Annexin A2 is a novel Cellular Redox Regulatory Protein involved in Tumorigenesis

Annexins are a structurally related family of calcium and phospholipid-binding proteins that are involved in the regulation of a wide range of molecular and cellular processes. Annexin A2 is unique among the annexins in that it possesses redox sensitive cysteine(s). The ubiquitous and abundant expression of ANXA2 in cells and its reactivity with hydrogen peroxide led us to hypothesize that this protein could play a role in cellular redox regulation. Here we show that ANXA2 protein levels are induced by hydrogen peroxide. Furthermore, depletion of ANXA2 resulted in the elevation of cellular reactive oxygen species (ROS) upon oxidative stress, increased activation of the ROS-induced pro-apoptotic kinases, JNK, p38 and Akt and elevated sensitivity to ROS-mediated cellular damage/death. ANXA2-null mice showed significantly elevated protein oxidation in the liver and lung tissues compared to WT mice. ANXA2 depleted cancer cells showed enhanced cellular protein oxidationconcomitant with decreased tumor growth compared to control cancer cells andboth the oxidation of cellular proteins and tumor growth deficit werereversed by the antioxidant N-acetyl cysteine, indicating that ANXA2 plays akey role in the regulation of cellular redox during tumorigenesis. Ex-vivo human cancer studies showed that up-regulation of the reduced form of ANXA2 is associated with protection of the tumor proteins from oxidation. In summary, our results indicate that ANXA2 plays an important role incellular redox regulation by protecting cells from oxidative stress, aneffect that is particularly important during tumorigenesis

Spatially localized cluster solutions in inhibitory neural networks

The final publication is available at Elsevier via http://dx.doi.org/10.1016/j.mbs.2021.108591. © 2021. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Neurons in the inhibitory network of the striatum display cell assembly firing patterns which recent results suggest may consist of spatially compact neural clusters. Previous computational modeling of striatal neural networks has indicated that non-monotonic, distance-dependent coupling may promote spatially localized cluster firing. Here, we identify conditions for the existence and stability of cluster firing solutions in which clusters consist of spatially adjacent neurons in inhibitory neural networks. We consider simple non-monotonic, distance-dependent connectivity schemes in weakly coupled 1-D networks where cells make stronger connections with their th nearest neighbors on each side and weaker connections with closer neighbors. Using the phase model reduction of the network system, we prove the existence of cluster solutions where neurons that are spatially close together are also synchronized in the same cluster, and find stability conditions for these solutions. Our analysis predicts the long-term behavior for networks of neurons, and we confirm our results by numerical simulations of biophysical neuron network models. Our results demonstrate that an inhibitory network with non-monotonic, distance-dependent connectivity can exhibit cluster solutions where adjacent cells fire together.American Institute of Mathematics, Structured Quartet Research Ensembles program || Natural Sciences and Engineering Research Council of Canada

Vitamin D Status of Anabaptist Children in Southwestern Ontario, Canada

The objective was to determine vitamin D status of Old Order Anabaptist children in rural Southwestern, Ontario, Canada, given concerns of community healthcare professionals. Fifty-two children (2.5 months - 6.5 years) (56% female) were recruited. Finger prick blood spot (BSp) samples were analyzed for 25-hydroxy (OH) vitamins D2 & D3 (BSp25(OH)D). Three-day food records were evaluated using Dietary Reference Intakes and Canada’s Food Guide (CFG) (Bush, et al. 2007). Compared to national Canadian data: mean BSp25(OH)D concentrations (78±31 nmol/L) were similar; a slightly smaller proportion (0% vs 2%) were at risk of deficiency (\u3c30 nmol/L) or had inadequate status (4% vs 7%) (\u3c40 nmol/L); and 10% vs 1% had BSp25(OH)D higher than 125 nmol/L. BSp25(OH)D was significantly associated (r2=0.358; p=0.001) with total vitamin D intake. From food alone, vitamin D intake was 68±39 IU/day, lower than the Recommended Dietary Allowance (RDA) of 600 IU/day, and intakes were all below the Estimated Average Requirement (EAR) of 400 IU. Even including supplemental vitamin D, 87% were below the EAR (total intake=213±194 IU/day). No children had vitamin D intakes greater than the Upper Limit. Servings of milk and alternates were 1.6±0.8/day (CFG=2/day). Unfortified farm milk was consumed by 88% of children and 89% received a vitamin D supplement. Results were comparable to recent Canadian data suggesting that most children have adequate vitamin D status. Nevertheless, these findings support the need to encourage appropriate vitamin D intake (from food and supplements) to achieve the RDA for Old Order Anabaptist children in these communities. [Abstract by authors.

Prediction of HIV transmission cluster growth with statewide surveillance data

Background:Prediction of HIV transmission cluster growth may help guide public health action. We developed a predictive model for cluster growth in North Carolina (NC) using routine HIV surveillance data.Methods:We identified putative transmission clusters with ≥2 members through pairwise genetic distances ≤1.5% from HIV-1 pol sequences sampled November 2010-December 2017 in NC. Clusters established by a baseline of January 2015 with any sequences sampled within 2 years before baseline were assessed for growth (new diagnoses) over 18 months. We developed a predictive model for cluster growth incorporating demographic, clinical, temporal, and contact tracing characteristics of baseline cluster members. We internally and temporally externally validated the final model in the periods January 2015-June 2016 and July 2016-December 2017.Results:Cluster growth was predicted by larger baseline cluster size, shorter time between diagnosis and HIV care entry, younger age, shorter time since the most recent HIV diagnosis, higher proportion with no named contacts, and higher proportion with HIV viremia. The model showed areas under the receiver-operating characteristic curves of 0.82 and 0.83 in the internal and temporal external validation samples.Conclusions:The predictive model developed and validated here is a novel means of identifying HIV transmission clusters that may benefit from targeted HIV control resources. © 2018 Wolters Kluwer Health, Inc. All rights reserved

Isolation of SARS-CoV-2 in viral cell culture in immunocompromised patients with persistently positive RT-PCR results

Immunocompromised adults can have prolonged acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive RT-PCR results, long after the initial diagnosis of coronavirus disease 2019 (COVID-19). This study aimed to determine if SARS-CoV-2 virus can be recovered in viral cell culture from immunocompromised adults with persistently positive SARS-CoV-2 RT-PCR tests. We obtained 20 remnant SARS-CoV-2 PCR positive nasopharyngeal swabs from 20 immunocompromised adults with a positive RT-PCR test ≥14 days after the initial positive test. The patients\u27

The case for change : a student-staff partnership to decolonise a medical school's case-based learning curriculum

Over the last few years, there has been increasing work across higher education (HE) on the attainment gap (Universities UK and NUS, 2019), anti-racism pedagogy (Ono-George, 2019) and the need for decolonisation of curricula (Liyanage, 2020). Decolonisation is the process of reviewing and changing the HE curricula of post-colonial countries so that they become diverse, inclusive and representative of minority ethnicities (Mbaki and Todorova, 2020). In our graduate entry programme, black, Asian and minority ethnic (BAME) students were awarded fewer merits and distinctions despite fulfilling the same entrance requirements as their peers (Sorinola et al., 2019). A survey of medical students for the University’s Student Union Decolonise Project confirmed the need to decolonise our medical curriculum (Akojie and Seth, 2019). Therefore, as we use a case-based learning (CBL) curriculum, we formed a student-staff partnership to review it

'To live and die [for] Dixie': Irish civilians and the Confederate States of America

Around 20,000 Irishmen served in the Confederate army in the Civil War. As a result, they left behind, in various Southern towns and cities, large numbers of friends, family, and community leaders. As with native-born Confederates, Irish civilian support was crucial to Irish participation in the Confederate military effort. Also, Irish civilians served in various supporting roles: in factories and hospitals, on railroads and diplomatic missions, and as boosters for the cause. They also, however, suffered in bombardments, sieges, and the blockade. Usually poorer than their native neighbours, they could not afford to become 'refugees' and move away from the centres of conflict. This essay, based on research from manuscript collections, contemporary newspapers, British Consular records, and Federal military records, will examine the role of Irish civilians in the Confederacy, and assess the role this activity had on their integration into Southern communities. It will also look at Irish civilians in the defeat of the Confederacy, particularly when they came under Union occupation. Initial research shows that Irish civilians were not as upset as other whites in the South about Union victory. They welcomed a return to normalcy, and often 'collaborated' with Union authorities. Also, Irish desertion rates in the Confederate army were particularly high, and I will attempt to gauge whether Irish civilians played a role in this. All of the research in this paper will thus be put in the context of the Drew Gilpin Faust/Gary Gallagher debate on the influence of the Confederate homefront on military performance. By studying the Irish civilian experience one can assess how strong the Confederate national experiment was. Was it a nation without a nationalism

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Subcortical brain atrophy persists even in HAART-regulated HIV disease

The purpose of this study was to determine the pattern and extent of caudate nucleus and putamen atrophy in HIV-infected men with well-controlled immune status and viral replication. 155 men underwent structural brain magnetic resonance imaging; 84 were HIV-infected and 71 were uninfected controls. MRI data were processed using the Fully Deformable Segmentation routine, producing volumes for the right and left caudate nucleus and putamen, and 3-D maps of spatial patterns of thickness. There was significant atrophy in the HIV-infected men in both the caudate and putamen, principally in the anterior regions. The volume of the basal ganglia was inversely associated with the time since first seropositivity, suggesting that either there is a chronic, subclinical process that continues in spite of therapy, or that the extent of the initial insult caused the extent of atrophy

Cross-cutting principles for planetary health education

Since the 2015 launch of the Rockefeller Foundation Lancet Commission on planetary health,1 an enormous groundswell of interest in planetary health education has emerged across many disciplines, institutions, and geographical regions. Advancing these global efforts in planetary health education will equip the next generation of scholars to address crucial questions in this emerging field and support the development of a community of practice. To provide a foundation for the growing interest and efforts in this field, the Planetary Health Alliance has facilitated the first attempt to create a set of principles for planetary health education that intersect education at all levels, across all scales, and in all regions of the world—ie, a set of cross-cutting principles