123 research outputs found
Do Human Resource Departments Act as Strategic Partners? Strategic Human Capital Management Adoption by County Governments
Drawing on qualitative data from forty counties in New York and North Carolina, this article examines the adoption of strategic human capital management (SHCM) principles and practices at the county level and presents a typology of five levels of SHCM adoption. The level of SHCM implementation in a county depends on: the view of the HR function by executive county leadership, the capacity of the county to engage in strategic planning and management, and the capacity of the HR director to think strategically about the role of HR in the government. The article concludes with recommendations for practice, which focus on educating a diverse set of actors about SHCM, building executive level support, developing HR skill and competencies, and applying basic change management practices
Adaptive modulation of antibiotic resistance through intragenomic coevolution
Bacteria gain antibiotic resistance genes by horizontal acquisition of mobile genetic elements (MGEs) from other lineages. Newly acquired MGEs are often poorly adapted causing intragenomic conflicts; these are resolved by either compensatory adaptation - of the chromosome or the MGE - or reciprocal coadaptation. The footprints of such intragenomic coevolution are present in bacterial genomes, suggesting an important role promoting genomic integration of horizontally acquired genes, but direct experimental evidence of the process is limited. Here we show adaptive modulation of tetracycline resistance via intragenomic coevolution between Escherichia coli and the multidrug resistant plasmid RK2. Tetracycline treatments, including monotherapy or combination therapies with ampicillin, favoured de novo chromosomal resistance mutations coupled with mutations on RK2 impairing the plasmid-encoded tetracycline efflux pump. These mutations together provided increased tetracycline resistance at reduced cost. Additionally, the chromosomal resistance mutations conferred cross-resistance to chloramphenicol. Reciprocal coadaptation was not observed under ampicillin-only or no antibiotic selection. Intragenomic coevolution can create genomes comprising multiple replicons that together provide high-level, low-cost resistance, but the resulting co-dependence may limit the spread of coadapted MGEs to other lineages
The evolution of plasmid-carried antibiotic resistance
BACKGROUND: Antibiotic resistance represents a significant public health problem. When resistance genes are mobile, being carried on plasmids or phages, their spread can be greatly accelerated. Plasmids in particular have been implicated in the spread of antibiotic resistance genes. However, the selective pressures which favour plasmid-carried resistance genes have not been fully established. Here we address this issue with mathematical models of plasmid dynamics in response to different antibiotic treatment regimes. RESULTS: We show that transmission of plasmids is a key factor influencing plasmid-borne antibiotic resistance, but the dosage and interval between treatments is also important. Our results also hold when plasmids carrying the resistance gene are in competition with other plasmids that do not carry the resistance gene. By altering the interval between antibiotic treatments, and the dosage of antibiotic, we show that different treatment regimes can select for either plasmid-carried, or chromosome-carried, resistance. CONCLUSIONS: Our research addresses the effect of environmental variation on the evolution of plasmid-carried antibiotic resistance
Volume EM Reconstruction of Spinal Cord Reveals Wiring Specificity in Speed-Related Motor Circuits
Spinal interneurons coordinate the activity of motoneurons to generate the spatiotemporal patterns of muscle contractions required for vertebrate locomotion. It is controversial to what degree the orderly, gradual recruitment of motoneurons is determined by biophysical differences among them rather than by specific connections from presynaptic interneurons to subsets of motoneurons. To answer this question, we mapped all connections from two types of interneurons onto all motoneurons in a larval zebrafish spinal cord hemisegment, using serial block-face electron microscopy (SBEM). We found specific synaptic connectivity from dorsal but not from ventral excitatory ipsilateral interneurons, with large motoneurons, active only when strong force is required, receiving specific inputs from dorsally located interneurons, active only during fast swims. By contrast, the connectivity between inhibitory commissural interneurons and motoneurons lacks any discernible pattern. The wiring pattern is consistent with a recruitment mechanism that depends to a considerable extent on specific connectivity
Automated synaptic connectivity inference for volume electron microscopy
Teravoxel volume electron microscopy data sets from neural tissue can now be acquired in weeks, but data analysis requires years of manual labor. We developed the SyConn framework, which uses deep convolutional neural networks and random forest classifiers to infer a richly annotated synaptic connectivity matrix from manual neurite skeleton reconstructions by automatically identifying mitochondria, synapses and their types, axons, dendrites, spines, myelin, somata and cell types. We tested our approach on serial block-face electron microscopy data sets from zebrafish, mouse and zebra finch, and computed the synaptic wiring of songbird basal ganglia. We found that, for example, basal-ganglia cell types with high firing rates in vivo had higher densities of mitochondria and vesicles and that synapse sizes and quantities scaled systematically, depending on the innervated postsynaptic cell types
The anatomical substrate of precise timing in zebra finch HVC
The sequential activation of neurons has been observed during a range of behaviors and cognitive states and is central to many models of neural circuit function, but the synaptic connections enabling such dynamics are poorly understood. Song production in the zebra finch depends on a cortical region called HVC, which contains a major class of excitatory (HVC(RA)) neurons that fire action potential bursts in a fixed, sequential pattern during singing. These neurons not only project to downstream motor centers but also make numerous connections within HVC and could, therefore, form a sequence-generating synaptic chain. Evidence for this network architecture has, however, been either indirect or inconclusive. Here we employ light and transsynaptic electron microscopy to explore the synaptic connectivity of HVC(RA) neurons. We find that HVC(RA) cells receive the vast majority of their excitatory connections from distal sites on the axons of other HVC(RA) cells; proximal axonal sites, on the other hand, nearly always target inhibitory interneurons. Overall, this connectivity pattern provides evidence for a distributed excitatory synaptic chain supported by local inhibition, characteristic of coupled winner-take-all architectures
EM connectomics reveals axonal target variation in a sequence-generating network
The sequential activation of neurons has been observed in various areas of the brain, but in no case is the underlying network structure well understood. Here we examined the circuit anatomy of zebra finch HVC, a cortical region that generates sequences underlying the temporal progression of the song. We combined serial block-face electron microscopy with light microscopy to determine the cell types targeted by HVC(RA) neurons, which control song timing. Close to their soma, axons almost exclusively targeted inhibitory interneurons, consistent with what had been found with electrical recordings from pairs of cells. Conversely, far from the soma the targets were mostly other excitatory neurons, about half of these being other HVC(RA) cells. Both observations are consistent with the notion that the neural sequences that pace the song are generated by global synaptic chains in HVC embedded within local inhibitory networks
- …