Inclusion of MUC1 (Ma695) in a panel of immunohistochemical markers is useful for distinguishing between endocervical and endometrial mucinous adenocarcinoma*

BACKGROUND: Distinguishing endocervical adenocarcinoma (ECA) from endometrial mucinous adenocarcinoma (EMMA) is clinically significant in view of the differences in their management and prognosis. In this study, we used a panel of tumor markers to determine their ability to distinguish between primary endocervical adenocarcinoma and primary endometrial mucinous adenocarcinoma. METHODS: Immunohistochemistry using monoclonal antibodies to MUC1 (Ma695), p16, estrogen receptor (ER), progesterone receptor (PR), and vimentin, was performed to examine 32 cases, including 18 EMMAs and 14 ECAs. For MUC1, cases were scored based on the percentage of staining pattern, apical, apical and cytoplasmic (A/C), or negative. For p16, cases were scored based on the percentage of cells stained. For the rest of the antibodies, semiquantitative scoring system was carried out. RESULTS: For MUC1, majority of EMMA (14 of 18 cases, 78%) showed A/C staining, whereas only few ECA (2 of 14, 14%) were positive. The difference of MUC1 expression in the two groups of malignancy was statistically significant (p < 0.001). Staining for p16 was positive in 10 of 14 (71%) ECA and 4 of 18 (22%) EMMA. Estrogen receptor was positive in 3 of 14 (21%) ECA and 17 of 18 (94%) EMMA. Progesterone receptor was positive in 3 of 14 (21%) ECA and 16 of 18 (89%) EMMA. Vimentin was positive in 1 of 14 (7%) ECA, and 9 of 18 (50%) EMA, with median and range of 0 (0–6), and 1.5 (0–9) respectively. CONCLUSION: A panel of immunohistochemical markers including MUC1, p16, ER, PR, and vimentin is recommended, when there is morphological and clinical doubt as to the primary site of endocervical or endometrial origin

Maturation of the functional mouse CRES amyloid from globular form

The epididymal lumen contains a complex cystatin-rich nonpathological amyloid matrix with putative roles in sperm maturation and sperm protection. Given our growing understanding for the biological function of this and other functional amyloids, the problem still remains: how functional amyloids assemble including their initial transition to early oligomeric forms. To examine this, we developed a protocol for the purification of nondenatured mouse CRES, a component of the epididymal amyloid matrix, allowing us to examine its assembly to amyloid under conditions that may mimic those in vivo. Herein we use X-ray crystallography, solution-state NMR, and solid-state NMR to follow at the atomic level the assembly of the CRES amyloidogenic precursor as it progressed from monomeric folded protein to an advanced amyloid. We show the CRES monomer has a typical cystatin fold that assembles into highly branched amyloid matrices, comparable to those in vivo, by forming β-sheet assemblies that our data suggest occur via two distinct mechanisms: a unique conformational switch of a highly flexible disulfide-anchored loop to a rigid β-strand and by traditional cystatin domain swapping. Our results provide key insight into our understanding of functional amyloid assembly by revealing the earliest structural transitions from monomer to oligomer and by showing that some functional amyloid structures may be built by multiple and distinctive assembly mechanisms

Towards a new phenotype for tick resistance in beef and dairy cattle:a review

About 80% of the world's cattle are affected by ticks and tick-borne diseases, both of which cause significant production losses. Cattle host resistance to ticks is the most important factor affecting the economics of tick control, but it is largely neglected in tick-control programs due to technical difficulties and costs associated with identifying individual-animal variation in resistance. The present paper reviews the scientific literature to identify factors affecting resistance of cattle to ticks and the biological mechanisms of host tick resistance, to develop alternative phenotype(s) for tick resistance. If new cost-effective phenotype(s) can be developed and validated, then tick resistance of cattle could be genetically improved using genomic selection, and incorporated into breeding objectives to simultaneously improve cattle productive attributes and tick resistance. The phenotype(s) could also be used to improve tick control by using cattle management. On the basis of the present review, it is recommended that three possible phenotypes (haemolytic analysis measures of skin hypersensitivity reactions simplified artificial tick infestations) be further developed to determine their practical feasibility for consistently, cost-effectively and reliably measuring cattle tick resistance in thousands of individual animals in commercial and smallholder farmer herds in tropical and subtropical areas globally. During evaluation of these potential new phenotypes, additional measurements should be included to determine the possibility of developing a volatile-based resistance phenotype, to simultaneously improve cattle resistance to both ticks and biting flies. Because the current measurements of volatile chemistry do not satisfy the requirements of a simple, cost-effective phenotype for use in commercial cattle herds, consideration should also be given to inclusion of potentially simpler measures to enable indirect genetic selection for volatile-based resistance to ticks

Test item priorities for a screening tool to identify cognitive-communication disorder after right hemisphere stroke

202303 bckwAccepted ManuscriptOthersThe Prince Charles Hospital Foundation Building Innovation and Capacity GrantPublishe