Explore the vast range of titles available.

At marine cold seeps, gaseous and liquid hydrocarbons migrate from deep subsurface origins to the sediment-water interface. Cold seep sediments are known to host taxonomically diverse microorganisms, but little is known about their metabolic potential and depth distribution in relation to hydrocarbon and electron acceptor availability. Here we combined geophysical, geochemical, metagenomic and metabolomic measurements to profile microbial activities at a newly discovered cold seep in the deep sea. Metagenomic profiling revealed compositional and functional differentiation between near-surface sediments and deeper subsurface layers. In both sulfate-rich and sulfate-depleted depths, various archaeal and bacterial community members are actively oxidizing thermogenic hydrocarbons anaerobically. Depth distributions of hydrocarbon-oxidizing archaea revealed that they are not necessarily associated with sulfate reduction, which is especially surprising for anaerobic ethane and butane oxidizers. Overall, these findings link subseafloor microbiomes to various biochemical mechanisms for the anaerobic degradation of deeply-sourced thermogenic hydrocarbons. Describing anaerobic short chain alkane degrading archaea at a newly discovered cold seep, the authors here suggest that these organisms play much more important roles in submarine carbon cycling globally than previously thought.

Ependymal cells are ciliated-epithelial glial cells that develop from radial glia along the surface of the ventricles of the brain and the spinal canal. They play a critical role in cerebrospinal fluid (CSF) homeostasis, brain metabolism, and the clearance of waste from the brain. These cells have been implicated in disease across the lifespan including developmental disorders, cancer, and neurodegenerative disease. Despite this, ependymal cells remain largely understudied. Using single-cell RNA sequencing data extracted from publicly available datasets, we make key findings regarding the remarkable conservation of ependymal cell gene signatures across age, region, and species. Through this unbiased analysis, we have discovered that one of the most overrepresented ependymal cell functions that we observed relates to a critically understudied role in metal ion homeostasis. Our analysis also revealed distinct subtypes and states of ependymal cells across regions and ages of the nervous system. For example, neonatal ependymal cells maintained a gene signature consistent with developmental processes such as determination of left/right symmetry; while adult ventricular ependymal cells, not spinal canal ependymal cells, appeared to express genes involved in regulating cellular transport and inflammation. Together, these findings highlight underappreciated functions of ependymal cells, which will be important to investigate in order to better understand these cells in health and disease.

Preserving the in vivo cell transcriptome is essential for accurate profiling, yet factors during cell isolation including time ex vivo and temperature induce artifactual gene expression, particularly in stress-responsive immune cells. In this study, we investigated two methods to mitigate ex vivo activation signature gene (ASG) expression in peripheral blood mononuclear cells (PBMCs): transcription and translation inhibitors (TTis) and cold temperatures during isolation. Comparative analysis of PBMCs isolated with TTis revealed reduced ASG expression. However, TTi treatment impaired responsiveness to LPS stimulation in subsequent in vitro experiments. In contrast, cold isolation methods also prevented ASG expression; up to a point where the addition of TTis during cold isolation offered minimal additional advantage. These findings highlight the importance of considering the advantages and drawbacks of different isolation methods to ensure accurate interpretation of PBMC transcriptomic profiles.

Background Astrocytes are the most numerous glial cell type with important roles in maintaining homeostasis and responding to diseases in the brain. Astrocyte function is subject to modulation by microRNAs (miRs), which are short nucleotide strands that regulate protein expression in a post-transcriptional manner. Understanding the miR expression profile of astrocytes in disease settings provides insight into the cellular stresses present in the microenvironment and may uncover pathways of therapeutic interest. Methods Laser-capture microdissection was used to isolate human astrocytes surrounding stroke lesions and those from neurological control tissue. Astrocytic miR expression profiles were examined using quantitative reverse transcription polymerase chain reaction (RT-qPCR). Primary human fetal astrocytes were cultured under in vitro stress conditions and transfection of a miR mimic was used to better understand how altered levels of miR-210 affect astrocyte function. The astrocytic response to stress was studied using qPCR, enzyme-linked immunosorbent assays (ELISAs), measurement of released lactate, and Seahorse. Results Here, we measured miR expression levels in astrocytes around human ischemic stroke lesions and observed differential expression of miR-210 in chronic stroke astrocytes compared to astrocytes from neurological control tissue. We also identified increased expression of miR-210 in mouse white matter tissue around middle cerebral artery occlusion (MCAO) brain lesions. We aimed to understand the role of miR-210 in primary human fetal astrocytes by developing an in vitro assay of hypoxic, metabolic, and inflammatory stresses . A combination of hypoxic and inflammatory stresses was observed to upregulate miR-210 expression. Transfection with miR-210-mimic (210M) increased glycolysis, enhanced lactate export, and promoted an anti-inflammatory transcriptional and translational signature in astrocytes. Additionally, 210M transfection resulted in decreased expression of complement 3 ( C3 ) and semaphorin 5b (Sema5b) . Conclusions We conclude that miR-210 expression in human astrocytes is modulated in response to ischemic stroke disease and under in vitro stress conditions, supporting a role for miR-210 in the astrocytic response to disease conditions. Further, the anti-inflammatory and pro-glycolytic impact of miR-210 on astrocytes makes it a potential candidate for further research as a neuroprotective agent.

Microbiome analysis through 16S rRNA gene sequencing is a crucial tool for understanding the microbial ecology of any habitat or ecosystem. However, workflows require large equipment, stable internet, and extensive computing power such that most of the work is performed far away from sample collection in both space and time. Performing amplicon sequencing and analysis at sample collection would have positive implications in many instances including remote fieldwork and point-of-care medical diagnoses. Here we present SituSeq, an offline and portable workflow for the sequencing and analysis of 16S rRNA gene amplicons using Nanopore sequencing and a standard laptop computer. SituSeq was validated by comparing Nanopore 16S rRNA gene amplicons, Illumina 16S rRNA gene amplicons, and Illumina metagenomes, sequenced using the same environmental DNA. Comparisons revealed consistent community composition, ecological trends, and sequence identity across platforms. Correlation between the abundance of taxa in each taxonomic level in Illumina and Nanopore data sets was high (Pearson’s r > 0.9), and over 70% of Illumina 16S rRNA gene sequences matched a Nanopore sequence with greater than 97% sequence identity. On board a research vessel on the open ocean, SituSeq was used to analyze amplicon sequences from deep sea sediments less than 2 h after sequencing, and 8 h after sample collection. The rapidly available results informed decisions about subsequent sampling in near real-time while the offshore expedition was still underway. SituSeq is a portable and user-friendly workflow that helps to bring the power of microbial genomics and diagnostics to many more researchers and situations.

Parkinson’s disease is characterized by a period of non-motor symptoms, including gastrointestinal dysfunction, preceding motor deficits by several years to decades. This long prodrome is suggestive of peripheral immunity involvement in the initiation of disease. We previously developed a model system in PINK1 KO mice displaying PD-like motor symptoms at late stages following intestinal infections. Herein, we map the initiating immune events at the site of infection in this model. Using single-cell RNAseq, we demonstrate that peripheral myeloid cells are the earliest highly dysregulated immune cell type followed by an aberrant T cell response shortly after. We also demonstrate an increased propensity for antigen presentation and that activated myeloid cells acquire a proinflammatory profile capable of inducing cytotoxic T cell responses. Together, our study provides the first evidence that PINK1 is a key regulator of immune functions in the gut underlying early PD-related disease mechanisms.

In 2011, after more than 20 years of direct rule, the Tatmadaw transferred formal authority to a nominally civilian government following Myanmar's first multi-party election since 1990 as part of a transformation of the political system to a presidential republic. Within this new arena, though, electoral manipulations and constitutional stipulations have brought to power a government consisting mostly of former military officers who are closely aligned to the Tatmadaw. These reforms, therefore, have changed the nature and organization of the ruling regime from that of a military one to an Electoral Authoritarian form. Elections now have become the main conduit to accessing power. Despite the maintenance of authoritarian rule (and the unclear motivations promoting such system change) the opening of the political realm and civil society creates avenues for new actors, identities, interests, and relationships to be constructed. A number of developments over the past few years are tentatively positive signs that Myanmar is undergoing a fundamental political change distinct from the years of military rule. In particular, the interactions of actors within and across civil-military, central-regional, and foreign relations will come to define the future trajectory of these reforms. Ultimately, the willingness of the Tatmadaw to abandon its praetorian ethos of directing the political process, specifically over security policy areas, will determine whether the system remains primarily in the service of regime maintenance or becomes an arena of increasingly diverse, free, and fair political discord with the possibility of power being assumed by those that are non-military.

The Tatmadaw (the Myanmar armed forces) and the Royal Thai Armed Forces (RTAF) are two of the most resilient and enduring politically active militaries in the world, engaging in a decades long process of the institutionalization of a system of military tutelage. There are, however, significant differences in the strategies pursued and the degree of success achieved in each. These variations are due to the combination of three factors creating the environmental context within which they have pursued these projects: (1) the existence of political allies and cohesiveness of the military; (2) degree of unification of domestic opposition elements against them; and (3) international pressures and influences. Based on a Historical Institutionalist perspective, this paper will map the interplay of these factors over time within each case to explain the different pathways these projects have proceeded. With a lack of allies, a fragmented opposition, and various degrees of international pressure the Tatmadaw has been unsuccessful in creating a durable system of tutelage, resulting in lengthy periods of direct rule while attempting wholesale recreations of the state. In Thailand, the RTAF's alliance with the Monarchy combined with a fragmented but at times united opposition and weak international pressure has resulted in frequent coups to remove elected governments, but usually for short durations resulting in their limited institutionalization into the political system. The current democracy projects in both states, in part due to domestic and international pressures, are not about replacing but rather embedding the military's involvement in the political system, though their freedom of action has been constrained to a certain extent. Myanmar and Thailand are best characterized as perpetual transitions as an intentional project to maintain a defective-democratic, tutelary system. Defective in that the military maintains the prerogative to involve itself in electoral politics and tutelary in that the military has cordoned off reserve domains of policy which ensure the system, regardless of who is in charge, supports their interests.

There is growing consensus that Canada needs to “do more” in the Indo-Pacific region as it becomes the centre of gravity in a changing international landscape—a landscape challenging several traditional assumptions about the nature and configuration of global power which Canadian foreign policy has rested upon for decades, specifically due to the emergence of Sino-American rivalry. It is clear Canada needs a regional approach which is rooted in and better informed by geopolitical considerations, but there remains an absence of analytical frameworks to compare and evaluate alternative approaches. In addressing this void, this paper sketches out and compares four possible orientations Canada could pursue towards the Indo-Pacific region: Minimal Engagement, US-Aligned Confrontation, Regional Multilateralism, and Selective Minilateralism. Remaining agnostic about which one(s) Canada should choose, the paper is designed to highlight the stark trade-offs Canada must increasingly confront as it navigates this uncertain environment.

The late Cenozoic seismic stratigraphy of the continental slope south of western Newfoundland is interpreted using new seismic reflection profiles. New Miocene-Pliocene biostratigraphic (palynology) age determinations on the Hermine E-94 well on the northwestern Grand Banks of Newfoundland are correlated to the study area. The Quaternary section of St. Pierre Slope is disrupted by numerous failure scarps and mass-transport deposits, but correlation from the mid-slope to the continental rise is achieved using major mass-transport deposits as markers. On the upper slope, stacked downslope-thinning wedges of acoustically incoherent sediment are interpreted as till deposits of mid-to late Pleistocene age. Sedimentation rates in the youngest part of the succession are estimated from a 30 ka radiocarbon date 25 m below the horizon of the youngest till tongue, which is exposed on a 60 m deep failure surface. Extrapolation of sedimentation rates and comparison with dated sections on the J-Anomaly Ridge and Bermuda Rise provides a consistent interpreted age model for the till tongues that corresponds to marine isotope stages 2, 4, 6, 8, 10, and 12.