Discovering the role of the adrenal gland in the control of body function

This essay looks at the historical significance of three APS classic papers that are freely available online: Cannon WB and de la Paz D. Emotional stimulation of adrenal secretion. Am J Physiol 28: 64-70, 1911 (http://ajplegacy.physiology.org/cgi/reprint/28/1/64). Cannon WB. The emergency function of the adrenal medulla in pain and the major emotions. Am J Physiol 33: 356-372, 1914 (http://ajplegacy.physiology.org/cgi/reprint/33/2/356). Cannon WB. Studies on the conditions of activity in endocrine glands. V. The isolated heart as an indicator of adrenal secretion induced by pain, asphyxia and excitement. Am J Physiol 50: 399-432, 1919 (http://ajplegacy.physiology.org/cgi/reprint/50/3/399).     

Design and evaluation of a national set of learning objectives: the medical physiology learning objectives project

In 1998, the American Physiological Society (APS) and the Association of Chairs of Departments of Physiology (ACDP) began collaboration on a project to develop a set of physiology learning objectives for medical students. Over the next 2 years, more than 50 physiologists collaborated in the development a comprehensive draft containing its 695 learning objectives. Faculty in 31 medical schools in the United States, Canada, and Puerto Rico evaluated these objectives. On the basis of this evaluation, the ACDP recommended deleting 13 of them. The final project, containing 682 objectives, was approved in December 2000 by the ACDP and published on the APS website http://www.the-aps.org/education/MedPhysObj/medcor.htm. The identification of the "content" of medical physiology instruction provides the APS and the ACDP with a tool to introduce emerging topics, such as the physiology of aging and gender differences, at a national level. The medical physiology learning objectives project provides a guide for directing current and future medical physiology instruction in the United States.     

Teaching the effects of gravity and intravascular and alveolar pressures on the distribution of pulmonary blood flow using a classic paper by West et al

"Distribution of blood flow in isolated lung; relation to vascular and alveolar pressures" by J. B. West, C. T. Dollery, and A. Naimark (J Appl Physiol 19: 713-724, 1964) is a classic paper, although it has not yet been included in the Essays on the American Physiological Society Classic Papers Project (http://www.the-aps.org/publications/classics/). This is the paper that originally described the "zones of the lung." The final figure in the paper, which synthesizes the results and discussion, is now seen in most textbooks of physiology or respiratory physiology. The paper is also a model of clear, concise writing. The paper and its final figure can be used to teach or review a number of physiological concepts. These include the effects of gravity on pulmonary blood flow and pulmonary vascular resistance; recruitment and distention of pulmonary vessels; the importance of the transmural pressure on the diameter of collapsible distensible vessels; the Starling resistor; the interplay of the pulmonary artery, pulmonary vein, and alveolar pressures; and the vascular waterfall. In addition, the figure can be used to generate discovery learning and discussion of several physiological or pathophysiological effects on pulmonary vascular resistance and the distribution of pulmonary blood flow.     

Proteome analysis of adrenal cortical tumors

Introduction: Adrenal tumor is a relatively common tumor. The discrimination between adrenal cortical adenoma (ACA) and adrenal cortical carcinoma (ACC) is crucial as these two diseases have distinct prognosis. ACA is a benign tumor curable by surgical excision, while the prognosis of ACC is extremely poor, with a 5-year mortality of 75–90%. Therefore, previous proteomic studies focused on markers allowing the differentiation between ACA and ACC.

Areas covered: Several proteomic approaches based on the analysis of various samples such as human tissues, urine, and cell lines. In this review, we focused on proteomic studies performed to improve adrenal tumor diagnosis and identify ACC therapeutic targets.

Expert commentary: The rapid development of cancer genomics provided a lot of information, which affects functional proteomics. In practice, differentially expressed proteins between ACA and ACC have been suggested in several proteomic studies and had a biologic implication in ACC.     

How to choose a mentor

Mentors will play important roles in the careers of most successful scientists. Mentors are trusted advisors that give constructive criticism and provide information in many areas of a scientific life. Mentors will likely change throughout your career as your position changes and thus the areas of advice needed changes. Despite the fact that you gain new mentors, the relationships with the old mentors likely will continue and often grow into strong friendships. The American Physiological Society is a member of MentorNet, which is an award-winning, free, one-on-one electronic mentoring program for graduate students, postdoctoral fellows, and early career scientists who are APS members. Mentees and mentors are matched based on their responses to several questionnaires regarding research interests, mentoring needs, time needed, etc. Once assigned, mentors and mentees are allowed to approve their matches, and once done, contact information is given to each pair. A new mentor can be assigned every eight months. These electronic mentoring relationships are especially helpful if you are not comfortable discussing certain things with your thesis or postdoctoral advisor. APS encourages all members to participate either as a mentee or mentor in this valuable program. To comment on this article, go to http://www.the-aps.org/careers/ careers 1/mentor/mentoring.htm.     

Review of biomarkers to assess the effects of switching from cigarettes to modified risk tobacco products

Context: One approach to reducing the harm caused by cigarette smoking, at both individual and population level, is to develop, assess and commercialize modified risk alternatives that adult smokers can switch to. Studies to demonstrate the exposure and risk reduction potential of such products generally involve the measuring of biomarkers, of both exposure and effect, sampled in various biological matrices.

Objective: In this review, we detail the pros and cons for using several biomarkers as indicators of effects of changing from conventional cigarettes to modified risk products.

Materials and methods: English language publications between 2008 and 2017 were retrieved from PubMed using the same search criteria for each of the 25 assessed biomarkers. Nine exclusion criteria were applied to exclude non-relevant publications.

Results: A total of 8876 articles were retrieved (of which 7476 were excluded according to the exclusion criteria). The literature indicates that not all assessed biomarkers return to baseline levels following smoking cessation during the study periods but that nine had potential for use in medium to long-term studies.

Discussion and conclusion: In clinical studies, it is important to choose biomarkers that show the biological effect of cessation within the duration of the study.     

Searching the literature for proteins facilitates the identification of biological processes,if advanced methods of analysis are linked: a case study on microgravity-caused changes in cells

Background: More than one hundred reports were published about the characterization of cells from malignant and healthy tissues, as well as of endothelial cells and stem cells exposed to microgravity conditions.

Methods: We retrieved publications about microgravity related studies on each type of cells, extracted the proteins mentioned therein and analyzed them aiming to identify biological processes affected by microgravity culture conditions.

Results: The analysis revealed 66 different biological processes, 19 of them were always detected when papers about the four types of cells were analyzed.

Conclusion: Since a response to the removal of gravity is common to the different cell types, some of the 19 biological processes could play a role in cellular adaption to microgravity. Applying computer programs, to extract and analyze proteins and genes mentioned in publications becomes essential for scientists interested to get an overview of the rapidly growing fields of gravitational biology and space medicine.     

The pioneering use of systems analysis to study cardiac output regulation

This essay examines the historical significance of an APS classic paper that is freely available online: Guyton AC, Lindsey AW, and Kaufmann BN. Effect of mean circulatory filling pressure and other peripheral circulatory factors on cardiac output. Am J Physiol 180: 463-468, 1955 (http://ajplegacy.physiology.org/cgi/reprint/180/3/463).     

Editorial Retraction

Upon a thorough investigation, it has been determined that the paper titled “Integrating Microbial Composting and Vermicomposting for Effective Utilization of By-Products of Sugar Cane-Processing Industries” by Shweta, Rahul Kumar, B.L. Singh, and Verma Deepshikha published in the Bioremediation Journal, 2010, Volume 14, pages 158–167, was simultaneously submitted and published in two journals. The same study with minor textual variations titled “Composting of sugar-cane waste by-products through treatment with microorganisms and subsequent vermicomposting” also written by Shweta, Rahul Kumar, B.L. Singh, and Verma Deepshikha published in the Elsevier publication, Bioresource Technology, 2010, 6707–6711, three months prior to publishing in Bioremedation Journal.

As a result the article published in Bioremediation Journal has been retracted and should not be cited in the electronic or print version of the journal.

Dr. Hanadi S. Rifai

Editor-in-Chief

Bioremediation Journal

Please click here to view the article to which this statement of retraction relates.     

Beta-2-glycoprotein-1 and alpha-1-antitrypsin as urinary markers of renal cancer in von Hippel–Lindau patients

Context: Von Hippel–Lindau disease (VHLD) is a rare inherited neoplastic syndrome. Among all the VHLD-associated tumors, clear cell renal cell carcinoma (ccRCC) is the major cause of death.

Objective: The aim of this paper is the discovery of new non-invasive biomarker for the monitoring of VHLD patients.

Materials and methods: We compared the urinary proteome of VHLD patients, ccRCC patients and healthy volunteers.

Results: Among all differentially expressed proteins, alpha-1-antitrypsin (A1AT) and APOH (beta-2-glycoprotein-1) are strongly over-abundant only in the urine of VHLD patients with a history of ccRCC.

Discussion and conclusion: A1AT and APOH could be promising non-invasive biomarkers.     

Urinary biomarkers for renal tract malformations

Introduction: Renal tract malformations (RTMs) are congenital anomalies of the kidneys and urinary tract, which are the major cause of end-stage renal disease in children. Using immunoassay-based approaches (ELISA, western blot), individual urinary proteins including transforming growth factor β, tumor necrosis factor and monocyte attractant proteins 1 were found to be associated to RTMs. However, only mass spectrometry (MS) based methods leading to the identification of panels of protein-based markers composed of fragments of the extracellular matrix allowed the prediction of progression of RTMs and its complications.

Areas covered: In this review, we summarized relevant studies identified in “Pubmed” using the keywords “urinary biomarkers” and “proteomics” and “renal tract malformations” or “hydronephrosis” or “ureteropelvic junction obstruction” or “posterior urethral valves” or “vesicoureteral reflux”. These publications represent studies on potential protein-based biomarkers, either individually or combined in panels, of RTMs in human and animal models.

Expert commentary: Successful use in the clinic of these protein-based biomarkers will need to involve larger scale studies to reach sufficient power. Improved performance will potentially come from combining immunoassay- and MS-based markers.     

Hypothalamic control of body temperature: insights from the past

This essay looks at the historical significance of three APS classic papers that are freely available online: Hammel HT, Hardy JD, and Fusco MM. Thermoregulatory responses to hypothalamic cooling in unanesthetized dogs. Am J Physiol 198: 481-486, 1960 (http://ajplegacy.physiology.org/cgi/reprint/198/3/481). Hammel HT, Jackson DC, Stolwijk JAJ, Hardy JD, and Stromme SB. Temperature regulation by hypothalamic proportional control with an adjustable set point. J Appl Physiol 18: 1146-1154, 1963 (http://jap.physiology.org/cgi/reprint/18/6/1146). Hellstrom B and Hammel HT. Some characteristics of temperature regulation in the unanesthetized dog. Am J Physiol 213: 547-556, 1967 (http://ajplegacy.physiology.org/cgi/reprint/213/2/547).     

Circulating microparticles in cardiovascular disease: going on stage!

Context: Cardiovascular diseases (CVDs) are the leading cause of death worldwide. In spite of the fact that treatments are based on risk calculators which in turn are based on population characteristics, it is well known that these methods have definite levels of uncertainty. Recently, more precise diagnostic or predictive methods have been developed based on indicators of vascular and/or cardiac damage in order to supplement this risk evaluation.

Objective: In this review, we describe the main discoveries leading to the idea of using circulating microparticles as a promising and complementary tool in the evaluation of cardiovascular risk.

Methods: A Medline search for the terms cardiovascular diseases, microparticles, miRNAs, diagnosis, prognosis, biomarkers and microvesicles was performed.

Results: We found (i) nine articles, which were relevant to forming the idea of using microparticles as biomarkers in CVDs, and (ii) 15 and 12 experimental clinical studies which describe their potential in primary and secondary CVD prevention, respectively.

Conclusions: The levels of circulating microparticles have been associated with cardiovascular damage in asymptomatic patients as well as in patients who suffered a cardiovascular event, becoming promising diagnostics or prediction biomarkers in recent years.     

Association between high-sensitivity cardiac troponin T and future cardiovascular incidence in a general Japanese population: results from the Tohoku medical megabank project

Purpose: Elevation of high-sensitivity cardiac troponin T (hs-cTnT) is associated with an increased risk of cardiovascular disease (CVD). This study determined whether hs-cTnT was detectable with N-terminal pro-b-type natriuretic peptide (NT-proBNP) and related to CV risk factors in a general Japanese population.

Materials and methods: The Tohoku Medical Megabank Organization pooled individual participant data for a population-based cohort study in the Iwate prefecture (n?=?30,193, age = 60.2?±?11.5?year).

Results: Hs-cTnT levels were higher in participants with hypertension, diabetes mellitus than in participants without these conditions (all ps < 0.001). Logistic regression analysis demonstrated that NT-proBNP was strongly associated with elevation of hs-cTnT (OR = 3.35, 95% CI = 2.90–3.89, p?<?0.001). The receiver operating characteristic curve analysis showed that hs-cTnT was one of useful biomarker for the differentiation of high risk for CVD (the Suita score ≥ 56) from a general population. Logistic regression analysis demonstrated hs-cTnT levels were related to the CVD high risk group (OR = 2.67, 95% CI = 2.28–3.14, p?<?0.001).

Conclusions: Hs-cTnT levels are associated with elevation of NT-proBNP and high Suita score, which suggests that elevated hs-cTnT is related to subclinical myocardial damage and indicates CV risk.     

Impact assessment of risk parameters of underground coal mining on the environment

Coal is an important energy source but it has a significant negative impact on the environmental processes. This paper analyses the impact, measurement, and input of parameters representing potential environmental polluters in the information system (IS).

The methodology of recording and systematization includes the following parameters: coal deposits; climate parameters; roads; rivers; land and surrounding objects; air polluters; water polluters; and soil polluters. Methods for calculating land deformation, air polluter emissions, and noise impact are also presented.

Based on the number and specificity of analyzed data, the paper provides a concept of the IS and an overview of environmental impact of underground coal mine technological units. The concept was used to present the results of a research conducted at the underground coal mine “Soko” in Serbia.

The results of this research can help many potential users realize their goals. Those goals are preventive by nature, since negative environmental impact can be predicted, which enables the environmental protection experts to take appropriate measures.     

Understanding pulmonary gas exchange: ventilation-perfusion relationships

This essay looks at the historical significance of four APS classic papers that are freely available online: Fenn WO, Rahn H, and OTIS AB. A theoretical study of the composition of the alveolar air at altitude. Am J Physiol 146: 637-653. 1946 (http://ajplegacy.physiology.org/cgi/reprint/146/5/637). Rahn H. A concept of mean alveolar air and the ventilation-bloodflow relationships during pulmonary gas exchange. Am J Physiol 158: 21-30, 1949 (http://ajplegacy.physiology.org/cgi/reprint/158/1/21)). Riley RL. And Cournand A. "Ideal" Alveolar air and the analysis of ventilation-perfusion relationships in the lungs. J Appl Physiol 1: 825-847. 1949 (http://jap.physiology.org/cgi/reprint/1/12/825). Riley RL. And Cournand A. Analysis of factors affecting partial pressures of oxygen and carbon dioxide in gas and blood of lungs: theory. J Appl Physiol 4: 77-101. 1951 (http://jap.physiology.org/cgi/reprint/4/2/77).     

The pharmacologic characterization of allosteric molecules: Gq protein activation

Context: Drugs such as positive allosteric modulators (PAMs) produce complex behaviors when acting on tissues in different physiological contexts in vivo.

Objective: This study describes the use of functional assays of varying receptor sensitivity to unveil the various behaviors of PAMs and thus quantify allosteric effect through system independent scales.

Materials and methods: Muscarinic receptor activation with acetylcholine (ACh) was used to the demonstrate activity of the PAM agonist 1–(4-methoxybenzyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, Benzyl quinolone carboxylic acid (BQCA) in terms of direct agonism, potentiation of ACh affinity, and ACh efficacy. Concentration–response curves were fit to the functional allosteric model to yield indices of agonism (τ_B), effects on affinity (α cooperativity), and efficacy (β cooperativity).

Results: It is shown that a highly sensitive functional assay revealed the direct efficacy of BQCA as an agonist and relatively insensitive cells (produced by chemical alkylation of muscarinic receptor with phenoxybenzamine) revealed a positive allosteric effect of BQCA on ACh efficacy. A wide range of functional assay sensitivities produced a complex pattern of behavior for BQCA all of which was accurately quantified through the system-independent parameters of the functional allosteric model.

Conclusions: The study of complex allosteric molecules in a range of functional assays of varying sensitivity allows the measurement of the complete array of activities of these molecules on receptors and also better predicts which will be seen with these in vivo where a range of tissue sensitivities is encountered.     

Populations evolving towards failure: costs of adaptation under competition at the range edge of an invasive perennial plant

Background: Species undergoing range expansion adapt to novel and stressful environments at range fronts. These adaptations of the edge populations may incur fitness costs. These costs may play a crucial role in stopping range expansion before absolute physiological and evolutionary limits were reached. Costs however have proven to be elusive. These may be specifically expressed under competition.

Aims: Here, we assessed the costs of adaptation in range-edge populations of an invasive plant by evaluating plant responses under competition.

Methods: We grew plants from range-centre and edge populations under competition treatments in a glasshouse. We predicted that plants from the range-edge would express lower reproductive efficiency under competition compared with centre population plants, and this would indicate a potentially maladaptive response.

Results: Under high competition, plants from the range-edge expressed lower reproductive efficiency relative to range-centre plants which supported our prediction. In addition, they were more heavily affected by competition.

Conclusions: Adaptation to novel environments at the range-edge has incurred a cost as a potentially maladaptive response under competition, which may contribute to the formation of the range-edge. This finding suggests that these costs likely form part of the classic trade-offs involved with stress-tolerance and may have effects on range evolution.