Primer design for the amplification of the ammonium transporter genes from the uncultured haptophyte algal species symbiotic with the marine nitrogen-fixing cyanobacterium UCYN-A1.

The multiple symbiotic partnerships between closely related species of the haptophyte algae Braarudosphaera bigelowii and the nitrogen-fixing cyanobacteria Candidatus Atelocyanobacterium thalassa (UCYN-A) contribute importantly to the nitrogen and carbon cycles in vast areas of the ocean. The diversity of the eukaryotic 18S rDNA phylogenetic gene marker has helped to identify some of these symbiotic haptophyte species, yet we still lack a genetic marker to assess its diversity at a finer scale. One of such genes is the ammonium transporter (amt) gene, which encodes the protein that might be involved in the uptake of ammonium from UCYN-A in these symbiotic haptophytes. Here, we designed three specific PCR primer sets targeting the amt gene of the haptophyte species (A1-Host) symbiotic with the open ocean UCYN-A1 sublineage, and tested them in samples collected from open ocean and near-shore environments. Regardless of the primer pair used at Station ALOHA, which is where UCYN-A1 is the pre-dominant UCYN-A sublineage, the most abundant amt amplicon sequence variant (ASV) was taxonomically classified as A1-Host. In addition, two out of the three PCR primer sets revealed the existence of closely-related divergent haptophyte amt ASVs (>95% nucleotide identity). These divergent amt ASVs had higher relative abundances than the haptophyte typically associated with UCYN-A1 in the Bering Sea, or co-occurred with the previously identified A1-Host in the Coral Sea, suggesting the presence of new diversity of closely-related A1-Hosts in polar and temperate waters. Therefore, our study reveals an overlooked diversity of haptophytes species with distinct biogeographic distributions partnering with UCYN-A, and provides new primers that will help to gain new knowledge of the UCYN-A/haptophyte symbiosis.

Nifedipine Ameliorates Cellular Differentiation Defects of Smn-Deficient Motor Neurons and Enhances Neuromuscular Transmission in SMA Mice.

In spinal muscular atrophy (SMA), mutations in or loss of the Survival Motor Neuron 1 (SMN1) gene reduce full-length SMN protein levels, which leads to the degeneration of a percentage of motor neurons. In mouse models of SMA, the development and maintenance of spinal motor neurons and the neuromuscular junction (NMJ) function are altered. Since nifedipine is known to be neuroprotective and increases neurotransmission in nerve terminals, we investigated its effects on cultured spinal cord motor neurons and motor nerve terminals of control and SMA mice. We found that application of nifedipine increased the frequency of spontaneous Ca2+ transients, growth cone size, cluster-like formations of Cav2.2 channels, and it normalized axon extension in SMA neurons in culture. At the NMJ, nifedipine significantly increased evoked and spontaneous release at low-frequency stimulation in both genotypes. High-strength stimulation revealed that nifedipine increased the size of the readily releasable pool (RRP) of vesicles in control but not SMA mice. These findings provide experimental evidence about the ability of nifedipine to prevent the appearance of developmental defects in SMA embryonic motor neurons in culture and reveal to which extent nifedipine could still increase neurotransmission at the NMJ in SMA mice under different functional demands.

Transcriptional Mechanisms of Thermal Acclimation in Prochlorococcus.

Low temperature limits the growth and the distribution of the key oceanic primary producer Prochlorococcus, which does not proliferate above a latitude of ca. 40°. Yet, the molecular basis of thermal acclimation in this cyanobacterium remains unexplored. We analyzed the transcriptional response of the Prochlorococcus marinus strain MIT9301 in long-term acclimations and in natural Prochlorococcus populations along a temperature range enabling its growth (17 to 30°C). MIT9301 upregulated mechanisms of the global stress response at the temperature minimum (17°C) but maintained the expression levels of genes involved in essential metabolic pathways (e.g., ATP synthesis and carbon fixation) along the whole thermal niche. Notably, the declining growth of MIT9301 from the optimum to the minimum temperature was coincident with a transcriptional suppression of the photosynthetic apparatus and a dampening of its circadian expression patterns, indicating a loss in their regulatory capacity under cold conditions. Under warm conditions, the cellular transcript inventory of MIT9301 was strongly streamlined, which may also induce regulatory imbalances due to stochasticity in gene expression. The daytime transcriptional suppression of photosynthetic genes at low temperature was also observed in metatranscriptomic reads mapping to MIT9301 across the global ocean, implying that this molecular mechanism may be associated with the restricted distribution of Prochlorococcus to temperate zones. IMPORTANCE Prochlorococcus is a major marine primary producer with a global impact on atmospheric CO2 fixation. This cyanobacterium is widely distributed across the temperate ocean, but virtually absent at latitudes above 40° for yet unknown reasons. Temperature has been suggested as a major limiting factor, but the exact mechanisms behind Prochlorococcus thermal growth restriction remain unexplored. This study brings us closer to understanding how Prochlorococcus functions under challenging temperature conditions, by focusing on its transcriptional response after long-term acclimation from its optimum to its thermal thresholds. Our results show that the drop in Prochlorococcus growth rate under cold conditions was paralleled by a transcriptional suppression of the photosynthetic machinery during daytime and a loss in the organism's regulatory capacity to maintain circadian expression patterns. Notably, warm temperature induced a marked shrinkage of the organism's cellular transcript inventory, which may also induce regulatory imbalances in the future functioning of this cyanobacterium.

Full protection from SARS-CoV-2 brain infection and damage in susceptible transgenic mice conferred by MVA-CoV2-S vaccine candidate.

Vaccines against SARS-CoV-2 have been shown to be safe and effective but their protective efficacy against infection in the brain is yet unclear. Here, in the susceptible transgenic K18-hACE2 mouse model of severe coronavirus disease 2019 (COVID-19), we report a spatiotemporal description of SARS-CoV-2 infection and replication through the brain. SARS-CoV-2 brain replication occurs primarily in neurons, leading to neuronal loss, signs of glial activation and vascular damage in mice infected with SARS-CoV-2. One or two doses of a modified vaccinia virus Ankara (MVA) vector expressing the SARS-CoV-2 spike (S) protein (MVA-CoV2-S) conferred full protection against SARS-CoV-2 cerebral infection, preventing virus replication in all areas of the brain and its associated damage. This protection was maintained even after SARS-CoV-2 reinfection. These findings further support the use of MVA-CoV2-S as a promising vaccine candidate against SARS-CoV-2/COVID-19.

Oxygen regulation of breathing is abolished in mitochondrial complex III-deficient arterial chemoreceptors.

Acute oxygen (O2) sensing is essential for adaptation of organisms to hypoxic environments or medical conditions with restricted exchange of gases in the lung. The main acute O2-sensing organ is the carotid body (CB), which contains neurosecretory chemoreceptor (glomus) cells innervated by sensory fibers whose activation by hypoxia elicits hyperventilation and increased cardiac output. Glomus cells have mitochondria with specialized metabolic and electron transport chain (ETC) properties. Reduced mitochondrial complex (MC) IV activity by hypoxia leads to production of signaling molecules (NADH and reactive O2 species) in MCI and MCIII that modulate membrane ion channel activity. We studied mice with conditional genetic ablation of MCIII that disrupts the ETC in the CB and other catecholaminergic tissues. Glomus cells survived MCIII dysfunction but showed selective abolition of responsiveness to hypoxia (increased [Ca2+] and transmitter release) with normal responses to other stimuli. Mitochondrial hypoxic NADH and reactive O2 species signals were also suppressed. MCIII-deficient mice exhibited strong inhibition of the hypoxic ventilatory response and altered acclimatization to sustained hypoxia. These data indicate that a functional ETC, with coupling between MCI and MCIV, is required for acute O2 sensing. O2 regulation of breathing results from the integrated action of mitochondrial ETC complexes in arterial chemoreceptors.

Succinate dehydrogenase/complex II is critical for metabolic and epigenetic regulation of T cell proliferation and inflammation.

Effective T cell-mediated immune responses require the proper allocation of metabolic resources to sustain growth, proliferation, and cytokine production. Epigenetic control of the genome also governs T cell transcriptome and T cell lineage commitment and maintenance. Cellular metabolic programs interact with epigenetic regulation by providing substrates for covalent modifications of chromatin. By using complementary genetic, epigenetic, and metabolic approaches, we revealed that tricarboxylic acid (TCA) cycle flux fueled biosynthetic processes while controlling the ratio of succinate/α-ketoglutarate (α-KG) to modulate the activities of dioxygenases that are critical for driving T cell inflammation. In contrast to cancer cells, where succinate dehydrogenase (SDH)/complex II inactivation drives cell transformation and growth, SDH/complex II deficiency in T cells caused proliferation and survival defects when the TCA cycle was truncated, blocking carbon flux to support nucleoside biosynthesis. Replenishing the intracellular nucleoside pool partially relieved the dependence of T cells on SDH/complex II for proliferation and survival. SDH deficiency induced a proinflammatory gene signature in T cells and promoted T helper 1 and T helper 17 lineage differentiation. An increasing succinate/α-KG ratio in SDH-deficient T cells promoted inflammation by changing the pattern of the transcriptional and chromatin accessibility signatures and consequentially increasing the expression of the transcription factor, PR domain zinc finger protein 1. Collectively, our studies revealed a role of SDH/complex II in allocating carbon resources for anabolic processes and epigenetic regulation in T cell proliferation and inflammation.

Light and depth dependency of nitrogen fixation by the non-photosynthetic, symbiotic cyanobacterium UCYN-A.

The symbiotic cyanobacterium UCYN-A is one of the most globally abundant marine dinitrogen (N2 )-fixers, but cultures have not been available and its biology and ecology are poorly understood. We used cultivation-independent approaches to investigate how UCYN-A single-cell N2 fixation rates (NFRs) and nifH gene expression vary as a function of depth and photoperiod. Twelve-hour day/night incubations showed that UCYN-A only fixed N2 during the day. Experiments conducted using in situ arrays showed a light-dependence of NFRs by the UCYN-A symbiosis, with the highest rates in surface waters (5-45 m) and lower rates at depth (≥ 75 m). Analysis of NFRs versus in situ light intensity yielded a light saturation parameter (Ik ) for UCYN-A of 44 µmol quanta m-2  s-1 . This is low compared with other marine diazotrophs, suggesting an ecological advantage for the UCYN-A symbiosis under low-light conditions. In contrast to cell-specific NFRs, nifH gene-specific expression levels did not vary with depth, indicating that light regulates N2 fixation by UCYN-A through processes other than transcription, likely including host-symbiont interactions. These results offer new insights into the physiology of the UCYN-A symbiosis in the subtropical North Pacific Ocean and provide clues to the environmental drivers of its global distributions.

Unexpected presence of the nitrogen-fixing symbiotic cyanobacterium UCYN-A in Monterey Bay, California.

In the last decade, the known biogeography of nitrogen fixation in the ocean has been expanded to colder and nitrogen-rich coastal environments. The symbiotic nitrogen-fixing cyanobacteria group A (UCYN-A) has been revealed as one of the most abundant and widespread nitrogen-fixers, and includes several sublineages that live associated with genetically distinct but closely related prymnesiophyte hosts. The UCYN-A1 sublineage is associated with an open ocean picoplanktonic prymnesiophyte, whereas UCYN-A2 is associated with the coastal nanoplanktonic coccolithophore Braarudosphaera bigelowii, suggesting that different sublineages may be adapted to different environments. Here, we study the diversity of nifH genes present at the Santa Cruz Municipal Wharf in the Monterey Bay (MB), California, and report for the first time the presence of multiple UCYN-A sublineages, unexpectedly dominated by the UCYN-A2 sublineage. Sequence and quantitative PCR data over an 8-year time-series (2011-2018) showed a shift toward increasing UCYN-A2 abundances after 2013, and a marked seasonality for this sublineage which was present during summer-fall months, coinciding with the upwelling-relaxation period in the MB. Increased abundances corresponded to positive temperature anomalies in MB, and we discuss the possibility of a benthic life stage of the associated coccolithophore host to explain the seasonal pattern. The dominance of UCYN-A2 in coastal waters of the MB underscores the need to further explore the habitat preference of the different sublineages in order to provide additional support for the hypothesis that UCYN-A1 and UCYN-A2 sublineages are different ecotypes.

Mitochondrial Complex I Function Is Essential for Neural Stem/Progenitor Cells Proliferation and Differentiation.

Neurogenesis in developing and adult mammalian brain is a tightly regulated process that relies on neural stem cell (NSC) activity. There is increasing evidence that mitochondrial metabolism affects NSC homeostasis and differentiation but the precise role of mitochondrial function in the neurogenic process requires further investigation. Here, we have analyzed how mitochondrial complex I (MCI) dysfunction affects NSC viability, proliferation and differentiation, as well as survival of the neural progeny. We have generated a conditional knockout model (hGFAP-NDUFS2 mice) in which expression of the NDUFS2 protein, essential for MCI function, is suppressed in cells expressing the Cre recombinase under the human glial fibrillary acidic protein promoter, active in mouse radial glial cells (RGCs) and in neural stem cells (NSCs) that reside in adult neurogenic niches. In this model we observed that survival of central NSC population does not appear to be severely affected by MCI dysfunction. However, perinatal brain development was markedly inhibited and Ndufs2 knockout mice died before the tenth postnatal day. In addition, in vitro studies of subventricular zone NSCs showed that active neural progenitors require a functional MCI to produce ATP and to proliferate. In vitro differentiation of neural precursors into neurons and oligodendrocytes was also profoundly affected. These data indicate the need of a correct MCI function and oxidative phosphorylation for glia-like NSC proliferation, differentiation and subsequent oligodendrocyte or neuronal maturation.

Histone depletion prevents telomere fusions in pre-senescent cells.

Upon telomerase inactivation, telomeres gradually shorten with each cell division until cells enter replicative senescence. In Saccharomyces cerevisiae, the kinases Mec1/ATR and Tel1/ATM protect the genome during pre-senescence by preventing telomere-telomere fusions (T-TFs) and the subsequent genetic instability associated with fusion-bridge-breakage cycles. Here we report that T-TFs in mec1Δ tel1Δ cells can be suppressed by reducing the pool of available histones. This protection associates neither with changes in bulk telomere length nor with major changes in the structure of subtelomeric chromatin. We show that the absence of Mec1 and Tel1 strongly augments double-strand break (DSB) repair by non-homologous end joining (NHEJ), which might contribute to the high frequency of T-TFs in mec1Δ tel1Δ cells. However, histone depletion does not prevent telomere fusions by inhibiting NHEJ, which is actually increased in histone-depleted cells. Rather, histone depletion protects telomeres from fusions by homologous recombination (HR), even though HR is proficient in maintaining the proliferative state of pre-senescent mec1Δ tel1Δ cells. Therefore, HR during pre-senescence not only helps stalled replication forks but also prevents T-TFs by a mechanism that, in contrast to the previous one, is promoted by a reduction in the histone pool and can occur in the absence of Rad51. Our results further suggest that the Mec1-dependent depletion of histones that occurs during pre-senescence in cells without telomerase (tlc1Δ) prevents T-TFs by favoring the processing of unprotected telomeres by Rad51-independent HR.

ZATT (ZNF451)-mediated resolution of topoisomerase 2 DNA-protein cross-links.

Topoisomerase 2 (TOP2) DNA transactions proceed via formation of the TOP2 cleavage complex (TOP2cc), a covalent enzyme-DNA reaction intermediate that is vulnerable to trapping by potent anticancer TOP2 drugs. How genotoxic TOP2 DNA-protein cross-links are resolved is unclear. We found that the SUMO (small ubiquitin-related modifier) ligase ZATT (ZNF451) is a multifunctional DNA repair factor that controls cellular responses to TOP2 damage. ZATT binding to TOP2cc facilitates a proteasome-independent tyrosyl-DNA phosphodiesterase 2 (TDP2) hydrolase activity on stalled TOP2cc. The ZATT SUMO ligase activity further promotes TDP2 interactions with SUMOylated TOP2, regulating efficient TDP2 recruitment through a "split-SIM" SUMO2 engagement platform. These findings uncover a ZATT-TDP2-catalyzed and SUMO2-modulated pathway for direct resolution of TOP2cc.

Vertical distribution of major photosynthetic picoeukaryotic groups in stratified marine waters.

Photosynthetic picoeukaryotes (PPEs) are fundamental contributors to oceanic primary production and form diverse communities dominated by prymnesiophytes, chlorophytes, pelagophytes and chrysophytes. Here, we studied the vertical distribution of these major groups in two offshore regions of the northern Iberian Peninsula during summer stratification. We performed a fine-scale vertical sampling (every ∼2 m) across the DCM and used fluorescence in situ hybridization (FISH) to determine the PPE composition and to explore the possible segregation of target groups in the light, nutrient and temperature gradients. Chlorophytes, pelagophytes and prymnesiophytes, in this order of abundance, accounted for the total PPEs recorded by flow cytometry in the Avilés canyon, and for more than half in the Galicia Bank, whereas chrysophytes were undetected. Among the three detected groups, often the prymnesiophytes were dominant in biomass. In general, all groups were present throughout the water column with abundance peaks around the DCM, but their distributions differed: pelagophytes were located deeper than the other two groups, chlorophytes presented two peaks and prymnesiophytes exhibited surface abundances comparable to those at the DCM. This study offers first indications that the vertical distribution of different PPE groups is heterogeneous within the DCM.

Cyanobacterial symbionts diverged in the late Cretaceous towards lineage-specific nitrogen fixation factories in single-celled phytoplankton.

The unicellular cyanobacterium UCYN-A, one of the major contributors to nitrogen fixation in the open ocean, lives in symbiosis with single-celled phytoplankton. UCYN-A includes several closely related lineages whose partner fidelity, genome-wide expression and time of evolutionary divergence remain to be resolved. Here we detect and distinguish UCYN-A1 and UCYN-A2 lineages in symbiosis with two distinct prymnesiophyte partners in the South Atlantic Ocean. Both symbiotic systems are lineage specific and differ in the number of UCYN-A cells involved. Our analyses infer a streamlined genome expression towards nitrogen fixation in both UCYN-A lineages. Comparative genomics reveal a strong purifying selection in UCYN-A1 and UCYN-A2 with a diversification process ∼91 Myr ago, in the late Cretaceous, after the low-nutrient regime period occurred during the Jurassic. These findings suggest that UCYN-A diversified in a co-evolutionary process, wherein their prymnesiophyte partners acted as a barrier driving an allopatric speciation of extant UCYN-A lineages.

Global distribution and vertical patterns of a prymnesiophyte-cyanobacteria obligate symbiosis.

A marine symbiosis has been recently discovered between prymnesiophyte species and the unicellular diazotrophic cyanobacterium UCYN-A. At least two different UCYN-A phylotypes exist, the clade UCYN-A1 in symbiosis with an uncultured small prymnesiophyte and the clade UCYN-A2 in symbiosis with the larger Braarudosphaera bigelowii. We targeted the prymnesiophyte-UCYN-A1 symbiosis by double CARD-FISH (catalyzed reporter deposition-fluorescence in situ hybridization) and analyzed its abundance in surface samples from the MALASPINA circumnavigation expedition. Our use of a specific probe for the prymnesiophyte partner allowed us to verify that this algal species virtually always carried the UCYN-A symbiont, indicating that the association was also obligate for the host. The prymnesiophyte-UCYN-A1 symbiosis was detected in all ocean basins, displaying a patchy distribution with abundances (up to 500 cells ml(-1)) that could vary orders of magnitude. Additional vertical profiles taken at the NE Atlantic showed that this symbiosis occupied the upper water column and disappeared towards the Deep Chlorophyll Maximum, where the biomass of the prymnesiophyte assemblage peaked. Moreover, sequences of both prymnesiophyte partners were searched within a large 18S rDNA metabarcoding data set from the Tara-Oceans expedition around the world. This sequence-based analysis supported the patchy distribution of the UCYN-A1 host observed by CARD-FISH and highlighted an unexpected homogeneous distribution (at low relative abundance) of B. bigelowii in the open ocean. Our results demonstrate that partners are always in symbiosis in nature and show contrasted ecological patterns of the two related lineages.

Defective histone supply causes changes in RNA polymerase II elongation rate and cotranscriptional pre-mRNA splicing.

RNA polymerase II (RNAPII) transcription elongation is a highly regulated process that greatly influences mRNA levels as well as pre-mRNA splicing. Despite many studies in vitro, how chromatin modulates RNAPII elongation in vivo is still unclear. Here, we show that a decrease in the level of available canonical histones leads to more accessible chromatin with decreased levels of canonical histones and variants H2A.X and H2A.Z and increased levels of H3.3. With this altered chromatin structure, the RNAPII elongation rate increases, and the kinetics of pre-mRNA splicing is delayed with respect to RNAPII elongation. Consistent with the kinetic model of cotranscriptional splicing, the rapid RNAPII elongation induced by histone depletion promotes the skipping of variable exons in the CD44 gene. Indeed, a slowly elongating mutant of RNAPII was able to rescue this defect, indicating that the defective splicing induced by histone depletion is a direct consequence of the increased elongation rate. In addition, genome-wide analysis evidenced that histone reduction promotes widespread alterations in pre-mRNA processing, including intron retention and changes in alternative splicing. Our data demonstrate that pre-mRNA splicing may be regulated by chromatin structure through the modulation of the RNAPII elongation rate.

Ocean plankton. Determinants of community structure in the global plankton interactome.

Species interaction networks are shaped by abiotic and biotic factors. Here, as part of the Tara Oceans project, we studied the photic zone interactome using environmental factors and organismal abundance profiles and found that environmental factors are incomplete predictors of community structure. We found associations across plankton functional types and phylogenetic groups to be nonrandomly distributed on the network and driven by both local and global patterns. We identified interactions among grazers, primary producers, viruses, and (mainly parasitic) symbionts and validated network-generated hypotheses using microscopy to confirm symbiotic relationships. We have thus provided a resource to support further research on ocean food webs and integrating biological components into ocean models.

Rad51 replication fork recruitment is required for DNA damage tolerance.

Homologous recombination (HR) is essential for genome integrity. Recombination proteins participate in tolerating DNA lesions that interfere with DNA replication, but can also generate toxic recombination intermediates and genetic instability when they are not properly regulated. Here, we have studied the role of the recombination proteins Rad51 and Rad52 at replication forks and replicative DNA lesions. We show that Rad52 loads Rad51 onto unperturbed replication forks, where they facilitate replication of alkylated DNA by non-repair functions. The recruitment of Rad52 and Rad51 to chromatin during DNA replication is a prerequisite for the repair of the non-DSB DNA lesions, presumably single-stranded DNA gaps, which are generated during the replication of alkylated DNA. We also show that the repair of these lesions requires CDK1 and is not coupled to the fork but rather restricted to G2/M by the replicative checkpoint. We propose a new scenario for HR where Rad52 and Rad51 are recruited to the fork to promote DNA damage tolerance by distinct and cell cycle-regulated replicative and repair functions.

MicroRNA regulation of Cbx7 mediates a switch of Polycomb orthologs during ESC differentiation.

The Polycomb Group (PcG) of chromatin modifiers regulates pluripotency and differentiation. Mammalian genomes encode multiple homologs of the Polycomb repressive complex 1 (PRC1) components, including five orthologs of the Drosophila Polycomb protein (Cbx2, Cbx4, Cbx6, Cbx7, and Cbx8). We have identified Cbx7 as the primary Polycomb ortholog of PRC1 complexes in embryonic stem cells (ESCs). The expression of Cbx7 is downregulated during ESC differentiation, preceding the upregulation of Cbx2, Cbx4, and Cbx8, which are directly repressed by Cbx7. Ectopic expression of Cbx7 inhibits differentiation and X chromosome inactivation and enhances ESC self-renewal. Conversely, Cbx7 knockdown induces differentiation and derepresses lineage-specific markers. In a functional screen, we identified the miR-125 and miR-181 families as regulators of Cbx7 that are induced during ESC differentiation. Ectopic expression of these miRNAs accelerates ESC differentiation via regulation of Cbx7. These observations establish a critical role for Cbx7 and its regulatory miRNAs in determining pluripotency.

Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a.

Expression of the INK4b/ARF/INK4a tumor suppressor locus in normal and cancerous cell growth is controlled by methylation of histone H3 at lysine 27 (H3K27me) as directed by the Polycomb group proteins. The antisense noncoding RNA ANRIL of the INK4b/ARF/INK4a locus is also important for expression of the protein-coding genes in cis, but its mechanism has remained elusive. Here we report that chromobox 7 (CBX7) within the polycomb repressive complex 1 binds to ANRIL, and both CBX7 and ANRIL are found at elevated levels in prostate cancer tissues. In concert with H3K27me recognition, binding to RNA contributes to CBX7 function, and disruption of either interaction impacts the ability of CBX7 to repress the INK4b/ARF/INK4a locus and control senescence. Structure-guided analysis reveals the molecular interplay between noncoding RNA and H3K27me as mediated by the conserved chromodomain. Our study suggests a mechanism by which noncoding RNA participates directly in epigenetic transcriptional repression.

AQP1 mediates water transport in the carotid body.

In this study, we explored the presence of aquaporins (AQPs), a family of membrane water channel proteins, in carotid body (CB) type I chemoreceptor cells. The CB is a polymodal chemoreceptor whose major function is to detect changes in arterial O2 tension to elicit hyperventilation during hypoxia. The CB has also been proposed to function as a systemic osmoreceptor, thus we hypothesized that the presence of AQPs in type I cell membrane may confer higher sensitivity to osmolarity changes and hence accelerate the activation of chemoreceptor cells. We detected the expression of AQP1, AQP7, and AQP8 in the CB and confirmed the location of AQP1 in type I cells. We have also shown that inhibition of AQP1 expression clearly reduced type I cell swelling after a hyposmotic shock, demonstrating that AQP1 has a major contribution in transmembrane water movement in these chemoreceptor cells. Interestingly, CB AQP1 expression levels change during postnatal development, increasing during the first postnatal weeks as the organ matures. In conclusion, in this study, we report the novel observation that AQPs are expressed in the CB. We also show that AQP1 mediates water transport across the cell membrane of type I cells, supporting the contribution of this protein to the osmoreception function of the CB.