In this respect, behavior associated with immediate reward can be considered the default behavior in general, and thus should require control to be overcome. Consistent with this view, neuroimaging studies of intertemporal choice, beyond those focused on exploration or foraging, suggest that patient behavior (i.e., choices for longer term over immediate reward) rely on neural mechanisms associated with cognitive control ( Figner et al., 2010, McClure et al., 2007 and McClure et al., 2004), including the dACC. In these cases, as in general, the EVC model buy BMN 673 proposes that the role of dACC is to

determine the EVC of the control-demanding behavior, and specify the control signal needed to pursue it. This assumes that it has access to information Enzalutamide about the value of the options in contention that is represented in other structures, such as ventral regions of mPFC ( Floresco et al., 2008, Haber and Knutson, 2010, Prévost

et al., 2010, Rangel and Hare, 2010 and Rushworth et al., 2011). The expected value of a control-demanding behavior depends not only on the reward it promises, but also on the expenditures needed to procure that reward; that is, it depends on the cost of control (Cost(signal) in Equation 1). As reviewed earlier, behavioral evidence supports the idea that the exertion of control is associated with subjective disutility manifest as the avoidance of control-demanding tasks (Kool and Botvinick, 2012; Kool et al., 2010). The EVC model proposes that the dACC registers PIK-5 the costs of control in a manner that is proportional to the intensity of control and that it specifies control signals in a way that is sensitive to such costs. This proposal generates several predictions concerning dACC function and its relation to behavior. First, and most simply, the dACC should be sensitive to demands for control and/or to the intensity of the current control signal.

As reviewed in the preceding sections, there is abundant evidence in support of this prediction. Second, the dACC should encode the exertion of control as costly. Evidence consistent with this idea has come from several recent studies. For example, Botvinick and colleagues (2009a) found that, during performance of a cognitively demanding task, a greater dACC response predicted decreased subsequent responses in nucleus accumbens to monetary reward, interpreted as “payment” for the task. This effect is consistent with cognitive effort discounting; that is, a reduction in the subjective value attached to a reward based on cognitive costs borne to attain it. Other studies have shown that dACC responses to such costs predict subsequent decisions about control. In one, Magno and colleagues (2006) presented participants with a series of attentionally demanding search arrays and, for each array, gave them the choice to identify the presence or absence of a target or to indicate that they would like to forgo the search on that trial.

, 2008) which is an activator of RGS4 (Huang et al., 2007), whose inhibition increases the efficacy of muscarinic autoreceptor function (Ding et al., 2006) (Figure 8C). Lowered cholinergic tone, a reduction of striatal GDNF levels due to progressive degeneration of ACh neurons, and a lack of functional adaptations by surviving ACh neurons should all influence the physiology of surviving

DA neurons in Shh-nLZC/C/Dat-Cre mice. Consistent with this expectation, we observe highly dynamic distortions in DA tissue content in both the vMB and the striatum. Hence, our results suggest that surviving DA neurons, but not surviving ACh neuron, are able to adapt their physiology dynamically in the face of progressive neurodegeneration and decreased ACh and GDNF/Ret signaling during early adulthood. ABT-263 mw However, by 10 months of age, we find the manifestation of discrete locomotion and gait disturbances,

indicating that the progressive deterioration of the mesostriatal circuit surpasses the compensatory capacity of DA neurons in aged Shh-nLZC/C/Dat-Cre mice ( Figure 8D). Archetypes of basal ganglia models imply that an imbalance of cholinergic and dopaminergic signaling in the striatum is responsible for the hyper- and hypokinetic manifestations of progressive movement disorders such as PD (Obeso et al., 2010). Our work describes a mouse paradigm that recapitulates many of the key features of the progressive cellular, neurochemical, and functional pathologies observed in PD with this website apparent face-, construct-, and predictive-validity since the functional phenotype that is associated with progressive neuronal loss can be ameliorated with DA supplementation or a muscarinic antagonist also used in the Glyceronephosphate O-acyltransferase management of PD. Yet, the resemblance of the phenotype of Shh-nLZC/C/Dat-Cre mice with PD does not extend to the absolute direction of alterations in cholinergic tone. In PD, ACh tone is increased (Wooten, 1990), while in our paradigm ACh tone is decreased

in the absence of Shh signaling from DA neurons, which also must occur in PD. How can these findings be reconciled? Our data points to the possibility that Shh production is increased in still functioning DA neurons in response to the mounting pathophysiological cell stress in the basal ganglia of PD patients. This notion is supported by several in vivo experiments described herein: we demonstrate that the transcription of Shh in DA neurons is strongly upregulated upon (1) injection of 6-OHDA into the mFB, (2) induction of cholinergic dysfunction in the striatum, (3) induction of cholinergic dysfunction in the PPTg, and (4) the genetic ablation of part of the Shh locus which abrogates the production of functional Shh by DA neurons.

, 1967). The relationship between early life inhibitors stress exposure and subsequent resilience in both primates and rodents follows selleck compound the abovementioned U-shaped curve. Prolonged maternal separation and social isolation in infant rhesus monkeys produce an increased stress response and “despair-like” behavior in subsequent social separation tests (Young et al., 1973). Rats exposed to moderate early life stress show enhanced measures of resilience compared to both severely and minimally stressed rats (Macri and Wurbel, 2007). For example, early postnatal rats exposed to brief daily handling (a moderate stressor) subsequently show attenuated stress response compared to undisturbed pups and pups

exposed to prolonged daily maternal separation (a more severe stressor) (Plotsky and Meaney, 1993 and Macri et al., 2004). Chronic unpredictable stress (CUS) is a useful model for examining stress vulnerability and resilience in rodents (Ricon et al., 2012 and LaPlant et al., 2009). In CUS paradigms, animals are exposed to varying mild stressors sequentially for a period of 1–7 weeks (Krishnan and Nestler, 2011 and Willner, 1997).

Stressors can include mild foot shock, physical restraint, tail suspension, light/dark cycle disruption, food or water restriction, changes to cage mate, etc., and are changed after several hours to minimize habituation (LaPlant et al., 2009 and Willner, 1997). CUS produces a range of depression and anxiety-like behaviors in rodents including learn more Adenosine anhedonia, measured as decreased sucrose preference, despair-like behavior, measured as increased immobility in the forced swim and tail suspension tests, and novelty suppressed feeding, measured as a decrease in approach to a

novel food item (Krishnan and Nestler, 2011, Mineur et al., 2006 and Feng et al., 2012). Mice exposed to CUS also display decreased grooming, aggression, and sexual behaviors. Certain CUS-induced behavioral changes, such as novelty suppressed feeding, can be reversed only by chronic antidepressant treatment (Willner, 1997), making CUS relevant to human antidepressant responses. Female mice display immobility in the forced swim test after just 6 days of subchronic unpredictable stress (SCUS) whereas males are generally resilient to SCUS and require 20–28 days of CUS exposure to elicit depression- and anxiety-like behavior (Hodes, G.E. et al., Soc. Neurosci. Abstr. 219.01, 2011). Interestingly, age is a factor in response to CUS—male rats exposed to 60 days of CUS in the juvenile period exhibit greater memory retention in a two-way shuttle avoidance task compared to rats exposed to the same stressor in adulthood, indicating enhanced cognitive resilience ( Ricon et al., 2012). Sex differences and age effects in susceptibility to CUS-induced depression and anxiety-like behavior make this a powerful tool for investigating the hormonal and neural basis for stress vulnerability and resilience across the lifespan.

Members do not receive payment for serving on the CTV. Provided that the Chairman

is not a member of the civil service (usually the case), the Chairman is remunerated for meetings over which he or she presides. Other members, for example the authors of reports, can be remunerated as well. There are a number of ex-officio members who represent agencies affiliated with the Ministry of Health, or other ministries and various institutions. While they do not have voting power, they do have the right to participate actively in discussions. The information provided by two organizations, the INVS (Institut de Veille Sanitaire or the Sanitary Surveillance selleck kinase inhibitor Institute) and the AFSSAPS (Agence Française de Sécurité Sanitaire des Produits de Santé or the French Sanitary Safety Agency for Health Products), often have a major impact on decision making. Usually, the texts are voted upon to reach consensus. The committee is currently being evaluated by the Inspection Générale des Affaires Sociales (IGAS) or the General Inspection for Social Affairs. This assessment may result in changes to the membership appointment structure in the next year. Routine reporting of any inhibitors conflicts of interest regarding committee members is a requirement, and the management of conflicts of interest is a major concern. The CTV has a conflict of interest

charter, which is coupled with a procedure to assess for conflicts of interest. Possible conflicts of interest must be declared annually, and these declarations

must be kept up-to-date. At the start of each meeting, members must selleckchem disclose any possible conflicts of interest they may have concerning topics on the agenda. Rolziracetam The situation for each CTV member is analyzed before each plenary session by the Secretariat of the HCSP and possibly by the CTV Chairman as well. This also applies to members of CTV working groups. Action is taken if a member has any apparent interests in relation to a vaccine or intervention to be discussed. The conflicts of interest charter consists of classification of potential conflicts of interest based on the AFSSAPS’ classification of conflicts of interest [4]. If the conflict is classified as minor (e.g., a person was invited to a conference where industry paid registration fees and accommodation but provided no other benefits or compensation), this person may participate in debates and votes concerning the relevant topic. If conflict of interest concerning a particular topic is classified as major, the expert in question is excluded both from debates and votes pertaining to that topic. For example, an expert who is a coordinating investigator for clinical trials of a certain vaccine would be excluded from debates and votes concerning that vaccine, or competing vaccines or interventions. Members are not required to sign a confidentiality form or similar kinds of agreement. They are informed, however, that the content of any CTV proceeding is confidential.

In our study, we considered hospital wastes as a potential source of MDR bacteria. All the media used in the present study were procured from HiMedia Laboratories Pvt. Ltd., and all the chemicals and reagents used during the study were purchased from Merck India Pvt. Ltd. MDR bacteria were isolated from contaminated cotton and bandages collected from Assam Medical College Hospital, Dibrugarh (India). The MDR strains were screened by treating the pure isolates with a number of commercially available antibiotic discs. The MDR isolates

were identified on the basis of Bcl-2 inhibitor staining techniques and biochemical characteristics. Citrate stabilized AgNPs were synthesized by using the technique described by Borah et al15 Here, sodium citrate acted as both reducing and stabilizing reagent. The reaction mechanism could be expressed as follows: 4Ag++C6H5O7Na3+2H2O→4Ag0 + C6H5O7H3 + 3Na++H++O2 The AgNPs were synthesized by taking 10 g of surface sterilized finely chopped fresh leaves of O. sanctum in 50 mL of deionized water. It was then stirred at 60 °C for 1 h. The mixture was then cooled and filtered using 0.45μ membrane filters (HiMedia India Ltd.) and stored at 4 °C for further use. 5 mL of the leaf extract was added in 45 mL of 10−3 M silver nitrate (AgNO3)

solution. The change of colour from pale VRT752271 purchase yellow to reddish brown indicates the formation of Ag nanoparticles. The synthesis of AgNPs was initially confirmed by taking the absorbance in the range of 300–500 nm using the UV/VIS spectrophotometer (Shimadzu U.V-1800) and the size of the synthesized

AgNPs were confirmed by nanoparticle size analyser (Brookhaven Instruments Corporation 90 Plus Particle Sizing, USA). The antimicrobial activity of silver nanoparticles was examined using the standard broth dilution method in Luria–Bertani (LB) broth. Sterile conical flasks, each containing 100 mL of LB broth were sonicated (Sartorius inhibitors Stedim Labsonic, Germany Ltd.) for 10 min at an amplitude of 100% for one cycle after adding different concentration of nanoparticles (20, 40…200 μL), to prevent aggregation of nanoparticles. Subsequently, the flasks were inoculated with 1 mL of freshly prepared Cell press bacterial suspension in order to maintain initial bacterial concentration (103–104 CFU/mL) and then incubated in an orbital shaker at 200 rpm and 37 °C (Sartorius Stedim–Certomat BS-1 shaker incubator, Germany Ltd.). Bacterial growth was measured as increase in absorbance at 600 nm determined using a spectrophotometer (Shimadzu UV-1800). The experiments include a control (flask containing inoculum and LB broth, devoid of nanoparticles). The MDR bacterial strains were isolated from contaminated cotton and bandages and were identified as Staphylococcus aureus and Bacillus megaterium. The strains were identified on the basis of biochemical characteristics. S.

For this analysis, we only considered sGFP cells within 400 μm from the PCs, because the probability for these interneurons to be connected becomes negligible selleck chemicals beyond 400 μm (Figure 4C). We defined this probability as the number of common inputs divided by the total number of stimulated interneurons

and observed that it was similar between connected (0.42 ± 0.08, n = 8) and unconnected PCs (0.35 ± 0.03, n = 33; p = 0.36, Mann-Whitney; Figure 7F). This indicates that synaptically connected PCs, which are part of the same synaptic circuits, receive as many common sGFP inputs as unconnected PCs. These results overall suggest that sGFP cells appear to connect with PCs in a similar fashion, without discriminating whether these PCs are connected or not and therefore do not form specific subnetworks. We performed our initial mapping experiments with young animals (P11–P16), relatively early in the MAPK inhibitor development of these circuits. It was therefore possible that the dense and unspecific

organization of inhibitory circuit would be a transitory developmental state and that similar mapping in older animals could yield sparser, perhaps more specific, functional maps. To test this hypothesis, we performed optical mapping experiments with older animals, in a range of developmental stages from P11 to P41, which encompass the normal maturation of mouse neocortical circuits through critical periods and into adulthood (Fagiolini and Hensch, 2000). We observed that the connection probability was similar throughout the range of ages examined (p > 0.05, one-way ANOVA): P11 to P12 (0.49 ± 0.04, n = 26), P13 to P14 (0.38 ± 0.03, n = 28), P15 to P17 (0.47 ± 0.06, n = 10), P18 to P20 (0.56 ± 0.06, n = 11), P22 to P23 (0.55 ± 0.05, n = 10), P26 to P30 (0.52 ± 0.12, n = 4), P34 to P35 (0.56 ± 0.04, n = 8), and P36 to P41 (0.54 ± 0.05, n = 7) (Figure 8A). It should be noted that there was a small significant

decrease in connection probability at P13–P14 (p = 0.04, compared to P11–P12; Mann-Whitney), which could indicate a potential remodeling of the connectivity in the Rutecarpine cortical circuits at the opening eyes stage of the development. The proportions of connected, unconnected interneurons and false positive were not significantly different for young (P11–P16) versus mature (P20–P41). The mature mapping revealed 55.8% ± 2.4% of connected sGFP cells (versus 43.2% ± 2.5% for young, p = 0.65, t test), 39.0% ± 2.5% of unconnected sGFP cells (versus 44.3% ± 2.6% for young, p = 0.85, t test) and 5.3% ± 1.0% of false positives (versus 12.5% ± 1.6% for young animals, p = 0.67, t test).

We crushed the sciatic nerve, waited 3 days,

and then cultured adult DRG neurons for 16 hr in order to evaluate their regeneration capacity. We assessed axon regrowth by measuring the length of the longest axon from each neuron. Prior nerve injury markedly potentiates axon regrowth in WT DRG culture, as previously demonstrated (Smith and Skene, 1997), leading to a significant increase in the ratio of neurons bearing long (>400 μm) selleckchem axons (p < 0.001) and a significant decrease in the ratio of neurons with short (<75 μm) axons (p < 0.001) (Figures 2D and 2E). However, this accelerated axonal growth was blocked in DLK KO neurons (p < 0.001) (Figures 2D and 2E), demonstrating the requirement of DLK for the preconditioning effect. Importantly, these in vitro results highlight that the reduced in vivo regeneration in DLK KOs is unlikely to be secondary to the delayed degeneration of the check details distal

stump in the absence of DLK (Miller et al., 2009). Instead, our data show that DLK directly promotes the preconditioning effect in injured neurons. We next investigated mechanisms by which DLK promotes neuronal response to injury. Nerve injury activates molecular pathways that contribute positively to axonal regeneration. We hypothesized that DLK is required for these injury-induced signals and so assayed markers of these injury-induced pathways. Of these, the most likely candidate is the transcription factor cJun, a downstream target of the DLK/JNK pathway that is phosphorylated upon axonal injury and promotes axon regeneration in the mouse peripheral nervous system (Raivich et al., 2004). Rutecarpine We used immunofluorescence to detect p-cJun in the nuclei of DRG neurons from WT and Wnt1-Cre conditional DLK KO animals 3 days after sciatic nerve lesion and found that the injury-induced increase in the number of cells expressing p-cJun is blocked in DLK KO mice (p < 0.001) ( Figure S4).

These data are consistent with the previous report by Itoh et al. (2009) using DLK gene-trap mice. To our surprise, however, this was not the only injury signaling pathway blocked by the loss of DLK. Upon injury, the transcription factor STAT3 is phosphorylated and accumulates in DRG cell bodies, where it promotes axonal regeneration ( Bareyre et al., 2011; Qiu et al., 2005). In the absence of DLK, however, this accumulation of p-STAT3 is blocked. In WT DRGs, there is a 2-fold increase in the p-STAT3 levels in DRG cell bodies upon nerve injury; however, there is no significant increase in p-STAT3 in DLK KO DRGs (p < 0.05) ( Figures 3A and 3B). Hence, DLK is required for the activation of two proregenerative pathways in the cell bodies of injured neurons. STAT3 is phosphorylated by JAK kinase (Qiu et al., 2005), so the decrease in p-STAT3 in the DLK KO was surprising. Although STAT3 is a transcription factor, it is present in axons, locally phosphorylated after a nerve injury, and retrogradely transported after injury (Ben-Yaakov et al., 2012).

The spike generation threshold (dotted line, Figure 5E,F) was constrained such that the orientation selectivity and tuning sharpness of spikes matched experimentally measured Pyr cell spike tuning properties (modeled suprathreshold Raf activity OSI = 0.7 and HWHH = 24 deg; Figure 5F, black trace). To test the impact of PV cell suppression on model

Pyr cell responses, we decreased the inhibitory conductance by 10%, as experimentally determined. Notably, this reduction in inhibition not only resulted in a substantial increase in the modeled spiking response (∼50%) but did so in a manner that was strikingly consistent with the experimentally observed linear transformation—i.e., a small decrease in OSI (ΔOSI = 0.08) and no impact on tuning sharpness (ΔHWHH < 2 degrees; Figure 5F, Inset). The model robustly accounted for the transformation of Pyr cells over the wide range of Pyr cell orientation selectivity (Figure S3). Thus, this conductance-based model provides insight into how even slight changes in PV cell-mediated inhibition can lead to robust changes in response of Pyr cells to visual stimuli without having a major impact on their tuning properties. By manipulating the activity of PV cells bidirectionally we have determined that while these neurons minimally affect tuning properties, they have profound impact on the response of cortex to stimuli

at all contrasts and orientations. We identified a specific and basic computation contributed

by these neurons found during cortical visual processing: a linear transformation of Pyr cell responses, CHIR 99021 both additive and multiplicative. This linear transformation of course operates in the presence of a threshold, as firing rates cannot be reduced below zero. The bidirectional control of PV cells during visual stimulation has also allowed us to demonstrate the consistency of this transformation over a range of PV cell activity levels, from ∼20% below to 40% above control levels (Figure 2). While suppressing PV cell activity with Arch revealed their function under control conditions, increasing PV cell activity with ChR2 demonstrates their further potential for linearly transforming visual responses in layer 2/3 of the cortex. Finally we showed, using in vivo whole-cell recordings, that the robust changes caused by PV cell perturbation on visually evoked responses in Pyr cells result from relatively small modulations in synaptic inhibition. A conductance-based model provides a likely explanation for how this small yet systematic change in inhibition can lead not only to the observed change in spiking response but also to the observed linear transformation. Because of their powerful effect on firing rate, minor effect on direction and orientation selectivity and no systematic effects on tuning sharpness, PV-expressing interneurons appear ideally suited to modulate response gain in layer 2/3 of visual cortex (Figure 4).

, 2012 and Perin et al., 2011). In particular, we account for the presence of neocortical (S1, hindlimb area) excitatory (layer 4, L4, and layer

5, L5, pyramidal neurons) and inhibitory (L4 and L5 basket cells) neurons. We investigate the impact of slow (approximately 1 Hz) external activity impinging on neurons and its effect on the resulting LFP signature. Such rhythmic activity is relevant, for example, in the case of the most prominent of cortical processing, slow-wave activity (SWA, 0.1–1 Hz). Found in humans (Achermann and Borbély, 1997) and animals (Steriade et al., 1993a, Steriade et al., 1993b and Steriade et al., 1993c), SWA involves large areas of neocortex, along with various subcortical structures, that are synchronized into cyclical http://www.selleckchem.com/products/BIBW2992.html periods of global excitation followed by widespread silence. SWA is a defining characteristic of slow-wave, deep, or non-REM sleep but also occurs under anesthesia and in isolated cortical preparations. Neocortical cells discharge during the trough Trametinib of the LFP and remain silent during the peak of the LFP recorded from deep layers of cortex. Active and silent periods of this slow oscillation are referred to as UP (high conductance) and DOWN (low conductance) states. This robust neocortical oscillation coordinates various other rhythms, including spindles and delta waves (Steriade et al., 1993a, Steriade et al., 1993b and Steriade

et al., 1993c) and faster activity (Mukovski et al., 2007). Although we do not attempt to emulate the biophysical details of SWA involving a multitude of internal and external inputs, our large-scale, bottom-up biophysical model provides insights into the origin of the LFP signal, in the presence of active membrane conductances, realistic neural morphologies, and network connectivity patterns. Based on hundreds of morphologically and functionally reconstructed neurons (Druckmann et al., 2007 and Hay et al., 2011) (Figure S1 available online), the network model Resveratrol was built to capture many aspects of connectivity (Figure 1) (Hill et al., 2012, Oberlaender et al., 2012 and Perin et al., 2011). Neural membrane processing

of every compartment of every neuron is reflected in Ve by superposing membrane current contributions from each neural compartment using the line source approximation (Holt and Koch, 1999). That is, Ve at every location in extracellular space results from the linear summation of all membrane currents throughout the volume, scaled (to a first order inversely) by the distance to the current source (see the Experimental Procedures). In the present study, we focus on how the microscopic currents across each membrane sum to give rise to the macroscopic LFP signal and neglect any contributions that the LFP, in turn, might have on the voltage across each membrane (Anastassiou et al., 2010, Anastassiou et al., 2011 and Jefferys, 1995).

, 2010 and Smith et al., 2010). Confocal z stacks were collected for each RNAi clone. We used z projections to count 2° dendrites in each animal. The 2° dendrites were scored as PVD lateral branches that reached the location of either the dorsal or the ventral sublateral nerve cord ( Smith et al., 2010). Other defects in PVD development were also noted. A positive hit was defined as any RNAi clone that resulted in PVD defects in more than one animal in at least two replicates. The MI-773 price experimenter was blind to the identity of RNAi clones for all screens. Calcium transients generated by harsh touch and cold temperature were measured with optical recordings as previously

described (Chatzigeorgiou et al., 2010b) (see Supplemental Experimental

Procedures). For the glycerol experiments, animals were placed under the microscope in a perfusion chamber (RC-26GLP,Warner Instruments) under constant flow rate (0.4 ml/min) of “neuronal buffer” (100 mM NaCl, 1 mM MgSO4, 10 mM HEPES-NaOH [pH 7.1]) using a perfusion pencil (AutoMate). Outflow was regulated using a peristaltic pump (Econo Pump, Biorad). http://www.selleckchem.com/products/pd-0332991-palbociclib-isethionate.html Repellents were delivered with manually controlled valves. Glycerol was dissolved in M13 buffer (30 mM Tris-HCl [pH 7.0] 100 mM NaCl, 10 mM KCl) (Wood, 1988) to a final concentration of 1 M. We thank J. Powell-Coffman for pJ360 and ZG628 and O. Hobert for otIs181, otIs236, and advice. Some of the strains used in this work were provided by the C. elegans Genetics Center, which is supported by the National Institutes of Health (NIH) National Center for Research Resources. This work was supported by NIH Grants R01 NS26115, R01 NS079611, R21 N206882, and

U01 HG004263 to D.M.M.; NIH Grant F31 NS071801 to C.J.S.; and Deutsche Forschungsgemeinschaft Grants EXC115, GO1011/3-1, and GO1011/4-1 to A.G. S.J.H. was a Long-Term fellow of the Human Frontiers Science Program Organization. C.J.S., T.O., and D.M.M. designed experiments; C.J.S. and T.O. performed experiments with advice from D.M.M.; W.C.S. helped with microarray data out analysis; E.F.-L. helped with phenotypic analysis of ahr-1 and zag-1 strains and FISH experiments; M.C. and W.R.S. performed calcium imaging experiments; S.H. and S.M. generated deletion alleles of T24F1.4; S.J.H. and A.G. performed optogenetic experiments; and C.J.S., T.O., and D.M.M. wrote the paper with input from coauthors. “
“Circadian clocks are endogenous, self-sustained oscillators, which enable organisms to synchronize their molecular, cellular, and behavioral processes to daily environmental changes. The core timekeeping mechanism operates within individual cells and is comprised of multiple, interlocked transcriptional/translational feedback loops. In D.