Alternate forms of the PolII transcription initiation machinery have been proposed to play a role in selective activation of cell-type-specific gene expression programs during cellular differentiation. The cannonball(can) gene of Drosophila encodes a homolog of a TBP-associated factor (dTAF5) protein expressed only in spermatocytes, where it is required for normal transcription of genes required for spermatid differentiation. We show that Drosophila primary spermatocytes also express four additional tissue-specific TAFs: nht (homolog of dTAF4), mia (homolog of dTAF6), sa (homolog of dTAF8) and rye (homolog of dTAF12). Mutations in nht, mia and sa have similar effects in primary spermatocytes on transcription of several target genes involved in spermatid differentiation, and cause the same phenotypes as mutations in can, blocking both meiotic cell cycle progression and spermatid differentiation. The nht, mia, sa and rye proteins contain histone fold domain dimerization motifs. The nht and rye proteins interact structurally when co-expressed in bacteria, similarly to their generally expressed homologs TAF4 and TAF12,which heterodimerize. Strikingly, the structural interaction is tissue specific: nht did not interact with dTAF12 and dTAF4 did not interact with rye in a bacterial co-expression assay. We propose that the products of the five Drosophila genes encoding testis TAF homologs collaborate in an alternative TAF-containing protein complex to regulate a testis-specific gene expression program in primary spermatocytes required for terminal differentiation of male germ cells.

Alternate forms of the general transcription machinery have been described in several tissues or cell types. However, the role of tissue-specific TBP-associated factors (TAF II s) and other tissue-specific transcription components in regulating differential gene expression during development was not clear. Here we show that the cannonball gene of Drosophila encodes a cell type-specific homolog of a more ubiquitously expressed component of the general transcription factor TFIID. cannonball is required in vivo for high level transcription of a set of stage-and tissue-specific target genes during male gametogenesis. Regulation of transcription by cannonball is absolutely required for spermatogenesis, as null mutations block meiotic cell cycle progression and result in a complete failure of spermatid differentiation. Our results demonstrate that cell type-specific TAF II s play an important role in developmental regulation of gene expression.

Summary Ictal respiratory dysfunction occurs in patients with epilepsy and may contribute to sudden unexplained death in epilepsy (SUDEP). Fluoxetine reverses respiratory arrest in a mouse model of epilepsy, suggesting that selective serotonin reuptake inhibitors (SSRIs) may reduce ictal respiratory dysfunction. Video–electroencephalography (EEG) and pulse oximetry data from 496 seizures in 73 consecutive patients with partial epilepsy was reviewed, including 87 seizures in 16 patients taking SSRIs (SSRI+) and 409 seizures in 57 patients not taking SSRIs (SSRI−). The proportion of ictal‐related oxygen desaturation <85% with partial seizures without secondary convulsions in SSRI+ patients was reduced relative to SSRI− patients (p = 0.011). There was no statistically significant difference in ictal oxygen desaturation for secondarily generalized convulsions. SSRIs are associated with reduced likelihood of ictal oxygen desaturation in patients with partial seizures.

SUMMARYPurpose: The rate of sudden unexpected death in epilepsy (SUDEP) approaches 9 per 1,000 patient-years in patients with refractory epilepsy. Respiratory causes are implicated in SUDEP. We reported that ictal hypoxemia occurs in one-third of seizures in localization-related epilepsy. We now report on respiratory changes in the ictal/ postictal period including changes in end-tidal CO 2 (ETCO 2 ) that correlate directly with alveolar CO 2 , allowing a precise evaluation of seizure-related respiratory disturbances. Methods: One hundred eighty-seven seizures were recorded in 33 patients with localization-related epilepsy, with or without secondarily generalized convulsions, undergoing video-electroencephalography (EEG) telemetry with recording of respiratory data. Results: The ictal/postictal ETCO 2 increase from baseline was 14 ± 11 mm Hg (11, )1 to 50) [mean ± standard deviation (SD) (median, range)]. ETCO 2 peak was at or above 50 mm Hg with 35 of 94 seizures, 60 mm Hg with 15, and 70 mm Hg with five seizures. Eleven of the 33 patients had seizures with ETCO 2 elevation above 50 mm Hg. The duration of ictal/postictal ETCO 2 increase above baseline was 424 ± 807 s (154, 4 to 6225). The duration of ictal apnea was 49 ± 46 s (31, 6-222); most ictal apneic events were central. Oxygen desaturation to 60% or less occurred with 10 seizures, including five that did not progress to generalized convulsions. Respiratory rate and amplitude increased postictally. The peak ictal ETCO 2 change and duration of change were not associated with apnea duration or seizure duration. Peak ETCO 2 change was significantly associated with contralateral seizure spread. Conclusions: Severe and prolonged increases in ETCO 2 occur with seizures. Postictally, respiratory effort is not impaired. Ictally triggered ventilation-perfusion inequality from pulmonary shunting or transient neurogenic pulmonary edema may account for these findings. KEY WORDS: Sudden unexpected death in epilepsy, Hypercapnia, Hypoxemia, Seizure, Localization-related epilepsy.Sudden unexpected death in epilepsy (SUDEP) has an incidence of 0.09-9 per 1,000 patient years, with the highest incidence in patients with refractory epilepsy (Tomson et al., 2008). Both cardiac and respiratory mechanisms are implicated in SUDEP (Surges et al., 2009). Seizures are associated with hypoxemia (Hewertson et al., 1996;Nashef et al., 1996;Blum et al., 2000;Bateman et al., 2008). We demonstrated a high incidence of ictal/postictal hypoxemia in patients with localization-related epilepsy undergoing inpatient video-EEG telemetry (VET) (Bateman et al., 2008). Ictal hypoxemia may be severe and prolonged in partial-onset seizures (Bateman et al., 2008). Respiratory changes in the ictal and postictal period are not well characterized. End-tidal CO 2 (ETCO 2 ) measurements correlate directly with changes in alveolar P CO2 and may, therefore, allow a precise evaluation of seizure-related respiratory disturbances. In contrast, oxygen saturation (SaO 2 ) recorded by digital pulse oximetry has ...

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