Cell and Molecular Biology Research Papers (original) (raw)
Research shows that cellular and mitochondrial (ΔΨm) membrane potentials are strong indicators of cellular physiology. In this paper we review further research suggesting that microcurrent frequencies can positively influence both these... more
Research shows that cellular and mitochondrial (ΔΨm) membrane potentials are strong indicators of cellular physiology. In this paper we review further research suggesting that microcurrent frequencies can positively influence both these membrane potentials. The goal of this research is to show how microcurrent might stimulate physiological potentials in order to support a healthy function of bioelectric fields of cells and organs. In the second part of the article, a study to examine the effects of microcurrent application on the body's response to electric measurements is presented, in particular to a change in voltage-current lag known as a phase angle. The test involved measuring bioimpedance of a person before and after a 30-minute application with microcurrent stimulation. Fifteen healthy subjects were examined through impedance measurements taken on one arm. The results showed a consistent increase in phase angle directly after the stimulation, confirming a widely accepted indication of health improvement on a cellular level. These results are encouraging and justify further investigations on the effect of microcurrent stimulation on the human body in relation to general cellular health and regenerative functions.
A cross-sectional study was conducted at Gumbo slaughter slab in Juba, Central Equatoria State (CES) in South Sudan, between October and December 2015, to determine the prevalence of cystic echinococcosis (CE) and to estimate the direct... more
A cross-sectional study was conducted at Gumbo slaughter slab in Juba, Central Equatoria
State (CES) in South Sudan, between October and December 2015, to determine the prevalence of cystic echinococcosis (CE) and to estimate the direct economic losses associated with condemnation of infected organs in slaughtered goats. A thorough postmortem examination was conducted on carcasses of a total of 1126 goats selected by systematic random sampling for detection of CE in
the lungs, liver, heart, kidneys, and the spleen. Moreover, CE-related direct financial losses were
estimated by using a standardized formula. The overall prevalence of CE was found to be 281 (24.9%,
95% CI 22.5–27.6). Furthermore, old age (OR = 2.61, p value < 0.001), Mubende breed (OR = 2.97,
p value < 0.001), and Ugandan geographical origin (OR = 2.97, p value < 0.001) were associated
with higher prevalence of CE. The lungs were the most affected organ with a prevalence of 55.2%
followed by liver (44.1%), and the spleen (0.07%). A direct CE-related monetary loss of 78,820 South
Sudanese Pounds (SSP) per year was estimated. This loss is equivalent to USD 43,788. In conclusion, CE is considerably prevalent and is associated with significant direct financial losses among goats slaughtered at Gumbo slaughter slab in Juba, CES, South Sudan.
Autophagy is a catabolic process where cytosolic cellular components are delivered to the lysosome for degradation. Recent studies have indicated the existence of specific receptors, such as p62, which link ubiquitinated targets to... more
Autophagy is a catabolic process where cytosolic cellular components are delivered to the lysosome for degradation. Recent studies have indicated the existence of specific receptors, such as p62, which link ubiquitinated targets to autophagosomal degradation pathways. Here we show that NBR1 (neighbor of BRCA1 gene 1) is an autophagy receptor containing LC3-and ubiquitin (Ub)-binding domains. NBR1 is recruited to Ub-positive protein aggregates and degraded by autophagy depending on an LC3-interacting region (LIR) and LC3 family modifiers. Although NBR1 and p62 interact and form oligomers, they can function independently, as shown by autophagosomal clearance of NBR1 in p62-deficient cells. NBR1 was localized to Ub-positive inclusions in patients with liver dysfunction, and depletion of NBR1 abolished the formation of Ub-positive p62 bodies upon puromycin treatment of cells. We propose that NBR1 and p62 act as receptors for selective autophagosomal degradation of ubiquitinated targets.
onset of anaphase, cohesion has to be dissolved. In and Jan-Michael Peters 1,5 budding yeast, this event depends on the proteolytic 1 Research Institute of Molecular Pathology (IMP) cleavage of the cohesin subunit Scc1/Mcd1 (Uhlmann Dr.... more
onset of anaphase, cohesion has to be dissolved. In and Jan-Michael Peters 1,5 budding yeast, this event depends on the proteolytic 1 Research Institute of Molecular Pathology (IMP) cleavage of the cohesin subunit Scc1/Mcd1 (Uhlmann Dr. Bohr-Gasse 7 et al., 1999) and coincides with the complete removal A-1030 Vienna of cohesin from chromosomes (Michaelis et al., 1997). Austria The removal of cohesin from chromosomes may there-2 Department of Biochemistry and Molecular Genetics fore directly dissolve cohesion between sisters. University of Virginia Medical School Cleavage of yeast cohesin is catalyzed by an endopep-Charlottesville, Virginia 22908 tidase called separase (Uhlmann et al., 1999; Uhlmann 3 Max-Planck Institute for Biochemistry et al., 2000). Separase is activated at the metaphase-Department of Cell Biology anaphase transition by ubiquitin-dependent degrada-Am Klopferspitz 18a tion of the separase inhibitor securin (Cohen-Fix et al., D-82152 Martinsried 1996; Ciosk et al., 1998; Uhlmann et al., 1999). This 4 Boehringer Ingelheim Pharma KG reaction is initiated by the anaphase-promoting com-Department of Metabolic Research plex/cyclosome (APC), a ubiquitin ligase that targets D-88397 Biberach mitotic proteins for destruction by the 26S proteasome Germany (reviewed in Peters, 1999). Cohesin cleavage is further activated by the Polo-like kinase Cdc5, which phosphorylates Scc1/Mcd1 and thereby enhances its cleavability Summary (Alexandru et al., 2001). Most if not all of yeast cohesin is removed from chromosomes at the onset of anaphase The separation of sister chromatids in anaphase deby separase-dependent cleavage. Newly synthesized pends on the dissociation of cohesin from chromocohesin can rebind to chromatin only at the subsequent somes. In vertebrates, some cohesin is removed from G1-S transition, presumably once separase has been chromosomes at the onset of anaphase by proteolytic inactivated by securin reaccumulation (Uhlmann et al., cleavage. In contrast, the bulk of cohesin is removed 1999). from chromosomes already in prophase and prometa-In other eukaryotes, the situation is very different. In phase by an unknown mechanism that does not invertebrates, two different pathways dissociate cohesin volve cohesin cleavage. We show that Polo-like kinase from mitotic chromosomes (Waizenegger et al., 2000).
World Health organization has identified the domestic violence as a matter directly related to public health, the most of such cases reaches to the severity during the period of pregnancy. Domestic violence may originate in the home; it... more
World Health organization has identified the domestic violence as a matter directly related to public health, the most of such cases reaches to the severity during the period of pregnancy. Domestic violence may originate in the home; it can spill over into the world of work. All females, males and children might be its victims. It includes a combination of violence i.e., wife battering, psychology torture, sexual violence and both simultaneous physical and sexual violence. Other type of violence may lead to anxiety and depression in the females. Studies show that living with domestic violence can cause physical and emotional harm to fry and young people in the way of life like ongoing anxiety and impression, emotional suffering etc. Male casualties of abusive behavior at home once in a while report their episodes of misuse. Domestic violence directly affects the behavior health and emotions of victim and violator that will ultimately affect relations with relatives, their workplace, their neighbors and their fellows.
BACKGROUND: In spite of its indusrial usefulness and varied daily uses, lead (Pb) pollution is a widespread ecological problem that faces the humans in the 21th century. Pb was found to produces a wide range of toxic effects including... more
BACKGROUND:
In spite of its indusrial usefulness and varied daily uses, lead (Pb) pollution is a widespread ecological problem that faces the humans in the 21th century. Pb was found to produces a wide range of toxic effects including neurotoxicity especially to the developing and young offspring. Recently, the utilization of herbal plants has received a significant attention where there has been rising awareness in their therapeutic use; among these is the garlic.
AIM OF THE WORK:
In light of the above, the current study is designed experimentally in female pregnant rats in order to investigate the beneficial role of garlic extract in the protection from the maternal and fetal cerebellar damage that produced by administration of different doses of Pb during pregnancy.
MATERIALS AND METHODS:
Positively pregnant female rats were divided into five groups; one control group, two Pb-treated groups (exposed to 160 and 320 mg/kg b.wt. of Pb, respectively) and two groups treated with both Pb and garlic (exposed to Pb as previous groups together with 250 mg/ kg b.wt. /day of garlic extract). Treatments started from day 1 till day 20 of pregnancy, where the mother rats of different experimental groups were sacrified to obtain the fetuses. Pb level in the maternal nd fetal blood and cerebellum was estimated by spectrophotometry. Specimens of the cerebellum of different mother and fetal groups were processed to histological and immunohistochemical staining for microscopic examination.
RESULTS:
The results showed that administration of Pb to pregnant rats resulted in a dose-dependent toxicity for both mothers and fetuses in the form of decrease of maternal weight gain, placental and fetal weights, brain weight and diminished fetal growth parameters, which were prominent in rat's group treated with larger dose of Pb. In Pb-treated rats, Pb level in blood and cerebellum was high when compared to the control. The histopathological examination of the cerebellum of treated dams and fetuses showed marked alterations mainly in the form of Purkinje cell degeneration and lack of deveopmet of fetal cerebellum. Co-treatment of garlic extract along with Pb resulted in a significant decrease in Pb levels as compared with those treated with Pb alone with improvement of the histopathological changes.
CONCLUSIONS:
This study was useful in evaluating the hazardous effects of uncontrolled use of Pb in general and in assessing the developmental and neurotoxicity of fetuses due to exposure during pregnancy in particular. Co-administration of garlic has beneficial effects in amelioration of Pb-induced neurotoxicity and reversing the histopathological changes of the cerebellum of mother rats and fetuses.
KEYWORDS:
garlic; glial fibrillary acidic protein; lead; purkinje cells
All the objecte are rod blood-wrpuscles done to one and the t*ime ficaie, whieli is at the foot of the drawing. The whole length m* the eeak represents 7 ± π of an English inch, and each one of it« ten divisions j^'-j^ of an inch, as... more
All the objecte are rod blood-wrpuscles done to one and the t*ime ficaie, whieli is at the foot of the drawing. The whole length m* the eeak represents 7 ± π of an English inch, and each one of it« ten divisions j^'-j^ of an inch, as described at page 475. Only corpuscles of the average sizes and quite regular shapes are given; and they are all raagniilod to the same, or nearly the same, degree--to wit, about 800 diameters. VERTEBRATA Homo. l. ; Corpuscle lying flat. 2. The same on edge. 3. Membranous base of the same, after removal by water of the co*ouring-matter.
The phosphorylation of ribosomal protein S6 (rpS6) has been described for the first time about four decades ago. Since then, numerous studies have shown that this modification occurs in response to a wide variety of stimuli on five... more
The phosphorylation of ribosomal protein S6 (rpS6) has been described for the first time about four decades ago. Since then, numerous studies have shown that this modification occurs in response to a wide variety of stimuli on five evolutionarily conserved serine residues. However, despite a large body of information on the respective kinases and the signal transduction pathways, the physiological role of rpS6 phosphorylation remained obscure until genetic manipulations were applied in both yeast and mammals in an attempt to block this modification. Thus, studies based on both mice and cultured cells subjected to disruption of the genes encoding rpS6 and the respective kinases, as well as the substitution of the phosphorylatable serine residues in rpS6, have laid the ground for the elucidation of the multiple roles of this protein and its posttranslational modification. This review focuses primarily on newly identified kinases that phosphorylate rpS6, pathways that transduce various signals into rpS6 phosphorylation, and the recently established physiological functions of this modification. It should be noted, however, that despite the significant progress made in the last decade, the molecular mechanism(s) underlying the diverse effects of rpS6 phosphorylation on cellular and organismal physiology are still poorly understood.
Phenylhydrazine (PHZ), a potent chemical causes toxicity on various tissues at various levels. Administration of phenylhydrazine mainly causes haematotoxicity which leads to the haemolytic anemia. In mammals PHZ induced anemia increased... more
Phenylhydrazine (PHZ), a potent chemical causes toxicity on various tissues at various levels. Administration of phenylhydrazine mainly causes haematotoxicity which leads to the haemolytic anemia. In mammals PHZ induced anemia increased the iron absorption in spleen, liver and duodenum and finally iron metabolism was altered. Local demand and supply of Fe would increase erythropoeitic activity of the spleen so the size of spleen was increased that create the splenomegaly. PHZ induced anemia activate immune response which triggers phagocytosis in the spleen and liver. Apart from this administration of PHZ interfere the binding of erythropoietin (EPO) with erythropoietin receptors (EPOR) so that JAK-STAT would be affected.PHZ also showed genotoxic effect by creating single strand DNA damage.
Ayu Tri Agustin
Mekanisme Regulasi Homeostatis Glukosa Darah dalam Tubuh
In time past, to date combating against diseases and fatal disorders (of known or idiopathic cause) is a major effort among the human race. The emergence of several, novel and pathogenic viral infections have posed a great threat to... more
In time past, to date combating against diseases and fatal disorders (of known or idiopathic cause) is a major effort among the human race. The emergence of several, novel and pathogenic viral infections have posed a great threat to humanity and could wipe us out of existence if there are no counter measures. Among the increasing number of pathogenic viruses in this past decade, the advent of the recent imperial SARS-CoV-2 coronavirus type cannot be underestimated as it is not just a malady endemic to a nation, but have also triggered an emergency of public health across the globe. SARS-CoV-2 a memorial of the initial Severe Acute Respiratory Syndrome (SARS) reported in China in (2003) is the etiological agent of the mysterious COVID-19 reported to originate from Wuhan, Hubei province, China in 2019. Though the virus exhibit mild pathogenicity compared to other previously emerged human coronaviruses (HCoV-OC43, HCoV-HKU1, MERS-CoV, and SARS-CoV), however, the high transmissibility and infectivity among human is alarming. In spite the evidences from the increasing number of substantiated global cases and deaths resulting from the epidemic outbreak to date, curative measures to curtail and treat this disease are still lacking. Just like SARS-CoV, it has been revealed that SARS-CoV-2 also uses similar receptor for infectivity and shares similar disease pathogenesis. This knowledge presents a therapeutic target against COVID-19. The presence of cross-reactive epitopes in the spike protein subunit of SARS-CoV and SARS-CoV-2 present the use of neutralization antibodies from convalescent SARS challenged patients against COVID 19. However, limited cross-neutralization due to lower sequence conservation in the Spike protein subunit could render this approach ineffective. Realizing the urgent need for developing potent therapeutics against the imminent risk of COVID-19 on humanity, this review article, suggests the use of SARS-CoV-2 recombinant Spike protein-based vaccine as an immunotherapeutic target to combat COVID-19 based on garnered knowledge from researches on consanguineal coronaviruses (SARS-CoV, and MERS-CoV), and current trends in vaccine development against this infection.
Certificate of Excellence in Reviewing - The 5th Virtual Multidisciplinary Conference (QUAESTI 2017)
Polyploidy, which arises through complex genetic and ecological processes, is an important mode of plant speciation. This review provides an overview of recent advances in understanding why plant polyploid species are so ubiquitous and... more
Polyploidy, which arises through complex genetic and ecological processes, is an important mode of plant speciation. This review provides an overview of recent advances in understanding why plant polyploid species are so ubiquitous and diverse. We consider how the modern framework for understanding genetic mechanisms of speciation could be used to study allopolyploid speciation that occurs through hybrid genome doubling, that is, whole genome doubling of interspecific F1 hybrids by the union of male and female unreduced gametes. We outline genetic and ecological mechanisms that may have positive or negative impacts on the process of allopolyploid speciation through hybrid genome doubling. We also discuss the current status of studies on the underlying genetic mechanisms focusing on the wheat (Triticum and Aegilops) hybrid-specific reproductive phenomena that are well known but deserve renewed attention from an evolutionary viewpoint.
Novel findings on fabrication techniques for bioactive materials, discovering further basic knowledge about wound healing process, and availability of stem cells as alternative candidate for differentiated cells have highly encouraged... more
Novel findings on fabrication techniques for bioactive materials, discovering further basic knowledge about wound healing process, and availability of stem cells as alternative candidate for differentiated cells have highly encouraged scientists for developing new bioengineered skin substitutes (BSS) that offer an effective remedy for a specific wound type. However, technical, clinical, legislative and economic reasons hamper widespread commercialization and clinical translation of BSS. Among the various types of strategies that target skin repair and regeneration, tissue engineering with stem cells is most promising route. Tissue engineering by cooperation of several disciplines forms a context on which the commercial development of BSS is possible to provide benefits for patients who currently have limited or no cure options. The principles of tissue engineering are to initiate cell cultures in vitro, grow them in monolayer or on porous scaffolds and transplant the composite into a patient with a specific wound indication in vivo. The potential for creating of custom-designed biomaterials and availability of stem cells from either autologous or allogenic sources have helped to produce novel innovative BSS. Currently, wide range of skin substitutes are already being fabricated for clinical use in different wound indications but not yet definitively established. Therefore, many novel engineered constructs might be fabricated in the future. In this review, we describe the progress that has been made to date in the field of skin substitutes and the critical issues that are still hindering successful production and bench to bedside translation of BSS and restricting the availability of these innovative therapeutic constructs. Integrity of the science and technology, interdisciplinary expertise collaborations, and early interaction with regulatory entities such as Food and Drug Administration (FDA) and European Medicines Agency (EMA), together with other critical determinants, is vital to the successful commercialization of tissue engineering products into the marketplace/clinic.
Corneal opacification due to limbal stem cell deficiency (LSCD) is an important cause for ocular morbidity, resulting from a number of intrinsic and extrinsic factors. While the extrinsic factors include conditions such as chemical or... more
Corneal opacification due to limbal stem cell deficiency (LSCD) is an important cause for ocular morbidity, resulting from a number of intrinsic and extrinsic factors. While the extrinsic factors include conditions such as chemical or thermal injuries, intrinsic include dysfunction, or reduction in the number of stem cells either due to pathological changes in autoimmune diseases or secondary to certain clinical conditions such as diabetes, dry eye disorders, or multiple previous eye surgeries. LSCD is characterized by a classic triad of signs—conjunctivalization, neovascularization and decrease in vision. With the increasing knowledge of limbal stem cells, the treatment of this condition has evolved from simple debridement to use of biological materials, direct transplantation of the healthy limbal tissue from the contralateral eye, or allogenic source to the use of cultivated limbal epithelial sheets. This chapter provides an update on the disease pathology, various treatment meth...
Profound chromatin changes occur during mitosis to allow for gene silencing and chromosome segregation followed by re-activation of memorized transcription states in daughter cells. Using genome-wide sequencing, we found H2A.Z containing... more
Profound chromatin changes occur during mitosis to allow for gene silencing and chromosome segregation followed by re-activation of memorized transcription states in daughter cells. Using genome-wide sequencing, we found H2A.Z containing +1 nucleosomes of active genes shift upstream to occupy TSSs during mitosis, significantly reducing nucleosome-depleted regions. Single molecule analysis confirmed nucleosome shifting and demonstrated that mitotic shifting is specific to active genes that are silenced during mitosis and thus is not seen on promoters, which are silenced by methylation or mitotically expressed genes. Using the GRP78 promoter as a model, we found H3K4 tri-methylation is also maintained while other indicators of active chromatin are lost and expression is decreased. These key changes provide a potential mechanism for rapid silencing and re-activation of genes during the cell cycle.
The endoplasmic reticulum (ER) is a dynamic intracellular organelle with multiple functions essential for cellular homeostasis, development, and stress responsiveness. In response to cellular stress, a well-established signaling cascade,... more
The endoplasmic reticulum (ER) is a dynamic intracellular organelle with multiple functions essential for cellular homeostasis, development, and stress responsiveness. In response to cellular stress, a well-established signaling cascade, the unfolded protein response (UPR), is activated. This intricate mechanism is an important means of reestablishing cellular homeostasis and alleviating the inciting stress. Now, emerging evidence has demonstrated that the UPR influences cellular metabolism through diverse mechanisms, including calcium and lipid transfer, raising the prospect of involvement of these processes in the pathogenesis of disease, including neurodegeneration, cancer, diabetes mellitus and cardiovascular disease. Here, we review the distinct functions of the ER and UPR from a metabolic point of view, highlighting their association with prevalent pathologies.
Expert peer review at Medicine® Journal Hesham N. Mustafa Presented April 8, 2018 (Wolters Kluwer)
closely related cloacin DF13; reviewed in James et al., 1996); or (3) inhibition of protein synthesis by RNase Case Western Reserve University Cleveland, Ohio 44106 cleavage of specific tRNAs which contain the modified base queuine at the... more
closely related cloacin DF13; reviewed in James et al., 1996); or (3) inhibition of protein synthesis by RNase Case Western Reserve University Cleveland, Ohio 44106 cleavage of specific tRNAs which contain the modified base queuine at the wobble position of the anticodon 2 Department of Physiology and Biophysics Albert Einstein College of Medicine (colicin E5; Ogawa et al., 1999). There are three distinct steps in the killing of a sensi-Bronx, New York 10461 tive E. coli by colicins, each of which is carried out by a separate domain of the molecule (Figure 1). The first step, receptor binding, is mediated by the R domain, Summary which lies in the central part of the primary sequence. The N-terminal T domain mediates the second step, Colicins kill E. coli by a process that involves binding translocation from the outer membrane receptor to the to a surface receptor, entering the cell, and, finally, colicin's target in the cell. Finally, the killing activity reintoxicating it. The lethal action of colicin E3 is a spesides in the carboxy-terminal C (catalytic or channelcific cleavage in the ribosomal decoding A site. The forming) domain. crystal structure of colicin E3, reported here in a binary Colicin E3 kills the target cell by inactivation of its complex with its immunity protein (IP), reveals a protein biosynthetic machinery (Nomura, 1967; Nomura Y-shaped molecule with the receptor binding domain et al., 1974). The mode of action involves the cleavage forming a 100 Å long stalk and the two globular heads of a single phosphodiester bond of E. coli 16S ribosomal of the translocation domain (T) and the catalytic do-RNA in the 30S subunit at a specific site (Bowman et main (C) comprising the two arms. Active site residues al., 1971a; Senior and Holland, 1971; Dahlberg and Dahlare D510, H513, E517, and R545. IP is buried between T berg, 1975). This site, between adenine 1493 and guaand C. Rather than blocking the active site, IP prevents nine 1494, is on a bubble of the penultimate helix close access of the active site to the ribosome. to the 3Ј end and the interface between the small and large ribosomal subunits and is at a critical position near Introduction where interactions of the A site tRNA and the mRNA occur on the ribosome (Cate et al., 1999). The same Bacteriocins are protein antibiotics that kill bacteria cleavage occurs in vitro when isolated 70S ribosomes closely related to the producing species. Colicins constiare incubated with purified colicin E3 (Boon, 1971; Bowtute the subgroup of bacteriocins that are produced and man et al., 1971b). secreted by E. coli (Braun et al., 1994). The lethal action
vivo as a transcription corepressor was provided by University of California, San Diego experiments carried out in Drosophila. Drosophila CtBP La Jolla, California 92093 (dCtBP) is maternally expressed and uniformly distrib-4 Structural... more
vivo as a transcription corepressor was provided by University of California, San Diego experiments carried out in Drosophila. Drosophila CtBP La Jolla, California 92093 (dCtBP) is maternally expressed and uniformly distrib-4 Structural Biology Program uted throughout the early embryo. Mutations in dCtBP Department of Physiology and Biophysics cause severe segmentation and patterning defects that Mount Sinai School of Medicine have been attributed to the combined loss of repression New York, New York 10029 activities of Knirps, Krü ppel, and Snail; factors critical for early development and repression of genes such as even skipped, rhomboid, and fushi tarazu (Nibu et al., Summary 1998a, 1998b; Poortinga et al. , 1998). All three of these sequence-specific repressors contain PXDLS-related Transcriptional repression is based on the selective motifs that have been shown in vitro and in vivo to actions of recruited corepressor complexes, including be important in recruiting dCtBP. CtBP1 and CtBP2, a those with enzymatic activities. One well-characterized second highly related factor in vertebrates, have been developmentally important corepressor is the C-terlinked to a host of disparate transcription factors includminal binding protein (CtBP). Although intriguingly reing several that are important in cellular proliferation, lated in sequence to D2 hydroxyacid dehydrogenases, homeostasis, and development by a conserved PXDLSthe mechanism by which CtBP functions remains unlike motif (Chinnadurai, 2002).
Corneal opacification due to limbal stem cell deficiency (LSCD) is an important cause for ocular morbidity, resulting from a number of intrinsic and extrinsic factors. While the extrinsic factors include conditions such as chemical or... more
Corneal opacification due to limbal stem cell deficiency (LSCD) is an important cause for ocular morbidity, resulting from a number of intrinsic and extrinsic factors. While the extrinsic factors include conditions such as chemical or thermal injuries, intrinsic include dysfunction, or reduction in the number of stem cells either due to pathological changes in autoimmune diseases or secondary to certain clinical conditions such as diabetes, dry eye disorders, or multiple previous eye surgeries. LSCD is characterized by a classic triad of signs-conjunctivalization, neovascularization and decrease in vision. With the increasing knowledge of limbal stem cells, the treatment of this condition has evolved from simple debridement to use of biological materials, direct transplantation of the healthy limbal tissue from the contralateral eye, or allogenic source to the use of cultivated limbal epithelial sheets. This chapter provides an update on the disease pathology, various treatment methodologies, with specific emphasis on the fast developing field of cell therapy and tissue engineering.
The phosphorylation of ribosomal protein S6 (rpS6), which occurs in response to a wide variety of stimuli on five evolutionarily conserved serine residues, has attracted much attention since its discovery more than three decades ago.... more
The phosphorylation of ribosomal protein S6 (rpS6), which occurs in response to a wide variety of stimuli on five evolutionarily conserved serine residues, has attracted much attention since its discovery more than three decades ago. However, despite a large body of information on the respective kinases and the signal transduction pathways, the role of this phosphorylation remained obscure. It is only recent that targeting the genes encoding rpS6, the phosphorylatable serine residues or the respective kinases that the unique role of rpS6 and its posttranslational modification have started to be elucidated. This review focuses primarily on the critical role of rpS6 for mouse development, the pathways that transduce various signals into rpS6 phosphorylation, and the physiological functions of this modification. The mechanism(s) underlying the diverse effects of rpS6 phosphorylation on cellular and organismal physiology has yet to be determined. However, a model emerging from the curre...
Mast cells are best known as multifunctional entities that may confer a benefit on immune system. This review presents the known facts on mast-cell system and breakthroughs in mast-cell biology in fish, amphibians, reptiles, and birds. As... more
Mast cells are best known as multifunctional entities that may confer a benefit on immune system. This review presents the known facts on mast-cell system and breakthroughs in mast-cell biology in fish, amphibians, reptiles, and birds. As compared to mammals, there are relatively few data available on mast cells in many nonmammalian vertebrates. Nevertheless, like in mammals, mast cells in nonmammalian vertebrates contain a wide range of bioactive compounds including histamine, heparin, neuropeptides, and neutral proteases. In bony fishes, these cells secrete antimicrobial peptides as well. Mast cells have a widespread distribution in the brain, endocrine glands, intestine, liver, kidney, skin, tongue, and lungs, the highest concentration occurring in different tissues in the different taxa. Currently, researchers are grappling with the nature of scientific support to substantiate the functional importance of mast cells in
Genome-wide DNA methylation reprogramming occurs in mouse primordial germ cells (PGCs) and preimplantation embryos, but the precise dynamics and biological outcomes are largely unknown. We have carried out whole-genome bisulfite... more
Genome-wide DNA methylation reprogramming occurs in mouse primordial germ cells (PGCs) and preimplantation embryos, but the precise dynamics and biological outcomes are largely unknown. We have carried out whole-genome bisulfite sequencing (BS-Seq) and RNA-Seq across key stages from E6.5 epiblast to E16.5 PGCs. Global loss of methylation takes place during PGC expansion and migration with evidence for passive demethylation, but sequences that carry long-term epigenetic memory (imprints, CpG islands on the X chromosome, germline-specific genes) only become demethylated upon entry of PGCs into the gonads. The transcriptional profile of PGCs is tightly controlled despite global hypomethylation, with transient expression of the pluripotency network, suggesting that reprogramming and pluripotency are inextricably linked. Our results provide a framework for the understanding of the epigenetic ground state of pluripotency in the germline.
Homologous recombination (HR) is essential for repair of meiotic DNA double-strand breaks (DSBs). Although the mechanisms of RAD-51-DNA filament assembly and strand exchange are well characterized, the subsequent steps of HR are less well... more
Homologous recombination (HR) is essential for repair of meiotic DNA double-strand breaks (DSBs). Although the mechanisms of RAD-51-DNA filament assembly and strand exchange are well characterized, the subsequent steps of HR are less well defined. Here, we describe a synthetic lethal interaction between the C. elegans helicase helq-1 and RAD-51 paralog rfs-1, which results in a block to meiotic DSB repair after strand invasion. Whereas RAD-51-ssDNA filaments assemble at meiotic DSBs with normal kinetics in helq-1, rfs-1 double mutants, persistence of RAD-51 foci and genetic interactions with rtel-1 suggest a failure to disassemble RAD-51 from strand invasion intermediates. Indeed, purified HELQ-1 and RFS-1 independently bind to and promote the disassembly of RAD-51 from doublestranded, but not single-stranded, DNA filaments via distinct mechanisms in vitro. These results indicate that two compensating activities are required to promote postsynaptic RAD-51 filament disassembly, which are collectively essential for completion of meiotic DSB repair.
Caldesmon (CaD) is a multimodular protein that regulates contractility and actin cytoskeleton remodeling in smooth muscle and nonmuscle cells. A single gene (CALD1) encodes high molecular mass CaD (h-CaD) and low molecular mass CaD... more
Caldesmon (CaD) is a multimodular protein that regulates contractility and actin cytoskeleton remodeling in smooth muscle and nonmuscle cells. A single gene (CALD1) encodes high molecular mass CaD (h-CaD) and low molecular mass CaD (l-CaD) by alternative splicings. The h-CaD exclusively expresses in smooth muscle, whereas the l-CaD ubiquitously expresses in all cell types except skeletal muscle. The h-CaD/l-CaD ratio could be a marker for monitoring differentiating and pathological states of smooth muscles. The l-CaD associates with stress fibers and membrane ruffles in nonmuscle cells and with the actin core of podosomes in highly motile/invasive cells. Together with tropomyosin, CaD stabilizes actin filaments and inhibits actin-tropomyosin-activated myosin ATPase activity. This inhibition can be effectively released by Ca(2+)-calmodulin and/or by phosphorylation with various kinases. Through its interactions with a spectrum of actin-binding proteins, CaD modulates dynamics of cort...
In skin tissue engineering, surface feature of the scaffolds plays an important role in cell adhesion and proliferation. In this study, non-woven fibrous substrate based on poly (lactic-co-glycolic acid) (PLGA) (75/25) were hy-drolyzed in... more
In skin tissue engineering, surface feature of the scaffolds plays an important role in cell adhesion and proliferation. In this study, non-woven fibrous substrate based on poly (lactic-co-glycolic acid) (PLGA) (75/25) were hy-drolyzed in various concentrations of NaOH (0.05 N, 0.1 N, 0.3 N) to increase carboxyl and hydroxyl groups on the fiber surfaces. These functional groups were activated by EDC/NHS to create chemical bonding with collagen. To improve bioactivity, the activated substrates were coated with a collagen solution (2 mg/ml) and cross-linking was carried out using the EDC/NHS in MES buffer. The effectiveness of the method was evaluated by contact angle measurements, porosimetry, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), tensile and degradation tests as well as in vitro cell attachment and cytotoxicity assays. Cell culture results of human dermal fibroblasts (HDF) and keratinocytes cell line (HaCat) revealed that the cells could attach to the scaffold. Further investigation with MTT assay showed that the cell proliferation of HaCat significantly increases with collagen coating. It seems that sufficient stability of collagen on the surface due to proper chemical bonding and cross-linking has increased the bioactivity of surface remarkably which can be promising for bioengineered skin applications.