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Abstract In May and June of 2021, marine microbial samples were collected for DNA sequencing in East Sound, WA, USA every 4 hours for 22 days. This high temporal resolution sampling effort captured the last 3 days of a Rhizosolenia sp. bloom, the initiation and complete bloom cycle of Chaetoceros socialis (8 days), and the following bacterial bloom (2 days). Metagenomes were completed on the time series, and the dataset includes 128 size-fractionated microbial samples (0.22–1.2 µm), providing gene abundances for the dominant members of bacteria, archaea, and viruses. This dataset also has time-matched nutrient analyses, flow cytometry data, and physical parameters of the environment at a single point of sampling within a coastal ecosystem that experiences regular bloom events, facilitating a range of modeling efforts that can be leveraged to understand microbial community structure and their influences on the growth, maintenance, and senescence of phytoplankton blooms.

Abstract Clonal hematopoiesis (CH) is a risk factor for the development of therapy-related myelodysplastic syndromes (tMDS) and acute myeloid leukemia (tAML). Adoption of targeted-immunotherapeutics since 2011, may alter the risk of CH progression to tMDS/AML. To study this, we evaluated risk of tMDS and tAML in 667 588 ≥ 1-year survivors of non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), melanoma and multiple-myeloma (MM) diagnosed during: 2000–2005, 2006–2010 and 2011–2016. The risk of tMDS increased significantly after NSCLC across all time periods (Ptrend = 0.002) while tAML risk decreased from 2006–2010 to 2011–2016, coinciding with increasing use of non-chemotherapeutic agents. tAML risk after RCC decreased (Ptrend = 0.007) whereas tMDS risk did not significantly change over time. After melanoma, tMDS and tAML risks were similar to the general population. tMDS and tAML risk after MM increased from the first to second time-period, however, only risk of tMDS decreased during last period. We report diverging trends in the risk of tAML and tMDS after adoption of modern cancer therapies for specific cancers. It is imperative to further explore impact of contemporary treatment strategies on clonal evolution. Modern treatments via their discrete mechanism of actions on pre-existing CH may alter the risk of subsequent tMDS and tAML.

Abstract Amyloid precursor protein (APP) is expressed in many tissues in human, mice and in zebrafish. In zebrafish, there are two orthologues, Appa and Appb. Interestingly, some cellular processes associated with APP overlap with cilia-mediated functions. Whereas the localization of APP to primary cilia of in vitro-cultured cells has been reported, we addressed the presence of APP in motile and in non-motile sensory cilia and its potential implication for ciliogenesis using zebrafish, mouse, and human samples. We report that Appa and Appb are expressed by ciliated cells and become localized at the membrane of cilia in the olfactory epithelium, otic vesicle and in the brain ventricles of zebrafish embryos. App in ependymal cilia persisted in adult zebrafish and was also detected in mouse and human brain. Finally, we found morphologically abnormal ependymal cilia and smaller brain ventricles in appa −/− appb −/− mutant zebrafish. Our findings demonstrate an evolutionary conserved localisation of APP to cilia and suggest a role of App in ciliogenesis and cilia-related functions.

BackgroundWith the dire economic situation in Lebanon, many of the basic resources of the hospitals needed to help fight COVID-19 infections are not available. In this paper, we studied the possible factors associated with increased mortality in a sample of Lebanese adults enrolled in three hospitals.MethodIn this retrospective cohort study, we analyzed data from 416 adults hospitalized in three institutions for a COVID-19 infection, from the opening of the COVID unit until their closure (period extending from March 2020 to June 2021). We used multivariate analyses to assess potential factors associated with COVID-19 mortality: gender, age, the presence of underlying medical conditions, and some medication taken during hospitalization.ResultsUsing variables related to baseline characteristics entered as independent variables, acute kidney injury (aOR = 4.057) and older age (aOR = 1.053) were associated with a higher probability of death. After adjusting baseline characteristics and factors related to admission entered as independent variables, enoxaparin intake (aOR = 0.435) was significantly associated with a lower probability of death, whereas old age (aOR = 1.049) and ventilation (aOR = 1.2) were significantly associated with higher odds of death. When all variables that showed significance in bivariate analysis were entered, old age (aOR = 1.243) and highest PaCO2 during hospitalization (aOR = 1.192) were significantly associated with higher mortality. With a weak effect, atrial fibrillation, COPD, and higher leucocyte counts on admission were significantly associated with higher odds of death.ConclusionThese findings could help us prevent severe diseases in patients with several comorbidities and adjust therapeutic care to improve future outcomes. More studies should compare the outcome of different COVID-19 strains as well as the impact of vaccination on those with multiple comorbidities, especially on the mortality rate culminating from disease complications.

Background With the dire economic situation in Lebanon, many of the basic resources of the hospitals needed to help fight COVID-19 infections are not available. In this paper, we studied the possible factors associated with increased mortality in a sample of Lebanese adults enrolled in three hospitals. Method In this retrospective cohort study, we analyzed data from 416 adults hospitalized in three institutions for a COVID-19 infection, from the opening of the COVID unit until their closure (period extending from March 2020 to June 2021). We used multivariate analyses to assess potential factors associated with COVID-19 mortality: gender, age, the presence of underlying medical conditions, and some medication taken during hospitalization. Results Using variables related to baseline characteristics entered as independent variables, acute kidney injury (aOR = 4.057) and older age (aOR = 1.053) were associated with a higher probability of death. After adjusting baseline characteristics and factors related to admission entered as independent variables, enoxaparin intake (aOR = 0.435) was significantly associated with a lower probability of death, whereas old age (aOR = 1.049) and ventilation (aOR = 1.2) were significantly associated with higher odds of death. When all variables that showed significance in bivariate analysis were entered, old age (aOR = 1.243) and highest PaCO2 during hospitalization (aOR = 1.192) were significantly associated with higher mortality. With a weak effect, atrial fibrillation, COPD, and higher leucocyte counts on admission were significantly associated with higher odds of death. Conclusion These findings could help us prevent severe diseases in patients with several comorbidities and adjust therapeutic care to improve future outcomes. More studies should compare the outcome of different COVID-19 strains as well as the impact of vaccination on those with multiple comorbidities, especially on the mortality rate culminating from disease complications.

In agroecosystems, soil biodiversity is increasingly becoming more recognized as providing benefits to both plants and human health. It performs a wide variety of ecological services beyond the recycling of nutrients to plant growth and manage pests and diseases below the economic injury level. This study investigated the effects of three Pseudomonas isolates (Q172B, Q110B and Q036B), isolated from untreated tomato rhizospheric soil, as a biological control agent of Bemisia tabaci which is a key pest of tomato crops. The study was conducted under laboratory and glasshouse conditions and the water treatment was used as a control. Adult mortality rates were assessed during three days at 24h interval and larva mortality rates were evaluated during six days after treatment at 48h interval. Results indicate that Q036B isolate has a faster effect on B. tabaci adult and larvae. Under laboratory conditions, all three Pseudomonas isolates (Q110B, Q036B and Q172B) have a significant effect on B. tabaci adult mortality compared to control. The earliest and the most important mortality rate of 76% was recorded by Q036B. Two isolates Q036B and Q110B caused a significant mortality on B. tabaci larvae; with highest mortality effect (79%) was observed for Q036B compared to control. However, Q172B has no mortality effects on B. tabaci larvae under laboratory conditions. In glasshouse conditions, only Q036B provided high mortality rates of 91% at 168h after treatment. The results of this study indicate that the Pseudomonas isolate Q036B significantly suppresses B. tabaci in tomato plant and could substitute the excessive use of chemicals. Current research indicates that soil biodiversity could be promising to preserve agro-ecological sustainability.

Abstract The progression of human immunodeficiency virus (HIV) is associated with mucosal damage in the gastrointestinal (GI) tract. This damage enables bacterial translocation from the gut and leads to subsequent inflammation. Dextran sulfate sodium (DSS-exposure) is an established animal model for experimental colitis that was recently shown to recapitulate the link between GI-tract damage and pathogenic features of SIV infection. The current study tested the protective properties of ABX464, a first-in-class anti-HIV drug candidate currently in phase II clinical trials. ABX464 treatment strongly attenuated DSS-induced colitis in mice and produced a long-term protection against prolonged DSS-exposure after drug cessation. Consistently, ABX464 reduced the colonic production of the inflammatory cytokines IL-6 and TNFα as well as that of the chemoattractant MCP-1. However, RNA profiling analysis revealed the capacity of ABX464 to induce the expression of IL-22, a cytokine involved in colitis tissue repair, both in DSS-treated mice and in LPS-stimulated bone marrow-derived macrophages. Importantly, anti-IL-22 antibodies significantly reduced the protective effect of ABX464 on colitis in DSS-treated mice. Because reduced IL-22 production in the gut mucosa is an established factor of HIV and DSS-induced immunopathogenesis, our data suggest that the anti-inflammatory properties of ABX464 warrant exploration in both HIV and inflammatory ulcerative colitis (UC) disease.

Partial agonists weakly activate receptors even when occupying all available binding sites. Here the authors show that partial agonists of the AMPA receptor drive the adoption of multiple inactive forms, accounting for their limited efficacy.

Abnormal torsion could be associated with cyclovertical strabismus, but torsion measurements are not reliable in children. To assess an objective fundus torsion evaluation in a paediatric population, we used Non-Mydriatic Fundus photography (NMFP) in healthy and cyclovertical strabismus patients to evaluate the disc-foveal angle over time and observers.We used a retrospective set of NMFP including 24 A or V-pattern strabismus and 27 age-matched normal children (mean age 6.4 and 6.7 years respectively), taken during 2 distinct follow-up consultations (separated by 251 and 479 days respectively). Each disc-foveal angle measurement (from which the ocular torsion can be assessed) was performed by 5 different observers, using graphical software and based on reproducible fundus anatomical marks. Statistical analysis was performed with a multivariate ANOVA using group, time and observers as factors, in addition to intraclass coefficient correlation (ICC) to assess measurement reproducibility.A significant difference of disc-foveal angle measures was observed between groups (p0,97).Abnormal amount of objective torsion could be associated with alphabet-pattern strabismus. Disc-foveal angle evaluation by NMFP in a children population appears as a non-invasive, reliable and reproducible method.

Plants are able to sense the magnitude and direction of gravity. This capacity is thought to reside in selected cell types within the plant body that are equipped with specialized organelles called statoliths. However, most plant cells do not possess statoliths, yet they respond to changes in gravitational acceleration. To understand the effect of gravity on the metabolism and cellular functioning of non-specialized plant cells, we investigated a rapidly growing plant cell devoid of known statoliths and without gravitropic behavior, the pollen tube. The effects of hyper-gravity and omnidirectional exposure to gravity on intracellular trafficking and on cell wall assembly were assessed in Camellia pollen tubes, a model system with highly reproducible growth behavior in vitro. Using an epi-fluorescence microscope mounted on the Large Diameter Centrifuge at the European Space Agency, we were able to demonstrate that vesicular trafficking is reduced under hyper-gravity conditions. Immuno-cytochemistry confirmed that both in hyper and omnidirectional gravity conditions, the characteristic spatial profiles of cellulose and callose distribution in the pollen tube wall were altered, in accordance with a dose-dependent effect on pollen tube diameter. Our findings suggest that in response to gravity induced stress, the pollen tube responds by modifying cell wall assembly to compensate for the altered mechanical load. The effect was reversible within few minutes demonstrating that the pollen tube is able to quickly adapt to changing stress conditions.

BACKGROUND: The c-fos proto-oncogene is an archetype for rapid and integrative transcriptional activation. Innumerable studies have focused on the canonical promoter, located upstream from the transcriptional start site. However, several regulatory sequences have been found in the first intron. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe an extremely conserved region in c-fos first intron that contains a putative TATA box, and functional TRE and CRE sites. This fragment drives reporter gene activation in fibroblasts, which is enhanced by increasing intracellular calcium and cAMP and by cotransfection of CREB or c-Fos/c-Jun expression vectors. We produced transgenic mice expressing a lacZ reporter controlled by the intronic promoter. Lac Z expression of this promoter is restricted to the developing central nervous system (CNS) and the mesenchyme of developing mammary buds in embryos 12.5 days post-conception, and to brain tissue in adults. RT-QPCR analysis of tissue mRNA, including the anlage of the mammary gland and the CNS, confirms the existence of a novel, nested mRNA initiated in the first intron. CONCLUSIONS/SIGNIFICANCE: Our results provide evidence for a novel, developmentally regulated promoter in the first intron of the c-fos gene.