Cutting Through the Gordian Knot: It’s Time to Revise Rule 17d-1 Under the Investment Company Act of 1940

This article reviews the legislative and administrative history of Section 17(d) of the Investment Company Act of 1940 and Rule 17d-1 under that Section, which broadly prohibit any affiliated person or principal underwriter of a mutual fund or other registered investment company (a “Fund”) or any affiliated person of such a person or underwriter, from participating in a joint transaction with the Fund unless an application regarding the transaction has been filed with and approved by the SEC. The author maintains that the Rule’s scope is far broader than what is necessary to achieve the statutory purpose of protecting Funds and their shareholders from being unfairly taken advantage of by Fund insiders. The article proposes that the SEC amend to the Rule to allow transactions with affiliated persons who are not connected with management of the Fund, relying on a Fund’s independent directors to protect the interests of the Fund and its shareholders

Mitochondrial ROS cause motor deficits induced by synaptic inactivity:implications for synapse pruning

Developmental synapse pruning refines burgeoning connectomes. The basic mechanisms of mitochondrial reactive oxygen species (ROS) production suggest they select inactive synapses for pruning: whether they do so is unknown. To begin to unravel whether mitochondrial ROS regulate pruning, we made the local consequences of neuromuscular junction (NMJ) pruning detectable as motor deficits by using disparate exogenous and endogenous models to induce synaptic inactivity en masse in developing Xenopus laevis tadpoles. We resolved whether: (1) synaptic inactivity increases mitochondrial ROS; and (2) antioxidants rescue synaptic inactivity induced motor deficits. Regardless of whether it was achieved with muscle (α-bugarotoxin), nerve (α-latrotoxin) targeted neurotoxins or an endogenous pruning cue (SPARC), synaptic inactivity increased mitochondrial ROS in vivo. The manganese porphyrins MnTE-2-PyP5+ and/or MnTnBuOE-2-PyP5+ blocked mitochondrial ROS to significantly reduce neurotoxin and endogenous pruning cue induced motor deficits. Selectively inducing mitochondrial ROS—using mitochondria-targeted Paraquat (MitoPQ)—recapitulated synaptic inactivity induced motor deficits; which were significantly reduced by blocking mitochondrial ROS with MnTnBuOE-2-PyP5+. We unveil mitochondrial ROS as synaptic activity sentinels that regulate the phenotypical consequences of forced synaptic inactivity at the NMJ. Our novel results are relevant to pruning because synaptic inactivity is one of its defining features

Managing the entanglement: complexity leadership in public sector systems

Complexity in public sector systems requires leaders to balance the administrative practices necessary to be aligned and efficient in the management of routine challenges and the adaptive practices required to respond to dynamic circumstances. Conventional notions of leadership in the field of public administration do not fully explain the role of leadership in balancing the entanglement of formal, top-down, administrative functions and informal, emergent, adaptive functions within public sector settings with different levels of complexity. Drawing on and extending existing complexity leadership constructs, this article explores how leadership is enacted over the duration of six urban regeneration projects representing high, medium, and low levels of project complexity. The article suggests that greater attention needs to be paid to the tensions inherent in enabling leadership if actors are to cope with the complex, collaborative, cross-boundary, adaptive work in which they are increasingly engage

Loss of F-box only protein 2 (Fbxo2) disrupts levels and localization of select NMDA receptor subunits, and promotes aberrant synaptic connectivity

NMDA receptors (NMDARs) play an essential role in some forms of synaptic plasticity, learning, and memory. Therefore, these receptors are highly regulated with respect to their localization, activation, and abundance both within and on the surface of mammalian neurons. Fundamental questions remain, however, regarding how this complex regulation is achieved. Using cell-based models and F-box Only Protein 2 (Fbxo2) knock-out mice, we found that the ubiquitin ligase substrate adaptor protein Fbxo2, previously reported to facilitate the degradation of the NMDAR subunit GluN1 in vitro, also functions to regulate GluN1 and GluN2A subunit levels in the adult mouse brain. In contrast, GluN2B subunit levels are not affected by the loss of Fbxo2. The loss of Fbxo2 results in greater surface localization of GluN1 and GluN2A, together with increases in the synaptic markers PSD-95 and Vglut1. These synaptic changes do not manifest as neurophysiological differences or alterations in dendritic spine density in Fbxo2 knock-out mice, but result instead in increased axo-dendritic shaft synapses. Together, these findings suggest that Fbxo2 controls the abundance and localization of specific NMDAR subunits in the brain and may influence synapse formation and maintenance

Nucleotide-binding sites can enhance N-acylation of nearby protein lysine residues.

Acyl-CoAs are reactive metabolites that can non-enzymatically S-acylate and N-acylate protein cysteine and lysine residues, respectively. N-acylation is irreversible and enhanced if a nearby cysteine residue undergoes an initial reversible S-acylation, as proximity leads to rapid S → N-transfer of the acyl moiety. We reasoned that protein-bound acyl-CoA could also facilitate S → N-transfer of acyl groups to proximal lysine residues. Furthermore, as CoA contains an ADP backbone this may extend beyond CoA-binding sites and include abundant Rossmann-fold motifs that bind the ADP moiety of NADH, NADPH, FADH and ATP. Here, we show that excess nucleotides decrease protein lysine N-acetylation in vitro. Furthermore, by generating modelled structures of proteins N-acetylated in mouse liver, we show that proximity to a nucleotide-binding site increases the risk of N-acetylation and identify where nucleotide binding could enhance N-acylation in vivo. Finally, using glutamate dehydrogenase as a case study, we observe increased in vitro lysine N-malonylation by malonyl-CoA near nucleotide-binding sites which overlaps with in vivo N-acetylation and N-succinylation. Furthermore, excess NADPH, GTP and ADP greatly diminish N-malonylation near their nucleotide-binding sites, but not at distant lysine residues. Thus, lysine N-acylation by acyl-CoAs is enhanced by nucleotide-binding sites and may contribute to higher stoichiometry protein N-acylation in vivo

Effects of Acute Lower Body Resistance Exercise on Body Composition Parameters Assessed by Bioelectrical Impedance Analysis

Bioelectrical Impedance Analysis (BIA) has the capability to estimate skeletal muscle mass (SMM), total body water, and body fat mass (FM) for assessment of body composition. Various factors are thought to influence the accuracy of BIA estimated body composition. PURPOSE: The purpose of this study was to investigate acute changes in BIA SMM and FM results after a prescribed lower body exercise compared to a non-exercise treatment. METHODS: Participants (n = 14; 22.71 ± 1.63 years; 169.42 ± 13.23 cm; 80.79 ± 17.71 kg) completed each trial in a randomly assigned crossover experimental design: resting conditions (REST) and a prescribed lower body workout (LBRE) consisting of 4 sets of 12 repetitions on leg press, leg curls, leg extension, and kettlebell squat. BIA scans were conducted prior to LBRE, immediately post LBRE, and again at 30 and 60 minutes. Linear mixed-effects models were used to evaluate the effect of time, condition, and their interaction, while random intercepts were included to account for between-participant variability. The model was fitted using restricted maximum likelihood estimation. Data was analyzed using R software. RESULTS: No condition by time interactions were present for any BIA body composition variable. However, select effects of time or condition were found. Irrespective of condition, total lean mass estimates at 60 minutes post exercise were ~0.6 kg lower than at baseline (ppCONCLUSIONS: Although it is thought that exercise may affect the reliability of the BIA, an acute bout of lower body resistance exercise did not meaningfully influence group-level BIA estimates in a recreationally active population. Thus, guidelines suggesting to abstain from resistance exercise prior to a BIA might not be essential for some applications, which could allow for greater flexibility in scheduling of body composition assessments

Resting-State Connectivity of the Left Frontal Cortex to the Default Mode and Dorsal Attention Network Supports Reserve in Mild Cognitive Impairment

Reserve refers to the phenomenon of relatively preserved cognition in disproportion to the extent of neuropathology, e.g., in Alzheimer’s disease. A putative functional neural substrate underlying reserve is global functional connectivity of the left lateral frontal cortex (LFC, Brodmann Area 6/44). Resting-state fMRI-assessed global LFC-connectivity is associated with protective factors (education) and better maintenance of memory in mild cognitive impairment (MCI). Since the LFC is a hub of the fronto-parietal control network that regulates the activity of other networks, the question arises whether LFC-connectivity to specific networks rather than the whole-brain may underlie reserve. We assessed resting-state fMRI in 24 MCI and 16 healthy controls (HC) and in an independent validation sample (23 MCI/32 HC). Seed-based LFC-connectivity to seven major resting-state networks (i.e., fronto-parietal, limbic, dorsal-attention, somatomotor, default-mode, ventral-attention, visual) was computed, reserve was quantified as residualized memory performance after accounting for age and hippocampal atrophy. In both samples of MCI, LFC-activity was anti-correlated with the default-mode network (DMN), but positively correlated with the dorsal-attention network (DAN). Greater education predicted stronger LFC-DMN-connectivity (anti-correlation) and LFC-DAN-connectivity. Stronger LFC-DMN and LFC-DAN-connectivity each predicted higher reserve, consistently in both MCI samples. No associations were detected for LFC-connectivity to other networks. These novel results extend our previous findings on global functional connectivity of the LFC, showing that LFC-connectivity specifically to the DAN and DMN, two core memory networks, enhances reserve in the memory domain in MCI

New multicellular marine macroalgae from the early Tonian of northwestern Canada

Molecular phylogenetic data suggest that photosynthetic eukaryotes first evolved in freshwater environments in the early Proterozoic and diversified into marine environments by the Tonian Period, but early algal evolution is poorly reflected in the fossil record. Here, we report newly discovered, millimeter- to centimeter-scale macrofossils from outershelf marine facies of the ca. 950–900 Ma (Re-Os minimum age constraint = 898 ± 68 Ma) Dolores Creek Formation in the Wernecke Mountains, northwestern Canada. These fossils, variably preserved by iron oxides and clay minerals, represent two size classes. The larger forms feature unbranching thalli with uniform cells, differentiated cell walls, longitudinal striations, and probable holdfasts, whereas the smaller specimens display branching but no other diagnostic features. While the smaller population remains unresolved phylogenetically and may represent cyanobacteria, we interpret the larger fossils as multicellular eukaryotic macroalgae with a plausible green algal affinity based on their large size and presence of rib-like wall ornamentation. Considered as such, the latter are among the few green algae and some of the largest macroscopic eukaryotes yet recognized in the early Neoproterozoic. Together with other Tonian fossils, the Dolores Creek fossils indicate that eukaryotic algae, including green algae, colonized marine environments by the early Neoproterozoic Era