PPM-1, a PP2Cα/β phosphatase, Regulates Axon Termination and Synapse Formation in Caenorhabditis elegans

The PHR (Pam/Highwire/RPM-1) proteins are evolutionarily conserved ubiquitin ligases that regulate axon guidance and synapse formation in Caenorhabditis elegans, Drosophila, zebrafish, and mice. In C. elegans, RPM-1 (Regulator of Presynaptic Morphology-1) functions in synapse formation, axon guidance, axon termination, and postsynaptic GLR-1 trafficking. Acting as an E3 ubiquitin ligase, RPM-1 negatively regulates a MAP kinase pathway that includes: dlk-1, mkk-4, and the p38 MAPK, pmk-3. Here we provide evidence that ppm-1, a serine/threonine phosphatase homologous to human PP2Cα(PPM1A) and PP2Cβ(PPM1B) acts as a second negative regulatory mechanism to control the dlk-1 pathway. We show that ppm-1 functions through its phosphatase activity in a parallel genetic pathway with glo-4 and fsn-1 to regulate both synapse formation in the GABAergic motorneurons and axon termination in the mechanosensory neurons. Our transgenic analysis shows that ppm-1 acts downstream of rpm-1 to negatively regulate the DLK-1 pathway, with PPM-1 most likely acting at the level of pmk-3. Our study provides insight into the negative regulatory mechanisms that control the dlk-1 pathway in neurons and demonstrates a new role for the PP2C/PPM phosphatases as regulators of neuronal development

Why human rights matter for marine conservation

Human rights matter for marine conservation because people and nature are inextricably linked. A thriving planet cannot be one that contains widespread human suffering or stifles human potential; and a thriving humanity cannot exist on a dying planet. While the field of marine conservation is increasingly considering human well-being, it retains a legacy in some places of protectionism, colonialism, and fortress conservation. Here, we i) provide an overview of human rights principles and how they relate to marine conservation, ii) document cases where tensions have occurred between marine conservation goals and human rights, iii) review the legal and ethical obligations, and practical benefits, for marine conservation to support human rights, and iv) provide practical guidance on integrating human rights principles into marine conservation. We argue that adopting a human rights-based approach to marine conservation, that is integrating equity as a rights-based condition rather than a charitable principle, will not only help meet legal and ethical obligations to respect, protect, and fulfil human rights, but will also result in greater and more enduring conservation impact

Outcomes in patients with gunshot wounds to the brain.

Introduction:Gunshot wounds to the brain (GSWB) confer high lethality and uncertain recovery. It is unclear which patients benefit from aggressive resuscitation, and furthermore whether patients with GSWB undergoing cardiopulmonary resuscitation (CPR) have potential for survival or organ donation. Therefore, we sought to determine the rates of survival and organ donation, as well as identify factors associated with both outcomes in patients with GSWB undergoing CPR. Methods:We performed a retrospective, multicenter study at 25 US trauma centers including dates between June 1, 2011 and December 31, 2017. Patients were included if they suffered isolated GSWB and required CPR at a referring hospital, in the field, or in the trauma resuscitation room. Patients were excluded for significant torso or extremity injuries, or if pregnant. Binomial regression models were used to determine predictors of survival/organ donation. Results:825 patients met study criteria; the majority were male (87.6%) with a mean age of 36.5 years. Most (67%) underwent CPR in the field and 2.1% (n=17) survived to discharge. Of the non-survivors, 17.5% (n=141) were considered eligible donors, with a donation rate of 58.9% (n=83) in this group. Regression models found several predictors of survival. Hormone replacement was predictive of both survival and organ donation. Conclusion:We found that GSWB requiring CPR during trauma resuscitation was associated with a 2.1% survival rate and overall organ donation rate of 10.3%. Several factors appear to be favorably associated with survival, although predictions are uncertain due to the low number of survivors in this patient population. Hormone replacement was predictive of both survival and organ donation. These results are a starting point for determining appropriate treatment algorithms for this devastating clinical condition. Level of evidence:Level II

Why human rights matter for marine conservation

Human rights matter for marine conservation because people and nature are inextricably linked. A thriving planet cannot be one that contains widespread human suffering or stifles human potential; and a thriving humanity cannot exist on a dying planet. While the field of marine conservation is increasingly considering human well-being, it retains a legacy in some places of protectionism, colonialism, and fortress conservation. Here, we i) provide an overview of human rights principles and how they relate to marine conservation, ii) document cases where tensions have occurred between marine conservation goals and human rights, iii) review the legal and ethical obligations, and practical benefits, for marine conservation to support human rights, and iv) provide practical guidance on integrating human rights principles into marine conservation. We argue that adopting a human rights-based approach to marine conservation, that is integrating equity as a rights-based condition rather than a charitable principle, will not only help meet legal and ethical obligations to respect, protect, and fulfil human rights, but will also result in greater and more enduring conservation impact

The TLQP-21 Peptide Activates the G-Protein-Coupled Receptor C3aR1 via a Folding-upon-Binding Mechanism

TLQP-21, a VGF-encoded peptide is emerging as a novel target for obesity-associated disorders. TLQP-21 is found in the sympathetic nerve terminals in the adipose tissue and targets the G-protein-coupled-receptor (GPCR) Complement-3a-Receptor1 (C3aR1). So far, the mechanisms of TLQP-21-induced receptor activation remained unexplored. Here, we report that TLQP-21 is intrinsically disordered and undergoes a disorder-to-order transition, adopting an α-helical conformation, upon targeting cells expressing the C3aR1. We determined that the hot spots for TLQP-21 are located at the C-terminus, with mutations in the last four amino acids progressively reducing the bioactivity and, a single site mutation (R21A) or C-terminal amidation abolishing its function completely. Interestingly, the human TLQP-21 sequence carrying a S20A substitution activates the human C3aR1 receptor with lower potency compared to the rodent sequence. These studies reveal the mechanism of action of TLQP-21 and provide molecular templates for designing agonists and antagonists to modulate C3aR1 functions

Understanding of Coupled Terrestrial Carbon, Nitrogen and Water Dynamics—An Overview

Coupled terrestrial carbon (C), nitrogen (N) and hydrological processes play a crucial role in the climate system, providing both positive and negative feedbacks to climate change. In this review we summarize published research results to gain an increased understanding of the dynamics between vegetation and atmosphere processes. A variety of methods, including monitoring (e.g., eddy covariance flux tower, remote sensing, etc.) and modeling (i.e., ecosystem, hydrology and atmospheric inversion modeling) the terrestrial carbon and water budgeting, are evaluated and compared. We highlight two major research areas where additional research could be focused: (i) Conceptually, the hydrological and biogeochemical processes are closely linked, however, the coupling processes between terrestrial C, N and hydrological processes are far from well understood; and (ii) there are significant uncertainties in estimates of the components of the C balance, especially at landscape and regional scales. To address these two questions, a synthetic research framework is needed which includes both bottom-up and top-down approaches integrating scalable (footprint and ecosystem) models and a spatially nested hierarchy of observations which include multispectral remote sensing, inventories, existing regional clusters of eddy-covariance flux towers and CO2 mixing ratio towers and chambers

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Models of classroom assessment for course-based research experiences

Course-based research pedagogy involves positioning students as contributors to authentic research projects as part of an engaging educational experience that promotes their learning and persistence in science. To develop a model for assessing and grading students engaged in this type of learning experience, the assessment aims and practices of a community of experienced course-based research instructors were collected and analyzed. This approach defines four aims of course-based research assessment—(1) Assessing Laboratory Work and Scientific Thinking; (2) Evaluating Mastery of Concepts, Quantitative Thinking and Skills; (3) Appraising Forms of Scientific Communication; and (4) Metacognition of Learning—along with a set of practices for each aim. These aims and practices of assessment were then integrated with previously developed models of course-based research instruction to reveal an assessment program in which instructors provide extensive feedback to support productive student engagement in research while grading those aspects of research that are necessary for the student to succeed. Assessment conducted in this way delicately balances the need to facilitate students’ ongoing research with the requirement of a final grade without undercutting the important aims of a CRE education

Grooved stripes for plow-resistant wet-night lane delineation. Phase II. Recessed reflector delineation. Final report.

Federal Highway Administration, Office of Research and Development, Washington, D.C.Mode of access: Internet.Author corporate affiliation: New York State Department of Transportation, Engineering Research and Development Bureau, Albany, N.Y.Report covers the period June 1975 through June 1976Subject code: BPSubject code: CDFDSubject code: CICSubject code: CIHSubject code: DEHJSubject code: LCCSubject code: MSDSubject code: NOSubject code: PMK