Hypoxia has profound and diverse effects on aerobic organisms, disrupting oxidative phosphorylation and activating several protective pathways. Predictions have been made that exposure to mild intermittent hypoxia may be protective against more severe exposure and may extend lifespan. Both effects are likely to depend on prior selection on phenotypic and transcriptional plasticity in response to hypoxia, and may therefore show signs of local adaptation. Here we report the lifespan effects of chronic, mild, intermittent hypoxia (CMIH) and short-term survival in acute severe hypoxia (ASH) in four clones of Daphnia magna originating from either permanent or intermittent habitats, the latter regularly drying up with frequent hypoxic conditions. We show that CMIH extended the lifespan in the two clones originating from intermittent habitats but had the opposite effect in the two clones from permanent habitats, which also showed lower tolerance to ASH. Exposure to CMIH did not protect against ASH; to the contrary, Daphnia from the CMIH treatment had lower ASH tolerance than normoxic controls. Few transcripts changed their abundance in response to the CMIH treatment in any of the clones. After 12 hours of ASH treatment, the transcriptional response was more pronounced, with numerous protein-coding genes with functionality in mitochondrial and respiratory metabolism, oxygen transport, and, unexpectedly, gluconeogenesis showing up-regulation. While clones from intermittent habitats showed somewhat stronger differential expression in response to ASH than those from permanent habitats, there were no significant hypoxia-by-habitat of origin or CMIH-by-ASH interactions. GO enrichment analysis revealed a possible hypoxia tolerance role by accelerating the molting cycle and regulating neuron survival through up-regulation of cuticular proteins and neurotrophins, respectively.
Habitat divergence among close relatives is a common theme in ecology. While recent studies have frequently found that the abundance and diversity of plant species are regulated by soil microbes, little is known whether soil microbes can also affect the habitat distributions of plants. To fill in this knowledge gap, we investigated whether interactions with soil microbes restrict habitat distributions of closely related oaks (Quercus spp.) in eastern North America. We performed a soil inoculum experiment using two pairs of sister species that show habitat divergence: Quercus alba (local species) vs. Q. michauxii (foreign), and Q. shumardii (local) vs. Q. acerifolia (foreign). To test whether host-specific soil microbes are responsible for habitat restriction, we investigated the impact of local sister live soil (containing soil microbes associated with local sister species) on the survival and growth of local and foreign species. Secondly, to test whether habitat-specific soil microbes are responsible for habitat restriction, we also examined the effect of local habitat live soil (containing soil microbes within local sister’s habitats, but not directly associated with roots of local sister species) on the seedlings of local and foreign species. We found that local sister live soil decreased the survival and biomass of foreign species’ seedlings while increased those of local species, which supports the roles of host-specific microbes in mediating habitat exclusion. In contrast, local habitat live soil did not differentially affect the survival or biomass of the local vs. foreign sister species, providing no support for the roles of habitat-specific microbes. Our study indicates that soil microbes associated with one sister species can suppress the recruitment of the other host species, contributing to habitat partitioning of the closely related oaks. Our findings emphasize that considering the complex interactions with soil microbes is essential for understanding habitat distributions of closely related plants.
The blacklegged tick, Ixodes scapularis, is a vector of Borrelia burgdorferi sensu stricto (s.s.), the causative agent of Lyme disease, part of a slow-moving epidemic of Lyme borreliosis spreading across the northern hemisphere. There are well-known geographic differences in the vectorial capacity of these ticks associated with genetic variation. Despite the need for detailed genetic information in this disease system, previous phylogeographic studies of these ticks have been restricted to relatively few populations or genetic loci. Here we present the most comprehensive phylogeographic study of I. scapularis conducted by using 3RAD and surveying 353 ticks from 33 counties throughout the range of I. scapularis. We found limited genetic variation among populations from the Northeast and Upper Midwest, where Lyme disease is most common, and higher genetic variation among populations from the South. We identify four genetic clusters of I. scapularis that are consistent with four major geographic regions, plus a distinct Central Florida group. In regions where Lyme disease is increasing in frequency, the I. scapularis populations genetically group with ticks from historically highly Lyme-endemic regions. Finally, we identify ten variable DNA sites that contribute the most to population differentiation. These variable sites cluster on one of the chromosome-scale scaffolds for I. scapularis and are within identified genes. Our findings illuminate the need for additional research to identify loci causing variation in the vectorial capacity of I. scapularis and where additional tick sampling would be most valuable to further understand disease trends caused by pathogens transmitted by I. scapularis.
A 48-year-old male diagnosed with Acute promyelocytic leukemia (APL) started on all-trans retinoic acid and arsenic trioxide, developed typical symptoms of differentiation syndrome, and improved dramatically on steroids. Hence, any APL patient started on chemotherapy, needs to be monitored closely for developing differentiation syndrome and to start steroid upon suspicion.
Objective: Peripartum cardiomyopathy (PPCM) diagnosis made by excluding identifiable causes of heart failure (HF) and occurs end of the pregnancy or during the postpartum period of five months. It presents a clinical HF spectrum with left ventricular systolic dysfunction. Background: The purpose of this study is to retrospectively evaluate the clinical characteristics, cardiac magnetic resonance (CMR) imaging features, and end-points consisting of left ventricle recovery, left ventricular assist device implantation, heart transplantation, and all-cause mortality. Method: Outpatient HF records between 2008 to 2021 were screened. Thirty-seven patients were defined as PPCM. Twenty-five patients had CMR evaluation at the time of diagnosis, and six patients were re-evaluated with CMR. Results: The mean age was 30.5±5.6 years, and the mean LVEF was 28.2±6.7%. In thirteen(35.7%) patients, LVEF recovered during the follow-up course. The median recovery time was 281(IQR [78-358]) days. LVEF on CMR was 35.3±10.5, and three patients exhibited late gadolinium enhancement(LGE) patterns. Sub-endocardial and mid-wall uptake pattern types were detected. 18(75%) patients met the Petersen left ventricle non-compaction cardiomyopathy(LVNC) criteria. Patients with NC/C ratio lower than 2.3 had lower LVEDVi and LVESVi (124.9±35.4,86.4±7.5, p=0.003;86.8±34.6,52.6±7.6, p=0.006), respectively. The median follow-up time was 2129 (IQR [911-2634]) days. The primary endpoint-free one-year survival was 88.9%(event rate 11.1%), and five-year survival was 75.7%(event rate 24.3%). Conclusion: In a retrospective cohort of PPCM patients, 35.7% of patients’ LVEF recovered, and the primary end-point of free-five-year survival was 75%. Twenty-five patients were assessed with CMR; three of four met the Petersen CMR-derived LVNC at initial evaluation.
Objective: Observational studies have described associations between obesity and adverse outcomes of pregnancy. Mendelian randomization (MR) takes advantage of the ‘natural’ genetic randomization to risk of an exposure such as body mass index (BMI) to study the effects of the exposure on outcomes. Similar to randomization in a clinical trial, this limits the potential for confounding and bias. Design: A two-sample MR study. Setting: Summary statistics from published genome wide association studies (GWAS) in European ancestry populations. Population or Sample: Instrumental variants for body mass index (BMI) were obtained from a study on 434,794 females. Female-specific genetic association estimates for outcomes were extracted from the sixth round of analysis of the FINNGEN cohort data. Methods: Inverse-variance weighted MR was used to assess the association between BMI and all outcomes. Sensitivity analyses with weighted median and MR-Egger were also performed. Results: A 1-SD increase in BMI was associated with higher risk of pre-eclampsia (OR 1.68, 95%CI 1.46-1.94, p=8.74x10-13), gestational diabetes (OR 1.67, 95%CI 1.46-1.92, p=5.35x10-14), polyhydramnios (OR 1.40, 95%CI 1.00-1.96, p=0.049). There was evidence suggestive of a potential association with higher risk of premature rupture of membranes (OR 1.16, 95%CI 1.00-1.36, p=0.050) and postpartum depression (OR 1.12, 95%CI 0.99-1.27, p=0.062). Conclusions: Higher maternal BMI is associated with marked increase in risk of pre-eclampsia, gestational diabetes and polyhydramnios. The relationship between BMI and premature rupture of membranes and postpartum depression should be assessed in further studies. Our study supports efforts to target BMI as a cardinal risk factor for maternal morbidity.
Local adaptation is a major driver of biological diversity, and related species may develop analogous (parallel evolution) or alternative (divergent evolution) solutions to similar ecological challenges. We expect these adaptive solutions between closely related organisms would culminate in both phenotypic and genotypic signals. In this study, we employ a reciprocal transplant, glasshouse experiment with two Eucalyptus species ( E. grandis and E. tereticornis) with large, overlapping distributions grown under contrasting ‘local’ temperature conditions (tropic and temperate) to investigate the independent contribution of adaptation, plasticity, and their interaction at molecular, physiological and morphological levels. We find key traits differ in their response. The link between gene expression and traits markedly differed between species. Divergent evolution was the dominant pattern driving adaptation as unique gene responses (91% of all significant genes) was the greatest factor driving differentiation; but overlapping gene (homologous) responses were dependent on the determining factor (plastic, adaptive, or genotype by environment interaction). 98% of the plastic homologs were similarly regulated, while 50% of the adaptive homologs and 100% of the interaction homologs were antagonistically regulated. Therefore, parallel evolution for the adaptive effect in homologous genes was greater than expected but not in favour of divergent evolution. Further, heat shock proteins for E. grandis were almost entirely driven by adaptive responses, while plasticity drove the response in E. tereticornis. These results suggest divergent molecular evolutionary solutions dominated the adaptive mechanisms among species, even in similar ecological circumstances. Thus, trees with overlapping distributions are unlikely to equally persist in the future, suggesting that management of future forests to changing temperature conditions must be species specific.
Patagonia is an understudied area, especially when it comes to population genomic studies with relevance to fishery management. However, the dynamic and heterogeneous landscape in this area can harbor important but cryptic genetic population structure. Once such information is revealed, it can be integrated into the management of infrequently investigated species. Eleginops maclovinus is a protandrous hermaphrodite species with economic importance for local communities that is currently managed as a single genetic unit. In this study, we sampled five locations distributed across a salinity cline from Northern Patagonia to investigate the genetic population structure of E. maclovinus. We use Restriction-site Associated DNA (RAD) sequencing and outlier tests to obtain neutral and adaptive loci, using FST and GEA approaches. We identified a spatial pattern of structuration with gene flow and spatial selection by environmental association. Neutral and adaptive loci showed two and three genetic groups, respectively. The effective population sizes estimated ranged from 572 (Chepu) to 14,454 (Chaitén) and were influenced more by locality than salinity cline. We found loci putatively associated with salinity suggesting that salinity may act as a selective driver in E. maclovinus populations. These results suggest a complex interaction between genetic drift, geneflow, and natural selection in this area. Our findings suggest several units in this area, and the information should be integrated into the management of this species. We discuss the significance of these results for fishery management and suggest future directions to improve our understanding of how E. maclovinus is adapted to the dynamic waters of Northern Patagonia.
anomalous pulmonary veins drain into the right side of the left atrium is an uncommon variety of anomalous pulmonary venous return. Rarely, anomalous pulmonary venous drainage combined with cor triatriatum and atrial septal defect. We presented the imaging findings of a male patient who had anomalous pulmonary venous drainage which has not previously been described.
Background: Influenza is a persistent public health problem associated with severe morbidity and mortality. Drug use is related to myriad health complications, but the relationship between drug use and severe influenza outcomes is not well understood. The study objective was to evaluate the relationship between drug use and severe influenza-associated outcomes. Methods: Data were collected by the Influenza Hospitalization Surveillance Network (FluSurv-NET) from the 2016-2017 through 2018-2019 influenza seasons. Among persons hospitalized with influenza, descriptive statistics and logistic regression models were used to analyze differences in demographic characteristics, risk and behavioral factors, and severe outcomes (intensive care unit [ICU] admission, mechanical ventilation, or death) between people who used drugs (PWUD), defined as having documented drug use within the past year, and non-PWUD. Results: Among 48,430 eligible hospitalized influenza cases, 2,019 were PWUD and 46,411 were non-PWUD. PWUD were younger than non-PWUD and more likely to be male, non-Hispanic Black or Hispanic/Latino, smoke tobacco, abuse alcohol, and have chronic conditions including asthma, chronic liver disease, chronic lung disease, or immunosuppressive conditions. PWUD had greater odds of ICU admission and mechanical ventilation, but not death compared with non-PWUD. Opioid use specifically was associated with increased risk of ICU admission and mechanical ventilation. Conclusion: PWUD had greater odds of ICU admission and mechanical ventilation than non-PWUD hospitalized with influenza. These results support targeted initiatives to prevent influenza and associated severe outcomes among this population.
Background: The identification of protein-protein interactions is of great challenge. Therefore, we conducted this study to fabricate a gold surface biochip with activated sophorolipids in combination with 16-amino-1-hexadecanethiol hydrochloride. Methods: We designed a direct on-chip immunological assay strategy for measuring ligand-receptor interactions in a forward or reverse manner, that is, a ligand was immobilized on the biochip surface and allowed to interact with its specific free receptor in the liquid phase and vice versa. The specificity of molecular interactions on the biochip was evaluated using an immunological blocking assay and a chemiluminescent immunoassay. To test the potential utilization of biochip, we used the serum of hemophagocytic lymphohistiocytosis (HLH) patients as an experimental entity. Results: The receptor CD25-based IL-2 and ligand IL-2-based CD25 assays revealed that the detection limits on the biochip were as low as 156pg/mL and 78pg/mL, respectively. Meanwhile, using the receptor- or ligand-based platforms, we found that the positive rates of free IL-2 and soluble CD25 (sCD25) monomers in the sera of HLH patients were 14.3% and 71.4%, respectively, like our previous specific-antibody-based biochip investigation. Also, the biochip shared a good compatibility with CLIA assay in the measurement of sCD25(r=0.77, P<0.01). Conclusions: The biochip platform can be expanded to protein-specific serological diagnosis as a potential substitute for immunoprecipitation and ELISA to understand the interactions between proteins, ligands and receptors, and enzymes and substrates.
As a rapidly developing cell engineering technique, cell electrofusion has been increasingly applied in the field of hybridoma preparation in recent years. However, electrofusion is a certain degree of difficulty to completely replace the polyethylene glycol-mediated cell fusion. The key elements limiting electrofusion in the field of hybridoma preparation are practical complicated. This review summarizes the state of art of cell electrofusion in hybridoma preparation based on recent published literatures, mainly focusing on electrofusion instruments and their components, process control, cell treatment, and process characterization. The review provides new information and insightful commentary, critically important to the promotion of further electrofusion development in the field of hybridoma preparation.
There has been an important change in the clinical characteristics and immune profile of COVID-19 patients during the pandemic thanks to the extensive vaccination programs. Here, we highlight recent studies on COVID-19, from the clinical and immunological characteristics to the protective and risk factors for severity and mortality of COVID-19. The efficacy COVID-19 vaccines and potential allergic reactions after administration are also discussed. The occurrence of new variants of concerns such as Omicron BA.2, BA.4 and BA.5 and the global administration of COVID-19 vaccines have changed the clinical scenario of COVID-19. Multisystem inflammatory syndrome in children (MIS-C) has been identified as an important cause of death of children with COVID-19. Perturbations in immunity of T cells, B cells, and mast cells, as well as autoantibodies and metabolic reprogramming may contribute to the long-term symptoms of COVID-19. Atopic diseases, such as allergic asthma and rhinitis, have been shown to be associated with a lower susceptibility and better outcomes of COVID-19. At the beginning of pandemic, EAACI developed guidelines that provided timely information for the management of allergic diseases and preventive measures to reduce transmission in the allergic clinics. The global distribution of COVID-19 vaccines and emerging SARS-CoV-2 variants with reduced pathogenic potential dramatically decreased the morbidity, severity, and mortality of COVID-19. Nevertheless, breakthrough infection remains a challenge for disease control. Hypersensitivity reactions (HSR) to COVID-19 vaccines are low compared to other vaccines, and these were addressed in EAACI statements that provided indications for the management of allergic reactions, including anaphylaxis to COVID-19 vaccines. We have gained a depth knowledge and experience in the over 2 years since the start of the pandemic, and yet a full eradication of SARS-CoV-2 is not on the horizon. Novel strategies are warranted to prevent severe disease in high-risk groups, the development of MIS-C and long COVID.
While our survey showed that PwCF felt that the COVID-19 pandemic had impacted their mental health more than ETI therapy, around 9% of survey responders felt that ETI did cause an increase in either anxiety or depression. This finding was similar to the numbers Spoletini and colleagues found in their adult clinic. They also found that a dose reduction of ETI improved or resolved mental health adverse events for most patients.  A recently published study by Guimbellot and colleagues studied ivacaftor levels in PwCF who were on ivacaftor monotherapy and showed many patients had levels higher than the published minimum effective concentrations. Thus, there may be a correlation between ETI levels and mental health adverse events that should be further explored in a prospective manner.
We conducted a cross-sectional study using a questionnaire to explore the late effects in survivors of juvenile myelomonocytic leukemia (JMML). The attending pediatric hematologist oncologists completed the questionnaires. All survivors (N=30) had undergone allogeneic hematopoietic stem cell transplantation. Approximately 83% survivors showed more than one late effect. The identified late effects included endocrine, dental, skin, ophthalmologic, musculoskeletal, pulmonary, neurocognitive, and cardiovascular dysfunction. The prevalence of short stature and cardiovascular and kidney dysfunction was significantly elevated among survivors aged ≥18 years. Therefore, a multidisciplinary follow-up system for survivors of JMML is crucial.
Oxygen, as a terminal electron acceptor, is an essential substrate in the aerobic bio-oxidation process, affecting bacterial vitality and bio-oxidation performance. In this study, a new and smart platform biotechnology of sealed-oxygen supply bioreactor (SOS-BR) was developed by improving gas pressure to significantly intensify oxygen transfer rate and resolving the formidable barriers of aerobic catalysis. In virtue of SOS-BR, the bio-productivity was greatly improved for three representative substrates (xylose, furfural, glycerol) bio-oxidation with the whole-cell catalysis of Gluconobacter oxydans. The determination of oxygen transfer coefficient (KLα) established an upgraded theoretical dynamic model for gas pressure intersification biosystem. Additionally, viscosity measurement and combined pressure control strategy explained the inflection point phenomenon of productivity and confirmed the intensify mechanism. The new strategy of significantly intensifying oxygen transfer provided insightful ideas for overcoming the subbon obstacle of obligate aerobic catalysis, and further promoted industrial practicability of bio-oxidation.