The health of Māori, the Indigenous peoples of Aotearoa, New Zealand, like that of almost all Indigenous peoples worldwide, is characterised by systematic inequities in health outcomes, differential ...exposure to the determinants of health, inequitable access to and through health and social systems, disproportionate marginalisation and inadequate representation in the health workforce. As health providers, we are often taught that ‘taking a history’ is a critical component of a patient consultation to ensure that the underlying conditions are treated rather than the often superficial presenting symptoms. In the same way, attempts to make sense of the health and well-being of Indigenous peoples is inadequate unless health providers engage critically with the history of their respective nations and any subsequent patterns of privilege or disadvantage. Understanding this history, within the framework of western imperialism and other similar colonial projects, allows us to make sense of international patterns of Indigenous health status.
While health commentators acknowledge the unequal health outcomes of Indigenous people, and an increasing number also link these inequities to Indigenous marginalisation resulting from historic events, very few go further and expose the deep relationship between racism and coloniality and how these continue to be the basic determinants of Indigenous health today. This work includes honest examination of the role that science and the health disciplines have played historically in colonisation through the subjugation of Indigenous ways of knowing and knowledge production, as well as being complicit in the creation and maintenance of a fabricated hierarchy of humankind. Despite the ‘science’ of this racial hierarchy being discredited, it retains a false validity in our societies. As long as oppressive systems that continue to re-inscribe racism and white privilege remain in communities, including our academic communities, coloniality continues its discrimination.
Indigenous voices on migration, ethnicity, racisma and health will always demand the elimination of inequities in health but to do so will require a parallel commitment to critically interrogating all of our histories and our disciplines, as well as examining how our practice, including research, disrupts or maintains global systems of racism and coloniality.
•Persistent, compelling health inequities exist for Indigenous peoples worldwide.•Science, ‘race’ and colonialism are intricately linked for Indigenous peoples.•Understanding colonial histories is critical to making sense of Indigenous health.•Indigenous voices offer challenges and opportunities in global health futures.
Juvenile amyotrophic lateral sclerosis (ALS) with basophilic inclusions is a form of ALS characterized by protein deposits in motor neurons that are morphologically and tinctorially distinct from ...those of classic sporadic ALS. The nosologic position of this type of ALS in the molecular pathologic and genetic classification of ALS is unknown.
We identified neuropathologically 4 patients with juvenile ALS with basophilic inclusions and tested the hypothesis that specific RNA binding protein pathology may define this type of ALS. Immunohistochemical findings prompted us to sequence the fused in sarcoma (FUS) gene.
Motor symptoms began between ages 17 and 22. Disease progression was rapid without dementia. No family history was identified. Basophilic inclusions were strongly positive for FUS protein but negative for TAR DNA binding protein 43 (TDP-43). Granular and compact FUS deposits were identified in glia and neuronal cytoplasm and nuclei. Ultrastructure of aggregates was in keeping with origin from fragmented rough endoplasmic reticulum. Sequencing of all 15 exons of the FUS gene in 3 patients revealed a novel deletion mutation (c.1554_1557delACAG) in 1 individual and the c.1574C>T (P525L) mutation in 2 others.
Juvenile ALS with basophilic inclusions is a FUS proteinopathy and should be classified as ALS-FUS. The FUS c.1574C>T (P525L) and c.1554_1557delACAG mutations are associated with this distinct phenotype. The molecular genetic relationship with frontotemporal lobar degeneration with FUS pathology remains to be clarified.
The Wars for Asia, 1911–1949 shows that the Western treatment of World War II, the Second Sino-Japanese War and the Chinese Civil War as separate events misrepresents their overlapping connections ...and causes. The Chinese Civil War precipitated a long regional war between China and Japan that went global in 1941 when the Chinese found themselves fighting a civil war within a regional war within an overarching global war. The global war that consumed Western attentions resulted from Japan's peripheral strategy to cut foreign aid to China by attacking Pearl Harbour and Western interests throughout the Pacific in 1941. S. C. M. Paine emphasizes the fears and ambitions of Japan, China and Russia, and the pivotal decisions that set them on a collision course in the 1920s and 1930s. The resulting wars together yielded a viscerally anti-Japanese and unified Communist China, the still-angry rising power of the early twenty-first century.
Males of advanced age represent a rapidly growing population at risk for prostate cancer. In the contemporary setting of earlier detection, a majority of prostate carcinomas are still clinically ...localized and often treated using radiation therapy. Our recent studies have shown that premature cellular senescence, rather than apoptosis, accounts for most of the clonogenic death induced by clinically relevant doses of irradiation in prostate cancer cells. We show here that this treatment-induced senescence was associated with a significantly increased release of exosome-like microvesicles. In premature senescence, this novel secretory phenotype was dependent on the activation of p53. In addition, the release of exosome-like microvesicles also increased during proliferative senescence in normal human diploid fibroblasts. These data support the hypothesis that senescence, initiated either by telomere attrition (e.g., aging) or DNA damage (e.g., radiotherapy), may induce a p53-dependent increase in the biogenesis of exosome-like vesicles. Ultrastructural analysis and RNA interference-mediated knockdown of Tsg101 provided significant evidence that the additional exosomes released by prematurely senescent prostate cancer cells were principally derived from multivesicular endosomes. Moreover, these exosomes were enriched in B7-H3 protein, a recently identified diagnostic marker for prostate cancer, and an abundance of what has recently been termed "exosomal shuttle RNA." Our findings are consistent with the proposal that exosomes can transfer cargos, with both immunoregulatory potential and genetic information, between cells through a novel mechanism that may be recruited to increase exosome release during accelerated and replicative cellular senescence.
Ruminants are recognised to suffer from Cu-responsive disorders. Present understanding of Cu transport and metabolism is limited and inconsistent across vets and veterinary professionals. There has ...been much progress from the studies of the 1980s and early 1990s in cellular Cu transport and liver metabolism which has not been translated into agricultural practice. Cu metabolism operates in regulated pathways of Cu trafficking rather than in pools of Cu lability. Cu in the cell is chaperoned to enzyme production, retention within metallothionein or excretion via the Golgi into the blood. The hepatocyte differs in that Cu-containing caeruloplasmin can be synthesised to provide systemic Cu supply and excess Cu is excreted via bile. The aim of the present review is to improve understanding and highlight the relevant progress in relation to ruminants through the translation of newer findings from medicine and non-ruminant animal models into ruminants.
ABSTRACT
Fast radio bursts (FRBs) are short-duration radio pulses of cosmological origin. Among the most common sources predicted to explain this phenomenon are bright pulses from a class of ...extremely highly magnetized neutron stars known as magnetars. Motivated by the discovery of an FRB-like pulse from the Galactic magnetar SGR 1935+2154, we searched for similar events in Messier 82 (M82). With a star formation rate 40 times that of the Milky Way, one might expect that the implied rate of events similar to that seen from SGR 1935+2154 from M82 should be 40 times higher than that of the Milky Way. We observed M82 at 1.4 GHz with the 20-m telescope at the Green Bank Observatory for 34.8 d. While we found many candidate events, none had a signal-to-noise ratio greater than 8. We also show that there are insufficient numbers of repeating low-significance events at similar dispersion measures to constitute a statistically significant detection. From these results, we place an upper bound for the rate of radio pulses from M82 to be 30 yr−1 above a fluence limit of 8.5 Jy ms. While this is less than nine times the rate of radio bursts from magnetars in the Milky Way inferred from the previous radio detections of SGR 1935+2154, it is possible that propagation effects from interstellar scattering are currently limiting our ability to detect sources in M82. Further searches of M82 and other nearby galaxies are encouraged to probe this putative FRB population.
We report a case of isolated myxopapillary ependymoma (MPE) of the fourth ventricle. This is the thirteenth reported case of primary intracranial MPE and the fourth reported case of MPE originating ...from the fourth ventricle. We suggest that exhaustive clinical and radiological investigation of a spinal ependymoma must be undertaken in all cases of intracranial ependymoma.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Previously we reported the identification of a homozygous COL27A1 (c.2089G>C; p.Gly697Arg) missense variant and proposed it as a founder allele in Puerto Rico segregating with Steel syndrome (STLS, ...MIM #615155); a rare osteochondrodysplasia characterized by short stature, congenital bilateral hip dysplasia, carpal coalitions, and scoliosis. We now report segregation of this variant in five probands from the initial clinical report defining the syndrome and an additional family of Puerto Rican descent with multiple affected adult individuals. We modeled the orthologous variant in murine Col27a1 and found it recapitulates some of the major Steel syndrome associated skeletal features including reduced body length, scoliosis, and a more rounded skull shape. Characterization of the in vivo murine model shows abnormal collagen deposition in the extracellular matrix and disorganization of the proliferative zone of the growth plate. We report additional COL27A1 pathogenic variant alleles identified in unrelated consanguineous Turkish kindreds suggesting Clan Genomics and identity-by-descent homozygosity contributing to disease in this population. The hypothesis that carrier states for this autosomal recessive osteochondrodysplasia may contribute to common complex traits is further explored in a large clinical population cohort. Our findings augment our understanding of COL27A1 biology and its role in skeletal development; and expand the functional allelic architecture in this gene underlying both rare and common disease phenotypes.
Incidence of human yersiniosis in New Zealand has increased between 2013 and 2017. For surveillance and outbreak investigations it is essential that an appropriate level of discrimination between ...pathogenic Yersinia enterocolitica isolates is provided, in order to support epidemiological linking of connected cases. Subtyping of 227 Y. enterocolitica isolates was performed using a range of different typing methods, including biotyping, serotyping and seven loci multiple-locus variable-number tandem-repeat analysis (MLVA). In addition, core genome single-nucleotide polymorphism (core SNP) analysis and multi-locus sequence typing were performed on a subset of 69 isolates. Sixty-seven different MLVA types were identified. One MLVA profile was associated with an outbreak in the Bay of Plenty region, supported by epidemiological data. Core SNP analysis showed that all the outbreak-related isolates clustered together. The subtyping and epidemiological evidence suggests that the outbreak of yersiniosis in the Bay of Plenty region between October and December 2016 could be attributed to a point source. However, subtyping results further suggest that the same clone was isolated from several regions between August 2016 and March 2017. Core SNP analysis and MLVA typing failed to differentiate between Y. enterocolitica biotype 2 and biotype 3. For this reason, we propose that these biotypes should be reported as a single type namely: Y. enterocolitica biotype 2/3 and that the serotype should be prioritised as an indicator of prevalence.
N-Benzyl substitution of 5-HT2A receptor agonists of the phenethylamine structural class of psychedelics (such as 4-bromo-2,5-dimethoxyphenethylamine, often referred to as 2C-B) confer a significant ...increase in binding affinity as well as functional activity of the receptor. We have prepared a series of 48 compounds with structural variations in both the phenethylamine and N-benzyl part of the molecule to determine the effects on receptor binding affinity and functional activity at 5-HT2A and 5-HT2C receptors. The compounds generally had high affinity for the 5-HT2A receptor with 8b having the highest affinity at 0.29 nM but with several other compounds also exhibiting subnanomolar binding affinities. The functional activity of the compounds was distributed over a wider range with 1b being the most potent at 0.074 nM. Most of the compounds exhibited low to moderate selectivity (1- to 40-fold) for the 5-HT2A receptor in the binding assays, although one compound 6b showed an impressive 100-fold selectivity for the 5-HT2A receptor. In the functional assay, selectivity was generally higher with 1b being more than 400-fold selective for the 5-HT2A receptor.
PDF
