Screening, Identification and Preliminary Investigation of Target Transporters in Pregnancy Pathologies

Screening, Identification and Preliminary Investigation of Target Transporters in Pregnancy Pathologies. INTRODUCTION: Pre-eclampsia (PE), intrauterine growth restriction (IUGR) and gestational diabetes mellitus (GDM) are major sources of clinical morbidity and mortality in pregnant women worldwide. The mechanisms underlying these gestational diseases are complex and not yet fully understood, but one factor contributing to their development is impaired maternal-fetal nutrient transport. Therefore, we aimed to identify candidate membrane transporters involved in transplacental nutrient transfer associated with PE/IUGR or GDM. METHODS: Using in silico strategies, we analysed various gene expression data sets generated on different platforms focusing on solute carriers, ABC transporters and TRP channels in order to identify transporters that are differently expressed between patients and gestational age-matched controls. These bioinformatic analyses were combined with literature data to define a catalogue of target transporters that could be involved in the development of PE/IUGR or GDM. Transporters of interest were then analysed for gene expression using qRT-PCR in placental tissues of patients and controls. For validating the results on protein and functional level, we started to establish an in vitro assay using freshly isolated primary cytotrophoblast cells polarized on the Transwell® system. RESULTS: Using bioinformatics approaches, we initially identified 37 target membrane proteins which were mainly associated with the transport of amino acids, vitamins, and trace elements. At the current state of analysis, the amino acid transporters SLC7A7, SLC38A2, SLC38A5, and the thiamine transporter SLC19A3 showed significant differences in placental mRNA expression between controls and patients affected by PE and/or IUGR. Subsequent gene expression analysis in our in-house GDM placental tissue bank is still ongoing. CONCLUSIONS: Based on our in silico analyses, literature data and first follow-up in vitro validations, we were able to define potentially interesting candidate transporters implicated in PE/IUGR or GDM. To date, additional newly defined candidate targets are being analysed on mRNA level in PE/IUGR and GDM. Subsequent analyses on protein and functional level will reveal whether these targets could be of diagnostic or therapeutical interest in these pregnancy pathologies.

Placental Uric Acid Transport System: Glucose Transporter 9 (SLC2A9)

Placental Uric Acid Transport System: Glucose Transporter 9 (SLC2A9). INTRODUCTION: Pre-eclampsia, a pregnancy-specific disease, contributes substantially to perinatal morbidity and mortality of both the mother and her child. Pre-eclampsia is often associated with high maternal urate serum levels, which in turn has been shown to play a role in the pathogenesis of this disease. The aim of this study was to investigate the glucose transporter GLUT9-mediated placental uric acid transport system. METHODS: In this study western blot, immunofluorescence techniques as well as a transepithelial transport (Transwell) model were used to assess GLUT9 protein expression and, respectively, uric acid transport activity. Electrophysiological techniques and transmission electron microscopy (TEM) were used to characterize the properties and the structure of GLUT9. RESULTS: Uric acid is transported across a BeWo choriocarcinoma cell monolayer with 530 pmol/min. We could successfully overexpress and for the first time purify the GLUT9b isoform using the Xenopus laevis oocytes expression system. Chloride seems to modulate the urate transport system. TEM revealed that GLUT9b isoform is present as monomer and dimmer in the Xenopus laevis overexpression model. A class average of all the particles allowed us to develop a first model of human GLUT9b structure, which was derived from the published crystal structure of the bacterial homologue of GLUT1-4. CONCLUSIONS: In vitro the “materno-fetal” transport of uric acid is slow indicating that in vivo the fetus might be protected from short-term fluctuations of maternal urate serum levels. The low-resolution structure obtained from TEM validates the proposed homology model regarding the structure of human GLUT9b. In ongoing studies this model is used to perform virtual screening to identify novel modulators of the urate transport system enabling the development of novel therapies in pregnancy complications.

Localization and production of peptide endocannabinoids in the rodent CNS and adrenal medulla.

The endocannabinoid system (ECS) comprises the cannabinoid receptors CB1 and CB2 and their endogenous arachidonic acid-derived agonists 2-arachidonoyl glycerol and anandamide, which play important neuromodulatory roles. Recently, a novel class of negative allosteric CB1 receptor peptide ligands, hemopressin-like peptides derived from alpha hemoglobin, has been described, with yet unknown origin and function in the CNS. Using monoclonal antibodies we now identified the localization of RVD-hemopressin (pepcan-12) and N-terminally extended peptide endocannabinoids (pepcans) in the CNS and determined their neuronal origin. Immunohistochemical analyses in rodents revealed distinctive and specific staining in major groups of noradrenergic neurons, including the locus coeruleus (LC), A1, A5 and A7 neurons, which appear to be major sites of production/release in the CNS. No staining was detected in dopaminergic neurons. Peptidergic axons were seen throughout the brain (notably hippocampus and cerebral cortex) and spinal cord, indicative of anterograde axonal transport of pepcans. Intriguingly, the chromaffin cells in the adrenal medulla were also strongly stained for pepcans. We found specific co-expression of pepcans with galanin, both in the LC and adrenal gland. Using LC-MS/MS, pepcan-12 was only detected in non-perfused brain (∼40 pmol/g), suggesting that in the CNS it is secreted and present in extracellular compartments. In adrenal glands, significantly more pepcan-12 (400-700 pmol/g) was measured in both non-perfused and perfused tissue. Thus, chromaffin cells may be a major production site of pepcan-12 found in blood. These data uncover important areas of peptide endocannabinoid occurrence with exclusive noradrenergic immunohistochemical staining, opening new doors to investigate their potential physiological function in the ECS. This article is part of a Special Issue entitled 'Fluorescent Neuro-Ligands'.

A numerical model for inert gas transport in the lung based on fractal airway morphology

Patients suffering from cystic fibrosis (CF) show thick secretions, mucus plugging and bronchiectasis in bronchial and alveolar ducts. This results in substantial structural changes of the airway morphology and heterogeneous ventilation. Disease progression and treatment effects are monitored by so-called gas washout tests, where the change in concentration of an inert gas is measured over a single or multiple breaths. The result of the tests based on the profile of the measured concentration is a marker for the severity of the ventilation inhomogeneity strongly affected by the airway morphology. However, it is hard to localize underlying obstructions to specific parts of the airways, especially if occurring in the lung periphery. In order to support the analysis of lung function tests (e.g. multi-breath washout), we developed a numerical model of the entire airway tree, coupling a lumped parameter model for the lung ventilation with a 4th-order accurate finite difference model of a 1D advection-diffusion equation for the transport of an inert gas. The boundary conditions for the flow problem comprise the pressure and flow profile at the mouth, which is typically known from clinical washout tests. The natural asymmetry of the lung morphology is approximated by a generic, fractal, asymmetric branching scheme which we applied for the conducting airways. A conducting airway ends when its dimension falls below a predefined limit. A model acinus is then connected to each terminal airway. The morphology of an acinus unit comprises a network of expandable cells. A regional, linear constitutive law describes the pressure-volume relation between the pleural gap and the acinus. The cyclic expansion (breathing) of each acinus unit depends on the resistance of the feeding airway and on the flow resistance and stiffness of the cells themselves. Special care was taken in the development of a conservative numerical scheme for the gas transport across bifurcations, handling spatially and temporally varying advective and diffusive fluxes over a wide range of scales. Implicit time integration was applied to account for the numerical stiffness resulting from the discretized transport equation. Local or regional modification of the airway dimension, resistance or tissue stiffness are introduced to mimic pathological airway restrictions typical for CF. This leads to a more heterogeneous ventilation of the model lung. As a result the concentration in some distal parts of the lung model remains increased for a longer duration. The inert gas concentration at the mouth towards the end of the expirations is composed of gas from regions with very different washout efficiency. This results in a steeper slope of the corresponding part of the washout profile.

Regulation of human trophoblast GLUT1 glucose transporter by insulin-like growth factor I (IGF-I)

Glucose transport to the fetus across the placenta takes place via glucose transporters in the opposing faces of the barrier layer, the microvillous and basal membranes of the syncytiotrophoblast. While basal membrane content of the GLUT1 glucose transporter appears to be the rate-limiting step in transplacental transport, the factors regulating transporter expression and activity are largely unknown. In view of the many studies showing an association between IGF-I and fetal growth, we investigated the effects of IGF-I on placental glucose transport and GLUT1 transporter expression. Treatment of BeWo choriocarcinoma cells with IGF-I increased cellular GLUT1 protein. There was increased basolateral (but not microvillous) uptake of glucose and increased transepithelial transport of glucose across the BeWo monolayer. Primary syncytial cells treated with IGF-I also demonstrated an increase in GLUT1 protein. Term placental explants treated with IGF-I showed an increase in syncytial basal membrane GLUT1 but microvillous membrane GLUT1 was not affected. The placental dual perfusion model was used to assess the effects of fetally perfused IGF-I on transplacental glucose transport and syncytial GLUT1 content. In control perfusions there was a decrease in transplacental glucose transport over the course of the perfusion, whereas in tissues perfused with IGF-I through the fetal circulation there was no change. Syncytial basal membranes from IGF-I perfused tissues showed an increase in GLUT1 content. These results demonstrate that IGF-I, whether acting via microvillous or basal membrane receptors, increases the basal membrane content of GLUT1 and up-regulates basal membrane transport of glucose, leading to increased transepithelial glucose transport. These observations provide a partial explanation for the mechanism by which IGF-I controls nutrient supply in the regulation of fetal growth.

Modeling the formation and aging of secondary organic aerosols during CalNex 2010

Four different literature parameterizations for the formation and evolution of urban secondary organic aerosol (SOA) frequently used in 3-D models are evaluated using a 0-D box model representing the Los Angeles metropolitan region during the California Research at the Nexus of Air Quality and Climate Change (CalNex) 2010 campaign. We constrain the model predictions with measurements from several platforms and compare predictions with particle- and gas-phase observations from the CalNex Pasadena ground site. That site provides a unique opportunity to study aerosol formation close to anthropogenic emission sources with limited recirculation. The model SOA that formed only from the oxidation of VOCs (V-SOA) is insufficient to explain the observed SOA concentrations, even when using SOA parameterizations with multi-generation oxidation that produce much higher yields than have been observed in chamber experiments, or when increasing yields to their upper limit estimates accounting for recently reported losses of vapors to chamber walls. The Community Multiscale Air Quality (WRF-CMAQ) model (version 5.0.1) provides excellent predictions of secondary inorganic particle species but underestimates the observed SOA mass by a factor of 25 when an older VOC-only parameterization is used, which is consistent with many previous model–measurement comparisons for pre-2007 anthropogenic SOA modules in urban areas. Including SOA from primary semi-volatile and intermediate-volatility organic compounds (P-S/IVOCs) following the parameterizations of Robinson et al. (2007), Grieshop et al. (2009), or Pye and Seinfeld (2010) improves model–measurement agreement for mass concentration. The results from the three parameterizations show large differences (e.g., a factor of 3 in SOA mass) and are not well constrained, underscoring the current uncertainties in this area. Our results strongly suggest that other precursors besides VOCs, such as P-S/IVOCs, are needed to explain the observed SOA concentrations in Pasadena. All the recent parameterizations overpredict urban SOA formation at long photochemical ages (3 days) compared to observations from multiple sites, which can lead to problems in regional and especially global modeling. However, reducing IVOC emissions by one-half in the model to better match recent IVOC measurements improves SOA predictions at these long photochemical ages. Among the explicitly modeled VOCs, the precursor compounds that contribute the greatest SOA mass are methylbenzenes. Measured polycyclic aromatic hydrocarbons (naphthalenes) contribute 0.7% of the modeled SOA mass. The amounts of SOA mass from diesel vehicles, gasoline vehicles, and cooking emissions are estimated to be 16–27, 35–61, and 19–35 %, respectively, depending on the parameterization used, which is consistent with the observed fossil fraction of urban SOA, 71(+-3) %. The relative contribution of each source is uncertain by almost a factor of 2 depending on the parameterization used. In-basin biogenic VOCs are predicted to contribute only a few percent to SOA. A regional SOA background of approximately 2.1 μgm-3 is also present due to the long-distance transport of highly aged OA, likely with a substantial contribution from regional biogenic SOA. The percentage of SOA from diesel vehicle emissions is the same, within the estimated uncertainty, as reported in previous work that analyzed the weekly cycles in OA concentrations (Bahreini et al., 2012; Hayes et al., 2013). However, the modeling work presented here suggests a strong anthropogenic source of modern carbon in SOA, due to cooking emissions, which was not accounted for in those previous studies and which is higher on weekends. Lastly, this work adapts a simple two-parameter model to predict SOA concentration and O/C from urban emissions. This model successfully predicts SOA concentration, and the optimal parameter combination is very similar to that found for Mexico City. This approach provides a computationally inexpensive method for predicting urban SOA in global and climate models. We estimate pollution SOA to account for 26 Tg yr-1 of SOA globally, or 17% of global SOA, one third of which is likely to be non-fossil.

Modelling woody material transport and deposition in alpine rivers

Recent flood events in Switzerland and Western Austria in 2005 were characterised by an increase in impacts and associated losses due to the transport of woody material. As a consequence, protection measures and bridges suffered considerable damages. Furthermore, cross-sectional obstructions due to woody material entrapment caused unexpected flood plain inundations resulting in severe damage to elements at risk. Until now, the transport of woody material is neither sufficiently taken into account nor systematically considered, leading to prediction inaccuracies during the procedure of hazard mapping. To close this gap, we propose a modelling approach that (1) allows the estimation of woody material recruitment from wood-covered banks and flood plains; (2) allows the evaluation of the disposition for woody material entrainment and transport to selected critical configurations along the stream and that (3) enables the delineation of hazard process patterns at these critical configurations. Results from a case study suggest the general applicability of the concept. This contribution to woody material transport analysis refines flood hazard assessments due to the consideration of woody material transport scenarios.

Coupling of lysosomal and mitochondrial membrane permeabilization in trypanolysis by APOL1

Humans resist infection by the African parasite Trypanosoma brucei owing to the trypanolytic activity of the serum apolipoprotein L1 (APOL1). Following uptake by endocytosis in the parasite, APOL1 forms pores in endolysosomal membranes and triggers lysosome swelling. Here we show that APOL1 induces both lysosomal and mitochondrial membrane permeabilization (LMP and MMP). Trypanolysis coincides with MMP and consecutive release of the mitochondrial TbEndoG endonuclease to the nucleus. APOL1 is associated with the kinesin TbKIFC1, of which both the motor and vesicular trafficking VHS domains are required for MMP, but not for LMP. The presence of APOL1 in the mitochondrion is accompanied by mitochondrial membrane fenestration, which can be mimicked by knockdown of a mitochondrial mitofusin-like protein (TbMFNL). The BH3-like peptide of APOL1 is required for LMP, MMP and trypanolysis. Thus, trypanolysis by APOL1 is linked to apoptosis-like MMP occurring together with TbKIFC1-mediated transport of APOL1 from endolysosomal membranes to the mitochondrion.

The role of seasonality of mineral dust concentration and size on glacial/interglacial dust changes in the EPICA Dronning Maud Land ice core

We present a record of particulate dust concentration and size distribution in subannual resolution measured on the European Project for Ice Coring in Antarctica (EPICA) Dronning Maud Land (EDML) ice core drilled in the Atlantic sector of the East Antarctic plateau. The record reaches from present day back to the penultimate glacial until 145,000 years B.P. with subannual resolution from 60,000 years B.P. to the present. Mean dust concentrations are a factor of 46 higher during the glacial (~850–4600 ng/mL) compared to the Holocene (~16–112 ng/mL) with slightly smaller dust particles during the glacial comparedto the Holocene and with an absolute minimum in the dust size at 16,000 years B.P. The changes in dust concentration are mainly attributed to changes in source conditions in southern South America. An increase in the modal value of the dust size suggests that at 16,000 years B.P. a major change in atmospheric circulation apparently allowed more direct transport of dust particles to the EDML drill site. We find a clear in-phase relation of the seasonal variation in dust mass concentration and dust size during the glacial (r(conc,size) = 0.8) but no clear phase relationship during the Holocene (0 transport of the dust to the ice sheet using the size as an indicator for transport intensity, we find that the effect of the changes in the seasonality of the source emission strength and the transport intensity on the dust decrease over Transition 1 can significantly contribute to the large decrease of dust concentration from the glacial to the Holocene.

Dynamics of Sodium‐22 and Cesium‐134 in Young Wheat Plants

The dynamics of the two alkali metals sodium and cesium in crop plants are relevant in an ecological context. Redistribution processes for these elements in young wheat plants were investigated in the work reported here. Two days old wheat plants (Triticum aestivum L. cv. Arina) were fed for 24 h with sodium‐22 (22Na) and cesium‐134 (134Cs) via the main root and incubated afterwards in a culture room. Cesium‐134 accumulated in newly formed parts of the main root and in the expanding leaves during the first 20 days after labeling, while 22Na accumulated transiently in these plant parts, reached a peak and declined after a few days. A high percentage of 22Na was released from the roots to the medium. Total Na in leaves also accumulated transiently, but its highest accumulation appeared later than the peak of 22Na. Therefore, the distribution and retranslocation processes differ considerably for sodium and cesium in wheat plants. Such differences must be considered for the evaluation of environmental effects (e.g., release of pollutants into the environment) on the quality of harvested cereal products.

Impact of oceanic circulation changes on atmospheric δ¹³ CO₂

δ¹³ CO₂ measured in Antarctic ice cores provides constraints on oceanic and terrestrial carbon cycle processes linked with millennial-scale changes in atmospheric CO₂. However, the interpretation of δ¹³ CO₂ is not straight-forward. Using carbon isotope-enabled versions of the LOVECLIM and Bern3D models, we perform a set of sensitivity experiments in which the formation rates of North Atlantic Deep Water (NADW), North Pacific Deep Water (NPDW), Antarctic Bottom Water (AABW), and Antarctic Intermediate Water (AAIW) are varied. We study the impact of these circulation changes on atmospheric δ¹³ CO₂ as well as on the oceanic δ¹³ CO₂ distribution. In general, we find that the formation rates of AABW, NADW, NPDW, and AAIW are negatively correlated with changes in δ¹³ CO₂: namely, strong oceanic ventilation decreases atmospheric δ¹³ CO₂. However, since large-scale oceanic circulation reorganizations also impact nutrient utilization and the Earth’s climate, the relationship between atmospheric δ¹³ CO₂ levels and ocean ventilation rate is not unequivocal. In both models atmospheric δ¹³ CO₂ is very sensitive to changes in AABW formation rates: increased AABW formation enhances the transport of low δ¹³ CO₂ waters to the surface and decreases atmospheric δ¹³ CO₂. By contrast, the impact of NADW changes on atmospheric δ¹³ CO₂ is less robust and might be model dependent. This results from complex interplay between global climate, carbon cycle, and the formation rate of NADW, a water body characterized by relatively high δ¹³ CO₂.

Discovery and characterization of a novel non-competitive inhibitor of the divalent metal transporter DMT1/SLC11A2

Divalent metal transporter-1 (SLC11A2/DMT1) uses the H+ electrochemical gradient as the driving force to transport divalent metal ions such as Fe2+, Mn2+ and others metals into mammalian cells. DMT1 is ubiquitously expressed, most notably in proximal duodenum, immature erythroid cells, brain and kidney. This transporter mediates H+-coupled transport of ferrous iron across the apical membrane of enterocytes. In addition, in cells such as to erythroid precursors, following transferrin receptor (TfR) mediated endocytosis; it mediates H+-coupled exit of ferrous iron from endocytic vesicles into the cytosol. Dysfunction of human DMT1 is associated with several pathologies such as iron deficiency anemia hemochromatosis, Parkinson's disease and Alzheimer's disease, as well as colorectal cancer and esophageal adenocarcinoma, making DMT1 an attractive target for drug discovery. In the present study, we performed a ligand-based virtual screening of the Princeton database (700,000 commercially available compounds) to search for pharmacophore shape analogs of recently reported DMT1 inhibitors. We discovered a new compound, named pyrimidinone 8, which mediates a reversible linear non-competitive inhibition of human DMT1 (hDMT1) transport activity with a Ki of ∼20 μM. This compound does not affect hDMT1 cell surface expression and shows no dependence on extracellular pH. To our knowledge, this is the first experimental evidence that hDMT1 can be allosterically modulated by pharmacological agents. Pyrimidinone 8 represents a novel versatile tool compound and it may serve as a lead structure for the development of therapeutic compounds for pre-clinical assessment.

Functional proteomics and biochemistry: working together to unravel mitochondrial phenomena of African trypanosomes

Eukaryotic cells are compartmentalized into membrane-bound organelles in order to provide sheltered reaction rooms for various specific processes. Organelles are not randomly distributed in a cell or operate isolated from each other. At the contrary — some organelles are closely linked and their functions are tightly orchestrated. The most well-known example of two such organelles acting in concert are the ER and the mitochondrion that work together in order to coordinate cellular lipid biosynthesis, maintain Ca2+-homeostasis, regulate mitochondrial division and control mitochondrial/ER shape as well as to synchronize the movement of these organelles within a cell. To study the mitochondrion and its interface to the ER requires a simplified mitochondrial system. African trypanosomes represent such a system. The unicellular parasite that causes devastating diseases in humans and animals has only one large mitochondrion that does not undergo fission/fusion events except for the context of cell division. Moreover, mitochondrial functions and morphology are highly regulated throughout the life cycle of the protozoan. Central to the understanding of how mitochondria control their morphology, communicate with their surroundings and manage exchange of metabolites and transport of biopolymers (proteins, RNAs) is the mitochondrial outer membrane (MOM), as the MOM defines the boundary of the organelle. Recently, we have purified the MOM of T. brucei and characterized its proteome using label-free quantitative mass spectrometry for protein abundance profiling in combination with statistical analysis. Our results show that the trypanosomal MOM proteome consists of 82 proteins, two thirds of which have never been associated with mitochondria before. Among these, we identified novel factors required to regulate mitochondrial morphology and the long-elusive protein import machinery of T. brucei. A comparison with the MOM proteome of yeast defines a set of 17 common proteins that are likely present in the mitochondrial outer membrane of all eukaryotes. One of these is the Miro-GTPase Gem1. In yeast, this Ca2+-EF-Hand containing polypeptide is thought to be involved in a protein complex that physically tethers the mitochondrion to the ER. Interestingly, a putative tethering complex in mammalian cells was linked to the mitochondrial fusion/fission machinery. Thus, the concept of a protein complex-mediated connection seems to be a general and conserved feature. We are currently investigating, if such a protein complex exists in T. brucei and if the trypanosomal Gem1 protein is involved. This ER-subdomain associated with mitochondria has been termed mitochondria-associated ER-membranes or MAM. The MAM has recently been implicated to play a key role in Alzheimer’s disease. It is therefore of broad and general interest to establish other eukaryotic model systems in order to investigate the MAM-MOM connection in more detail.

Introduction to the Maïdo Lidar Calibration Campaign dedicated to the validation of upper air meteorological parameters

The first operations at the new High-altitude Maïdo Observatory at La Réunion began in 2013. The Maïdo Lidar Calibration Campaign (MALICCA) was organized there in April 2013 and has focused on the validation of the thermodynamic parameters (temperature, water vapor, and wind) measured with many instruments including the new very large lidar for water vapor and temperature profiles. The aim of this publication consists of providing an overview of the different instruments deployed during this campaign and their status, some of the targeted scientific questions and associated instrumental issues. Some specific detailed studies for some individual techniques were addressed elsewhere. This study shows that temperature profiles were obtained from the ground to the mesopause (80 km) thanks to the lidar and regular meteorological balloon-borne sondes with an overlap range showing good agreement. Water vapor is also monitored from the ground to the mesopause by using the Raman lidar and microwave techniques. Both techniques need to be pushed to their limit to reduce the missing range in the lower stratosphere. Total columns obtained from global positioning system or spectrometers are valuable for checking the calibration and ensuring vertical continuity. The lidar can also provide the vertical cloud structure that is a valuable complementary piece of information when investigating the water vapor cycle. Finally, wind vertical profiles, which were obtained from sondes, are now also retrieved at Maïdo from the newly implemented microwave technique and the lidar. Stable calibrations as well as a small-scale dynamical structure are required to monitor the thermodynamic state of the middle atmosphere, ensure validation of satellite sensors, study the transport of water vapor in the vicinity of the tropical tropopause and study their link with cirrus clouds and cyclones and the impact of small-scale dynamics (gravity waves) and their link with the mean state of the mesosphere.

A role for tuned levels of nucleosome remodeler subunit ACF1 during Drosophila oogenesis

The Chromatin Accessibility Complex (CHRAC) consists of the ATPase ISWI, the large ACF1 subunit and a pair of small histone-like proteins, CHRAC-14/16. CHRAC is a prototypical nucleosome sliding factor that mobilizes nucleosomes to improve the regularity and integrity of the chromatin fiber. This may facilitate the formation of repressive chromatin. Expression of the signature subunit ACF1 is restricted during embryonic development, but remains high in primordial germ cells. Therefore, we explored roles for ACF1 during Drosophila oogenesis. ACF1 is expressed in somatic and germline cells, with notable enrichment in germline stem cells and oocytes. The asymmetrical localization of ACF1 to these cells depends on the transport of the Acf1 mRNA by the Bicaudal-D/Egalitarian complex. Loss of ACF1 function in the novel Acf1(7) allele leads to defective egg chambers and their elimination through apoptosis. In addition, we find a variety of unusual 16-cell cyst packaging phenotypes in the previously known Acf1(1) allele, with a striking prevalence of egg chambers with two functional oocytes at opposite poles. Surprisingly, we found that the Acf1(1) deletion - despite disruption of the Acf1 reading frame - expresses low levels of a PHD-bromodomain module from the C-terminus of ACF1 that becomes enriched in oocytes. Expression of this module from the Acf1 genomic locus leads to packaging defects in the absence of functional ACF1, suggesting competitive interactions with unknown target molecules. Remarkably, a two-fold overexpression of CHRAC (ACF1 and CHRAC-16) leads to increased apoptosis and packaging defects. Evidently, finely tuned CHRAC levels are required for proper oogenesis.