Biology Of Humans Research Articles

CRISPR-based genome editing of a diurnal rodent, Nile grass rat (Arvicanthis niloticus)

BackgroundDiurnal and nocturnal mammals have evolved distinct pathways to optimize survival for their chronotype-specific lifestyles. Conventional rodent models, being nocturnal, may not sufficiently recapitulate the biology of diurnal humans in health and disease. Although diurnal rodents are potentially advantageous for translational research, until recently, they have not been genetically tractable. The present study aims to address this major limitation by developing experimental procedures necessary for genome editing in a well-established diurnal rodent model, the Nile grass rat (Arvicanthis niloticus).ResultsA superovulation protocol was established, which yielded nearly 30 eggs per female grass rat. Fertilized eggs were cultured in a modified rat 1-cell embryo culture medium (mR1ECM), in which grass rat embryos developed from the 1-cell stage into blastocysts. A CRISPR-based approach was then used for gene editing in vivo and in vitro, targeting Retinoic acid-induced 1 (Rai1), the causal gene for Smith-Magenis Syndrome, a neurodevelopmental disorder. The CRISPR reagents were delivered in vivo by electroporation using an improved Genome-editing via Oviductal Nucleic Acids Delivery (i-GONAD) method. The in vivo approach produced several edited founder grass rats with Rai1 null mutations, which showed stable transmission of the targeted allele to the next generation. CRISPR reagents were also microinjected into 2-cell embryos in vitro. Large deletion of the Rai1 gene was confirmed in 70% of the embryos injected, demonstrating high-efficiency genome editing in vitro.ConclusionWe have established a set of methods that enabled the first successful CRISPR-based genome editing in Nile grass rats. The methods developed will guide future genome editing of this and other diurnal rodent species, which will promote greater utility of these models in basic and translational research.

Equine Endothelial Cells Show Pro-Angiogenic Behaviours in Response to Fibroblast Growth Factor 2 but Not Vascular Endothelial Growth Factor A.

Understanding the factors which control endothelial cell (EC) function and angiogenesis is crucial for developing the horse as a disease model, but equine ECs remain poorly studied. In this study, we have optimised methods for the isolation and culture of equine aortic endothelial cells (EAoECs) and characterised their angiogenic functions in vitro. Mechanical dissociation, followed by magnetic purification using an anti-VE-cadherin antibody, resulted in EC-enriched cultures suitable for further study. Fibroblast growth factor 2 (FGF2) increased the EAoEC proliferation rate and stimulated scratch wound closure and tube formation by EAoECs on the extracellular matrix. Pharmacological inhibitors of FGF receptor 1 (FGFR1) (SU5402) or mitogen-activated protein kinase (MEK) (PD184352) blocked FGF2-induced extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and functional responses, suggesting that these are dependent on FGFR1/MEK-ERK signalling. In marked contrast, vascular endothelial growth factor-A (VEGF-A) had no effect on EAoEC proliferation, migration, or tubulogenesis and did not promote ERK1/2 phosphorylation, indicating a lack of sensitivity to this classical pro-angiogenic growth factor. Gene expression analysis showed that unlike human ECs, FGFR1 is expressed by EAoECs at a much higher level than both VEGF receptor (VEGFR)1 and VEGFR2. These results suggest a predominant role for FGF2 versus VEGF-A in controlling the angiogenic functions of equine ECs. Collectively, our novel data provide a sound basis for studying angiogenic processes in horses and lay the foundations for comparative studies of EC biology in horses versus humans.

Natural killer cell therapies.

Natural killer (NK) cells are lymphocytes of the innate immune system. A key feature of NK cells is their ability to recognize a wide range of cells in distress, particularly tumour cells and cells infected with viruses. They combine both direct effector functions against their cellular targets and participate in the generation, shaping and maintenance of a multicellular immune response. As our understanding has deepened, several therapeutic strategies focused on NK cells have been conceived and are currently in various stages of development, from preclinical investigations to clinical trials. Here we explore in detail the complexity of NK cell biology in humans and highlight the role of these cells in cancer immunity. We also analyse the harnessing of NK cell immunity through immune checkpoint inhibitors, NK cell engagers, and infusions of preactivated or genetically modified, autologous or allogeneic NK cell products.

How Old Are You in Chimpanzee Years?

It is fascinating to think about biology and behavior in humans and other animals. Chimpanzees are particularly interesting because they are humans’ closest living relatives. In this article, we will tell you about how humans grow up and age compared to chimpanzees, and how to calculate your age in chimpanzee years. Humans and chimpanzees are roughly similar in age after birth, but humans take a bit longer to mature and age. Also, some humans live much longer than chimpanzees do. This means many of us live long enough to interact with our grandchildren and also struggle with aging-related problems, but this is less the case for chimpanzees.

Establishment and characterization of six canine hepatocellular carcinoma cell lines.

Hepatocellular carcinoma (HCC) is the most common malignant liver tumor in dogs. Although surgical resection is a major treatment option for canine HCC, there are no distinct strategies for unresectable tumor subtypes or adjuvant chemotherapy for tumors with positive margins. We aimed to establish and characterize novel HCC cell lines from canine patients. The cellular morphology, general growth features and tumorigenicity of the established cell lines were evaluated. We also examined the sensitivity of the cell lines to multi-target tyrosine kinase inhibitors (TKIs). We established novel canine HCC cell lines from hepatic tumors and an additional kidney tumor of six canine patients. All cell lines showed colony forming and migratory ability. KU-cHCC-001 and KU-cHCC-001-Kidney, two cell lines exhibiting high epithelial-mesenchymal transition characteristics, showed tumorigenicity in xenografted mice. Toceranib, a veterinary TKI that targets vascular endothelial growth factor (VEGFR)/platelet-derived growth factor receptor (PDGFR)/c-kit, effectively inhibited the mitogen-activated protein kinase pathway and induced apoptosis. The established canine HCC cell lines showed greater sensitivity to toceranib than to sorafenib, a first-line treatment for human HCC targeting RAF/VEGFR/PDGFR. Sorafenib showed improved anti-tumor effects when co-treated with SCH772984, an extracellular signal-regulated kinase inhibitor. Our study suggests new therapeutic strategies for canine HCC, and these cell lines are valuable research materials for understanding HCC tumor biology in both humans and dogs.

Vishva Dixit Shares Insights on His Early Influences, Research Career, Key Findings, and What it Takes to Be Successful in Science.

In this interview, Vishva Dixit, MD, talks with Neil S. Greenspan, MD, PhD, senior editor of Pathogens and Immunity aboutwhat his career in science has revealed about biology in humans, but also what it has revealed about how to be successful in science. Dr. Dixit is a world-famous immunologist and biochemist who has made major contributions to the study of innate immunity in general and particularly to understanding inflammasome activation. He is vice president and senior fellow in physiological chemistry at Genentech.

A primary study on rat fetal development and brain-derived neurotrophic factor levels under the control of electromagnetic fields.

In previous researches, electromagnetic fields have been shown to adversely affect the behavior and biology of humans and animals; however, body growth and brain-derived neurotrophic factor levels were not evaluated. The original investigation aimed to examine whether Electromagnetic Fields (EMF) exposure had adverse effects on spatial learning and motor function in rats and if physical activity could diminish the damaging effects of EMF exposure. In this study, we measured anthropometric measurements and brain-derived neurotrophic factor (BDNF) levels in pregnant rats' offspring to determine if Wi-Fi EMF also affected their growth. These data we report for the first time in this publication. Twenty Albino-Wistar pregnant rats were divided randomly into EMF and control (CON) groups, and after delivery, 12 male fetuses were randomly selected. For assessing the body growth change of offspring beginning at delivery, then at 21 postnatal days, and finally at 56 post-natal days, the crown-rump length of the body was assessed using a digital caliper. Examining BDNF factor levels, an Enzyme-linked immunosorbent assay ELISA kit was taken. Bodyweight was recorded by digital scale. Outcomes of the anthropometric measurements demonstrated that EMF blocked body growth in rats exposed to EMF. The results of the BDNF test illustrated that the BDNF in the EMF liter group was remarkably decreased compared to the CON group. The results indicate that EMF exposure could affect BDNF levels and harm body growth in pregnant rats' offspring. The results suggest that EMF exposure could affect BDNF levels and impair body growth in pregnant rats' offspring.

Tobacco smoking and vascular biology and function: evidence from human studies

Tobacco cigarette smoking is among the most complex and least understood health risk factors. A deeper insight into the pathophysiological actions of smoking exposure is of special importance as smoking is a major cause of chronic non-communicable diseases, in particular of cardiovascular disease as well as risk factors such as atherosclerosis and arterial hypertension. It is well known that smoking exerts its negative effects on cardiovascular health through various interdependent pathophysiological actions including hemodynamic and autonomic alterations, oxidative stress, inflammation, endothelial dysfunction, thrombosis, and hyperlipidemia. Importantly, impaired vascular endothelial function is acknowledged as an early key event in the initiation and progression of smoking-induced atherosclerosis. Increasing evidence from human studies indicates that cigarette smoke exposure associates with a pathological state of the vascular endothelium mainly characterized by reduced vascular nitric oxide bioavailability due to increased vascular superoxide production. In the present overview, we provide compact evidence on the effects of tobacco cigarette smoke exposure on vascular biology and function in humans centered on main drivers of adverse cardiovascular effects including endothelial dysfunction, inflammation, and oxidative stress.

Editorial introductions.

Current Opinion in Nephrology and Hypertension was launched in 1992. It is part of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of nephrology and hypertension is divided into 12 sections that are each reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Section Editors for this issue. SECTION EDITORS Nancy J. BrownNancy J. BrownNancy J. Brown, MD is the Jean and David W. Wallace Dean of Yale School of Medicine, USA, and the C.N.H. Long Professor of Internal Medicine. Prior to assuming the role of dean at Yale in 2020, Dr Brown served for nine years as the Chair of the Department of Medicine at Vanderbilt University Medical Centre, Tennessee, USA, where she established herself as a national leader in the development of infrastructure to promote the career success of physician-scientists. She founded the Vanderbilt Master of Science in Clinical Investigation program in 2000, served as Associate Dean for Clinical and Translational Scientist Development at Vanderbilt from 2006 to 2010, and as Director of the Division of Clinical Pharmacology from 2009 to 2010. Dr Brown's NIH-funded research focuses on cardiovascular pharmacology and vascular biology in humans. She is particularly interested in understanding the mechanisms of anti-hypertensive and anti-diabetic drugs that are peptidase inhibitors, including the angiotensin-converting enzyme inhibitors, dipeptidyl peptidase 4 inhibitors, and neprilysin inhibitors. Her group has elucidated not only how these drugs decrease inflammation, enhance fibrinolysis (the breakdown of blood clots), and improve glucose homeostasis, but also how they interact with one another and sometimes cause side effects. This understanding leads to optimizing outcomes in patients with hypertension and diabetes. Dr Brown received her A. B. in Molecular Biophysics and Biochemistry from Yale and her MD from Harvard Medical School, USA. She completed her clinical training and a fellowship in clinical pharmacology at Vanderbilt University, Tennessee, USA. Dr Brown is a Fellow of the American Association for the Advancement of Science and a member of the American Society of Clinical Investigation, the Association of American Physicians, the National Academy of Medicine, and the American Academy of Arts and Sciences. She is a Master of the American College of Physicians and a fellow of the Royal College of Physicians. She has served on the National Advisory Research Resources Council and the National Heart, Lung, and Blood Advisory Council of the National Institutes of Health. Dr Brown currently serves on the visiting committee for Harvard Medical School and the External Advisory Board for the Harvard-MIT Health Sciences and Technology program. She is a member of the Scientific Advisory Board of Alnylam Pharmaceuticals. David S. GoldfarbDavid S. GoldfarbDavid S. Goldfarb, MD is Professor of Medicine and Physiology at New York University Grossman School of Medicine, USA. He is the Clinical Chief of the Nephrology Division at New York University Langone Health, and Chief of the Nephrology Section and Director of the Hemodialysis Unit at the New York VA Medical Center in Manhattan, USA. He serves as the Director of the Kidney Stone Prevention Programs at NYU Langone and at New York VA Medical Center, USA. He graduated from Yale College and the Yale School of Medicine, USA, and trained in Internal Medicine at New York VA and New York University, USA, and Nephrology at New York University, USA. He teaches first year renal physiology and renal pathophysiology at NYU, where he has been Teacher of the Year on 3 occasions. Dr Goldfarb is an internationally renowned expert in kidney stone prevention. He is a principal investigator of the Rare Kidney Stone Consortium. Dr Goldfarb is the former President of the NY Society of Nephrology and of the ROCK Society (Research on Calculus Kinetics). He was vice-chair of the American Urological Association's guideline panel, representing the American Society of Nephrology, on Medical Management of Kidney Stones. He is a co-inventor of Moonstone, the first high citrate beverage. He was selected as “Stone Crusher of the Year” in 2014 by the Oxalosis and Hyperoxaluria Foundation and “Nephrologist of the Year” in 2016 by the American Kidney Fund. He has had three calcium oxalate stones.

Abstracts of the 1st International Noor-Al Hayat Fertility (INAF) Conference, 5–7 November 2022

Reproduction, Fertility and Development is an international journal publishing original research , review and comment in the fields of reproduction and developmental biology in humans, domestic animals and wildlife

Human generation times across the past 250,000 years

The generation times of our recent ancestors can tell us about both the biology and social organization of prehistoric humans, placing human evolution on an absolute time scale. We present a method for predicting historical male and female generation times based on changes in the mutation spectrum. Our analyses of whole-genome data reveal an average generation time of 26.9 years across the past 250,000 years, with fathers consistently older (30.7 years) than mothers (23.2 years). Shifts in sex-averaged generation times have been driven primarily by changes to the age of paternity, although we report a substantial increase in female generation times in the recent past. We also find a large difference in generation times among populations, reaching back to a time when all humans occupied Africa.

Challenges in the evaluation of endothelial cell dysfunction: a statement from the European Society of Hypertension Working Group on Endothelin and Endothelial Factors.

Endothelial cell function is mediated by different mechanisms in different vascular beds. Moreover, in humans, endothelial cell dysfunction triggers and accelerates the progression of cardiovascular and chronic kidney diseases. Progression of such diseases can be in part mitigated by the control of cardiovascular risk factors and drugs targeting different systems, including endothelin receptor antagonists (ERAs), renin-angiotensin aldosterone antagonists and agents affecting glucose metabolism, all of which were shown to improve endothelial cell function. In recent years, the microRNAs, which are endogenous regulators of gene expression, have been identified as transmitters of information from endothelial cells to vascular smooth muscle cells, suggesting that they can entail tools to assess the endothelial cell dysfunction in arterial hypertension and target for pharmacologic intervention. This article critically reviews current challenges and limitations of available techniques for the invasive and noninvasive assessment of endothelial cell function, and also discusses therapeutic aspects as well as directions for future research in the areas of endothelial cell biology and pathophysiology in humans.

48 Semiquantitative and quantitative assessments of phospholipase C zeta 1 in stallion sperm

Reproduction, Fertility and Development is an international journal publishing original research , review and comment in the fields of reproduction and developmental biology in humans, domestic animals and wildlife

46 Fertilising ability of Arabian stallion sperm frozen with different cryoprotective agents by heterologous IVF

Reproduction, Fertility and Development is an international journal publishing original research , review and comment in the fields of reproduction and developmental biology in humans, domestic animals and wildlife

137 Incubation conditions to improve equine sperm

Reproduction, Fertility and Development is an international journal publishing original research , review and comment in the fields of reproduction and developmental biology in humans, domestic animals and wildlife

IETS 2023 Editors and Reviewers

Reproduction, Fertility and Development is an international journal publishing original research , review and comment in the fields of reproduction and developmental biology in humans, domestic animals and wildlife

15 Pregnancy loss until 120 days of Nellore clone pregnancy

Reproduction, Fertility and Development is an international journal publishing original research , review and comment in the fields of reproduction and developmental biology in humans, domestic animals and wildlife

147 Profiling boar semen quality through near-infrared spectroscopy and proteomic tools

Reproduction, Fertility and Development is an international journal publishing original research , review and comment in the fields of reproduction and developmental biology in humans, domestic animals and wildlife

177 Application of sexed semen during timed artificial insemination following oestrous synchronisation in dairy and beef cows for emerging farmers in South Africa

Reproduction, Fertility and Development is an international journal publishing original research , review and comment in the fields of reproduction and developmental biology in humans, domestic animals and wildlife

103 Co-culture of porcine

Reproduction, Fertility and Development is an international journal publishing original research , review and comment in the fields of reproduction and developmental biology in humans, domestic animals and wildlife