Merging trait-based ecology and regime shift theory to anticipate community responses to warming.

Anthropogenic warming is altering species abundance, distribution, physiology, and more. How changes observed at the species level alter emergent community properties is an active and urgent area of research. Trait-based ecology and regime shift theory provide complementary ways to understand climate change impacts on communities, but these two bodies of work are only rarely integrated. Lack of integration handicaps our ability to understand community responses to warming, at a time when such understanding is critical. Therefore, we advocate for merging trait-based ecology with regime shift theory. We propose a general set of principles to guide this merger and apply these principles to research on marine communities in the rapidly warming North Atlantic. In our example, combining trait distribution and regime shift analyses at the community level yields greater insight than either alone. Looking forward, we identify a clear need for expanding quantitative approaches to collecting and merging trait-based and resilience metrics in order to advance our understanding of climate-driven community change.

The core apoptotic executioner proteins CED-3 and CED-4 promote initiation of neuronal regeneration in Caenorhabditis elegans.

A critical accomplishment in the rapidly developing field of regenerative medicine will be the ability to foster repair of neurons severed by injury, disease, or microsurgery. In C. elegans, individual visualized axons can be laser-cut in vivo and neuronal responses to damage can be monitored to decipher genetic requirements for regeneration. With an initial interest in how local environments manage cellular debris, we performed femtosecond laser axotomies in genetic backgrounds lacking cell death gene activities. Unexpectedly, we found that the CED-3 caspase, well known as the core apoptotic cell death executioner, acts in early responses to neuronal injury to promote rapid regeneration of dissociated axons. In ced-3 mutants, initial regenerative outgrowth dynamics are impaired and axon repair through reconnection of the two dissociated ends is delayed. The CED-3 activator, CED-4/Apaf-1, similarly promotes regeneration, but the upstream regulators of apoptosis CED-9/Bcl2 and BH3-domain proteins EGL-1 and CED-13 are not essential. Thus, a novel regulatory mechanism must be utilized to activate core apoptotic proteins for neuronal repair. Since calcium plays a conserved modulatory role in regeneration, we hypothesized calcium might play a critical regulatory role in the CED-3/CED-4 repair pathway. We used the calcium reporter cameleon to track in vivo calcium fluxes in the axotomized neuron. We show that when the endoplasmic reticulum calcium-storing chaperone calreticulin, CRT-1, is deleted, both calcium dynamics and initial regenerative outgrowth are impaired. Genetic data suggest that CED-3, CED-4, and CRT-1 act in the same pathway to promote early events in regeneration and that CED-3 might act downstream of CRT-1, but upstream of the conserved DLK-1 kinase implicated in regeneration across species. This study documents reconstructive roles for proteins known to orchestrate apoptotic death and links previously unconnected observations in the vertebrate literature to suggest a similar pathway may be conserved in higher organisms.

Compartmentalization of superoxide dismutase 1 (SOD1G93A) aggregates determines their toxicity.

Neurodegenerative diseases constitute a class of illnesses marked by pathological protein aggregation in the brains of affected individuals. Although these disorders are invariably characterized by the degeneration of highly specific subpopulations of neurons, protein aggregation occurs in all cells, which indicates that toxicity arises only in particular cell biological contexts. Aggregation-associated disorders are unified by a common cell biological feature: the deposition of the culprit proteins in inclusion bodies. The precise function of these inclusions remains unclear. The starting point for uncovering the origins of disease pathology must therefore be a thorough understanding of the general cell biological function of inclusions and their potential role in modulating the consequences of aggregation. Here, we show that in human cells certain aggregate inclusions are active compartments. We find that toxic aggregates localize to one of these compartments, the juxtanuclear quality control compartment (JUNQ), and interfere with its quality control function. The accumulation of SOD1G93A aggregates sequesters Hsp70, preventing the delivery of misfolded proteins to the proteasome. Preventing the accumulation of SOD1G93A in the JUNQ by enhancing its sequestration in an insoluble inclusion reduces the harmful effects of aggregation on cell viability.

Differential Spatiotemporal Expression of Type I and Type II Cadherins Associated With the Segmentation of the Central Nervous System and Formation of Brain Nuclei in the Developing Mouse.

Type I and type II classical cadherins comprise a family of cell adhesion molecules that regulate cell sorting and tissue separation by forming specific homo and heterophilic bonds. Factors that affect cadherin-mediated cell-cell adhesion include cadherin binding affinity and expression level. This study examines the expression pattern of type I cadherins (Cdh1, Cdh2, Cdh3, and Cdh4), type II cadherins (Cdh6, Cdh7, Cdh8, Cdh9, Cdh10, Cdh11, Cdh12, Cdh18, Cdh20, and Cdh24), and the atypical cadherin 13 (Cdh13) during distinct morphogenetic events in the developing mouse central nervous system from embryonic day 11.5 to postnatal day 56. Cadherin mRNA expression levels obtained from in situ hybridization experiments carried out at the Allen Institute for Brain Science (https://alleninstitute.org/) were retrieved from the Allen Developing Mouse Brain Atlas. Cdh2 is the most abundantly expressed type I cadherin throughout development, while Cdh1, Cdh3, and Cdh4 are expressed at low levels. Type II cadherins show a dynamic pattern of expression that varies between neuroanatomical structures and developmental ages. Atypical Cdh13 expression pattern correlates with Cdh2 in abundancy and localization. Analyses of cadherin-mediated relative adhesion estimated from their expression level and binding affinity show substantial differences in adhesive properties between regions of the neural tube associated with the segmentation along the anterior-posterior axis. Differences in relative adhesion were also observed between brain nuclei in the developing subpallium (basal ganglia), suggesting that differential cell adhesion contributes to the segregation of neuronal pools. In the adult cerebral cortex, type II cadherins Cdh6, Cdh8, Cdh10, and Cdh12 are abundant in intermediate layers, while Cdh11 shows a gradated expression from the deeper layer 6 to the superficial layer 1, and Cdh9, Cdh18, and Cdh24 are more abundant in the deeper layers. Person's correlation analyses of cadherins mRNA expression patterns between areas and layers of the cerebral cortex and the nuclei of the subpallium show significant correlations between certain cortical areas and the basal ganglia. The study shows that differential cadherin expression and cadherin-mediated adhesion are associated with a wide range of morphogenetic events in the developing central nervous system including the organization of neurons into layers, the segregation of neurons into nuclei, and the formation of neuronal circuits.

An Unusual Presentation of Chronic Subdural Hematoma with Isolated Footdrop.

BACKGROUND: Patients with chronic subdural hematoma (CSDH) typically present with symptoms of increased intracranial pressure, including headache, nausea/vomiting, and somnolence, or with contralateral weakness. Compression of the convexity cerebral cortex usually causes motor deficit that is more readily appreciated in the upper extremity rather than in the leg, and very subtle deficit may be detected only by looking for pronator drift. The precise pattern of signs and symptoms in CSDH may vary from case to case depending on the specific anatomy of compression, but isolated lower extremity weakness is rare. CASE DESCRIPTION: A 79-year-old woman presented with isolated footdrop. CSDH overlying the cerebral convexity was detected on computed tomography. The foot weakness resolved on surgical drainage. CONCLUSIONS: CSDH overlying the cerebral convexity may manifest with isolated foot weakness. Awareness of the potential for this unusual presentation of CSDH may be useful to the clinician assessing a patient with otherwise unexplained foot weakness.

Equivalent mutations in the eight subunits of the chaperonin CCT produce dramatically different cellular and gene expression phenotypes.

The eukaryotic cytoplasmic chaperonin-containing TCP-1 (CCT) is a complex formed by two back-to-back stacked hetero-octameric rings that assists the folding of actins, tubulins, and other proteins in an ATP-dependent manner. Here, we tested the significance of the hetero-oligomeric nature of CCT in its function by introducing, in each of the eight subunits in turn, an identical mutation at a position that is conserved in all the subunits and is involved in ATP hydrolysis, in order to establish the extent of 'individuality' of the various subunits. Our results show that these identical mutations lead to dramatically different phenotypes. For example, Saccharomyces cerevisiae yeast cells with the mutation in subunit CCT2 display heat sensitivity and cold sensitivity for growth, have an excess of actin patches, and are the only strain here generated that is pseudo-diploid. By contrast, cells with the mutation in subunit CCT7 are the only ones to accumulate juxtanuclear protein aggregates that may reflect an impaired stress response in this strain. System-level analysis of the strains using RNA microarrays reveals connections between CCT and several cellular networks, including ribosome biogenesis and TOR2, that help to explain the phenotypic variability observed.