Sensory ethnographers deploy methods such as drawing, video and photography in order to examine the more ineffable and non-representational aspects of practices. Usually, these studies are conducted ...by individual researchers who deal only with their own material. What happens when a team of ethnographers explores questions of a sensory or non-representational nature? How do they share their findings not only with their audiences, but also with each other? Team ethnography is becoming increasingly common across the social sciences and humanities, yet to date there has been little attention paid to the important work of communicating findings within a group. To explore this further, we conducted a methodological ‘proof of concept’ study, observing and documenting people learning to make omelettes. We found that sensory methods have a role not only in studying practices but crucially, in also facilitating a form of immersion into the ethnographic practices and imaginations of others within the team. In the end, we suggest that experiments with sensory methods, such as through proof of concept methodological studies, are useful for thinking about how teams of social scientists work together, whether their research deals with sensory topics or not.
Mutations in the gene encoding the microtubule severing ATPase spastin are the most frequent cause of hereditary spastic paraplegia, a genetic condition characterised by length-dependent axonal ...degeneration. Here, we show that HeLa cells lacking spastin and embryonic fibroblasts from a spastin knock-in mouse model become highly polarised and develop cellular protrusions. In HeLa cells, this phenotype was rescued by wild-type spastin, but not by forms unable to sever microtubules or interact with endosomal ESCRT-III proteins. Cells lacking the spastin-interacting ESCRT-III-associated proteins IST1 or CHMP1B also developed protrusions. The protrusion phenotype required protrudin, a RAB-interacting protein that interacts with spastin and localises to ER–endosome contact sites, where it promotes KIF5-dependent endosomal motility to protrusions. Consistent with this, the protrusion phenotype in cells lacking spastin also required KIF5. Lack or mutation of spastin resulted in functional consequences for receptor traffic of a pathway implicated in HSP, as Bone Morphogenetic Protein receptor distribution became polarised. Our results, therefore, identify a novel role for ESCRT-III proteins and spastin in regulating polarised membrane traffic.
Contacts between endosomes and the endoplasmic reticulum (ER) promote endosomal tubule fission, but the mechanisms involved and consequences of tubule fission failure are incompletely understood. We ...found that interaction between the microtubule-severing enzyme spastin and the ESCRT protein IST1 at ER-endosome contacts drives endosomal tubule fission. Failure of fission caused defective sorting of mannose 6-phosphate receptor, with consequently disrupted lysosomal enzyme trafficking and abnormal lysosomal morphology, including in mouse primary neurons and human stem cell-derived neurons. Consistent with a role for ER-mediated endosomal tubule fission in lysosome function, similar lysosomal abnormalities were seen in cellular models lacking the WASH complex component strumpellin or the ER morphogen REEP1. Mutations in
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cause hereditary spastic paraplegia (HSP), a disease characterized by axonal degeneration. Our results implicate failure of the ER-endosome contact process in axonopathy and suggest that coupling of ER-mediated endosomal tubule fission to lysosome function links different classes of HSP proteins, previously considered functionally distinct, into a unifying pathway for axonal degeneration.
A successful start to school correlates with positive later educational outcomes, both social and academic. Transitioning experience differs according to social context and this study was conducted ...in the UAE. Expatriate teachers, UAE national parents and expatriate parents were asked to complete a questionnaire of 20 child behaviours indicating the degree of agreement that each would indicate a successful transition. Differences according to role (teacher/parent) or culture (UAE national/expatriate) were found. The experience of transitioning is a highly context dependent phenomenon and each context warrants investigation to ensure as positive a start to school as possible for each child.
Objective
The aim of this analysis is to understand why young adult students in the US South marry in college or shortly afterwards.
Background
While the median age at first marriage in the United ...States has risen and marriage delay has become culturally normative, a substantial minority of young adults marry in their late teens or early 20's, particularly in the US South. Young adult college students who marry negotiate conflicting imperatives of marriage and educational attainment, and how these are negotiated or resolved sheds light on the social, cultural, and economic forces that inform family formation.
Method
This study draws from in‐depth interviews conducted with 45 18–23‐year‐old engaged or married college students in Mississippi.
Results
Entering college, most participants had expected to marry close to median ages, with marriage perceived as a hindrance to educational achievement. This marriage timeline was negotiated downwards with the influence of four interrelated factors: personal orientation to marriage; a marriage‐oriented culture, being in the “right” relationship; and social and financial supports for marriage.
Conclusion
The norm of marriage delay that these young adults embraced became perceived as inapplicable given evidence that marriage would not compromise college completion or financial stability. There were also social and cultural pressures toward marriage. “Why wait?” captures participants' sense of few barriers but clear incentives to marriage. Incentives were sometimes financial but also social, as marriage enabled students to establish themselves as more mature than peers.
The hereditary spastic paraplegias (HSPs) are genetic motor neuron diseases characterized by progressive degeneration of corticospinal tract axons. Mutations in SPAST, encoding the ...microtubule-severing ATPase spastin, are the most common causes of HSP. The broad SPAST mutational spectrum indicates a haploinsufficiency pathogenic mechanism in most cases. Most missense mutations cluster in the ATPase domain, where they disrupt the protein's ability to sever microtubules. However, several putative missense mutations in the protein's microtubule interacting and trafficking (MIT) domain have also been described, but the pathogenicity of these mutations has not been verified with functional studies. Spastin promotes endosomal tubule fission, and defects in this lead to lysosomal enzyme mistrafficking and downstream lysosomal abnormalities. We investigated the function of three disease-associated spastin MIT mutants and found that none was able to promote normal endosomal tubule fission, lysosomal enzyme receptor trafficking, or lysosomal morphology. One of the mutations affected recruitment of spastin to endosomes, a property that requires the canonical function of the MIT domain in binding endosomal sorting complex required for transport (ESCRT)-III proteins. However, the other mutants did not affect spastin's endosomal recruitment, raising the possibility of pathologically important non-canonical roles for the MIT domain. In conclusion, we demonstrate that spastin MIT mutants cause functional abnormalities related to the pathogenesis of HSP. These mutations do not directly affect spastin's microtubule-severing capacity, and so we identify a new molecular pathological mechanism by which spastin mutations may cause disease.
Purpose The purpose was to assess ultrasound-guided injections through patient satisfaction in a comparative internally controlled study of fluoroscopic versus ultrasound technique and to quantitate ...the reliability of the ultrasound method. In addition, the reliability of the ultrasound method was quantitated. Methods This study consisted of the first 50 consecutive patients to undergo ultrasound-guided intra-articular injection of the hip (by a nurse practitioner) and who had previously undergone fluoroscopy-guided intra-articular injections by our center's fellowship-trained musculoskeletal radiologists. The patients rated the ultrasound and fluoroscopic experiences on a scale from 1 to 10 for convenience and pain; in addition, they indicated their preference between the 2 techniques. Success of the injection was documented among a total of 206 consecutive patients who underwent ultrasound-guided injections during the period of the controlled study. Results For convenience, ultrasound injection had a mean rating of 9.8 whereas fluoroscopic injection had a mean rating of 3.1. For pain, ultrasound had a mean rating of 3 and fluoroscopy had a mean rating of 5.6. These differences were statistically significant ( P < .01) in favor of ultrasound. For preference, 49 of 50 patients in the control study (98%) stated that they would prefer the ultrasound injection, whereas 1 was uncertain. The injection was successful in 202 of the first 206 patients (98%) to undergo ultrasound injection, whereas 4 patients required a second pass for successful injection. Conclusions In this study in-office ultrasound-guided injections of the hip were more convenient and less painful than fluoroscopy-guided hospital-based injections and were preferred by patients who have undergone both. Furthermore, the ultrasound-guided injections were performed by a recently trained physician extender in contrast to the fluoroscopic method, which was performed by experienced fellowship-trained musculoskeletal radiologists. The procedure is highly successful in the hands of a properly trained clinician. Level of Evidence Level II, prospective comparative study.
The endosomal sorting complexes required for transport (ESCRTs) are essential for multiple membrane modeling and membrane-independent cellular processes. Here we describe six unrelated individuals ...with de novo missense variants affecting the ATPase domain of VPS4A, a critical enzyme regulating ESCRT function. Probands had structural brain abnormalities, severe neurodevelopmental delay, cataracts, growth impairment, and anemia. In cultured cells, overexpression of VPS4A mutants caused enlarged endosomal vacuoles resembling those induced by expression of known dominant-negative ATPase-defective forms of VPS4A. Proband-derived fibroblasts had enlarged endosomal structures with abnormal accumulation of the ESCRT protein IST1 on the limiting membrane. VPS4A function was also required for normal endosomal morphology and IST1 localization in iPSC-derived human neurons. Mutations affected other ESCRT-dependent cellular processes, including regulation of centrosome number, primary cilium morphology, nuclear membrane morphology, chromosome segregation, mitotic spindle formation, and cell cycle progression. We thus characterize a distinct multisystem disorder caused by mutations affecting VPS4A and demonstrate that its normal function is required for multiple human developmental and cellular processes.
Mechanisms coordinating endosomal degradation and recycling are poorly understood, as are the cellular roles of microtubule (MT) severing. We show that cells lacking the MT-severing protein spastin ...had increased tubulation of and defective receptor sorting through endosomal tubular recycling compartments. Spastin required the ability to sever MTs and to interact with ESCRT-III (a complex controlling cargo degradation) proteins to regulate endosomal tubulation. Cells lacking IST1 (increased sodium tolerance 1), an endosomal sorting complex required for transport (ESCRT) component to which spastin binds, also had increased endosomal tubulation. Our results suggest that inclusion of IST1 into the ESCRT complex allows recruitment of spastin to promote fission of recycling tubules from the endosome. Thus, we reveal a novel cellular role for MT severing and identify a mechanism by which endosomal recycling can be coordinated with the degradative machinery. Spastin is mutated in the axonopathy hereditary spastic paraplegia. Zebrafish spinal motor axons depleted of spastin or IST1 also had abnormal endosomal tubulation, so we propose this phenotype is important for axonal degeneration.
The hereditary spastic paraplegias (HSPs) are genetic conditions in which there is progressive axonal degeneration in the corticospinal tract. Autosomal dominant mutations, including nonsense, ...frameshift and missense changes, in the gene encoding the microtubule severing ATPase spastin are the most common cause of HSP in North America and northern Europe. In this study we report quantitative gait analysis using a motorized treadmill system, carried out on mice knocked-in for a disease-associated mutation affecting a critical residue in the Walker A motif of the spastin ATPase domain. At 4 months and at one year of age homozygous mutant mice had a number of abnormal gait parameters, including in stride length and stride duration, compared to heterozygous and wild-type littermates. Gait parameters in heterozygous animals did not differ from wild-type littermates. We conclude that quantitative gait analysis using the DigiGait system sensitively detects motor abnormalities in a hereditary spastic paraplegia model, and would be a useful method for analyzing the effects of pharmacological treatments for HSP.
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