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Multiple sclerosis (MS) is a complex disease of the CNS thought to require an environmental trigger. Gut dysbiosis is common in MS, but specific causative species are unknown. To address this knowledge gap, we used sensitive and quantitative PCR detection to show that people with MS were more likely to harbor and show a greater abundance of epsilon toxin-producing (ETX-producing) strains of C. perfringens within their gut microbiomes compared with individuals who are healthy controls (HCs). Isolates derived from patients with MS produced functional ETX and had a genetic architecture typical of highly conjugative plasmids. In the active immunization model of experimental autoimmune encephalomyelitis (EAE), where pertussis toxin (PTX) is used to overcome CNS immune privilege, ETX can substitute for PTX. In contrast to PTX-induced EAE, where inflammatory demyelination is largely restricted to the spinal cord, ETX-induced EAE caused demyelination in the corpus callosum, thalamus, cerebellum, brainstem, and spinal cord, more akin to the neuroanatomical lesion distribution seen in MS. CNS endothelial cell transcriptional profiles revealed ETX-induced genes that are known to play a role in overcoming CNS immune privilege. Together, these findings suggest that ETX-producing C. perfringens strains are biologically plausible pathogens in MS that trigger inflammatory demyelination in the context of circulating myelin autoreactive lymphocytes.

As a result of a rapidly aging population and the increasing prevalence of dementia among older adults, technological solutions are increasingly being considered to facilitate caregiving. This research investigates the perspectives of 20 caregiving dyads on VGo, a telepresence social robot with features designed to support caregiving. Care recipients (CRs), aged 65 and older, diagnosed with Alzheimer’s disease and related dementias, along with their primary caregivers (CGs), evaluated the robot through an online interview study. The interviews integrated informative videos showcasing VGo’s features and functions. Insights from the interviews revealed diverse expectations, interests, and reservations. The majority of CGs and their CRs perceived the robot’s features as beneficial. In particular, the voice command capability was appreciated as an alternative to using smartphones and as a way to manage home appliances. The community feature, however, did not align well with many participants’ lifestyles, and participants had a number of suggestions to enhance the robot’s notification function. Based on the interview results, the study offers a set of design recommendations for telepresence social robots in home caregiving contexts. This investigation highlights the promise of social robots in caregiving contexts and underscores the need for further improvements to ensure they fit users’ needs.

Point-of-care ultrasound (POCUS) is an imaging modality used to make expedient patient care decisions at bedside. Though its diagnostic utility has been extensively described, POCUS is not yet considered standard of care in inpatient settings. Data from emergency department settings suggest that POCUS may yield socioemotional benefits beyond its diagnostic utility; furthermore, elements of the POCUS experience are known to promote placebo effects. These elements likely contribute to a placebo-like "POCUS positive care effect" (PPCE) with socioemotional benefits for receptive patients. Our objective is to provide the first characterization of the PPCE and its facilitating factors in an inpatient setting. In this novel mixed-methods study, we recruited 30 adult patients admitted to internal medicine floors in an urban academic medical center, recorded observations during their routine POCUS encounters, and administered post-encounter surveys. We conducted complementary quantitative and qualitative analyses to define and assess the magnitude of the PPCE. We also aimed to identify factors associated with and facilitating receptiveness to the PPCE. The results indicated that POCUS improves patients' satisfaction with their hospital providers and care overall, as well as perceived care efficiency. Mutual engagement, strong therapeutic alliances, and interpreting POCUS images to provide reassurance are most closely associated with this PPCE. Patients who have lower anxiety levels, less severe illness, and received efficient care delivery during their hospitalizations are most receptive to the PPCE. We conclude that diagnostic POCUS has the potential to exert a positive care effect for hospitalized patients. This PPCE is associated with modifiable factors at the patient, provider, and environment levels. Together, our findings lay the groundwork for an optimized "therapeutic POCUS" that yields maximal socioemotional benefits for receptive patients.

Multiple sclerosis (MS) is a complex disease of the CNS thought to require an environmental trigger. Gut dysbiosis is common in MS, but specific causative species are unknown. To address this knowledge gap, we used sensitive and quantitative PCR detection to show that people with MS were more likely to harbor and show a greater abundance of epsilon toxin–producing (ETX-producing) strains of C. perfringens within their gut microbiomes compared with individuals who are healthy controls (HCs). Isolates derived from patients with MS produced functional ETX and had a genetic architecture typical of highly conjugative plasmids. In the active immunization model of experimental autoimmune encephalomyelitis (EAE), where pertussis toxin (PTX) is used to overcome CNS immune privilege, ETX can substitute for PTX. In contrast to PTX-induced EAE, where inflammatory demyelination is largely restricted to the spinal cord, ETX-induced EAE caused demyelination in the corpus callosum, thalamus, cerebellum, brainstem, and spinal cord, more akin to the neuroanatomical lesion distribution seen in MS. CNS endothelial cell transcriptional profiles revealed ETX-induced genes that are known to play a role in overcoming CNS immune privilege. Together, these findings suggest that ETX-producing C. perfringens strains are biologically plausible pathogens in MS that trigger inflammatory demyelination in the context of circulating myelin autoreactive lymphocytes.

As a result of a rapidly aging population and the increasing prevalence of dementia among older adults, technological solutions are increasingly being considered to facilitate caregiving. This research investigates the perspectives of 20 caregiving dyads on VGo, a telepresence social robot with features designed to support caregiving. Care recipients (CRs), aged 65 and older, diagnosed with Alzheimer's disease and related dementias, along with their primary caregivers (CGs), evaluated the robot through an online interview study. The interviews integrated informative videos showcasing VGo's features and functions. Insights from the interviews revealed diverse expectations, interests, and reservations. The majority of CGs and their CRs perceived the robot's features as beneficial. In particular, the voice command capability was appreciated as an alternative to using smartphones and as a way to manage home appliances. The community feature, however, did not align well with many participants' lifestyles, and participants had a number of suggestions to enhance the robot's notification function. Based on the interview results, the study offers a set of design recommendations for telepresence social robots in home caregiving contexts. This investigation highlights the promise of social robots in caregiving contexts and underscores the need for further improvements to ensure they fit users' needs. [ABSTRACT FROM AUTHOR]

The evolutionary importance of hybridization and introgression has long been debated. Hybrids are usually rare and unfit, but even infrequent hybridization can aid adaptation by transferring beneficial traits between species. Here we use genomic tools to investigate introgression in Heliconius, a rapidly radiating genus of neotropical butterflies widely used in studies of ecology, behaviour, mimicry and speciation. We sequenced the genome of Heliconius melpomene and compared it with other taxa to investigate chromosomal evolution in Lepidoptera and gene flow among multiple Heliconius species and races. Among 12,669 predicted genes, biologically important expansions of families of chemosensory and Hox genes are particularly noteworthy. Chromosomal organization has remained broadly conserved since the Cretaceous period, when butterflies split from the Bombyx (silkmoth) lineage. Using genomic resequencing, we show hybrid exchange of genes between three co-mimics, Heliconius melpomene, Heliconius timareta and Heliconius elevatus, especially at two genomic regions that control mimicry pattern. We infer that closely related Heliconius species exchange protective colour-pattern genes promiscuously, implying that hybridization has an important role in adaptive radiation.

Introduction White matter tracts in the CNS largely comprise long axons, associated glial cells, and the ensheathment of axons with myelin. While the role of myelin for axonal conduction and [...], The underlying cellular mechanisms of catatonia, an executive "psychomotor" syndrome that is observed across neuropsychiatric diseases, have remained obscure. In humans and mice, reduced expression of the structural myelin protein CNP is associated with catatonic signs in an age-dependent manner, pointing to the involvement of myelin-producing oligodendrocytes. Here, we showed that the underlying cause of catatonic signs is the low-grade inflammation of white matter tracts, which marks a final common pathway in Cnp-deficient and other mutant mice with minor myelin abnormalities. The inhibitor of CSF1 receptor kinase signaling PLX5622 depleted microglia and alleviated the catatonic symptoms of Cnp mutants. Thus, microglia and low-grade inflammation of myelinated tracts emerged as the trigger of a previously unexplained mental condition. We observed a very high (25%) prevalence of individuals with catatonic signs in a deeply phenotyped schizophrenia sample (n = 1095). Additionally, we found the loss-of-function allele of a myelin-specific gene (CNP rs2070106-AA) associated with catatonia in 2 independent schizophrenia cohorts and also associated with white matter hyperintensities in a general population sample. Since the catatonic syndrome is likely a surrogate marker for other executive function defects, we suggest that microglia-directed therapies may be considered in psychiatric disorders associated with myelin abnormalities.

Tomato Prf encodes a nucleotide-binding domain shared by Apaf-1, certain R proteins, and CED-4 fused to C-terminal leucine-rich repeats (NBARC-LRR) protein that is required for bacterial immunity to Pseudomonas syringae and sensitivity to the organophosphate fenthion. The signaling pathways involve two highly related protein kinases. Pto kinase mediates direct recognition of the bacterial effector proteins AvrPto or AvrPtoB. Fen kinase is required for fenthion sensitivity and recognition of bacterial effectors related to AvrPtoB. The role of Pto and its association with Prf has been characterized but Fen is poorly described. We show that, similar to Pto, Fen requires N-myristoylation and kinase activity for signaling and interacts with the N-terminal domain of Prf. Thus, the mechanisms of activation of Prf by the respective protein kinases are similar. Prf–Fen interaction is underlined by coregulatory mechanisms in which Prf negatively regulates Fen, most likely by controlling kinase activity. We further characterized negative regulation of Prf by Pto, and show that regulation is mediated by the previously described negative regulatory patch. Remarkably, the effectors released negative regulation of Prf in a manner dependent on Pto kinase activity. The data suggest a model in which Prf associates generally with Pto-like kinases in tightly regulated complexes, which are activated by effector-mediated disruption of negative regulation. Release of negative regulation may be a general feature of activation of NBARC-LRR proteins by cognate effectors.

How generalist parasites with wide host ranges can evolve is a central question in parasite evolution. Albugo candida is an obligate biotrophic parasite that consists of many physiological races that each specialize on distinct Brassicaceae host species. By analyzing genome sequence assemblies of five isolates, we show they represent three races that are genetically diverged by ∼1%. Despite this divergence, their genomes are mosaic-like, with ∼25% being introgressed from other races. Sequential infection experiments show that infection by adapted races enables subsequent infection of hosts by normally non-infecting races. This facilitates introgression and the exchange of effector repertoires, and may enable the evolution of novel races that can undergo clonal population expansion on new hosts. We discuss recent studies on hybridization in other eukaryotes such as yeast, Heliconius butterflies, Darwin's finches, sunflowers and cichlid fishes, and the implications of introgression for pathogen evolution in an agro-ecological environment.