Little is known about the molecular processes that govern female gametophyte (FG) development and function, and few FG-expressed genes have been identified. We report the identification and phenotypic analysis of 31 new FG mutants in Arabidopsis. These mutants have defects throughout development, indicating that FG-expressed genes govern essentially every step of FG development. To identify genes involved in cell death during FG development, we analyzed this mutant collection for lines with cell death defects. From this analysis, we identified one mutant, gfa2 , with a defect in synergid cell death. Additionally, the gfa2 mutant has a defect in fusion of the polar nuclei. We isolated the GFA2 gene and show that it encodes a J-domain-containing protein. Of the J-domain-containing proteins in Saccharomyces cerevisiae (budding yeast), GFA2 is most similar to Mdj1p, which functions as a chaperone in the mitochondrial matrix. GFA2 is targeted to mitochondria in Arabidopsis and partially complements a yeast mdj1 mutant, suggesting that GFA2 is the Arabidopsis ortholog of yeast Mdj1p. These data suggest a role for mitochondria in cell death in plants.

Nearly half of all heart failure (HF) patients have diastolic HF (DHF) or clinical HF with normal or near-normal left ventricular ejection fraction (LVEF). Although the terminology has not been clearly defined, it is increasingly being referred to as HF with preserved ejection fraction (HFPEF). The prevalence of HFPEF increases with age, especially among older women. Identifying HFPEF is important because the etiology, pathogenesis, prognosis, and optimal management may differ from that for systolic HF (SHF) or HF with reduced ejection fraction. The clinical presentation of HF is similar for both SHF and HFPEF. As in SHF, HFPEF is a clinical diagnosis. Once a clinical diagnosis of HF has been made, the presence of HFPEF can be established by confirming a normal or near-normal LVEF, often by an echocardiogram. HFPEF is often associated with a history of hypertension, concentric left ventricular hypertrophy, vascular stiffness, and left ventricular diastolic dysfunction. As in SHF, HFPEF is also associated with poor outcomes. While therapies with angiotensin-converting enzyme inhibitors and beta-blockers improve outcomes in SHF, there is currently no such evidence of their benefits in older HFPEF patients. In this review recent advances in the diagnosis and management of HFPEF in older adults are discussed.

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Low-level lead (Pb) exposure is a risk factor for learning disabilities, attention deficit hyperactivity disorder (ADHD), and other neurological dysfunction. It is not known how Pb produces these behavioral deficits, but low-level exposure during development is associated with auditory temporal processing deficits in an avian model, while hearing thresholds remain normal. Similar auditory processing deficits are found in children with learning disabilities and ADHD. To identify cellular changes underlying this functional deficit, Pb-induced alterations of neurons and glia within the mammalian auditory brainstem nuclei were quantified in control and Pb-exposed mice at postnatal day 21 by using immunohistochemistry, Western blotting, and 2D gel electrophoresis. Pb-treated mice were exposed to either 0.1 mM (low) or 2 mM (high) Pb acetate throughout gestation and through 21 days postnatally. Pb exposure results in little change in glial proteins such as glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), or F4/80 as determined by Western blot analysis and immunohistochemistry. In contrast, Pb exposure alters neuronal structural proteins by inducing increased phosphorylation of both the medium (NFM) and high-weight (NFH) forms of neurofilament within auditory brainstem nuclei. Axons immunolabeled for neurofilament protein show neuritic beading following Pb exposure both in vivo and in vitro, suggesting that Pb exposure also impairs axonal transport. Functional assessment shows no significant loss of peripheral function, but does reveal impairments in brainstem conduction time and temporal processing within the brainstem. These results provide evidence that Pb exposure during development alters axonal structure and function within brainstem auditory nuclei.