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The neuronal substrate for binge eating, which can at times lead to obesity, is not clear. We find that optogenetic stimulation of mouse zona incerta (ZI) γ-aminobutyric acid (GABA) neurons or their axonal projections to paraventricular thalamus (PVT) excitatory neurons immediately (in 2 to 3 seconds) evoked binge-like eating. Minimal intermittent stimulation led to body weight gain; ZI GABA neuron ablation reduced weight. ZI stimulation generated 35% of normal 24-hour food intake in just 10 minutes. The ZI cells were excited by food deprivation and the gut hunger signal ghrelin. In contrast, stimulation of excitatory axons from the parasubthalamic nucleus to PVT or direct stimulation of PVT glutamate neurons reduced food intake. These data suggest an unexpected robust orexigenic potential for the ZI GABA neurons.

The authors show that hypothalamic neurons that synthesize tyrosine hydroxylase regulate food intake and body weight. By a combination of dopamine and GABA release, these neurons modulate the activity of both pro-opiomelanocortin neurons and paraventricular nucleus neurons that also contribute to energy homeostasis. Energy homeostasis, food intake, and body weight are regulated by specific brain circuits. Here we introduce an unexpected neuron, the tyrosine hydroxylase (TH) neuron of the arcuate nucleus (ARC), that we show makes an orexigenic contribution. Optogenetic stimulation of mouse ARC TH neurons increased food intake; attenuating transmitter release reduced body weight. Optogenetic stimulation of ARC TH cells inhibited pro-opiomelanocortin (POMC) neurons through synaptic mechanisms. ARC TH cells project to the hypothalamic paraventricular nucleus; optogenetic stimulation of ARC TH axons inhibited paraventricular nucleus neurons by dopamine and GABA co-release. Dopamine excited orexigenic neurons that synthesize agouti-related peptide and neuropeptide Y but inhibited anorexigenic neurons that synthesize POMC, as determined by whole cell recording. Food deprivation increased c-fos expression and spike frequency in ARC TH neurons. The gut peptide ghrelin evoked direct excitatory effects, suggesting these neurons monitor metabolic cues. Together these data support the view that ARC TH cells play an unrecognized and influential positive role in energy homeostasis.

The discovery of a radioactively powered kilonova associated with the binary neutron-star merger GW170817 remains the only confirmed electromagnetic counterpart to a gravitational-wave event 1 , 2 . Observations of the late-time electromagnetic emission, however, do not agree with the expectations from standard neutron-star merger models. Although the large measured ejecta mass 3 , 4 could be explained by a progenitor system that is asymmetric in terms of the stellar component masses (that is, with a mass ratio q of 0.7 to 0.8) 5 , the known Galactic population of merging double neutron-star systems (that is, those that will coalesce within billions of years or less) has until now consisted only of nearly equal-mass ( q  > 0.9) binaries 6 . The pulsar PSR J1913+1102 is a double system in a five-hour, low-eccentricity (0.09) orbit, with an orbital separation of 1.8 solar radii 7 , and the two neutron stars are predicted to coalesce in 470 − 11 + 12 million years owing to gravitational-wave emission. Here we report that the masses of the pulsar and the companion neutron star, as measured by a dedicated pulsar timing campaign, are 1.62 ± 0.03 and 1.27 ± 0.03 solar masses, respectively. With a measured mass ratio of q  = 0.78 ± 0.03, this is the most asymmetric merging system reported so far. On the basis of this detection, our population synthesis analysis implies that such asymmetric binaries represent between 2 and 30 per cent (90 per cent confidence) of the total population of merging binaries. The coalescence of a member of this population offers a possible explanation for the anomalous properties of GW170817, including the observed kilonova emission from that event. Pulsar timing measurements show a mass ratio of about 0.8 for the double neutron-star system PSR J1913+1102, and population synthesis models indicate that such asymmetric systems represent 2–30% of merging binaries.

Continued timing observations of the double pulsar PSR J0737–3039A/B, which consists of two active radio pulsars (A and B) that orbit each other with a period of 2.45 h in a mildly eccentric ( e=0.088 ) binary system, have led to large improvements in the measurement of relativistic effects in this system. With a 16-yr data span, the results enable precision tests of theories of gravity for strongly self-gravitating bodies and also reveal new relativistic effects that have been expected but are now observed for the first time. These include effects of light propagation in strong gravitational fields which are currently not testable by any other method. In particular, we observe the effects of retardation and aberrational light bending that allow determination of the spin direction of the pulsar. In total, we detect seven post-Keplerian parameters in this system, more than for any other known binary pulsar. For some of these effects, the measurement precision is now so high that for the first time we have to take higher-order contributions into account. These include the contribution of the A pulsar’s effective mass loss (due to spin-down) to the observed orbital period decay, a relativistic deformation of the orbit, and the effects of the equation of state of superdense matter on the observed post-Keplerian parameters via relativistic spin-orbit coupling. We discuss the implications of our findings, including those for the moment of inertia of neutron stars, and present the currently most precise test of general relativity’s quadrupolar description of gravitational waves, validating the prediction of general relativity at a level of 1.3×10-4 with 95% confidence. We demonstrate the utility of the double pulsar for tests of alternative theories of gravity by focusing on two specific examples and also discuss some implications of the observations for studies of the interstellar medium and models for the formation of the double pulsar system. Finally, we provide context to other types of related experiments and prospects for the future.

DURING BRAIN DEVELOPMENT, THERE IS A PROGRESSIVE REDUCTION OF INTRACELLULAR CHLORIDE ASSOCIATED WITH A SHIFT IN GABA POLARITY: GABA depolarizes and occasionally excites immature neurons, subsequently hyperpolarizing them at later stages of development. This sequence, which has been observed in a wide range of animal species, brain structures and preparations, is thought to play an important role in activity-dependent formation and modulation of functional circuits. This sequence has also been considerably reinforced recently with new data pointing to an evolutionary preserved rule. In a recent \"Hypothesis and Theory Article,\" the excitatory action of GABA in early brain development is suggested to be \"an experimental artefact\" (Bregestovski and Bernard, 2012). The authors suggest that the excitatory action of GABA is due to an inadequate/insufficient energy supply in glucose-perfused slices and/or to the damage produced by the slicing procedure. However, these observations have been repeatedly contradicted by many groups and are inconsistent with a large body of evidence including the fact that the developmental shift is neither restricted to slices nor to rodents. We summarize the overwhelming evidence in support of both excitatory GABA during development, and the implications this has in developmental neurobiology.

ABSTRACT Solitary fibrous tumor (SFT) is a rare mesenchymal tumor of fibroblastic origin commonly occurring in pleura. It can occur at many extrapleural sites but is rare in orbit. Most cases are benign and recurrence is not unusual in the head and neck and orbit and is usually due to incomplete surgical excision. However, malignant transformation (MT) in orbital SFT is extremely unusual. We present a case of orbital SFT in adult male who developed recurrence with MT eight years after initial surgical excision. He underwent left orbital exenteration. The recurrent tumor revealed features of malignancy with areas exhibiting morphology typical of SFT. The immunochemistry confirmed the diagnosis of SFT with MT. The patient was given adjuvant radiation and was disease free for the last 18 months. Identification of malignancy in orbital SFT is important for the patient to receive appropriate postoperative treatment, as seen in the present case.

Rhabdomyosarcoma (RMS) masquerading as acute leukemia (AL) is very rare. We report a case which presented as acute leukemia subsequently diagnosed to be Alveolar RMS of Urinary Bladder. Although cases of RMS with leukemic presentation have been reported, to our knowledge this is the first case of Alveolar RMS of Urinary Bladder with leukemic picture at initial presentation. We would like to emphasize that this critical error can have serious consequences on the treatment and outcome of these patients.

Background: Renal oncocytomas are benign epithelial tumors usually detected incidentally. They are typically solid,well-circumscribed,homogenous,mahoganybrown with a central stellate scar.Sometimes,they can have cystic degenerationand rarely present as a multilocular cyst which can be mistaken for other cystic renal carcinomas. Methods: We describe a case of incidentally detected multilocular cystic renal oncocytoma having an unusual gross appearance of multiloculation with perinephric fat invasion. The tumor exhibited tubulocystic architecture posed a diagnostic dilemma. Detailed study of multiple sections coupled with immunohisto chemistry helped elucidate the diagnosis. Till date, only eight cases of multicystic renal oncocytoma have been reported in the English literature. Conclusions: We emphasize the importance of awareness of this unusual morphologic variation to ensure correct diagnosis.

Aims: To explore clinical, histopathological and immunohistochemistry (IHC) features of mammary analogue secretory carcinoma (MASC) with systematic literature review. Settings and Design: Hospital based cross-sectional study. Subjects and Methods: The data of all cases of MASC diagnosed over a period of 1 year i.e., from July 2017 to July 2018 were retrieved. The haematoxylin and eosin (H and E) sections, and IHC sections were studied. A strict histological and recently updated criteria were applied and patients with a confirmed diagnosis of MASC were included in the study. A systematic literature review was conducted by searching the PubMed and National Centre for Biotechnology Information database. Statistical Analysis Used: Microsoft Excel 2010. Results: The present case series is 27th in the English literature and 1stcase series describing its histopathology in the Indian literature. The mean age of presentation is 43 years. Female preponderance was found i.e., M:F ratio of 0.5. Conclusion: Histopathology and if necessary, followed by IHC is required for the confirmation of diagnosis of MASC. We should be aware about this recently described entity which is usually mistaken for other low grade salivary gland carcinomas like Acinic cell carcinoma (AciCC) and Mucoepidermoid carcinoma (MEC). The knowledge about its typical morphology, high degree of suspicion and IHC confirmation with both S-100 and Mammaglobin help in precise diagnosis.

We describe a hypothalamus-specific mRNA that encodes preprohypocretin, the putative precursor of a pair of peptides that share substantial amino acid identities with the gut hormone secretin. The hypocretin (Hcrt) protein products are restricted to neuronal cell bodies of the dorsal and lateral hypothalamic areas. The fibers of these neurons are widespread throughout the posterior hypothalamus and project to multiple targets in other areas, including brainstem and thalamus. Hcrt immunoreactivity is associated with large granular vesicles at synapses. One of the Hcrt peptides was excitatory when applied to cultured, synaptically coupled hypothalamic neurons, but not hippocampal neurons. These observations suggest that the hypocretins function within the CNS as neurotransmitters.