Small Brain Research Articles

A Rare Mutation Associated with Cerebral Arteriopathy with Subcortical Infarct and Leukoencephalopathy (CADASIL) (P2-5.002)

<h3>Objective:</h3> To report a rare cause of CADASIL with a point mutation in exon 5 of NOTCH 3 gene causing a non-cysteine change and its implication. <h3>Background:</h3> CADASIL is a rare genetic non-amyloid arteriopathy primarily affecting small brain vessels. Its prevalence in population is 2 to 5/100,000, but may be underestimated and underdiagnosed. Although there is over 200 different NOTCH-3 mutations described worldwide, 95% of them are missense mutation in the exons 2–24, which leads to a gain or loss of a cysteine residue in one of 34 epidermal growth factor-like repeat (EGFr) domains of the NOTCH3 protein. Non-cysteine mutations are rare and their role is not well determined. <h3>Design/Methods:</h3> Case report <h3>Results:</h3> 58-year-old man with a three-year progressive cognitive decline, history of headaches, fatigue, and generalized weakness was admitted to the neurology wards for worsening weakness and increased need for assistance in daily life. Neurological exam was significant for mild left hemiparesis. MoCA score was 19/30. Brain MRI showed one subacute and numerous chronic lacunar ischemic strokes including in the corpus callosum, also seen on previous outpatient MRIs. These changes had been attributed to demyelinating disease by the outpatient physician. An extensive workup including autoimmune was unrevealing. Classical leukoencephalopathy was not present, but hyperintensities in the temporal lobe raised concern for CADASIL. DNA sequencing revealed a non-cysteine mutation with c.754 G&gt;A transition in exon 5 of NOTCH 3 gene resulting in a substitution of Valine to Methionine (V252M). This is the second case of this mutation reported in the literature. Non-cysteine mutation may affect NOTCH-3 signaling output and possibly lead to a milder leukoencephalopathy and extensive involvement of corpus callosum with lacunar infarctions resembling demyelinating disease. <h3>Conclusions:</h3> CADASIL with a point mutation in exon 5 of NOTCH 3 gene causing a non-cysteine change may present with milder disease and not classical MRI changes. <b>Disclosure:</b> Dr. Delpirou Nouh has nothing to disclose. Dr. Mahmoud has nothing to disclose. Juliane Chainakul has nothing to disclose. Robert Hamilton has nothing to disclose. Dr. Sidorov has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Allergan. Dr. Sidorov has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BioHaven .

391 The relative frequency of small vessel cerebrovascular disease and brain atrophy in MRI of patients with psoriasis

391 The relative frequency of small vessel cerebrovascular disease and brain atrophy in MRI of patients with psoriasis

Comparison of 116 Radiosurgery Treatment Plans for Multi-Leaf and Cone Collimator on a Varian Edge Linac: Are Cones Superior in the Daily Routine?

Delivering focused radiation doses via linear accelerators is a crucial component of stereotactic radiosurgery (SRS) for brain metastases. The Varian Edge linear accelerator provides highly conformal radiation therapy through a high-definition multi-leaf collimator (HD120 MLC) and conical collimator (CC). HD120 MLC adapts to the shape of the target volume using movable tungsten leaves, while CC has a block of conical shape (cones). CC in SRS treatments of small brain metastases is preferred due to its mechanical stability and steeper dose fall-off, potentially sparing organs at risk (OARs) and the brain better than HD120 MLC. This study aims to determine if CC offers significant advantages over HD120 MLC for SRS treatments. For 116 metastatic lesions, CC and HD120 MLC treatment plans were created in Varian Eclipse TPS and compared based on various dose parameters, robustness tests, and QA measurements. The results indicate that CC provides no significant advantages over HD120 MLC, except for slight, clinically insignificant benefits in brain sparing and dose fall-off for the smallest lesions. HD120 MLC outperforms CC in almost every aspect, making it a better choice for irradiating brain metastases with 0.1 cm3 or higher volumes.

Fighting Flies: Quantifying and Analyzing Drosophila Aggression.

Aggression is an innate behavior that likely evolved in the framework of defending or obtaining resources. This complex social behavior is influenced by genetic, environmental, and internal factors. Drosophila melanogaster remains an effective and exciting model organism with which to unravel the mechanistic basis of aggression due to its small but sophisticated brain, an impressive array of neurogenetic tools, and robust stereotypical behavioral patterns. The investigations of many laboratories have led to the identification of external and internal state factors that promote aggression, sex differences in the patterns and outcome of aggression, and neurotransmitters that regulate aggression.

The Differential Effects of APOEɛ4 on Cerebral Volumetric Structures in Different Lifespan in Community-Dwelling Populations.

Apolipoprotein E (APOE) is closely related to Alzheimer's disease and other age-related diseases. In recent years, several studies have shown an interaction of APOE by age on brain volume. However, validation in larger cohorts is required. We explored the age-related effect of APOE on brain volumes in a community-dwelling cohort. Inhabitants in Shunyi District in Beijing aged≥35 years were invited to join this study from 2013 to 2016. The baseline assessments, APOE genotyping and brain magnetic resonance imaging were performed. Neuroimaging small vessel disease characteristics and brain volumes (global measures, cerebral lobes, hippocampus, brainstem, and subcortical nuclei) were acquired. The general linear model was used to analyze the interaction of APOE genotypes by age on brain volumes, and the age of 60 years was chosen as a cut-off value for stratification analysis. A total of 1,105 subjects were enrolled in the final analysis with a mean age of 56.18 (9.30) years, and 37.7% were men. APOEɛ3/ɛ3 carriers account for 71.8%, ɛ2 (+) 14.0%, and ɛ4 (+) 14.2%. Compared with APOEɛ3/ɛ3, a significant protective effect for APOEɛ4 (+) on brain parenchyma fraction (β = 0.450, p = 0.048) was observed in subjects aged≤60 years; in participants aged > 60 years, a negative effect for APOEɛ4 (+) on hippocampus (β = 1.087, p = 0.021) was found. Our study reveals that APOEɛ4 has differential effects on cerebral structures in different stages of lifespan, suggesting its complicated biological function and underlying antagonistic pleiotropy.

Extractive foraging behaviour in woodpeckers evolves in species that retain a large ancestral brain

Identifying ecological factors that influence brain size evolution is a major challenge in organismal biology. The extractive foraging hypothesis proposes that large brains are more likely to evolve in taxa that extract prey items from hard-to-access substrates, but this idea has received relatively little attention. Here, we provide a comprehensive test of the extractive foraging hypothesis in woodpeckers, a family of relatively large-brained birds that contains many species that feed on wood-boring larvae extracted from trees. Our results show strong support for the extractive foraging hypothesis. First, woodpeckers that use extractive foraging have relatively larger brains compared to species that forage using other tactics. Second, our comparative analyses suggest not only that big brains are the likely ancestral phenotype among all woodpecker taxa, but also that this trait is associated with innovation in foraging behaviour. We suspect that retaining an ancestral large brain likely increases the probability that a given species evolves to become an extractive forager who eats largely wood-boring larvae, given that species that transitioned to a small brain evolved different diets. Thus, the extractive foraging hypothesis likely applies to woodpeckers because of a historical contingency (large brains) that sets the stage for behavioural innovations to better exploit ecological opportunities.

Wilson’s disease classification using higher-order Gabor tensors and various classifiers on a small and imbalanced brain MRI dataset

Wilson’s disease classification using higher-order Gabor tensors and various classifiers on a small and imbalanced brain MRI dataset

Small animal cerebral microvascular imaging with super-resolution ultrasound: Techniques and applications

Super-resolution ultrasound (SR-US) is an emerging microvascular imaging technology that provides a micron-scale spatial resolution with tens of millimeters of depth of imaging penetration. The unmatched combination of high spatial resolution and deep imaging penetration opened new doors for many brain imaging applications that benefit from cerebrovascular biomarkers. Recently, SR-US has found its niche in small animal brain applications thanks to its unique capabilities of extending the optical-imaging-level spatial resolution to subcortical, deep brain regions. In this presentation, I will first introduce existing SR-US imaging techniques that are tailored to small animal brain imaging applications. Topics include fast SR-US methods, 3D SR-US imaging, and phase aberration correction for intact skull imaging. I will then focus on reviewing brain imaging applications that use SR-US to characterize cerebral mirovasculature in the aging, stroke, and Alzheimer’s Disease brain. Finally, I will introduce the new functional super-resolution imaging technique that combines SR-US with functional ultrasound (fUS) to realize whole-brain neural activity recording at a micron-scale spatial resolution.

Effect of long-term antihypertensive treatment on cerebrovascular structure and function in hypertensive rats

Midlife hypertension is an important risk factor for cognitive impairment and dementia, including Alzheimer’s disease. We investigated the effects of long-term treatment with two classes of antihypertensive drugs to determine whether diverging mechanisms of blood pressure lowering impact the brain differently. Spontaneously hypertensive rats (SHR) were either left untreated or treated with a calcium channel blocker (amlodipine) or beta blocker (atenolol) until one year of age. The normotensive Wistar Kyoto rat (WKY) was used as a reference group. Both drugs lowered blood pressure equally, while only atenolol decreased heart rate. Cerebrovascular resistance was increased in SHR, which was prevented by amlodipine but not atenolol. SHR showed a larger carotid artery diameter with impaired pulsatility, which was prevented by atenolol. Cerebral arteries demonstrated inward remodelling, stiffening and endothelial dysfunction in SHR. Both treatments similarly improved these parameters. MRI revealed that SHR have smaller brains with enlarged ventricles. In addition, neurofilament light levels were increased in cerebrospinal fluid of SHR. However, neither treatment affected these parameters. In conclusion, amlodipine and atenolol both lower blood pressure, but elicit a different hemodynamic profile. Both medications improve cerebral artery structure and function, but neither drug prevented indices of brain damage in this model of hypertension.

Angiotensin-converting enzyme: a well-known stranger. Part II

The angiotensin-converting enzyme (ACE) is constitutively expressed on the surface of endothelial, epithelial and immune system cells (macrophages, dendritic cells). The lungs are believed to be the main source of circulating ACE. However, other organs such as the small intestine, kidneys, heart, brain, epididymis, and prostate have also been found to express ACE at levels comparable to those in the lungs. ACE expression is regulated not only passively by the number of endothelial cells, but also by endothelial function. In general, the biochemical environment is the driving force behind the enzymatic activity of ACE, influencing cells capable of expressing ACE and regulatory proteins. The discovery of tissue ACE has changed our understanding of the pathophysiology of many diseases. In particular, it turned out that renal versus circulating ACE is more important in the development of arterial hypertension, diabetic nephropathy, acute and chronic kidney disease.

Extra-criteria antiphospholipid antibodies in patients with small vessel brain lesions and clinical manifestations associated with antiphospholipid syndrome

ObjectivesNeurological manifestations compatible with small vessel brain lesions (SVBL), such as migraine, cognitive impairment, seizures, and transverse myelitis, may be related to antiphospholipid syndrome (APS) and patients could need APS therapies even though they do not fit into thrombosis or obstetric morbidity. Furthermore, extra-criteria antiphospholipid antibodies (aPL) provide an increase in sensitivity in patients with clinical manifestations related to APS but negative for IgG/IgM anticardiolipin (aCL), anti-β2 glycoprotein I (aβ2GPI), and lupus anticoagulant, which are the antibodies included in the classification criteria for APS. MethodsWe determined extra-criteria aPL in 65 SVBL patients with neurological traits and Magnetic Resonance Imaging suggestive of APS but negative for APS classification criteria, 47 of whom were prospectively followed and tested over three years. A group of 95 patients with autoimmune diseases (AD) but without clinical traits of APS was also studied. ResultsA persistent presence of extra-criteria aPL was detected in 27.7% of patients: 12.77% IgM anti- prothrombin (PT), 6.38% IgG anti-PT, 6.38% IgM anti-phosphatidylethanolamine (PE), 4.26% IgA aβ2GPI, 2.13% IgG anti-phosphatidylserine/prothrombin (PS/PT) and 2.13% IgM anti-PS/PT.There was a tendency towards a higher prevalence of these aPL in SVBL patients than in AD – especially for IgA aβ2GPI – and a lack of IgG aPS/PT positivity in the AD group. We found no SVBL patient positive for IgA aCL, IgG anti-PE, annexin V, or aβ2GPI domain I. ConclusionsExtra-criteria aPL can improve sensitivity for APS diagnosis in patients with SVBL, especially IgA aβ2GPI and IgG anti-PS/PT antibodies.

A conformal TOF-DOI Prism-PET prototype scanner for high-resolution quantitative neuroimaging.

Positron emission tomography (PET) has had a transformative impact on oncological and neurological applications. However, still much of PET's potential remains untapped with limitations primarily driven by low spatial resolution, which severely hampers accurate quantitative PET imaging via the partial volume effect (PVE). We present experimental results of a practical and cost-effective ultra-high resolution brain-dedicated PET scanner, using our depth-encoding Prism-PET detectors arranged along a compact and conformal gantry, showing substantial reduction in PVE and accurate radiotracer uptake quantification in small regions. The decagon-shaped prototype scanner has a long diameter of 38.5cm, a short diameter of 29.1 cm, and an axial field-of-view (FOV) of 25.5mm with a single ring of 40 Prism-PET detector modules. Each module comprises a 16 × 16 array of 1.5 × 1.5 × 20-mm3 lutetium yttrium oxyorthosillicate (LYSO) scintillator crystals coupled 4-to-1 to an 8 × 8 array of silicon photomultiplier (SiPM) pixels on one end and to a prismatoid light guide array on the opposite end. The scanner's performance was evaluated by measuring depth-of-interaction (DOI) resolution, energy resolution, timing resolution, spatial resolution, sensitivity, and image quality of ultra-micro Derenzo and three-dimensional (3D) Hoffman brainphantoms. The full width at half maximum (FWHM) DOI, energy, and timing resolutions of the scanner are 2.85 mm, 12.6%, and 271 ps, respectively. Not considering artifacts due to mechanical misalignment of detector blocks, the intrinsic spatial resolution is 0.89-mm FWHM. Point source images reconstructed with 3D filtered back-projection (FBP) show an average spatial resolution of 1.53-mm FWHM across the entire FOV. The peak absolute sensitivity is 1.2% for an energy window of 400-650 keV. The ultra-micro Derenzo phantom study demonstrates the highest reported spatial resolution performance for a human brain PET scanner with perfect reconstruction of 1.00-mm diameter hot-rods. Reconstructed images of customized Hoffman brain phantoms prove that Prism-PET enables accurate radiotracer uptake quantification in small brain regions (2-3 mm). Prism-PET will substantially strengthen the utility of quantitative PET in neurology for early diagnosis of neurodegenerative diseases, and in neuro-oncology for improved management of both primary and metastatic brain tumors.

Modified Dynamic Conformal Arcs With Forward Planning for Radiosurgery of Small Brain Metastasis: Each Double Arc and Different To-and-Fro Leaf Margins to Optimize Dose Gradient Inside and Outside the Gross Tumor Boundary.

Dynamic conformal arcs (DCA) are a widely used technique for stereotactic radiosurgery (SRS) of brain metastases (BM) using a micro-multileaf collimator (mMLC), while the planning design and method considerably vary among institutions. In the usual forward planning of DCA, the steepness of the dose gradient outside and inside the gross tumor volume (GTV) boundary is simply defined by the leaf margin (LM) setting to the target volume edge. The dose fall-off outside the small GTV tends to be excessively precipitous, especially with an MLC of 2.5-mm leaf width, which is predisposed to the insufficient coverage of microscopic brain invasion and other inherent inaccuracies. Meanwhile, insufficient dose increase inside the GTV boundary, i.e., less inhomogeneous GTV dose, likely leads to inferior and less sustainable tumor response. The more inhomogeneous GTV dose is prone to the steeper dose gradient outside the GTV and vice versa. Herein, we describe an alternative simply modified DCA (mDCA) planning that was uniquely devised to optimize the dose gradient outside and inside the GTV boundary for further enhancing and consolidating local control of small BM. For a succinct exemplification, a 10-mm spherical target was assumed as a GTV for DCA planning using a 2.5-mm mMLC. The benchmark plan was generated by adding a 0-mm LM to the GTV edge byassigning a single fraction of 30 Gy to the isocenter, in which the GTV coverage by 24 Gy with 80% isodose surface (IDS) was 96%, i.e., D96%, while the coverage of GTV + isotropic 2 mm volume by 18 Gy with 60% IDS was 70%, with the D98% being 12 Gy with 40% IDS, viz., too steep dose fall-off outside the GTV boundary. Alternatively, the increase of LM with or without decreasing the isocenter dose enablesthe increase of the GTV + 2 mm coverage by 18 Gy while resulting in an inadequate GTV dose with either a less inhomogeneous dose or an excessive marginal dose. Meanwhile, in the newly devised mDCA planning, everysingle arc was converted to a double to-and-fro arcwith different LM settings under the same spatial arrangement, which enabled GTV + 2 mm volume coverage with 18 Gy while preserving the GTV marginal dose and inhomogeneity similar to those for the benchmark plan. Additionally, the different collimator angle (CA) setting for the to-and-fro arcs led to further trimming of the dose conformity. The limitations of general forward planning with only adjusting the LM for everysingle arc were demonstrated, which can be a contributing factor for local tumor progressionof small BM. Alternatively, the mDCA with each double to-and-fro arc and different LM and CA settings enables optimization of the dose gradient both outside and inside the GTV boundary according to the planners' intent, e.g., moderate dose spillage margin outside the GTV and steep dose increase inside the GTV boundary.

The Relative Frequency of Small Vessel Cerebrovascular Disease and Brain Atrophy in MRI of Patients with Psoriasis.

Psoriasis is a systemic autoimmune disease that is associated with numerous comorbidities. This study aimed to compare the prevalence of small vessel cerebrovascular disease (SVCD) and atrophic brain changes in MRI of patients with psoriasis and normal subjects. This case-control study was performed on 27 patients with psoriasis and 27 normal individuals who were referred to Shohada-e-Tajrish Hospital, Tehran, Iran during 2019 and 2020. Basic demographic and clinical information of participants were recorded. Brain MRI was performed for all individuals to examine the medial temporal atrophy (MTA) score, global cortical atrophy (GCA) score, and Fazekas scale. Finally, the relative frequencies of each parameter between the two groups were compared. There was no significant difference in the frequency of the Fazekas scale, GCA, and MTA scores between the two groups. However, a mild trend was found for a higher frequency of Fazekas scale, GCA, and MTA scores in controls in comparison with the case group. While there was no significant relationship between the Fazekas scale and disease duration (p=0.16), a significant and positive correlation was found between disease duration and GCA and MTA scores [p<0.001). There was no significant relationship between Fazekas, GCA and MTA status and other parameters. The increase in disease duration was significantly associated with an increase in the incidence of cerebral atrophy, which may suggest the need for screening in terms of CNS involvement in psoriasis patients.

Investigating the Modulation of the VTA Neurons in Nicotine-Exposed Pups during Early Maturation Using Optogenetics.

Advancing the understanding of the relationship between perinatal nicotine addiction and the reward mechanism of the brain is crucial for uncovering and implementing new treatments for addiction control and prevention. The mesolimbic pathway of the brain, also known as the reward pathway, consists of two main areas that regulate dopamine (DA) and addiction-related behaviors. The ventral tegmental area (VTA) releases DA when stimulated, causing the propagation of neuronal firing along the pathway. This ends in the release of DA into the extracellular space of the nucleus accumbens (NAc), which is directly modulated by the uptake of DA. Much research has been conducted on the effects of nicotine addiction, but little research has been conducted concerning nicotine addiction and the mesolimbic pathway regarding maturation due to the small brain size. In this study, we apply our novel microstimulation experimental system to rat pups that have been perinatally exposed to nicotine. By using our self-fabricated photo-stimulation (PS) device, we can stimulate the VTA and collect dialysate, which is then used to estimate DA released into the NAc. The proposed platform has demonstrated the potential to monitor neural pathways as the pups mature.

A knockout-first model of H3f3a gene targeting leads to developmental lethality.

Histone variant H3.3 is encoded by two genes, H3f3a and H3f3b, which can be expressed differentially depending on tissue type. Previous work in our lab has shown that knockout of H3f3b causes some neonatal lethality and infertility in mice, and chromosomal defects in mouse embryonic fibroblasts (MEFs). Studies of H3f3a and H3f3b null mice by others have produced generally similar phenotypes to what we found in our H3f3b nulls, but the relative impacts of the loss of either H3f3a or H3f3b have varied depending on the approach and genetic background. Here we used a knockout-first approach to target the H3f3a gene for inactivation in C57BL6 mice. Homozygous H3f3a targeting produced a lethal phenotype at or before birth. E13.5 null embryos had some potential morphological differences from WT littermates including smaller size and reduced head size. An E18.5 null embryowas smaller than its control littermates with several potential defects including small head and brain size as well as small lungs, which would be consistent with a late gestation lethal phenotype. Despite a reduction in H3.3 and total H3 protein levels, the only histone H3 post-translational modification in the small panel assessed that was significantly altered was the unique H3.3 mark phospho-Serine31, which was consistently increased in null neurospheres. H3f3a null neurospheres also exhibited consistent gene expression changes including in protocadherins. Overall, our findings are consistent with the model that there are differential, cell-type-specific contributions of H3f3a and H3f3b to H3.3 functions in epigenetic and developmental processes.

Electro-acupuncture treatment inhibits the inflammatory response by regulating γδ T and Treg cells in ischemic stroke

BackgroundElectro-acupuncture (EA) is an effective and safe treatment for ischemic stroke. It is not only capable of reducing cerebral damage but also alleviating intestinal inflammation. However, its mechanism has not been fully elucidated. MethodsAll rats were randomly divided into three experimental groups: the SHAM group, the MCAO group, and the MEA (MCAO+EA) group. Ischemic-reperfusion (I/R) injury was induced by MCAO surgery. Rats in the MEA group were treated with EA stimulation in the “Baihui” acupoint (1 mA, 2/15 Hz, 20 min for each time). The Real-time (RT)-qPCR was used to evaluate the mRNA expression of inflammation factors in the ischemic brain and the small intestine after I/R injury. In addition, our research evaluated the effects of EA on regulatory T cells (Tregs) and γδ T cells in the small intestine and brain via Flow cytometry analysis. Finally, we applied CM-Dil and CFSE injection and explored the potential connections of T cells between the ischemic hemisphere and the small intestine. ResultsOur results suggested that EA treatment could significantly reduce the inflammation response in the ischemic brain and small intestine 3 days after I/R injury in rats. To be specific, EA increased the percentage of Tregs in the brain and the small intestine and decreased intestinal and cerebral γδ T cells. Concomitantly, after EA treatment, the percentage of cerebral CD3+TCRγδ+CFSE+ cells dropped from 12.06% to 6.52% compared with the MCAO group. ConclusionsThese findings revealed that EA could regulate the Tregs and γδ T cells in the ischemic brain and the small intestine, which indicated its effect on inhibiting inflammation. And, EA could inhibit the mobilization of intestinal T cells, which may contribute to the protection of EA after ischemic stroke.

Third-line or above anlotinib in relapsed and refractory small cell lung cancer patients with brain metastases: A post hoc analysis of ALTER1202, a randomized, double-blind phase 2 study.

The prognosis of patients with small cell lung cancer (SCLC) and brain metastases (BM) was poor. This study aimed to explore the efficacy and safety of anlotinib as third-line or above treatment in SCLC with BM. This was a subgroup analysis of the ALTER1202 trial, which was a randomized, placebo-controlled trial aimed to evaluate the role of anlotinib as third-line treatment or above in patients with SCLC. This study included patients with BM at baseline. The efficacy and safety outcomes included progression-free survival (PFS), overall survival (OS), central nervous system (CNS), objective response rate (ORR), CNS disease control rate (DCR), time to CNS progression, and adverse events (AEs). Twenty-one and nine patients with BM were included in the anlotinib and placebo groups, respectively. The median PFS and OS were 3.8 months (95% confidence interval [CI]: 1.8-6.1) and 6.1 months (95% CI: 4.1-8.0) in the anlotinib group. Anlotinib was associated with a significant improvement in PFS (hazard ratio [HR] = 0.15, 95%CI: 0.04-0.51, p = 0.0005) and OS (HR = 0.26, 95%CI: 0.09-0.73, p = 0.0061) than placebo. Anlotinib significantly prolonged the time to CNS progression (p < 0.0001). The anlotinib group had a higher CNS DCR than placebo (95.2% vs. 22.2%, p = 0.0001). The most common grade 3 or higher AEs were increased lipase (19.0%), hypertension (14.3%), and hyponatremia (14.3%) in the anlotinib group. Anlotinib proved to have potential CNS activity and a manageable toxicity profile in patients with SCLC and BM, significantly delaying CNS progression.

Neuroendocrine regulation of reproduction by GnRH neurons: multidisciplinary studies using a small fish brain model.

After the discovery of GnRH, GnRH neurons have been considered to represent the final common pathway for the neural control of reproduction. There is now compelling data in mammals that two populations of kisspeptin neurons constitute two different systems to control the episodic and surge release of GnRH/LH for the control of different aspects of reproduction, follicular development and ovulation. However, accumulating evidence indicates that kisspeptin neurons in non-mammalian species do not serve as a regulator of reproduction, and the non-mammalian species are believed to show only surge release of GnRH to trigger ovulation. Therefore, the GnRH neurons in non-mammalian species may offer simpler models for the study of their functions in neuroendocrine regulation of reproduction, especially ovulation. Our research group has taken advantage of many unique technical advantages of small fish brain for the study of anatomy and physiology of GnRH neurons, which underly regular ovulatory cycles during the breeding season. Here, recent advances in multidisciplinary study of GnRH neurons are reviewed, with a focus on studies using small teleost fish models.

Parameter visibility: Next-generation energy management [Guest Editorial

In the aftermath of the 1965 blackout, the need for robust power system state estimators became apparent. Edward Teller, a member of the task force investigating the 1965 blackout, wrote “the electric power system is a dinosaur with a large body and a small brain.” The committee recognized the need to have a way of knowing the operating conditions of the power system in real time. Work following the 1965 blackout established many engineering principles by which we presently operate the electric power system. It is clear that the control and operation of power systems are primarily model based. State estimation provides the operating conditions as well as the real-time model of the system. Using the model and operating conditions, we compute control actions, including economic operation; the maximization of operational security; and other important operational controls.