Transcriptional Pathways Associated with Skeletal Muscle Changes after Spinal Cord Injury and Treadmill Locomotor Training.

The genetic and molecular events associated with changes in muscle mass and function after SCI and after the implementation of candidate therapeutic approaches are still not completely known. The overall objective of this study was to identify key molecular pathways activated with muscle remodeling after SCI and locomotor training. We implemented treadmill training in a well-characterized rat model of moderate SCI and performed genome wide expression profiling on soleus muscles at multiple time points: 3, 8, and 14 days after SCI. We found that the activity of the protein ubiquitination and mitochondrial function related pathways was altered with SCI and corrected with treadmill training. The BMP pathway was differentially activated with early treadmill training as shown by Ingenuity Pathway Analysis. The expression of several muscle mass regulators was modulated by treadmill training, including Fst, Jun, Bmpr2, Actr2b, and Smad3. In addition, key players in fatty acids metabolism (Lpl and Fabp3) responded to both SCI induced inactivity and reloading with training. The decrease in Smad3 and Fst early after the initiation of treadmill training was confirmed by RT-PCR. Our data suggest that TGFβ/Smad3 signaling may be mainly involved in the decrease in muscle mass observed with SCI, while the BMP pathway was activated with treadmill training

Transcriptional Pathways Associated with Skeletal Muscle Changes after Spinal Cord Injury and Treadmill Locomotor Training.

The genetic and molecular events associated with changes in muscle mass and function after SCI and after the implementation of candidate therapeutic approaches are still not completely known. The overall objective of this study was to identify key molecular pathways activated with muscle remodeling after SCI and locomotor training. We implemented treadmill training in a well-characterized rat model of moderate SCI and performed genome wide expression profiling on soleus muscles at multiple time points: 3, 8, and 14 days after SCI. We found that the activity of the protein ubiquitination and mitochondrial function related pathways was altered with SCI and corrected with treadmill training. The BMP pathway was differentially activated with early treadmill training as shown by Ingenuity Pathway Analysis. The expression of several muscle mass regulators was modulated by treadmill training, including Fst, Jun, Bmpr2, Actr2b, and Smad3. In addition, key players in fatty acids metabolism (Lpl and Fabp3) responded to both SCI induced inactivity and reloading with training. The decrease in Smad3 and Fst early after the initiation of treadmill training was confirmed by RT-PCR. Our data suggest that TGFβ/Smad3 signaling may be mainly involved in the decrease in muscle mass observed with SCI, while the BMP pathway was activated with treadmill training

Surmounting the Tower of Babel: Monolingual and bilingual 2-year-olds’ understanding of the nature of foreign language words

Languages function as independent and distinct conventional systems, and thus each language uses different words to label the same objects. This study investigated whether 2-year-old children recognize that speakers of their native language and speakers of a foreign language do not share the same knowledge. Two groups of children unfamiliar with Mandarin were tested: monolingual English- learning children (n = 24) and bilingual children learning English and another language (n = 24). An English speaker taught children the novel label fep. On English mutual exclusivity trials, the speaker asked for the referent of a novel label (wug) in the presence of the fep and a novel object. Both monolingual and bilingual children disambiguated the reference of the novel word using a mutual exclusivity strategy, choosing the novel object rather than the fep. On similar trials with a Mandarin speaker, children were asked to find the referent of a novel Mandarin label kuò. Monolinguals again chose the novel object rather than the object with the English label fep, even though the Mandarin speaker had no access to conventional English words. Bilinguals did not respond systematically to the Mandarin speaker, suggesting that they had enhanced understanding of the Mandarin speaker’s ignorance of English words. The results indicate that monolingual children initially expect words to be conventionally shared across all speakers, native and foreign. Early bilingual experience facilitates children’s discovery of the nature of foreign language words

Molecular signatures of differential responses to exercise trainings during rehabilitation.

The loss and recovery of muscle mass and function following injury and during rehabilitation varies among individuals. While recent expression profiling studies have illustrated transcriptomic responses to muscle disuse and remodeling, how these changes contribute to the physiological responses are not clear. In this study, we quantified the effects of immobilization and subsequent rehabilitation training on muscle size and identified molecular pathways associated with muscle responsiveness in an orthopaedic patient cohort study. The injured leg of 16 individuals with ankle injury was immobilized for a minimum of 4 weeks, followed by a 6-week rehabilitation program. The maximal cross-sectional area (CSA) of the medial gastrocnemius muscle of the immobilized and control legs were determined by T1-weighted axial MRI images. Genome-wide mRNA profiling data were used to identify molecular signatures that distinguish the patients who responded to immobilization and rehabilitation and those who were considered minimal responders. RESULTS: Using 6% change as the threshold to define responsiveness, a greater degree of changes in muscle size was noted in high responders (−14.9 ± 3.6%) compared to low responders (0.1 ± 0.0%) during immobilization. In addition, a greater degree of changes in muscle size was observed in high responders (20.5 ± 3.2%) compared to low responders (2.5 ± 0.9%) at 6-week rehabilitation. Microarray analysis showed a higher number of genes differentially expressed in the responders compared to low responders in general; with more expression changes observed at the acute stage of rehabilitation in both groups. Pathways analysis revealed top molecular pathways differentially affected in the groups, including genes involved in mitochondrial function, protein turn over, integrin signaling and inflammation. This study confirmed the extent of muscle atrophy due to immobilization and recovery by exercise training is associated with distinct remodeling signature, which can potentially be used for evaluating and predicting clinical outcomes

Sustainable Agriculture Undergraduate Degree Programs: A Land-Grant University Mission

There has been considerable growth in the number undergraduate degree programs in sustainable agriculture (SA) in universities and colleges across the country in the past 25 years. As a subset of this national trend, land-grant universities (LGUs) are emerging as catalysts in innovative SA program development, in part due to the LGU tripartite mission of education, extension, and research. This mission compels LGUs to develop undergraduate degree offerings to engage student, faculty, and community stakeholders who are increasingly interested in SA. In this article, which is an outcome of a gathering of faculty, staff and students from SA programs at LGUs at a workshop prior to the 4th National Sustainable Agriculture Education Association Conference in August 2011, we discuss the justification for SA programming at LGUs, the emergence of SA major and minor degrees at 11 LGUs to date, the common successes and challenges of current SA programs, strategies for improving existing SA programming, and systematic approaches for expanding SA education impact across institutional lines. We also introduce several additional topic-based articles that resulted from workshop dialogue that appear in this issue of the Journal of Agriculture, Food Systems, and Community Development, including civic engagement efforts in SA education through community-university partnerships, a critical documentation of the implicit inclusion of values into SA education, and efforts to internationalize SA curriculum

Condensation/immersion mode ice-nucleating particles in a boreal environment

Ice-nucleating particle (INP) measurements were performed in the boreal environment of southern Finland at the Station for Measuring Ecosystem-Atmosphere Relations (SMEAR II) in the winter-spring of 2018. Measurements with the Portable Ice Nucleation Chamber (PINC) were conducted at 242 K and 105 % relative humidity with respect to water. The median INP number concentration [INP] during a 6-week measurement period was 13 L-1. The [INP] spanned 3 orders of magnitude and showed a general increase from mid-February until early April. No single dominant local or regional sources of INPs in the boreal environment of southern Finland could be identified. Rather, it is hypothesised that the INPs detected at SMEAR II are a result of long-range transport and dilution of INPs sourced far from the measurement site. Despite high variability, the measured [INP] values fall within the range expected for the [INP] measured elsewhere under similar thermodynamic conditions. The [INP] did not correlate with any of the examined parameters during the entire field campaign, indicating that no one single parameter can be used to predict the [INP] at the measurement location during the examined time period. The absence of a correlation across the entire field campaign also suggests that a variety of particles act as INPs at different times, although it was indirectly determined that ambient INPs are most likely within the size range of 0.1-0.5 mu m in diameter on average. On shorter timescales, several particle species correlated well with the [INP]. Depending on the meteorological conditions, black carbon (BC), supermicron biological particles and sub-0.1 mu m particles, most likely nanoscale biological fragments such as ice-nucleating macromolecules (INMs), correlated with the INP signal. However, an increase in the concentration of any of these particle species may not necessarily lead to the increase in the [INP]; the reasons for this remain unknown. Limitations of the instrumental set-up and the necessity for future field INP studies are addressed.Peer reviewe

Sterically Induced Binding Selectivity of Single m-Terphenyl Isocyanide Ligands

Sterically encumbering m-terphenyl isocyanides are a class of metal-binding group that foster low-coordinate metal-center environments in coordination chemistry by exerting considerable intermolecular steric pressures between neighboring ligands. In the context of metal surfaces, the encumbering steric properties of the m-terphenyl isocyanides are shown to weaken the interaction between the metal-binding group and a planar substrate, leading to a preference for molecular adsorption at sites with convex curvature, such as the step edges and herringbone elbow sites on Au(111). Here, we investigate the site-selective binding of individual m-terphenyl isocyanide ligands on a Au(111) surface through scanning tunneling microscopy (STM) and inelastic electron tunneling spectroscopy (IETS). The site-dependent steric pressure alters the vibrational fingerprint of the m-terphenyl isocyanides, which is characterized with single-molecule precision through joint experimental and theoretical approaches. This study for the first time provides molecular-level insights into the steric-pressure-enabled surface binding selectivity as well as its effect on the chemical properties of individual m-terphenyl isocyanide ligands, thereby highlighting the potential to control the physical and chemical properties of metal surfaces through tailored ligand design

Reduced malignancy as a mechanism for longevity in mice with adenylyl cyclase type 5 disruption

Disruption of adenylyl cyclase type 5 (AC5) knockout (KO) is a novel model for longevity. Because malignancy is a major cause of death and reduced lifespan in mice, the goal of this investigation was to examine the role of AC5KO in protecting against cancer. There have been numerous discoveries in genetically engineered mice over the past several decades, but few have been translated to the bedside. One major reason is that it is difficult to alter a gene in patients, but rather a pharmacological approach is more appropriate. The current investigation employs a parallel construction to examine the extent to which inhibiting AC5, either in a genetic knockout (KO) or by a specific pharmacological inhibitor protects against cancer. This study is unique, not only because a combined genetic and pharmacological approach is rare, but also there are no prior studies on the extent to which AC5 affects cancer. We found that AC5KO delayed age-related tumor incidence significantly, as well as protecting against mammary tumor development in AC5KO × MMTV-HER-2 neu mice, and B16F10 melanoma tumor growth, which can explain why AC5KO is a model of longevity. In addition, a Food and Drug Administration approved antiviral agent, adenine 9-β-D-arabinofuranoside (Vidarabine or AraAde), which specifically inhibits AC5, reduces LP07 lung and B16F10 melanoma tumor growth in syngeneic mice. Thus, inhibition of AC5 is a previously unreported mechanism for prevention of cancers associated with aging and that can be targeted by an available pharmacologic inhibitor, with potential consequent extension of lifespan.Fil: De Lorenzo, Mariana S.. State University of New Jersey; Estados UnidosFil: Chen, Wen. Clemson University; Estados UnidosFil: Baljinnyam, Erdene. State University of New Jersey; Estados UnidosFil: Carlini, María José. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncologia "Angel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: La Perle, Krista. Ohio State University; Estados UnidosFil: Bishop, Sanford P.. State University of New Jersey; Estados UnidosFil: Wagner, Thomas E.. Clemson University; Estados UnidosFil: Rabson, Arnold B.. State University of New Jersey; Estados UnidosFil: Vatner, Dorothy E.. State University of New Jersey; Estados UnidosFil: Puricelli, Lydia Ines. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncologia "Angel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vatner, Stephen F.. State University of New Jersey; Estados Unido