bluuebunny/crossref_metadata_2025 huggingface dataset:
Cell “hashing” with barcoded antibodies enables multiplexing and doublet detection for single cell genomics
Authors: Stoeckius Marlon , Zheng Shiwei , Houck-Loomis Brian , Hao Stephanie , Yeung Bertrand Z. , Smibert Peter , Satija Rahul
Published: December 2017

Despite rapid developments in single cell sequencing technology, sample-specific batch effects, detection of cell doublets, and the cost of generating massive datasets remain outstanding challenges. Here, we introduce cell “hashing”, where oligo-tagged antibodies against ubiquitously expressed surface proteins are used to uniquely label cells from distinct samples, which can be subsequently pooled. By sequencing these tags alongside the cellular transcriptome, we can assign each cell to its sample of origin, and robustly identify doublets originating from multiple samples. We demonstrate our approach by pooling eight human PBMC samples on a single run of the 10x Chromium system, substantially reducing our per-cell costs for library generation. Cell “hashing” is inspired by, and complementary to, elegant multiplexing strategies based on genetic variation, which we also leverage to validate our results. We therefore envision that our approach will help to generalize the benefits of single cell multiplexing to diverse samples and experimental designs.
A Testis ER Chaperone Marks Mature Olfactory and Vomeronasal Sensory Neurons
Authors: Dalton Ryan P
Published: December 2017

The proper folding of most secreted and membrane proteins involves interaction with endoplasmic reticulum-resident, glycan-binding chaperones. Some of these chaperones, such as Calreticulin and Calnexin, are nearly ubiquitous, while others are found only in specific cell types, presumably reflecting a role in biosynthesis of proteins specific to those cells. Herein, I have identified Calmegin (Clgn), a chaperone required for fertile spermatogenesis, as a marker of mature neurons in the olfactory system. CLGN was expressed by olfactory marker protein (OMP)-positive neurons in both the main olfactory epithelium (MOE) and the vomeronasal organ (VNO). CLGN was detected both in the perinuclear ER network and in axons. Finally expression of Atf5, a transcription factor required for OSN and VSN development, was both required and sufficient for robust CLGN expression in OSNs and VSNs. Together these findings establish that an ER chaperone required for sperm fertility is developmentally regulated in olfactory neurons, provide a novel marker of mature olfactory neurons, and suggest common mechanisms of secretory protein biogenesis in these cell types.
Cellular diversity in theDrosophilamidbrain revealed by single-cell transcriptomics
Authors: Croset Vincent , Treiber Christoph D , Waddell Scott
Published: December 2017

To understand the brain, molecular details need to be overlaid onto neural wiring diagrams so that synaptic mode, neuromodulation and critical signaling operations can be considered. Single-cell transcriptomics provide a unique opportunity to collect this information. Here we present an initial analysis of thousands of individual cells fromDrosophilamidbrain, that were acquired using Drop-Seq. A number of approaches permitted the assignment of transcriptional profiles to several major brain regions and cell-types. Expression of biosynthetic enzymes and reuptake mechanisms allows all the neurons to be typed according to the neurotransmitter or neuromodulator that they produce and presumably release. Some neuropeptides are preferentially co-expressed in neurons using a particular fast-acting transmitter, or monoamine. Neuromodulatory and neurotransmitter receptor subunit expression illustrates the potential of these molecules in generating complexity in neural circuit function. This cell atlas dataset provides an important resource to link molecular operations to brain regions and complex neural processes.
Uterine progesterone signaling is a target for metformin therapy in PCOS-like rats
Authors: Hu Min , Zhang Yuehui , Feng Jiaxing , Xu Xue , Zhang Jiao , Zhao Wei , Guo Xiaozhu , Li Juan , Vestin Edvin , Cui Peng , Li Xin , Wu Xiao-ke , Brännström Mats , Shao Linus R , Billig Håkan
Published: December 2017

Impaired progesterone (P4) signaling is linked to endometrial dysfunction and infertility in women with polycystic ovary syndrome (PCOS). Here we report for the first time that elevated expression of progesterone receptor (PGR) isoforms A and B parallels increased estrogen receptor (ER) expression in PCOS-like rat uteri. The aberrant PGR-targeted gene expression in PCOS-like rats before and after implantation overlaps with dysregulated expression of Fkbp52 and Ncoa2, two genes that contribute to the development of uterine P4 resistance. In vivo and in vitro studies of the effects of metformin on the regulation of the uterine P4 signaling pathway under PCOS conditions showed that metformin directly inhibits the expression of PGR and ER along with the regulation of several genes that are targeted dependently or independently of PGR-mediated uterine implantation. Functionally, metformin treatment corrected the abnormal expression of cell-specific PGR and ER and some PGR-target genes in PCOS-like rats with implantation. Additionally, we documented how metformin contributes to the regulation of the PGR-associated MAPK/ERK/p38 signaling pathway in the PCOS-like rat uterus. Our data provide novel insights into how metformin therapy regulates uterine P4 signaling molecules under PCOS conditions.
MinION-based long-read sequencing and assembly extends the Caenorhabditis elegans reference genome
Authors: Tyson John R. , O'Neil Nigel J. , Jain Miten , Olsen Hugh E. , Hieter Philip , Snutch Terrance P.
Published: December 2017

Advances in long-read single molecule sequencing have opened new possibilities for ‘benchtop’ whole-genome sequencing. The Oxford Nanopore Technologies MinION is a portable device that uses nanopore technology that can directly sequence DNA molecules. MinION single molecule long sequence reads are well suited for de novo assembly of complex genomes as they facilitate the construction of highly contiguous physical genome maps obviating the need for labor-intensive physical genome mapping. Long sequence reads can also be used to delineate complex chromosomal rearrangements, such as those that occur in tumor cells, that can confound analysis using short reads. Here, we assessed MinION long-read-derived sequences for feasibility concerning: (1) the de novo assembly of a large complex genome, and (2) the elucidation of complex rearrangements. The genomes of two Caenorhabditis elegans strains, a wild-type strain and a strain containing two complex rearrangements, were sequenced with MinION. Up to 42-fold coverage was obtained from a single flow cell, and the best pooled data assembly produced a highly contiguous wild-type C. elegans genome containing 48 contigs (N50 contig length = 3.99 Mb) covering >99% of the 100,286,401-base reference genome. Further, the MinION-derived genome assembly expanded the C. elegans reference genome by >2 Mb due to a more accurate determination of repetitive sequence elements and assembled the complete genomes of two co-extracted bacteria. MinION long-read sequence data also facilitated the elucidation of complex rearrangements in a mutagenized strain. The sequence accuracy of the MinION long-read contigs (∼98%) was improved using Illumina-derived sequence data to polish the final genome assembly to 99.8% nucleotide accuracy when compared to the reference assembly.
Crystal structure of 6,7-dehydroroyleanone isolated fromTaxodium distichum(L.) Rich.
Authors: Chen Li , Ma Xinhua , Deng ShiHao , Yang XinZhou , Song Ping
Published: December 2017

The title compound, 6,7-dehydroroyleanone, C20H26O3[systematic name: (4bS)-3-hydroxy-2-isopropyl-4b,8,8-trimethyl-4b,5,6,7,8,8a-hexahydrophenanthrene-1,4-dione] was isolated fromTaxodium distichum(L.) Rich. The compound crystallizes in the space groupP21. The crystal structure features two O—H...O hydrogen bonds, forming chains along the [010] direction.
Structure of Rubisco fromArabidopsis thalianain complex with 2-carboxyarabinitol-1,5-bisphosphate
Authors: Valegård Karin , Hasse Dirk , Andersson Inger , Gunn Laura H.
Published: December 2017

The crystal structure of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) fromArabidopsis thalianais reported at 1.5 Å resolution. In light of the importance ofA. thalianaas a model organism for understanding higher plant biology, and the pivotal role of Rubisco in photosynthetic carbon assimilation, there has been a notable absence of anA. thalianaRubisco crystal structure.A. thalianaRubisco is an L8S8hexadecamer comprising eight plastome-encoded catalytic large (L) subunits and eight nuclear-encoded small (S) subunits.A. thalianaproduces four distinct small-subunit isoforms (RbcS1A, RbcS1B, RbcS2B and RbcS3B), and this crystal structure provides a snapshot ofA. thalianaRubisco containing the low-abundance RbcS3B small-subunit isoform. Crystals were obtained in the presence of the transition-state analogue 2-carboxy-D-arabinitol-1,5-bisphosphate.A. thalianaRubisco shares the overall fold characteristic of higher plant Rubiscos, but exhibits an interesting disparity between sequence and structural relatedness to other Rubisco isoforms. These results provide the structural framework to understandA. thalianaRubisco and the potential catalytic differences that could be conferred by alternativeA. thalianaRubisco small-subunit isoforms.
Analysing the impact of different classical controller strategies on the dynamics performance of production-inventory systems using state space approach
Authors: AL-Khazraji Huthaifa , Cole Colin , Guo William
Published: December 2017

Purpose

The purpose of this paper is to examine the impact of applying two classical controller strategies, including two proportional (P) controllers with two feedback loops and one proportional–integral–derivative (PID) controller with one feedback loop, on the order and inventory performance within a production-inventory control system.

Design/methodology/approach

The simulation experiments of the dynamics behaviour of the production-inventory control system are conducted using a model based on control theory techniques. The Laplace transformation of an Order–Up–To (OUT) model is obtained using a state-space approach, and then the state-space representation is used to design and simulate a controlled model. The simulations of each model with two control configurations are tested by subjecting the system to a random retail sales pattern. The performance of inventory level is quantified by using the Integral of Absolute Error (IAE), whereas the bullwhip effect is measured by using the Variance ratio (Var).

Findings

The simulation results show that one PID controller with one feedback loop outperforms two P controllers with two feedback loops at reducing the bullwhip effect and regulating the inventory level.

Originality/value

The production-inventory control system is broken down into three components, namely: the forecasting mechanism, controller strategy and production-inventory process. A state-space approach is adopted to design and simulate the different controller strategy.
Employment Effects of the CAP in Italian Agriculture: Territorial Diversity and Policy Effectiveness
Authors: Mantino Francesco
Published: December 2017

The objectives of this article are to provide insights on the employment impacts of CAP measures in Italian agriculture over the period 2007–14, and to explore the diversity of these impacts in four types of area. The main policy tools of the First Pillar have debatable impacts on agricultural employment in all area types, although they were not specifically designed to create jobs but to ensure food production and socio‐environmentally sustainable land management practices. Second Pillar measures bring positive and significant rural development effects to the areas of Italy studied, but these effects differ according to the type of measure: farm and agro‐industrial investment support generates higher employment effects than measures for the agri‐environment, less favoured areas, or rural diversification. The intensity of these effects is higher in those areas where conditions for development are more favourable. They still have positive effects in Peripheral Areas, but the cost of creating new jobs in such areas is higher. It can be argued that we need a more flexible CAP, capable of fitting diverse territorial needs, and strengthened by rules of policy design and implementation more oriented towards the pursuit of territorial cohesion.
Material Needs of Emergency Department Patients: A Systematic Review
Authors: Malecha Patrick W. , Williams James H. , Kunzler Nathan M. , Goldfrank Lewis R. , Alter Harrison J. , Doran Kelly M.
Published: December 2017

Background

Interest in social determinants of health (SDOH) has expanded in recent years, driven by a recognition that such factors may influence health outcomes, services use, and health care costs. One subset of SDOH is material needs such as housing and food. We conducted a systematic review of the literature on material needs among emergency department (ED) patients in the United States.

Methods

We followed PRISMA guidelines for systematic review methodology. With the assistance of a research librarian, four databases were searched for studies examining material needs among ED patients. Two reviewers independently screened titles, abstracts, and full text to identify eligible articles. Information was abstracted systematically from eligible articles.

Results

Forty‐three articles were eligible for inclusion. There was heterogeneity in study methods; single‐center, cross‐sectional studies were most common. Specific material needs examined included homelessness, poverty, housing insecurity, housing quality, food insecurity, unemployment, difficulty paying for health care, and difficulty affording basic expenses. Studies overwhelmingly supported the notion that ED patients have a high prevalence of a number of material needs.

Conclusions

Despite some limitations in the individual studies examined in this review, the plurality of prior research confirms that the ED serves a vulnerable population with high rates of material needs. Future research is needed to better understand the role these needs play for ED patients and how to best address them.
Dielectric relaxation induced internal electric field and its effect on magnetoelectric state in Co4Nb2O9
Authors: Xie Yuanmiao , Zang Hao , Ceng Wen‐Dan , Wang Shuting , Wang Chunchang
Published: December 2017

Pyrocurrent and dielectric properties of magnetoelectric antiferromagnet Co4Nb2O9 have been investigated. The sample shows 2 thermally activated dielectric relaxations in the temperature range far above Néel temperature with the low‐ and high‐temperature ones being a dipolar and Maxwell‐Wagner relaxations, respectively. Two types of dipoles: relaxing dipoles and magnetic‐field‐induced dipoles were found in the sample. An internal electric field is formed due to the ordering of relaxing dipoles. Three current peaks were observed. The 2 higher temperature current peaks correspond to the dielectric relaxations. The lowest temperature current peak contains a positive tip and negative dip. The tip and dip are related to the depolarization of ferroelectricity induced by external and internal fields, respectively.
Postprandial walking reduces glucose levels in women with gestational diabetes mellitus
Authors: Coe Dawn P. , Conger Scott A. , Kendrick Jo M. , Howard Bobby C. , Thompson Dixie L. , Bassett David R. , White Jennifer D.
Published: December 2017

The purpose of this study was to investigate blood glucose changes, as measured by a continuous glucose monitoring system, that occur in women with gestational diabetes mellitus (GDM) following an acute bout of moderate-intensity walking after consuming a high-carbohydrate/low-fat meal. This study found that moderate-intensity walking induced greater postprandial glucose control compared with sedentary activity and it appears that moderate-intensity activity may be used to reduce postprandial glucose levels in women with GDM.
Nitrate and ammonium uptake in 21 common species of moss from Vancouver Island, British Columbia
Authors: Hawkins B.J. , May E. , Robbins S.
Published: December 2017

Mosses play key ecological roles in water and nutrient retention in many ecosystems, yet relatively little is known of the functional characteristics of moss species, particularly nutritional characteristics. We investigated the net flux of ammonium, nitrate, and protons, using a microelectrode ion flux measurement system, in the gametophytes of 21 common species of moss from three contrasting locations in southern coastal British Columbia. The general location from which mosses were collected did not significantly affect ammonium or nitrate uptake. Proton efflux was greatest in mosses from locations with high rainfall. Rates of nitrate uptake differed among moss families, but there were no significant differences in uptake among species within families. Ammonium net flux differed among moss families, but also among species nested within family, with some species showing uptake and other showing ammonium efflux. In general, moss species native to dry habitats appeared to have higher rates of nitrogen uptake when ammonium and nitrate were available under favourable conditions.
Knowledge Graph Embedding
Authors: Jia Yantao , Wang Yuanzhuo , Jin Xiaolong , Lin Hailun , Cheng Xueqi
Published: December 2017

A knowledge graph is a graph with entities of different types as nodes and various relations among them as edges. The construction of knowledge graphs in the past decades facilitates many applications, such as link prediction, web search analysis, question answering, and so on. Knowledge graph embedding aims to represent entities and relations in a large-scale knowledge graph as elements in a continuous vector space. Existing methods, for example, TransE, TransH, and TransR, learn the embedding representation by defining a global margin-based loss function over the data. However, the loss function is determined during experiments whose parameters are examined among a closed set of candidates. Moreover, embeddings over two knowledge graphs with different entities and relations share the same set of candidates, ignoring the locality of both graphs. This leads to the limited performance of embedding related applications. In this article, a locally adaptive translation method for knowledge graph embedding, called TransA, is proposed to find the loss function by adaptively determining its margin over different knowledge graphs. Then the convergence of TransA is verified from the aspect of its uniform stability. To make the embedding methods up-to-date when new vertices and edges are added into the knowledge graph, the incremental algorithm for TransA, called iTransA, is proposed by adaptively adjusting the optimal margin over time. Experiments on four benchmark data sets demonstrate the superiority of the proposed method, as compared to the state-of-the-art ones.
Solutions for environment, economy, and democracy (SEED)
Authors: Bennett W. Lance , Borning Alan , Gruen Deric
Published: December 2017

In this forum we highlight innovative thought, design, and research in the area of interaction design and sustainability, illustrating the diversity of approaches across HCI communities.
--- Lisa Nathan, Editor
Radar sensing in human-computer interaction
Authors: Yeo Hui-Shyong , Quigley Aaron
Published: December 2017

Envisioning, designing, and implementing the user interface require a comprehensive understanding of interaction technologies. In this forum we scout trends and discuss new technologies with the potential to influence interaction design.
---Albrecht Schmidt, Editor
Biological Insight from Super-Resolution Microscopy: What We Can Learn from Localization-Based Images
Authors: Baddeley David , Bewersdorf Joerg
Published: December 2017

Super-resolution optical imaging based on the switching and localization of individual fluorescent molecules [photoactivated localization microscopy (PALM), stochastic optical reconstruction microscopy (STORM), etc.] has evolved remarkably over the last decade. Originally driven by pushing technological limits, it has become a tool of biological discovery. The initial demand for impressive pictures showing well-studied biological structures has been replaced by a need for quantitative, reliable data providing dependable evidence for specific unresolved biological hypotheses. In this review, we highlight applications that showcase this development, identify the features that led to their success, and discuss remaining challenges and difficulties. In this context, we consider the complex topic of defining resolution for this imaging modality and address some of the more common analytical methods used with this data.
Role of Proteins on Formation, Drainage, and Stability of Liquid Food Foams
Authors: Narsimhan Ganesan , Xiang Ning
Published: December 2017

Foam is a high-volume fraction dispersion of gas into a liquid or a solid. It is important to understand the effect of formulation on shelf life and texture of food foams. The objective of this review is to elucidate mechanisms of formation and stability of foams and relate them to the formulations. Emulsifiers are important in foam formation, whereas proteins are generally preferred to provide long-term stability. Syneresis in foams is a precursor to their collapse in many instances. Intermolecular forces, conformation, and flexibility of proteins play an important role in foam stabilization. An adsorbed protein layer at air/water interfaces imparts interfacial rheology that is necessary to improve the shelf life of foam products. Wettability and spreading of food particles at the interface can stabilize or destabilize foams, depending on their properties. More studies are needed to fully understand the complex interplay of various mechanisms of destabilization in a real-food formulation.
Non-steady state: error analysis of Steele's model and developments for glucose kinetics
Authors: Cobelli C. , Mari A. , Ferrannini E.
Published: December 2017

The model proposed by Steele (Ann. NY Acad. Sci. 82: 420-430, 1959) to compute rates of appearance and disappearance in non-steady state is subjected to theoretical analysis. It is shown that this model introduces an error with two components, one dependent on the volume of the compartment, the other related to the complex configuration of the system. The errors depend on the time course of specific activity, change differently with time, and may take the opposite sign but they do not, in general, cancel each other. Corollaries of this analysis are the following: there is no single pool-fraction value satisfactory under all non-steady-state situations; keeping tracer specific activity as constant as possible during the experiment minimizes both errors; and non-steady-state analysis demands proper modeling of the system. Tracer experiments were carried out in five normal volunteers. Plasma [3-3H]glucose concentration was first brought to equilibrium by means of a primed constant 2-h infusion, and then the steady state was perturbed by a 2-h euglycemic insulin (1 mU X min-1 X kg-1) clamp, realizing a transition between a basal and a euglycemic hyperinsulinemic steady state. These data were analyzed with Steele's equation, the two compartment models of Radziuk et al. [Am. J. Physiol. 234 (Endocrinol. Metab. Gastrointest. Physiol. 3): E84-E93, 1978], and a new model based on a study on glucose kinetics carried out in the two steady states separately. Steele's equation yielded negative values for hepatic glucose production already 40 min into the clamp and throughout the study. The average value of glucose production during the 2nd h was -0.88 mg X min-1 X kg-1; the suppression of basal release over the 2-h period was 115%. In contrast, the new model calculated a mean glucose production of 0.37 mg X min-1 X kg-1 during the 2nd h and an overall suppression of 62%; no negative values were obtained.
Hydroosmotic responses to short pulses of vasotocin by toad bladder
Authors: Eggena P.
Published: December 2017

When toads, Bufo marinus, were mildly dehydrated, the permeability to water of their urinary bladders increased, but blood samples placed directly on the wall of an isolated assay bladder did not contain enough arginine vasotocin (AVT) to induce the observed response. One explanation for this discrepancy is that AVT is secreted intermittently and rapidly cleared from the blood, even though the hydroosmotic response persists. The hydroosmotic response of bladders to pulsatile secretion of AVT was simulated by dipping isolated bladders for 1 min in Ringer's fluid with AVT followed by washout of hormone. Bladders developed the characteristic increase in membrane permeability to water several minutes after AVT had been removed from the serosal bathing solution. With short periods of bladder exposure to hormone, higher concentrations were required for triggering responses equivalent to those induced with continuous stimulation. This requirement was greater for vasopressin than it was for AVT. Studies with tritium-labeled vasopressin indicated that there is a "receptor reserve" for the hydroosmotic action of vasopressin in the toad bladder. The magnitude of this reserve is reduced as the duration of stimulation with hormone is diminished. It is suggested that pulsatile exposure of the bladder to AVT increases the specificity of the hormone for hydroosmotic receptors and minimizes the development of target organ resistance. The large receptor reserve in this tissue may be required to capture short bursts of AVT secreted into blood, although this remains to be demonstrated.
Increased uptake and phosphorylation of 2-deoxyglucose by skeletal muscles in endotoxin-treated rats
Authors: Meszaros K. , Bagby G. J. , Lang C. H. , Spitzer J. J.
Published: December 2017

Glucose metabolism of respiratory and nonrespiratory muscles of different fiber composition was investigated in conscious rats. The accumulation of phosphorylated 2-deoxyglucose (2DGP) was increased in skeletal muscles by 56-102% and in diaphragm by 236% at 3 h after treatment with 100 micrograms/100 g endotoxin. The increase was still marked at 24 h, whereas it diminished at 48 h in the diaphragm, abdominal muscle, and white portion of the quadriceps. In the red portion of this muscle 2DGP accumulation was less than that in time-matched controls at 24 and 48 h. Whole gastrocnemius (mixed-fiber types) showed no changes after 24 h. The high 2DGP accumulation in brain remained stable. The retention of 2DGP in tissues, studied by sequential double labeling, did not change 3 h after endotoxin. The lumped constant was similar in the isolated epitrochlear muscles of endotoxemic and control rats. Whole-body glucose utilization (Rd) was increased by 68% 3 h after endotoxin, but it was normal at 24 and 48 h. The increase of glucose utilization by the entire skeletal muscle mass was responsible for approximately 25% of the increase in Rd; therefore it appears that other tissues also contributed significantly to the endotoxin-induced alterations in carbohydrate metabolism.
Decreased myofibrillar proteolysis after refeeding requires dietary protein or amino acids
Authors: Goodman M. N. , del Pilar Gomez M.
Published: December 2017

Previous studies have demonstrated that brief fasting augments and refeeding a complete diet diminishes the breakdown of myofibrillar proteins in rat skeletal muscle. The purpose of the present study was to determine which dietary component(s) was responsible for this effect and to determine the role of insulin and amino acids. Myofibrillar proteolysis was evaluated by measuring the release of 3-methylhistidine by perfused rat muscle of 1-day fasted rats and 1-day fasted rats refed for 4–24 h with a complete, protein-free, or lipid meal. For comparison, tyrosine release by perfused muscle was measured in the absence and presence of cycloheximide to evaluate net and total proteolysis, respectively. Refeeding of either diet increased plasma insulin. Despite this, myofibrillar proteolysis decreased only when protein or amino acids was included in the test meal. On the other hand, the complete or protein-free meal decreased tyrosine release in the absence but not in the presence of cycloheximide, suggesting that either diet enhanced muscle protein synthesis. Most amino acids in plasma and muscle decreased after refeeding the protein-free meal, whereas after the complete meal some amino acids in plasma and muscle increased, whereas other decreased or changed little. These results indicate that decreased myofibrillar proteolysis in muscle after refeeding of food-deprived rats requires dietary protein or amino acids. They also suggest that hormonal and/or nutritional factors other than insulin and amino acids may orchestrate this response. However, a role of amino acids cannot yet be excluded, because it is conceivable that changes in specific amino acids in plasma instead of muscle may signal diminished proteolysis.
Triacylglycerol kinetics in endotoxic rats with suppressed lipoprotein lipase activity
Authors: Bagby G. J. , Corll C. B. , Martinez R. R.
Published: December 2017

Hypertriglyceridemia observed in animals after bacterial endotoxin administration and some forms of sepsis can result from increased hepatic triacylglycerol (TG) output or decreased TG clearance by extrahepatic tissues. To differentiate between these two possibilities, TG and free fatty acid (FFA) kinetics were determined in control and endotoxin-injected (0.1–0.5 mg/100 g) rats 18 h after treatment. Plasma TG and FFA kinetics were assessed by a constant intravenous infusion with [9,10-3H]palmitate-labeled very low-density lipoprotein and [1–14C]palmitate bound to albumin, respectively. In addition, lipoprotein lipase (LPL) activity was determined in heart, skeletal muscle, and adipose tissue as well as in postheparin plasma of functionally hepatectomized, adrenalectomized, and gonadectomized rats. Plasma FFA acid concentrations were slightly increased in endotoxin-treated rats but their turnover did not differ from control. Endotoxin-treated rats had a threefold increase in plasma TG concentrations and decreased heart, skeletal muscle, and post-heparin plasma LPL activity. Plasma TG turnover was decreased, indicating that hypertriglyceridemia was not due to an increased TG output by the liver. Instead, the endotoxin-induced increase in plasma TG concentration was a consequence of the 80% reduction in TG metabolic clearance rate. Thus, suppression of LPL activity in endotoxic animals impairs TG clearance resulting in hypertriglyceridemia. Furthermore, endotoxin administration reduced the delivery of TG-FFA to extrahepatic tissues because hepatic synthesis and secretion of TG from plasma FFA was decreased and LPL activity was suppressed.
Nervous control of glycogenolysis and blood flow in arterially and portally perfused liver
Authors: Gardemann A. , Strulik H. , Jungermann K.
Published: December 2017

In a recently developed model for the simultaneous perfusion of isolated rat liver via both the hepatic artery (120 mmHg, 20-35% flow) and the portal vein (10 mmHg, 80-65% flow), the arterial and portal nerve plexuses were stimulated (20 V, 2 ms, 2.5-20 Hz for 0.33-5 min) either jointly in the liver hilus or separately at the common hepatic artery and the mesenteric vein, respectively. Stimulation of the arterial plexus alone caused an increase of glucose output, a shift from lactate uptake to output, and a decrease of arterial and, "transhepatically," also of portal flow. Stimulation of the portal plexus alone elicited the same yet clearly smaller metabolic and transhepatic hemodynamic effects. The sum of the metabolic actions of single arterial and portal stimulations but not the sum of the hemodynamic actions was equal to the effects of simultaneous separate stimulations of the hepatic artery and mesenteric vein or joint stimulations in the liver hilus. Half-maximal and maximal effects were reached during 5-min stimulation periods within the physiological range of frequencies, i.e., at 5-6 and 10 Hz for metabolic alterations and at 8 and 20 Hz for hemodynamic changes. At a frequency of 10 Hz, half-maximal and maximal effects were observed with stimulation periods of 0.5 and 1 min for metabolic alterations and with 2 and 5 min for hemodynamic changes. The described model of isolated rat liver perfusion is well suited for the study of the complex metabolic and hemodynamic actions of the arterial and portal nerves, their mutual interactions, and modulations by circulating factors.
Evidence for cAMP as a mediator of gonadotropin secretion from female pituitaries
Authors: Bourne G. A. , Baldwin D. M.
Published: December 2017

Sodium flufenamate, which inhibited gonadotropin-releasing hormone (GnRH)-stimulated increases in adenosine 3',5'-cyclic monophosphate (cAMP), was used to evaluate the potential role of cAMP as a mediator of GnRH-stimulated gonadotropin secretion. Quartered pituitaries from diestrous II female rats were perifused at 37 degrees C, and sequential effluent fractions were collected every 10 min. Administration of GnRH resulted in a characteristic biphasic response for both luteinizing hormone (LH) and follicle-stimulating hormone (FSH), whereas 5 microM cycloheximide inhibited the secondary augmented responses (phase II) of both hormones. Infusions of 0.1 mM flufenamate inhibited GnRH-stimulated gonadotropin secretion in a manner similar to that of cycloheximide, whereas the administration of 5 mM dibutyryl cAMP in combination with GnRH and flufenamate resulted in the restoration of LH and FSH secretion. The dibutyryl cAMP-restored response appeared to be protein synthesis dependent and specific for cAMP. These results suggest that although the cyclic nucleotide is not involved in the acute release of LH and FSH, it does appear to play a pivotal but indirect role in phase II release of the hormones, by effects involving the stimulation of de novo protein synthesis.
Muscle glycogen repletion during active postexercise recovery
Authors: Peters Futre E. M. , Noakes T. D. , Raine R. I. , Terblanche S. E.
Published: December 2017

High-intensity intermittent bicycle exercise was used to deplete muscle glycogen levels by 70% and elevate blood lactate levels to greater than 13.0 mmol/l. Thereafter subjects either cycled with one leg for 45 min followed by 45 min of passive recovery (partially active recovery) or rested for 90 min (passive recovery). During the first 45 min of partially active recovery 1) blood lactate (P less than 0.05) and pH levels (P less than 0.05) returned more rapidly to preexercise values than during passive recovery, 2) the rate of net glycogen resynthesis (0.28 mumol . g-1 . min-1) was the same in both legs, and 3) muscle lactate levels were significantly lower (P less than 0.05) in the passive than in the active leg. Thereafter the rate of net muscle glycogen resynthesis was unchanged (0.26 mumol . g-1 . min-1) and lactate removal could theoretically account for only 18% of the glycogen resynthesized. Overall, the rate of muscle glycogen resynthesis and muscle lactate removal was not different from that measured during passive recovery. After high-intensity exercise 1) glycogen repletion is not impeded by light exercise, and 2) blood glucose is an important substrate for glycogen resynthesis.
Physiological increments in epinephrine stimulate metabolic rate in humans
Authors: Staten M. A. , Matthews D. E. , Cryer P. E. , Bier D. M.
Published: December 2017

Markedly elevated plasma epinephrine is known to increase metabolic rate (MR), but such levels of epinephrine are encountered infrequently in normal free-living subjects. We studied whether epinephrine levels common in usual daily activities can affect MR and thus possibly regulate caloric expenditure. To aid definition of a MR threshold, we first measured the hourly and daily variation in MR within individuals by measuring the MR of four individuals by indirect calorimetry for 6 h on six separate occasions without any intervention. We found that hour-to-hour variation (2.0 +/- 0.9%) and the day-to-day variation (2.7 +/- 0.9%) were low, thus allowing confident detection of small increments in metabolic rate during epinephrine infusion. To define a threshold for epinephrine's effect to increase MR, we studied five normal-weight postabsorptive young men on four separate occasions. During the 1st h of each 5-h study period, saline was infused intravenously. Then, during the subsequent 4 h, subjects received intravenous infusion of saline or epinephrine at 0.1, 0.5, and 1.0 microgram/min (randomized). A significant increase in MR (3.6 +/- 1.0% SE) was measured with the lowest epinephrine infusion rate (venous plasma concentration, 94 +/- 32 pg/ml). The increases in MR correlated (r = 0.85, P less than 0.001) with increases in plasma epinephrine. The threshold concentration (upper 95% confidence limit) of epinephrine to affect MR was 90 pg/ml, a concentration frequently occurring in daily life. Thus epinephrine may play an important role in weight maintenance by affecting energy expenditure.
Metabolites of 2-deoxyglucose in rat brain at 12-24 h: bounds on kinetic constants
Authors: Bass L. , Bodsch W. , Robinson P. J. , Young M. O.
Published: December 2017

Activities of 2-deoxy-D-glucose and its metabolites in rat brain were examined at 12, 16, 20, and 24 h after intraperitoneal injection of 14C-labeled 2-deoxy-D-glucose. Plasma radioactivity was monitored for 2 h before each of these determinations. As proportion of total brain radioactivity, 2-deoxy-D-glucose decreased monotonically from the unexpectedly high value of 22% at 12 h to 11% at 24 h after injection, 2-deoxy-D-glucose 6-phosphate decreased monotonically from 69% at 12 h to 23% at 24 h, and unphosphorylated products (of high and low molecular weight) increased from 10% at 12 h to 64% at 24 h. The data were analyzed in terms of a four-compartment model. Secure lower and upper bounds on the rate constant, k4*, for the dephosphorylation of 2-deoxy-D-glucose 6-phosphate were established: k4* was at least 0.0158 +/- 0.0014 . min-1 and at most 0.0385 +/- 0.0037 . min-1. If k4* is constant in time, then appreciable dephosphorylation occurs within the 45-min experimental period commonly used in the standard 2-deoxy-D-glucose method for estimating local cerebral glucose utilization. The possibility that the effective k4* is lower at such early times is reviewed in the light of a reanalysis of previously published data. Implications of these results for the 2-deoxy-D-glucose method are discussed from the points of view of numerical analysis and capillary heterogeneity.
Restricted passage of insulin across capillary endothelium in perfused rat adipose tissue
Authors: Chernick S. S. , Gardiner R. J. , Scow R. O.
Published: December 2017

Passage of insulin across capillary endothelium was monitored in perfused rat parametrial adipose tissue by the effect of intra-arterially infused insulin on oxidation of [U-14C]glucose to CO2. Glucose oxidation was constant at 34 nmol C.g-1.min-1 for 90 min in tissues perfused with 0 or 50 microU/ml. The rate of oxidation was doubled in 90 min at 100 microU/ml and maximal (4 X control) in 40 min at 200 microU/ml and in 20-30 min at 500 microU/ml. The slow decline in oxidation rate when insulin infusion was stopped suggested that insulin was sequestered in the tissue. Although half-maximal response to insulin occurred in perfused tissues at 100 microU/ml, it occurred at 8 microU/ml in incubated adipocytes and at 30 microU/ml in incubated tissue. In addition, the time required for maximal response to insulin was longer in perfused adipose tissue than in incubated cells and tissues. The data indicate that transfer of insulin from blood to parenchymal cells in perfused tissue was restricted. The minimal amount of insulin needed for a response by adipocytes in perfused tissue was estimated to be less than 1% of that in blood. Our findings are consistent with the concept that insulin is transferred across capillary endothelium by a receptor-mediated process.
Rat hepatic mRNA-S14 and lipogenic enzymes during weaning: role of S14 in lipogenesis
Authors: Perez-Castillo A. , Schwartz H. L. , Oppenheimer J. H.
Published: December 2017

The rapid and marked response of hepatic mRNA-S14 sequence to both triiodothyronine and carbohydrate intake has made this sequence an attractive model for studying the action of hormonal and dietary factors. Because it is highly expressed and regulated only in lipogenic tissues, we have suggested that it plays a role in some aspect of lipid synthesis, transport, or metabolism. To provide more precise information regarding the function of S14 we have measured lipogenesis, lipogenic enzymes, beta-oxidation, and mRNA-S14 levels in spontaneously weaning neonatal rats and in rats prematurely weaned to a laboratory diet on postnatal day 17. After birth, the levels of lipogenesis, mRNA-S14, and the lipogenic enzymes malic enzyme (ME) and fatty acid synthase (FAS) were almost undetectable but increased with the onset of spontaneous weaning. Coincident with these changes, beta-oxidation decreased. Premature weaning beginning on day 17 resulted in an earlier and even more marked increase in lipogenesis, ME, FAS, and mRNA-S14. On day 19, ME and FAS activities were 6- to 19-fold more than activities in control suckling pups, whereas mRNA-S14 levels had risen to greater than 100 times the control values. Thus directional shifts in mRNA-S14 corresponded with indices of lipogenesis and were opposite to indices reflecting beta-oxidation. The response of mRNA-S14 therefore suggests that it may be related to the synthesis of fatty acids. On the other hand, the level of lipogenesis in the fetus was high despite the fact that the levels of both mRNA-S14 and ME were low. This dissociation raises the possibility that the S14 protein participates in lipogenesis in the neonate and adult but not in the fetus.
Cellular and subcellular distribution of exogenously administered renal renin in rat liver and kidney
Authors: Kim S. , Iwao H. , Nakamura N. , Ikemoto F. , Yamamoto K. , Mizuhira V. , Yokofujita J.
Published: December 2017

Using highly purified 125I-labeled rat renal renin, we have demonstrated that both the liver and kidney are responsible for clearance of renal renin. In the present study, light and electron microscope autoradiography of intravenously administered 125I-labeled rat renal renin was performed in rat liver and kidney to observe the cellular and subcellular distribution of the renin. Fifteen and 60 min after the injection, the liver and kidneys were removed and fixed with 0.1 M sodium phosphate buffer, pH 6.8, containing 2.5% glutaraldehyde and 0.5% tannic acid, which allowed for the removal of breakdown products of the labeled renin, and then autoradiography was performed. In the liver, silver grains were mainly localized in Kupffer cells and not in hepatocytes. In the kidney, silver grains were evident in the proximal tubule cells. In both liver and kidney cells, silver grains were mainly located over the lysosomes. Gel permeation high-performance liquid chromatography analysis of the liver and kidney extracts indicated two main fractions, including immunoreactive 125I-renin and the breakdown products (free 125I and 125I-tyrosine). In conclusion, circulating renal renin is mainly taken up by Kupffer cells and proximal tubule cells and is subsequently transported to the lysosomes to be degraded. These results, taken together with our previous finding that nonglycosylated submaxillary renin does not distribute in the liver, suggest that the carbohydrate moieties of renal renin are necessary for the recognition by Kupffer cells.
Regulation of Ca2+ homeostasis by islet endoplasmic reticulum and its role in insulin secretion
Authors: Wolf B. A. , Colca J. R. , Turk J. , Florholmen J. , McDaniel M. L.
Published: December 2017

Changes in intracellular Ca2+ concentrations have a major role in the regulation of insulin secretion by islet beta-cells. It has recently become apparent that the endoplasmic reticulum plays a prominent role in the regulation of intracellular Ca2+ concentrations under basal conditions and during insulin secretion. This review describes biochemical properties of the endoplasmic reticulum that contribute to intracellular Ca2+ homeostasis including 1) an ATP-dependent Ca2+ uptake pump associated with a Ca2+-ATPase located in the endoplasmic reticulum; 2) Ca2+ release from the endoplasmic reticulum induced by the second messengers inositol trisphosphate and arachidonic acid as well as the guanine nucleotide GTP; and 3) a Ca2+ sequestration mechanism localized to the endoplasmic reticulum that is regulated by glucose 6-phosphate and glucose-6-phosphatase. The hypothesis is developed that these biochemical mechanisms participate in the regulation of intracellular Ca2+ concentrations and represent central intracellular events involved in the first phase of glucose-induced insulin secretion.
Metabolism of 25-hydroxyvitamin D in copper-laden rat: a model of Wilson's disease
Authors: Carpenter T. O. , Pendrak M. L. , Anast C. S.
Published: December 2017

Wilson's disease results in excess tissue accumulation of copper and is often complicated by skeletal and mineral abnormalities. We investigated vitamin D metabolism in rats fed a copper-laden diet rendering hepatic copper content comparable with that found in Wilson's disease. Injection of 25-hydroxyvitamin D3 [25(OH)D3] resulted in reduced 1,25-dihydroxyvitamin D [1,25(OH)2D] levels in copper-intoxicated rats. In vitro 25(OH)D-1 alpha-hydroxylase activity was impaired in renal mitochondria from copper-intoxicated animals. Activity was also inhibited in mitochondria from controls when copper was added to incubation media. Impaired conversion of 25(OH)D to 1,25(OH)2D occurs in copper intoxication and suggests that altered vitamin D metabolism is a potential factor in the development of bone and mineral abnormalities in Wilson's disease.
Effects of diabetes and starvation on skeletal muscle branched-chain alpha-keto acid dehydrogenase activity
Authors: Aftring R. P. , Miller W. J. , Buse M. G.
Published: December 2017

The activation state of branched-chain alpha-keto acid dehydrogenase (BCDH) was studied in rat hindlimb muscles during starvation and insulinopenic diabetes, conditions in which circulating branched-chain amino acids (BCAA) are increased and their oxidation is accelerated. Muscle BCDH is predominantly inactive (phosphorylated) in postabsorptive rats but is activated by increased circulating leucine. Diabetes (streptozotocin-induced and spontaneous BB/W) increased circulating BCAA four- to fivefold and BCDH activity approximately threefold. Insulin treatment caused near normalization of circulating BCAA without correcting BCDH activity. Adrenalectomy of diabetics decreased (without normalizing) circulating BCAA and BCDH activation. Starvation caused mild, progressive increases in circulating BCAA and significant activation of BCDH only after 4 days. Leucine infusion activated BCDH in muscle but the activation by leucine was markedly blunted by diabetes. In isolated perfused hindlimbs (control and diabetic) insulin did not affect BCDH significantly; perfusion with leucine activated BCDH, and this response appeared blunted in diabetics. Activation of muscle BCDH may contribute to increased BCAA catabolism in diabetes; the blunted activation response to hyperleucinemia may spare BCAA and contribute to their persistent elevation in plasma.