bluuebunny/crossref_metadata_2025_split huggingface dataset:
A thermogenic‐like brown adipose tissue phenotype is dispensable for enhanced glucose tolerance in female mice
Authors: Winn Nathan , Acin‐Perez Rebeca , Woodford Makenzie , Hansen Sarah , Haney Megan , Ayedun Lolade , Rector R. Scott , Vieira‐Potter Victoria , Shirihai Orian , Sacks Harold , Kanaley Jill , Padilla Jaume 
Published: June 2021

The prevailing dogma is that thermogenic brown adipose tissue (BAT) contributes to improvements in glucose homeostasis in obesogenic animal models; though, much of the evidence supporting this premise is from thermostressed rodents. Whether modulation of the BAT morphology/function drives changes in glucoregulation at thermoneutrality requires further investigation. We utilized loss and gain‐of‐function approaches including genetic manipulation of the lipolytic enzyme Pnpla2, change in environmental temperature, and lifestyle interventions to comprehensively test the premise that a thermogenic‐like BAT phenotype is coupled with enhanced glucose tolerance in female mice. In contrast to this hypothesis, we found that: (i) compared to mice kept at thermoneutrality, enhanced activation of BAT and its thermogenic phenotype via chronic mild cold stress does not improve glucose tolerance in obese mice; (ii) silencing of the Pnpla2 in interscapular BAT causes a brown‐to‐white phenotypic shift but does not disturb glucose tolerance in lean mice; and (iii) exercise and low‐fat diet improve glucose tolerance in obese mice but these effects do not track with a thermogenic BAT phenotype. Collectively, these findings indicate that a thermogenic‐like BAT phenotype is not linked to heightened glucose tolerance in female mice.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
hNAG‐1 improves insulin sensitivity and ovarian function in young and aged female mice upon high fat diet treatment
Authors: wang Yujie , Wu Kaikai , Guo Dandan , Guo Chenjie , Pan Haitao , Sang Tingting , Wang Ying , Wang Xingya 
Published: June 2021

Nonsteroidal anti‐inflammatory drug‐activated gene‐1 (NAG‐1) is a distant member of the TGF‐β superfamily. Female hNAG‐1 transgenic mice are resistant to high fat diet (HFD)‐induced obesity and have increased lifespan. Progressive gonadal dysfunction has been shown to be an important sign of aging in experimental animals. Whether hNAG‐1 transgenic mice have improved ovarian function has not been studied. We examined the ovarian function in both young (20–28week) and old (50–56 week) female mice upon feeding with high or low fat diets for 16 weeks. We found that ovarian function is improved in hNAG‐1 mice compared to wild type littermates upon both diets, with the most prominent effects observed in older mice. We observed decreased body weight, abdominal fat and lower serum glucose, leptin, insulin and insulin‐like growth factor‐1(IGF‐1) levels, and increased steroid production and increased insulin sensitivity in hNAG‐1 mice compared to wild type mice. These observations were correlated with deregulation of the expression of pro‐inflammatory cytokines and follicular development regulatory genes that suggesting improved ovarian function in hNAG‐1 mice. Histological analysis of the ovaries showed a decrease in the number of primary and secondary follicles in both genotypes upon HFD treatment. However, the ovaries from wild type mice showed an increase in the number of hemorrhagic follicles compared to hNAG‐1 mice, suggesting that hNAG‐1 may improve ovarian function through preserving primordial follicles and increasing oocyte quality. In addition, western blot analysis demonstrated that expression of mTOR/IGF‐1/TLR4 signaling pathways were decreased in young and old hNAG‐1 mice ovaries, and an increase of Foxo/SIRT1 signaling pathway was observed in old hNAG‐1 mice. Taken together, the present results suggested that hNAG‐1 play an important role in improving ovarian function and insulin sensitivity in femaleSupport or Funding InformationNational Natural Science Foundation of China (Grant No. 81400822).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Impaired Acute Hypoxic Sensing in Olfactory Receptor 78 Knockout Mice
Authors: Peng Ying‐Jie , Nanduri Jayasri , Wang Ning , Girdina Anna , Fox Aaron , Prabhakar Nanduri R 
Published: June 2021

Chang et al. (2015) reported that olfactory receptor 78 knockout (Olfr78 KO) mice exhibit impaired breathing and carotid body (CB) responses to hypoxia. However, a recent study questioned this finding (Lopez‐Barneo et al. 2018). To resolve the controversy, present study was performed on age and gender matched wild‐type (WT) and Olfr78 KO mice on Bl6 and Jax background strains (n=10 mice each genotype). Breathing was monitored in conscious mice by plethysmography and expressed as minute ventilation; VE/VO2, as well as by recording phrenic nerve activity (minute neural respiration; MNR, AU) in anesthetized mice. Hypoxia (12%O2)‐evoked increase in VE/VO2 and MNR were significantly attenuated in Olfr78 KO mice on Bl6 and Jax backgrounds, respectively as compared to WT mice (p<0.01). Hypoxia (pO2 ~35mmHg)–induced CB sensory excitation was 61 and 43% less in Olfr78‐Bl6 and Jax, respectively as compared to WT mice (p<0.01), and this effect was associated with 78% reduction in [Ca2+]i response of CB glomus cells to hypoxia (p< 0.01). In contrast, breathing and CB sensory nerve responses to 10%CO2 were comparable between Olfr78 KO (both Bl6 and Jax) and WT mice. These findings demonstrate that Olfr78 KO mice have impaired breathing, CB sensory, and glomus cell responses to acute hypoxia.Support or Funding InformationSupported by NIH‐HLBI P01‐HL‐90554This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Inhibition of the Rho‐kinase (ROCK) pathway improves morphology and stress granule formation in ALS4 patient iPSC‐derived motor neurons
Authors: Amaya Joshua , Grunseich Christopher , Fischbeck Kenneth 
Published: June 2021

Amyotrophic lateral sclerosis type 4 (ALS4) is an autosomal dominant motor neuron disorder caused by mutation in the senataxin gene (SETX), which is associated with upregulation of the TGFβ signaling pathway. ALS4 is characterized by early onset motor weakness, with distal muscle predominance and slow progression. The mechanism by which TGFβ pathway disruption may lead to degeneration of motor neurons is not clear. We used patient‐derived iPSC‐motor neurons to study the neuronal phenotype of ALS4. After 7 days of differentiation, ALS4 patient motor neuron‐like cells were found to have less morphological complexity, as defined by fewer branch points per soma and shorter axonal lengths, and this was reversed with Rho‐kinase inhibitor (RI) treatment. Morphological characterization was done using in vitro live cell imaging. In addition, stress granule formation, as quantified by immunofluorescence staining with G3BP antibody, was increased in ALS4 cells compared to controls. Analysis was done after 7 days of motor neuron differentiation. In summary, these results suggest that Rho‐kinase pathway inhibition can rescue abnormal morphological features in ALS4 patient‐derived motor neurons. In addition, we found that exogenous TGFβ treatment of motor neurons for 24 hours decreases the soma count in both patients and controls, recapitulating the toxicity of TGFβ stimulation. Understanding how the ROCK pathway modulates motor neuron biology and TGFβ upregulation may provide insight into the mechanism of the disease.Support or Funding InformationNational Institute of Neurological Disorders and Stroke (NINDS) intramural funding.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Pharmacological activation of the cholinergic system attenuates lung inflammation in a Murine Model of acute respiratory distress syndrome
Authors: Choque Pamela NIthzi Bricher , de Paula Vieira Rodolfo , Ulloa Luis , Lira Beatriz , de Oliveira Ana Paula Ligeiro , Consolim‐Colombo Fernanda Marciano 
Published: June 2021

Acute respiratory distress syndrome (ARDS) is characterized by acute lung inflammation involving both the recruitment and activation inflammatory cells as well as the release of inflammatory factors that cause lung injury and contributes to systemic inflammation. Despite advances in understanding the underlying pathogenic mechanisms of ARDS, no effective therapeutic approach has emerged. The anti‐inflammatory cholinergic reflex has been postulated as an important mechanism that modulates the immune system in both aseptic and septic experimental models. Pyridostigmine bromide (PB) is a reversible anticholinesterase agent that causes increased availability of acetylcholine and parasympathetic activity is routinely used in the treatment of myasthenia gravis. The aim of this study was to investigate the effect of cholinergic stimulation through the PB treatment on the pulmonary and systemic inflammatory response in an experimental model of LPS‐induced ARDS.MethodsC57Bl/6 male mice (n=24) were distributed into four groups Control (Control), pyridostigmine‐treated (PB), LPS installation (LPS), LPS installation and pyridostigmine treatment (PB+LPS) Animals were monitored for 72 hours. Acute respiratory distress syndrome (ARDS) model: Mice were anesthetized (ketamine 100 mg/kg and xylazine 10 mg/kg) and given one intratracheal instillation of 10 μg LPS/day per mice, during 3 days. Cholinergic stimulation: Pyridostigmine bromide (PB) 3 mg/kg/day was administered twice a day by oral gavage at 1h post‐LPS to achieve around 85–90% cholinergic inhibition as previously reported. After 72h, bronchoalveolar lavage fluid (BALF) was obtained to measure leukocyte infiltration and cytokine (IL‐6, IFN‐γ, IL‐1β e TNF and IL‐10) level in BALF and plasma.ResultsTreatment with PB after the bacterial endotoxin significantly reduced the number of both total cells and neutrophils in BAL fluid (p<0.001) and in the lung parenchyma (p<0.01). Reduced the levels of all of the inflammatory cytokines TNF, IL‐6 (p<0,001), and IL‐1β, IFN‐γ (p<0,01) but not IL‐10 levels in BALF when compared with LPS group. Reduced the levels of all of the inflammatory cytokines TNF (p<0,001), IL‐6, IL‐1β, IFN‐γ (p<0,01) and IL‐1β (p<0,05) but not the levels IL‐10 in plasma when compared with LPS group at 72 hours post‐treatment. In conclusion, the treatment with BP can activate the cholinergic system to attenuate lung inflammation in an experimental model of LPS‐induced ARDS. These results support the cholinergic system as an important pharmacological target for ARDS treatment.Support or Funding InformationSupport Post‐graduate stricto sensu Program UNINOVE and CAPESThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Changes in Pain Threshold in the Early Stages of Type I Diabetes
Authors: YBARBO KAI , GROTLE ANN‐KATRIN , HUO YU , STONE AUDREY 
Published: June 2021

Type 1 diabetes mellitus (T1DM) is a metabolic disease in which chronic hyperglycemia increases the risk of developing peripheral neuropathy. A common early symptom of peripheral neuropathy is mechanical allodynia, which is characterized as painful sensation to a normally non‐painful stimulus. However, whether the expression of mechanical allodynia changes with the progression of the disease is not fully understood. Therefore, the purpose of this study was to determine changes in pain threshold to mechanical stimulation during the early stages of T1DM. Adult male and female Sprague‐Dawley rats were given 3–4 sessions of acclimation to cereal and the von Frey testing cage and were not deprived of food at any time. Pain threshold was measured with von Frey monofilaments, which were applied to the L5 dermatome on the plantar surface of the rat's hindpaw until the filament bent. The lowest force that elicited a quick paw withdrawal was measured and averaged between the responses of both hindpaws. We defined mechanical allodynia as a significant reduction in force required to elicit paw withdrawal compared to baseline levels. Following baseline measurements of pain threshold, non‐fasted blood glucose level, and body weight, rats were injected with either streptozotocin (STZ; 50mg/kg i.p.), a known toxin that destroys pancreatic beta cells and induces T1DM, or citrate buffer (CTL), the vehicle control for STZ. One week and two weeks post injection, body weight, blood glucose level, and pain threshold were again measured. We found that pain threshold was significantly reduced (p<0.05) 2 weeks after STZ injection (before STZ: 88 ± 10 g, n=4; after STZ: 22 ± 10 g, n=4), but not 1 week after STZ injection (before STZ: 32 ± 15 g, n=7; after STZ: 12 ± 5 g, n=7) compared to baseline. No significant difference was seen in CTL rats 1 week after injection (before CTL: 56 ± 23 g, n=6; after CTL: 48 ± 14 g, n=6) compared to baseline. Body weight was significantly reduced (p<0.05) in STZ rats at 1 week (before STZ: 426 ± 42 g, n=7; after STZ: 377 ± 31 g, n=7) and 2 weeks (before STZ: 397 ± 8 g, n=4; after STZ: 300 ± 8 g, n=4) after injection, but did not change in CTL rats (before CTL: 436 ± 29 g, n=6; after CTL: 446 ± 29 g, n=6). These findings suggest that mechanical allodynia is present as early as 2 weeks following the destruction of insulin producing beta cells.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cardiovascular Reflexes Control Hemodynamic Responses During LPS‐induced Systemic Inflammation in Conscious Rats
Authors: Amorim Mateus R. , de Deus Júnia L. , Cazuza Rafael A. , Mota Clarissa M. D. , da Silva Luiz E. V. , Borges Gabriela S. , Batalhão Marcelo E. , Cárnio Evelin C. , Branco Luiz G. S. 
Published: June 2021

Lipopolysaccharide (LPS)‐induced systemic inflammation (SI) is associated with hypotension, tachycardia, and multiple organs dysfunctions. SI, a hallmark of sepsis can lead to cardiovascular impairment and death. Considering that the nervous system regulates immunity and that cardiovascular reflexes, i.e. baroreflex, chemoreflex, and Bezold‐Jarish reflex, are important regulators of hemodynamic function, we investigated these cardiovascular reflexes control acutely and 24 hours after LPS‐induced SI. We combined cardiovascular recordings, immunofluorescence and molecular approaches in male Wistar rats that received intravenous administration of LPS (1.5 or 2.5 mg.kg−1, CEUA #2017.1.585.58.9). LPS induced hypotension and tachycardia and reduction in baroreflex gain. On the other hand, SI caused no significant impairment in hemodynamic responses to chemoreflex and Bezold‐Jarish reflexes, despite an increased number of activated microglia and IL‐1β levels in the nucleus tractus solitarius. The present data are consistent with the notion that cardiovascular reflexes are kept functional even with central nervous system inflammation. These findings provide insights into the mechanisms that regulate the cardiovascular system during SI and indicate that the improvement of these reflexes responsiveness can be useful for the therapeutic management of sepsis.Support or Funding InformationFAPESP, CAPES and CNPqThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Development of glyco‐conjugated chlorin e6 for photodynamic therapy
Authors: Yano Shigenobu , Kataoka Hiromi , Nomoto Hiroyuki , Osaki Tomohiro 
Published: June 2021

PDT (photodynamic therapy) has much attracted as less invasive method for treating cancer.1 To increase the antitumor effects and shorten the light shielding duration, we developed third‐generation photosensitizers for PDT. We have focused much attention to the glyco‐conjugation of chlorin derivatives mainly for the purpose of improving their biocompatibility and tumor selectivity. Generally, cancer cells uptake higher level of glucose than normal cells in a phenomenon known as Warburg's effect, which is also utilized in positron emission tomography (19FDG‐PET‐CT). We developed a number of glyco‐conjugated chlorins resulting finally in Glc‐chlorin e6, which showed the strongest antitumor effects in PDT ever reported for synthesized glyco‐conjugated chlorins.2 Furthermore, Glc‐chlorin e6 is discharged very fast from the body. We also confirmed extremely promising antitumor effects of 40% CR in vivo under conditions that killed all mice in the comparable TS (talaporfin sodium) PDT group. We have also already synthesized 14C‐labeled Glc‐chlorin e6 and examined its pharmacokinetics in rat to reveal a plasma half‐life of 42.65 h, which is shorted than that of TS. In rat, 14C‐labeled Glc‐chlorin e6 was mainly discharged in bile and faster than TS. Single time toxicity test of Glc‐chlorin e6 in mouse also showed the lowest published lethal dose of 250 mg/kg. From these findings, we consider that Glc‐chlorin e6 is the ideal sugar for conjugating to chlorin, evidenced by the remarkable antitumor PDT effects, rapid excretion, and low toxicity demonstrated herein. Glc‐chlorin e6 is considered to be the best candidate PS thus far for third‐generation PDT and we plan to continue with our investigatory studies with the ultimate aim of clinical trials. We examined the efficacy of PDT with Glc‐chlorin e6 for tumor‐bearing dogs.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
ALDOSTERONE AND HYPERTENSION IN OVARIECTOMIZED FEMALE DAHL SALT SENSITIVE RATS ON LOW SALT DIET
Authors: LOPEZ‐RUIZ ARNALDO FABIAN , RECKELHOFF JANE F. 
Published: June 2021

Blood pressure (BP) increases in postmenopausal women. Ovariectomy increases BP in female Dahl salt sensitive rats (DS) even if maintained on low salt diet. OVX also have higher aldosterone (ALDO) levels and develop more renal injury than intact females. Since ALDO can cause increases in BP and renal injury, the hypothesis was tested that the mineralcorticoid receptor antagonist, eplerenone (EPL), would reduce BP and renal injury in OVX DS. Female DS, 16 weeks of age, kept on low salt diet from birth, were divided into four groups: intact females (INT), intact females + eplerenone (100mg/kg/day by gavage; INT/EPL), ovariectomized females (OVX) and OVX + eplerenone (OVX/EPL) for 10 days. BP was measured by telemetry; renal injury was evaluated by urinary albumin excretion. Sgk‐1 and NGAL expression, indexes of renal tubular damage, were measured in kidney cortex by western blot. Plasma ALDO levels were also measured. As shown in the table below, OVX DS had higher BP and albuminuria than INT, and EPL reduced both only in OVX. Sgk‐1 and NGAL renal expression was higher in OVX than INT, and was reduced with EPL. These data show that increased aldosterone plays an important role in the higher BP and renal injury in OVX DS.*p<0.05, compared with INT control; #p<0.05, compared with control OVX.The data show that aldosterone plays an important role in the hypertension and renal injury in OVX DS rats. These data suggest that in postmenopausal women, aldosterone may play a role in mediating the increase in blood pressure.
Student's perception on two different teaching modalities followed in the Medical Pharmacology course
Authors: Rajasekaran Senthil Kumar , Senthilkumar Uma 
Published: June 2021

The traditional format for the transmission of knowledge in the class room has been the delivery of the teaching material in a didactic lecture format. With the Medical education growing tremendously, there are numerous alternatives in order to provide opportunities for students to engage actively in the construction of knowledge. In Medical Pharmacology course, we have embarked on teaching a part of the course using the case based teaching format allowing short discussions among students in between the lectures. This alternative was expected to help the students to evoke critical thinking that is central to understanding the discipline.This study is not an argument to support the superiority of this kind of teaching, but just to learn about the student's perception on two different teaching methodologies in the Medical Pharmacology course.Students enrolled in the Medical Pharmacology took part in this study. This study involved the students answering a questionnaire rating specific components (on a 5 point scale) in each teaching methodology.A total of 119 responses were received. The analysis of results is shown in the table below.One item in the questionnaire asked about the duration of time students spend on an average understanding the topics following these two teaching methodologies. The results showed that on an average the students spent 4.5 hours and 2.5 hours following the traditional didactic teaching and the new case based teaching format respectively.Overall results clearly show that the students' preferred case based teaching case based teaching format allowing short discussions among students in between the lectures This in their perception had:• Reduced the time required for further studying and understanding of the topic• Enhanced their communication skills• Helped in integration of pharmacology and medicine• Created an interest in learning• Evoked parallel thinking
Exogenous Citrulline (Cit) on Renal Uptake in Various Stages of 5/6 Ablation/Infarction (A/I) Chronic Kidney Disease (CKD)
Authors: Chen Gin‐Fu , Baylis Chris 
Published: June 2021

The kidney is a major site of L‐Arginine (arg) synthesis, and with renal disease arg synthesis may be compromised. The first and rate‐limiting step in renal arg synthesis is the rate of cit delivery to the renal cortex. Using the 5/6 renal ablation/infarction (A/I) injury model, we measured renal cit delivery and extraction at 2 stages of disease progression (4‐5 wk; n=7 and 10‐12 wk; n=6) after A/I vs. sham (n=7). The arterial‐renal venous difference was measured at baseline and during cit infusion. Both stages of injury resulted in decreased baseline cit delivery to the kidney due to marked reductions in renal plasma flow (RPF) and despite increased plasma cit. The % cit extraction at baseline was unaffected by CKD, hence cit uptake fell markedly with injury. Cit infusion increased RPF only in healthy rats (possibly through increased NO production). Plasma cit increased in all groups resulting in increased renal cit delivery vs baseline. In healthy kidneys cit extraction and uptake increased. However, despite increased delivery neither renal cit extraction nor uptake was increased at either stage of injury. The inability of the injured kidney to take up cit indicates a marked reduction and saturation of the renal cit transport capacity.*p<0.05, *p<0.01, ***p<0.001 vs. Sham, +p<0.05, ++p<0.01, +++p<0.001 vs. baseline within group.