Twelve genes of the PIN family in rice were analyzed for gene and protein structures and an evolutionary relationship with reported AtPINs in Arabidopsis. Four members of PIN1 (designated as OsPIN1a-d), one gene paired with AtPIN2 (OsPIN2), three members of PIN5 (OsPIN5a-c), one gene paired with AtPIN8 (OsPIN8), and three monocot-specific PINs (OsPIN9, OsPIN10a, and b) were identified from the phylogenetic analysis. Tissue-specific expression patterns of nine PIN genes among them were investigated using RT-PCR and GUS reporter. The wide variations in the expression domain in different tissues of the PIN genes were observed. In general, PIN genes are up-regulated by exogenous auxin, while different responses of different PIN genes to other hormones were found.

Both Xp11 translocation renal cell carcinomas and the corresponding mesenchymal neoplasms are characterized by a variety of gene fusions involving TFE3. It has been known that tumors with different gene fusions may have different clinicopathologic features; however, further in-depth investigations of subtyping Xp11 translocation-associated cancers are needed in order to explore more meaningful clinicopathologic correlations. A total of 22 unusual cases of Xp11 translocation-associated cancers were selected for the current study; 20 cases were further analyzed by RNA sequencing to explore their TFE3 gene fusion partners. RNA sequencing identified 17 of 20 cases (85%) with TFE3-associated gene fusions, including 4 ASPSCR1/ASPL-TFE3, 3 PRCC-TFE3, 3 SFPQ/PSF-TFE3, 1 NONO-TFE3, 4 MED15-TFE3, 1 MATR3-TFE3, and 1 FUBP1-TFE3. The results have been verified by fusion fluorescence in situ hybridization (FISH) assays or reverse transcriptase polymerase chain reaction (RT-PCR). The remaining 2 cases with specific pathologic features highly suggestive of MED15-TFE3 renal cell carcinoma were identified by fusion FISH assay. We provide the detailed morphologic and immunophenotypic description of the MED15-TFE3 renal cell carcinomas, which frequently demonstrate extensively cystic architecture, similar to multilocular cystic renal neoplasm of low malignant potential, and expressed cathepsin K and melanotic biomarker Melan A. This is the first time to correlate the MED15-TFE3 renal cell carcinoma with specific clinicopathologic features. We also report the first case of the corresponding mesenchymal neoplasm with MED15-TFE3 gene fusion. Additional novel TFE3 gene fusion partners, MATR3 and FUBP1, were identified. Cases with ASPSCR1-TFE3, SFPQ-TFE3, PRCC-TFE3, and NONO-TFE3 gene fusion showed a wide variability in morphologic features, including invasive tubulopapillary pattern simulating collecting duct carcinoma, extensive calcification and ossification, and overlapping and high columnar cells with nuclear grooves mimicking tall cell variant of papillary thyroid carcinoma. Furthermore, we respectively evaluated the ability of TFE3 immunohistochemistry, TFE3 FISH, RT-PCR, and RNA sequencing to subclassify Xp11 translocation-associated cancers. In summary, our study expands the list of TFE3 gene fusion partners and the clinicopathologic features of Xp11 translocation-associated cancers, and highlights the importance of subtyping Xp11 translocation-associated cancers combining morphology, immunohistochemistry, and multiple molecular techniques.

TP53-induced glycolysis and apoptosis regulator (TIGAR) inhibits glycolysis and increases the flow of pentose phosphate pathway (PPP), which generates NADPH and pentose. We hypothesized that TIGAR plays a neuroprotective role in brain ischemia as neurons do not rely on glycolysis but are vulnerable to oxidative stress. We found that TIGAR was highly expressed in brain neurons and was rapidly upregulated in response to ischemia/reperfusion insult in a TP53-independent manner. Overexpression of TIGAR in normal mice with lentivirus reduced ischemic neuronal injury, whereas lentivirus-mediated TIGAR knockdown aggravated it. In cultured primary neurons, increasing TIGAR expression reduced oxygen and glucose deprivation (OGD)/reoxygenation-induced injury, whereas decreasing its expression worsened the injury. The glucose 6-phosphate dehydrogenase was upregulated in mouse and cellular models of stroke, and its upregulation was further enhanced by overexpression of TIGAR. Supplementation of NADPH also reduced ischemia/reperfusion brain injury and alleviated TIGAR knockdown-induced aggravation of ischemic injury. In animal and cellular stroke models, ischemia/ reperfusion increased mitochondrial localization of TIGAR. OGD/reoxygenation-induced elevation of ROS, reduction of GSH, dysfunction of mitochondria, and activation of caspase-3 were rescued by overexpression of TIGAR or supplementation of NADPH, while knockdown of TIGAR aggravated these changes. Together, our results show that TIGAR protects ischemic brain injury via enhancing PPP flux and preserving mitochondria function, and thus may be a valuable therapeutic target for ischemic brain injury.

Primary high-grade neuroendocrine carcinoma of the esophagus (HNCE) is rare and poorly understood. In this study, we aimed at delineating the clinicopathologic and immunohistochemical characteristics of HNCE diagnosed on the basis of the World Health Organization criteria for pulmonary neuroendocrine carcinomas. We identified 42 (3.8%) consecutive resection cases of HNCE among 1105 esophageal cancers over a 7-year period. Patients' mean age was 62 years (range, 47 to 79 y) with a male to female ratio of 3.7. Dysphagia was present in 79% of patients and tobacco abuse in 50%. Most tumors were centered in the middle (52%) or lower (36%) esophagus; 48% were ulcerated and 31% exophytic. All tumors were sharply demarcated with a pushing border in either solid sheet (83%) or nodular (17%) growth patterns. Pure HNCE was found in 57%, and the remainder also exhibited small components of squamous cell carcinoma (SqCC) or glandular, signet ring cell differentiations. SqCC in situ was present in 50%. Most tumors (88%) were the small cell type with pure oat-like cells in 52%, and the larger spindled, anaplastic, and giant cells were common. Tumor crush artifact (98%) and the Azzopardi effect (88%) were widespread. Extensive lymphovascular (50%) and perineural (33%) invasion and metastasis to regional (48%) and abdominal celiac lymph nodes (29%) were observed. Neoplastic cells were immunoreactive to synaptophysin (100%), CD56 (93%), chromogranin A (67%), p63 (55%), TTF-1 (71%), CK8/18 (90%), CD117 (86%), HER2 (16%), and p16 (84%) antibodies. The 5-year survival rate was 25%, similar to that of SqCC. Lymphovascular and perineural invasion was associated with a worse prognosis.

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