Melanin Pigmentation in Mammalian Skin and Its Hormonal Regulation

2004 ◽  
Vol 84 (4) ◽  
pp. 1155-1228 ◽  
Author(s):  
Andrzej Slominski ◽  
Desmond J. Tobin ◽  
Shigeki Shibahara ◽  
Jacobo Wortsman
Keyword(s):  
Hormonal Regulation ◽  
Critical Role ◽  
Cellular Level ◽  
Multiple Roles ◽  
Regulatory Control ◽  
Melanin Pigmentation ◽  
Agouti Protein ◽  
In Series ◽  
Functional Regulation ◽  
Structured System

Cutaneous melanin pigment plays a critical role in camouflage, mimicry, social communication, and protection against harmful effects of solar radiation. Melanogenesis is under complex regulatory control by multiple agents interacting via pathways activated by receptor-dependent and -independent mechanisms, in hormonal, auto-, para-, or intracrine fashion. Because of the multidirectional nature and heterogeneous character of the melanogenesis modifying agents, its controlling factors are not organized into simple linear sequences, but they interphase instead in a multidimensional network, with extensive functional overlapping with connections arranged both in series and in parallel. The most important positive regulator of melanogenesis is the MC1 receptor with its ligands melanocortins and ACTH, whereas among the negative regulators agouti protein stands out, determining intensity of melanogenesis and also the type of melanin synthesized. Within the context of the skin as a stress organ, melanogenic activity serves as a unique molecular sensor and transducer of noxious signals and as regulator of local homeostasis. In keeping with these multiple roles, melanogenesis is controlled by a highly structured system, active since early embryogenesis and capable of superselective functional regulation that may reach down to the cellular level represented by single melanocytes. Indeed, the significance of melanogenesis extends beyond the mere assignment of a color trait.

scholarly journals Role of Somatostatin in the Regulation of Central and Peripheral Factors of Satiety and Obesity

2020 ◽  
Vol 21 (7) ◽  
pp. 2568
Author(s):  
Ujendra Kumar ◽  
Sneha Singh
Keyword(s):  
Food Intake ◽  
Hormonal Regulation ◽  
Critical Role ◽  
Eating Behaviour ◽  
Peripheral Tissues ◽  
Complex Process ◽  
The Many ◽  
The One ◽  
Food Seeking

Obesity is one of the major social and health problems globally and often associated with various other pathological conditions. In addition to unregulated eating behaviour, circulating peptide-mediated hormonal secretion and signaling pathways play a critical role in food intake induced obesity. Amongst the many peptides involved in the regulation of food-seeking behaviour, somatostatin (SST) is the one which plays a determinant role in the complex process of appetite. SST is involved in the regulation of release and secretion of other peptides, neuronal integrity, and hormonal regulation. Based on past and recent studies, SST might serve as a bridge between central and peripheral tissues with a significant impact on obesity-associated with food intake behaviour and energy expenditure. Here, we present a comprehensive review describing the role of SST in the modulation of multiple central and peripheral signaling molecules. In addition, we highlight recent progress and contribution of SST and its receptors in food-seeking behaviour, obesity (orexigenic), and satiety (anorexigenic) associated pathways and mechanism.

scholarly journals N-Cadherin Is Critical for the Survival of Germ Cells, the Formation of Steroidogenic Cells, and the Architecture of Developing Mouse Gonads

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1610 ◽  
Author(s):  
Rafal P. Piprek ◽  
Michal Kolasa ◽  
Dagmara Podkowa ◽  
Malgorzata Kloc ◽  
Jacek Z. Kubiak
Keyword(s):  
Germ Cells ◽  
Hormonal Regulation ◽  
Critical Role ◽  
Somatic Cells ◽  
Gonad Development ◽  
Knock Out ◽  
Gonad Differentiation ◽  
Steroidogenic Cells ◽  
The Individual ◽  
And Function

Normal gonad development assures the fertility of the individual. The properly functioning gonads must contain a sufficient number of the viable germ cells, possess a correct architecture and tissue structure, and assure the proper hormonal regulation. This is achieved by the interplay between the germ cells and different types of somatic cells. N-cadherin coded by the Cdh2 gene plays a critical role in this interplay. To gain an insight into the role of N-cadherin in the development of mouse gonads, we used the Cre-loxP system to knock out N-cadherin separately in two cell lines: the SF1+ somatic cells and the OCT4+ germ cells. We observed that N-cadherin plays a key role in the survival of both female and male germ cells. However, the N-cadherin is not necessary for the differentiation of the Sertoli cells or the initiation of the formation of testis cords or ovigerous cords. In the later stages of gonad development, N-cadherin is important for the maintenance of testis cord structure and is required for the formation of steroidogenic cells. In the ovaries, N-cadherin is necessary for the formation of the ovarian follicles. These results indicate that N-cadherin plays a major role in gonad differentiation, structuralization, and function.

RETHINKING INNATENESS: A CONNECTIONIST PERSPECTIVE ON DEVELOPMENT.Jeffrey L. Elman, Elizabeth A. Bates, Mark H. Johnson, Annette Karmiloff-Smith, Domenico Parisi, & Kim Plunkett. Cambridge, MA: MIT Press, 1996. Pp. xviii + 447. $45.00 cloth.

1998 ◽  
Vol 20 (3) ◽  
pp. 451-451
Author(s):  
Nick Ellis
Keyword(s):  
Cognitive Psychology ◽  
Dynamical Systems ◽  
Cellular Level ◽  
Regulatory Control ◽  
Synaptic Connectivity ◽  
Special Focus ◽  
Human Cortex ◽  
Domain Specific ◽  
Molecular Arrangement ◽  
And Behavior

In this provocative book, six coauthors, representing cognitive psychology, connectionism, neurobiology, and dynamical-systems theory, synthesize a new theoretical framework for cognitive development with special focus on language acquisition. In the Emergentist perspective, interactions occurring at all levels, from genes to environment, give rise to emergent forms and behavior. These outcomes may be highly constrained and universal, but they are not themselves directly contained in the genes in any domain-specific way. The human body contains perhaps 5 × 1028 bits of information in its molecular arrangement, but our genome contains only about 105 bits of information. Thus, we are over 20 orders of magnitude short of being mosaic organisms, where development is prespecified in the genes. Our development is under regulatory control, where precise pathways to adulthood reflect numerous interactions at the cellular level occurring throughout development. The human cortex is plastic, its architecture reflects experience; innate specification of synaptic connectivity in the cortex is highly unlikely. Theories of language must reflect this—they must be biologically, developmentally, and ecologically plausible. Linguistic representational nativism is just not tenable. It is so implausible that UG could be directly encoded in the genotype that we must explore the alternatives. So the answer is not “Nature.” Nor, as the authors so clearly argue, is it “Nature or Nuture.” Rather, it is “Nature and Nurture.”

scholarly journals Exploring the Superior Colliculus In Vitro

2009 ◽  
Vol 102 (5) ◽  
pp. 2581-2593 ◽  
Author(s):  
Tadashi Isa ◽  
William C. Hall
Keyword(s):  
Superior Colliculus ◽  
Sensorimotor Integration ◽  
Cellular Level ◽  
Multiple Roles ◽  
Whole Cell Patch Clamp ◽  
Parabrachial Nuclei ◽  
And Function ◽  
Compare And Contrast ◽  
Selection Of

The superior colliculus plays an important role in the translation of sensory signals that encode the location of objects in space into motor signals that encode vectors of the shifts in gaze direction called saccades. Since the late 1990s, our two laboratories have been applying whole cell patch-clamp techniques to in vitro slice preparations of rodent superior colliculus to analyze the structure and function of its circuitry at the cellular level. This review describes the results of these experiments and discusses their contributions to our understanding of the mechanisms responsible for sensorimotor integration in the superior colliculus. The experiments analyze vertical interactions between its superficial visuosensory and intermediate premotor layers and propose how they might contribute to express saccades and to saccadic suppression. They also compare and contrast the circuitry within each of these layers and propose how this circuitry might contribute to the selection of the targets for saccades and to the build-up of the premotor commands that precede saccades. Experiments also explore in vitro the roles of extrinsic inputs to the superior colliculus, including cholinergic inputs from the parabigeminal and parabrachial nuclei and GABAergic inputs from the substantia nigra pars reticulata, in modulating the activity of the collicular circuitry. The results extend and clarify our understanding of the multiple roles the superior colliculus plays in sensorimotor integration.

scholarly journals Adaptive reprogramming during early seed germination requires temporarily enhanced fermentation a critical role for alternative oxidase (AOX) regulation that concerns also microbiota effectiveness

2021 ◽  
Author(s):  
Bharadwaj Revuru ◽  
Carlos Noceda ◽  
Mohanapriya Gunasekharan ◽  
Sarma Rajeev Kumar ◽  
Karine Leitao Lima Thiers ◽  
...  
Keyword(s):  
Seed Germination ◽  
Mycorrhizal Fungi ◽  
Alternative Oxidase ◽  
Low Cost ◽  
Critical Role ◽  
Arbuscular Mycorrhizal ◽  
Reproductive Organs ◽  
Cellular Level ◽  
Simple Method

Plants respond to environmental cues via adaptive cell reprogramming that can affect whole plant and ecosystem functionality. Microbiota constitutes part of plants inner and outer environment. This Umwelt underlies steady dynamics, due to complex local and global biotic and abiotic changes. Hence, adaptive plant holobiont responses are crucial for continuous metabolic adjustment at systems levels. Plants require oxygen-dependent respiration for energy-dependent adaptive morphology, such as, germination, root and shoot growth, formation of adventitious, clonal and reproductive organs, fruits and seeds. Fermentative paths can help in acclimation and, to our view the role of alternative oxidase (AOX) in coordinating complex metabolic and physiologic adjustments is underestimated. Cellular level of sucrose is an important sensor of environmental stress. We explored the role of exogenous sucrose and its interplay with AOX during early seed germination. We found that sucrose-dependent initiation of fermentation during the first 12 hours after imbibition (HAI) was beneficial to germination. However, parallel enhanced AOX expression was essential to control negative effects by prolonged sucrose treatment. Early down-regulated AOX activity until 12 HAI improved germination efficiency in the absence of sucrose, but suppressed early germination in its presence. Our results also suggest that seeds-inoculated arbuscular mycorrhizal fungi can buffer sucrose stress during germination to restore normal respiration more efficiently. Following this approach, we propose a simple method to identify organic seeds and low-cost on-farm perspectives for early selection on disease tolerance, predicting plant holobiont behavior and improving germination. Furthermore, our research strengthens the view that AOX can serve as powerful functional marker source for seed hologenomes.

scholarly journals Multiple roles for laccase2 in butterfly wing pigmentation, scale development, and cuticle tanning

2019 ◽  
Author(s):  
Ceili L. Peng ◽  
Anyi Mazo-Vargas ◽  
Benjamin J. Brack ◽  
Robert D. Reed
Keyword(s):  
Scale Development ◽  
Multiple Roles ◽  
Melanin Pigmentation ◽  
Lepidopteran Insect ◽  
Genetic Mechanisms ◽  
Nymphalid Butterfly ◽  
Encoding Gene ◽  
Mutant Phenotypes ◽  
Insight Into ◽  
Wing Scales

ABSTRACTLepidopteran wing scales play important roles in a number of functions including color patterning and thermoregulation. Despite the importance of wing scales, however, we still have a limited understanding of the genetic mechanisms that underlie scale patterning, development, and coloration. Here we explore the function of the phenoloxidase-encoding gene laccase2 in wing and scale development in the nymphalid butterfly Vanessa cardui. Somatic deletion mosaics of laccase2 generated by CRISPR/Cas9 genome editing presented several distinct mutant phenotypes. Consistent with work in other non-lepidopteran insect groups, we observed reductions in melanin pigmentation and defects in cuticle formation. We were also surprised, however, to see distinct effects on scale development including complete loss of wing scales. This work highlights laccase2 as a gene that plays multiple roles in wing and scale development and provides new insight into the evolution of lepidopteran wing coloration.

scholarly journals The Multiple Cellular Roles of SMUG1 in Genome Maintenance and Cancer

2021 ◽  
Author(s):  
Sripriya Raja ◽  
Bennett Van Houten
Keyword(s):  
Genome Stability ◽  
Excision Repair ◽  
Critical Role ◽  
Multiple Roles ◽  
Genome Maintenance ◽  
Uracil Dna Glycosylase ◽  
Damage Recognition ◽  
Base Excision ◽  
Cellular Phenotypes ◽  
Moonlighting Functions

Single-stand selective monofunctional uracil DNA glycosylase 1 (SMUG1) works to remove uracil and certain oxidized bases from DNA during base excision repair (BER). This review provides a historical characterization of SMUG1 and 5-hydroxymethyl-2'-deoxyuridine (5-hmdU) one important substrate of this enzyme. Biochemical and structural analyses provide remarkable insight into the mechanism of this glycosylase revealing SMUG1 has a unique helical wedge which influences damage recognition during repair. Rodent studies suggest that, while SMUG1 shares substrate specificity with another uracil glycosylase UNG2, loss of SMUG1 can have unique cellular phenotypes. This review highlights the multiple roles SMUG1 may play in preserving genome stability, and how the loss of SMUG1 activity may promote cancer. Finally, we discuss recent studies indicating SMUG1 has moonlighting functions beyond BER, playing a critical role in RNA processing including the RNA component of telomerase.

scholarly journals Rapid removal of phagosomal ferroportin in macrophages contributes to nutritional immunity

2021 ◽  
Vol 5 (2) ◽  
pp. 459-474
Author(s):  
Ronald S. Flannagan ◽  
Tayler J. Farrell ◽  
Steven M. Trothen ◽  
Jimmy D. Dikeakos ◽  
David E. Heinrichs
Keyword(s):  
Fluorescent Protein ◽  
Critical Role ◽  
Cellular Level ◽  
Protein Fusion ◽  
Extracellular Milieu ◽  
Nutritional Immunity ◽  
Protein Receptor ◽  
Serovar Typhimurium ◽  
Green Fluorescent ◽  
Phagosomal Membrane

Abstract Nutrient sequestration is an essential facet of host innate immunity. Macrophages play a critical role in controlling iron availability through expression of the iron transport protein ferroportin (FPN), which extrudes iron from the cytoplasm to the extracellular milieu. During phagocytosis, the limiting phagosomal membrane, which derives from the plasmalemma, can be decorated with FPN and, if functional, will move iron from the cytosol into the phagosome lumen. This serves to feed iron to phagocytosed microbes and would be counterproductive to the many other known host mechanisms working to starve microbes of this essential metal. To understand how FPN is regulated during phagocytosis, we expressed FPN as a green fluorescent protein–fusion protein in macrophages and monitored its localization during uptake of various phagocytic targets, including Staphylococcus aureus, Salmonella enterica serovar Typhimurium, human erythrocytes, and immunoglobulin G opsonized latex beads. We find that FPN is rapidly removed, independently of Vps34 and PI(3)P, from early phagosomes and does not follow recycling pathways that regulate transferrin receptor recycling. Live-cell video microscopy showed that FPN movement on the phagosome is dynamic, with punctate and tubular structures forming before FPN is trafficked back to the plasmalemma. N-ethylmaleimide–sensitive factor, which disrupts soluble NSF attachment protein receptor (SNARE)–mediated membrane fusion and trafficking, prevented FPN removal from the phagosome. Our data support the hypothesis that removal of FPN from the limiting phagosomal membrane will, at the cellular level, ensure that iron cannot be pumped into phagosomes. We propose this as yet another mechanism of host nutritional immunity to subvert microbial growth.

scholarly journals S-adenosylhomocysteine hydrolase regulates anterior patterning in Dugesia japonica

2020 ◽  
Author(s):  
Kristina Reinmets ◽  
Johanna Bischof ◽  
Emily Taketa ◽  
Michael Levin ◽  
Stephen M. Fuchs
Keyword(s):  
Critical Role ◽  
Cellular Level ◽  
The Body ◽  
Metabolic Reprogramming ◽  
Brain Morphology ◽  
Adenosylhomocysteine Hydrolase ◽  
Spatial Shift ◽  
Dugesia Japonica ◽  
Wide Scale ◽  
Anterior Patterning

AbstractBackgroundBiological methylation requires S-adenosylmethionine (SAM) and participates in a range of processes from modulation of gene expression via histone modifications to neurotransmitter synthesis. An important factor in all methylation reactions is the concentration ratio of SAM to methylation byproduct S-adenosylhomocysteine (SAH). SAH hydrolase, also known as adenosylhomocysteinase, depletes SAH and thereby facilitates metabolite recycling and maintains the methylation permissive SAM/SAH ratio. While the importance of SAH hydrolase in sustaining methylation is obvious on the cellular level, the function of this metabolic process on the organismal scale is not clear.ResultsWe used planarian Dugesia japonica to investigate the role SAH hydrolase in physiological homeostasis on the body-wide scale. Remarkably, pharmacological inhibition of the SAH hydrolase results in regression of anterior tissues and is accompanied by extensive apoptosis throughout the planarian body. Moreover, exposure to the SAHH inhibitor AdOx leads to changes in brain morphology and spatial shift in the expression of Wnt-modulator Notum. Strikingly, planarians are able to overcome these destructive patterning defects through regeneration of the anterior tissues and adaptation to the used inhibitor. Transcriptome analysis indicates that resistance to the SAHH inhibitor is at least partly mediated by changes in folate cycle and lipid metabolism.ConclusionsSAH hydrolase plays a critical role in planarian homeostasis and anterior patterning potentially through modulation of Wnt signaling. Moreover, planarian adaptation to the SAHH inhibitor via metabolic reprogramming suggests potential targets for addressing methylation-related human conditions.

scholarly journals Distinct effects of tubulin isotype mutations on neurite growth in Caenorhabditis elegans

2017 ◽  
Vol 28 (21) ◽  
pp. 2786-2801 ◽  
Author(s):  
Chaogu Zheng ◽  
Margarete Diaz-Cuadros ◽  
Ken C. Q. Nguyen ◽  
David H. Hall ◽  
Martin Chalfie
Keyword(s):  
Caenorhabditis Elegans ◽  
Neuronal Development ◽  
Function Analysis ◽  
Critical Role ◽  
Neurite Growth ◽  
Cellular Level ◽  
Missense Mutations ◽  
Loss Of Function ◽  
Exterior Surface ◽  
C Elegans

Tubulins, the building block of microtubules (MTs), play a critical role in both supporting and regulating neurite growth. Eukaryotic genomes contain multiple tubulin isotypes, and their missense mutations cause a range of neurodevelopmental defects. Using the Caenorhabditis elegans touch receptor neurons, we analyzed the effects of 67 tubulin missense mutations on neurite growth. Three types of mutations emerged: 1) loss-of-function mutations, which cause mild defects in neurite growth; 2) antimorphic mutations, which map to the GTP binding site and intradimer and interdimer interfaces, significantly reduce MT stability, and cause severe neurite growth defects; and 3) neomorphic mutations, which map to the exterior surface, increase MT stability, and cause ectopic neurite growth. Structure-function analysis reveals a causal relationship between tubulin structure and MT stability. This stability affects neuronal morphogenesis. As part of this analysis, we engineered several disease-associated human tubulin mutations into C. elegans genes and examined their impact on neuronal development at the cellular level. We also discovered an α-tubulin (TBA-7) that appears to destabilize MTs. Loss of TBA-7 led to the formation of hyperstable MTs and the generation of ectopic neurites; the lack of potential sites for polyamination and polyglutamination on TBA-7 may be responsible for this destabilization.

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