Antarctic sponge associated microbial chemistry with biomedical relevance– the need for ecologically driven studies

Sponges are known to be a rich source of structurally diverse bioactive natural products, accounting for approximately one third of the 25,000 novel marine natural products discovered to date. The advancement of molecular techniques, especially next generation sequencing, has revealed a highly diverse and complex microbial consortia associated with sponges. Currently, research is on-going to investigate the role of these microorganisms in symbiosis and in the production of these sponge-associated secondary metabolites. It is hypothesised that adaptations to extreme temperatures and oxygen levels in the Antarctic may result in novel microbial strains with unprecedented bioactive metabolites. Although ecological and environmental factors are believed to play a crucial role in the expression of microbial bioactive secondary metabolites, underpinning the ecological function of microorganism-sponge interactions within Antarctica is poorly understood, despite mounting evidence that these metabolites play an important role in chemical defence and microbial community structure. The importance of the Antarctic ecosystem as a research resource will be underpinned by future global change; therefore it will be vital for ecological approaches to be addressed in addition to these biomedical functions. This review collates studies that assess the biomedical activity of secondary metabolites produced by Antarctic sponge associated microorganisms, which may stimulate the ecological function to be addressed by the community

Eliciting specialized metabolites from marine microalgae using abiotic stress

Advanced mass spectrometry and molecular networking techniques have led to an increase in the discovery of novel metabolites from bacteria and fungi. However, a systematic approach to exploring the metabolite profiles of microalgae in response to stress has not been performed. Unlocking the chemical potential of microalgae could provide further biotechnology applications in nutraceutical, biofuel, and cosmetic industries. This study explored the changes in metabolite production of strains of the three microalgae Dunaliella primolecta, Nannochloropsis oculata, and Phaeodactylum tricornutum cultured under varying nitrate, NaCl, salinity and pH conditions. A total of 2284 metabolites were detected across all strains and conditions, with 49% of those metabolites specific to cultures grown under stress (i.e., not present in the control). From comparison with 33 libraries of mass spectral data, only five metabolites were identified, stressing the need for more open-access natural product databases specifically focused on microalgae

Puzzling It Out: The Current State of Scientific Knowledge on Pre-Kindergarten Effects - A Consensus Statement

Scientific research has established that if all children are to achieve their developmental potential, it is important to lay the foundation during the earliest years for lifelong health, learning, and positive behavior. A central question is how well our public pre-kindergarten (pre-K) programs are doing to build this foundation.Forty-two states and the District of Columbia, through 57 pre-K programs, have introduced substantial innovations in their early education systems by developing the infrastructure, program sites, and workforce required to accommodate pre-K education. These programs now serve nearly 30 percent of the nation's 4-year-olds and 5 percent of 3-year-olds

Atypical chemokine receptor 4 shapes activated B cell fate

Activated B cells can initially differentiate into three functionally distinct fates-early plasmablasts (PBs), germinal center (GC) B cells, or early memory B cells-by mechanisms that remain poorly understood. Here, we identify atypical chemokine receptor 4 (ACKR4), a decoy receptor that binds and degrades CCR7 ligands CCL19/CCL21, as a regulator of early activated B cell differentiation. By restricting initial access to splenic interfollicular zones (IFZs), ACKR4 limits the early proliferation of activated B cells, reducing the numbers available for subsequent differentiation. Consequently, ACKR4 deficiency enhanced early PB and GC B cell responses in a CCL19/CCL21-dependent and B cell-intrinsic manner. Conversely, aberrant localization of ACKR4-deficient activated B cells to the IFZ was associated with their preferential commitment to the early PB linage. Our results reveal a regulatory mechanism of B cell trafficking via an atypical chemokine receptor that shapes activated B cell fate

Linking genomics and metabolomics to chart specialized metabolic diversity

Microbial and plant specialized metabolites constitute an immense chemical diversity, and play key roles in mediating ecological interactions between organisms. Also referred to as natural products, they have been widely applied in medicine, agriculture, cosmetic and food industries. Traditionally, the main discovery strategies have centered around the use of activity-guided fractionation of metabolite extracts. Increasingly, omics data is being used to complement this, as it has the potential to reduce rediscovery rates, guide experimental work towards the most promising metabolites, and identify enzymatic pathways that enable their biosynthetic production. In recent years, genomic and metabolomic analyses of specialized metabolic diversity have been scaled up to study thousands of samples simultaneously. Here, we survey data analysis technologies that facilitate the effective exploration of large genomic and metabolomic datasets, and discuss various emerging strategies to integrate these two types of omics data in order to further accelerate discovery

Combining hyperspectral imaging and electrochemical sensing for detection of Pseudomonas aeruginosa through pyocyanin production

Despite bacterial biofilms representing a common form of infection, notably on medical devices post implantation, their detection and characterisation with existing methods is not sufficient to inform clinicians about biofilm presence or treatment response in affected patients. This study reports the development and use of a combined hyperspectral imaging (HSI) and electrochemical platform to monitor biofilm formation optically and electrochemically. Firstly, production of pyocyanin, a common pigmented and redox active secondary metabolite produced by P. aeruginosa, is monitored by combined HSI and square-wave voltammetry. Secondly, P. aeruginosa biofilm formation is characterised directly using electrochemical impedance spectroscopy. This suite of optical and electrochemical measurements allows for combined monitoring of secondary metabolite/virulence factor production along with direct monitoring of biofilm formation on the sensor surface. Crucially, the easy to deploy and low-cost nature of the selected sensing technologies means the approach can be developed for enhanced study of biofilms and/or at the point of care

Comparative metabologenomics analysis of polar actinomycetes.

Biosynthetic and chemical datasets are the two major pillars for microbial drug discovery in the omics era. Despite the advancement of analysis tools and platforms for multi-strain metabolomics and genomics, linking these information sources remains a considerable bottleneck in strain prioritisation and natural product discovery. In this study, molecular networking of the 100 metabolite extracts derived from applying the OSMAC approach to 25 Polar bacterial strains, showed growth media specificity and potential chemical novelty was suggested. Moreover, the metabolite extracts were screened for antibacterial activity and promising selective bioactivity against drug-persistent pathogens such as Klebsiella pneumoniae and Acinetobacter baumannii was observed. Genome sequencing data were combined with metabolomics experiments in the recently developed computational approach, NPLinker, which was used to link BGC and molecular features to prioritise strains for further investigation based on biosynthetic and chemical information. Herein, we putatively identified the known metabolites ectoine and chrloramphenicol which, through NPLinker, were linked to their associated BGCs. The metabologenomics approach followed in this study can potentially be applied to any large microbial datasets for accelerating the discovery of new (bioactive) specialised metabolites

Combining morphological and genomic evidence to resolve species diversity and study speciation processes of the Pallenopsis patagonica (Pycnogonida) species complex

Background: Pallenopsis patagonica (Hoek, 1881) is a morphologically and genetically variable sea spider species whose taxonomic classification is challenging. Currently, it is considered as a species complex including several genetic lineages, many of which have not been formally described as species. Members of this species complex occur on the Patagonian and Antarctic continental shelves as well as around sub-Antarctic islands. These habitats have been strongly influenced by historical large-scale glaciations and previous studies suggested that communities were limited to very few refugia during glacial maxima. Therefore, allopatric speciation in these independent refugia is regarded as a common mechanism leading to high biodiversity of marine benthic taxa in the high-latitude Southern Hemisphere. However, other mechanisms such as ecological speciation have rarely been considered or tested. Therefore, we conducted an integrative morphological and genetic study on the P. patagonica species complex to i) resolve species diversity using a target hybrid enrichment approach to obtain multiple genomic markers, ii) find morphological characters and analyze morphometric measurements to distinguish species, and iii) investigate the speciation processes that led to multiple lineages within the species complex. Results: Phylogenomic results support most of the previously reported lineages within the P. patagonica species complex and morphological data show that several lineages are distinct species with diagnostic characters. Two lineages are proposed as new species, P. aulaeturcarum sp. nov. Dömel & Melzer, 2019 and P. obstaculumsuperavit sp. nov. Dömel, 2019, respectively. However, not all lineages could be distinguished morphologically and thus likely represent cryptic species that can only be identified with genetic tools. Further, morphometric data of 135 measurements showed a high amount of variability within and between species without clear support of adaptive divergence in sympatry. Conclusions: We generated an unprecedented molecular data set for members of the P. patagonica sea spider species complex with a target hybrid enrichment approach, which we combined with extensive morphological and morphometric analyses to investigate the taxonomy, phylogeny and biogeography of this group. The extensive data set enabled us to delineate species boundaries, on the basis of which we formally described two new species. No consistent evidence for positive selection was found, rendering speciation in allopatric glacial refugia as the most likely model of speciation

Effectiveness of continuous glucose monitoring in pregnant women with diabetes: randomised clinical trial

Objective To evaluate the effectiveness of continuous glucose monitoring during pregnancy on maternal glycaemic control, infant birth weight, and risk of macrosomia in women with type 1 and type 2 diabetes