The rs1076560 polymorphism of DRD2 (encoding dopamine receptor D2) is associated with alternative splicing and cognitive functioning; however, a mechanistic relationship to schizophrenia has not been ...shown. Here, we demonstrate that rs1076560(T) imparts a small but reliable risk for schizophrenia in a sample of 616 affected families and five independent replication samples totaling 4017 affected and 4704 unaffected individuals (odds ratio=1.1; P=0.004). rs1076560(T) was associated with impaired verbal fluency and comprehension in schizophrenia but improved performance among healthy comparison subjects. rs1076560(T) also associated with lower D2 short isoform expression in postmortem brain. rs1076560(T) disrupted a binding site for the splicing factor ZRANB2, diminished binding affinity between DRD2 pre-mRNA and ZRANB2 and abolished the ability of ZRANB2 to modulate short:long isoform-expression ratios of DRD2 minigenes in cell culture. Collectively, this work implicates rs1076560(T) as one possible risk factor for schizophrenia in the Han Chinese population, and suggests molecular mechanisms by which it may exert such influence.
Executive Summary
Return of samples from the surface of Mars has been a goal of the international Mars science community for many years. Affirmation by NASA and ESA of the importance of Mars ...exploration led the agencies to establish the international MSR Objectives and Samples Team (iMOST). The purpose of the team is to re‐evaluate and update the sample‐related science and engineering objectives of a Mars Sample Return (MSR) campaign. The iMOST team has also undertaken to define the measurements and the types of samples that can best address the objectives.
Seven objectives have been defined for MSR, traceable through two decades of previously published international priorities. The first two objectives are further divided into sub‐objectives. Within the main part of the report, the importance to science and/or engineering of each objective is described, critical measurements that would address the objectives are specified, and the kinds of samples that would be most likely to carry key information are identified. These seven objectives provide a framework for demonstrating how the first set of returned Martian samples would impact future Martian science and exploration. They also have implications for how analogous investigations might be conducted for samples returned by future missions from other solar system bodies, especially those that may harbor biologically relevant or sensitive material, such as Ocean Worlds (Europa, Enceladus, Titan) and others.
Summary of Objectives and Sub‐Objectives for MSR Identified by iMOST
Objective 1
Interpret the primary geologic processes and history that formed the Martian geologic record, with an emphasis on the role of water.
Intent
To investigate the geologic environment(s) represented at the Mars 2020 landing site, provide definitive geologic context for collected samples, and detail any characteristics that might relate to past biologic processesThis objective is divided into five sub‐objectives that would apply at different landing sites.
1.1 Characterize the essential stratigraphic, sedimentologic, and facies variations of a sequence of Martian sedimentary rocks.
Intent
To understand the preserved Martian sedimentary record.
Samples
A suite of sedimentary rocks that span the range of variation.
Importance
Basic inputs into the history of water, climate change, and the possibility of life
1.2 Understand an ancient Martian hydrothermal system through study of its mineralization products and morphological expression.
Intent
To evaluate at least one potentially life‐bearing “habitable” environment
Samples
A suite of rocks formed and/or altered by hydrothermal fluids.
Importance
Identification of a potentially habitable geochemical environment with high preservation potential.
1.3 Understand the rocks and minerals representative of a deep subsurface groundwater environment.
Intent
To evaluate definitively the role of water in the subsurface.
Samples
Suites of rocks/veins representing water/rock interaction in the subsurface.
Importance
May constitute the longest‐lived habitable environments and a key to the hydrologic cycle.
1.4 Understand water/rock/atmosphere interactions at the Martian surface and how they have changed with time.
Intent
To constrain time‐variable factors necessary to preserve records of microbial life.
Samples
Regolith, paleosols, and evaporites.
Importance
Subaerial near‐surface processes could support and preserve microbial life.
1.5 Determine the petrogenesis of Martian igneous rocks in time and space.
Intent
To provide definitive characterization of igneous rocks on Mars.
Samples
Diverse suites of ancient igneous rocks.
Importance
Thermochemical record of the planet and nature of the interior.
Objective 2
Assess and interpret the potential biological history of Mars, including assaying returned samples for the evidence of life.
Intent
To investigate the nature and extent of Martian habitability, the conditions and processes that supported or challenged life, how different environments might have influenced the preservation of biosignatures and created nonbiological “mimics,” and to look for biosignatures of past or present life.This objective has three sub‐objectives:
2.1 Assess and characterize carbon, including possible organic and pre‐biotic chemistry.
Samples
All samples collected as part of Objective 1.
Importance
Any biologic molecular scaffolding on Mars would likely be carbon‐based.
2.2 Assay for the presence of biosignatures of past life at sites that hosted habitable environments and could have preserved any biosignatures.
Samples
All samples collected as part of Objective 1.
Importance
Provides the means of discovering ancient life.
2.3 Assess the possibility that any life forms detected are alive, or were recently alive.
Samples
All samples collected as part of Objective 1.
Importance
Planetary protection, and arguably the most important scientific discovery possible.
Objective 3
Quantitatively determine the evolutionary timeline of Mars.
Intent
To provide a radioisotope‐based time scale for major events, including magmatic, tectonic, fluvial, and impact events, and the formation of major sedimentary deposits and geomorphological features.
Samples
Ancient igneous rocks that bound critical stratigraphic intervals or correlate with crater‐dated surfaces.
Importance
Quantification of Martian geologic history.
Objective 4
Constrain the inventory of Martian volatiles as a function of geologic time and determine the ways in which these volatiles have interacted with Mars as a geologic system.
Intent
To recognize and quantify the major roles that volatiles (in the atmosphere and in the hydrosphere) play in Martian geologic and possibly biologic evolution.
Samples
Current atmospheric gas, ancient atmospheric gas trapped in older rocks, and minerals that equilibrated with the ancient atmosphere.
Importance
Key to understanding climate and environmental evolution.
Objective 5
Reconstruct the processes that have affected the origin and modification of the interior, including the crust, mantle, core and the evolution of the Martian dynamo.
Intent
To quantify processes that have shaped the planet's crust and underlying structure, including planetary differentiation, core segregation and state of the magnetic dynamo, and cratering.
Samples
Igneous, potentially magnetized rocks (both igneous and sedimentary) and impact‐generated samples.
Importance
Elucidate fundamental processes for comparative planetology.
Objective 6
Understand and quantify the potential Martian environmental hazards to future human exploration and the terrestrial biosphere.
Intent
To define and mitigate an array of health risks related to the Martian environment associated with the potential future human exploration of Mars.
Samples
Fine‐grained dust and regolith samples.
Importance
Key input to planetary protection planning and astronaut health.
Objective 7
Evaluate the type and distribution of in‐situ resources to support potential future Mars exploration.
Intent
To quantify the potential for obtaining Martian resources, including use of Martian materials as a source of water for human consumption, fuel production, building fabrication, and agriculture.
Samples
Regolith.
Importance
Production of simulants that will facilitate long‐term human presence on Mars.
Summary of iMOST Findings
Several specific findings were identified during the iMOST study. While they are not explicit recommendations, we suggest that they should serve as guidelines for future decision making regarding planning of potential future MSR missions.
The samples to be collected by the Mars 2020 (M‐2020) rover will be of sufficient size and quality to address and solve a wide variety of scientific questions.
Samples, by definition, are a statistical representation of a larger entity. Our ability to interpret the source geologic units and processes by studying sample sub sets is highly dependent on the quality of the sample context. In the case of the M‐2020 samples, the context is expected to be excellent, and at multiple scales. (A) Regional and planetary context will be established by the on‐going work of the multi‐agency fleet of Mars orbiters. (B) Local context will be established at field area‐ to outcrop‐ to hand sample‐ to hand lens scale using the instruments carried by M‐2020.
A significant fraction of the value of the MSR sample collection would come from its organization into sample suites, which are small groupings of samples designed to represent key aspects of geologic or geochemical variation.
If the Mars 2020 rover acquires a scientifically well‐chosen set of samples, with sufficient geological diversity, and if those samples were returned to Earth, then major progress can be expected on all seven of the objectives proposed in this study, regardless of the final choice of landing site. The specifics of which parts of Objective 1 could be achieved would be different at each of the final three candidate landing sites, but some combination of critically important progress could be made at any of them.
An aspect of the search for evidence of life is that we do not know in advance how evidence for Martian life would be preserved in the geologic record. In order for the returned samples to be most useful for both understanding geologic processes (Objective 1) and the search for life (Objective 2), the sample collection should contain BOTH typical and unusual samples from the rock units explored. This consideration should be incorporated into sample selection and the design of the suites.
The retrieval missions of a MSR campaign should (1) minimize stray magnetic fields to which the samples would be exposed and carry a magnetic witness plate to record exposure, (2) collect and return atmospheric gas sample(s), and (3) collect additional dust and/or regolith sample mass if possible.
The goal of this study was to use bioengineered injectable microgels to enhance the action of bone morphogenetic protein 2 (BMP2) and stimulate cartilage matrix repair in a reversible animal model of ...osteoarthritis (OA). A module of perlecan (PlnD1) bearing heparan sulfate (HS) chains was covalently immobilized to hyaluronic acid (HA) microgels for the controlled release of BMP2 in vivo. Articular cartilage damage was induced in mice using a reversible model of experimental OA and was treated by intra-articular injection of PlnD1-HA particles with BMP2 bound to HS. Control injections consisted of BMP2-free PlnD1-HA particles, HA particles, free BMP2 or saline. Knees dissected following these injections were analyzed using histological, immunostaining and gene expression approaches. Our results show that knees treated with PlnD1-HA/BMP2 had lesser OA-like damage compared to control knees. In addition, the PlnD1-HA/BMP2-treated knees had higher mRNA levels encoding for type II collagen, proteoglycans and xylosyltransferase 1, a rate-limiting anabolic enzyme involved in the biosynthesis of glycosaminoglycan chains, relative to control knees (PlnD1-HA). This finding was paralleled by enhanced levels of aggrecan in the articular cartilage of PlnD1-HA/BMP2-treated knees. Additionally, decreases in the mRNA levels encoding for cartilage-degrading enzymes and type X collagen were seen relative to controls. In conclusion, PlnD1-HA microgels constitute a formulation improvement compared to HA for efficient in vivo delivery and stimulation of proteoglycan and cartilage matrix synthesis in mouse articular cartilage. Ultimately, PlnD1-HA/BMP2 may serve as an injectable therapeutic agent for slowing or inhibiting the onset of OA after knee injury.
Sjögren's disease (SjD) is a systemic autoimmune exocrinopathy with key features of dryness, pain, and fatigue. SjD can affect any organ system with a variety of presentations across individuals. ...This heterogeneity is one of the major barriers for developing effective disease modifying treatments. Defining core disease domains comprising both specific clinical features and incorporating the patient experience is a critical first step to define this complex disease. The OMERACT SjD Working Group held its first international collaborative hybrid meeting in 2023, applying the OMERACT 2.2 filter toward identification of core domains. We accomplished our first goal, a scoping literature review that was presented at the Special Interest Group held in May 2023. Building on the domains identified in the scoping review, we uniquely deployed multidisciplinary experts as part of our collaborative team to generate a provisional domain list that captures SjD heterogeneity.
Executive Summary
Return of samples from the surface of Mars has been a goal of the international Mars science community for many years. Affirmation by
NASA
and
ESA
of the importance of Mars ...exploration led the agencies to establish the international
MSR
Objectives and Samples Team (
iMOST
). The purpose of the team is to re‐evaluate and update the sample‐related science and engineering
objectives
of a Mars Sample Return (
MSR
) campaign. The
iMOST
team has also undertaken to define the
measurements
and the
types of samples
that can best address the objectives.
Seven objectives have been defined for
MSR
, traceable through two decades of previously published international priorities. The first two objectives are further divided into sub‐objectives. Within the main part of the report, the importance to science and/or engineering of each objective is described, critical measurements that would address the objectives are specified, and the kinds of samples that would be most likely to carry key information are identified. These seven objectives provide a framework for demonstrating how the first set of returned Martian samples would impact future Martian science and exploration. They also have implications for how analogous investigations might be conducted for samples returned by future missions from other solar system bodies, especially those that may harbor biologically relevant or sensitive material, such as Ocean Worlds (Europa, Enceladus, Titan) and others.
Summary of Objectives and Sub‐Objectives for MSR Identified by iMOST
Objective 1
Interpret the primary geologic processes and history that formed the Martian geologic record, with an emphasis on the role of water.
Intent
To investigate the geologic environment(s) represented at the Mars 2020 landing site, provide definitive geologic context for collected samples, and detail any characteristics that might relate to past biologic processes
This objective is divided into five sub‐objectives that would apply at different landing sites.
Characterize the essential stratigraphic, sedimentologic, and facies variations of a sequence of Martian sedimentary rocks.
Intent
To understand the preserved Martian sedimentary record.
Samples
A suite of sedimentary rocks that span the range of variation.
Importance
Basic inputs into the history of water, climate change, and the possibility of life
Understand an ancient Martian hydrothermal system through study of its mineralization products and morphological expression.
Intent
To evaluate at least one potentially life‐bearing “habitable” environment
Samples
A suite of rocks formed and/or altered by hydrothermal fluids.
Importance
Identification of a potentially habitable geochemical environment with high preservation potential.
Understand the rocks and minerals representative of a deep subsurface groundwater environment.
Intent
To evaluate definitively the role of water in the subsurface.
Samples
Suites of rocks/veins representing water/rock interaction in the subsurface.
Importance
May constitute the longest‐lived habitable environments and a key to the hydrologic cycle.
Understand water/rock/atmosphere interactions at the Martian surface and how they have changed with time.
Intent
To constrain time‐variable factors necessary to preserve records of microbial life.
Samples
Regolith, paleosols, and evaporites.
Importance
Subaerial near‐surface processes could support and preserve microbial life.
Determine the petrogenesis of Martian igneous rocks in time and space.
Intent
To provide definitive characterization of igneous rocks on Mars.
Samples
Diverse suites of ancient igneous rocks.
Importance
Thermochemical record of the planet and nature of the interior.
Objective 2
Assess and interpret the potential biological history of Mars, including assaying returned samples for the evidence of life.
Intent
To investigate the nature and extent of Martian habitability, the conditions and processes that supported or challenged life, how different environments might have influenced the preservation of biosignatures and created nonbiological “mimics,” and to look for biosignatures of past or present life.
This objective has three sub‐objectives:
Assess and characterize carbon, including possible organic and pre‐biotic chemistry.
Samples
All samples collected as part of Objective 1.
Importance
Any biologic molecular scaffolding on Mars would likely be carbon‐based.
Assay for the presence of biosignatures of past life at sites that hosted habitable environments and could have preserved any biosignatures.
Samples
All samples collected as part of Objective 1.
Importance
Provides the means of discovering ancient life.
Assess the possibility that any life forms detected are alive, or were recently alive.
Samples
All samples collected as part of Objective 1.
Importance
Planetary protection, and arguably the most important scientific discovery possible.
Objective 3
Quantitatively determine the evolutionary timeline of Mars.
Intent
To provide a radioisotope‐based time scale for major events, including magmatic, tectonic, fluvial, and impact events, and the formation of major sedimentary deposits and geomorphological features.
Samples
Ancient igneous rocks that bound critical stratigraphic intervals or correlate with crater‐dated surfaces.
Importance
Quantification of Martian geologic history.
Objective 4
Constrain the inventory of Martian volatiles as a function of geologic time and determine the ways in which these volatiles have interacted with Mars as a geologic system.
Intent
To recognize and quantify the major roles that volatiles (in the atmosphere and in the hydrosphere) play in Martian geologic and possibly biologic evolution.
Samples
Current atmospheric gas, ancient atmospheric gas trapped in older rocks, and minerals that equilibrated with the ancient atmosphere.
Importance
Key to understanding climate and environmental evolution.
Objective 5
Reconstruct the processes that have affected the origin and modification of the interior, including the crust, mantle, core and the evolution of the Martian dynamo.
Intent
To quantify processes that have shaped the planet's crust and underlying structure, including planetary differentiation, core segregation and state of the magnetic dynamo, and cratering.
Samples
Igneous, potentially magnetized rocks (both igneous and sedimentary) and impact‐generated samples.
Importance
Elucidate fundamental processes for comparative planetology.
Objective 6
Understand and quantify the potential Martian environmental hazards to future human exploration and the terrestrial biosphere.
Intent
To define and mitigate an array of health risks related to the Martian environment associated with the potential future human exploration of Mars.
Samples
Fine‐grained dust and regolith samples.
Importance
Key input to planetary protection planning and astronaut health.
Objective 7
Evaluate the type and distribution of
in‐situ
resources to support potential future Mars exploration.
Intent
To quantify the potential for obtaining Martian resources, including use of Martian materials as a source of water for human consumption, fuel production, building fabrication, and agriculture.
Samples
Regolith.
Importance
Production of simulants that will facilitate long‐term human presence on Mars.
Summary of iMOST Findings
Several specific findings were identified during the
iMOST
study. While they are not explicit recommendations, we suggest that they should serve as guidelines for future decision making regarding planning of potential future
MSR
missions.
The samples to be collected by the Mars 2020 (M‐2020) rover will be of sufficient size and quality to address and solve a wide variety of scientific questions.
Samples, by definition, are a statistical representation of a larger entity. Our ability to interpret the source geologic units and processes by studying sample sub sets is highly dependent on the quality of the sample context. In the case of the M‐2020 samples, the context is expected to be excellent, and at multiple scales. (A) Regional and planetary context will be established by the on‐going work of the multi‐agency fleet of Mars orbiters. (B) Local context will be established at field area‐ to outcrop‐ to hand sample‐ to hand lens scale using the instruments carried by M‐2020.
A significant fraction of the value of the MSR sample collection would come from its organization into sample suites, which are small groupings of samples designed to represent key aspects of geologic or geochemical variation.
If the Mars 2020 rover acquires a scientifically well‐chosen set of samples, with sufficient geological diversity, and if those samples were returned to Earth, then major progress can be expected on all seven of the objectives proposed in this study, regardless of the final choice of landing site. The specifics of which parts of Objective 1 could be achieved would be different at each of the final three candidate landing sites, but some combination of critically important progress could be made at any of them.
An aspect of the search for evidence of life is that we do not know in advance how evidence for Martian life would be preserved in the geologic record. In order for the returned samples to be most useful for both understanding geologic processes (Objective 1) and the search for life (Objective 2), the sample collection should contain BOTH typical and unusual samples from the rock units explored. This consideration should be incorporated into sample selection and the design of the suites.
The retrieval missions of a MSR campaign should (1) minimize stray magnetic fields to which the samples would be exposed and carry a magnetic witness plate to record exposure, (2) collect and return atmospheric gas sample(s), and (3) collect additional dust and/or regolith sample mass if possible.
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