Combination of inflammation-related cytokines promotes long-term muscle stem cell expansion

Muscle stem cells (MuSCs, satellite cells) are the major contributor to muscle regeneration. Like most adult stem cells, long-term expansion of MuSCs in vitro is difficult. The in vivo muscle regeneration abilities of MuSCs are quickly lost after culturing in vitro, which prevents the potential applications of MuSCs in cell-based therapies. Here, we establish a system to serially expand MuSCs in vitro for over 20 passages by mimicking the endogenous microenvironment. We identified that the combination of four pro-inflammatory cytokines, IL-1α, IL-13, TNF-α, and IFN-γ, secreted by T cells was able to stimulate MuSC proliferation in vivo upon injury and promote serial expansion of MuSCs in vitro. The expanded MuSCs can replenish the endogenous stem cell pool and are capable of repairing multiple rounds of muscle injuries in vivo after a single transplantation. The establishment of the in vitro system provides us a powerful method to expand functional MuSCs to repair muscle injuries.     

Release of arachidonic acid by NMDA-receptor activation in the rat hippocampus

In hippocampal slices arachidonic acid released after NMDA post-synaptic receptor activation is thought to act as a retrograde trans-synaptic messenger which facilitates the pre-synaptic release of L-glutamate to be involved in the expression of long-term synaptic potentiation (LTP). We measured the mass amount of arachidonic acid released from hippocampal slices incubated under conditions which maintain the electrophysiological responsiveness of the slice. Melittin released arachidonic, oleic and docosahexaenoic acids by phospholipase A₂ activation but not palmitic or stearic acids. Of greater interestl-glutamate, N-methyl-d-aspartate and incubation conditions known to induce LTP selectively and rapidly increased the release of archidonic acid in amounts over basal levels of 200–300 ng/mg protein. This is the first direct determination of the mass amount of arachidonic acid released following NMDA receptor activation in the hippocampus.Special issue dedicated to Dr. Louis Sokoloff.     

Climatic and temporal effects on the expression of secondary sexual characters: genetic and environmental components

Despite great interest in sexual selection, relatively little is known in detail about the genetic and environmental determinants of secondary sexual characters in natural populations. Such information is important for determining the way in which populations may respond to sexual selection. We report analyses of genetic and large-scale environmental components of phenotypic variation of two secondary sexual plumage characters (forehead and wing patch size) in the collared flycatcher Ficedula albicollis over a 22-year period. We found significant heritability for both characters but little genetic covariance between the two. We found a positive association between forehead patch size and a large-scale climatic index, the North Atlantic Oscillation (NAO) index, but not for wing patch. This pattern was observed in both cross-sectional and longitudinal data suggesting that the population response to NAO index can be explained as the result of phenotypic plasticity. Heritability of forehead patch size for old males, calculated under favorable conditions (NAO index > or = median), was greater than that under unfavorable conditions (NAO index < median). These changes occurred because there were opposing changes in additive genetic variance (VA) and residual variance (VR) under favorable and unfavorable conditions, with VA increasing and VR decreasing in good environments. However, no such effect was detected for young birds, or for wing patch size in either age class. In addition to these environmental effects on both phenotypic and genetic variances, we found evidence for a significant decrease of forehead patch size over time in older birds. This change appears to be caused by a change in the sign of viability selection on forehead patch size, which is associated with a decline in the breeding value of multiple breeders. Our data thus reveal complex patterns of environmental influence on the expression of secondary sexual characters, which may have important implications for understanding selection and evolution of these characters.     

Kinetic and Thermodynamic Solubility Values of Some Bioactive Compounds

Thermodynamic solubility is a decisive physicochemical property in drug development. The Chasing Equilibrium method offers an alternative to the classical procedures to measure the solubility of compounds with acid–base properties. The method is fast and yields accurate results. In this work, the solubility of several compounds including acids and bases was determined through the Chasing Equilibrium approach. A study of experimental conditions in terms of sample weight was performed to measure solubilities. The study shows that only a limited range of weights, depending on the nature and solubility of the compounds, is adequate to obtain reliable results.     

Synaptic transmission and plasticity in the amygdala

Numerous studies in both rats and humans indicate the importance of the amygdala in the acquisition and expression of learned fear. The identification of the amygdala as an essential neural substrate for fear conditioning has permitted neurophysiological examinations of synaptic processes in the amygdala that may mediate fear conditioning. One candidate cellular mechanism for fear conditioning is long-term potentiation (LTP), an enduring increase in synaptic transmission induced by high-frequency stimulation of excitatory afferents. At present, the mechanisms underlying the induction and expression of amygdaloid LTP are only beginning to be understood, and probably involve both theN-methyl-d-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) subclasses of glutamate receptors. This article will examine recent studies of synaptic transmission and plasticity in the amygdala in an effort to understand the relationships of these processes to aversive learning and memory.     

Survivorship and Spatial Patterns of an Urban Population of Texas Horned Lizards

Habitat fragmentation has negative consequences on threatened and endangered species by creating isolated populations. The Texas horned lizard (Phrynosoma cornutum) is experiencing population declines and localized extirpations throughout its range and has been classified as a species of greatest conservation need in Oklahoma, USA. Younger age classes have been poorly studied but may be vital to the stability of remaining populations. To address gaps in knowledge concerning subadult (hatchling and juvenile) morphometrics, survivorship, and home range sizes, we studied 2 cohorts of subadults, for 2 years each, covering their hatching and juvenile years (2016–2019). We used a combination of radio-telemetry and novel harmonic radar methodology to study a closed population of Texas horned lizards in 15 ha of native grassland at Tinker Air Force Base, Oklahoma. Population abundance for adults and juveniles was estimated as 56.5 ± 5.5 lizards and density as 7.96 lizards/ha. Our lowest estimates of survival indicated an average survival probability for the hatchling life stage of 0.285 (95% CI = 0.15–0.44), which is lower than for adults on the site. Average home range size increased from hatchling to adult life stages. Our results will have an immediate effect on the planning and assessment of ongoing headstart and management programs for Texas horned lizards. © 2021 The Authors. The Journal of Wildlife Management published by Wiley Periodicals LLC on behalf of The Wildlife Society.     

Trend,seasonality, cycle,and irregular fluctuations in primary productivity at Lake Tahoe,California-Nevada,USA

Primary productivity has been measured routinely at Lake Tahoe since 1967, and a number of mechanisms underlying variability in the productivity record have now been identified. A long-term trend due to nutrient loading dominates the series. Seasonality also is prominent, apparently controlled by direct physical factors unrelated to the trophic cascade. A 3-yr cycle has been detected and several possible mechanisms are considered. Irregular fluctuations also are present, caused in part by isolated events (a forest fire) and recurring but variable phenomena (spring mixing). Except possibly for the 3-yr cycle, the known sources of variability appear to operate bottom-up through direct physical and chemical effects on the phytoplankton.     

Cholecystokinin from the entorhinal cortex enables neural plasticity in the auditory cortex

Patients with damage to the medial temporal lobe show deficits in forming new declarative memories but can still recall older memories, suggesting that the medial temporal lobe is necessary for encoding memories in the neocortex. Here, we found that cortical projection neurons in the perirhinal and entorhinal cortices were mostly immunopositive for cholecystokinin (CCK). Local infusion of CCK in the auditory cortex of anesthetized rats induced plastic changes that enabled cortical neurons to potentiate their responses or to start responding to an auditory stimulus that was paired with a tone that robustly triggered action potentials. CCK infusion also enabled auditory neurons to start responding to a light stimulus that was paired with a noise burst. In vivo intracellular recordings in the auditory cortex showed that synaptic strength was potentiated after two pairings of presynaptic and postsynaptic activity in the presence of CCK. Infusion of a CCK_B antagonist in the auditory cortex prevented the formation of a visuo-auditory association in awake rats. Finally, activation of the entorhinal cortex potentiated neuronal responses in the auditory cortex, which was suppressed by infusion of a CCK_B antagonist. Together, these findings suggest that the medial temporal lobe influences neocortical plasticity via CCK-positive cortical projection neurons in the entorhinal cortex.     

Supersaturation-limited and Unlimited Phase Transitions Compete to Produce the Pathway Complexity in Amyloid Fibrillation

Although amyloid fibrils and amorphous aggregates are two types of aggregates formed by denatured proteins, their relationship currently remains unclear. We used β₂-microglobulin (β2m), a protein responsible for dialysis-related amyloidosis, to clarify the mechanism by which proteins form either amyloid fibrils or amorphous aggregates. When ultrasonication was used to accelerate the spontaneous fibrillation of β2m at pH 2.0, the effects observed depended on ultrasonic power; although stronger ultrasonic power effectively accelerated fibrillation, excessively strong ultrasonic power decreased the amount of fibrils formed, as monitored by thioflavin T fluorescence. An analysis of the products formed indicated that excessively strong ultrasonic power generated fibrillar aggregates that retained β-structures but without high efficiency as seeds. On the other hand, when the spontaneous fibrillation of β2m was induced at higher concentrations of NaCl at pH 2.0 with stirring, amorphous aggregates became more dominant than amyloid fibrils. These apparent complexities in fibrillation were explained comprehensively by a competitive mechanism in which supersaturation-limited reactions competed with supersaturation-unlimited reactions. We link the kinetics of protein aggregation and a conformational phase diagram, in which supersaturation played important roles.