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Malik, A.

Publications and source records attributed to Malik, A..

At least 37 records · Page 2Linked to original sources

Eosinophils protect against SARS-CoV-2 following a vaccine breakthrough infection

Waning immunity and the emergence of immune evasive SARS-CoV-2 variants jeopardize vaccine efficacy leading to breakthrough infections. We have previously shown that innate immune cells play a critical role in controlling SARS-CoV-2. To investigate the innate immune response during breakthrough infections, we modeled breakthrough infections by challenging low-dose vaccinated mice with a vaccine-mismatched SARS-CoV-2 Beta variant. We found that low-dose vaccinated infected mice had a 2-log reduction in lung viral burden, but increased immune cell infiltration in the lung parenchyma, characterized by monocytes, monocyte-derived macrophages, and eosinophils. Single cell RNA-seq revealed viral RNA was highly associated with eosinophils that corresponded to a unique IFN-{gamma} biased signature. Antibody-mediated depletion of eosinophils in vaccinated mice resulted in increased virus replication and dissemination in the lungs, demonstrating that eosinophils in the lungs are protective during SARS-CoV-2 breakthrough infections. These results highlight the critical role for the innate immune response in vaccine mediated protection against SARS-CoV-2.

immunology↗

Engineering the novel extremophile alga Chlamydomonas pacifica for high lipid and high starch production as a path to developing commercially relevant strains

Microalgae offer a compelling platform for the production of commodity products, due to their superior photosynthetic efficiency, adaptability to non-arable lands and non-potable water, and their capacity to produce a versatile array of bioproducts, including biofuels and biomaterials. However, the scalability of microalgae as a bioresource has been hindered by challenges such as costly biomass production related to vulnerability to pond crashes during large-scale cultivation. This study presents a pipeline for the genetic engineering and pilot-scale production of biodiesel and thermoplastic polyurethane precursors in the extremophile species Chlamydomonas pacifica. This extremophile microalga exhibits exceptional resilience to high pH, high salinity, and elevated temperatures. Initially, we evolved this strain to also have a high tolerance to high light intensity through mutagenesis, breeding, and selection. Subsequently, we genetically engineered C. pacifica to produce high levels of lipids and starch without compromising growth. We demonstrated the scalability of these engineered strains by cultivating them in pilot-scale raceway ponds and converting the resulting biomass into biodiesel and thermoplastic polyurethanes. This study showcases the complete cycle of transforming a newly discovered species into a commercially relevant commodity production strain. This research underscores the potential of extremophile algae, including C. pacifica, as a key species for the burgeoning sustainable bioeconomy, offering a viable path forward in mitigating environmental challenges and supporting global bioproduct demands. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=90 SRC="FIGDIR/small/604193v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@84948eorg.highwire.dtl.DTLVardef@352616org.highwire.dtl.DTLVardef@1577082org.highwire.dtl.DTLVardef@19b8644_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

Cre-Lox miRNA-delivery technology optimized for inducible microRNA and gene-silencing studies in zebrafish.

While many genetic tools exist for zebrafish, this animal model is still lacking a robust gene-silencing and microRNA-delivery technology enabling spatio-temporal control and reliable traceability. We have recently demonstrated that the use of engineered pri-miR backbones can be used to both trigger stable and heritable gene knockdown and/or express microRNA(s) of choice in this organism. This approach/material fills a gap that exists in the zebrafish genetic toolbox to study microRNA biology and has the potential to be a powerful complementary tool to CRISPR-knockout and CRISPR-interference approaches by enabling conditional, traceable tissue-specific and polygenic gene-silencing. However, to date, this miRNA-expressing technology still presents important limitations. First, to trigger potent knockdown(s), multiple synthetic-miRNAs must be expressed simultaneously which compromises the co-expression of fluorescent marker(s) and knockdown traceability, thereby reducing the interest and versatility of this approach. Second, when the gene knockdown triggers significant phenotypes, like homozygous mutants with severe early phenotypes, it is difficult, if not impossible, to maintain adult transgenic carriers. Here, to solve these problems and provide a mature RNAi and microRNA-delivery technology for zebrafish research, we have generated and validated new RNAi reagents and an inducible delivery system based on the Cre/Lox technology. This new system allows the creation of asymptomatic/silent carriers, easing the production of embryos with potent knockdowns that can be traced and spatiotemporally controlled. Following this technological development, we demonstrate the utility of our approach by generating novel inducible models of spinal muscular atrophy (SMA) that open new avenues for studying the normal and pathogenic functions of the smn1 gene, as well as for establishing large-scale screens. Finally, and very importantly, the materials and techniques developed here will simplify research into microRNA biology, as well as conditions involving haploinsufficiency and multiple genes.

molecular biology↗

RelQ-mediated alarmone signaling regulates growth, sporulation, and stress-induced biofilm formation in Clostridioides difficile

The bacterial stringent response (SR) is a conserved transcriptional reprogramming pathway mediated by the nucleotide signaling alarmones, (pp)pGpp. The SR has been implicated in antibiotic survival in Clostridioides difficile, a biofilm- and spore-forming pathogen that causes resilient, highly recurrent C. difficile infections. The role of the SR in other processes and the effectors by which it regulates C. difficile physiology are unknown. C. difficile RelQ is a clostridial alarmone synthetase. Deletion of relQ dysregulates C. difficile growth in unstressed conditions, affects susceptibility to antibiotic and oxidative stressors, and drastically reduces biofilm formation. While wild-type C. difficile displays increased biofilm formation in the presence of sub-lethal stress, the {Delta}relQ strain cannot upregulate biofilm production in response to stress. Deletion of relQ slows spore accumulation in planktonic cultures but accelerates it in biofilms. This work establishes biofilm formation and sporulation as alarmone-mediated processes in C. difficile and reveals the importance of RelQ in stress-induced biofilm regulation.

microbiology↗

Neural correlates of spatiotemporal properties of lightness induction

The lightness of a surface depends not only on the amount of light reflected off it but also on the context it is embedded in. Despite a long history of research, neural correlates of context-dependent lightness perception remain a question of ongoing debate. The current study seeks to expand upon the existing literature by measuring fMRI responses to a dynamic version of a classical effect called simultaneous lightness induction (SLI), where a central disk appears lighter when embedded in a darker surround compared to when embedded in a lighter surround. During the fMRI experiment, we presented ten participants with a dynamic SLI stimulus by modulating the luminance of either the achromatic surround (surround-modulation condition) or the achromatic disk (disk-modulation condition) at four different frequencies ranging from 1 to 8 Hz. Behaviorally, when the surround luminance is modulated at low frequencies, participants perceive an illusory change in the lightness of the disk (lightness induction). In contrast, they perceive little or no induction at higher frequencies. Utilizing this temporal dependence and controlling for long-range responses to border contrast and luminance changes, we found that activity in the primary visual cortex (V1) correlates with lightness induction. However, such a correlation was not evident in extrastriate areas, V2, V3, and V4. These findings provide evidence for the involvement of V1 in the processing of context-dependent lightness.

neuroscience↗

Neuronal Ndst1 depletion accelerates prion protein clearance and slows neurodegeneration in prion infection

Select prion diseases are characterized by widespread cerebral plaque-like deposits of amyloid fibrils enriched in heparan sulfate (HS), a major extracellular matrix component. HS facilitates fibril formation in vitro, yet how HS impacts fibrillar plaque growth within the brain is unclear. Here we found that prion-bound HS chains are highly sulfated, and that the sulfation is essential for HS accelerating prion conversion in vitro. Using conditional knockout mice to deplete the HS sulfation enzyme, Ndst1 (N-deacetylase, N-sulfotransferase), from neurons or astrocytes, we investigated how reducing HS sulfation impacts survival and prion aggregate distribution during a prion infection. Neuronal Ndst1-depleted mice survived longer and showed fewer and smaller parenchymal plaques, shorter fibrils, and increased vascular amyloid, consistent with enhanced aggregate transit toward perivascular drainage channels. The prolonged survival was strain-dependent, affecting mice infected with extracellular, plaque-forming, but not membrane bound, prion strains. Live PET imaging revealed rapid clearance of prion protein monomers into the CSF in mice expressing unsulfated HS, further suggesting that HS sulfate groups hinder transit of extracellular prion monomers. Our results directly show how a host cofactor slows the spread of prion protein through the extracellular space and identify an enzyme target to facilitate aggregate clearance. Author summaryPrions cause a rapidly progressive neurologic disease and death with no curative treatment available. Prion aggregates accumulate exponentially in the brain in affected individuals triggering neuronal loss and neuroinflammation. Yet the additional molecules that facilitate aggregation are largely unknown, and their identification may lead to new therapeutic targets. We have found that prions in the brain preferentially bind to a highly sulfated endogenous polysaccharide, known as heparan sulfate (HS). Here we use genetically modified mice that express poorly sulfated neuron-derived HS, and infect mice with different prions strains. We find that the mice infected with a plaque-forming prion strain show a prolonged survival and fewer plaques compared to the controls. We also found that the prion protein was efficiently transported in the interstitial fluid in mice having poorly sulfated HS, suggesting that the prion protein is more readily cleared from the brain. Our study provides insight into how HS retains prion aggregates in the brain to accelerate disease and indicates the specific HS biosynthetic enzymes to target for enhancing protein clearance.

pathology↗

An Unexpected Role of Neutrophils in Clearing Apoptotic Hepatocytes In Vivo

Billions of apoptotic cells are removed daily in a human adult by professional phagocytes (e.g. macrophages) and neighboring nonprofessional phagocytes (e.g. stromal cells). Despite being a type of professional phagocyte, neutrophils are thought to be excluded from apoptotic sites to avoid tissue inflammation. Here we report a fundamental and unexpected role of neutrophils as the predominant phagocyte responsible for the clearance of apoptotic hepatic cells in the steady state. In contrast to the engulfment of dead cells by macrophages, neutrophils burrowed directly into apoptotic hepatocytes, a process we term perforocytosis, and ingested the effete cells from the inside. The depletion of neutrophils caused defective removal of apoptotic bodies, induced tissue injury in the mouse liver and led to the generation of autoantibodies. Human autoimmune liver disease showed similar defects in the neutrophil-mediated clearance of apoptotic hepatic cells. Hence, neutrophils possess a specialized immunologically silent mechanism for the clearance of apoptotic hepatocytes through perforocytosis, and defects in this key housekeeping function of neutrophils contribute to the genesis of autoimmune liver disease.

physiology↗

Overexpression of Interleukin-8 and Interleukin-13 as potent immune markers associated with survival and dietary habits in esophageal squamous cell carcinoma.

BackgroundInterleukin-8 (IL8), Interleukin-12 (IL12) and Interleukin-13 (IL13) are cytokines that play regulatory role in cancer pathogenesis. We analysed their expression profile to evaluate as molecular biomarkers of esophageal squamous cell carcinoma (ESCC) and their association with different parameters. MethodsExpression analysis of IL8, IL12 and IL13 were performed by Real time qPCR in blood and tumor tissue of 120 ESCC patients. The expression profiles were associated with different clinicopathological and dietary factors. Survival and hazard analysis were also performed. ResultsWhen compared to normal controls, IL8 expression showed upregulation in 83% tissue samples (p=0.000) and 62% blood samples (p=0.388), IL12 expression showed upregulation in 62% tissue samples (p=0.435) and 57% blood samples (p=0.222) and IL13 expression showed upregulation in 83% tissue samples (p=0.001) and 68% blood samples (p=0.312). Significant positive correlation (p<0.05) was observed between tissue and blood level expression of IL8, IL12 and IL13. Different clinicopathological factors and dietary habits showed significant association (p<0.05) with IL8, IL12 and IL13 expression.. Statistically significant positive correlation were observed for IL8 and IL13 expression in tissue as well as IL13 and IL12 expression in both tissue and blood. Also significant negative correlation of IL8 and IL12 expression in blood and tissue were also observed. Tumor stage, node stage, metastasis, consumption of betel nut, tobacco, alcohol, hot food, smoked food, spices, IL8 expression in blood, IL13 expression in tissue and IL12 expression in blood and tissue showed significant association (p<0.05) with survival of ESCC patients. ConclusionsAltered expression of IL8, IL12 and IL13 may be associated with ESCC progression. Overexpression of IL8 and IL13 in tissue samples may be potential biomarkers for ECSS screening. Additionally, results from both survival and hazard analysis data indicate the effects of various parameters on the survival and mortality rate of ESCC patients.

immunology↗

Multisensory inputs control the regulation of time investment for mating by sexual experience in male Drosophila melanogaster

Males have finite resources to spend on reproduction. Thus, males rely on a time investment strategy to maximize their reproductive success. For example, male Drosophila melanogaster extends their mating duration when surrounded by conditions enriched with rivals. Here we report a novel form of behavioral plasticity whereby male fruit flies exhibit a shortened duration of mating when they are sexually experienced; we refer to this plasticity as shorter-mating-duration (SMD). SMD is a plastic behavior and requires sexually dimorphic taste neurons. We identified several neurons in the male foreleg and midleg that express specific sugar, pheromone and mechanosensory receptors. Using a cost-benefit model and behavioral experiments, we further show that SMD behavior exhibits adaptive behavioral plasticity in male flies. Thus, our study delineates the molecular and cellular basis of the sensory inputs required for SMD; this represents a plastic interval timing behavior that could serve as a model system to study how multisensory inputs converge to modify interval timing behavior for improved adaptation. ONE SENTENCE SUMMARYMale flies use information derived from their previous sexual experiences from multiple sensory inputs to optimize their investment in mating.

neuroscience↗

Scavenger receptor B1 facilitates the endocytosis of Escherichia coli via TLR4 signaling in mammary gland infection

SCARB1 belongs to class B of Scavenger receptors (SRs) that are known to be involved in binding and endocytosis of various pathogens. SRs have emerging role in regulating innate immunity and host-pathogen interactions by acting in co-ordination with Toll-like receptors. Little is known about the function of SCARB1 in milk-derived mammary epithelial cells (MECs). This study reports the role of SCARB1 in infection and its potential association in TLR4 signaling on bacterial challenge in Goat mammary epithelial cells (GMECs). The novelty in the establishment of MEC culture lies in the method that aims to enhance the viability of the cells with intact characteristics upto a higher passage number. We represent MEC culture to be used as a potential infection model for deeper understanding of animal physiology especially around the mammary gland. On E.coli challenge the expression of SCARB1 was significant in induced GMECs at 6 h. Endoribonuclease-esiRNA based silencing of SCARB1 affects the expression of TLR4 and its pathways i.e. MyD88 and TRIF pathways on infection. Knockdown also affected the endocytosis of E.coli in GMECs demonstrating that E.coli uses SCARB1 function to gain entry in cells. Furthermore, we predict 3 unique protein structures of uncharacterized SCARB1 (Capra hircus) protein. Overall, we highlight SCARB1 as a main participant in host defence and its function in antibacterial advances to check mammary gland infections.

immunology↗

Unmet Expectations About Material Properties Delay Perceptual Decisions

Based on our expectations about material properties we can implicitly predict an objects future states, e.g. a wine glass falling down will break when it hits the ground. How these expectations affect relatively low level perceptual decisions, however, has not been systematically studied previously. To seek an answer to this question we conducted a behavioral experiment using animations of various familiar objects (e.g. key, wine glass etc.) freely falling and hitting the ground. During a training session participants first built expectations about the dynamic properties of those objects. Half of the participants (N=28) built expectations consistent with our daily lives (e.g. a key bounces rigidly), whereas the other half learned an anomalous behavior (e.g. a key wobbles). This was followed by experimental sessions, in which expectations were unmet in 20% of the trials. In both training and experimental sessions, participants task was to report whether the objects broke or not upon hitting the ground. Critically a specific object always remained intact or broke, only the manner with which it did so differed. For example, a key could wobble or remain rigid, but it never broke. We found that participants reaction times were longer when expectations were unmet even when those expectations were anomalous and learned during the training session. Furthermore, we found an interplay between long-term and newly learned expectations, which could be predicted by a Bayesian updating approach. Overall, our results show that expectations about material properties can have an impact on relatively low-level perceptual decision making processes.

neuroscience↗

In vivo CRISPR screens reveal SCAF1 and USP15 as novel drivers of pancreatic cancer

Functionally characterizing the genetic alterations that drive pancreatic cancer progression is a prerequisite for Precision Medicine. Here, we developed a somatic CRISPR/Cas9 mutagenesis screen to assess the transforming potential of 125 recurrently mutated long-tail pancreatic cancer genes, which revealed USP15 and SCAF1 as novel and potent Pancreatic ductal adenocarcinoma PDAC tumor suppressors, with USP15 functioning in a haplo-insufficient manner. Mechanistically, we found that loss of USP15 leads to reduced inflammatory responses associated with TNF, TGF-{beta} and IL6 signaling and sensitizes pancreatic cancer cells to PARP inhibition and gemcitabine. Similarly, genetic ablation of SCAF1 reduced inflammatory responses linked to TNF, TGF-{beta} and mTOR signaling and increased sensitivity to PARP inhibition. Furthermore, we identified that loss of SCAF1 resulted in the formation of a truncated inactive USP15 isoform at the expense of full length USP15, functionally coupling SACF1 and USP15. Notably, USP15 and SCAF1 mutations or copy number losses are observed in 31% of PDAC patients. Together, our results demonstrate the utility of in vivo CRISPR to integrate human cancer genomics with mouse modeling to delineate novel cancer driver genes USP15 and SCAF1 such as with potential prognostic and therapeutic implications.

cancer biology↗

In vivo CRISPR screens reveal Serpinb9 and Adam2 as regulators of immune therapy response in lung cancer

How the genetic landscape of a tumor governs the tumors response to immunotherapy remains largely elusive. Here, we established a direct in vivo CRISPR/Cas9 gene editing methodology to assess the immune-modulatory capabilities of 573 putative cancer genes associated with altered cytotoxic activity in human cancers. Using KrasG12D- and BrafV600E-driven mouse lung cancer models, we identify Serpinb9 and Adam2 as our top immune suppressive and immune enhancing genes, respectively. Mechanistically, we show that Serpinb9 ablation in KrasG12D- and BrafV600E-mutant lung tumor cells greatly enhances the efficacy of cytotoxic T-cells in vitro and in vivo. ADAM2 is a cancer testis antigen broadly expressed in human cancers such as lung adenocarcinoma (13.9%), renal (74.7%), prostate (72.4%), uterine (28.6%) and invasive breast (9.5%) cancer. In our mouse models, we show that Adam2 expression is induced in KrasG12D- but not BrafV600E-driven murine lung tumors and that its expression is further enhanced by immunotherapy. We show that loss of Adam2 significantly decreases KrasG12D-lung tumor burden but blocks the efficacy of cytotoxic T-cells. Consistently, Adam2 overexpression dramatically increases tumor growth and enhances immunotherapy efficacy. Mechanistically, we find that Adam2s oncogenic function depends on modulating the tumor immune microenvironment by restraining productive type I and type II interferon responses as well as cytokine signaling, reducing the presentation of tumor-associated antigen, and modulating surface expression of several immunoregulatory receptors within Kras-driven lung tumors. Adam2 expression also leads to reduced levels of immune checkpoint inhibitors such as Pd-l1, Lag3, Tigit and Tim3. This reduced exhaustion within the tumor microenvironment may explain why ex vivo expanded and adoptively transferred cytotoxic T-cells show enhanced cytotoxic efficacy against Adam2 overexpressing lung tumors. Together, our study highlights the power of integrating cancer genomic with in vivo CRISPR/Cas9 screens to uncover how cancer-associated genetic alterations control responses to immunotherapies.

cancer biology↗

Rice Pan-genome Array (RPGA): an efficient genotyping solution for pan-genome-based accelerated crop improvement in rice

The advent of the pan-genome era has unraveled previously unknown genetic variation existing within diverse crop plants including rice. This untapped genetic variation is believed to account for a major portion of phenotypic variation existing in crop plants and might be responsible for missing heritability. However, the use of conventional single reference-guided genotyping often fails to capture large portion of this genetic variation leading to a reference bias. This makes it difficult to identify and utilize novel population/cultivar-specific genes for crop improvement. To overcome this challenge, we developed a rice pan-genome genotyping array (RPGA) includes 80K genome-wide SNPs which provides simple, user-friendly and cost-effective solution for rapid pan-genome-based genotyping in rice. The GWAS conducted using RPGA-SNP genotyping data of a rice diversity panel detected total of 42 loci, including previously known as well as novel genomic loci regulating grain size/weight traits in rice. Eight of the identified trait-associated loci (dispensable loci) could not be detected with conventional single reference genome-based GWAS and found to be missing from the commonly used Nipponbare reference genome. WD repeat-containing PROTEIN 12 gene underlying one of such dispensable locus on chromosome 7 (qLWR7) along with few other non-dispensable loci was subsequently detected using high-resolution QTL mapping confirming authenticity of RPGA-led GWAS. This demonstrates the potential of RPGA-based genotyping to overcome reference bias. Besides GWAS, the application of RPGA-based genotyping for natural allelic diversity and population structure analysis, seed purity and hybridity testing, ultra-high-density genetic map construction and chromosome level genome assembly, and marker-assisted foreground/background selection was successfully demonstrated. Based on these salient outcomes, a web application (http://www.rpgaweb.com) was also developed to provide easy to use platform for imputation of RPGA-based genotyping data using 3K Rice Reference Panel and subsequent GWAS in order to drive genetic improvement of rice.

genomics↗

Loss of epigenetic regulation disrupts lineage integrity, reactivatesmultipotency and promotes breast cancer

Systematically investigating the scores of genes mutated in cancer and discerning real drivers from inconsequential bystanders is a prerequisite for Precision Medicine, but remains challenging. Here, we developed a somatic CRISPR/Cas9 mutagenesis screen to study 215 recurrent long-tail breast cancer genes, which revealed epigenetic regulation as major tumor suppressive mechanism. We report that core or accessory components of the COMPASS histone methylase complex including KMT2C, KDM6A, BAP1 and ASXL2 ("EpiDrivers") cooperate with PIK3CAH1047R to transform mouse and human breast epithelial cells. Mechanistically, we find that Cre-mediated activation of PIK3CAH1047R elicited an aberrant alveolar lactation program in luminal cells, which was exacerbated upon loss of EpiDrivers. Remarkably, EpiDriver loss in basal cells also triggered an alveolar-like lineage conversion and accelerated formation of luminal-like tumors, suggesting a basal origin for luminal tumors. As EpiDrivers are mutated in 39% of human breast cancers, lineage infidelity and lactation mimicry may significantly contribute to early steps of breast cancer progression. Statement of significanceInfrequently mutated genes comprise most of the mutational burden in breast tumors but are poorly understood. In-vivo CRISPR screening identified functional tumor suppressors that converged on epigenetic regulation. Loss of epigenetic regulators accelerated tumorigenesis and revealed lineage infidelity and aberrant expression of lactation genes as potential early events in tumorigenesis.

cancer biology↗

De novo mutation rates at the single-mutation resolution in a human HBB gene-region associated with adaptation and genetic disease

While it is known that the mutation rate varies across the genome, previous estimates were based on averaging across various numbers of positions. Here we describe a method to measure the origination rates of target mutations at target base positions and apply it to a 6-bp region in the human {beta}-globin (HBB) gene and to the identical, homologous{delta} -globin (HBD) region in sperm cells from both African and European donors. The HBB region of interest (ROI) includes the site of the hemoglobin S (HbS) mutation, which protects against malaria, is common in Africa and has served as a classic example of adaptation by random mutation and natural selection. We found a significant correspondence between de novo mutation rates and past observations of alleles in carriers, showing that mutation rates vary substantially in a mutation-specific manner that contributes to the site frequency spectrum. We also found that the overall point mutation rate is significantly higher in Africans than Europeans in the HBB region studied. Finally, the rate of the 20A[->]T mutation, called the "HbS mutation" when it appears in HBB, is significantly higher than expected from the genome-wide average for this mutation type. Nine instances were observed in the African HBB ROI, where it is of adaptive significance, representing at least three independent originations, and no instances were observed in the European HBB ROI or in the European or African HBD ROI. Further studies will be needed to examine de novo mutation rates at the single-mutation resolution across these and other loci and organisms and to uncover the molecular mechanisms responsible.

evolutionary biology↗

Combined responses of primary coral polyps and their algal endosymbionts to decreasing seawater pH

With coral reefs declining globally, resilience of these ecosystems hinges on successful coral recruitment. However, knowledge of the acclimatory and/or adaptive potential in response to environmental challenges such as ocean acidification (OA) in earliest life stages is limited. Our combination of physiological measurements, microscopy, computed tomography techniques and gene expression analysis allowed us to thoroughly elucidate the mechanisms underlying the response of early life stages of corals, together with their algal partners, to the projected decline in oceanic pH. We observed extensive physiological, morphological and transcriptional changes in surviving recruits, and the transition to a less-skeleton/more-tissue phenotype. We found that decreased pH conditions stimulate photosynthesis and endosymbiont growth, and gene expression potentially linked to photosynthates translocation. Our unique holistic study discloses the previously unseen intricate net of interacting mechanisms that regulate the performance of these organisms in response to OA.

developmental biology↗

Cellular pathways during spawning induction in the starlet sea anemone Nematostella vectensis

In cnidarians, long-term ecological success relies on sexual reproduction. The sea anemone Nematostella vectensis, which has emerged as an important model organism for developmental studies, can be induced for spawning by temperature elevation and light exposure. To uncover molecular mechanisms and pathways underlying spawning, we characterized the transcriptome of Nematostella females before and during spawning induction. We identified an array of processes involving numerous receptors, circadian clock components, cytoskeleton, and extracellular transcripts that are upregulated upon spawning induction. Concurrently, processes related to the cell cycle, fatty acid metabolism, and other housekeeping functions are downregulated. Real-time qPCR revealed that light exposure has a minor effect on expression levels of most examined transcripts, implying that temperature change is a stronger inducer for spawning in Nematostella. Our findings reveal the mechanisms that may enable the mesenteries to serve as a gonad-like tissue for the developing oocytes and expand our understanding of sexual reproduction in cnidarians. Summary statementAnalysis of transcriptional changes during spawning induction in Nematostella vectensis, revealed upregulation of processes related to signal perception and cytoskeleton rearrangement and downregulation of fatty acid metabolism and housekeeping processes.

ecology↗