Unrecognized pretransplant and donor‐derived cryptococcal disease in organ transplant recipients.

BACKGROUND: Cryptococcosis occurring ≤30 days after transplantation is an unusual event, and its characteristics are not known. METHODS: Patients included 175 solid-organ transplant (SOT) recipients with cryptococcosis in a multicenter cohort. Very early-onset and late-onset cryptococcosis were defined as disease occurring ≤30 days or >30 days after transplantation, respectively. RESULTS: Very early-onset disease developed in 9 (5%) of the 175 patients at a mean of 5.7 days after transplantation. Overall, 55.6% (5 of 9) of the patients with very early-onset disease versus 25.9% (43 of 166) of the patients with late-onset disease were liver transplant recipients (P = .05). Very early cases were more likely to present with disease at unusual locations, including transplanted allograft and surgical fossa/site infections (55.6% vs 7.2%; P < .001). Two very early cases with onset on day 1 after transplantation (in a liver transplant recipient with Cryptococcus isolated from the lung and a heart transplant recipient with fungemia) likely were the result of undetected pretransplant disease. An additional 5 cases involving the allograft or surgical sites were likely the result of donor‐acquired infection. CONCLUSIONS: A subset of SOT recipients with cryptococcosis present very early after transplantation with disease that appears to occur preferentially in liver transplant recipients and involves unusual sites, such as the transplanted organ or the surgical site. These patients may have unrecognized pretransplant or donor-derived cryptococcosis.

Myosin VIIA, important for human auditory function, is necessary for Drosophila auditory organ development.

BACKGROUND: Myosin VIIA (MyoVIIA) is an unconventional myosin necessary for vertebrate audition [1]-[5]. Human auditory transduction occurs in sensory hair cells with a staircase-like arrangement of apical protrusions called stereocilia. In these hair cells, MyoVIIA maintains stereocilia organization [6]. Severe mutations in the Drosophila MyoVIIA orthologue, crinkled (ck), are semi-lethal [7] and lead to deafness by disrupting antennal auditory organ (Johnston's Organ, JO) organization [8]. ck/MyoVIIA mutations result in apical detachment of auditory transduction units (scolopidia) from the cuticle that transmits antennal vibrations as mechanical stimuli to JO. PRINCIPAL FINDINGS: Using flies expressing GFP-tagged NompA, a protein required for auditory organ organization in Drosophila, we examined the role of ck/MyoVIIA in JO development and maintenance through confocal microscopy and extracellular electrophysiology. Here we show that ck/MyoVIIA is necessary early in the developing antenna for initial apical attachment of the scolopidia to the articulating joint. ck/MyoVIIA is also necessary to maintain scolopidial attachment throughout adulthood. Moreover, in the adult JO, ck/MyoVIIA genetically interacts with the non-muscle myosin II (through its regulatory light chain protein and the myosin binding subunit of myosin II phosphatase). Such genetic interactions have not previously been observed in scolopidia. These factors are therefore candidates for modulating MyoVIIA activity in vertebrates. CONCLUSIONS: Our findings indicate that MyoVIIA plays evolutionarily conserved roles in auditory organ development and maintenance in invertebrates and vertebrates, enhancing our understanding of auditory organ development and function, as well as providing significant clues for future research.

Gene expression disruptions of organism versus organ in Drosophila species hybrids.

Hybrid dysfunctions, such as sterility, may result in part from disruptions in the regulation of gene expression. Studies of hybrids within the Drosophila simulans clade have reported genes expressed above or below the expression observed in their parent species, and such misexpression is associated with male sterility in multigenerational backcross hybrids. However, these studies often examined whole bodies rather than testes or had limited replication using less-sensitive but global techniques. Here, we use a new RNA isolation technique to re-examine hybrid gene expression disruptions in both testes and whole bodies from single Drosophila males by real-time quantitative RT-PCR. We find two early-spermatogenesis transcripts are underexpressed in hybrid whole-bodies but not in assays of testes alone, while two late-spermatogenesis transcripts seem to be underexpressed in both whole-bodies and testes alone. Although the number of transcripts surveyed is limited, these results provide some support for a previous hypothesis that the spermatogenesis pathway in these sterile hybrids may be disrupted sometime after the expression of the early meiotic arrest genes.

Selected Works from Character Pieces in the 19th - Early 20th Centuries

During the Romantic Era, the character piece flourished and became one of the most important genres. Even though character pieces existed as early as the eighteenth century, it was not until the nineteenth century that Romantic Era literary figures discovered that music was as powerful as any other artistic medium in expressing unspeakable emotions. The character piece allowed composers to express a definite mood, a programmatic idea, or a pictorial association. Character pieces often have titles that suggest briehess or casualness, such as a Beethoven Bagatelle, a Schubert Impromptu or Moment musicaux. Others have expressive programmatic titles, such as Schumann's Kreisleriana and Liszt's Apres une lecture de Dante. Ths dissertation was based on selected works from the nineteenth century and early-twentieth century in order to demonstrate the great variety of musical thought and stylistic development. I have examined composers from different countries and of different nationalities to establish what and how they contributed to the remarkable diversity in this genre. The selected works allowed for very personal programs. These concerts, in addition to being good combinations of pieces, are representative of the genre. The first program consisted of Chopin's Preludes, Op. 28; three pieces from Debussy7s Images Books I and 11; and Liszt7s Apres une lecture de Dante. The second program included seven of Beethoven's Bagatelles, Op. 33; Schumann's Kinderscenen, Op. 15; Poulenc's Mouvements perpetuels and Intermezzo in A-jlat Major; Faure7s Nocturne in B Major, Op. 33, No. 2 and Impromptu No. 2 in F Minor; three of Mompou's Canciones y Danzas; four of Villa-Lobos Prole do bebe Suite No. 1; and Albkniz's Navarra. The third and final program comprised four selections from Rachrnaninoff s Moment musicaux, Op. 16; five pieces from Grieg's Lyric Pieces; and Arensky7s Suite No. 1 for Two Pianos and Suite No. 2 for Two Pianos. I wanted to bring out nuances specific to the individual composers and show how their character pieces helped in shaping the Romantic Era. Even in the twenty-first century, an era of highly specialized musical tastes, the popularity and accessibility of character pieces stand out.

The role of B cells in solid organ transplantation.

The role of antibodies in chronic injury to organ transplants has been suggested for many years, but recently emphasized by new data. We have observed that when immunosuppressive potency decreases either by intentional weaning of maintenance agents or due to homeostatic repopulation after immune cell depletion, the threshold of B cell activation may be lowered. In human transplant recipients the result may be donor-specific antibody, C4d+ injury, and chronic rejection. This scenario has precise parallels in a rhesus monkey renal allograft model in which T cells are depleted with CD3 immunotoxin, or in a CD52-T cell transgenic mouse model using alemtuzumab to deplete T cells. Such animal models may be useful for the testing of therapeutic strategies to prevent DSA. We agree with others who suggest that weaning of immunosuppression may place transplant recipients at risk of chronic antibody-mediated rejection, and that strategies to prevent this scenario are needed if we are to improve long-term graft and patient outcomes in transplantation. We believe that animal models will play a crucial role in defining the pathophysiology of antibody-mediated rejection and in developing effective therapies to prevent graft injury. Two such animal models are described herein.

Primary vascularization of the graft determines the immunodominance of murine minor H antigens during organ transplantation.

Grafts can be rejected even when matched for MHC because of differences in the minor histocompatibility Ags (mH-Ags). H4- and H60-derived epitopes are known as immunodominant mH-Ags in H2(b)-compatible BALB.B to C57BL/6 transplantation settings. Although multiple explanations have been provided to explain immunodominance of Ags, the role of vascularization of the graft is yet to be determined. In this study, we used heart (vascularized) and skin (nonvascularized) transplantations to determine the role of primary vascularization of the graft. A higher IFN-γ response toward H60 peptide occurs in heart recipients. In contrast, a higher IFN-γ response was generated against H4 peptide in skin transplant recipients. Peptide-loaded tetramer staining revealed a distinct antigenic hierarchy between heart and skin transplantation: H60-specific CD8(+) T cells were the most abundant after heart transplantation, whereas H4-specific CD8(+) T cells were more abundant after skin graft. Neither the tissue-specific distribution of mH-Ags nor the draining lymph node-derived dendritic cells correlated with the observed immunodominance. Interestingly, non-primarily vascularized cardiac allografts mimicked skin grafts in the observed immunodominance, and H60 immunodominance was observed in primarily vascularized skin grafts. However, T cell depletion from the BALB.B donor prior to cardiac allograft induces H4 immunodominance in vascularized cardiac allograft. Collectively, our data suggest that immediate transmigration of donor T cells via primary vascularization is responsible for the immunodominance of H60 mH-Ag in organ and tissue transplantation.

THE PIANO MUSIC OF ROBERT SCHUMANN (1810-1856) AND JOHANNES BRAHMS (1833- 1897): A SURVEY OF CONCERTI, VARIATIONS, AND CHARACTER PIECES

Robert Schumann (1810-1856) and Johannes Brahms (1833-1897), in some ways Robert Schumann's artistic descendant, are the most important and representative German piano composers during the Romantic period. Schumann was already a mature and established musician in 1853 when he first met the young Brahms and recognized his talents, an encounter that had a long-lasting affect on the lives and careers of both men. After Schumann’s mental breakdown and death, Brahms maintained his admiration of Schumann’s music and preserved an intimate relationship with Clara Schumann. In spite of the personal and musical closeness of the two men, Schumann’s music is stylistically distinct from that of Brahms. Brahms followed traditions from Baroque and Classical music, and avoided using images and expressive titles in his music. Brahms extraordinarily intermingled earlier musical forms with multicolored tones of German Romanticism. In contrast, Schumann saw himself as a radical composer devoted to personal emotionalism and spontaneity. He favored programmatic titles for his character pieces and extra-musical references in his music. While developing their own musical styles as German Romantic composers, Schumann and Brahms both utilized the piano as a resourceful tool for self-realization and compositional development. To investigate and compare the main characteristics of Schumann and Brahms’s piano music, I looked at three genres. First, in the category of the piano concerto, I chose two major Romantic works, Schumann’s A minor concerto and Brahms’s B-flat major concerto. Second, for the category of piano variations I included two sets by Brahms because the variation framework was such an important vehicle for him to express his musical thoughts. Schumann’s unique motivic approach to variation is displayed vividly in his character-piece cycle Carnaval. Third, the category of the character piece, perhaps the favorite medium of Romantic expression at the piano, is shown by Schumann’s Papillons and Brahms’s sets of pieces Op.118 and Op.119. This performance dissertation consists of three recitals performed in the Gildenhorn Recital Hall at the University of Maryland, College Park. These recitals are documented on compact disc recordings that are housed within the University of Maryland Library System.

SELECTED CHARACTER PIECES OF FRÉDÉRIC CHOPIN (1810-1849), FRANZ LISZT (1811-1886) AND JOHANNES BRAHMS (1833-1897)

During the 19th century, Frédéric Chopin (1810-1849), Franz Liszt (1811- 1886), and Johannes Brahms (1833-1897) were among the most recognized composers of character pieces. Their compositions have been considered a significant milestone in piano literature. Frédéric Chopin (1810-1849) did not give descriptive titles to his character pieces. He grouped them into several genres such as Mazurkas, Polonaises. His Mazurkas and Polonaises are influenced by Polish dance music and inspired by the polish national idiom. Franz Liszt (1811-1886) was influenced in many ways by Chopin, and adopted Chopin’s lyricism, melodic style, and tempo rubato. However, Liszt frequently drew on non-musical subjects (e.g., art, literature) for inspiration. “Harmonies poétiques et religieuses” and “Années de pèlerinage” are especially representative of character pieces in which poetic and pictorial imagination are reflected. Johannes Brahms (1833-1897) was a conservative traditionalist, synthesizing Romantic expression and Classical tradition remarkably well. Like Chopin, Brahms avoided using programmatic titles for his works. The titles of Brahms’ short character pieces are often taken from traditional lyrical or dramatic genres such as ballade, rhapsody and scherzo. Because of his conservatism, Brahms was considered the main rival of Liszt in the Romantic Period. Brahms character pieces in his third period (e.g., Scherzo Op.4, Ballades of Op.10, and Rhapsodies of Op.79) are concise and focused. The form of Brahms’ character pieces is mostly simple ternary (ABA), and his style is introspective and lyrical. Through this recording project, I was able to get a better understanding of the styles of Chopin, Brahms and Liszt through their character pieces. This recording dissertation consists of two CDs recorded in the Dekelboum Concert Hall at the University of Maryland, College Park. These recordings are documented on compact disc recordings that are housed within the University of Maryland Library System.

Organ damage in Atlantic herring larvae as a result of ocean acidification

The dissolution of anthropogenically emitted excess carbon dioxide lowers the pH of the world's ocean water. The larvae of mass spawning marine fishes may be particularly vulnerable to such ocean acidification (OA), yet the generality of earlier results is unclear. Here we show the detrimental effects of OA on the development of a commercially important fish species, the Atlantic herring (Clupea harengus). Larvae were reared at three levels of CO2: today (0.0385 kPa), end of next century (0.183 kPa), and a coastal upwelling scenario (0.426 kPa), under near-natural conditions in large outdoor tanks. Exposure to elevated CO2 levels resulted in stunted growth and development, decreased condition, and severe tissue damage in many organs, with the degree of damage increasing with CO2 concentration. This complements earlier studies of OA on Atlantic cod larvae that revealed similar organ damage but at increased growth rates and no effect on condition.

A puzzle with many pieces: the genetic structure and diversity of Phaeocystis antarctica Karsten (Prymnesiophyta)

Strong ocean current systems characterize the Southern Ocean. The genetic structure of marine phytoplankton species is believed to depend mainly on currents. Genetic estimates of the relatedness of populations of phytoplankton species therefore should provide a proxy showing to what extent different geographic regions are interconnected by the ocean current systems. In this study, spatial and temporal patterns of genetic diversity were studied in the circumpolar prymnesiophyte Phaeocystis antarctica Karsten using seven nuclear microsatellite loci. Analyses were conducted for 86 P. antarctica isolates sampled around the Antarctic continent between 1982 and2007. The resultsrevealed highgenetic diversity without singlegenotypes recurringeven amongisolateswithin a bloom or originating from the same bucket of water. Populations of P. antarctica were significantly differentiated among the oceanic regions. However, some geographically distant populations were more closely related to each other than they were to other geographically close populations. Temporal haplotype turnover within regions was also suggested by the multilocus fingerprints. Our data suggest that even within blooms of P. antarctica genetic diversity and population sizes are large but exchange between different regions canbe limited. Positive and significant inbreeding coefficients hint at further regional substructure of populations, suggestingthat patches, once isolated from one another, may not reconnect. These data emphasize that even for planktonic species in a marine ecosystem that is influenced by strong currents, significant breaks in geneflow may occur.