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Aug 2026
A. Marcum JamesCorresponding author
The complexity of living systems, ranging from cellular networks to organisms to ecosystems, poses a significant challenge to the progress of contemporary biology and biomedicine. Living organisms are complex adaptive systems that are characterized by nonlinear interactions, causal-dynamic feedback loops, and context-dependent behaviors that give rise to emergent properties that are not completely explainable or predictable from the properties of the individual components alone. Investigating and understanding systemic complexity is therefore essential for advancing biology and biomedicine. Recently, artificial intelligence (AI) has been developed for analyzing large-scale, high-dimensional datasets generated by experimental and clinical research. AI enables the identification of correlations, causal patterns, and predictive relationships, which are difficult to discern using traditional analytical approaches. However, without an overarching framework, it risks being applied in fragmented or purely data-driven ways. Systems thinking (ST) provides a framework by emphasizing holism, interconnections, and dynamic behaviors across multiple organizational scales. By integrating ST and AI, researchers can creatively and effectively investigate living systems, ensuring that computational insights are meaningful and contextually grounded. An integrated ST–AI approach is proposed as a guiding framework for twenty-first century biology and biomedicine.
Sep 2024 DOI 10.14302/issn.2575-7881.jdrr-24-5255
O. Henderson JeffreyCorresponding author
This article surveys RBM45 from molecular function and RNA binding to cellular roles and evolutionary conservation. It summarizes emerging links to neurobiology and disease, and highlights tools and models to probe RBM45 biology.
Jun 2024 DOI 10.14302/issn.2578-8590.ipj-24-5107
Sclarosky SamuelCorresponding author
Maintaining Cardiac Hemodinamy and Electrophysiology
Jun 2022 DOI 10.14302/issn.2328-0182.japst-22-4193
Tariku Belay YilkalCorresponding author
School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda
The strategy for safe drug discovery and development has limited clinical success as compared to wasted time and resources annually. This is due to the fact that the results of multiphase preclinical trials are less likely to make an accurate early prediction on the safety of test compounds to progress into the clinic as a valuable therapeutic agent. A lot of time and resources has been wasted in the multistage processes of drug discovery and development that does not work at the end of the procedure every year. During pre-marketing stage, for instance, the number of unsuccessful clinical trials are greater than the successful one because of safety issues. A toxicity study at different stages of preclinical and clinical trials is a routine procedure to investigate the undesirable side effects of test compounds being manifested on the natural processes of living things. It deals with the effect and mechanism of toxicity of test compounds that triggers different biological responses on different organ systems. The biological responses that would be manifested as a result of interaction between the receptors and active molecules of a test compound could be desirable pharmacological effect or undesirable side effect or both responses are manifested simultaneously depending on the selectivity or specificity of the molecule of a test compound for its receptor subtype which makes safe drug discovery and development very challenging. The response efficiency of the body (the net outcome of the body’s biological reaction against the side effect) would determine the potency of a test compound to manifest undesirable pharmacologic effect. In other words, the amount of a drug required to cause a biological harm or injury depends on the magnitude of the body’s biological reaction in which the immune response plays a great pharmacological role by neutralizing and harmonizing xenobiotics with the biological molecules. The dose of a test compound at 100 mg/kg body weight, for instance, could be lethal to some of the study animals while it is still non-lethal to some other study animals depending on the response efficiency of the body. The immune system is well connected to each and every biological systems of the body which allows it to detect undesirable side effects being manifested through immunoglobulins signalling and activation mechanisms. This complex communication network helps to localize the diverse side effects of a test compound being manifested on different organ systems into the immune system which makes a toxicity study relatively simple to monitor. The cellular immune system becomes active following the molecule-receptor interaction and start producing antibodies which is also known as immunoglobulins to protect bodily harm and destruction. Under normal biological circumstances, the amount of immunoglobulins produced by the cellular immune system following exposure to a test compound is proportional to the number of harmful molecules interacted with its receptor subtype. Thus, with the reference to the changes in the immune response against the administered dose, it would be able to deal with the diverse undesirable side effects of a test compound being manifested on treated study animals using computational systemic biology.
Oct 2021 DOI 10.14302/issn.2641-5526.jmid-21-3900
Perez Jean-claudeCorresponding author
Phd Maths Computer Science Bordeaux University, RETIRED Interdisciplinary Researcher (IBM Emeritus, IBM European Research Center On Artificial Intelligence Montpellier) Bordeaux Metropole, France.
In this theoretical discovery of a law of Life, there is MATHEMATICS (Geometry, Bits and Numbers) that UNIFY 3 universes as complementary as ATOMIC MASS, WAVES, and INFORMATION (DNA, RNA and Amino Acids). The discovery of a simple numerical formula for the projection of all the atomic mass of life-sustaining CONHSP bioatoms leads to the emergence of a set of Nested CODES unifying all the biological, genetic and genomic components by unifying them from bioatoms up to 'to whole genomes. In particular, we demonstrate the existence of a digital meta-code common to the three languages of biology that are RNA, DNA and amino acid sequences. Through this meta-code, genomic and proteomic images appear almost analogous and correlated. The analysis of the textures of these images then reveals a binary code as well as an undulatory code whose analysis on the human genome makes it possible to predict the alternating bands constituting the cariotypes of the chromosomes. The application of these codes to perspectives in astrobiology, cancer, and specifically in INFORMATION THEORY with the emergence of binary codes and regions of local stability (voting process), whose fractal nature we demonstrate, is illustrated. PREFACE by Professor Luc Montagnier Addendum by Robert Friedman M.D After the discovery of the DNA double helix structure allowing both the stable storage of genetic information and its transfer through messenger RNA to protein synthesis organelles themselves structured by RNA most abundant in cells, the ribosomal. This wonder of nature exists in ALL living beings from the virus to humans and is based on two codes, the linear sequence of nucleotides and that derived from codons where three nucleotides allow with a certain flexibility - synonymous codons - the choice in the twenty amino acids. But we are missing a third CODE the one governing at multicellular beings from the rotifer to human, the stabilized modulation of gene expression in a nutshell the differentiation of cells from the single cell of the fertilized egg. It is logical to think that this program which begins as soon as fertilization is written in the DNA. We are also prone to associate it with non-coding DNA sequences although they control gene expression. I introduce here the notion developed by Jean-Claude Pérez of mathematical harmony, a higher order present in all living beings and whose existence it finds in genomes, including those of viruses. Thus the natural evolution of variants of the genome of coronavirus Covid 19 tends towards increasingly long Fibonacci series. It remains to determine the Who, the How and the Why of such developments. I will bet with my mathematician colleague that waves and fractals play a role. Luc Montagnier ADDENDUM Jean-claude has given scientists a strong new direction for research. He has identified a unified field of science guided by the Golden Ratio and Fibonacci Sequence. By identifying an overall guiding principle that makes possible fractal-like nesting at all levels of biological manifestation, future researchers can begin with the "whole" instead of the "parts". If we know that complex systems are organized at varying levels by the Golden Ratio and Fibonacci Sequence, we can look for those universal patterns first and then fill in the gaps with small details to complete the picture. It's like having an overall view of a crossword puzzle before beginning to assemble the individual pieces. Without an overarching vision and guiding principle, completing the puzzle is infinitely more difficult. Once scientists and researchers realize and begin using this "SECRET IN HIDDEN IN PLAIN SIGHT," their discoveries will be orders of magnitude more fruitful. Robert Friedman M.D
Aug 2021 DOI 10.14302/issn.2639-3166.jar-21-3858
Haroun Mohamed Adam AbubakerCorresponding author
Department of Crop Science, College of Agriculture, University of Bahri- Sudan.
The Fall armyworm (Spodoptera frugiperda) is considered among the economic important pests in Sudan. Therefore, it became necessary to study and understand its biology and find out the appropriate control measure (s). To achieve the above objective, experiments based on Randomized Complete Block Design (RCBD) were carried out during the period from September 2018 to August 2019, where the Fall armyworm (FAW) was reared in the laboratory and fed on a nutrient médium composed of Corn leaves. The results displayed the ranges of eggs laid by a female was 890–1169. The egg incubation period ranged between 3-13 days. The larval duration ranged between (13-50) days and the pupal duration was between (7-20) days under a temperature of 21-300c and a Relative Humidity (RH) of 65 ± 5%. The longevity of the adults was 1-20 days, and the range of the full lifecycle was (24-100). However, six generations of FAW were obtained within one year. This study concludes that in Sudan FAW breeds continously throughtout the year and it recommends further studies on the biology and effective management of this invasive pest
Jun 2018 DOI 10.14302/issn.2835-2165.jfsh-18-2162
Essam Eissa MostafaCorresponding author
Independent PhD Researcher, Faculty of Pharmacy, Cairo University, Cairo, Egypt
This article advocates for routine use of quantitative microbiological risk assessment to strengthen process control. It illustrates how modeling hazard levels and uncertainty informs critical limits, verification, and continuous improvement.
Dec 2025 DOI 10.14302/issn.2997-2108.jcc-25-5657
M Essam ZahraaCorresponding author
Viral infections contribute to a significant proportion of human cancers, with human papillomavirus (HPV) being one of the most well-established oncogenic viruses. This review summarizes HPV biology, transmission, classification, molecular mechanisms of carcinogenesis, epidemiology of HPV-associated cancers, and current and emerging preventive and therapeutic approaches. particularly HPV-16 and HPV-18, drives malignant transformation through the E6 and E7 oncoproteins, which disrupt tumor suppressor pathways p53 and Rb. Prophylactic vaccination programs have demonstrated remarkable success in reducing HPV-related disease burden, but disparities in coverage remain. Cutting-edge strategies such as CRISPR/Cas9 and RNA-based therapeutics offer promising avenues for treating established infections. Integrating these biomedical advances with robust public health initiatives is essential to ultimately eliminate HPV-associated cancers worldwide (Figure 1).
Dec 2025 DOI 10.14302/issn.2329-9487.jhc-25-5778
S Kallistratos ManolisCorresponding author
Calcium channel blockers (CCBs) are widely used for the treatment of arterial hypertension, but they differ in terms of pharmacology, tolerability, and pleiotropic actions. Lercanidipine, a highly lipophilic third generation dihydropyridine, reduces blood pressure (BP) effectively as monotherapy and in combination without inferiority to other major antihypertensive classes. We systematically searched PubMed and the Cochrane Library (last update: September 1, 2025) and screened reference lists for additional studies. Evidence from dose finding trials, randomized controlled studies, large observational cohorts, and meta analyses shows clinically meaningful reductions in office, home, and ambulatory BP with lercanidipine, including in patients with diabetes, obesity, chronic kidney disease, or high cardiovascular (CV) risk. Fixed- dose combinations with renin angiotensin system blockers (e.g., enalapril) provide greater BP reductions than monotherapy and are associated with favorable neurometabolic profiles. Beyond BP control, lercanidipine improves central hemodynamics and arterial stiffness, favors endothelial biology, and contributes to left ventricular hypertrophy regression. Across comparative trials, lercanidipine is generally better tolerated than older dihydropyridines. Presents lower rates of vasodilatory adverse events, less sympathetic activation, while discontinuations due to adverse events are uncommon. Overall, lercanidipine particularly within single pill combinations offers effective, durable BP lowering across diverse patient profiles with a favorable safety and tolerability profile and pleiotropic benefits that extend beyond BP reduction. Figure 1. Graphical Abstract: Pleiotropic effects of Lercanidipine
Nov 2025 DOI 10.14302/issn.2326-0793.jpgr-25-5573
E. Imiruaye OghenetegaCorresponding author
Advancements in proteomic and genomic technologies have transformed molecular biology by enabling comprehensive analysis of biological systems at the molecular level. This literature review explores the evolution, methodologies, and practical applications of key proteomic and genomic techniques. In proteomics, tools such as two-dimensional electrophoresis, mass spectrometry, Western blotting, Edman degradation, and functional protein microarrays have facilitated high-throughput protein identification, post-translational modification analysis, and biomarker discovery. Similarly, genomic methodologies like PCR, recombinant DNA technology, gel electrophoresis, and Southern blotting have revolutionized gene detection, manipulation, and expression profiling. The review also highlights the interdisciplinary impact of these technologies across clinical diagnostics, oncology, autoimmune disorders, infectious disease surveillance, cardiovascular research, and personalized nutrition. Integrative approaches combining proteomics and genomics are enabling the discovery of novel therapeutic targets, improving disease classification, and advancing precision medicine. Despite current limitations, such as the absence of amplification techniques for proteins and challenges in data interpretation, ongoing innovations promise to bridge these gaps. This synthesis underscores the pivotal role of molecular techniques in deepening our understanding of human biology and accelerating biomedical advancements for improved healthcare outcomes.
Sep 2024 DOI 10.14302/issn.2689-4602.jes-24-5245
Sanghani HunarCorresponding author
Charles Darwin's exploration of the Galápagos Islands in 1835 and his subsequent formulation of the theory of evolution in 1839 were significantly influenced by his observations of land-birds, including finches, larks, owls, and mockingthrushes. Despite a primary focus on geology during his voyage on the HMS Beagle, Darwin meticulously documented various species in his field notebooks. Early observations during his youth at Edinburgh University and the Beagle expedition reflected Darwin's growing curiosity about species variation. However, it was not until his return to England and his interaction with ornithologist John Gould that Darwin began to recognize the significance of the finches he had observed in the Galápagos. This review synthesizes existing literature on Darwin's transition from geological interests to his groundbreaking insights into evolution. By examining primary sources, historical interpretations, and contemporary analyses, this paper highlights how Darwin's observations and Gould's influence shaped his revolutionary theory of species transmutation—the gradual transformation of one species into another over time. The review aims to provide a comprehensive understanding of Darwin's contributions, illustrating how his Galápagos observations and collaboration with Gould laid the foundation for modern evolutionary biology and continue to influence scientific thought on species adaptation and natural selection.
Sep 2024 DOI 10.14302/issn.2690-4721.ijcm-24-5126
D. N Girah.Corresponding author
The development of medical therapy and patients profile has led to a rise in the incidence of nosocomial fungal infection. The frequency of candidiasis has surged worldwide, and the prevalent of healthcare diseases are now Candida species. Candida species causes a range of human infections known as Candidiasis. The non-albicans Candida (NAC) species have recently superseded Candida albicans as significant opportunistic pathogens. The study was conducted to determine the prevalence and antifungal susceptibility of Candida species isolated from various Clinical samples in Rivers State University Teaching Hospital, Port Harcourt, Nigeria. A total of 206 clinical specimens from male and female patients of all ages were sampled in the Department of Microbiology, Rivers State University Teaching Hospital, Port Harcourt, to investigate suspected Candida infections. The isolation and identification of Candida species was done by culture on SDA, Gram stain, sugar fermentation and phylogenetic profiling. Antifungal susceptibility pattern was done by Disc Diffusion method using Fluconazole, Ketoconazole, Miconazole, Nystatin and Itraconazole. The results showed that out of 206 specimens, 44 isolates (21.4%) were identified, with the majority (56.82%) from high vaginal swabs (HVS), followed by urine (31.82%) and oral swabs (11.36%). The age of patients ranged from four months to 73 years giving a Mean Age 1.86+ 0.344, with females (85.4%) outnumbering males (13.6%). Prevalence of Candida spp revealed Candida albicans (50%), Candida krusei (18.2%), Candida parapsilosis(11.4%), Candida glabrata and Candida tropicalis (9.1%) respectively and Candida pelliculosa (2.2%), with C. albicans being the most prevalent. The antifungal susceptibility testing among the azoles showed that Fluconazole (79.5%) and Ketoconazole (77.3%) were most sensitive agents against isolates from HVS, urine and oral swabs respectively and Itraconazole (34.1%) was most resistant especially to those from oral swabs. This study highlights the increasing prevalence of NAC species over Candida albicans and the growing resistance of Candida isolates to commonly used antifungal drugs. Diagnosis of these species of Candida and sensitivity to antifungal agents are critical components to treatment, particularly for patients with severe underlying illnesses who are hospitalized.
Jan 2024 DOI 10.14302/issn.2328-0182.japst-23-4771
Tariku Belay YilkalCorresponding author
Background Immunoglobulins are bio-receptors found embedded in the cell membrane with a biological role that detects the harmful molecules of a test compound. These bio-receptors interface between a biological system and its external environment that transduce information to the effector via intermediate messengers in which its response efficiency usually exhausts at high doses of exposure to external stimuli. The purpose of this review article is, therefore, to elaborate on the computational method for systemic biology which was designed to convert qualitative pharmacological data into the quantitative one that might help to determine the toxicity of a test compound. Methods First, acute toxicity studies using different levels of doses prepared from each test compound have been conducted on Balb c mice. Then, blood specimens from the tail and facial veins of each sampled Balb c mouse were collected 3 days before dosing as a reference test and 4 hr after dosing for comparison. The changes in the efficiency of immunoglobulins immune response (ΔIg) after dosing were determined using quantitative immunoassay and the body’s response against the dose as the toxic reaction rate (r) and the toxic severity (s) were finally determined using computational methods as r=d/t-ΔIg mg/sec and (s=r/w×100) %/sec respectively, where (w) represents the body weight of a study animal, (t) represents the period of time at which undesirable bio-physiological responses manifested on treated study animals and (ΔIg) represents the changes in the concentration of immunoglobulins in blood serum after dosing. Results The results of different studies revealed that the dose has never limited the toxic property of a test compound but the length of time at which the undesirable side effect was manifested on study animals. The period of time at which adverse effects manifested on treated Balb c mice was inversely related to the amount of dose administered in the oral route. The higher the dose of the administered test compound, the shorter the period of time at which the undesirable side effect was manifested on treated Balb c mice. This means that the adverse effect of test compounds was not because of the dose but rather due to its toxic reaction rate which ultimately determined the toxic severity in the natural process of treated Balb c mice. Balb c mice treated with a dose whose toxic reaction rate was ≤ 0 survived from death whereas Balb c mice treated with a dose that had a toxic reaction rate of > 0 died at different lengths of time after dosing depending on the toxic severity of a test compound. It could be a scientific fact to declare that a test compound is safe when the toxic reaction rate (r) and toxic severity (s) of a dose is ≤ 0 and toxic when it is > 0 in the natural processes of a study animal.
Apr 2023 DOI 10.14302/issn.2641-5518.jcci-23-4554
Botchorishvili IngaCorresponding author
This report details sequential rare complications arising from a vascular stent infection. Clinical course, microbiology, and imaging are outlined, with emphasis on early recognition and multidisciplinary management. Lessons for device surveillance and antimicrobial stewardship are highlighted.
Apr 2023 DOI 10.14302/issn.2372-6601.jhor-23-4530
Padaro EssohanaCorresponding author
Objective Drawing up a balance sheet of 16 years follow-up of the sole case of Diamond-Blackfan anemia diagnosed in Togo with arguments of molecular biology. Observation T.S a boy, born on 5th september 2006 has been followed up since he was three months, for Diamond-Blackfan anemia (DBA) in whom there has been found the mutation of ribosomial protein RPS19 in july 2010. It was the first observation in Subsaharian Africa. The treatment by transfusions from december 2006 to december 2022 has been associated with iron chelation through deferoxamin and promptly with corticotherapy at the dosage of 2mg/kg/day. The corticotherapy has been reduced as a consequence of corticoresistance from the fourth week, then definitely interrupted after four months. The evolution is marked by a clinical improvement with a staturo-balanced curve, and during the last control of 28th december 2022, the child was 53 kg heavy and 160 cm tall. The monthly physical tests did not reveal any signs of eventual overloading and the echocardiography of 26th december 2022 was normal. On the biological plan, the rate of the haemoglobin had been stable around 50g/l as a resultant of a transfusion each 4 to 6 weeks of red blood cell pellet. The chelation of iron had been done through deferoxamin with a monthly control of serum ferritin. That serum ferritin was 738,39ng/mg at diagnosis before the beginning of transfusions and during the follow-up, we noticed an average of 2977,3ng/ml (range 1817,1ng/ml and 4448,5ng/ml) Conclusion Thanks to the regular transfusions derived from the survey of the parameters of iron and the use of deferoxamin, we have succeded in keeping alive during sixteen years a patient who caught a disease whose evolution is unpredictable.
Feb 2023 DOI 10.14302/issn.2997-1977.jd-22-4378
Gautam KirtikaCorresponding author
Typhoid or enteric fever is caused by Salmonella serotype typhi and paratyphi. It is one of the major public health problem in developing countries including Nepal. In recent years, increased urbanization and growing population within Kathmandu valley, attributed mainly to improper sanitary condition and fecal contamination of drinking water. These all factors contributes to a very high prevalence of typhoid fever through out the country. Methods This study was laboratory based study carried out six month period from march 2017 to August 2017 at microbiology lab in Nepal Medical college. Results and conclusion In the present study, the prevalence of enteric fever is mainly caused by Salmonella. Typhi than Salmonella Paratyphi A was observed.
Aug 2021 DOI 10.14302/issn.2641-5518.jcci-21-3914
Yang LiCorresponding author
Department of Endocrinology, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan 410000, China.
A patient with Carney complex is reported with a previously undescribed PRKAR1A mutation. The article situates the variant within PKA pathway biology and clinical phenotype, underscoring the value of genetic testing for diagnosis, counseling, and surveillance.
Jun 2021 DOI 10.14302/issn.2474-3585.jpmc-21-3851
A. Njukeng PatrickCorresponding author
Global Health Systems Solutions, Douala, Cameroon
Background The rapid and ongoing spread of antimicrobial-resistant organisms threatens the ability to successfully prevent, control, or treat a growing number of infectious diseases in developed and developing countries. This study was designed to convey more insight on the profile of antimicrobial resistance and the capacity of laboratories conducting antimicrobial susceptibility testing in Cameroon. Methods A multicentre cross-sectional study was conducted from October 2019 to March 2020 in the Deido Health District. Laboratories that carry out culture and sensitivity testing within the Deido Health District were identified and assessed to determine their capacity as well as the quality of results from microbiological investigations. Information on antimicrobial susceptibility of various isolates was collected using tablet phones in which the study questionnaires had been incorporated. Results Gaps identified in antimicrobial susceptibility testing that cut across laboratories included; insufficient standard operating procedures, inadequate records on personnel training and competency assessment, lack of safety equipment such as biosafety cabinet, stock out and non-participation in external quality assurance program. The turnaround time for antimicrobial susceptibility testing ranged from 3 – 7 days. Out of the 1797 samples cultured, 437(24.3%) had at least one isolate. A total of 15 different isolates were identified with Candida albicans being the most frequent 178 (40.7%), followed by Escherichia coli 80(18.3%). Among the 15 classes of antimicrobial drugs used in this study, the overall resistance of the isolates showed that five classes had class median resistance above 40% (Cephalosporins, Penicillins, Beta-lactam, Macrolides, and Polyenes). Conclusion This study has shown the need to develop a coordinated national approach to fight antimicrobial resistance. Scaling-up of antimicrobial susceptibility testing will, therefore, require strengthening the microbiology units of laboratory systems as well as ensuring the use of laboratory data for decision making.
May 2021 DOI 10.14302/issn.2690-4721.ijcm-21-3835
Montes MilagrosaCorresponding author
Biodonostia Health Research Institute, Vaccine Preventable Diseases Group; Osakidetza Basque Health Service, Donostia University Hospital, Microbiology Department, 20014 San Sebastian, Spain.
Objective Real-time surveillance of SARS-CoV-2 variants of concern (VOC) is of essential public health importance. Rapid Antigen Detection Tests (RAgDT) have become first-line COVID-19 diagnostic methods in many regions, but this strategy can hamper the surveillance of the virus variants due to their decentralized performance. The aim of this study was to assess the usefulness of the remaining sample of a widely used RAgDT (Panbio) for the surveillance of the B.1.1.7 VOC using molecular methods. Methods Symptomatic individuals and asymptomatic close contacts of confirmed cases were routinely screened for SARS-CoV-2 infection using the RAgDT in Primary Health Care Centers. After performing the test, the extraction tubes containing the remaining biological material of RAgDT-positive cases were sent to the clinical microbiology laboratory where RT-PCRs detecting key mutations of the VOC were conducted. Results A valid result was obtained in 1770/1812 (97.7%) RAgDT-positive cases. Variant B.1.1.7 was detected in 34.7% of the patients, increasing from 0% to 87.7% between the weeks beginning January 4 and March 15, 2021. Conclusion The sample remaining after performing the Panbio RAgDT allowed to monitor the emergence and circulation of the B.1.1.7, greatly improving the population screened for the molecular study of SARS-CoV-2 variants.
Dec 2019 DOI 10.14302/issn.2575-1212.jvhc-19-3101
Rodrigues Reina Moreira PamelaCorresponding author
Department of Veterinary Pathology, UNESP – FCAV – Faculdade de Ciências Agrárias e Veterinárias, Jaboticabal city, São Paulo State, Brazil.
Papillary carcinoma is a mammary neoplasia of women and female dogs characterized by papillary fibrovascular projections lined by epithelial cells. Evaluation on the biology of these tumors can be done by immunohistochemistry through detection of alpha-smooth muscle actin protein in the papillary myoepithelium, which lacks such a molecule during malignant proliferations. Thus, this study aimed at determining the malignancy degree of papillary mammary tumors of female dogs by immunohistochemistry. Twenty samples of mammary neoplastic tissues collected from female dogs treated in the Veterinary Hospital at FCAV were evaluated by Hematoxylin and Eosin staining (H&E) and tumor cells were immunolabelled with monoclonal antibody to alpha-smooth muscle actin (α-SMA). Five out of 20 cases showed positive immunolabeling greater than 10% of the total immunolabeling. The remaining fourteen cases presented immunostaining lesser than 10% showing decrease or absence of α-SMA labeling in the myoepithelium of the papilla tumors. All those cases in which immunostained cell was over 10% of the neoplasm (5 immunostains of 20 total cases) were classified as benign whereas those below 10% of immunostained in the slid were considered as malignant. Therefore, immunohistochemistry played an essential role in differentiating benign and malignant papillary tumors of bitches as already described for female. Tumor classification by conventional methods, such as H&E staining, can lead to erroneous interpretations on the real biological behavior of the papillary mammary tumor.
Aug 2019 DOI 10.14302/issn.2572-3030.jcgb-19-2955
N Pak VladimirCorresponding author
Research scientist, Toronto, Ontario, Canada
This review revisits alpha‑fetoprotein (AFP) and AFP receptor biology beyond their classic role as oncofetal markers. It summarizes signaling, tumor biology, and clinical implications across malignancies, including diagnostic, prognostic, and therapeutic angles. The authors highlight opportunities and limitations for AFP‑targeted interventions.
May 2019 DOI 10.14302/issn.2644-1101.jhp-19-2766
Crespi FrancescoCorresponding author
Biology, CSK, Verona, Italy
Cholecystokinin (CCK) is found in high concentrations in cortical and limbic structures including the amygdala of rodents, and evidence has been gathered supporting a role for CCK in the neurobiology of anxiety. A variety of animal models have been used to study a central state of fear or anxiety, state that appears to produce a complex pattern of behaviors highly correlated with each other. It is now well established that the amygdala in particular is a critical link in the pathway through which sensory stimuli come to acquire fear evoking properties. The purpose of the proposed experiments is to study the role of the putative neurotransmitter CCK in fear and anxiety in vivo by means of a methodology coupling electrochemical and electrophysiological measurements in various brain areas. Indeed, the association of in vivo differential pulse voltammetry (DPV) with in vivo extracellular single unit recording could be able to provide concomitant physiological and neurochemical indications and to relate them to behavioral events. To further study and support the initial observations pharmacological experiments will also be performed by means of CCK receptor agonists and antagonists. This may eventually lead to development of more effective pharmacological strategies for treating clinical anxiety disorders.
Mar 2019 DOI 10.14302/issn.2576-6694.jbbs-19-2684
K. Srivastava RajeshCorresponding author
Department of Biotechnology, GIT, GITAM (Deemed to be University), Rushikonda, Visakhapatnam-530045 (A.P.), India.
Yeast as unicellular organism, has shown multiple application due to exhibition of noble ability in its cells. And engineered yeast has found more suitability in bioprocesses application as well as adverse conditions adaptation. Different types of yeast strains showed their best capability to adapt the salt and sugar rich environment with their optimal growth capability. These strains, used as suitable and novel cell factories for production of value added bio-products (via utilization of fermentation processes) and also for different types of bioprocesses. Application of yeast species in biotechnology field, enhanced in current periods, due to conversion of its wild to engineer strain, suitable for bioprocesses utilization and also for different types of biochemical synthesis. Different yeast species identified due to known their genetic, regulatory mechanism and also competitive metabolic pathways. In this regards, different type of engineering approaches (for genetic or pathways modification), applied to construct the optimal and suitable cell factories for different types of bioprocesses as utilized in different sectors (foods with mineral or protein rich, bread, brewing, cosmetics, chemical, agriculture, pharmacy and distillation industries) via improving the quality of bio-products. Further, in silico designed based metabolic engineering technique showed the improvement in performance of yeast strain. System and synthetic biology with engineering approaches applied to further improve the yeast mediated bioprocesses as well as biochemical products formation for industrial or biotechnological application. Some bio-products such as functional bio-molecule, different types of alcoholic biofuels, organic acids and enzymes etc are good examples of yeast mediated biochemicals products, utilized more frequently in our life. Author will focus recent research and development on bio-product formation or bioprocesses with their regulatory control mechanism in different yeast strains.
Dec 2018 DOI 10.14302/issn.2379-7835.ijn-18-2501
Mainardi PaoloCorresponding author
Kolfarma Srl, Viale B.Bisagno 14, 16167 Genova, Italy
In the last few years, gut microbiota has been identified to be an essential mediator in health and disease. In fact, it interacts with various organs and systems in the body, including brain, lung, liver, bone, cardiovascular system, and others. Microbiota-derived metabolites such as the short chain fatty acid (SCFA) butyrate are primary signals, which link the gut microbiota and physiology. Then, the findings on the roles of microbiota profoundly change not only the key concepts of biology and medicine, but also of nutrition. In fact, it is currently evident how the main task of nutrition is not to nourish us, but to maintain a comfortable environment for the intestinal microbiota. In this way, it works in symbiosis with us, correctly controlling the functioning of the organs, the physiological parameters and the cellular regenerative processes. It is also evident that the strength of reparative processes correlates with the ability of digestive system to process complex foods, which increases during weaning, a period of time in which the diversity of bacterial strains increases. Therefore, a task of food is to keep trained the digestive system, to which it corresponds an high microbiota diversity. Elderly leads to reduced microbiota diversity to which corresponds an intestinal frailty, responsible for the frailty of the elderly. In conclusion, a correct diet may not only keep us in good health but may also guarantee us longer longevity.
Dec 2018 DOI 10.14302/issn.2326-0793.jpgr-18-2422
Patra SatyajitCorresponding author
Associate Professor in Biochemistry and Genetics, American International Medical University, St. Lucia
This review summarizes tumor development in p53‑deficient mouse models, discussing tissue specificity, cooperating pathways, and insights into human cancer biology.
Oct 2018 DOI 10.14302/issn.2326-0793.jpgr-18-2312
Saad Zaghloul Salem MohammadCorresponding author
Professor of Medical Genetics, Faculty of Medicine, Ain-Shams University, Cairo, Egypt
All aspects of life activities in living cells are mediated/executed and regulated by a vast number of networks, comprising a wide spectrum of components, starting with simple biomolecules and ending with the whole organism, and functioning within a precisely organized tight framework. Proper mediation of cellular activities necessitates their inclusion within the context of structured and organized network systems capable of regulating/coordinating and synchronizing the countless numbers of biological processes occurring within living cells. The number of biological networks and pathways within the living cell is considerably huge, being dependent on the structural complexity and functional capabilities of the cell. Pathogenesis and progression of human diseases result from functional disturbances of biological networks within the cell as disturbed network function leads to deleterious effects on physiological processes dependent on, and mediated by, affected network(s). Ensuing pathological processes, defined by the nature of disturbed networks and the specific organs or tissues affected, pave the way for the development of pathognomonic and characteristic disease entities. As most network functions are dependent on relatively small number of key regulatory biomolecules, i.e. enzymes/proteins and signal transducing factors, it follows that functional disturbances of biological networks and pathogenesis of disease states can be attributed, in most instances, to quantitative and/or qualitative abnormalities of these key regulatory molecules. Study and analysis of the structural designs and the functional mechanisms of biological networks would have crucial and important impacts on many theoretical and applied aspects of biology, in general, and of medical sciences in particular. Meticulous study of biological networks represents an important and integral aspect in study of biology. Interpretation and analysis of key information deduced from observing and analyzing structural designs and functional characteristics and dynamics of biological networks discloses and defines the basic framework within which life activities in living cells are initiated, adapted to physiological requirements, maintained, and terminated upon completion of their aims. More important, however, is the contribution of this information to proper understanding of the different mechanisms responsible for regulating and synchronizing the functions and performances of the vast spectrum of different network categories within the cell. In addition to its vital scientific significance, discovering and defining the key pivotal structural and regulatory molecules within life-mediating networks, and along different pathways responsible for controlling functional dynamics of the network, represent an indispensable diagnostic approach insistent for designing proper therapeutic approaches to diseases caused by network defects.
Aug 2018
Paranina AlinaCorresponding author
Department of physical geography and environmental management, Herzen State Pedagogical University of Russia, Russia
Journal of Biosemiotic Research is a new periodical devoted to a young, actively developing science. A review of recent scientific publications shows that in the broad scientific space of biosemiotics contemporary questions and "eternal themes" interact, not finding an answer in the private sciences - anthropology, semiotics of culture and philosophy1,2. To solve them, the fundamental foundations of science and new achievements, the opportunities of the latest technologies and scientific communications are attracted. Like all young sciences, biosemiotics has many definitions. We give here the most famous ones. "Biosemiotics: (bios, life + semion = sign) is an interdisciplinary field of theoretical and empirical research, analyzing communication and signification in living systems. Signed processes, ranging from molecular to ecological and evolutionary, have been studied throughout the history of biology; however, very often descriptions of information and communication aspects of living systems were considered only metaphorical, believing that the essence of them can be understood with the help of physical and chemical descriptions. In biosemiotics, on the other hand, information sign processes are considered as the primordial, basic system of phenomena of life, requiring a new understanding..."3. "Biosemiotics explores sign systems of various levels: molecular biological (genetic code), intracellular (signal peptides), intercellular (mediators, immune interactions), intraorganism (hormones, conditioned reflex reactions) and interorganism (telergons, pheromones, attractants) ... In addition, biosemiotics covers all the problems associated with the problem of the existence of language and thinking in animals." However, today we can go further and add to the analysis the next stage of evolution, standing between animals and modern human (Homo sapiens sapiens).
Apr 2018 DOI 10.14302/issn.2326-0793.jpgr-18-2004
Anwar PervezCorresponding author
Department of Biochemistry and molecular Biology, University of Gujrat Sialkot subcampus, Pakistan
Human proteome project was revolutionized about 40 years ago with purpose of summarizing whole proteomic data at one place. It was launched after human genome project to map and observe all proteins. The goal related proteomic study is to draft the entire human proteome in disease diagnosis by using bioinformatics tools. Pillars of human proteome project provide different databases related to proteins at transcriptional and translational level. Human proteome organization(HUPO) published biology disease HUPO whose aim is to measure protein and proteome by life and processes related to human diseases. Different human organ like plasma, liver, brain and diabetic base project are used to characterize human disease and health. Major data resources accumulated in databases like peptides Atlas, GPMDB and neXtProt for proteins. Matrices of human proteome project identify and characterize the protein products as Post translational modification (PTM), splice various isoforms from 20,300 proteins. Matrices related to different years make proteomes counterpart by magnify the research biomedical community with high output of instruments and specimen pre-analytical protocols. CALIPHO multidisciplinary group provides information about protein complexities, interactions, function and structure complexities after Uniport and Swissprot. Different bioinformatics tools are used for structural and functional annotations of protein, disease diagnosis and mutations due to protein. Extensive study of human proteome project has been proved helpful in disease treatment at translational and post- translational levels. In future, human proteome project along with bioinformatics will include protein profiling, biomarkers, Mass spectrophotometer technique and cross analysis of different proteome projects.
Apr 2018 DOI 10.14302/issn.2768-0207.jbr-17-1925
Bai QifengCorresponding author
Key Lab of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu 730000, P. R. China
Big data research has become popular and exciting studies in almost all scientific fields such as biology, chemistry, epidemiology, medicine and drug discovery. The various systems and platforms produce large amounts of data every day. It will be very helpful for the researchers and workers to deal with big data if the practical database and useful software are introduced in time. The Journal of Big Data Research (JBR) supplies an efficient and open access publishing platform for big data research. The first issue of JBR aims to foster the dissemination of high-quality big data studies in the biological, medical and chemical database as well as the new algorithm and software for big data processing. The database and computing framework are selected to introduce the development of big data in the biological, medicine and drug discovery. The mature and functional database can be serviced in big data research of scientific fields. It promotes the scientists to extract the useful and essential dataset from the massive data. The grid computing and cloud computing supplies a new paradigm that offers an effective framework of computing and services. The research papers are welcomed from the scopes of the practical database, new algorithm and software for big data studies. All these kinds of papers not only provide the effective application methods and platforms, but also give a good promising future for big data research.
Feb 2018 DOI 10.14302/issn.2832-5311.jpcd-18-1955
Zhu Qian-HaoCorresponding author
CSIRO Agriculture and Food, GPO Box 1700, Canberra, ACT 2601, Australia
Circular RNAs (circRNAs) are covalently closed single-stranded loop RNA molecules with or without protein coding capability. CircRNAs were previously considered to be splicing intermediates or artifacts but are now found to be pervasively expressed in all eukaryotes studied with some demonstrated to have important molecular functions in various biological processes. CircRNA is now a hot study topic of molecular biology. In this review, we summarize the progress achieved so far on plant circRNAs, including identification and functional characterization, compare the similarities and differences of circRNAs between plants and animals, and discuss the challenges for confident detection and functional investigation of plant circRNAs. Similar to what have been found in animals, plant genomes contain a large number of circRNAs that potentially regulate a wide range of biological progresses related to plant development and biotic/abiotic responses. Despite only a few plant circRNAs have been functionally characterized, novel function/mechanism that has not been reported in animals was revealed, implying more exciting findings about plant circRNAs are expected in future studies.
Dec 2017 DOI 10.14302/issn.2998-4211.jalr-17-1884
Paganelli RobertoCorresponding author
Department of Medicine & Sciences of Aging, University “G. d’Annunzio” of Chieti-Pescara, Italy
This editorial for the Journal of Alzheimers Research and Therapy outlines persistent questions in Alzheimer biology and care, and highlights emerging tools and study designs. The journal aims to connect mechanistic insight with therapeutic development and practice. It invites interdisciplinary work to accelerate translation and improve outcomes for patients and caregivers.
Sep 2017 DOI 10.14302/issn.2575-7881.jdrr-17-1749
D. Bhilare KiranCorresponding author
Biocatalysis and Protein Engineering Group, Department of Pharmaceutical Technology (Biotechnology), National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Punjab, India
Though, directed evolution/In vitro evolution has greatly enhanced the applicability of natural biomolecules, there is still a big void in synthetic biology, which could be filled only when we are able to make novel/synthetic functional biomolecules. Terminal deoxyribonucleotidyl transferase (TdT) is the only known DNA polymerase, which can add deoxyribonucleotides without the requirement of a DNA template. Here, we are introducing the concept of Template-Independent Synthesis of Nucleic Acids (TISNA), where we have exploited the property of terminal deoxyribonucleotidyl transferase to add deoxyribonucleotides to the 3’ end of an oligonucleotide for the generation of de novo libraries of ssDNA, dsDNA coding sequences and RNA. We are able to generate libraries that have diversity not only in sequence but also in length in a single library itself. The length of double stranded random gene libraries generated using this approach ranges from 200 base pairs to 10 kilobase pairs. The ability to make random nucleic acid libraries from scratch (independent of any template information) in the laboratory could open up new avenues and holds promise for the pharmaceutical and biotechnological sectors.
Jul 2017 DOI 10.14302/issn.2326-0793.JPGR-17-1571
C. P. Figueiredo HenriqueCorresponding author
AQUACEN, National Reference Laboratory for Aquatic Animal Diseases, Ministry of Agriculture, Livestock and Food Supply, Federal University of Minas Gerais, Belo Horizonte, Brazil
Perkinsus marinus is an intracellular parasitic protozoan that is responsible for serious disease epizootics in marine bivalve mollusks worldwide. Despite all available information on P. marinus genomics, more baseline data is required at the proteomic level. Our aim was to study the proteome profile of in vitro cultured P. marinus isolated from oysters Crassostrea spp. using a label-free shotgun UDMSE approach. A total of 4073 non-redundant proteins were identified across three biological replicates with stringent identification. Proteins specifically related to adaptive survival, cell recognition, antioxidants, regulation of apoptosis and others were detected. Important virulence factors of P. marinus were identified including serine protease and iron-dependent superoxide dismutase. Other proteins with involvement in several pathogens invasion strategies were rhoptries, serine-threonine kinases, and protein phosphatases. Interestingly, peptides corresponding to retroviruses polyproteins were identified in all replicates. The interactomic analysis of P. marinus proteins demonstrated extensive clusters network related to biological processes. In conclusion, we provide the first comprehensive proteomic profile of P. marinus that can be useful for further investigations on Perkinsus biology and virulence mechanisms.
Jan 2017 DOI 10.14302/issn.2572-3030.jcgb-16-1307
Morales RafaelCorresponding author
Genetic Counselling Unit, Medical Oncology Department, Hospital La Mancha Centro, Av La Constitución, Nº 3, 13600, Alcázar de San Juan, Ciudad Real (Spain)
Interpreting variants of uncertain significance (VUS) for their effect on protein function, and therefore for the risk of developing cancer, has become a challenge in clinical practice for genetic counselling services. The present work combines structural bioinformatics and systems biology based mathematical modelling approaches with the aim of determining the pathogenicity of the mutation c.5434C->G (p.Pro1812Ala) in the BRCA1 gene (detected in a patient from a high risk family) and also to mechanistically understand the effect of this mutation in DNA damage response, a key process in cancer development. The results obtained showed that this mutation prevents the interaction of BRCA1 with key proteins of the cell cycle, subsequently impairing BRCA1-dependent induction of cell cycle arrest. The comparison of the molecular mechanisms associated with the native BRCA1 protein and the mutated variant function in DNA damage response showed that the latter undergoes a reduction in its ability to modulate pathways that are critical for DNA repair and cell cycle control. Therefore, this variant will not be able to exert its tumor suppressive action. Interestingly, these conclusions can be extrapolated to all mutations that, like c.5434C>G (p.Pro1812Ala) BRCA1, cause loss of BRCT domain activity.
Jan 2017 DOI 10.14302/issn.2574-4372.jesr-16-1395
Wakatsuki TetsuroCorresponding author
InvivoSciences, Inc., Madison, WI
Calcium (Ca2+) plays a central role in regulating many biological processes in the cell from muscle contraction to neurotransmitter release. The need for reliable fluorescent calcium indicator dyes is of vast importance for studying many aspects of cell biology as well as screening compounds using phenotypic high throughput assays. We have assessed two of the latest generation of calcium indicator dyes, FLIPR Calcium 6 and Cal-520 AM for studying calcium transients (CaTs) in induced pluripotent stem cell (iPSC) -derived human cardiomyocytes. FLIPR Calcium 6 and Cal-520 dyes both displayed robust CaTs with a high signal-to-noise ratio (SNR) and were non-toxic to the cells. The analysis showed that CaT amplitudes were stable between measurements, but CaT duration was more variable and tended to increase between reads. Two methods were compared for drug-screening hit-selection; difference in average (unstandardized) and standardized difference. The unstandardized difference was better for assessing CaT amplitude, whereas standardized difference was equal to or better for assessing CaT duration. In summary, FLIPR Calcium 6 and Cal-520 are suitable dyes for drug-screening using iPSC-derived human cardiomyocytes.
Jan 2017 DOI 10.14302/issn.2470-5020.jnrt-16-1288
Quenum KCorresponding author
Service de Neurochirurgie, hôpital des spécialités– Rabat, Maroc
Cerebral aspergillosis is a severe disease most commonly suspected in immunodeficient patients. The objective of this study is to determine the role of surgery in management of intracranial aspergillosis. We report three cases of immunocompetent patients presenting: posteriror fossa aspergillosis, sphenoidal extended to sellar region aspergillosis and post operative aspergillosis without extracerebral involvement. Microbiology and histological examination were carried out to provide the diagnosis. The patients underwent surgical procedure associated with medical treatment or not. In one case, surgical treatment was efficient. The outcome was good in two cases. Conclusion: Rapid diagnosis of invasive aspergillosis applying radiological and surgical procedures and immediate ignition of antifungal can be life saving.
Jun 2016
V. Seeman MaryCorresponding author
Professor Emerita, Department of Psychiatry, University of Toronto, 260 Heath St. W., Suite 605, Toronto, Ontario, M5P 3L6, Canada.
Background: There is a growing scientific interest in the phenomenon of earworms, which are melodies that are heard and re-heard despite the absence of an external stimulus. Aim: The aim of this paper is to determine whether understanding earworms can shed light on mechanisms underlying auditory hallucinations in psychosis. Method: Using recent data sources, this report briefly reviews what is most relevant about musical hallucinations and earworms. Results: Musical hallucinations, like hallucinated voices, are more prevalent in women. In the elderly, they are often associated with hearing impairment. They are most distressing when they first begin, with the degree of distress inversely proportional to the extent to which they can be controlled. Earworms can be provoked both by the memory of past events and by the anticipation of future events. Strong emotion can trigger earworms, but so can boredom. Limitations: The neurobiology potentially involved in the phenomenon of earworms is not explored in this paper. The pertinence of the literature about earworms and musical hallucinations, while interesting, is of unproven relevance to pathological voices in psychotic illness. Conclusions: The clinical relevance, while unproven, is that addressing recurring memories, as well as managing strong emotions and avoiding occupations that lead to boredom are all strategies worth trying when treating pathologicalauditory hallucinations
Jul 2014 DOI 10.14302/issn.2377-2549.jndc-14-edt-1.1
Zhu QianCorresponding author
Visiting Faculty in Cheminformatics, School of Informatics and Computing, Indiana University, Bloomington, USA
An inaugural editorial sets scope and standards for the journal, highlighting emerging areas in chemical methods, materials, and interfaces with biology and energy.
May 2014 DOI 10.14302/issn.2572-3030.jcgb-13-369
Khan AshrafCorresponding author
Departments of Pathology, UMass Memorial Medical Center, University of Massachusetts Medical School, Worcester, MA 01605, USA
Insulin receptor substrate (IRS) 1 and 2 are downstream signaling proteins that influence breast pathophysiology. IRS-1 promotes carcinoma cell proliferation; whereas IRS-2 regulates cell motility, invasion, and glycolysis. Our lab has shown that distinct cellular localization of IRS-2 also plays a role in carcinoma cell function. Oncotype DX (Genomic Health) (ODX) is a 21-gene expression profile used to classify carcinomas with low, intermediate, and high risk recurrence scores (RS). Our aim is to correlate expression and cellular localization of IRS proteins in breast carcinomas with their ODX RS. 97 breast carcinomas sent for ODX testing from 2006-2009 were collected and grouped according to their RS (low, intermediate or high). Immunohistochemistry for IRS-1/-2 was performed. Specific criteria were used to evaluate IRS staining patterns. Follow-up data, ranging from 3-6 years, was available. Statistical analysis was performed to correlate staining patterns of IRS-1/-2 with the three RS groups. IRS-1 staining, predominantly nuclear, did not significantly correlate with RS (P=.5645). IRS-2 expression patterns did show statistical significance amongst the three RS groups (P=.0371). Tumors with intermediate and low RS were more likely to exhibit punctate and diffuse cytoplasmic expression of IRS-2, and cell membrane expression was uncommon in this group. Expression and cellular localization of IRS proteins play an important role in breast cancer cell biology, and expression patterns for IRS-2 do demonstrate a significant correlation with ODX RS. Further studies are required to elucidate the significance of cellular localization of IRS-1/-2 proteins in breast carcinoma cells and their relationship to ODX scores.
Feb 2014 DOI 10.14302/issn.2372-6601.jhor-13-346
E. Clapham ChloeCorresponding author
Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
Targeting cell metabolism is a therapeutic approach which has been used for the treatment of cancers with high levels of proliferation. Inhibition of metabolic processes in cancer cells has shown synergy with current therapeutic options to reduce refractory disease and relapse. In contrast, chronic lymphocytic leukaemia (CLL) is a disease where expansion of the malignant clone results from a combination of enhanced cell survival coupled with low level proliferation. The purpose of this article is to highlight how further research is needed to determine whether targeting cell metabolism may be a viable therapeutic strategy in this disease. We discuss how lymphocyte doubling time (LDT) remains a robust prognostic indicator used in the current clinical management of CLL, and how recognition of CLL as a proliferative disease has led to a greater understanding of the importance of energy-generating processes in its pathobiology. We summarize what is currently known about normal B cell metabolism and consider whether there is evidence of the Warburg effect in CLL cells. Finally, we speculate on how CLL cells may exploit protective mechanisms such as autophagy during times of metabolic stress and how they might influence or be influenced by metabolic characteristics of the microenvironment.