A Work In Progress : Investigating the identity of the artist teacher/ freelance artist tutor and its implications for learning throughout the life course

Peer reviewedPublisher PD

Post-stroke lateropulsion and rehabilitation outcomes: A retrospective analysis

Purpose: A person with post-stroke lateropulsion actively pushes themselves toward their hemiplegic side, or resists moving onto their non-hemiplegic side. This study aimed to determine the association of lateropulsion severity with: • Change in function (Functional Independence Measure – FIM) and lateropulsion severity (Four-Point Pusher Score – 4PPS) during inpatient rehabilitation; • Inpatient rehabilitation length of stay (LOS); • Discharge destination from inpatient rehabilitation. Methods: Retrospective data for 1,087 participants (aged ≥65 years) admitted to a stroke rehabilitation unit (2005–2018) were analysed using multivariable regression models. Results: Complete resolution of lateropulsion was seen in 69.4% of those with mild lateropulsion on admission (n = 160), 49.3% of those with moderate lateropulsion (n = 142), and 18.8% of those with severe lateropulsion (n = 181). Average FIM change was lower in those with severe lateropulsion on admission than those with no lateropulsion (p \u3c 0.001). Higher admission 4PPS was associated with reduced FIM efficiency (p \u3c 0.001), longer LOS (p \u3c 0.001), (adjusted mean LOS: 35.6 days for those with severe lateropulsion versus 27.0 days for those without), and reduced likelihood of discharge home (p \u3c 0.001). Conclusion: Post-stroke lateropulsion is associated with reduced functional improvement and likelihood of discharge home. However, given a longer rehabilitation duration, most stroke survivors with moderate to severe lateropulsion can achieve important functional improvement. Implications for Rehabilitation: While people with post-stroke lateropulsion can be difficult to treat and require more resources than those without lateropulsion, the majority of those affected, even in severe cases, can make meaningful recovery with appropriate rehabilitation. Although those with moderate to severe post-stroke lateropulsion may have poorer outcomes (longer LOS and reduced likelihood of discharge home) it is still important to advocate for access to rehabilitation for this patient group to give them the opportunity for optimal functional recovery

A putative small solute transporter is responsible for the secretion of G377 and TRAP-containing secretory vesicles during Plasmodium gamete egress and sporozoite motility

Regulated protein secretion is required for malaria parasite life cycle progression and transmission between the mammalian host and mosquito vector. During transmission from the host to the vector, exocytosis of highly specialised secretory vesicles, such as osmiophilic bodies, is key to the dissolution of the red blood cell and parasitophorous vacuole membranes enabling gamete egress. The positioning of adhesins from the TRAP family, from micronemes to the sporozoite surface, is essential for gliding motility of the parasite and transmission from mosquito to mammalian host. Here we identify a conserved role for the putative pantothenate transporter PAT in Plasmodium berghei in vesicle fusion of two distinct classes of vesicles in gametocytes and sporozoites. PAT is a membrane component of osmiophilic bodies in gametocytes and micronemes in sporozoites. Despite normal formation and trafficking of osmiophilic bodies to the cell surface upon activation, PAT-deficient gametes fail to discharge their contents, remain intraerythrocytic and unavailable for fertilisation and further development in the mosquito. Sporozoites lacking PAT fail to secrete TRAP, are immotile and thus unable to infect the subsequent rodent host. Thus, P. berghei PAT appears to regulate exocytosis in two distinct populations of vesicles in two different life cycle forms rather than acting as pantothenic transporter during parasite transmission

Predicting the dispersal of SARS-CoV-2 RNA from the wastewater treatment plant to the coast

Viral pathogens including SARS-CoV-2 RNA have been detected in wastewater treatment effluent, and untreated sewage overflows, that pose an exposure hazard to humans. We assessed whether SARS-CoV-2 RNA was likely to have been present in detectable quantities in UK rivers and estuaries during the first wave of the Covid-19 pandemic. We simulated realistic viral concentrations parameterised on the Camel and Conwy catchments (UK) and their populations, showing detectable SARS-CoV-2 RNA concentrations for untreated but not for treated loading, but also being contingent on viral decay, hydrology, catchment type/shape, and location. Under mean or low river flow conditions, viral RNA concentrated within the estuaries allowing for viral build-up and caused a lag by up to several weeks between the peak in community infections and the viral peak in the environment. There was an increased hazard posed by SARS-CoV-2 RNA with a T90 decay rate >24 h, as the estuarine build-up effect increased. High discharge events transported the viral RNA downstream and offshore, increasing the exposure risk to coastal bathing waters and shellfisheries – although dilution in this case reduced viral concentrations well below detectable levels. Our results highlight the sensitivity of exposure to viral pathogens downstream of wastewater treatment, across a range of viral loadings and catchment characteristics – with implications to environmental surveillance

Knowledge, Attitudes, and Beliefs Regarding Breast and Cervical Cancer Screening among Cambodian, Laotian, Thai, and Tongan Women

Asian American Pacific Islander (AAPI) groups have low rates of breast and cervical cancer screening. This study examined knowledge, attitudes, and beliefs (KABs) regarding breast and cervical cancer on AAPI women. A cross-sectional survey of 1,808 AAPI women was included. Descriptive statistics and chi-square tests were provided and 55.3%, 68.6%, and 71.9% had received mammograms, clinical breast exam, and Pap smears, respectively. KABs on breast and cervical cancer varied between the four ethnic groups. Understanding the KABs toward cancer screening among AAPI women holds promise for identifying barriers to early detection and could aid in the creation of interventions

Evolutionarily distant I domains can functionally replace the essential ligand-binding domain of Plasmodium TRAP

Inserted (I) domains function as ligand-binding domains in adhesins that support cell adhesion and migration in many eukaryotic phyla. These adhesins include integrin alpha beta heterodimers in metazoans and single subunit transmembrane proteins in apicomplexans such as TRAP in Plasmodium and MIC2 in Toxoplasma. Here we show that the I domain of TRAP is essential for sporozoite gliding motility, mosquito salivary gland invasion and mouse infection. Its replacement with the I domain from Toxoplasma MIC2 fully restores tissue invasion and parasite transmission, while replacement with the aXI domain from human integrins still partially restores liver infection. Mutations around the ligand binding site allowed salivary gland invasion but led to inefficient transmission to the rodent host. These results suggest that apicomplexan parasites appropriated polyspecific I domains in part for their ability to engage with multiple ligands and to provide traction for emigration into diverse organs in distant phyla

Transient Overexpression of α-Ca2+/Calmodulin-Dependent Protein Kinase II in the Nucleus Accumbens Shell Enhances Behavioral Responding to Amphetamine

Ca2+/calmodulin-dependent protein kinase II (CaMKII) is known to contribute to the expression of psychostimulant sensitization by regulating dopamine (DA) overflow from DA neuron terminals in the nucleus accumbens (NAcc). The present experiments explored the contribution of CaMKII in NAcc neurons postsynaptic to these terminals where it is known to participate in a number of signaling pathways that regulate responding to psychostimulant drugs. Exposure to amphetamine transiently increased αCaMKII levels in the shell but not the core of the NAcc. Thus, HSV (herpes simplex viral) vectors were used to transiently overexpress αCaMKII in NAcc neurons in drug-naive rats, and behavioral responding to amphetamine was assessed. Transiently overexpressing αCaMKII in the NAcc shell led to long-lasting enhancement of amphetamine-induced locomotion and self-administration manifested when αCaMKII levels were elevated and persisting long after they had returned to baseline. Enhanced locomotion was not observed after infection in the NAcc core or sites adjacent to the NAcc. Transient elevation of NAcc shell αCaMKII levels also enhanced locomotor responding to NAcc AMPA and increased phosphorylation levels of GluR1 (Ser831), a CaMKII site, both soon and long after infection. Similar increases in pGluR1 (Ser831) were observed both soon and long after exposure to amphetamine. These results indicate that the transient increase in αCaMKII observed in neurons of the NAcc shell after viral-mediated gene transfer and likely exposure to amphetamine leads to neuroadaptations in AMPA receptor signaling in this site that may contribute to the long-lasting maintenance of behavioral and incentive sensitization by psychostimulant drugs like amphetamine

Riboneogenesis in Yeast

SummaryGlucose is catabolized in yeast via two fundamental routes, glycolysis and the oxidative pentose phosphate pathway, which produces NADPH and the essential nucleotide component ribose-5-phosphate. Here, we describe riboneogenesis, a thermodynamically driven pathway that converts glycolytic intermediates into ribose-5-phosphate without production of NADPH. Riboneogenesis begins with synthesis, by the combined action of transketolase and aldolase, of the seven-carbon bisphosphorylated sugar sedoheptulose-1,7-bisphosphate. In the pathway's committed step, sedoheptulose bisphosphate is hydrolyzed to sedoheptulose-7-phosphate by the enzyme sedoheptulose-1,7-bisphosphatase (SHB17), whose activity we identified based on metabolomic analysis of the corresponding knockout strain. The crystal structure of Shb17 in complex with sedoheptulose-1,7-bisphosphate reveals that the substrate binds in the closed furan form in the active site. Sedoheptulose-7-phosphate is ultimately converted by known enzymes of the nonoxidative pentose phosphate pathway to ribose-5-phosphate. Flux through SHB17 increases when ribose demand is high relative to demand for NADPH, including during ribosome biogenesis in metabolically synchronized yeast cells