Effects of Nocturnal Light on (Clock) Gene Expression in Peripheral Organs: A Role for the Autonomic Innervation of the Liver

BACKGROUND:The biological clock, located in the hypothalamic suprachiasmatic nucleus (SCN), controls the daily rhythms in physiology and behavior. Early studies demonstrated that light exposure not only affects the phase of the SCN but also the functional activity of peripheral organs. More recently it was shown that the same light stimulus induces immediate changes in clock gene expression in the pineal and adrenal, suggesting a role of peripheral clocks in the organ-specific output. In the present study, we further investigated the immediate effect of nocturnal light exposure on clock genes and metabolism-related genes in different organs of the rat. In addition, we investigated the role of the autonomic nervous system as a possible output pathway of the SCN to modify the activity of the liver after light exposure. METHODOLOGY AND PRINCIPAL FINDINGS:First, we demonstrated that light, applied at different circadian times, affects clock gene expression in a different manner, depending on the time of day and the organ. However, the changes in clock gene expression did not correlate in a consistent manner with those of the output genes (i.e., genes involved in the functional output of an organ). Then, by selectively removing the autonomic innervation to the liver, we demonstrated that light affects liver gene expression not only via the hormonal pathway but also via the autonomic input. CONCLUSION:Nocturnal light immediately affects peripheral clock gene expression but without a clear correlation with organ-specific output genes, raising the question whether the peripheral clock plays a "decisive" role in the immediate (functional) response of an organ to nocturnal light exposure. Interestingly, the autonomic innervation of the liver is essential to transmit the light information from the SCN, indicating that the autonomic nervous system is an important gateway for the SCN to cause an immediate resetting of peripheral physiology after phase-shift inducing light exposures

Hyperperfusion profiles after recanalization differentially associate with outcomes in a rat ischemic stroke model

Futile recanalization hampers prognoses of ischemic stroke after successful mechanical thrombectomy, hypothetically through post-recanalization perfusion deficits, onset-to-groin delays and sex effects. Clinically, acute multiparametric imaging studies remain challenging. We assessed possible relationships between these factors and disease outcome after experimental cerebral ischemia-reperfusion, using translational MRI, behavioral testing and multi-model inference analyses. Male and female rats (N = 60) were subjected to 45-/90-min filament-induced transient middle cerebral artery occlusion. Diffusion, T2- and perfusion-weighted MRI at occlusion, 0.5 h and four days after recanalization, enabled tracking of tissue fate, and relative regional cerebral blood flow (rrCBF) and -volume (rrCBV). Lesion areas were parcellated into core, salvageable tissue and delayed injury, verified by histology. Recanalization resulted in acute-to-subacute lesion volume reductions, most apparently in females (n = 19). Hyperacute normo-to-hyperperfusion in the post-ischemic lesion augmented towards day four, particularly in males (n = 23). Tissue suffering delayed injury contained higher ratios of hypoperfused voxels early after recanalization. Regressed against acute-to-subacute lesion volume change, increased rrCBF associated with lesion growth, but increased rrCBV with lesion reduction. Similar relationships were detected for behavioral outcome. Post-ischemic hyperperfusion may develop differentially in males and females, and can be beneficial or detrimental to disease outcome, depending on which perfusion parameter is used as explanatory variable.</p

Relativistically rotating dust

Dust configurations play an important role in astrophysics and are the simplest models for rotating bodies. The physical properties of the general--relativistic global solution for the rigidly rotating disk of dust, which has been found recently as the solution of a boundary value problem, are discussed.Comment: 18 pages, 11 figure

Memantine treatment does not affect compulsive behavior or frontostriatal connectivity in an adolescent rat model for quinpirole-induced compulsive checking behavior

RATIONALE: Compulsivity often develops during childhood and is associated with elevated glutamate levels within the frontostriatal system. This suggests that anti-glutamatergic drugs, like memantine, may be an effective treatment. OBJECTIVE: Our goal was to characterize the acute and chronic effect of memantine treatment on compulsive behavior and frontostriatal network structure and function in an adolescent rat model of compulsivity. METHODS: Juvenile Sprague-Dawley rats received repeated quinpirole, resulting in compulsive checking behavior (n = 32; compulsive) or saline injections (n = 32; control). Eight compulsive and control rats received chronic memantine treatment, and eight compulsive and control rats received saline treatment for seven consecutive days between the 10th and 12th quinpirole/saline injection. Compulsive checking behavior was assessed, and structural and functional brain connectivity was measured with diffusion MRI and resting-state fMRI before and after treatment. The other rats received an acute single memantine (compulsive: n = 12; control: n = 12) or saline injection (compulsive: n = 4; control: n = 4) during pharmacological MRI after the 12th quinpirole/saline injection. An additional group of rats received a single memantine injection after a single quinpirole injection (n = 8). RESULTS: Memantine treatment did not affect compulsive checking nor frontostriatal structural and functional connectivity in the quinpirole-induced adolescent rat model. While memantine activated the frontal cortex in control rats, no significant activation responses were measured after single or repeated quinpirole injections. CONCLUSIONS: The lack of a memantine treatment effect in quinpirole-induced compulsive adolescent rats may be partly explained by the interaction between glutamatergic and dopaminergic receptors in the brain, which can be evaluated with functional MRI

Propofol anesthesia improves stroke outcomes over isoflurane anesthesia—a longitudinal multiparametric MRI study in a rodent model of transient middle cerebral artery occlusion

General anesthesia is routinely used in endovascular thrombectomy procedures, for which volatile gas and/or intravenous propofol are recommended. Emerging evidence suggests propofol may have superior effects on disability and/or mortality rates, but a mode-of-action underlying these class-specific effects remains unknown. Here, a moderate isoflurane or propofol dosage on experimental stroke outcomes was retrospectively compared using serial multiparametric MRI and behavioral testing. Adult male rats (N = 26) were subjected to 90-min filament-induced transient middle cerebral artery occlusion. Diffusion-, T2- and perfusion-weighted MRI was performed during occlusion, 0.5 h after recanalization, and four days into the subacute phase. Sequels of ischemic damage—blood–brain barrier integrity, cerebrovascular reactivity and sensorimotor functioning—were assessed after four days. While size and severity of ischemia was comparable between groups during occlusion, isoflurane anesthesia was associated with larger lesion sizes and worsened sensorimotor functioning at follow-up. MRI markers indicated that cytotoxic edema persisted locally in the isoflurane group early after recanalization, coinciding with burgeoning vasogenic edema. At follow-up, sequels of ischemia were further aggravated in the post-ischemic lesion, manifesting as increased blood–brain barrier leakage, cerebrovascular paralysis and cerebral hyperperfusion. These findings shed new light on how isoflurane, and possibly similar volatile agents, associate with persisting injurious processes after recanalization that contribute to suboptimal treatment outcome

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Reply to Gentner et al.: As simple as possible, but not simpler

Animal science

Study of friction and wear of thermoplastic vulcanizates: The correlation with abraded surfaces topology

The work was focused on the study of friction and wear properties of thermoplastic vulcanizates (TPV) based on polypropylene (PP), natural rubber (NR) and styrene butadiene rubber (SBR) compounds containing all common additives and curatives using ball-on-flat method. Pure materials and binary TPV blends of PP/NR, as well those of PP/SBR with the compositions 95/5, 75/25 and 50/50 (in weight %) were compounded and analysed. It is very well known that the coefficient of friction (COF), as well as wear values of pure thermoplastic matrix are significantly lower than those for pure rubber. Thus, it was found that the friction coefficient and wear of TPVs significantly increased in accordance with increased content of rubber material. Surprisingly, NR compared with SBR of similar concentrations in PP matrix, considerably affected wear of samples and the friction coefficient remained almost unaffected. Finally the topology of abraded surfaces were examined by using scanning electron microscopy (SEM) in order to understand the relationship between the COF, wear process and the composition of TPVs. © Published under licence by IOP Publishing Ltd.Operational Program Research and Development for Innovations - European Regional Development Fund (ERDF); national budget of the Czech Republic [CZ.1.05/2.1.00/19.0409]; Ministry of Education, Youth and Sports of the Czech Republic - Program NPU I [LO1504

Simple rules can explain discrimination of putative recursive syntactic structures by a songbird species

According to a controversial hypothesis, a characteristic unique to human language is recursion. Contradicting this hypothesis, it has been claimed that the starling, one of the two animal species tested for this ability to date, is able to distinguish acoustic stimuli based on the presence or absence of a center-embedded recursive structure. In our experiment we show that another songbird species, the zebra finch, can also discriminate between artificial song stimuli with these structures. Zebra finches are able to generalize this discrimination to new songs constructed using novel elements belonging to the same categories, similar to starlings. However, to demonstrate that this is based on the ability to detect the putative recursive structure, it is critical to test whether the birds can also distinguish songs with the same structure consisting of elements belonging to unfamiliar categories. We performed this test and show that seven out of eight zebra finches failed it. This suggests that the acquired discrimination was based on phonetic rather than syntactic generalization. The eighth bird, however, must have used more abstract, structural cues. Nevertheless, further probe testing showed that the results of this bird, as well as those of others, could be explained by simpler rules than recursive ones. Although our study casts doubts on whether the rules used by starlings and zebra finches really provide evidence for the ability to detect recursion as present in “context-free” syntax, it also provides evidence for abstract learning of vocal structure in a songbird

Daily rhythms in metabolic liver enzymes and plasma glucose require a balance in the autonomic output to the liver

Daily variations in plasma glucose concentrations are controlled by the biological clock, located in the suprachiasmatic nucleus. Our previous studies indicated an important role for the sympathetic innervation of the liver in the generation of the daily glucose rhythm. In the present study, we investigated further the role of the autonomic nervous system (ANS) in the genesis of the plasma glucose rhythm. First, we showed that complete removal of the autonomic inputs to the liver did not impair the plasma glucose rhythm or the daily expression of the glucoregulatory enzymes in the liver. Consequently, we studied whether the daily glucose rhythm is driven by the daily feeding activity in denervated animals. Surprisingly, complete denervation combined with a noncircadian feeding schedule also did not abolish the 24-h profile in plasma glucose or all daily rhythms in the gene expression of liver enzymes. These results demonstrate that the mechanisms used by the suprachiasmatic nucleus to control the rhythmic expression of glucose-metabolizing enzymes and the 24-h rhythm in plasma glucose concentrations are highly versatile and the glucose rhythm can be maintained in absence of hepatic ANS input and/or a day/night rhythm in feeding activity. Interestingly, a hepatic sympathectomy or parasympathectomy did abolish the plasma glucose rhythm, demonstrating that a unilateral denervation of the liver is more deleterious to maintaining the rhythmic liver metabolism than a complete removal of both branches. This observation supports the notion that an unbalanced ANS in obesity and diabetes accounts for the disturbed glucose balance in these disorder