Challenges in advancing Schwann cell transplantation for spinal cord injury repair.

Background Aims: In this article we aimed to provide an expert synthesis of the current status of Schwann cell (SC)therapeutics and potential steps to increase their clinical utility.

Methods: We provide an expert synthesis based on preclinical, clinical and manufacturing experience.

Results: Schwann cells (SCs) are essential for peripheral nerve regeneration and are of interest in supporting axonal repair after spinal cord injury (SCI).

The Curiosity Rover's Exploration of Glen Torridon, Gale Crater, Mars: An Overview of the Campaign and Scientific Results.

The Mars Science Laboratory rover, , explored the clay mineral-bearing Glen Torridon region for 1 Martian year between January 2019 and January 2021, including a short campaign onto the Greenheugh pediment. The Glen Torridon campaign sought to characterize the geology of the area, seek evidence of habitable environments, and document the onset of a potentially global climatic transition during the Hesperian era. roved 5 km in total throughout Glen Torridon, from the Vera Rubin ridge to the northern margin of the Greenheugh pediment.

Orbital and In-Situ Investigation of Periodic Bedrock Ridges in Glen Torridon, Gale Crater, Mars.

Gale crater, the field site for NASA's Mars Science Laboratory Curiosity rover, contains a diverse and extensive record of aeolian deposition and erosion. This study focuses on a series of regularly spaced, curvilinear, and sometimes branching bedrock ridges that occur within the Glen Torridon region on the lower northwest flank of Aeolis Mons, the central mound within Gale crater. During Curiosity's exploration of Glen Torridon between sols ∼2300-3080, the rover drove through this field of ridges, providing the opportunity for in situ observation of these features.

Inverted channel variations identified on a distal portion of a bajada in the central Atacama Desert, Chile.

In deserts, the interplay between occasional fluvial events and persistent aeolian erosion can form composite modern and relict surfaces, especially on the distal portion of alluvial fans. There, relief inversion of alluvial deposits by differential erosion can form longitudinal ridges. We identified two distinct ridge types formed by relief inversion on converging alluvial fans in the hyperarid Chilean Atacama Desert.

Controls on the size distributions of shallow landslides.

Rainfall-triggered shallow landslides are destructive hazards and play an important role in landscape processes. A theory explaining the size distributions of such features remains elusive. Prior work connects size distributions to topography, but field-mapped inventories reveal pronounced similarities in the form, mode, and spread of distributions from diverse landscapes.

Mild Hyperthermia Aggravates Glucose Metabolic Consequences in Repetitive Concussion.

Traumatic brain injury (TBI) is one of the leading causes of mortality and disability around the world. Mild TBI (mTBI) makes up approximately 80% of reported cases and often results in transient psychological abnormalities and cognitive disruption. At-risk populations for mTBI include athletes and other active individuals who may sustain repetitive concussive injury during periods of exercise and exertion when core temperatures are elevated.

Farnesoid X Receptor Agonism, Acetyl-Coenzyme A Carboxylase Inhibition, and Back Translation of Clinically Observed Endpoints of Lipogenesis in a Murine NASH Model.

A promising approach for the treatment of nonalcoholic steatohepatitis (NASH) is the inhibition of enhanced hepatic lipogenesis (DNL), which is the synthesis of fatty acids from nonlipid sources. This study assesses three approaches to DNL suppression in a newly developed dietary NASH mouse model: i) dietary intervention (switch from NASH-inducing diet to normal diet); ii) inhibition of acetyl-coenzyme A carboxylase (ACC), the enzyme catalyzing the rate-limiting step in DNL; and iii) activation of farnesoid X receptor (FXR), a major transcriptional regulator of DNL. C57BL/6J mice on a high-fat diet combined with consumption of a fructose-sucrose solution developed several of the liver histologic features seen in human disease, including steatosis, inflammation, and fibrosis, accompanied by elevated fibrosis biomarkers and liver injury enzymes.

Tropifexor-Mediated Abrogation of Steatohepatitis and Fibrosis Is Associated With the Antioxidative Gene Expression Profile in Rodents.

Farnesoid X receptor (FXR) agonism is emerging as an important potential therapeutic mechanism of action for multiple chronic liver diseases. The bile acid-derived FXR agonist obeticholic acid (OCA) has shown promise in a phase 2 study in patients with nonalcoholic steatohepatitis (NASH). Here, we report efficacy of the novel nonbile acid FXR agonist tropifexor (LJN452) in two distinct preclinical models of NASH.

Anatomical Correlates and Surgical Considerations for Localized Therapeutic Hypothermia Application in Cochlear Implantation Surgery.

Hypothesis: Application of localized, mild therapeutic hypothermia during cochlear implantation (CI) surgery is feasible for residual hearing preservation.

Background: CI surgery often results in a loss of residual hearing. In preclinical studies, local application of controlled, mild therapeutic hypothermia has shown promising results as a hearing preservation strategy.

Discovery of Small Molecule Splicing Modulators of Survival Motor Neuron-2 (SMN2) for the Treatment of Spinal Muscular Atrophy (SMA).

Spinal muscular atrophy (SMA), a rare neuromuscular disorder, is the leading genetic cause of death in infants and toddlers. SMA is caused by the deletion or a loss of function mutation of the survival motor neuron 1 (SMN1) gene. In humans, a second closely related gene SMN2 exists; however it codes for a less stable SMN protein.

DPP9 enzymatic activity in hematopoietic cells is dispensable for mouse hematopoiesis.

Dipeptidyl peptidase 9 (DPP9) is a ubiquitously expressed intracellular prolyl peptidase implicated in immunoregulation. However, its physiological relevance in the immune system remains largely unknown. We investigated the role of DPP9 enzyme in immune system by characterizing DPP9 knock-in mice expressing a catalytically inactive S729A mutant of DPP9 enzyme (DPP9 mice).

Direct observations of rock moisture, a hidden component of the hydrologic cycle.

Recent theory and field observations suggest that a systematically varying weathering zone, that can be tens of meters thick, commonly develops in the bedrock underlying hillslopes. Weathering turns otherwise poorly conductive bedrock into a dynamic water storage reservoir. Infiltrating precipitation typically will pass through unsaturated weathered bedrock before reaching groundwater and running off to streams.

The Mars Science Laboratory (MSL) Mast cameras and Descent imager: Investigation and instrument descriptions.

The Mars Science Laboratory Mast camera and Descent Imager investigations were designed, built, and operated by Malin Space Science Systems of San Diego, CA. They share common electronics and focal plane designs but have different optics. There are two Mastcams of dissimilar focal length.

DPP9 enzyme activity controls survival of mouse migratory tongue muscle progenitors and its absence leads to neonatal lethality due to suckling defect.

Dipeptidyl peptidase 9 (DPP9) is an intracellular N-terminal post-proline-cleaving enzyme whose physiological function remains largely unknown. We investigated the role of DPP9 enzyme in vivo by characterizing knock-in mice expressing a catalytically inactive mutant form of DPP9 (S729A; DPP9 mice). We show that DPP9 mice die within 12-18h after birth.

Progression of Alport Kidney Disease in Col4a3 Knock Out Mice Is Independent of Sex or Macrophage Depletion by Clodronate Treatment.

Alport syndrome is a genetic disease of collagen IV (α3, 4, 5) resulting in renal failure. This study was designed to investigate sex-phenotype correlations and evaluate the contribution of macrophage infiltration to disease progression using Col4a3 knock out (Col4a3KO) mice, an established genetic model of autosomal recessive Alport syndrome. No sex differences in the evolution of body mass loss, renal pathology, biomarkers of tubular damage KIM-1 and NGAL, or deterioration of kidney function were observed during the life span of Col4a3KO mice.

A multidimensional stability model for predicting shallow landslide size and shape across landscapes.

The size of a shallow landslide is a fundamental control on both its hazard and geomorphic importance. Existing models are either unable to predict landslide size or are computationally intensive such that they cannot practically be applied across landscapes. We derive a model appropriate for natural slopes that is capable of predicting shallow landslide size but simple enough to be applied over entire watersheds.

A bottom-up control on fresh-bedrock topography under landscapes.

The depth to unweathered bedrock beneath landscapes influences subsurface runoff paths, erosional processes, moisture availability to biota, and water flux to the atmosphere. Here we propose a quantitative model to predict the vertical extent of weathered rock underlying soil-mantled hillslopes. We hypothesize that once fresh bedrock, saturated with nearly stagnant fluid, is advected into the near surface through uplift and erosion, channel incision produces a lateral head gradient within the fresh bedrock inducing drainage toward the channel.

Isotope ratios of H, C, and O in CO2 and H2O of the martian atmosphere.

Stable isotope ratios of H, C, and O are powerful indicators of a wide variety of planetary geophysical processes, and for Mars they reveal the record of loss of its atmosphere and subsequent interactions with its surface such as carbonate formation. We report in situ measurements of the isotopic ratios of D/H and (18)O/(16)O in water and (13)C/(12)C, (18)O/(16)O, (17)O/(16)O, and (13)C(18)O/(12)C(16)O in carbon dioxide, made in the martian atmosphere at Gale Crater from the Curiosity rover using the Sample Analysis at Mars (SAM)'s tunable laser spectrometer (TLS). Comparison between our measurements in the modern atmosphere and those of martian meteorites such as ALH 84001 implies that the martian reservoirs of CO2 and H2O were largely established ~4 billion years ago, but that atmospheric loss or surface interaction may be still ongoing.

The classical pink-eyed dilution mutation affects angiogenic responsiveness.

Angiogenesis is the process by which new blood vessels are formed from existing vessels. Mammalian populations, including humans and mice, harbor genetic variations that alter angiogenesis. Angiogenesis-regulating gene variants can result in increased susceptibility to multiple angiogenesis-dependent diseases in humans.

Systemic hypothermia for the treatment of acute cervical spinal cord injury in sports.

Spinal cord injury is a devastating condition that affects approximately 12,000 patients each year in the United States. Major causes for spinal cord injury include motor vehicle accidents, sports-related injuries, and direct trauma. Moderate hypothermia has gained attention as a potential therapy due to recent experimental and clinical studies and the use of modest systemic hypothermia (MSH) in high profile case of spinal cord injury in a National Football League (NFL) player.