Abstract
Chloroplasts communicate information by signalling to nuclei during acclimation to fluctuating light. Several potential operating signals originating from chloroplasts have been proposed, ...but none have been shown to move to nuclei to modulate gene expression. One proposed signal is hydrogen peroxide (H
2
O
2
) produced by chloroplasts in a light-dependent manner. Using HyPer2, a genetically encoded fluorescent H
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O
2
sensor, we show that in photosynthetic
Nicotiana benthamiana
epidermal cells, exposure to high light increases H
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O
2
production in chloroplast stroma, cytosol and nuclei. Critically, over-expression of stromal ascorbate peroxidase (H
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O
2
scavenger) or treatment with DCMU (photosynthesis inhibitor) attenuates nuclear H
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O
2
accumulation and high light-responsive gene expression. Cytosolic ascorbate peroxidase over-expression has little effect on nuclear H
2
O
2
accumulation and high light-responsive gene expression. This is because the H
2
O
2
derives from a sub-population of chloroplasts closely associated with nuclei. Therefore, direct H
2
O
2
transfer from chloroplasts to nuclei, avoiding the cytosol, enables photosynthetic control over gene expression.
BACKGROUND:SARS-CoV-2 infection continues to cause significant morbidity and mortality worldwide. Preliminary data on SARS-CoV-2 infection suggest that some immunocompromised hosts experience worse ...outcomes. We performed a retrospective matched cohort study to characterize outcomes in HIV-positive patients with SARS-CoV-2 infection.
METHODS:Leveraging data collected from electronic medical records for all patients hospitalized at NYU Langone Health with COVID-19 between March 2, 2020, and April 23, 2020, we matched 21 HIV-positive patients with 42 non-HIV patients using a greedy nearest-neighbor algorithm. Admission characteristics, laboratory test results, and hospital outcomes were recorded and compared between the 2 groups.
RESULTS:Although there was a trend toward increased rates of intensive care unit admission, mechanical ventilation, and mortality in HIV-positive patients, these differences were not statistically significant. Rates for these outcomes in our cohort are similar to those previously published for all patients hospitalized with COVID-19. HIV-positive patients had significantly higher admission and peak C-reactive protein values. Other inflammatory markers did not differ significantly between groups, although HIV-positive patients tended to have higher peak values during their clinical course. Three HIV-positive patients had superimposed bacterial pneumonia with positive sputum cultures, and all 3 patients died during hospitalization. There was no difference in frequency of thrombotic events or myocardial infarction between these groups.
CONCLUSIONS:This study provides evidence that HIV coinfection does not significantly impact presentation, hospital course, or outcomes of patients infected with SARS-CoV-2, when compared with matched non-HIV patients. A larger study is required to determine whether the trends we observed apply to all HIV-positive patients.
Amazonian biodiversity is increasingly threatened due to the weakening of policies for combating deforestation, especially in Brazil. Loss of animal and plant species, many not yet known to science, ...is just one among many negative consequences of Amazon deforestation. Deforestation affects indigenous communities, riverside as well as urban populations, and even planetary health. Amazonia has a prominent role in regulating the Earth's climate, with forest loss contributing to rising regional and global temperatures and intensification of extreme weather events. These climatic conditions are important drivers of emerging infectious diseases, and activities associated with deforestation contribute to the spread of disease vectors. This review presents the main impacts of Amazon deforestation on infectious-disease dynamics and public health from a One Health perspective. Because Brazil holds the largest area of Amazon rainforest, emphasis is given to the Brazilian scenario. Finally, potential solutions to mitigate deforestation and emerging infectious diseases are presented from the perspectives of researchers in different fields.
Hepatitis C virus (HCV) infection affects approximately 58 million people and causes ~300,000 deaths yearly. The only target for HCV neutralizing antibodies is the highly sequence diverse E1E2 ...glycoprotein. Eliciting broadly neutralizing antibodies that recognize conserved cross-neutralizing epitopes is important for an effective HCV vaccine. However, most recombinant HCV glycoprotein vaccines, which usually include only E2, induce only weak neutralizing antibody responses. Here, we describe recombinant soluble E1E2 immunogens that were generated by permutation of the E1 and E2 subunits. We displayed the E2E1 immunogens on two-component nanoparticles and these nanoparticles induce significantly more potent neutralizing antibody responses than E2. Next, we generated mosaic nanoparticles co-displaying six different E2E1 immunogens. These mosaic E2E1 nanoparticles elicit significantly improved neutralization compared to monovalent E2E1 nanoparticles. These results provide a roadmap for the generation of an HCV vaccine that induces potent and broad neutralization.
Although millions of distinct virus species likely exist, only approximately 9000 are catalogued in GenBank's RefSeq database. We selectively enriched for the genomes of circular DNA viruses in over ...70 animal samples, ranging from nematodes to human tissue specimens. A bioinformatics pipeline, Cenote-Taker, was developed to automatically annotate over 2500 complete genomes in a GenBank-compliant format. The new genomes belong to dozens of established and emerging viral families. Some appear to be the result of previously undescribed recombination events between ssDNA and ssRNA viruses. In addition, hundreds of circular DNA elements that do not encode any discernable similarities to previously characterized sequences were identified. To characterize these 'dark matter' sequences, we used an artificial neural network to identify candidate viral capsid proteins, several of which formed virus-like particles when expressed in culture. These data further the understanding of viral sequence diversity and allow for high throughput documentation of the virosphere.
The neuromuscular junction (NMJ) consists of a tripartite synapse with a presynaptic nerve terminal, Schwann cells that ensheathe the terminal bouton, and a highly specialized postsynaptic membrane. ...Synaptic structural integrity is crucial for efficient signal transmission. Congenital myasthenic syndromes (CMSs) are a heterogeneous group of inherited disorders that result from impaired neuromuscular transmission, caused by mutations in genes encoding proteins that are involved in synaptic transmission and in forming and maintaining the structural integrity of NMJs. To identify further causes of CMSs, we performed whole-exome sequencing (WES) in families without an identified mutation in known CMS-associated genes. In two families affected by a previously undefined CMS, we identified homozygous loss-of-function mutations in COL13A1, which encodes the alpha chain of an atypical non-fibrillar collagen with a single transmembrane domain. COL13A1 localized to the human muscle motor endplate. Using CRISPR-Cas9 genome editing, modeling of the COL13A1 c.1171delG (p.Leu392Sfs∗71) frameshift mutation in the C2C12 cell line reduced acetylcholine receptor (AChR) clustering during myotube differentiation. This highlights the crucial role of collagen XIII in the formation and maintenance of the NMJ. Our results therefore delineate a myasthenic disorder that is caused by loss-of-function mutations in COL13A1, encoding a protein involved in organization of the NMJ, and emphasize the importance of appropriate symptomatic treatment for these individuals.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
An algorithm is presented that aims to enhance the use of satellite‐based cloud‐profiling radar (CPR) data for the purpose of NWP data assimilation. It resembles the EarthCARE mission's scene ...construction algorithm: off‐nadir passive radiances get spectrally matched with nadir passive radiances, and the latter's collocated CPR profile gets replicated at the former's location. This process gets repeated until all passive pixels that cover an NWP domain D have a proxy column of CPR data. Only domain‐averaged profiles of CPR reflectivity ⟨ZdB⟩ and cloud fraction Ac are sought after for NWP domains measuring, nominally, 25 × 25 km. If CPR measurements intersect D, then in addition to using just the intersecting values to represent ⟨ZdB⟩ and Ac, the full array of proxy values get used. This is referred to as local estimation. If, however, CPR measurements do not intersect D, but are not too distant, this is referred to as non‐local estimation; estimates of ⟨ZdB⟩ and Ac rest entirely on proxies. Current and planned satellite‐based CPRs have nadir‐pointing narrow fields‐of‐view, so it is difficult to see how to verify the algorithm with anything other than synthetic observations. Thus, it was assessed here with simulated cloudy atmospheres and 2D and 3D distributions of associated passive radiances and CPR reflectivities. In general terms, for local domains the algorithm performs slightly better than simply averaging intersecting CPR profiles. This at least demonstrates that the proxies are not detrimental. For non‐local domains, where there are no intersecting measurements to average, the algorithm appears to perform well enough to include two or three 25 × 25 km NWP domains either side of sequences of local domains.
1. The objective is to expand the use of satellite‐based cloud‐profiling radar (CPR) observations for use in NWP data assimilation systems. 2. Uses an algorithm that matches off‐nadir passive radiances to nadir counterparts that also consist of a CPR profile (see attached figure). 3. Estimates of domain‐average profiles of CPR reflectivities and cloud fractions are constructed for NWP cells that both intersect and do not intersect CPR cross‐sections.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Temperature and water vapor profiles are essential to climate change studies and weather forecasting. Hyperspectral instruments are of great value for retrieving temperature and water vapor profiles, ...enabling accurate monitoring of their changes. Successful retrievals of temperature and water vapor profiles require accuracy of hyperspectral radiometer measurements. In this study, the radiometric accuracy of an airborne hyperspectral microwave radiometer, the High Spectral Resolution Airborne Microwave Sounder (HiSRAMS), and a ground-based hyperspectral infrared radiometer, the Atmospheric Emitted Radiance Interferometer (AERI), is simultaneously assessed by performing radiative closure tests under clear-sky conditions in Ottawa, Canada. As an airborne instrument, HiSRAMS has two radiometers measuring radiance in the oxygen band (49.6–58.3 GHz) and water vapor band (175.9–184.6 GHz) for zenith-pointing and nadir-pointing observations. AERI provides ground-based, zenith-pointing radiance measurements between 520 and 1800 cm−1. A systematic warm radiance bias is present in AERI observations in the window band. Upon removal of this bias, improved radiative closure was attained in the window band. The brightness temperature (BT) bias in nadir-pointing HiSRAMS observations is smaller than at the zenith. A novel but straightforward method is developed to diagnose the radiometric accuracy of the two instruments in comparison based on the relationship between radiometric bias and optical depth. Compared to AERI, HiSRAMS demonstrates similar radiometric accuracy for nadir-pointing measurements but exhibits relatively poor accuracy for zenith-pointing measurements, which requires further characterization. Future work on temperature and water vapor concentration retrievals using HiSRAMS and AERI is warranted.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract Anthropogenic activities like habitat degradation, excess nutrient runoff, and sewage outfalls can decrease seawater pH in coastal environments. Coastal waters can also experience frequent ...fluctuations in seawater pH due to biological activity (i.e., photosynthesis and respiration). Commercially important species like the Florida stone crab, Menippe mercenaria (Say, 1818), inhabit coastal waters and experience fluctuations in seawater pH on both diurnal and seasonal scales. Organisms exposed to reductions in seawater pH may have difficulty sensing chemical cues due to physiological changes and the associated metabolic stress of compensating for a more acidic environment. Here we determined the foraging activity of the Florida stone crab when exposed to reduced pH conditions (control pH 7.8, reduced pH 7.6). The impacts of reduced pH on foraging activity were determined by monitoring activity time, stress, predation attempts, and handling time when crabs were exposed to lower seawater pH for 12 hrs. Crabs exposed to reduced pH conditions experienced elevated stress levels and reduced activity than crabs in the control pH treatment. These results suggest that exposure to more extreme pH conditions may limit the foraging activity of stone crabs.
Objective
To characterize the phenotypic expression of children with conductance regulator‐related metabolic syndrome (CRMS)/cystic fibrosis screen positive inconclusive diagnosis (CFSPID) ...designation after positive newborn screening, reassign labeling if applicable and better define these children's prognosis.
Methods
A multicenter cohort with CRMS/CFSPID designation was matched with cystic fibrosis (CF)‐diagnosed cohort. Cohorts were prospectively compared on baseline characteristics, cumulative data and when they reached 6 to 7 years at endpoint assessment.
Results
Compared to infants with CF (n = 63), the CRMS/CFSPID cohort (n = 63) had initially lower immunoreactive trypsinogen (IRT) and sweat chloride (SC) values, delayed visits, less symptoms, and better nutritional status; during follow‐up, they had fewer hospitalizations, Pseudomonas aeruginosa and methicillin‐resistant Staphylococcus aureus identification, CF comorbidities, and treatment burden. At endpoint assessment, they presented a milder pulmonary phenotype on Brody computed tomography scores (0.00.0; 2.0 vs 132.0; 31.0; P < .0001, respectively), Wisconsin and Brasfield chest radiograph scores, pulmonary function tests, and improved nutritional status. Among the inconclusive CF diagnosis cohort, 28 cases (44%) converted to CF diagnosis based on genotype (44%), SC (28%) or both (28%); yet, comparing those with or without final CF diagnosis, we found no differences, possibly related to their young age and mild degree of lung disease. In the total cohort, we found significant associations between Brody scores and IRT, SC values, genotype, Wisconsin and Brasfield score and spirometry.
Conclusions
The matched CRMS/CFSPID and CF cohorts showed differences in outcomes. By a mean age of 7.6 years, a high proportion of the CRMS/CFSPID cohort converted to CF. Our results highlight that monitoring at CF clinics until at least 6 years is needed as well as further studies.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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