scholarly journals Development of on-off spiking in superior paraolivary nucleus neurons of the mouse

2013 ◽  
Vol 109 (11) ◽  
pp. 2691-2704 ◽  
Author(s):  
Richard A. Felix ◽  
Katrin Vonderschen ◽  
Albert S. Berrebi ◽  
Anna K. Magnusson
Keyword(s):  
Developmental Regulation ◽  
Cell Group ◽  
Sound Structure ◽  
Auditory Brain Stem ◽  
Superior Paraolivary Nucleus ◽  
Morphological Differences ◽  
Stimulus Offset ◽  
Rebound Spiking

The superior paraolivary nucleus (SPON) is a prominent cell group in the auditory brain stem that has been increasingly implicated in representing temporal sound structure. Although SPON neurons selectively respond to acoustic signals important for sound periodicity, the underlying physiological specializations enabling these responses are poorly understood. We used in vitro and in vivo recordings to investigate how SPON neurons develop intrinsic cellular properties that make them well suited for encoding temporal sound features. In addition to their hallmark rebound spiking at the stimulus offset, SPON neurons were characterized by spiking patterns termed onset, adapting, and burst in response to depolarizing stimuli in vitro. Cells with burst spiking had some morphological differences compared with other SPON neurons and were localized to the dorsolateral region of the nucleus. Both membrane and spiking properties underwent strong developmental regulation, becoming more temporally precise with age for both onset and offset spiking. Single-unit recordings obtained in young mice demonstrated that SPON neurons respond with temporally precise onset spiking upon tone stimulation in vivo, in addition to the typical offset spiking. Taken together, the results of the present study demonstrate that SPON neurons develop sharp on-off spiking, which may confer sensitivity to sound amplitude modulations or abrupt sound transients. These findings are consistent with the proposed involvement of the SPON in the processing of temporal sound structure, relevant for encoding communication cues.

Clock gene-independent daily regulation of haemoglobin oxidation in red blood cells

2021 ◽  
Author(s):  
Andrew D. Beale ◽  
Priya Crosby ◽  
Utham K. Valekunja ◽  
Rachel S. Edgar ◽  
Johanna E. Chesham ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Human Subjects ◽  
Developmental Regulation ◽  
Physiological Role ◽  
Cell Types ◽  
The Body

AbstractCellular circadian rhythms confer daily temporal organisation upon behaviour and physiology that is fundamental to human health and disease. Rhythms are present in red blood cells (RBCs), the most abundant cell type in the body. Being naturally anucleate, RBC circadian rhythms share key elements of post-translational, but not transcriptional, regulation with other cell types. The physiological function and developmental regulation of RBC circadian rhythms is poorly understood, however, partly due to the small number of appropriate techniques available. Here, we extend the RBC circadian toolkit with a novel biochemical assay for haemoglobin oxidation status, termed “Bloody Blotting”. Our approach relies on a redox-sensitive covalent haem-haemoglobin linkage that forms during cell lysis. Formation of this linkage exhibits daily rhythms in vitro, which are unaffected by mutations that affect the timing of circadian rhythms in nucleated cells. In vivo, haemoglobin oxidation rhythms demonstrate daily variation in the oxygen-carrying and nitrite reductase capacity of the blood, and are seen in human subjects under controlled laboratory conditions as well as in freely-behaving humans. These results extend our molecular understanding of RBC circadian rhythms and suggest they serve an important physiological role in gas transport.

Developmental regulation of heterochromatin-mediated gene silencing in Drosophila

Development ◽  
1998 ◽  
Vol 125 (12) ◽  
pp. 2223-2234 ◽  
Author(s):  
B.Y. Lu ◽  
J. Ma ◽  
J.C. Eissenberg
Keyword(s):  
Cell Cycle ◽  
Gene Silencing ◽  
Mitotic Activity ◽  
Larval Stage ◽  
Developmental Regulation ◽  
Promoter Strength ◽  
Lacz Gene ◽  
High Degree

The roles of differentiation, mitotic activity and intrinsic promoter strength in the maintenance of heterochromatic silencing were investigated during development using an inducible lacZ gene as an in vivo probe. Heterochromatic silencing is initiated at the onset of gastrulation, approximately 1 hour after heterochromatin is first visible cytologically. A high degree of silencing is maintained in the mitotically active imaginal cells from mid-embryogenesis until early third instar larval stage, and extensive relaxation of silencing is tightly associated with the onset of differentiation. Relaxation of silencing can be triggered in vitro by ecdysone. In contrast, timing and extent of silencing at both the initiation and relaxation stages are insensitive to changes in cell cycle activity, and intrinsic promoter strength also does not influence the extent of silencing by heterochromatin. These data suggest that the silencing activity of heterochromatin is developmentally programmed.

scholarly journals Characterization of the Anti-Inflammatory Capacity of IL-10-Producing Neutrophils in Response to Streptococcus pneumoniae Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Liliana A. González ◽  
Felipe Melo-González ◽  
Valentina P. Sebastián ◽  
Omar P. Vallejos ◽  
Loreani P. Noguera ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Lung Injury ◽  
Interleukin 10 ◽  
Effector Cells ◽  
Cellular Source ◽  
Lung Histopathology ◽  
Morphological Differences ◽  
Direct Recognition

Neutrophils are immune cells classically defined as pro-inflammatory effector cells. However, current accumulated evidence indicates that neutrophils have more versatile immune-modulating properties. During acute lung infection with Streptococcus pneumoniae in mice, interleukin-10 (IL-10) production is required to temper an excessive lung injury and to improve survival, yet the cellular source of IL-10 and the immunomodulatory role of neutrophils during S. pneumoniae infection remain unknown. Here we show that neutrophils are the main myeloid cells that produce IL-10 in the lungs during the first 48 h of infection. Importantly, in vitro assays with bone-marrow derived neutrophils confirmed that IL-10 can be induced by these cells by the direct recognition of pneumococcal antigens. In vivo, we identified the recruitment of two neutrophil subpopulations in the lungs following infection, which exhibited clear morphological differences and a distinctive profile of IL-10 production at 48 h post-infection. Furthermore, adoptive transfer of neutrophils from WT mice into IL-10 knockout mice (Il10-/-) fully restored IL-10 production in the lungs and reduced lung histopathology. These results suggest that IL-10 production by neutrophils induced by S. pneumoniae limits lung injury and is important to mediate an effective immune response required for host survival.

Inhibition of Mucociliary Clearance of the Eustachian Tube by Leukotrienes C4 and D4

1995 ◽  
Vol 104 (3) ◽  
pp. 231-236 ◽  
Author(s):  
Tetsuya Ganbo ◽  
Tsukasa Nakajima ◽  
Ken-Ichi Hisamaisu ◽  
Hajime Inoue ◽  
Shin-Ichi Shimomura ◽  
...  
Keyword(s):  
Eustachian Tube ◽  
Mucociliary Clearance ◽  
Ciliary Activity ◽  
Leukotriene D4 ◽  
Auditory Brain Stem Response ◽  
Auditory Brain Stem ◽  
Brain Stem Response ◽  
Ear Effusion

The effect of leukotrienes C4 (LTC4) and D4 (LTD4) and prostaglandin E2 (PGE2) on mucociliary clearance of the eustachian tube was investigated in vitro and in vivo. Normal ciliated epithelium was obtained from the eustachian tube of guinea pigs and incubated separately with LTC4, LTD4, and PGE2 at concentrations of 10−8 mol/L and 10−6 mol/L. Ciliary activity was measured photoelectrically. Leukotriene D4 progressively inhibited ciliary activity, while PGE2 promoted it. Leukotriene C4 also induced ciliary inhibition. One milliliter each of 10−5 mol/L LTC4, LTD4, and PGE2 was directly injected into the tympanic bullae of chinchillas under anesthesia. The middle ears were examined by otomicroscopy, tympanometry, and auditory brain stem response over time. Clearance of middle ear effusion was delayed by LTC4 and LTD4, as compared with PGE2 and the control. These findings indicate that LTC4 and LTD4 inhibit mucociliary clearance of the eusiachian tube.

scholarly journals Perinatal expression of IGFBPs in rat lung and its hormonal regulation in fetal lung explants

1997 ◽  
Vol 273 (6) ◽  
pp. L1174-L1181 ◽  
Author(s):  
J. Koenraad Van De Wetering ◽  
Robert H. Elfring ◽  
Marja A. Oosterlaken-Dijksterhuis ◽  
Jan A. Mol ◽  
Henk P. Haagsman ◽  
...  
Keyword(s):  
Hormonal Regulation ◽  
Developmental Regulation ◽  
Mrna Level ◽  
Rat Lung ◽  
Igf Binding Proteins ◽  
Igf System ◽  
Explant Cultures ◽  
Igfbp 3

To gain more insight into the regulation of the expression of insulin-like growth factor (IGF) binding proteins (IGFBPs) in the lung, the developmental patterns of the abundance of the mRNAs encoding IGFBPs were measured in the perinatal rat lung and in explant cultures of fetal rat lung. In hormone-free explant cultures, the levels of the mRNAs encoding IGFBP-2 through -5 changed with a pattern similar to that occurring in vivo (although in the case of IGFBP-3 to -5 at a faster rate), indicating that the developmental regulation of the expression of these IGFBPs in perinatal lung is mimicked in the explants. For the IGFBP-6 mRNA level, the pattern in vitro differed from that in vivo. In the explant cultures, dexamethasone decreased the production of IGFBP-3 and -4 and decreased the abundance of the mRNAs encoding IGFBP-2 to -5 but increased the abundance of IGFBP-6 mRNA. These observations indicate that glucocorticoids may be involved in the developmental regulation of the expression of these components of the IGF system and that the IGF system may be involved in the physiological effects of glucocorticoids on lung development. No appreciable effects of 3,3′,5-triiodothyronine on the expression of the IGFBPs were observed.

scholarly journals Mannose Modified Co-Loaded Zoledronic Liposomes Deplete M2-tumor-associated Macrophages to Enhance Anti-Tumor Effect of Doxorubicin on TNBC

2021 ◽  
Author(s):  
Wendong Yao ◽  
Hengwu Xu ◽  
Yanhong Chen ◽  
Yingying Xu ◽  
Feng Zhou ◽  
...  
Keyword(s):  
Tumor Therapy ◽  
Tumor Development ◽  
Cell Group ◽  
Tumor Associated Macrophages ◽  
Chemotherapy Drugs ◽  
Anticancer Effects ◽  
Nano Medicine ◽  
Doxorubicin Liposomes

Abstract As the most numerous inflammatory cell group in tumor microenvironment, tumor-associated macrophages (TAMs) have an essential effect in tumor therapy and are potential therapeutic targets. M2 type tumor-associated macrophages (M2-TAMs) were involved in the entire process of tumor development, invasion, and metastasis, obstructing the anti-tumor effect of chemotherapy drugs and nano-medicine. This study aimed to construct a mannose modified co-loaded zoledronic acid and doxorubicin liposomes (Man-LP@ZOL/DOX) for improving the anti-tumor effect by suppressing M2-TAMs on triple-negative breast cancer (TNBC). The size, PDI, and Zeta-potential of Man-LP@ZOL/DOX liposomes were determined to be 212.80±7.74 nm, 0.1413±0.0232, -33.63±0.49 mV, respectively. The Man-LP@ZOL/DOX's EE% and DL% of ZOL as measured were 17.21±2.26% and 1.56±0.21%, while for DOX, they were 84.42±2.05% and 5.12±0.14%. The uptake of Man-LP into cells was increased when it was modified with a TAMs target ligand. The liposomes inhibited the invasion of MDA-MB-231 cells induced by M2-TAMs, and expression of biomarkers on M2-TAMs (Arg1 and CD206 in vitro, CD68, and CD206 in vivo) was apparent. Moreover, co-loaded drugs liposome system remarkably enhanced anticancer effects both in vitro and vivo combined with ZOL. In conclusion, all these results established that Man-LP@ZOL/DOX could enhance anti-tumor effect of DOX via depleting M2-TAMs on TNBC.

scholarly journals Schistosome AMPK Is Required for Larval Viability and Regulates Glycogen Metabolism in Adult Parasites

2021 ◽  
Vol 12 ◽  
Author(s):  
Kasandra S. Hunter ◽  
André Miller ◽  
Margaret Mentink-Kane ◽  
Stephen J. Davies
Keyword(s):  
Developmental Regulation ◽  
Glucose Deprivation ◽  
Dry Weight ◽  
Glycogen Metabolism ◽  
Life Cycle Stage ◽  
Mammalian Host ◽  
Freshwater Environment ◽  
Compensatory Response

On entering the mammalian host, schistosomes transition from a freshwater environment where resources are scarce, to an environment where there is an unlimited supply of glucose, their preferred energy substrate. Adult schistosome glycolytic activity consumes almost five times the parasite’s dry weight in glucose per day to meet the parasite’s energy demands, and the schistosome glycolytic enzymes and mechanisms for glucose uptake that sustain this metabolic activity have previously been identified. However, little is known of the parasite processes that regulate schistosome glucose metabolism. We previously described the Schistosoma mansoni ortholog of 5′ AMP-Activated Protein Kinase (AMPK), which is a central regulator of energy metabolism in eukaryotes, and characterized the developmental regulation of its expression and activity in S. mansoni. Here we sought to explore the function of AMPK in schistosomes and test whether it regulates parasite glycolysis. Adult schistosomes mounted a compensatory response to chemical inhibition of AMPK α, resulting in increased AMPK α protein abundance and activity. RNAi inhibition of AMPK α expression, however, suggests that AMPK α is not required for adult schistosome viability in vitro. Larval schistosomula, on the other hand, are sensitive to chemical AMPK α inhibition, and this correlates with inactivity of the AMPK α gene in this life cycle stage that precludes a compensatory response to AMPK inhibition. While our data indicate that AMPK is not essential in adult schistosomes, our results suggest that AMPK regulates adult worm glycogen stores, influencing both glycogen utilization and synthesis. AMPK may therefore play a role in the ability of adult schistosomes to survive in vivo stressors such as transient glucose deprivation and oxidative stress. These findings suggest that AMPK warrants further investigation as a potential drug target, especially for interventions aimed at preventing establishment of a schistosome infection.

scholarly journals Spike afterpotentials shape the in-vivo burst activity of principal cells in medial entorhinal cortex

2019 ◽  
Author(s):  
Dóra É. Csordás ◽  
Caroline Fischer ◽  
Johannes Nagele ◽  
Martin Stemmler ◽  
Andreas V.M. Herz
Keyword(s):  
Entorhinal Cortex ◽  
High Frequency ◽  
Cell Group ◽  
Two Dimensional ◽  
Grid Cells ◽  
Spatial Coding ◽  
Medial Entorhinal Cortex ◽  
Whole Cell

AbstractPrincipal neurons in rodent medial entorhinal cortex (MEC) generate high-frequency bursts during natural behavior. While in vitro studies point to potential mechanisms that could support such burst sequences, it remains unclear whether these mechanisms are effective under in-vivo conditions. In this study, we focused on the membrane-potential dynamics immediately following action potentials, as measured in whole-cell recordings from male mice running in virtual corridors (Domnisoru et al., 2013). These afterpotentials consisted either of a hyperpolarization, an extended ramp-like shoulder, or a depolarization reminiscent of depolarizing afterpotentials (DAPs) recorded in vitro in MEC stellate and pyramidal neurons. Next, we correlated the afterpotentials with the cells’ propensity to fire bursts. All DAP cells with known location resided in Layer II, generated bursts, and their inter-spike intervals (ISIs) were typically between five and fifteen milliseconds. The ISI distributions of Layer-II cells without DAPs peaked sharply at around four milliseconds and varied only minimally across that group. This dichotomy in burst behavior is explained by cell-group-specific DAP dynamics. The same two groups of bursting neurons also emerged when we clustered extracellular spike-train autocorrelations measured in real two-dimensional arenas (Latuske et al., 2015). No difference in the spatial coding properties of the grid cells across all three groups was discernible. Layer III neurons were only sparsely bursting and had no DAPs. As various mechanisms for modulating the ion-channels underlying DAPs exist, our results suggest that the temporal features of MEC activity can be altered while maintaining the cells’ spatial tuning characteristics.Significance StatementDepolarizing afterpotentials (DAPs) are frequently observed in principal neurons from slice preparations of rodent medial entorhinal cortex (MEC), but their functional role in vivo is unknown. Analyzing whole-cell data from mice running on virtual tracks, we show that DAPs do occur during behavior. Cells with prominent DAPs are found in Layer II; their inter-spike intervals reflect DAP time-scales. In contrast, neither the rarely bursting cells in Layer III, nor the high-frequency bursters in Layer II, have a DAP. Extracellular recordings from mice exploring real two-dimensional arenas demonstrate that grid cells within these three groups have rather similar spatial coding properties. We conclude that DAPs shape the temporal but not the spatial response characteristics of principal neurons in MEC.Author contributionsAll authors designed research. DÉC, CF, and JN performed research and analyzed data (equal contribution). AVMH wrote and edited the paper with support from MS and the other authors.

scholarly journals Developmental Regulation of Neuronal K + Channels by Target-Derived TGFβ In Vivo and In Vitro

Neuron ◽  
1998 ◽  
Vol 21 (5) ◽  
pp. 1045-1053 ◽  
Author(s):  
Jill S Cameron ◽  
Loic Lhuillier ◽  
Priya Subramony ◽  
Stuart E Dryer
Keyword(s):  
Developmental Regulation ◽  
K Channels

scholarly journals Developmental and Transcriptional Consequences of Mutations in Drosophila TAFII60

2001 ◽  
Vol 21 (20) ◽  
pp. 6808-6819 ◽  
Author(s):  
Norikazu Aoyagi ◽  
David A. Wassarman
Keyword(s):  
Rna Polymerase Ii ◽  
Cell Fate ◽  
Transcription Initiation ◽  
Developmental Regulation ◽  
Regulation Of Gene Expression ◽  
Loss Of Function ◽  
Activator Proteins ◽  
Regulate Cell Growth

ABSTRACT In vitro, the TAFII60 component of the TFIID complex contributes to RNA polymerase II transcription initiation by serving as a coactivator that interacts with specific activator proteins and possibly as a promoter selectivity factor that interacts with the downstream promoter element. In vivo roles for TAFII60 in metazoan transcription are not as clear. Here we have investigated the developmental and transcriptional requirements for TAFII60 by analyzing four independent Drosophila melanogaster TAF II 60 mutants. Loss-of-function mutations in Drosophila TAF II 60 result in lethality, indicating that TAFII60 provides a nonredundant function in vivo. Molecular analysis of TAF II 60alleles revealed that essential TAFII60 functions are provided by two evolutionarily conserved regions located in the N-terminal half of the protein. TAFII60 is required at all stages of Drosophila development, in both germ cells and somatic cells. Expression of TAFII60 from a transgene rescued the lethality of TAF II 60mutants and exposed requirements for TAFII60 during imaginal development, spermatogenesis, and oogenesis. Phenotypes of rescued TAF II 60 mutant flies implicate TAFII60 in transcriptional mechanisms that regulate cell growth and cell fate specification and suggest that TAFII60 is a limiting component of the machinery that regulates the transcription of dosage-sensitive genes. Finally, TAFII60 plays roles in developmental regulation of gene expression that are distinct from those of other TAFIIproteins.

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