Ghrelin, a stomach-derived hormone implicated in numerous behaviors including feeding, reward, stress, and addictive behaviors, acts by binding to the growth hormone secretagogue receptor (GHSR). ...Here, we present the development, verification, and initial characterization of a novel GHSR knockout (KO) Wistar rat model created with CRISPR genome editing.
Using CRISPR/Cas9, we developed a GHSR KO in a Wistar background. Loss of GHSR mRNA expression was histologically verified using RNAscope in wild-type (WT; n = 2) and KO (n = 2) rats. We tested the effects of intraperitoneal acyl-ghrelin administration on food consumption and plasma growth hormone (GH) concentrations in WT (n = 8) and KO (n = 8) rats. We also analyzed locomotion, food consumption, and body fat composition in these animals. Body weight was monitored from early development to adulthood.
The RNAscope analysis revealed an abundance of GHSR mRNA expression in the hypothalamus, midbrain, and hippocampus in WTs, and no observed probe binding in KOs. Ghrelin administration increased plasma GH levels (p = 0.0067) and food consumption (p = 0.0448) in WT rats but not KOs. KO rats consumed less food overall at basal conditions and weighed significantly less compared with WTs throughout development (p = 0.0001). Compared with WTs, KOs presented higher concentrations of brown adipose tissue (BAT; p = 0.0322).
We have verified GHSR deletion in our KO model using histological, physiological, neuroendocrinological, and behavioral measures. Our findings indicate that GHSR deletion in rats is not only associated with a lack of response to ghrelin, but also associated with decreases in daily food consumption and body growth, and increases in BAT. This GHSR KO Wistar rat model provides a novel tool for studying the role of the ghrelin system in obesity and in a wide range of medical and neuropsychiatric disorders.
Abstract
Climate change is intensifying global wildfire activity, and people and wildlife are increasingly exposed to hazardous air pollution during large-scale smoke events. Although wildfire smoke ...is considered a growing risk to public health, few studies have investigated the impacts of wildfire smoke on wildlife, particularly among species that are vulnerable to smoke inhalation. In this review, we synthesized research to date on how wildfire smoke affects the health and behavior of wildlife. After executing a systematic search using Web of Science, we found only 41 relevant studies. We synthesized findings from this literature and incorporated knowledge gained from fields outside wildlife science, specifically veterinary medicine and air pollution toxicology. Although studies that directly investigated effects of smoke on wildlife were few in number, they show that wildfire smoke contributes to adverse acute and chronic health outcomes in wildlife and influences animal behavior. Our review demonstrates that smoke inhalation can lead to carbon monoxide poisoning, respiratory distress, neurological impairment, respiratory and cardiovascular disease, oxidative stress, and immunosuppression in wildlife, including terrestrial and aquatic species, and these health effects can contribute to changes in movement and vocalization. Some species also use smoke as a cue to engage in fire-avoidance behaviors or to conserve energy. However, our review also highlights significant gaps in our understanding of the impacts of wildfire smoke on wildlife. Most notably, the lack of robust air pollution measurements in existing studies limits meta-analyses and hinders construction of dose-response relationships, thereby precluding predictions of health outcomes and behaviors under different air quality conditions, especially during extreme smoke events. We recommend that future studies leverage existing data sets, infrastructure, and tools to rapidly advance research on this important conservation topic and highlight the potential value of interdisciplinary collaborations between ecologists and atmospheric chemists.
Reaction of U(TrenTIPS)(THF)BPh4 (1; TrenTIPS=N{CH2CH2NSi(iPr)3}3) with NaPH2 afforded the novel f‐block terminal parent phosphide complex U(TrenTIPS)(PH2) (2; U–P=2.883(2) Å). Treatment of 2 with ...one equivalent of KCH2C6H5 and two equivalents of benzo‐15‐crown‐5 ether (B15C5) afforded the unprecedented metal‐stabilized terminal parent phosphinidene complex U(TrenTIPS)(PH)K(B15C5)2 (4; UP=2.613(2) Å). DFT calculations reveal a polarized‐covalent UP bond with a Mayer bond order of 1.92.
Straightforward deprotonation of the first f‐block terminal parent phosphide complex and potassium ion results in the isolation of an unprecedented structurally authenticated metal‐stabilized terminal parent phosphinidene complex. B15C5=benzo‐15‐crown‐5 ether.
Abstract
We present
K
-band interferometric observations of the PDS 70 protoplanets along with their host star using VLTI/GRAVITY. We obtained
K
-band spectra and 100
μ
as precision astrometry of ...both PDS 70 b and c in two epochs, as well as spatially resolving the hot inner disk around the star. Rejecting unstable orbits, we found a nonzero eccentricity for PDS 70 b of 0.17 ± 0.06, a near-circular orbit for PDS 70 c, and an orbital configuration that is consistent with the planets migrating into a 2:1 mean motion resonance. Enforcing dynamical stability, we obtained a 95% upper limit on the mass of PDS 70 b of 10
M
Jup
, while the mass of PDS 70 c was unconstrained. The GRAVITY
K
-band spectra rules out pure blackbody models for the photospheres of both planets. Instead, the models with the most support from the data are planetary atmospheres that are dusty, but the nature of the dust is unclear. Any circumplanetary dust around these planets is not well constrained by the planets’ 1–5
μ
m spectral energy distributions (SEDs) and requires longer wavelength data to probe with SED analysis. However with VLTI/GRAVITY, we made the first observations of a circumplanetary environment with sub-astronomical-unit spatial resolution, placing an upper limit of 0.3 au on the size of a bright disk around PDS 70 b.
Determining the electronic structure of actinide complexes is intrinsically challenging because inter-electronic repulsion, crystal field, and spin-orbit coupling effects can be of similar magnitude. ...Moreover, such efforts have been hampered by the lack of structurally analogous families of complexes to study. Here we report an improved method to U≡N triple bonds, and assemble a family of uranium(V) nitrides. Along with an isoelectronic oxo, we quantify the electronic structure of this 5f
family by magnetometry, optical and electron paramagnetic resonance (EPR) spectroscopies and modelling. Thus, we define the relative importance of the spin-orbit and crystal field interactions, and explain the experimentally observed different ground states. We find optical absorption linewidths give a potential tool to identify spin-orbit coupled states, and show measurement of U
···U
super-exchange coupling in dimers by EPR. We show that observed slow magnetic relaxation occurs via two-phonon processes, with no obvious correlation to the crystal field.
To further our fundamental understanding of the nature and extent of covalency in uranium-ligand bonding, and the benefits that this may have for the design of new ligands for nuclear waste ...separation, there is burgeoning interest in the nature of uranium complexes with soft- and multiple-bond-donor ligands. Despite this, there have so far been no examples of structurally authenticated molecular uranium-arsenic bonds under ambient conditions. Here, we report molecular uranium(IV)-arsenic complexes featuring formal single, double and triple U-As bonding interactions. Compound formulations are supported by a range of characterization techniques, and theoretical calculations suggest the presence of polarized covalent one-, two- and threefold bonding interactions between uranium and arsenic in parent arsenide U-AsH2, terminal arsinidene U=AsH and arsenido U≡AsK2 complexes, respectively. These studies inform our understanding of the bonding of actinides with soft donor ligands and may be of use in future ligand design in this area.
Highlights • We used a human systems neuroscience approach to understand neural mechanisms by which attention improves visual performance. • Humans as a model system have an advantage as behaviors ...can be explicitly instructed and highly sophisticated. • Human neural measurements are generally noninvasive and indirect, but retinotopy and contrast–response are highly reliable. • Computational modeling allowed us to test various linking hypotheses between quantitative behavioral and neural measurements. • Human systems neuroscience should validate and extend animal model findings in humans and form a link to higher cognition.
As the drive to improve the cost, performance characteristics and safety of lithium-ion batteries increases with adoption, one area where significant value could be added is that of battery ...diagnostics. This paper documents an investigation into the use of plasmonic-based optical fibre sensors, inserted internally into 1.4 Ah lithium-ion pouch cells, as a real time and in-situ diagnostic technique. The successful implementation of the fibres inside pouch cells is detailed and promising correlation with battery state is reported, while having negligible impact on cell performance in terms of capacity and columbic efficiency. The testing carried out includes standard cycling and galvanostatic intermittent titration technique (GITT) tests, and the use of a reference electrode to correlate with the anode and cathode readings separately. Further observations are made around the sensor and analyte interaction mechanisms, robustness of sensors and suggested further developments. These finding show that a plasmonic-based optical fibre sensor may have potential as an opto-electrochemical diagnostic technique for lithium-ion batteries, offering an unprecedented view into internal cell phenomena.
A subset of atypical memory B cells accumulates in malaria and several infections, autoimmune disorders and aging in both humans and mice. It has been suggested these cells are exhausted long-lived ...memory B cells, and their accumulation may contribute to poor acquisition of long-lasting immunity to certain chronic infections, such as malaria and HIV. Here, we generated an immunoglobulin heavy chain knock-in mouse with a BCR that recognizes MSP1 of the rodent malaria parasite,
. In combination with a mosquito-initiated
infection, we show that
-specific atypical memory B cells are short-lived and disappear upon natural resolution of chronic infection. These cells show features of activation, proliferation, DNA replication, and plasmablasts. Our data demonstrate that
-specific atypical memory B cells are not a subset of long-lived memory B cells, but rather short-lived activated cells, and part of a physiologic ongoing B-cell response.
Aims/hypothesis
Although skeletal muscle insulin resistance has been associated with activation of c-Jun N-terminal kinase (JNK), whether increased JNK activity causes insulin resistance in this ...organ is not clear. In this study we examined the metabolic consequences of isolated JNK phosphorylation in muscle tissue.
Methods
Plasmids containing genes encoding a wild-type JNK1 (WT-
JNK
) or a JNK1/JNKK2 fusion protein (rendering JNK constitutively active; CA-
Jnk
) were electroporated into one tibialis anterior (TA) muscle of C57Bl/6 mice, with the contralateral TA injected with an empty vector (CON) to serve as a within-animal control.
Results
Overproduction of WT-JNK resulted in a modest (∼25%) increase in phosphorylation (Thr
183
/Tyr
185
) of JNK, but no differences were observed in Ser
307
phosphorylation of insulin receptor substrate 1 (IRS-1) or total IRS-1 protein, nor in insulin-stimulated glucose clearance into the TA muscle when comparing WT-
JNK
with CON. By contrast, overexpression of CA-
Jnk
, which markedly increased the phosphorylation of CA-JNK, also increased serine phosphorylation of IRS-1, markedly decreased total IRS-1 protein, and decreased insulin-stimulated phosphorylation of the insulin receptor (Tyr
1361
) and phosphorylation of Akt at (Ser
473
and Thr
308
) compared with CON. Moreover, overexpression of CA-
Jnk
decreased insulin-stimulated glucose clearance into the TA muscle compared with CON and these effects were observed without changes in intramuscular lipid species.
Conclusions/interpretation
Constitutive activation of JNK in skeletal muscle impairs insulin signalling at the level of IRS-1 and Akt, a process which results in the disruption of normal glucose clearance into the muscle.
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