Growth and Differentiation of the Larval Mosquito Midgut

Factors affecting larval growth and nutrition have consequences on adult fecundity. Since the mosquito larval midgut is the primary organ of digestion and nutrient absorption, factors that affect the growth and development of the midgut may have potential consequences on the reproductive potential of the adult. To gain a better understanding of mosquito midgut development the growth and metamorphic remodeling of the Aedes aegypti L. and Culex pipiens L. (Diptera: Culicidae) midguts were investigated. Cytological evidence was obtained suggesting that, in both the anterior and posterior Ae. aegypti larval midgut, diploid regenerative cells give rise to new endoreplicating cells that significantly contribute to the growth and metabolism of the midgut. This hypothesis was supported by BrdU incorporation studies showing that diploid cells, as well as large and small endoreplicating cells, synthesize DNA during the 2nd, 3rd and 4th instars. Cytological studies of the Cx. pipiens larval midgut suggest that anterior midgut growth in this species is primarily by cell enlargement. To study metamorphic remodeling of the midgut, DNA synthesis in Ae. aegypti 4th instar midguts was followed by using 5-bromo-2-deoxyuridine (BrdU) incorporation. During the 24 hr period after the last larval-larval molt both endoreplicating and diploid cells incorporate BrdU. After the critical weight is achieved, endoreplicating cell BrdU incorporation gradually ceases while diploid cells continue to replicate. The period of maximum diploid cell incorporation correlated with the period of maximum ecdysone titer

Inactivation of Ppp1r15a minimises weight gain and insulin resistance during caloric excess in female mice.

Phosphorylation of the translation initiation factor eIF2α within the mediobasal hypothalamus is known to suppress food intake, but the role of the eIF2α phosphatases in regulating body weight is poorly understood. Mice deficient in active PPP1R15A, a stress-inducible eIF2α phosphatase, are healthy and more resistant to endoplasmic reticulum stress than wild type controls. We report that when female Ppp1r15a mutant mice are fed a high fat diet they gain less weight than wild type littermates owing to reduced food intake. This results in healthy leaner Ppp1r15a mutant animals with reduced hepatic steatosis and improved insulin sensitivity, albeit with a possible modest defect in insulin secretion. By contrast, no weight differences are observed between wild type and Ppp1r15a deficient mice fed a standard diet. We conclude that female mice lacking the C-terminal PP1-binding domain of PPP1R15A show reduced dietary intake and preserved glucose tolerance. Our data indicate that this results in reduced weight gain and protection from diet-induced obesity.The work was also supported by Diabetes UK and the MRC [G1002610]. VP held an Arthur and Sadie Pethybridge PhD Studentship from Diabetes UK. The CIMR microscopy core facility is supported by a Wellcome Trust Strategic Award [100140] and a Wellcome Trust equipment grant [093026]

Equipping for risk: Lessons learnt from the UK shale-gas experience on assessing environmental risks for the future geoenergy use of the deep subsurface

\ua9 2024 The Authors. Summary findings are presented from an investigation to improve understanding of the environmental risks associated with developing an unconventional-hydrocarbons industry in the UK. The EQUIPT4RISK project, funded by UK Research Councils, focused on investigations around Preston New Road (PNR), Fylde, Lancashire, and Kirby Misperton Site A (KMA), North Yorkshire, where operator licences to explore for shale gas by hydraulic fracturing (HF) were issued in 2016, although exploration only took place at PNR. EQUIPT4RISK considered atmospheric (greenhouse gases, air quality), water (groundwater quality) and solid-earth (seismicity) compartments to characterise and model local conditions and environmental responses to HF activities. Risk assessment was based on the source-pathway-receptor approach. Baseline monitoring of air around the two sites characterised the variability with meteorological conditions, and isotopic signatures were able to discriminate biogenic methane (cattle) from thermogenic (natural-gas) sources. Monitoring of a post-HF nitrogen-lift (well-cleaning) operation at PNR detected the release of atmospheric emissions of methane (4.2 \ub1 1.4 t CH4). Groundwater monitoring around KMA identified high baseline methane concentrations and detected ethane and propane at some locations. Dissolved methane was inferred from stable-isotopic evidence as overwhelmingly of biogenic origin. Groundwater-quality monitoring around PNR found no evidence of HF-induced impacts. Two approaches for modelling induced seismicity and associated seismic risk were developed using observations of seismicity and operational parameters from PNR in 2018 and 2019. Novel methodologies developed for monitoring include use of machine learning to identify fugitive atmospheric methane, Bayesian statistics to assess changes to groundwater quality, a seismicity forecasting model seeded by the HF-fluid injection rate and high-resolution monitoring of soil-gas methane. The project developed a risk-assessment framework, aligned with ISO 31000 risk-management principles, to assess the theoretical combined and cumulative environmental risks from operations over time. This demonstrated the spatial and temporal evolution of risk profiles: seismic and atmospheric impacts from the shale-gas operations are modelled to be localised and short-lived, while risk to groundwater quality is longer-term

Distinctive dendritic cell subsets expressing factor XIIIa, CD1a, CD1b and CD1c in mycosis fungoides and psoriasis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73825/1/j.1600-0560.1995.tb00742.x.pd

The X-inactivation trans-activator Rnf12 is negatively regulated by pluripotency factors in embryonic stem cells

X-inactivation, the molecular mechanism enabling dosage compensation in mammals, is tightly controlled during mouse early embryogenesis. In the morula, X-inactivation is imprinted with exclusive silencing of the paternally inherited X-chromosome. In contrast, in the post-implantation epiblast, X-inactivation affects randomly either the paternal or the maternal X-chromosome. The transition from imprinted to random X-inactivation takes place in the inner cell mass (ICM) of the blastocyst from which embryonic stem (ES) cells are derived. The trigger of X-inactivation, Xist, is specifically downregulated in the pluripotent cells of the ICM, thereby ensuring the reactivation of the inactive paternal X-chromosome and the transient presence of two active X-chromosomes. Moreover, Tsix, a critical cis-repressor of Xist, is upregulated in the ICM and in ES cells where it imposes a particular chromatin state at the Xist promoter that ensures the establishment of random X-inactivation upon differentiation. Recently, we have shown that key transcription factors supporting pluripotency directly repress Xist and activate Tsix and thus couple Xist/Tsix control to pluripotency. In this manuscript, we report that Rnf12, a third X-linked gene critical for the regulation of X-inactivation, is under the control of Nanog, Oct4 and Sox2, the three factors lying at the heart of the pluripotency network. We conclude that in mouse ES cells the pluripotency-associated machinery exerts an exhaustive control of X-inactivation by taking over the regulation of all three major regulators of X-inactivation: Xist, Tsix, and Rnf12

Twisted fallopian tube in pregnancy: a case report

BACKGROUND: Isolated twisted fallopian tube is an uncommon event, isolated twisted fallopian tube in pregnancy is also very rare. The diagnosis is often difficult and established during the operation. The right fallopian tube is most common affected. CASE PRESENTATION: We report an uncommon twisted left fallopian tube in pregnancy. A 34-year-old G(3)P(2) 28 weeks pregnant woman presented with acute left lower abdominal pain. The clinical and ultrasonographic findings led to diagnosis of twisted left ovarian cyst. Emergency exploratory laparotomy was performed. A twisted left fallopian tube and paratubal cyst was noted and left salpingectomy was performed. The postoperative course was uneventful and the pregnancy continued until term without complication. CONCLUSIONS: Although isolated twisted fallopian tube during pregnancy is very rare, it should be included in the differential diagnosis of acute abdomen in pregnancy. Early surgical intervention will decrease obstetric morbidity and may allow preservation of the fallopian tube

Photo-antagonism of the GABAA receptor

Neurotransmitter receptor trafficking is fundamentally important for synaptic transmission and neural network activity. GABAA receptors and inhibitory synapses are vital components of brain function, yet much of our knowledge regarding receptor mobility and function at inhibitory synapses is derived indirectly from using recombinant receptors, antibody-tagged native receptors and pharmacological treatments. Here we describe the use of a set of research tools that can irreversibly bind to and affect the function of recombinant and neuronal GABAA receptors following ultraviolet photoactivation. These compounds are based on the competitive antagonist gabazine and incorporate a variety of photoactive groups. By using site-directed mutagenesis and ligand-docking studies, they reveal new areas of the GABA binding site at the interface between receptor β and α subunits. These compounds enable the selected inactivation of native GABAA receptor populations providing new insight into the function of inhibitory synapses and extrasynaptic receptors in controlling neuronal excitation

Phoenix Is Required for Mechanosensory Hair Cell Regeneration in the Zebrafish Lateral Line

In humans, the absence or irreversible loss of hair cells, the sensory mechanoreceptors in the cochlea, accounts for a large majority of acquired and congenital hearing disorders. In the auditory and vestibular neuroepithelia of the inner ear, hair cells are accompanied by another cell type called supporting cells. This second cell population has been described as having stem cell-like properties, allowing efficient hair cell replacement during embryonic and larval/fetal development of all vertebrates. However, mammals lose their regenerative capacity in most inner ear neuroepithelia in postnatal life. Remarkably, reptiles, birds, amphibians, and fish are different in that they can regenerate hair cells throughout their lifespan. The lateral line in amphibians and in fish is an additional sensory organ, which is used to detect water movements and is comprised of neuroepithelial patches, called neuromasts. These are similar in ultra-structure to the inner ear's neuroepithelia and they share the expression of various molecular markers. We examined the regeneration process in hair cells of the lateral line of zebrafish larvae carrying a retroviral integration in a previously uncharacterized gene, phoenix (pho). Phoenix mutant larvae develop normally and display a morphologically intact lateral line. However, after ablation of hair cells with copper or neomycin, their regeneration in pho mutants is severely impaired. We show that proliferation in the supporting cells is strongly decreased after damage to hair cells and correlates with the reduction of newly formed hair cells in the regenerating phoenix mutant neuromasts. The retroviral integration linked to the phenotype is in a novel gene with no known homologs showing high expression in neuromast supporting cells. Whereas its role during early development of the lateral line remains to be addressed, in later larval stages phoenix defines a new class of proteins implicated in hair cell regeneration

Changes in Gray Matter Induced by Learning—Revisited

BACKGROUND: Recently, activation-dependant structural brain plasticity in humans has been demonstrated in adults after three months of training a visio-motor skill. Learning three-ball cascade juggling was associated with a transient and highly selective increase in brain gray matter in the occipito-temporal cortex comprising the motion sensitive area hMT/V5 bilaterally. However, the exact time-scale of usage-dependant structural changes occur is still unknown. A better understanding of the temporal parameters may help to elucidate to what extent this type of cortical plasticity contributes to fast adapting cortical processes that may be relevant to learning. PRINCIPAL FINDINGS: Using a 3 Tesla scanner and monitoring whole brain structure we repeated and extended our original study in 20 healthy adult volunteers, focussing on the temporal aspects of the structural changes and investigated whether these changes are performance or exercise dependant. The data confirmed our earlier observation using a mean effects analysis and in addition showed that learning to juggle can alter gray matter in the occipito-temporal cortex as early as after 7 days of training. Neither performance nor exercise alone could explain these changes. CONCLUSION: We suggest that the qualitative change (i.e. learning of a new task) is more critical for the brain to change its structure than continued training of an already-learned task