Endocytic cargo and Rab GTPases are segregated to distinct domains of an endosome. These domains maintain their identity until they undergo fission to traffic cargo. It is not fully understood how ...segregation of cargo or Rab proteins is maintained along the continuous endosomal membrane or what machinery is required for fission. Endosomes form contact sites with the endoplasmic reticulum (ER) that are maintained during trafficking. Here, we show that stable contacts form between the ER and endosome at constricted sorting domains, and free diffusion of cargo is limited at these positions. We demonstrate that the site of constriction and fission for early and late endosomes is spatially and temporally linked to contact sites with the ER. Lastly, we show that altering ER structure and dynamics reduces the efficiency of endosome fission. Together, these data reveal a surprising role for ER contact in defining the timing and position of endosome fission.
Display omitted
Display omitted
•ER tubules are recruited to cargo-sorting domains on early and late endosomes•Diffusion of endosomal cargo is restricted at ER-marked constrictions•ER tubules contact early and late endosomes at the position of fission•Recruitment of ER tubules to sorting domains defines the timing of fission
ER tubules are recruited to cargo-sorting domains on early and late endosomes, and disruptions to ER structure and dynamics impede endosome fission.
It is a wide-spread assumption about footbinding that footbound girls and women were more of an economic burden on their families than those never bound. It is often presumed that government policies ...and missionary campaigns ended footbinding.
We use regression and log-likelihood tests, with bootstrapping for confirmation, to analyze which of a series of ethnographically and historically hypothesized variables significantly correlate with footbinding. We also consider an indirect measure of government prohibitions. We analyze two large datasets based on oral surveys with elderly women of the last footbound generations from 12 inland Chinese provinces.
Handicraft production, particularly commercial handicraft production, correlates with whether Chinese girls were subjected to footbinding before 1950. Girlhood knowledge of government prohibitions against footbinding, an indirect measure of awareness by the adults who decided whether to bind a girl's feet, did not correlate with whether women were ever footbound. Spinning cotton thread for commercial purposes (sale, wage, direct exchange) correlated with greater daily production, with great county-level variation in quantity produced. Moreover, Chinese commercial spinners labored more years before marriage than domestic spinners.
Chinese daughters-whether footbound or not-made important economic contributions to rural households, thus suggesting a need to revise our understanding of China's gender and economic history. Further implications of our results are that research is warranted on the assumed efficacy of government prohibitions-in both rural and urban areas-and on the presumption that footbinding among elite Chinese women was unrelated to economic concerns, including handicraft production. The demonstrated economic correlates of footbinding in inland, rural China also suggest a need to reevaluate whether contemporary customs controlling and cloistering girls and women, such as female genital cutting in Africa and the threat of honor killings of girls and women in South Asia, might have economic correlates.
Objective
Primary chronic rhinosinusitis (CRS) is typically a diffuse process and the extent of endoscopic sinus surgery (ESS) performed for medically recalcitrant CRS is impacted by many factors. ...However, some third‐party payors have implemented policies to authorize coverage for ESS in a sinus‐by‐sinus manner based on a minimal measurement of millimeters of mucosal thickening or sinus opacification in the corresponding sinus that is being surgically addressed. Our objective was to determine whether such policies are based on scientific evidence that in patients with medically recalcitrant CRS, a minimum measurement of mucosal thickening or sinus opacification is a predictor of CRS in that sinus or improved outcomes after ESS on a sinus‐by‐sinus basis.
Data Sources
Medline, Embase, Scopus, and Web of Science databases, from inception through May 2022.
Review Methods
A systematic review was performed. The Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) guidelines were followed.
Results
We identified 6070 s which were screened and from which 112 studies ultimately underwent a full‐text review. From these studies, we found that none investigated (or provided evidence of) whether any minimal degree of radiographic mucosal thickening or sinus opacification predicted CRS or better outcomes after ESS in a sinus‐specific manner.
Conclusion
We were unable to find evidence supporting a minimum millimeter measurement of mucosal thickening or sinus opacification as predictors of CRS or better post‐ESS outcomes in a sinus‐specific manner in patients with medically recalcitrant CRS. The extent of ESS for CRS should be determined through personalized medical decision‐making that considers all patient‐specific factors.
Rapid and efficient judgments about the significance of social threat are important for species survival and may recruit specialized neurocognitive systems, consistent with biological models of ...threat processing
1. We review cognitive, psychophysiological, neuropsychological, and neuroimaging evidence in support of specialized neural networks subserving the processing of facial displays of threat. Cognitive research suggests that faces depicting anger are detected quickly when presented amongst other facial expressions, on the basis of distinguishing facial features. Psychophysiological investigations using visual scanpath techniques provide evidence for increased foveal attention to facial features of threat-related expressions (anger, fear), which may facilitate rapid detection and subsequent appraisal of the significance of threat (such as the direction of impending threat). Neuropsychological and neuroimaging studies implicate a primary role for the amygdale and pre-frontal cortices in interpreting signs of danger from facial expressions and other social stimuli. Subtle disturbances in these neurocognitive systems underlying efficient threat detection (manifesting in attentional biases and aberrant neural activity) may result in abnormally heightened perception of social threat, as seen in clinical levels of social anxiety and/or persecutory delusions in schizophrenia. Clinical states of paranoia may therefore reflect normal variation (i.e. biases) in the adaptive mechanisms which have evolved, in the Darwinian sense, to facilitate efficient threat detection in humans. As such, clinical levels of paranoia may represent the inevitable cost of efficient threat perception—or ‘justified’ suspicion—that is necessary for survival of the human species.
To determine the effect of baseline cognition on gait outcomes after a treadmill training program for people with Parkinson's disease (PD).
This pilot clinical trial involved people with PD who were ...classified as having no cognitive impairment (PD-NCI) or mild cognitive impairment (PD-MCI). Baseline executive function and memory were assessed. The intervention was a 10-week gait training program (twice-weekly treadmill sessions), with structured speed and distance progression and verbal cues for gait quality. Response to intervention was assessed by gait speed measured after week 2 (short-term) and week 10 (long-term).
Participants (n = 19; 12 PD-NCI, 7 PD-MCI) had a mean (standard deviation) age of 66.5 (6.3) years, disease duration of 8.8 (6.3) years, and MDS-UPDRS III score of 21.3 (10.7). Gait speed increased at short-term and long-term assessments. The response did not differ between PD-NCI and PD-MCI groups; however, better baseline memory performance and milder PD motor severity were independently associated with greater improvements in gait speed in unadjusted and adjusted models.
These findings suggest that memory impairments and more severe motor involvement can influence the response to gait rehabilitation in PD and highlight the need for treatments optimized for people with greater cognitive and motor impairment.
IMPLICATIONS FOR REHABILITATION
Cognitive deficits in Parkinson's disease (PD) could impact motor learning and gait rehabilitation, yet little is known about the effects of cognitive impairments on the response to rehabilitation in people with PD.
This study demonstrates that the response to gait rehabilitation did not differ between people with PD who had no cognitive impairment and those with mild cognitive impairment.
Across all participants, better baseline memory was associated with greater improvements in gait speed.
Rehabilitation professionals should be mindful of PD severity, as those with more substantial memory and motor impairments may require additional dosing or support to maximize gait training benefits.
Objective
Best practices for calculation of the minimal clinically important difference (MCID) of outcome measures include the use of complementary methodologies (broadly classified as anchor‐based ...and distribution‐based) and reporting of the MCID's predictive ability. We sought to determine MCID calculation and reporting patterns within the otolaryngology literature.
Methods
A systematic search strategy of Embase, PubMed, and Web of Science databases was developed and implemented to identify studies reporting the determination of an MCID for an outcome measure. Studies specifically within the otolaryngology literature (defined as journals classified as “otorhinolaryngology” in the Journal Citation Reports database) were included. All those journals were additionally searched for relevant articles.
Results
There were 35 articles that met the inclusion criteria. Of these studies, 88.6% reported MCID of a patient‐reported outcome measure and the remainder were for objective outcome measurements. Anchor‐based methods were used by 82.9% of studies and distribution‐based methods were used by 68.6% of studies. Of all studies, 31.4% utilized anchor‐based methods alone, 17.1% utilized distribution‐based methods alone, and 51.4% used both methods. Only 25.7% of studies reported the sensitivity (median: 60.8%, range: 40.5%–86.7%) and specificity (median: 80.4%, range: 63.5%–88.0%) of the MCID to detect patients experiencing clinically important change.
Conclusion
Deviation from best practices in MCID calculation and reporting exists within the otolaryngology literature, with almost half of all studies only using one method of MCID calculation and almost three‐quarters not reporting the predictive ability (sensitivity/specificity) of the calculated MCID. When predictive ability is reported, however, MCIDs appear to be more specific than sensitive.
Level of Evidence
NA Laryngoscope, 134:2059–2069, 2024
Purpose
Disease control is conceptually recognized to be an important outcome measure for chronic rhinosinusitis (CRS). However, inconsistent usage is a significant factor in disadoption of important ...concepts and it is presently unclear how consistently the construct of CRS ‘control’ is being defined/applied. The objective of this study was to determine the heterogeneity of CRS disease control definitions in the scientific literature.
Methods
Systematic review of PubMed and Web of Science databases from inception through December 31, 2022. Included studies used CRS disease control as an explicitly stated outcome measure. The definitions of CRS disease control were collected.
Results
Thirty-one studies were identified with more than half published in 2021 or later. Definitions of CRS control were variable, although 48.4% of studies used the EPOS (2012 or 2020) criteria to define control, 14 other unique definitions of CRS disease control were also implemented. Most studies included the burden CRS symptoms (80.6%), need for antibiotics or systemic corticosteroids (77.4%) or nasal endoscopy findings (61.3%) as criteria in their definitions of CRS disease control. However, the specific combination of these criteria and prior time periods over which they were assessed were highly variable.
Conclusion
CRS disease control is not consistently defined in the scientific literature. Although many studies conceptually treated ‘control’ as the goal of CRS treatment, 15 different criteria were used to define CRS disease control, representing significant heterogeneity. Scientific derivation of criteria and collaborative consensus building are needed for the development of a widely-accepted and -applied definition of CRS disease control.
Genomes are organized into high-level three-dimensional structures, and DNA elements separated by long genomic distances can in principle interact functionally. Many transcription factors bind to ...regulatory DNA elements distant from gene promoters. Although distal binding sites have been shown to regulate transcription by long-range chromatin interactions at a few loci, chromatin interactions and their impact on transcription regulation have not been investigated in a genome-wide manner. Here we describe the development of a new strategy, chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) for the de novo detection of global chromatin interactions, with which we have comprehensively mapped the chromatin interaction network bound by oestrogen receptor alpha (ER-alpha) in the human genome. We found that most high-confidence remote ER-alpha-binding sites are anchored at gene promoters through long-range chromatin interactions, suggesting that ER-alpha functions by extensive chromatin looping to bring genes together for coordinated transcriptional regulation. We propose that chromatin interactions constitute a primary mechanism for regulating transcription in mammalian genomes.
Nonnative plant pests cause billions of dollars in damages. It is critical to prevent or reduce these losses by intervening at various stages of the invasion process, including pathway risk ...management (to prevent pest arrival), surveillance and eradication (to counter establishment), and management of established pests (to limit damages). Quantifying benefits and costs of these interventions is important to justify and prioritize investments and to inform biosecurity policy. However, approaches for these estimations differ in (1) the assumed relationship between supply, demand, and prices, and (2) the ability to assess different types of direct and indirect costs at invasion stages, for a given arrival or establishment probability. Here we review economic approaches available to estimate benefits and costs of biosecurity interventions to inform the appropriate selection of approaches. In doing so, we complement previous studies and reviews on estimates of damages from invasive species by considering the influence of economic and methodological assumptions. Cost accounting is suitable for rapid decisions, specific impacts, and simple methodological assumptions but fails to account for feedbacks, such as market adjustments, and may overestimate long-term economic impacts. Partial equilibrium models consider changes in consumer and producer surplus due to pest impacts or interventions and can account for feedbacks in affected sectors but require specialized economic models, comprehensive data sets, and estimates of commodity supply and demand curves. More intensive computable general equilibrium models can account for feedbacks across entire economies, including capital and labor, and linkages among these. The two major considerations in choosing an approach are (1) the goals of the analysis (e.g., consideration of a single pest or intervention with a limited range of impacts vs. multiple interventions, pests or sectors), and (2) the resources available for analysis such as knowledge, budget and time.
The merits of students exchanging views through the so-called human continuum exercise (HCE) are well established. The current article describes the creation of the virtual human continuum (VHC), an ...online platform that facilitates the same teaching exercise. It also reports feedback on the VHC from veterinary science students (
= 38). First-year Doctor of Veterinary Medicine students at the University of Sydney, Australia, trialed the platform and provided feedback. Most students agreed or strongly agreed that the VHC offered: a non-threatening environment for discussing emotive and challenging issues; and an opportunity to see how other people form ideas. It also made them think about how to express their ideas and make arguments; and left them feeling more comfortable about expressing their views using it than they would discussing ideas face-to-face (98%, 84%, 79% and 76%, respectively). All respondents agreed or strongly agreed that the VHC encouraged them to consider other opinions. These data suggest that the transition of the HCE to an online platform facilitates dialogue on difficult ethical issues in a supportive environment.
PDF
