Apical extracellular matrices (aECMs) are the extracellular layers on the apical sides of epithelia. aECMs form the outer layer of the skin in most animals and line the luminal surface of internal tubular epithelia. Compared to the more conserved basal ECMs (basement membranes), aECMs are highly diverse between tissues and between organisms and have been more challenging to understand at mechanistic levels. Studies in several genetic model organisms are revealing new insights into aECM composition, biogenesis, and function and have begun to illuminate common principles and themes of aECM organization. There is emerging evidence that, in addition to mechanical or structural roles, aECMs can participate in reciprocal signaling with associated epithelia and other cell types. Studies are also revealing mechanisms underlying the intricate nanopatterns exhibited by many aECMs. In this review, we highlight recent findings from well-studied model systems, including the external cuticle and ductal aECMs of Caenorhabditis elegans, Drosophila melanogaster, and other insects and the internal aECMs of the vertebrate inner ear.

Some types of collagens, including transmembrane MACIT collagens and C. elegans cuticle collagens, are N-terminally cleaved at a dibasic site that resembles the consensus for furin or other proprotein convertases of the subtilisin/kexin (PCSK) family. Such cleavage may release transmembrane collagens from the plasma membrane and affect extracellular matrix assembly or structure. However, the functional consequences of such cleavage are unclear and evidence for the role of specific PCSKs is lacking. Here, we used endogenous collagen fusions to fluorescent proteins to visualize the secretion and assembly of the first collagen-based cuticle in C. elegans and then tested the role of the PCSK BLI-4 in these processes. Unexpectedly, we found that cuticle collagens SQT-3 and DPY-17 are secreted into the extraembryonic space several hours before cuticle matrix assembly. Furthermore, this early secretion depends on BLI-4/PCSK; in bli-4 and cleavage-site mutants, SQT-3 and DPY-17 are not efficiently secreted and instead form large intracellular puncta. Their later assembly into cuticle matrix is reduced but not entirely blocked. These data reveal a role for collagen N-terminal processing in intracellular trafficking and the control of matrix assembly in vivo. Our observations also prompt a revision of the classic model for C. elegans cuticle matrix assembly and the pre-cuticle-to-cuticle transition, suggesting that cuticle layer assembly proceeds via a series of regulated steps and not simply by sequential secretion and deposition.

Apical extracellular matrices (aECMs) are complex extracellular compartments that form important interfaces between animals and their environment. In the adult C. elegans cuticle, layers are connected by regularly spaced columnar structures known as struts. Defects in struts result in swelling of the fluid-filled medial cuticle layer (blistering, Bli). Here we show that three cuticle collagens BLI-1, BLI-2, and BLI-6, play key roles in struts. BLI-1 and BLI-2 are essential for strut formation whereas activating mutations in BLI-6 disrupt strut formation. BLI-1, BLI-2, and BLI-6 precisely colocalize to arrays of puncta in the adult cuticle, corresponding to struts, initially deposited in diffuse stripes adjacent to cuticle furrows. They eventually exhibit tube-like morphology, with the basal ends of BLI-containing struts contact regularly spaced holes in the cuticle. Genetic interaction studies indicate that BLI strut patterning involves interactions with other cuticle components. Our results reveal strut formation as a tractable example of precise aECM patterning at the nanoscale.

Salmonella infection causes epidemic death in wild songbirds, with potential to spread to humans. In February 2021, public health officials in Oregon and Washington, USA, isolated a strain of Salmonella enterica serovar Typhimurium from humans and a wild songbird. Investigation by public health partners ultimately identified 30 illnesses in 12 states linked to an epidemic of Salmonella Typhimurium in songbirds. We report a multistate outbreak of human salmonellosis associated with songbirds, resulting from direct handling of sick and dead birds or indirect contact with contaminated birdfeeders. Companion animals might have contributed to the spread of Salmonella between songbirds and patients; the outbreak strain was detected in 1 ill dog, and a cat became ill after contact with a wild bird. This outbreak highlights a One Health issue where actions like regular cleaning of birdfeeders might reduce the health risk to wildlife, companion animals, and humans.

Introduction

Low- and middle-income countries have rapidly increasing numbers of people with dementia, yet little evidence on family caregiving interventions. We tested the preliminary efficacy and feasibility of a family caregiving intervention in northern Vietnam.

Methods

Nine clusters comprising 60 family caregivers were randomized to a culturally adapted version of a four- to six-session, multicomponent intervention delivered in-home over 2 to 3 months, or enhanced control. Eligible caregivers were ≥18 years of age and scored ≥6 on the Zarit Burden Inventory (ZBI).

Results

Fifty-one caregivers (85%) completed the study. Using analysis of covariance with 3-month assessment as the outcome and baseline assessment as a covariate, intervention group caregivers had an average ZBI (primary outcome) score 1.2 standard deviation (SD) lower (P = .02) and Patient Health Questionnaire-4 (psychological distress) score 0.7 SD lower (P = .03) than controls.

Discussion

In the first study of its kind in Vietnam, a culturally adapted, manualized, family caregiver intervention was both efficacious and feasible.