Discocytes Research Articles

Novel single-cell measurements suggest irreversibly sickled cells are neither dense nor dehydrated

In sickle cell anemia, deoxygenation causes erythrocytes to distort, while reoxygenation permits them to recover a normal biconcave disk shape. Irreversibly sickled cells (ISCs) remain distorted when reoxygenated and have been thought to have among the highest intracellular hemoglobin concentrations of the sickle red cell population and therefore the greatest vulnerability to vasoocclusion. Using a new optical method, which we describe, we have made precise measurements of the intracellular hemoglobin concentration, and intracellular O2 saturation, of ISCs, as well as oxygenated sickle cells with a normal biconcave disc shape, and cells with shapes distorted by the sickle fibers they contain. This method also provides good estimates of cell volumes, and hemoglobin per red cell. The concentration distribution of the ISCs is found to be similar to normal, discoid cells. Average ISC volumes exceed their discoid counterparts, with a much broader distribution, arguing against dehydration as their origin. The concentration distribution of the polymer-laden sickled cells is significantly higher in mean value, and their volume distributions indicate some dehydration. Previous assumptions about ISCs may have thus been colored by the presence of sickle cells that did contain polymer, and true ISCs may be much more benign than once thought, which underscores the importance of accurate measurement on individual cells. This method could be used to follow changes in individual cell properties under various specific perturbations, and where characterization by flow cytometry is infeasible.

A Review on Resealed Erythrocytes as a Novel Drug Delivery System

The most prevalent form of blood cell is the red blood cell. RBCs resemble biconcave discs with a 7.8 mm diameter and a thickness of about 2.2 mm. There are two ways that erythrocytes can be used as carriers: Targeting a specific tissue or organ, for continuous or extended medication release. For the delivery of medications, various kinds of mammalian erythrocytes have been employed. There are numerous techniques, including the hypo-osmotic method, the dilution method, the dialysis method, the press well method, the isotonic osmotic lyses, the electrical breakdown method, the endocytosis method, the membrane perturbation method, the normal transport method, and the lipid fusion method. After erythrocytes have been loaded with the therapeutic drug, carrier cells are subjected to physical, cellular, and biological examinations. Several invitro tests have shown the value of carrier RBCs. The RBC mediated microinjection that occurs most frequently invitro. Today, a wide range of uses for resealed erythrocytes as medication carriers, enzyme replacement treatment, etc. have been proposed.

EFFECTS OF ANTICOAGULANTS ON BLOOD CELLS MORPHOLOGY AND BIOCHEMISTRY

Blood is a particular type of connective tissue that majorly contains red blood cells (RBCs), white blood cells (WBCs), and platelets (Plts). Anticoagulants are used to preserve the fluidity of blood and retard morphological changes in blood cells. Anticoagulants like EDTA, heparin, sodium citrate, and CPDA-1 are used. However, these anticoagulants also have some disadvantages, summarized in this review. This chemical causes the lysis of many cells, including RBCs, and some of them, like EDTA, cause agglutination of platelets, which not only causes a decrease in platelet count but also causes a spurious increase in WBC count. These substances also alter the shapes of various cells present in blood. RBCs and platelets may become spherical from the normal biconcave disc and plate-like structures. Commonly used anticoagulants contribute to alterations of many hematological parameters, including hematocrit, hemoglobin concentration, and packed cell volume of RBCs. Certain chemicals used in anticoagulant solutions, such as potassium and sodium in EDTA solution, make the blood unsuitable for determining these electrolytes in the sample. They also induce many changes in the biochemical composition of the sample. The most affected biochemical changes are observed in 2,3-DPG, D-dimer concentration, blood gas estimation, and cytokine levels. As they contain different chemicals, they have varying pH, so they alter blood pH.

Electromagnetism - Properties of Erythrocytes

At the onset of blood flow, red blood cells (RBCs) align along the central plane of the vessels. In capillaries, RBCs transform from a biconcave disk into a parachute shape. As blood transitions from the arterial to the venous end, the hemoglobin in erythrocytes alters its magnetic susceptibility. Within approximately 0.6-0.8 seconds, oxygen is displaced from RBCs through diffusion. This study explores the fundamentals and interconnections of these processes.
 
 Blood samples from 35 different healthy individuals were analyzed. The research examined magnetic field induction in ferromagnetic toroids, formed by the alternative electric field with a square wave signal, and studied the AC in the secondary coil - a tube filled with blood. This study discusses the impact of RBC geometry and hemoglobin allosteric transitions on electric signal generation and its relevance to cellular metabolic activity in the body.
 
 The findings suggest that the AC field, originating from the heart's rotational dipole, can generate a magnetic field in RBCs, facilitating the allosteric transformations of hemoglobin. Hemoglobin's thermoelastic expansion and magnetostriction cause biconcave membrane oscillations at ultrasound frequencies. The resulting electroacoustic wave rotates charges at the cell's z-potential area, aids RBC migration into the flow plane, and enhances trans capillary diffusion of substances.
 
 An electroacoustic standing wave emerges between the oscillating RBCs, coinciding with the wavenumber of externally penetrating infrared light. The synergic influence on hemoglobin in capillaries causes the RBC membrane to create a temporally frequency-modulated wave, carrying resonance molecular frequencies. This wave regulates biochemical processes within and outside body cells.

A Comparative Study of Temporomandibular Joints in Adults with Definite Sleep Bruxism on Magnetic Resonance Imaging and Cone-Beam Computer Tomography Images.

The aim was to study the imaging characteristics of the temporomandibular joint (TMJ) of definite sleep bruxers through magnetic resonance imaging (MRI) and cone-beam computer tomography (CBCT). Nineteen definite sleep bruxers diagnosed by polysomnography and twenty asymptomatic non-bruxers matched by age, gender, and education level participated in this study. After obtaining MRI and CBCT images of all TMJs of the subjects, evaluation and measurement were conducted, respectively. The analyzed parameters included disc position, disc configuration, joint effusion (JE), joint space or condyle position, and condylar bony changes. Of the 38 joints in the study group, disc deformity and disc displacement of TMJs were both 57.9% when the mouth was closed, and 76.3% showed condylar bony changes, while when the mouth was open, 82% of all TMJs showed physiological biconcave discs. Comparison of joint space revealed that the anterior space was larger in the study group. There was no significant difference between the mild and the moderate to severe sleep bruxism subgroups in the changes of TMJ. The results demonstrated that a higher prevalence of disc deformity, disc displacement, JE, and condylar bony changes occurred in temporomandibular joints of sleep bruxers. These changes were not related to the severity of sleep bruxism.

Bionic design of a curvature-adjustable flexure hinge inspired by red blood cells

Recent years have witnessed an ever-increasing research interest in experience-driven and topology-optimization design of flexure hinges for use in compliant mechanisms. In this paper, we report the bionic design of a new notch flexure hinge with adjustable curvatures inspired by the biconcave disk morphology of red blood cells. The biconcave shape maintains red blood cells excellent deformability and surface properties that motivates the bio-inspired design by learning from nature. By imitating the biconcave shape of red blood cells using the quartic Bézier curve, the contour of a cluster of bio-inspired flexure hinges in the presence of positive and negative curvatures can be parametrically adjusted. The closed-form equations of compliance, precision and the maximum stress of the bio-inspired flexure hinge are derived based on Castigliano's second theorem and Timoshenko beam theory. Comparative studies verify the well precision and low stress of such a new flexure hinge. At last, an amplified piezoelectric actuator is designed with the bio-inspired flexure hinge as an application case. Also interestingly, adjustable curvatures of the presented bio-inspired flexure hinge make the simultaneous shape and parameter optimization effective.

Boundary integral simulations of boundary layers in linear viscoelastic flow

We investigate the disturbance flow generated by the oscillatory motion of a solid particle in linear viscoelastic (LVE) fluids. We begin with one-mode Maxwell fluids and then add Newtonian components so we can examine a spectrum of Weissenberg numbers and frequency parameters. We compute the fluid dynamics using an accurate boundary integral method with third-order accuracy in space. A unique feature of our method is that we can calculate the stress on the particle surface for a prescribed particle velocity profile. It is well known that a boundary layer develops along an infinite plate under oscillatory motion in a Newtonian fluid. However, when the flow becomes viscoelastic, the boundary layers are fundamentally different from those observed in Newtonian fluids. We perform a series of numerical simulations for the geometry of spheroids, dumbbells, and biconcave disks, and characterize streamlines around these particles and shear stress distributions on the surface of the particles. Specifically, two main results emerge from our investigations: (i) there is a sequence of eddies produced in LVE rather than a single one as in the Newtonian fluid case; and (ii) the eddies develop in the interior of the LVE and barely travel, while in the Newtonian fluid, the eddy is generated on the particle surface and propagates into the fluid. Our numerical findings go beyond the well-known dynamical regimes for Newtonian fluids and highlight the level of complexity of particle dynamics in viscoelastic fluids.

Magnetic resonance imaging and fractal analysis findings in temporomandibular joints with disk perforation

This study compared magnetic resonance imaging (MRI) findings and fractal dimension (FD) values in the temporomandibular joints (TMJs) of study patients with disk perforation vs control patients. Of 75 TMJs examined with MRI for characteristics of the disk and condyle, 45 were included in the study group and 30 in the control group. MRI findings and FD values were compared for significance of differences between the groups. The frequency of subclassifications was analyzed for differences between the two forms of disk configuration and grades of effusion. Mean FD values were analyzed for differences among subclassifications of MRI findings and between groups. Examination of MRI variables revealed that the study group had significantly greater frequencies of flattened disks, disk displacement, flattening and combined defects in condylar morphology, and grade 2 effusion (P=.001) Joints with perforated disks had a large percentage of normal disk-condyle relationships (73.3%). Significant differences were discovered between biconcave and flattened disk configuration in the frequencies of internal disk status and condylar morphology. FD values of all patients varied significantly among the subclassifications of disk configuration, internal disk status, and effusion. Mean FD values were significantly lower in the study group with perforated disks (1.07) compared with the control group (1.20, P=.001). MRI variables and FD can be useful in investigating intra-articular TMJ status.

Membrane skeleton hyperstability due to a novel alternatively spliced 4.1R can account for ellipsoidal camelid red cells with decreased deformability

The red blood cells (RBCs) of vertebrates have evolved into two basic shapes, with nucleated nonmammalian RBCs having a biconvex ellipsoidal shape and anuclear mammalian RBCs having a biconcave disk shape. In contrast, camelid RBCs are flat ellipsoids with reduced membrane deformability, suggesting altered membrane skeletal organization. However, the mechanisms responsible for their elliptocytic shape and reduced deformability have not been determined. In the present study, we showed that in alpaca RBCs, protein 4.1R, a major component of the membrane skeleton, contains an alternatively spliced exon 14-derived cassette (e14) not observed in the highly conserved 80 kDa 4.1R of other highly deformable biconcave mammalian RBCs. The inclusion of this exon, along with the preceding unordered proline- and glutamic acid-rich peptide (PE), results in a larger and unique 90 kDa camelid 4.1R. Human 4.1R containing e14 and PE, but not PE alone, showed markedly increased ability to form a spectrin-actin-4.1R ternary complex in viscosity assays. A similar facilitated ternary complex was formed by human 4.1R possessing a duplication of the spectrin-actin-binding domain, one of the mutations known to cause human hereditary elliptocytosis. The e14- and PE-containing mutant also exhibited an increased binding affinity to β-spectrin compared with wild-type 4.1R. Taken together, these findings indicate that 4.1R protein with the e14 cassette results in the formation and maintenance of a hyperstable membrane skeleton, resulting in rigid red ellipsoidal cells in camelid species, and suggest that membrane structure is evolutionarily regulated by alternative splicing of exons in the 4.1R gene.

Peripheral blood cells of native pig (Zovawk) of Mizoram, India: Light and scanning electron microscopy analysis

The literature on the blood cells of Zovawk pigs is scanty; thus, this study was designed to elaborate the light microscopy (LM) and scanning electron microscopy (SEM) characterization of blood cells of Zovawk pigs by LM and SEM. Twelve different blood samples were aseptically obtained from adult healthy Zovawk pigs, irrespective of sex. To determine the cytomorphological and cytochemical structures of the many produced constituents of blood, blood smears were stained with various stains. The blood samples were treated with various substrates for cytoenzymatic research, and the alterations were noted. A 1000× magnification Olympus Trinocular Research microscope was used to examine the smears. The blood samples were prepared for electron microscopy according to the standard procedure. The prepared samples were delivered to the Sophisticated Analytical Instrumentation Facility (SAIF), All India Institute of Medical Sciences (AIIMS), New Delhi, for SEM imaging. On LM, pig erythrocytes were spherical and nonnucleated. The cytoplasm of the neutrophils was spherical and included cytoplasmic granules. The eosinophils had prominent cytoplasmic granules and were round. Basophils were infrequently present and had cytoplasmic granules that were clear blue. The sizes of small, medium and large lymphocytes were noted. The monocytes were oval or circular. The platelets ranged in form from asymmetric to round. The blood samples were stained for cytochemical analyses using acid ferrocyanide stain for iron, Sudan black blue stain for lipids, toluidine blue stain for mucopolysaccharides, and periodic acid Schiff's stain for glycogen. The cytoenzymatic characteristics were evaluated and compared with substrates treated with acid phosphatase, alkaline phosphatase, peroxidase, arylsulfatase, cytochrome oxidase, beta-glucuronidase, and succinate dehydrogenase. Erythrocytes appeared as biconcave disks under SEM. Two forms of leukocytes were observed, having a rough and pointed cell surface like a flower. It can be concluded that the LM and SEM morphology of blood cells of Zovawk pigs resembled other domestic animals, however, few differences were observed among the discussed animals.

Ray Optics Model for Optical Trapping of Biconcave Red Blood Cells.

Red blood cells (RBCs) or erythrocytes are essential for oxygenating the peripherical tissue in the human body. Impairment of their physical properties may lead to severe diseases. Optical tweezers have in experiments been shown to be a powerful tool for assessing the biochemical and biophysical properties of RBCs. Despite this success there has been little theoretical work investigating of the stability of erythrocytes in optical tweezers. In this paper we report a numerical study of the trapping of RBCs in the healthy, native biconcave disk conformation in optical tweezers using the ray optics approximation. We study trapping using both single- and dual-beam optical tweezers and show that the complex biconcave shape of the RBC is a significant factor in determining the optical forces and torques on the cell, and ultimately the equilibrium configuration of the RBC within the trap. We also numerically demonstrate how the addition of a third or even fourth trapping laser beam can be used to control the cell orientation in the optical trap. The present investigation sheds light on the trapping mechanism of healthy erythrocytes and can be exploited by experimentalist to envisage new experiments.

Dynamic Sickling Assay: Using Enzymatically Induced Hypoxia to Assess Real-Time Sickling Scalable from Large Erythrocyte Populations to Individual Cells

Background: There is a pressing need for assays to assess both patient condition and to monitor the progress of Sickle Cell Disease (SCD) therapies. It would be beneficial for an assay to allow assessment of oxygen dissociation, hemoglobin polymerization and Red Blood Cell (RBc) sickling under both equilibrium (mimicking longer-term effects) and non-equilibrium (simulating in-vivo process) conditions. Also desirable is the CLIA-waived system suitable for use in clinical trials and ultimately for clinical management of patients on SCD therapies including those those targeting Hb oxygen affinity. Our proposed work introduces an RBC hypoxia-induced sickling assay as a clinical tool to assess SCD patient condition and to assist in development, monitoring, and optimization of SCD therapies. Methods: The system uses an enzymatic oxygen scrubbing system allowing for a wide range of deoxygenation rates and final hypoxia severity. Diluted blood samples were supplemented with Protocatechuic acid (PCA) and then with Protocatechuate 3,4-Dioxygenase (PCD) enzyme inducing hypoxia at a predetermined rate. The sample was injected into an anaerobic microfluidic chamber with the resulting Red Blood Cell (RBC) morphological changes observed through time-lapsed photography. Image analysis allows for identification and quantification of sickled RBC linked to different polymerization scenarios/mechanisms. An oxygen probe was used to track the rate of medium deoxygenation. Sickling profiles were constructed to represent a percent of sickled RBC in a total cell population measured every two seconds after the enzymatic reaction is initiated. Profiles were assessed though i) percent sickling at normoxia, ii) morphological Point of Sickling (mPoS) and iii) time delay of sickling both measured at 5% increase in sickling over the normoxia sickling baseline, iv rate of sickling, v) size of the sickling fraction and vi) Area under the Curve (AUC). The last four parameters are measured for each sickling fraction if more than one such is present. Results: In control experiments PCA/PCD system was shown to allow reliable and reproducible sample deoxygenation currently enabled in a range from seconds to hours. Comprehensive multidimensional profiles were constructed presenting fraction of sickled RBC as a function of a) time from enzymatic reaction initiation, and b) one or more of rate of oxygen consumption, end of reaction hypoxia level, or oxygen tension in the medium. Such profiling allows for fast optimization of assay parameters to target assay conditions most suitable for detection of desired effects.Significant changes in sickling profiles, with marked delay in sickling, were observed upon treatment of RBC with hemoglobin-modifying drugs like voxelotor.Sickling profiles of Sickle Trait (SCT) patients showed significant delay in sickling compared to SS-type SCD patients. The method shows the potential to differentiate SCT patients based on the risk of adverse conditions to occur due to the patient's trait status.By stopping the flow, the system allows tracking of morphological status of individual cells over the full course of medium deoxygenation. Individual cells show pronounced differences in their propensity to sickle, potentially correlated to individual cell Hb F content. Change in morphology of sickling cells from biconcave disk to crescent and then to holly leaf and granular forms had been observed upon progressively decreasing medium oxygen tension.RBC microparticle formation can be observed and tracked over time as an additional metric of erythrocyte response to developing hypoxia Conclusions: By using enzymatically induced hypoxia in a microfluidic environment, presented system allows comprehensive analysis of RBC sickling dynamics in a wide range of deoxygenation rates and conditions. It would find utility in SCD therapy development by offering a robust and high throughput method for assessing critical RBC response to therapies. With no need for cumbersome gas cylinders and low training requirements, a stand-alone system with single use disposable cartridges would also have utility in clinical trials both in the US and abroad, due to simplicity of use suitable for developing countries with limited infrastructure. When validated, the system can be adapted for Point of Care use either as complementary to other blood tests or in an independent monitoring mode.

DISEASE DETECTION BY ABNORMALITIES IN ERYTHROCYTE USING IMAGE PROCESSING

Erythrocytes, also known as RBCs, are biconcave disks having diameter of 7 to 8 μm. The size, shape and number of RBCs can affect person's health. In laboratories the analysis of blood cells is carried out by human observations. The classical manual methods are time consuming and not precise. This paper gives an algorithm for automatic classication of microscopic blood smear images as normal (normocytic) or abnormal (Microcytic) based on Red blood cells. Different image processing techniques are used for feature extractions and classications. Slides are prepared and primed to sense the count of “parasitemia” beneath BX53 Olympus microscope. Images obtained by placing the high-denition 1024x1360 resolution camera. For dataset, 40 samples from each normal person and abnormal person were collected. Various image processing techniques such as DWT, Pixel count ratio and histogram for feature extraction and LDC, QDC are used for classication. LDC classier gave 91 % and QDC classier gave 89 % accuracy for the feature vector of pixel count ratio of binary image

The Effect of Disc Displacement on Temporomandibular Joint Morphology in Patients with Disc Displacement

Objective: To examine the morphological properties of temporomandibular joint structures by magnetic resonance imaging (MRI) on patients with and without disc displacement (DD). Methods: Thirty-eight patients with disc displacement and 13 patients without disc displacement were included. Age, gender, and clinical findings such as pain, joint sounds of patients were recorded. The patients were classified as anterior disc displacement with reduction (ADDWR) group, anterior disc displacement without reduction (ADDWoR) group, and control group on MRI. Disc morphology was categorized as biconcave, hemiconvex, biconvex, biplanar, or folded. Condyle morphology was characterized as convex, angled, flat, or rounded. Articular eminence morphology was classified as sigmoid, flattened, box, or deformed. A one-way analysis of variance was used to establish the differences between the values. Results: Biconcave disc and sigmoid articular eminence were the greatest incidence both in ADDWR and control group, folded disc and deformed articular eminence were the most in ADDWoR group. The most frequent types of condyle in DD and control group were flattened and convex, respectively. Statistical difference was found between pain and articular eminence morphology (p=0.02). The statistical difference regarding articular disc (p=0.001) and articular eminence morphology (p=0.02) was determined among the groups. A significant difference between condyle morphology and the presence of self-reported bruxism was detected (p= 0.03). Conclusion: The morphological characteristics of the articular disc and articular eminence are related to DD. It can be said that the morphological changes of temporomandibular joint structures point to DD.

Observations on the cytomorphology and ultrastructure of the peripheral blood cells of native cattle (Zobawng) of Mizoram, India.

This study aims to characterize the cytomorphology and ultrastructure of blood cells of native cattle of Mizoram. Twelve numbers of blood samples (10ml) were collected from the Zobawng cattle, irrespective of sex. Blood smears were prepared and stained with different stains for cytomorphological study. The standard protocol has been followed for preparing blood samples for electron microscopy. Under a light microscope, erythrocytes of cattle were non-nucleated and round. The neutrophils were round, and the cytoplasm contained cytoplasmic granules. The eosinophils were rounded in outline with distinct cytoplasmic granules. The presence of basophils was infrequent with distinct blue color cytoplasmic granules. Small, medium, and large types of lymphocytes were recorded. The monocytes were round to oval in outline. Platelets were irregular to round. The reticulocytes were recorded occasionally, like small blue thin rods or granules. The cytoplasm and nucleus of granulocytes fluoresced greenish-yellow and red, respectively, with supravital stain. Under scanning electron microscopy (SEM), the erythrocytes appeared as biconcave discs. Different leukocytes were observed with their finger-like, plate-like, and narrow cell processes on their surface. Platelets were irregular structures. In transmission electron microscopy (TEM), the erythrocytes appeared anucleated biconcave elongated, neutrophils were roughly rounded with small cytoplasmic processes, and eosinophils were roughly circular with small cytoplasmic processes, the basophils were roughly circular with oval to elongated cytoplasmic granules, lymphocytes were roughly circular with centrally placed well-marked oval indented nucleus and some cytoplasmic processes, monocytes appeared spherical with long thick cytoplasmic processes and the non-nucleated platelets appeared roughly round to elongated. RESEARCH HIGHLIGHTS: Blood tests are a very good tool for determining animal health and diagnosing hematological illnesses. This study showed the cytomorphological and ultrastructural features of the blood cells of native cattle (Zobawng) of Mizoram state of India. The cytomorphological studies revealed that the morphological features of the blood cells of Zobawng cattle resembled to other domestic and wild animals, however, there were some differences in the cellular components. Nuclear DNA appeared orthochromatically greenish-yellow, but cytoplasmic RNA was observed to be metachromatically red under the fluorescence microscope. scanning electron microscopic (SEM) and transmission electron microscopic (TEM) results revealed that the ultrastructural features of the blood cells of Zobawng cattle contain certain cellular morphological differences as compared to the other domestic and wild animals.

Mem3DG: Modeling membrane mechanochemical dynamics in 3D using discrete differential geometry

Biomembranes adopt varying morphologies that are vital to cellular functions. Many studies use computational modeling to understand how various mechanochemical factors contribute to membrane shape transformations. Compared with approximation-based methods (e.g., finite element method [FEM]), the class of discrete mesh models offers greater flexibility to simulate complex physics and shapes in three dimensions; its formulation produces an efficient algorithm while maintaining coordinate-free geometric descriptions. However, ambiguities in geometric definitions in the discrete context have led to a lack of consensus on which discrete mesh model is theoretically and numerically optimal; a bijective relationship between the terms contributing to both the energy and forces from the discrete and smooth geometric theories remains to be established. We address this and present an extensible framework, Mem3DG, for modeling 3D mechanochemical dynamics of membranes based on discrete differential geometry (DDG) on triangulated meshes. The formalism of DDG resolves the inconsistency and provides a unifying perspective on how to relate the smooth and discrete energy and forces. To demonstrate, Mem3DG is used to model a sequence of examples with increasing mechanochemical complexity: recovering classical shape transformations such as 1) biconcave disk, dumbbell, and unduloid; and 2) spherical bud on spherical, flat-patch membrane; investigating how the coupling of membrane mechanics with protein mobility jointly affects phase and shape transformation. As high-resolution 3D imaging of membrane ultrastructure becomes more readily available, we envision Mem3DG to be applied as an end-to-end tool to simulate realistic cell geometry under user-specified mechanochemical conditions.

Red Blood Cell Function and Disorders of Iron Metabolism

The red blood cell, or erythrocyte, is an anucleate biconcave disk, approximately 7 µm in diameter. The principal function of the red blood cell is to exchange carbon dioxide for oxygen while in the pulmonary circulation, exchange that oxygen for carbon dioxide in the peripheral tissue, and carry that carbon dioxide back to the lungs. The physicochemical composition of the red cell is aligned to optimize that function. The state of tissue oxygenation, in turn, regulates the production of red cells. This review covers red blood cell function, iron metabolism, iron deficiency, iron overload, and primary iron overload. Figures show a model of the hemoglobin molecule showing the relative alignment of the α chains and β chains; the normal oxygen-hemoglobin dissociation curve shifted by changes in temperature, pH, and the intracellular concentration of 2,3-diphosphoglycerate; body iron supply and storage; regulation of hepcidin expression and its role in disease; blood smear from a patient with iron deficiency; and mechanisms contributing to iron overload in iron-loading anemias. Tables list laboratory results associated with decreased iron balance, causes of iron deficiency, oral iron replacement therapy, parenteral iron replacement therapy, primary iron overload syndromes, secondary iron overload syndromes, laboratory results associated with increased iron stores, and other rare disorders of iron overload. This review contains 6 figures, 20 tables, and 111 references Keywords: Red blood cell, iron deficiency anemia, iron overload, hemochromatosis, hemoglobin, iron balance

Red Blood Cell Function and Disorders of Iron Metabolism

The red blood cell, or erythrocyte, is an anucleate biconcave disk, approximately 7 µm in diameter. The principal function of the red blood cell is to exchange carbon dioxide for oxygen while in the pulmonary circulation, exchange that oxygen for carbon dioxide in the peripheral tissue, and carry that carbon dioxide back to the lungs. The physicochemical composition of the red cell is aligned to optimize that function. The state of tissue oxygenation, in turn, regulates the production of red cells. This review covers red blood cell function, iron metabolism, iron deficiency, iron overload, and primary iron overload. Figures show a model of the hemoglobin molecule showing the relative alignment of the α chains and β chains; the normal oxygen-hemoglobin dissociation curve shifted by changes in temperature, pH, and the intracellular concentration of 2,3-diphosphoglycerate; body iron supply and storage; regulation of hepcidin expression and its role in disease; blood smear from a patient with iron deficiency; and mechanisms contributing to iron overload in iron-loading anemias. Tables list laboratory results associated with decreased iron balance, causes of iron deficiency, oral iron replacement therapy, parenteral iron replacement therapy, primary iron overload syndromes, secondary iron overload syndromes, laboratory results associated with increased iron stores, and other rare disorders of iron overload. This review contains 6 figures, 20 tables, and 111 references Keywords: Red blood cell, iron deficiency anemia, iron overload, hemochromatosis, hemoglobin, iron balance

Mem3DG: modeling membrane mechanochemical dynamics in 3D using discrete differential geometry

Biomembranes adopt varying morphologies that are vital to cellular functions. Many studies use computational modeling to understand how various mechanochemical factors contribute to membrane shape transformations. Compared to approximation-based methods (e.g., finite element method), the class of discrete mesh models offers greater flexibility to simulate complex physics and shapes in three dimensions; its formulation produces an efficient algorithm while maintaining coordinate-free geometric descriptions. However, ambiguities in geometric definitions in the discrete context have led to a lack of consensus on which discrete mesh model is theoretically and numerically optimal; a bijective relationship between the terms contributing to both the energy and forces from the discrete and smooth geometric theories remains to be established. We address this and present an extensible framework, $\texttt{Mem3DG}$, for modeling 3D mechanochemical dynamics of membranes based on Discrete Differential Geometry (DDG) on triangulated meshes. The formalism of DDG resolves the inconsistency and provides a unifying perspective on how to relate the smooth and discrete energy and forces. To demonstrate, $\texttt{Mem3DG}$ is used to model a sequence of examples with increasing mechanochemical complexity: recovering classical shape transformations such as 1) biconcave disk, dumbbell, and unduloid and 2) spherical bud on spherical, flat-patch membrane; investigating how the coupling of membrane mechanics with protein mobility jointly affects phase and shape transformation. As high-resolution 3D imaging of membrane ultrastructure becomes more readily available, we envision Mem3DG to be applied as an end-to-end tool to simulate realistic cell geometry under user-specified mechanochemical conditions.

An Evaluation of Morphological Changes and Deformability of Suspended Red Blood Cells Prepared Using Whole Blood with Different Hemoglobin Levels of Tibetans

Background: The hypoxic environment stimulates the human body to increase the levels of hemoglobin (HGB) and hematocrit and the number of red blood cells. Such enhancements have individual differences, leading to a wide range of HGB in Tibetans’ whole blood (WB). Study Design: WB of male Tibetans was divided into 3 groups according to different HGB (i.e., A: >120 but ≤185 g/L, B: >185 but ≤210 g/L, and C: >210 g/L). Suspended red blood cells (SRBC) processed by collected WB and stored in standard conditions were examined aseptically on days 1, 14, 21, and 35 after storage. The routine biochemical indexes, deformability, cell morphology, and membrane proteins were tested. Results: Mean corpuscular volume, adenosine triphosphate, pH, and deformability were not different in group A vs. those in storage (p > 0.05). The increased rate of irreversible morphology of red blood cells was different among the 3 groups, but there was no difference in the percentage of red blood cells with an irreversible morphology after 35 days of storage. Group C performed better in terms of osmotic fragility and showed a lower rigid index than group A. Furthermore, SDS-PAGE revealed similar cross-linking degrees of cell membrane protein but the band 3 protein of group C seemed to experience weaker clustering than that of group A as detected by Western Blot analysis after 35 days of storage. Conclusions: There was no difference in deformability or morphological changes in the 3 groups over the 35 days of storage. High HGB levels of plateau SRBC did not accelerate the RBC change from a biconcave disc into a spherical shape and it did not cause a reduction in deformability during 35 days of preservation in bank conditions.