Infection by HIV-1 involves the fusion of viral and cellular membranes with subsequent transfer of viral genetic material into the cell. The HIV-1 envelope glycoprotein that mediates fusion consists of the surface subunit gp120 and the transmembrane subunit gp41. gp120 directs virion attachment to the cell-surface receptors, and gp41 then promotes viral-cell membrane fusion. A soluble, ␣-helical, trimeric complex within gp41 composed of N-terminal and C-terminal extraviral segments has been proposed to represent the core of the fusion-active conformation of the HIV-1 envelope. A thermostable subdomain denoted N34(L6)C28 can be formed by the N-34 and C-28 peptides connected by a f lexible linker in place of the disulfide-bonded loop region. Threedimensional structure of N34(L6)C28 reveals that three molecules fold into a six-stranded helical bundle. Three Nterminal helices within the bundle form a central, parallel, trimeric coiled coil, whereas three C-terminal helices pack in the reverse direction into three hydrophobic grooves on the surface of the N-terminal trimer. This thermostable subdomain displays the salient features of the core structure of the isolated gp41 subunit and thus provides a possible target for therapeutics designed selectively to block HIV-1 entry.

The International Society of Urological Pathology 2012 Consensus Conference made recommendations regarding classification, prognostic factors, staging, and immunohistochemical and molecular assessment of adult renal tumors. Issues relating to prognostic factors were coordinated by a workgroup who identified tumor morphotype, sarcomatoid/rhabdoid differentiation, tumor necrosis, grading, and microvascular invasion as potential prognostic parameters. There was consensus that the main morphotypes of renal cell carcinoma (RCC) were of prognostic significance, that subtyping of papillary RCC (types 1 and 2) provided additional prognostic information, and that clear cell tubulopapillary RCC was associated with a more favorable outcome. For tumors showing sarcomatoid or rhabdoid differentiation, there was consensus that a minimum proportion of tumor was not required for diagnostic purposes. It was also agreed upon that the underlying subtype of carcinoma should be reported. For sarcomatoid carcinoma, it was further agreed upon that if the underlying carcinoma subtype was absent the tumor should be classified as a grade 4 unclassified carcinoma with a sarcomatoid component. Tumor necrosis was considered to have prognostic significance, with assessment based on macroscopic and microscopic examination of the tumor. It was recommended that for clear cell RCC the amount of necrosis should be quantified. There was consensus that nucleolar prominence defined grades 1 to 3 of clear cell and papillary RCCs, whereas extreme nuclear pleomorphism or sarcomatoid and/or rhabdoid differentiation defined grade 4 tumors. It was agreed upon that chromophobe RCC should not be graded. There was consensus that microvascular invasion should not be included as a staging criterion for RCC.

A challenge in the treatment of Staphylococcus aureus infections is the high prevalence of methicillin-resistant S. aureus (MRSA) strains and the formation of non-growing, dormant 'persister' subpopulations that exhibit high levels of tolerance to antibiotics and have a role in chronic or recurrent infections. As conventional antibiotics are not effective in the treatment of infections caused by such bacteria, novel antibacterial therapeutics are urgently required. Here we used a Caenorhabditis elegans-MRSA infection screen to identify two synthetic retinoids, CD437 and CD1530, which kill both growing and persister MRSA cells by disrupting lipid bilayers. CD437 and CD1530 exhibit high killing rates, synergism with gentamicin, and a low probability of resistance selection. All-atom molecular dynamics simulations demonstrated that the ability of retinoids to penetrate and embed in lipid bilayers correlates with their bactericidal ability. An analogue of CD437 was found to retain anti-persister activity and show an improved cytotoxicity profile. Both CD437 and this analogue, alone or in combination with gentamicin, exhibit considerable efficacy in a mouse model of chronic MRSA infection. With further development and optimization, synthetic retinoids have the potential to become a new class of antimicrobials for the treatment of Gram-positive bacterial infections that are currently difficult to cure.

PAX 8 is a transcription factor that is essential for embryonic development of the kidney, Mü llerian organs, and thyroid. It may also have a role in tumor development in these organs. The diagnostic utility of PAX 8 has not been comprehensively studied. Formalin-fixed, paraffin-embedded tissue samples for non-neoplastic tissues (n ¼ 1601), primary neoplasms (n ¼ 933), and metastatic neoplasms (n ¼ 496) were subjected to PAX 8 immunostain. In non-neoplastic tissues, PAX 8 was consistently noted in glomerular parietal epithelial cells, renal collecting ductal cells, atrophic renal tubular epithelial cells regardless of nephronic segments, and epithelial cells of the endocervix, endometrium, fallopian tube, seminal vesicle, epidydimis, thyroid, pancreatic islet cells, and lymphoid cells. PAX 8 was not seen in the rest of the tissue samples. In primary neoplasms, PAX 8 was expressed by 194 of 240 (89%) renal cell neoplasms, by 238 of 267 (89%) Mü llerian-type neoplasms, by 65 of 65 (100%) thyroid follicular cell neoplasms, by 8 of 8 (100%) nephrogenic adenomas, and by 17 of 17 (100%) lymphomas. Weak focal staining was noted in 5 of 12 (42%) cases of parathyroid hyperplasia/adenoma and in 6 of 17 (35%) well-differentiated neuroendocrine tumors of the pancreas. PAX 8 was not seen in other neoplasms. In metastatic neoplasms, PAX 8 was expressed by 90 of 102 (88%) metastatic renal cell carcinomas, by 57 of 63 metastatic Mü llerian tumors (90%), and by 6 of 6 metastatic papillary thyroid carcinomas (100%). There was also weak focal staining for 1 of 15 metastatic small cell carcinomas and for 1 of 9 metastatic well-differentiated neuroendocrine carcinomas. PAX 8 was not seen in other metastatic neoplasms. It can be successfully identified in routinely processed tissue samples, and its expression is mostly nuclear. PAX 8 expression in nonneoplastic mature tissues is limited to the organs, the embryonic development of which depends on this transcription factor. This tissue/cell-specific expression is maintained during both neoplastic transformation and metastasis. PAX 8 is a sensitive and specific marker for tumors of renal, Mü llerian, or thyroid origin in both primary and metastatic sites.

Laboratories must document successful analytic validation of all immunohistochemical tests before applying to patient specimens. The parameters for cases included in validation sets, including number, expression levels, fixative and processing methods, should take into account intended use and should be sufficient to ensure that the test accurately measures the analyte of interest in specimens tested in that laboratory. Recommendations are also provided for confirming assay performance when there are changes in test methods, reagents, or equipment.

Immunosurveillance of secondary lymphoid organs (SLO) is performed by central memory T cells that recirculate through blood. Resident memory T (Trm) cells remain parked in nonlymphoid tissues and often stably express CD69. We recently identified Trm cells within SLO, but the origin and phenotype of these cells remains unclear. Using parabiosis of "dirty" mice, we found that CD69 expression is insufficient to infer stable residence of SLO Trm cells. Restimulation of nonlymphoid memory CD8 T cells within the skin or mucosa resulted in a substantial increase in bona fide Trm cells specifically within draining lymph nodes. SLO Trm cells derived from emigrants from nonlymphoid tissues and shared some transcriptional and phenotypic signatures associated with nonlymphoid Trm cells. These data indicate that nonlymphoid cells can give rise to SLO Trm cells and suggest vaccination strategies by which memory CD8 T cell immunosurveillance can be regionalized to specific lymph nodes.

Nap-A is superior to TTF-1 in distinguishing primary lung ACA from other carcinomas (except kidney), particularly primary lung small cell carcinoma, and primary thyroid carcinoma. A combination of Nap-A and TTF-1 is useful in the distinction of primary lung ACA (Nap-A(+), TTF-1(+)) from primary lung squamous cell carcinoma (Nap-A(-), TTF-1(-)) and primary lung small cell carcinoma (Nap-A(-), TTF-1(+)).

We report a case of a newborn infant who had simultaneous sialoblastoma and hepatoblastoma tumours at birth. The diagnoses were made on post mortem examination. Both of these are rare tumours in the neonatal period. Pediatr Blood Cancer 2009;52:883–885. © 2009 Wiley‐Liss, Inc.