bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microglia Prevent the Loss of Visual Function in the Aging Retina by Maintaining the Health of Retinal Pigment Epithelial Cells
Authors: Karg Margarete M. , Moorefield May , Hoffmann Emma , Shu Daisy , Krasniqi Drenushe , Philipose Hannah , Ksander Bruce R. , Saint‐Geniez Magali 
Published: May 2022

Even in healthy individuals, aging leads to the progressive deterioration of visual function that coincides with increasing cellular dysfunction in retinal neurons and retinal pigment epithelial (RPE) cells. Interestingly, aging also coincides with the migration of microglia from the inner to the outer retina where they reside in the subretinal space between photoreceptor outer segments and the apical surface of RPE. Healthy young microglia act as the immune sentinels of the retina, and thus are protective and maintain retinal homeostasis. However, age alters cellular functions and the role of aging subretinal microglia is not known. Here we investigated whether aged microglia residing in the subretinal space are either preventing or promoting loss of visual function.Microglia were depleted in 33‐month‐old C57/BL6 mice fed for 6 weeks with a chow containing PLX5622, a small molecule inhibitor of colony‐stimulating factor‐1 receptor (Csf1r) which is expressed by microglia and is required for their proliferation, differentiation, and survival. As a negative control, age‐matched mice received a control diet. Following microglia depletion, the optomotor reflex (OMR) was used to assess visual acuity and contrast sensitivity and electroretinogram (ERG) assessed retinal function. Morphological analysis was determined by immunohistochemical staining and TEM.To distinguish microglia from infiltrating macrophages, retinas from old mice were stained with P2RY12, a microglia‐specific marker. The vast majority of cells residing between the photoreceptor outer segments and RPE layer in old mice were P2RY12+ microglia. These cells displayed a highly amoeboid and activated morphology and were filled with autofluorescence droplets similar to lipofuscin. PLX5622 treatment depleted up to 90% of the microglia. Microglia preserved visual function, and in the absence of microglia, there was a significant loss of contrast sensitivity and ERG c‐wave, as compared with untreated controls. Loss of microglia coincided with a loss of RPE cells and increased RPE swelling indicating that microglia support RPE in aged animals. TEM indicates that subretinal microglia actively phagocytize shed photoreceptor outer segments, thereby compensating for the known age‐related decline of RPE phagocytosis.We conclude that microglia in aging mice migrate to the subretinal space of the outer retina to support and maintain RPE cell functions that preserves vision.
Histological Influences of Food Restriction on Brown Adipose Tissue in Young OLETF Rats
Authors: Nishihira Misuzu , Nguyen Son T. , Nagamori Keita , Fujita Naoto , Urakawa Susumu 
Published: May 2022

Whitening of brown adipose tissue (BAT) promotes obesity and causes obesity‐related health problems. It has been suggested that food restriction can prevent BAT whitening and inhibit the decline of BAT function with obesity. However, details of the histological feature remain unknown. The purpose of the present study was to investigate the influences of food restriction during childhood on histological features of BAT in Otsuka Long‐Evans Tokushima fatty (OLETF) rats.Male OLETF rats and Long‐Evans Tokushima Otsuka (LETO) rats were used as models of obesity and non‐obesity, respectively. OLETF rats were divided into the food restriction and ad libitum feeding groups. OLETF rats with food restriction were received the daily average amount of food consumed by same‐age LETO rats. The others were fed ad libitum with standard laboratory rodent chow from 4‐ to 20‐week‐old. At 20‐week‐old, the BAT was collected from the interscapular region and the sections were stained with hematoxylin and eosin for histological observation. This study was approved by the Institutional Animal Care and Use Committee of Hiroshima University (A19‐163) and conducted in accordance with the Hiroshima University Regulations for Animal Experimentation. All experiments complied with the National Institute of Health Guidelines for the Care and Use of Laboratory Animals.Body weight of OLETF rats ad libitum feeding was significantly higher than those of LETO rats and OLETF rats with food restriction at 20‐week‐old. Enlarged unilocular adipocytes were often located in the peripheral area of the adipose lobule, the number appeared to be higher in OLETF rats ad libitum feeding than in LETO rats. Although the number of whitened unilocular adipocytes located in the central area was significantly lower in OLETF rats with food restriction than in OLETF rats ad libitum feeding, the number of enlarged unilocular adipocytes located in the peripheral area was a bit less in OLETF rats with food restriction.These results suggest that BAT whitening in young OLETF rats is started from the peripheral area of the adipose lobule, adipocytes located in the central area of the lobule translate from multilocular to unilocular with the progression of hyperphagia‐induced obesity.
Accessory Muscle Support of Breathing in Young Dystrophin‐deficient mdx Mice
Authors: Slyne Aoife D. , O'Halloran Ken D. , Burns David P. 
Published: May 2022

Duchenne muscular dystrophy (DMD) is a genetic neuromuscular disorder that occurs due to the absence of the structural protein dystrophin and secondary consequences. DMD is characterized by severe and progressive skeletal muscle weakness, which extends to the respiratory muscles. In young dystrophin‐deficient mdx mice, peak inspiratory pressure‐generating capacity is preserved despite diaphragm muscle weakness and reduced electromyogram (EMG) activitya. Our overarching hypothesis is that accessory muscle compensation limits ventilatory deficit in early dystrophic disease. Four‐month‐old male wild‐type (n=39) and mdx (n=41) mice were studied. Breathing was assessed in conscious mice using whole body plethysmography during normoxia and chemochallenge (10% O2/6% CO2). Thoracic oesophageal pressure and obligatory (diaphragm and external intercostal) respiratory muscle EMG activities were recorded in urethane (1.7g/kg i.p.) anaesthetised spontaneously breathing mice during baseline and sustained tracheal occlusion (maximal muscle activation). Diaphragm and scalene (accessory respiratory muscle) force output were examined ex vivo. Data were statistically compared using unpaired Student’s t test or two‐way ANOVA with Bonferroni post hoc test. Peak diaphragm force ex vivo (P < 0.0001) and baseline diaphragm EMG activity (P = 0.01) were significantly lower in mdx compared with wild‐type. Minute ventilation was equivalent in age‐matched wild‐type and mdx mice during baseline and chemochallenge (P = 0.1). Peak diaphragm (P < 0.0001) and external intercostal (P = 0.01) EMG activities during obstruction were significantly lower in mdx mice compared to wild‐type, while peak inspiratory pressure was equivalent (P = 0.4). Interestingly, peak scalene muscle force ex vivo was preserved in 4‐month‐old mdx mice (P = 0.8). Despite a decline in diaphragm muscle performance (decreased EMG activity and mechanical weakness) at baseline, ventilatory capacity is preserved in mdx mice. Furthermore, despite lower peak electrical activation of the obligatory muscles of breathing and diaphragm muscle functional deficit, peak inspiratory pressure is preserved in 4‐month‐old mdx mice, confirming our previous findings in 2‐month‐old micea. Our finding of preserved scalene muscle force suggests that compensation may be provided by accessory muscles to support ventilatory and non‐ventilatory behaviours in early dystrophic disease. Current studies are examining the EMG activity of accessory respiratory muscles (e.g. scalene, sternomastoid, cleidomastoid and trapezius) in early and advanced dystrophic disease in mdx mice.References a Burns DP, Murphy KH, Lucking EF, O'Halloran KD. Inspiratory pressure‐generating capacity is preserved during ventilatory and non‐ventilatory behaviours in young dystrophic mdx mice despite profound diaphragm muscle weakness. J. Physiol. 2019;597(3):831‐848.
Yo‐Yo Diet Has Adverse Effects on Cardiac Function and Insulin Sensitivity in Female Fischer Rats
Authors: de Souza Aline , Ji Hong , Korolowicz Kyle , Rodriguez Olga , Albanese Chris , Ecelbarger Carolyn , Sandberg Kathryn 
Published: May 2022

IntroductionWe have shown in female rats on a severe food restricted (sFR) diet that rapid body weight (BW) loss is associated with long term cardiovascular dysfunction months after BW has returned to normal levels due to refeeding. To further investigate the long term adverse cardiovascular effects of a sFR diet, we studied a model of BW cycling in which BW is rapidly lost, gained back, then lost again, since BW cycling is common in individuals who voluntarily diet (e.g., yo‐yo dieting) or those exposed involuntarily to inadequate caloric consumption (e.g., due to poverty).MethodsThree‐month‐old female Fischer rats were divided into 2 groups and maintained on a control (CT; regular chow ad libitum for duration of study, n=8) or sFR (60% reduction of daily food intake, n=8) diet for 2 weeks. The sFR rats then received regular chow ad libitum for 3 weeks. This cycle of 2 weeks sFR diet plus 3 weeks of refeeding (c‐sFR) was repeated twice more. Cardiac and renal function were assessed using ultrasound and insulin sensitivity was evaluated using the homeostatic model assessment of insulin resistance (HOMA‐IR) index.ResultsDuring the 1st c‐sFR, rats lost 20% of their BW after 14 days on the sFR diet; however, their BW rapidly returned to CT levels during the 3‐week refeeding period. The 2nd and 3rd c‐sFR led to similar BW losses (20% and 19%, respectively). No differences were observed in mean arterial pressure (MAP) and heart rate (HR) after the 3rd c‐sFR compared to CT rats. However, the c‐sFR rats (n=4) showed 20‐40% reductions in renal artery flow (mm/s: CT, 295±12 vs c‐sFR, 235±6; p<0.05), cardiac output (mL/min: CT, 43±2 vs c‐sFR, 31±3; p<0.05) and stroke volume (mL: CT, 153±4 vs c‐sFR, 89±10; p<0.05) while the HOMA‐IR index was 2.6‐fold higher (AU: CT, 3±0.8 vs c‐sFR, 8±1.9; p<0.05) compared to CT rats (n=4).ConclusionDespite normalization of BW, MAP and HR after 3 c‐sFR periods, c‐sFR rats had reduced heart and kidney function and higher insulin resistance when compared to CT rats. This study suggests individuals who engage in yo‐yo dieting or have experienced BW cycling due to inadequate food intake from other causes (e.g., very low food security, war, natural disasters) are at increased risk for developing cardio‐metabolic disease.
Hyperpolarization‐Activated Current Shows Excitatory Effect on Fictive Locomotion in the Neonatal Mouse Under Hyperdopaminergic Conditions
Authors: Raymond Abigail , Diaz‐Rios Manuel 
Published: May 2022

Restless Leg Syndrome (RLS) is a chronic sensorimotor disorder that has recently been linked to a downregulation in adenosine A1 receptors (A1R), leading to decreased formation of adenosine‐dopamine heteromers and a disinhibited or hyperdopaminergic transmission pathway within the central nervous system. Dopamine D1 receptor (D1R) activation has been shown to modulate HCN1 channels via its stimulatory effect on cAMP production to increase the hyperpolarization‐activated cation current (Ih). Ih has been related to the regulation of bursting activity in rhythmic motor networks, specifically in controlling the firing frequency of the system. Our study aims to establish the importance of Ih in mammalian locomotion under hyperdopaminergic conditions mimicking those seen in RLS patients. We hypothesized that blocking Ih would increase the cycle period and destabilize the rhythm.MethodsWe isolated the spinal cords of neonatal (P0‐P5; n = 6) Swiss Webster mice via ventral laminectomy and recorded the extracellular activity of ventral roots L2 and L5 using suction electrodes to assess burst amplitude, burst duration, and cycle period. Fictive locomotion was induced using serotonin (5HT; 9‐15μM) and N‐methyl‐D‐aspartate (NMDA; 6 μM) before adding dopamine (DA; 50μM) to determine the effect of DA on the system. We then used ZD7288 (1μM) block HCN1 channels to investigate the role of Ih in motor‐like activity.ResultsBlocking Ih caused a significant increase in all three parameters relative to the 5HT/NMDA control in the L2 roots, but only cycle period was significantly increased relative to the high dopamine condition. There were no significant changes in any of the parameters in the L5 roots.ConclusionsOur results suggest that Ih primarily plays an excitatory role in locomotor regulation under hyperdopaminergic conditions, such as those seen in RLS. The differential effects between roots may suggest that one is more susceptible to the blockade of Ih by ZD7288; however, given the large degree of variability in the L5 data, a larger sample size is needed to confirm this hypothesis. Future experiments include collecting more data on L5 to confirm if there are differential effects, as well as pharmacological approaches to confirm that D1R is upregulating Ih via the cAMP pathway.
Learning Anatomy in a developing country under COVID‐19 lockdown measures: How did the learners perceive it?
Authors: Mbagwu Smart I. , Edem Edem E. , Akunna Gabriel G. , Makanjuola Victor O. , Adegbilero‐Iwari Oluwaseun , Ogbo Felix , Enye Linus A. 
Published: May 2022

IntroductionAcknowledging the fundamental role anatomy education plays in medical training and taking into consideration the nascence of online anatomy education in Nigeria, we evaluated the current and future perceptions of medical and allied‐health students towards online anatomy education during the COVID‐19 lockdown in Nigeria.MethodsGoogle Form questionnaires were distributed via different social and academic platforms to medical and allied‐health students in Nigeria between September 28 –December 17, 2020, using a purposive sampling. 954 students responded to questions on what they felt about the online anatomy teaching including how it could affect their academic performance in anatomy. Additionally, they were asked to give their opinion of the future of e‐learning in anatomy in Nigeria. The data collected from the study were analyzed using descriptive and inferential techniques.ResultsOut of a total of 954 students who participated in the study, 947 valid responses were recorded. From the responses, most of the students (77.6%) had computer/IT skills. Unexpectedly, many ofthe students (60%) did not favor online learning approaches as effective tools for instructions in the anatomical sciences while more than a half of the students (55%) did not find the online classes in anatomy interesting. On the other hand, a majority (84%) believed that physical classes would have improved their performance in anatomy. Almost all the students (91.5%) believed anatomy educators in Nigeria need advanced skills for online education and that anatomy online teaching needs more advanced technology to be implemented in Nigeria(94.2%).ConclusionAfter evaluating online anatomy education experience during the COVID‐19 lockdown in Nigeria from medical and allied‐health students’ position, it was observed that there was an inclusive negative perception about the suitability and effectiveness of online education with regards to the anatomical sciences in Nigerian medical/health training. Majority of the students indicated that there is need for the enhancement of online teaching and quality training of the anatomy educators. Addressing the challenges that were presented during online anatomy education at the heat of the pandemic is recommended. This will incline science education towards the development and implementation of a workable and sustainable online education model in anatomical sciences for Nigeria.
Anatomical variations of the splenic artery and its relationship with vascular or abdominal pathologies: Systematic review
Authors: Valenzuela Juan Jose J. , Orquera Paulo , Perez Daniela , Santana Andres , Vargas Pamela , Orellana Mathias I. 
Published: May 2022

IntroductionThe spleen is an abdominal organ whose weight represents 0.2% of total body weight. It contains 3% of cardiac output, constituting one of the most vascularized abdominal organs. This corresponds to the thickness of your blood vessels and their main function, which is to destroy old erythrocytes and the production of blood cells for the maintenance of a blood reserve.MethodsA systematized search was carried out in electronic databases, in order to compile the available literature on the subject to be treated. The search process was carried out in the following databases; MEDLINE, SCIELO, WOS, CINHAL, SCOPUS and GOOGLE SCHOLAR, using as search terms; “Splenic artery”, “Vacularization splenic,” Anatomical variations “,” Splenic organ “and” Clinical anatomy “.ResultsOf a total of 16 studies included in this review, 8 studies reported in their results clinical correlations of anatomical variations in the splenic artery with surgical procedures in the abdominal region, mostly associated with surgery of the pancreas, liver, stomach and bile ducts. While 8 studies reported clinical correlations of the anatomical variations in the splenic artery in their results with the diagnostic and therapeutic study through images of the abdominal region, the included studies were analyzed with the respective risk of bias for anatomical studies.ConclusionKnowing the normal anatomy and the anatomical variants of the splenic artery are crucial for knowledge both for professionals in the morphological area and for clinical professionals who address the abdominal region and its vascular components, in this review we have been able to know that the variation of the splenic artery can be in different regions of its trajectory, which gives us to understand that in any abdominal intervention of the region of the trajectory of this artery there could be some complication if the possible variations of the splenic artery are not known, for which It is suggested to carry out new clinical anatomical studies that consider this variation in both the diagnostic and surgical processes.
Klebsiella pneumoniae Cross‐feeds Clostridioides difficile and Enhances Colonic Pro‐inflammatory Responses
Authors: Ticer Taylor , Stine Rachel , Ellis Terri , Horvath Thomas D. , Haidacher Sigmund J. , Hoch Kathleen M. , Haag Anthony M. , Engevik Amy C. , Engevik Melinda A. 
Published: May 2022

BackgroundRecent in‐depth analysis of the human gut microbiota demonstrates that many intestinal disorders are polymicrobial in origin and manifestation. Select microbes can interact synergistically with pathobionts to induce virulence traits, modify environmental niches, and modulate host responses. In the setting of Clostridioides difficile infection, polymicrobial interactions are incompletely understood. C. difficile is an intestinal pathogen responsible for 500,000 infections and 30,000 deaths annually in the US. Using stool‐seeded bioreactors with mucus‐coated inserts, we identified Klebsiella pneumoniae in the mucus‐associated microbiota along with C. difficile.HypothesisWe hypothesized that K. pneumoniaemay enhance C. difficile traits required for colonization.Methods & ResultsTo test this hypothesis, we cultured 11 K. pneumoniae strains with four C. difficile strains (representing 4 different ribotypes) in a fully defined bacteria media ZMB1. We observed that cell‐free supernatant from all K. pneumoniae strains enhanced the growth of all C. difficile strains, indicating that metabolites produced by K. pneumoniae enhanced C. difficile growth. Importantly, C. difficile grew well with K. pneumoniae bacteria and both bacteria were identified in co‐cultures by gram staining. Non‐targeted metabolomics revealed that K. pneumoniae shifted the metabolism of C. difficile away from amino acid utilization. K. pneumoniae metabolites also suppressed toxin production in an in vitro model of nutrient starvation as assessed by live‐imaging of LifeAct expressing Vero cell rounding. These findings further confirm the ability of K. pneumoniae to cross‐feed C. difficile. Although K. pneumoniae is well known for robust biofilm production, K. pneumoniae did not significantly enhance C. difficile biofilm formation, indicating that biofilm synthesis is not a significant component of C. difficile‐Klebsiella interactions. RNA sequencing of mouse colonic inside‐out organoids incubated with live C. difficile and/or K. pneumoniae revealed increased pro‐inflammatory responses when the two microbes were added together compared to either microbe alone or media controls.ConclusionsThese results suggest that K. pneumoniae can cross‐feed and shift the metabolism of C. difficile, as well as enhance the pro‐inflammatory capacity of C. difficile. We speculate that interspecies interactions could be among the earliest events that occur as C. difficile colonizes the host. As a result, we believe that an improved understanding of how mucus associated microbes like K. pneumoniae interact with C. difficile will continue to clarify the mechanisms of C. difficile infection.