bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simultaneous Loss of NCKX4 and CNG Channel Desensitization Impairs Olfactory Sensitivity
Authors: Ferguson Christopher H. , Zhao Haiqing 
Published: November 2016

In vertebrate olfactory sensory neurons (OSNs), Ca2+plays key roles in both mediating and regulating the olfactory response. Ca2+enters OSN cilia during the response through the olfactory cyclic nucleotide-gated (CNG) channel and stimulates a depolarizing chloride current by opening the olfactory Ca2+-activated chloride channel to amplify the response. Ca2+also exerts negative regulation on the olfactory transduction cascade, through mechanisms that include reducing the CNG current by desensitizing the CNG channel via Ca2+/calmodulin (CaM), to reduce the response. Ca2+is removed from the cilia primarily by the K+-dependent Na+/Ca2+exchanger 4 (NCKX4), and the removal of Ca2+leads to closure of the chloride channel and response termination. In this study, we investigate how two mechanisms conventionally considered negative regulatory mechanisms of olfactory transduction, Ca2+removal by NCKX4, and desensitization of the CNG channel by Ca2+/CaM, interact to regulate the olfactory response. We performed electro-olfactogram (EOG) recordings on the double-mutant mice,NCKX4−/−;CNGB1ΔCaM, which are simultaneously lacking NCKX4 (NCKX4−/−) and Ca2+/CaM-mediated CNG channel desensitization (CNGB1ΔCaM). Despite exhibiting alterations in various response attributes, including termination kinetics and adaption properties, OSNs in eitherNCKX4−/−mice orCNGB1ΔCaMmice show normal resting sensitivity, as determined by their unchanged EOG response amplitude. We found that OSNs inNCKX4−/−;CNGB1ΔCaMmice displayed markedly reduced EOG amplitude accompanied by alterations in other response attributes. This study suggests that what are conventionally considered negative regulatory mechanisms of olfactory transduction also play a role in setting the resting sensitivity in OSNs.SIGNIFICANCE STATEMENTSensory receptor cells maintain high sensitivity at rest. Although the mechanisms responsible for setting the resting sensitivity of sensory receptor cells are not well understood, it has generally been assumed that the sensitivity is set primarily by how effectively the components in the activation cascade of sensory transduction can be stimulated. Our findings in mouse olfactory sensory neurons suggest that mechanisms that are primarily responsible for terminating the olfactory response are also critical for proper resting sensitivity.
Ventral Pallidum Output Pathways in Context-Induced Reinstatement of Alcohol Seeking
Authors: Prasad Asheeta A. , McNally Gavan P. 
Published: November 2016

Ventral pallidum (VP) is a well-established locus for the reinforcing effects of drugs of abuse and reinstatement of drug seeking. However, VP neurons are at the origin of multiple output pathways, with strong projections to ventral tegmental area (VTA), subthalamic nucleus (STN), lateral hypothalamus, among others, and the roles of these VP output pathways in reinstatement of drug seeking remain poorly understood. Here we addressed these issues using a combination of neuroanatomical tracing and chemogenetic approaches. First, using dual-retrograde tracing, we show that VP neurons projecting to either VTA or STN are recruited during context-induced reinstatement of extinguished alcohol seeking in rats. Then, using chemogenetics, we show modulation of context-induced reinstatement and reacquisition of alcohol seeking via designer receptors exclusively activated by designer drugs excitation or inhibition of the VP. To determine the causal roles of VP → VTA and VP → STN pathways in context-induced reinstatement and reacquisition we used a chemogenetic disconnection approach and show that silencing either the VP → VTA or VP → STN pathways is sufficient to reduce both reinstatement and reacquisition of alcohol seeking. Moreover, these disconnections also each reduced responding and motivation during a progressive ratio test but had no effect on locomotor activity. Together, these results show that multiple ventral pallidal output pathways contribute to relapse to alcohol seeking.SIGNIFICANCE STATEMENTVentral pallidum (VP) serves important roles in reward and motivation and is a critical node in the neural circuitry for reinstatement of drug seeking. Despite being a common locus for different forms of reinstatement, fundamental aspects of neural circuitry for these VP contributions to reinstatement of drug seeking remain unknown. Here we used a combination of neuroanatomical tracing and chemogenetic approaches to map the VP output pathways for context-induced reinstatement and reacquisition of alcohol seeking. We show that VP output pathways to the subthalamic nucleus and also to the ventral tegmental area are necessary for these forms of reinstatement.
Endogenously Released Neuropeptide Y Suppresses Hippocampal Short-Term Facilitation and Is Impaired by Stress-Induced Anxiety
Authors: Li Qin , Bartley Aundrea F. , Dobrunz Lynn E. 
Published: November 2016

Neuropeptide Y (NPY) has robust anxiolytic properties and is reduced in patients with anxiety disorders. However, the mechanisms by which NPY modulates circuit function to reduce anxiety behavior are not known. Anxiolytic effects of NPY are mediated in the CA1 region of hippocampus, and NPY injection into hippocampus alleviates anxiety symptoms in the predator scent stress model of stress-induced anxiety. The mechanisms that regulate NPY release, and its effects on CA1 synaptic function, are not fully understood. Here we show in acute hippocampal slices from mice that endogenous NPY, released in response to optogenetic stimulation or synaptically evoked spiking of NPY+ cells, suppresses both of the feedforward pathways to CA1. Stimulation of temporoammonic synapses with a physiologically derived spike train causes NPY release that reduces short-term facilitation, whereas the release of NPY that modulates Schaffer collateral synapses requires integration of both the Schaffer collateral and temporoammonic pathways. Pathway specificity of NPY release is conferred by three functionally distinct NPY+ cell types, with differences in intrinsic excitability and short-term plasticity of their inputs. Predator scent stress abolishes the release of endogenous NPY onto temporoammonic synapses, a stress-sensitive pathway, thereby causing enhanced short-term facilitation. Our results demonstrate how stress alters CA1 circuit function through the impairment of endogenous NPY release, potentially contributing to heightened anxiety.SIGNIFICANCE STATEMENTNeuropeptide Y (NPY) has robust anxiolytic properties, and its levels are reduced in patients with post-traumatic stress disorder. The effects of endogenously released NPY during physiologically relevant stimulation, and the impact of stress-induced reductions in NPY on circuit function, are unknown. By demonstrating that NPY release modulates hippocampal synaptic plasticity and is impaired by predator scent stress, our results provide a novel mechanism by which stress-induced anxiety alters circuit function. These studies fill an important gap in knowledge between the molecular and behavioral effects of NPY. This article also advances the understanding of NPY+ cells and the factors that regulate their spiking, which could pave the way for new therapeutic targets to increase endogenous NPY release in patients in a spatially and temporally appropriate manner.
Genetic Deletion of Neuronal PPARγ Enhances the Emotional Response to Acute Stress and Exacerbates Anxiety: An Effect Reversed by Rescue of Amygdala PPARγ Function
Authors: Domi Esi , Uhrig Stefanie , Soverchia Laura , Spanagel Rainer , Hansson Anita C. , Barbier Estelle , Heilig Markus , Ciccocioppo Roberto , Ubaldi Massimo 
Published: November 2016

PPARγ is one of the three isoforms of the Peroxisome Proliferator-Activated Receptors (PPARs). PPARγ is activated by thiazolidinediones such as pioglitazone and is targeted to treat insulin resistance. PPARγ is densely expressed in brain areas involved in regulation of motivational and emotional processes. Here, we investigated the role of PPARγ in the brain and explored its role in anxiety and stress responses in mice. The results show that stimulation of PPARγ by pioglitazone did not affect basal anxiety, but fully prevented the anxiogenic effect of acute stress. Using mice with genetic ablation of neuronal PPARγ (PPARγNestinCre), we demonstrated that a lack of receptors, specifically in neurons, exacerbated basal anxiety and enhanced stress sensitivity. The administration of GW9662, a selective PPARγ antagonist, elicited a marked anxiogenic response in PPARγ wild-type (WT), but not in PPARγNestinCreknock-out (KO) mice. Using c-Fos immunohistochemistry, we observed that acute stress exposure resulted in a different pattern of neuronal activation in the amygdala (AMY) and the hippocampus (HIPP) of PPARγNestinCreKO mice compared with WT mice. No differences were found between WT and KO mice in hypothalamic regions responsible for hormonal response to stress or in blood corticosterone levels. Microinjection of pioglitazone into the AMY, but not into the HIPP, abolished the anxiogenic response elicited by acute stress. Results also showed that, in both regions, PPARγ colocalizes with GABAergic cells. These findings demonstrate that neuronal PPARγ is involved the regulation of the stress response and that the AMY is a key substrate for the anxiolytic effect of PPARγ.SIGNIFICANCE STATEMENTPeroxisome Proliferator-Activated Receptor Gamma (PPARγ) is a classical target for antidiabetic therapies with thiazolidinedione compounds. PPARγ agonists such as rosiglitazone and pioglitazone are in clinical use for the treatment of insulin resistance. PPARγ has recently attracted attention for its involvement in the regulation of CNS immune response and functions. Here, we demonstrate that neuronal PPARγ activation prevented the negative emotional effects of stress and exerted anxiolytic actions without influencing hypothalamic–pituitary–adrenal axis function. Conversely, pharmacological blockade or genetic deletion of PPARγ enhanced anxiogenic responses and increased vulnerability to stress. These effects appear to be controlled by PPARγ neuronal-mediated mechanisms in the amygdala.
A rare case of gestational thyrotoxicosis as a cause of acute myocardial infarction
Authors: Nannaka Varalaxmi Bhavani , Lvovsky Dmitry 
Published: November 2016

Summary
Angina pectoris in pregnancy is unusual and Prinzmetal’s angina is much rarer. It accounts for 2% of all cases of angina. It is caused by vasospasm, but the mechanism of spasm is unknown but has been linked with hyperthyroidism in some studies. Patients with thyrotoxicosis-induced acute myocardial infarction are unusual and almost all reported cases have been associated with Graves’ disease. Human chorionic gonadotropin hormone-induced hyperthyroidism occurs in about 1.4% of pregnant women, mostly when hCG levels are above 70–80 000 IU/L. Gestational transient thyrotoxicosis is transient and generally resolves spontaneously in the latter half of pregnancy, and specific antithyroid treatment is not required. Treatment with calcium channel blockers or nitrates reduces spasm in most of these patients. Overall, the prognosis for hyperthyroidism-associated coronary vasospasm is good. We describe a very rare case of an acute myocardial infarction in a 27-year-old female, at 9 weeks of gestation due to right coronary artery spasm secondary to gestational hyperthyroidism with free thyroxine of 7.7 ng/dL and TSH <0.07 IU/L.

Learning points:

AMI and cardiac arrest due to GTT despite optimal medical therapy is extremely rare.

Gestational hyperthyroidism should be considered in pregnant patients presenting with ACS-like symptoms especially in the setting of hyperemesis gravidarum.

Our case highlights the need for increased awareness of general medical community that GTT can lead to significant cardiac events. Novel methods of controlling GTT as well as medical interventions like ICD need further study.
Effectiveness of first-line pegvisomant monotherapy in acromegaly: an ACROSTUDY analysis
Authors: Tritos Nicholas A , Chanson Philippe , Jimenez Camilo , King Donna , Jönsson Peter J , Klibanski Anne , Biller Beverly M K 
Published: November 2016

Objective
To examine the effectiveness and safety of primary pegvisomant monotherapy.

Design
Retrospective analysis of data extracted from ACROSTUDY (global observational outcomes study of patients with acromegaly treated with pegvisomant).

Methods
The earliest time to insulin-like growth factor 1 (IGF-1) normalization on pegvisomant monotherapy was determined. Both the proportion of patients who achieved IGF-1 normalization and the time to IGF-1 normalization on pegvisomant monotherapy were assessed.

Results
Eligible patients included 28 subjects on primary medical therapy (PT) and 176 controls on adjunctive pegvisomant therapy treated postoperatively, including 43 who were naïve to medical therapy (NMT) and 133 who were previously treated medically and were washed out (WASH). IGF-1 normalization occurred in 76.9% (PT), 85.2% (NMT) and 78.3% (WASH) patients (P = NS). Median times to IGF-1 normalization were 0.5 year (PT), 0.7 year (NMT) and 0.6 year (WASH), P = NS. On survival analysis, the fraction of patients controlled on pegvisomant monotherapy was not different between groups. Higher baseline IGF-1 levels, obtained at study entry, predicted a lower likelihood of IGF-1 normalization on monotherapy (P = 0.012). Safety data include low prevalence of skin rashes, injection site reactions and reversible transaminase elevations. There was one patient (NMT) with a verified increase in tumor size.

Conclusions
Pegvisomant monotherapy, administered either as primary medical therapy or as adjunctive therapy according to local practice, led to IGF-1 normalization in >75% of patients. Pegvisomant monotherapy had a favorable safety profile, consistent with previous observations. Prospective data are needed to further evaluate the role of primary pegvisomant monotherapy in acromegaly.
Pretense as Creative Hallucination
Authors: West Donna E. E. 
Published: November 2016

Ch. S. Peirce’s concept of “creative hallucination” (EP 2:192 1903) captures the myriad ways in which sterile conventional practices can be informed by word and role play. Word and person substitutions constitute not errors of judgment, but attain the status of metaphor, would-be propositions, and cultural myth. Naming practices come to represent instances of word play, in which metaphor and myth permeate new object identities, which, in turn reveal cultural dispositions. Accordingly, these newly conceived action habits express analogies of another to another other – illustrating potentialities for filling slots in role-play scenarios.
In short, different cultures develop creative action-habits from distinctive mechanisms according to culturally driven processes, but they all culminate in representational diversity, by persons/entities becoming another. These creative hallucinations supply iconic and indexical scaffolds to supersede literal word use, and conventional person identities. But for the holistic parameters which nascent envisionment provides, the painter’s hunch that changing the colour to enhance the product may never have arisen.
Caracterización química de material particulado PM10 en la atmósfera de La Guajira Colombia
Authors: Doria Argumedo Carlos Julio , Fagundo Castillo Juan Reynero 
Published: November 2016

Durante el año 2013, se realizó un estudio en La Guajira, Colombia, con el fin de determinar la composición química del material particulado PM10, producto de las actividades mineras de carbón a cielo abierto que ocupan casi 30% del territorio; también se evaluó su asociación a fuentes naturales y antropogénicas. La recolección de filtros se realizó por medio de un sistema de monitoreo conformado por catorce estaciones mediante equipos muestreadores de alto volumen PM10 (Thermo Scientific VFC-PM10 High Volume Air Sampler). Para el análisis, los filtros de cuarzo fueron sometidos a extracción acuosa en caliente y se determinaron los iones por espectrofotometría UV-VIS e ICP-MS. Las concentraciones más altas corresponden a la especies SO42- (0,25 µg/m3), Cl- (0,19 µg/m3), NH4+ (0,032 µg/m3), Na+ (1,98µg/m3), Ca2+ (0,40 µg/m3) y Mg2+ (0,31 µg/m3). Los resultados indican que las principales fuentes responsables del material particulado corresponden al aerosol marino impulsado por las corrientes (Cl- y Na+) de origen natural, y las actividades agrícolas, pecuarias (NH4+) y mineras (SO42-, Ca2+ y Mg2+) de origen antropogénico.
KEBUTUHAN ASAM AMINO LISIN UNTUK BENIH IKAN KERAPU BEBEK (Cromileptes altivelis)
Authors: Giri Nyoman Adiasmara , Suwirya Ketut , Marzuqi Muhammad 
Published: November 2016

Percobaan penentuan kebutuhan asam amino lisin untuk benih ikan kerapu bebek (Cromileptes altivelis) telah dilakukan dengan metode pemeliharaan ikan menggunakan pakan yang mempunyai kandungan lisin berbeda. Ikan dengan bobot rata-rata 4,4 ± 0,3 gram dipelihara dalam bak polikarbonat volume 100 L dengan kepadatan 12 ekor ikan per bak. Setiap bak dilengkapi dengan sistem air mengalir dan aerasi. Pakan percobaan dibuat dalam bentuk pelet kering dengan kandungan protein 49% yang bersumber dari kasein dan tepung ikan serta campuran asam amino murni sehingga menyerupai komposisi asam amino tubuh ikan kerapu bebek, kecuali untuk lisin. Pakan percobaan mempunyai kandungan lisin berbeda, yaitu 1,77%; 2,27%; 2,77%; 3,27%; 3,77%; dan 4,27%. Ikan diberi pakan percobaan 2 kali sehari pada level satiasi selama 63 hari. Hasil percobaan menunjukkan bahwa bobot ikan akhir, persen pertambahan bobot, laju pertumbuhan spesifik, efisiensi pakan, retensi protein, dan kandungan protein tubuh ikan dipengaruhi oleh kandungan lisin pakan. Kadar optimum lisin dalam pakan untuk benih ikan kerapu bebek dihitung dengan regresi broken line berdasarkan data persen pertambahan bobot. Dari perhitungan ini diperoleh bahwa kebutuhan lisin untuk benih ikan kerapu bebek mencapai 2,77% dalam pakan atau setara dengan 5,63% dari protein pakan.The experiment to find out an amino acid lysine requirement for growth of humpback grouper juvenile has been conducted in 18 polycarbonate tanks, 100 liters volume. Each tank is equipped with flow-through water system. Twelve juveniles of humpback grouper (4.4 ± 0.3 gram in body weight), which were produced in hatchery, were randomly selected, and stock in each tank. Fish fed with experimental diets twice everyday at satiation level for 63 days. Experimental diets were prepared as dry pellet with casein and fish meal as the intact protein sources, and the mixture of crystalline amino acids to reach protein level of 49% and the composition of amino acid similar to the amino acid composition of whole body protein of humpback grouper, except for lysine content. Basal diet (diet-1) contains 1.77% lysine that was supplied from casein and fish meal. Graded level (0.5%) of crystalline lysine was added to the basal diet to get the final lysine level in each diet of 1.77%, 2.27%, 2.77%, 3.27%, 3.77%, and 4.27%. The experiment was designed according to completely random design (CRD) with 6 treatments (lysine levels) and three replicates for each treatment. Result of the experiment showed that dietary lysine content influenced final weight, weight gain, specific growth rate, feed efficiency, protein retention, and body protein content of humpback grouper juvenile. Optimum dietary lysine for humpback grouper juvenile was calculated using broken line regression analysis. Optimum dietary lysine requirement for growth of juvenile humpback grouper is 2.77% or equal to 5.63% of dietary protein.
KARAKTER GENETIK POPULASI IKAN MAS, C yprinus carpio HASIL PERSILANGAN
Authors: Ariyanto Didik , Nugroho Estu , Subagyo Subagyo 
Published: November 2016

Evaluasi karakter genetik populasi ikan mas hasil persilangan telah dilakukan dengan menggunakan metode elektroforesis protein secara horisontal. Sampel ikan sebanyak 120 ekor yang mewakili 6 populasi ikan mas adalah hasil persilangan resiprokal antara 3 strain ikan mas unggul yaitu strain majalaya, rajadanu dan sutisna. Bagian tubuh yang diambil untuk pengamatan karakter genetik adalah jaringan otot sedangkan sebagai media elektroforesis digunakan gel pati. Pada penelitian ini digunakan 12 sistem enzim untuk analisis. Hasil analisis menunjukkan bahwa 3 lokus polimorfik dari 7 lokus yang teridentifikasi, yaitu Ldh-1, Mdh-1 dan Me. Heterozigositas rata-rata sebesar 0,23 (kategori rendah). Nilai jarak genetik paling dekat sebesar 0 diperoleh antara populasi rajadanu dengan sutisna dan nilai terjauh sebesar 0,0018 antara populasi rajadanu dan sutisna dengan majalaya. Populasi rajadanu dan sutisna mempunyai pengaruh kuat terhadap struktur genetik populasi keturunan hasil persilangan dibandingkan dengan populasi majalaya.Evaluation of genetic characterization of the hybrid populations of common carp using protein electrophoresis method was conducted. The samples of 120 fishes were taken from Research Institute for Fish-breeding and Aquaculture Technology, Sukamandi. The samples has been extracted from muscle and potato starch gel was used to assess the level of genetic characters. Twelve enzymes were examined in this experiment. The result showed that 7 loci were identified that 3 of loci were polymorphs i.e. : Ldh-1, Mdh-1 and Me. An average of heterozigosity : 0.23 (low category). Genetic distance value between rajadanu and sutisna population was 0. Genetic distance value between both of rajadanu and sutisna populations from majalaya population was 0.0018. Rajadanu and sutisna strains have stronger influence to genetic structure of its offspring compared than majalaya strain.
PENAPISAN ISOLAT BAKTERI Streptococcus spp. SEBAGAI KANDIDAT ANTIGEN DALAM PEMBUATAN VAKSIN, SERTA EFIKASINYA UNTUK PENCEGAHAN PENYAKIT STREPTOCOCCOSIS PADA IKAN NILA, Oreochromis niloticus
Authors: Taukhid Taukhid , Purwaningsih Uni 
Published: November 2016

Riset dengan tujuan untuk memperoleh isolat kandidat yang imunogenik bagi pembuatan vaksin untuk pengendalian penyakit streptococcosis pada ikan nila telah dilakukan. Karakterisasi dilakukan secara biokimia dan API 20 STREP terhadap 15 isolat bakteri Streptococcus spp. Uji Koch’s Postulate kemudian dilakukan untuk mengetahui peran bakteri pada infeksi streptococcosis pada ikan nila. Konfirmasi taksonomis hingga level spesies isolat bakteri S. agalactiae dilakukan dengan teknik Polymerase Chain Reaction (PCR) dengan menggunakan primer spesifik. Uji patogenisitas dilakukan terhadap 6 isolat yang terdiri atas 5 isolat S. agalactiae (N3M, N4M, N14G, N17O, NK1) dan 1 isolat S. iniae (N2O). Hasil penapisan menunjukkan bahwa bakteri S. agalactiae (N4M) memiliki nilai LD50 terkecil, dan nilai terbesar dimiliki oleh bakteri S. iniae (N2O). Isolat bakteri N4M digunakan sebagai sumber antigen dalam pembuatan vaksin anti streptococcosis. Vaksin disiapkan dalam bentuk sel utuh dan diinaktivasi dengan formalin, pemanasan, dan sonikasi. Nilai titer antibodi dan sintasan tertinggi diperoleh pada kelompok ikan yang divaksin dengan formalin killed vaccine dibandingkan dengan teknik inaktivasi lainnya (heat killed vaccine dan sonicated vaccine).