niches

Uncoupling the functions of CALM in VAMP sorting and clathrin-coated pit formation.

CALM (clathrin assembly lymphoid myeloid leukemia protein) is a cargo-selective adaptor for the post-Golgi R-SNAREs VAMPs 2, 3, and 8, and it also regulates the size of clathrin-coated pits and vesicles at the plasma membrane. The present study has two objectives: to determine whether CALM can sort additional VAMPs, and to investigate whether VAMP sorting contributes to CALM-dependent vesicle size regulation. Using a flow cytometry-based endocytosis efficiency assay, we demonstrate that CALM is also able to sort VAMPs 4 and 7, even though they have sorting signals for other clathrin adaptors. CALM homologues are present in nearly every eukaryote, suggesting that the CALM family may have evolved as adaptors for retrieving all post-Golgi VAMPs from the plasma membrane. Using a knockdown/rescue system, we show that wild-type CALM restores normal VAMP sorting in CALM-depleted cells, but that two non-VAMP-binding mutants do not. However, when we assayed the effect of CALM depletion on coated pit morphology, using a fluorescence microscopy-based assay, we found that the two mutants were as effective as wild-type CALM. Thus, we can uncouple the sorting function of CALM from its structural role

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO

The Type III Secreted Protein BspR Regulates the Virulence Genes in Bordetella bronchiseptica

Bordetella bronchiseptica is closely related with B. pertussis and B. parapertussis, the causative agents of whooping cough. These pathogenic species share a number of virulence genes, including the gene locus for the type III secretion system (T3SS) that delivers effector proteins. To identify unknown type III effectors in Bordetella, secreted proteins in the bacterial culture supernatants of wild-type B. bronchiseptica and an isogenic T3SS-deficient mutant were compared with iTRAQ-based, quantitative proteomic analysis method. BB1639, annotated as a hypothetical protein, was identified as a novel type III secreted protein and was designated BspR (Bordetella secreted protein regulator). The virulence of a BspR mutant (ΔbspR) in B. bronchiseptica was significantly attenuated in a mouse infection model. BspR was also highly conserved in B. pertussis and B. parapertussis, suggesting that BspR is an essential virulence factor in these three Bordetella species. Interestingly, the BspR-deficient strain showed hyper-secretion of T3SS-related proteins. Furthermore, T3SS-dependent host cell cytotoxicity and hemolytic activity were also enhanced in the absence of BspR. By contrast, the expression of filamentous hemagglutinin, pertactin, and adenylate cyclase toxin was completely abolished in the BspR-deficient strain. Finally, we demonstrated that BspR is involved in the iron-responsive regulation of T3SS. Thus, Bordetella virulence factors are coordinately but inversely controlled by BspR, which functions as a regulator in response to iron starvation