NDRG2 promotes myoblast proliferation and caspase 3/7 activities during differentiation, and attenuates hydrogen peroxide - but not palmitate-induced toxicity

The function of the stress-responsive N-myc downstream-regulated gene 2 (NDRG2) in the control of myoblast growth, and the amino acids contributing to its function, are not well characterized. Here, we investigated the effect of increased NDRG2 levels on the proliferation, differentiation and apoptosis in skeletal muscle cells under basal and stress conditions. NDRG2 overexpression increased C2C12 myoblast proliferation and the expression of positive cell cycle regulators, cdk2, cyclin B and cyclin D, and phosphorylation of Rb, while the serine/threonine-deficient NDRG2, 3A-NDRG2, had less effect. The onset of differentiation was enhanced by NDRG2 as determined through the myogenic regulatory factor expression profiles and myocyte fusion index. However, the overall level of differentiation in myotubes was not different. While NDRG2 up-regulated caspase 3/7 activities during differentiation, no increase in apoptosis was measured by TUNEL assay or through cleavage of caspase 3 and PARP proteins. During H2O2 treatment to induce oxidative stress, NDRG2 helped protect against the loss of proliferation and ER stress as measured by GRP78 expression with 3A-NDRG2 displaying less protection. NDRG2 also attenuated apoptosis by reducing cleavage of PARP and caspase 3 and expression of pro-apoptotic Bax while enhancing the pro-survival Bcl-2 and Bcl-xL levels. In contrast, Mcl-1 was not altered, and NDRG2 did not protect against palmitate-induced lipotoxicity. Our findings show that NDRG2 overexpression increases myoblast proliferation and caspase 3/7 activities without increasing overall differentiation. Furthermore, NDRG2 attenuates H2O2-induced oxidative stress and specific serine and threonine amino acid residues appear to contribute to its function in muscle cells

Equilibrium and stability of a whirling rod-mass system

A two-degree-of-freedom lumped-mass model is used to gain understanding of the equilibrium and stability of a circularly towed cable. Particular cases considered are those of no drag, viscous drag, and viscous drag with a crosswind.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23021/1/0000590.pd

Beyond Strain Release: Delocalization-Enabled Organic Reactivity

The release of strain energy is a fundamental driving force for organic reactions. However, absolute strain energy alone is an insufficient predictor of reactivity, evidenced by the similar ring strain but disparate reactivity of cyclopropanes and cyclobutanes. In this work, we demonstrate that electronic delocalization is a key factor that operates alongside strain release to boost, or even dominate, reactivity. This delocalization principle extends across a wide range of molecules containing three-membered rings such as epoxides, aziridines, and propellanes and also applies to strain-driven cycloaddition reactions. Our findings lead to a “rule of thumb” for the accurate prediction of activation barriers in such systems, which can be easily applied to reactions involving many of the strained building blocks commonly encountered in organic synthesis, medicinal chemistry, polymer science, and bioconjugation. Given the significance of electronic delocalization in organic chemistry, for example in aromatic π-systems and hyperconjugation, we anticipate that this concept will serve as a versatile tool to understand and predict organic reactivity

Fluid/solid transition in a hard-core system

We prove that a system of particles in the plane, interacting only with a certain hard-core constraint, undergoes a fluid/solid phase transition

Assembly and use of new task rules in fronto-parietal cortex

Severe capacity limits, closely associated with fluid intelligence, arise in learning and use of new task rules. We used fMRI to investigate these limits in a series of multirule tasks involving different stimuli, rules, and response keys. Data were analyzed both during presentation of instructions and during later task execution. Between tasks, we manipulated the number of rules specified in task instructions, and within tasks, we manipulated the number of rules operative in each trial block. Replicating previous results, rule failures were strongly predicted by fluid intelligence and increased with the number of operative rules. In fMRI data, analyses of the instruction period showed that the bilateral inferior frontal sulcus, intraparietal sulcus, and presupplementary motor area were phasically active with presentation of each new rule. In a broader range of frontal and parietal regions, baseline activity gradually increased as successive rules were instructed. During task performance, we observed contrasting fronto-parietal patterns of sustained (block-related) and transient (trial-related) activity. Block, but not trial, activity showed effects of task complexity. We suggest that, as a new task is learned, a fronto-parietal representation of relevant rules and facts is assembled for future control of behavior. Capacity limits in learning and executing new rules, and their association with fluid intelligence, may be mediated by this load-sensitive fronto-parietal network

Identifying Priority Areas for Chronic Wasting Disease Surveillance in Montana

Chronic Wasting Disease is a fatal prion disease affecting ungulate species throughout North America.  As of 2013, no CWD positive deer have been found in the state of Montana, however, several surrounding states and provinces have identified multiple cases of the disease.  We used information on mule deer habitat selection, abundance, and locations of CWD cases in surrounding states to identify priority areas in Montana for CWD surveillance. The habitat selection models were based on over 10000 VHF and GPS locations collected from mule deer from 1975-2011, and predicted resource selection function (RSF) values for winter and summer in 5 of the 7 wildlife management regions in the state of Montana. We estimated mule deer density using the aerial survey counts weighted by the value of the RSF for each pixel. High priority areas were those that contained the highest densities of mule deer and were closest to locations with CWD positive deer. This information can be used to inform Montana’s CWD surveillance program for mule deer. We concluded that based on mule deer distribution and movement patterns several mule deer herds in Montana were at risk of coming into contact with deer from known infected herds

EMIC Waves in the Outer Magnetosphere: Observations of an Off-Equator Source Region.

Electromagnetic ion cyclotron (EMIC) waves at large L shells were observed away from the magnetic equator by the Magnetospheric MultiScale (MMS) mission nearly continuously for over four hours on 28 October 2015. During this event, the wave Poynting vector direction systematically changed from parallel to the magnetic field (toward the equator), to bidirectional, to antiparallel (away from the equator). These changes coincide with the shift in the location of the minimum in the magnetic field in the southern hemisphere from poleward to equatorward of MMS. The local plasma conditions measured with the EMIC waves also suggest that the outer magnetospheric region sampled during this event was generally unstable to EMIC wave growth. Together, these observations indicate that the bidirectionally propagating wave packets were not a result of reflection at high latitudes but that MMS passed through an off-equator EMIC wave source region associated with the local minimum in the magnetic field

Cofactor NAD(P)H regeneration inspired by heterogeneous pathways

This work was supported by The Carnegie Trust for the Universities of Scotland (70265), The Royal Society (RG150001 and IE150611) and Scottish Carbon Capture and Storage (SCCS) program. J.S. also acknowledges financial support from The National Natural Science Foundation of China (21406163 and 91534126). T.S. was supported by a University of Aberdeen Elphinstone PhD Scholarship.Peer reviewedPostprin

Affective state influences retrieval-induced forgetting for integrated knowledge

Selectively testing parts of learned materials can impair later memory for nontested materials. Research has shown that such retrieval-induced forgetting occurs for low-integrated materials but may be prevented for high-integrated materials. However, previous research has neglected one factor that is ubiquitous in real-life testing: affective stat