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• 851. [Article] In Cod We Trust: Who Are Qualified to Decide Regarding Fisheries Management?

  Suggested Bibliographic Reference: Challenging New Frontiers in the Global Seafood Sector: Proceedings of the Eighteenth Biennial Conference of the International Institute of Fisheries Economics and Trade, ...

  Citation × Citation Citation Abstract Copy Title: In Cod We Trust: Who Are Qualified to Decide Regarding Fisheries Management? Author: Kataria, Mitesh, Lampi, Elina, Eggert, Håkan Year: 2016 Suggested Bibliographic Reference: Challenging New Frontiers in the Global Seafood Sector: Proceedings of the Eighteenth Biennial Conference of the International Institute of Fisheries Economics and Trade, July 11-15, 2016. Compiled by Stefani J. Evers and Ann L. Shriver. International Institute of Fisheries Economics and Trade (IIFET), Corvallis, 2016. Title: In Cod We Trust: Who Are Qualified to Decide Regarding Fisheries Management? Author: Kataria, Mitesh, Lampi, Elina, Eggert, Håkan Year: 2016 Suggested Bibliographic Reference: Challenging New Frontiers in the Global Seafood Sector: Proceedings of the Eighteenth Biennial Conference of the International Institute of Fisheries Economics and Trade, July 11-15, 2016. Compiled by Stefani J. Evers and Ann L. Shriver. International Institute of Fisheries Economics and Trade (IIFET), Corvallis, 2016. Close

• 852. [Article] Shore protection structures in Oregon: an analysis of demand and the implementation of engineering recommendations

  Stabilization structures are the most commonly used form of shore protection along the Oregon coast. Eighty-five percent of the hard stabilization structures built in Oregon from 1976 – 1999 were riprap ...

  Citation × Citation Citation Abstract Copy Title: Shore protection structures in Oregon: an analysis of demand and the implementation of engineering recommendations Author: Chenault, Carla Diane Stabilization structures are the most commonly used form of shore protection along the Oregon coast. Eighty-five percent of the hard stabilization structures built in Oregon from 1976 – 1999 were riprap revetments. An evaluation was conducted of 143 riprap revetments in the northern three counties of Oregon. Clear trends exist in the distribution and demand for shore protection structures in Oregon with 78% of structures evaluated built immediately following an El Nino event and 55% of structures built in southern ends of littoral cells, indicating that erosion is not entirely unpredictable. The Oregon Parks and Recreation Department (OPRD) has the ultimate responsibility of issuing permits for the construction of riprap revetments. Although previous studies have shown that adverse impacts may be associated with the improper design of structures, OPRD does not regulate the structure design. The question has been raised whether design standards are practiced if not regulated and if design should be regulated. Sample sites were individually evaluated based on five criteria that have been identified as critical to the structural integrity of a structures: height of structure, size of rock, slope of structure, texture and shape of material, the use of filter material and a toe trench, and whether the material was placed in an interlocking structure. Variations exist in the compliance with the individual elements. An analysis of overall structure stability, as determined by the evaluation of permit applications, revealed that 59% of structures are built according to the minimum necessary requirements while 14% were designed to a higher set of standards. There is some variation in the quality of structures designed by specific groups with contractors slightly more likely than engineers to design structures to higher standards and both engineers and contractors far more likely than individual homeowners to respect engineering recommendations. Little change in compliance with recommended engineering standards has been seen throughout time. In general, not enough information is given during the application process for shore protection structures to determine if engineering standards are implemented. Title: Shore protection structures in Oregon: an analysis of demand and the implementation of engineering recommendations Author: Chenault, Carla Diane Stabilization structures are the most commonly used form of shore protection along the Oregon coast. Eighty-five percent of the hard stabilization structures built in Oregon from 1976 – 1999 were riprap revetments. An evaluation was conducted of 143 riprap revetments in the northern three counties of Oregon. Clear trends exist in the distribution and demand for shore protection structures in Oregon with 78% of structures evaluated built immediately following an El Nino event and 55% of structures built in southern ends of littoral cells, indicating that erosion is not entirely unpredictable. The Oregon Parks and Recreation Department (OPRD) has the ultimate responsibility of issuing permits for the construction of riprap revetments. Although previous studies have shown that adverse impacts may be associated with the improper design of structures, OPRD does not regulate the structure design. The question has been raised whether design standards are practiced if not regulated and if design should be regulated. Sample sites were individually evaluated based on five criteria that have been identified as critical to the structural integrity of a structures: height of structure, size of rock, slope of structure, texture and shape of material, the use of filter material and a toe trench, and whether the material was placed in an interlocking structure. Variations exist in the compliance with the individual elements. An analysis of overall structure stability, as determined by the evaluation of permit applications, revealed that 59% of structures are built according to the minimum necessary requirements while 14% were designed to a higher set of standards. There is some variation in the quality of structures designed by specific groups with contractors slightly more likely than engineers to design structures to higher standards and both engineers and contractors far more likely than individual homeowners to respect engineering recommendations. Little change in compliance with recommended engineering standards has been seen throughout time. In general, not enough information is given during the application process for shore protection structures to determine if engineering standards are implemented. Close

• 853. [Article] Ganglionic circulation and regulation of cardiovascular activity in Aplysia californica

  Neurons in the abdominal ganglion of the marine mollusk, Aplysia californica , appear to respond directly to changes in blood flow and oxygen tension within the ganglion. When circulation through the ganglion ...

  Citation × Citation Citation Abstract Copy Title: Ganglionic circulation and regulation of cardiovascular activity in Aplysia californica Author: Furgal, Sheryl M. Neurons in the abdominal ganglion of the marine mollusk, Aplysia californica , appear to respond directly to changes in blood flow and oxygen tension within the ganglion. When circulation through the ganglion is reduced, the spontaneous activity of some identifiable neurons are excited while others are inhibited. Many of the neurons which respond most strongly are cells involved in regulating the activity of the heart and vasculature. Most notably, the heart excitor interneuron, L10, is excited for prolonged periods when ganglionic circulation is reduced, and this response is reversed when flow resumes. The neurosecretory white cells (R3-R14), which innervate major arteries and the branchial vein, are also excited during periods of reduced ganglionic circulation. Injection of ink-gelatin mixtures into the vasculature of the abdominal ganglion shows that blood enters the ganglion through a stereotypical pattern of arterial branches. The cell bodies of larger neurons in the ganglion are surrounded by vascular spaces while the neuropil is not vascularized. The cell body of the heart excitor interneuron, L10, is positioned near the caudal artery where it enters the ganglion. This close morphological relationship between ganglionic vasculature and motor circuits controlling the heart suggests a basis for feedback regulation of cardiovascular functions. In dissected preparations of the respiratory organs and the heart with intact innervation from the abdominal ganglion, reduced circulation to the ganglion stimulated two physiological responses that increased cardiac output. The initial response was contraction of the gill, stimulated by a burst of activity in the respiratory pumping circuit and interneuron II. The second response involved long-term excitation of the heart which was correlated with the excitation of the heart excitor interneuron, L10. The physiological importance of this direct interaction between ganglionic circulation and central neurons controlling circulation is discussed. Title: Ganglionic circulation and regulation of cardiovascular activity in Aplysia californica Author: Furgal, Sheryl M. Neurons in the abdominal ganglion of the marine mollusk, Aplysia californica , appear to respond directly to changes in blood flow and oxygen tension within the ganglion. When circulation through the ganglion is reduced, the spontaneous activity of some identifiable neurons are excited while others are inhibited. Many of the neurons which respond most strongly are cells involved in regulating the activity of the heart and vasculature. Most notably, the heart excitor interneuron, L10, is excited for prolonged periods when ganglionic circulation is reduced, and this response is reversed when flow resumes. The neurosecretory white cells (R3-R14), which innervate major arteries and the branchial vein, are also excited during periods of reduced ganglionic circulation. Injection of ink-gelatin mixtures into the vasculature of the abdominal ganglion shows that blood enters the ganglion through a stereotypical pattern of arterial branches. The cell bodies of larger neurons in the ganglion are surrounded by vascular spaces while the neuropil is not vascularized. The cell body of the heart excitor interneuron, L10, is positioned near the caudal artery where it enters the ganglion. This close morphological relationship between ganglionic vasculature and motor circuits controlling the heart suggests a basis for feedback regulation of cardiovascular functions. In dissected preparations of the respiratory organs and the heart with intact innervation from the abdominal ganglion, reduced circulation to the ganglion stimulated two physiological responses that increased cardiac output. The initial response was contraction of the gill, stimulated by a burst of activity in the respiratory pumping circuit and interneuron II. The second response involved long-term excitation of the heart which was correlated with the excitation of the heart excitor interneuron, L10. The physiological importance of this direct interaction between ganglionic circulation and central neurons controlling circulation is discussed. Close

• 854. [Article] Digitally assisted control techniques for high performance switching DC-DC converters

  Digitally controlled switching DC-DC converters have recently emerged as an attractive alternative to conventional switching converters based on analog control techniques. This research focuses on eliminating ...

  Citation × Citation Citation Abstract Copy Title: Digitally assisted control techniques for high performance switching DC-DC converters Author: Khan, Qadeer Ahmad Digitally controlled switching DC-DC converters have recently emerged as an attractive alternative to conventional switching converters based on analog control techniques. This research focuses on eliminating the issues associated with the state of the art switching converters by proposing three novel control techniques: (1) a digitally controlled Buck-Boost converter uses a fully synthesized constant ON/OFF time-based fractional-N controller to regulate the output over a 3.3V-to-5.5V input voltage range and provides seamless transition from buck to buck-boost modes (2) a hysteretic buck converter that employs a highly digital hybrid voltage/current mode control to regulate output voltage and switching frequency independently (3) a 10MHz continuous time PID controller using time based signal processing which alleviates the speed limitations associated with conventional analog and digital. All the three techniques employ digitally assisted control techniques and require no external compensation thus making the controllers fully integrated and highly cost effective. Title: Digitally assisted control techniques for high performance switching DC-DC converters Author: Khan, Qadeer Ahmad Digitally controlled switching DC-DC converters have recently emerged as an attractive alternative to conventional switching converters based on analog control techniques. This research focuses on eliminating the issues associated with the state of the art switching converters by proposing three novel control techniques: (1) a digitally controlled Buck-Boost converter uses a fully synthesized constant ON/OFF time-based fractional-N controller to regulate the output over a 3.3V-to-5.5V input voltage range and provides seamless transition from buck to buck-boost modes (2) a hysteretic buck converter that employs a highly digital hybrid voltage/current mode control to regulate output voltage and switching frequency independently (3) a 10MHz continuous time PID controller using time based signal processing which alleviates the speed limitations associated with conventional analog and digital. All the three techniques employ digitally assisted control techniques and require no external compensation thus making the controllers fully integrated and highly cost effective. Close

• 855. [Article] Impacts of MPA on Coastal Communities‚ Resource Use Behaviour: Case of Mafia Island Marine Park, Tanzania

  Abstract Only

  Citation × Citation Citation Abstract Copy Title: Impacts of MPA on Coastal Communities‚ Resource Use Behaviour: Case of Mafia Island Marine Park, Tanzania Author: Mulyila, Esther Abstract Only Title: Impacts of MPA on Coastal Communities‚ Resource Use Behaviour: Case of Mafia Island Marine Park, Tanzania Author: Mulyila, Esther Abstract Only Close

• 856. [Article] Regulation of cnidarian–dinoflagellate mutualisms: Evidence that activation of a host TGFβ innate immune pathway promotes tolerance of the symbiont

  This is the author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Elsevier and can be found at: http://www.journals.elsevier.com/developmental-a...

  Citation × Citation Citation Abstract Copy Title: Regulation of cnidarian–dinoflagellate mutualisms: Evidence that activation of a host TGFβ innate immune pathway promotes tolerance of the symbiont Author: Weis, Virginia M., Schnitzler, Christine E., Poole, Angela, Detournay, Olivier This is the author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Elsevier and can be found at: http://www.journals.elsevier.com/developmental-and-comparative-immunology/. Title: Regulation of cnidarian–dinoflagellate mutualisms: Evidence that activation of a host TGFβ innate immune pathway promotes tolerance of the symbiont Author: Weis, Virginia M., Schnitzler, Christine E., Poole, Angela, Detournay, Olivier This is the author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Elsevier and can be found at: http://www.journals.elsevier.com/developmental-and-comparative-immunology/. Close

• 857. [Article] Updates on the sporulation process in Clostridium species

  This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by the Institut Pasteur and published by Elsevier. It can be found at: http://www...

  Citation × Citation Citation Abstract Copy Title: Updates on the sporulation process in Clostridium species Author: Olguin-Araneda, Valeria, Alnoman, Maryam, Sarker, Mahfuzur R., Paredes-Sabja, Daniel, Talukdar, Prabhat K. This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by the Institut Pasteur and published by Elsevier. It can be found at: http://www.journals.elsevier.com/research-in-microbiology/ Title: Updates on the sporulation process in Clostridium species Author: Olguin-Araneda, Valeria, Alnoman, Maryam, Sarker, Mahfuzur R., Paredes-Sabja, Daniel, Talukdar, Prabhat K. This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by the Institut Pasteur and published by Elsevier. It can be found at: http://www.journals.elsevier.com/research-in-microbiology/ Close

• 858. [Article] Preseason Report II, Analysis of Proposed Regulatory Options for 1998, Ocean Salmon Fisheries

  Abstract -- This document has been prepared by the staff of the Pacific Fishery Management Council (Council) and the Salmon Technical Team (STT) to describe the Council's proposed ocean salmon management options ...

  Citation × Citation Citation Abstract Copy Title: Preseason Report II, Analysis of Proposed Regulatory Options for 1998, Ocean Salmon Fisheries Abstract -- This document has been prepared by the staff of the Pacific Fishery Management Council (Council) and the Salmon Technical Team (STT) to describe the Council's proposed ocean salmon management options for 1998 and characterize their expected impacts on ocean salmon fisheries and the stocks which support them. The Council solicits public comments on the proposed management options in preparation for adopting final management recommendations on Friday, April 10, in Portland, Oregon. Oral and written comments may be presented at public hearings at the times and locations displayed on the inside front cover of this report. Additional comment will be accepted at the April Council meeting in the Doubletree Hotel Columbia River, Portland, Oregon. Written comments received at the Council office by April 1, 1998, will be copied and distributed to all Council members (Council staff cannot assure distribution of comments received after April 1 ). The Council's final ocean salmon season recommendations will be based on the range of options presented in this report and guidance received through public comments. The Council's final management recommendations may vary in several respects from those in the proposed options. In particular, catch quotas are subject to change depending upon final determination of allocations between fishery participants, allowable harvest levels, and the final impact analyses completed by the STT. Elements of the options may be recombined to result in modified season patterns and changes in measures such as bag limits, days of fishing per week, special landing restrictions and in other specific regulatory details. In addition, inseason modification of management measures may be used to assure achievement of the Council's preseason management objectives. Specific details pertaining to season structure and special regulations for the treaty Indian troll fishery north of Cape Falcon are established through tribal regulations. Chinook and coho quota levels for the treaty Indian troll fishery may be adjusted if significant changes in incidental fishing mortality result from tribal regulations. Title: Preseason Report II, Analysis of Proposed Regulatory Options for 1998, Ocean Salmon Fisheries Abstract -- This document has been prepared by the staff of the Pacific Fishery Management Council (Council) and the Salmon Technical Team (STT) to describe the Council's proposed ocean salmon management options for 1998 and characterize their expected impacts on ocean salmon fisheries and the stocks which support them. The Council solicits public comments on the proposed management options in preparation for adopting final management recommendations on Friday, April 10, in Portland, Oregon. Oral and written comments may be presented at public hearings at the times and locations displayed on the inside front cover of this report. Additional comment will be accepted at the April Council meeting in the Doubletree Hotel Columbia River, Portland, Oregon. Written comments received at the Council office by April 1, 1998, will be copied and distributed to all Council members (Council staff cannot assure distribution of comments received after April 1 ). The Council's final ocean salmon season recommendations will be based on the range of options presented in this report and guidance received through public comments. The Council's final management recommendations may vary in several respects from those in the proposed options. In particular, catch quotas are subject to change depending upon final determination of allocations between fishery participants, allowable harvest levels, and the final impact analyses completed by the STT. Elements of the options may be recombined to result in modified season patterns and changes in measures such as bag limits, days of fishing per week, special landing restrictions and in other specific regulatory details. In addition, inseason modification of management measures may be used to assure achievement of the Council's preseason management objectives. Specific details pertaining to season structure and special regulations for the treaty Indian troll fishery north of Cape Falcon are established through tribal regulations. Chinook and coho quota levels for the treaty Indian troll fishery may be adjusted if significant changes in incidental fishing mortality result from tribal regulations. Close

• 859. [Article] Investigations of the AhR-induced Treg : transcriptional regulation and suppressive mechanisms

  The aryl hydrocarbon receptor (AhR) has recently been described as a novel therapeutic target, given the potent suppression of multiple immune-mediated diseases following activation by the prototypic ligand, ...

  Citation × Citation Citation Abstract Copy Title: Investigations of the AhR-induced Treg : transcriptional regulation and suppressive mechanisms Author: Rohlman, Diana The aryl hydrocarbon receptor (AhR) has recently been described as a novel therapeutic target, given the potent suppression of multiple immune-mediated diseases following activation by the prototypic ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In the parent-into-F1 graft-versus-host (GVH) model, suppression of the cytotoxic T-lymphocyte (CTL) response is associated with the presence of CD25⁺CTLA-4⁺IL-10⁺Foxp3[superscript neg] regulatory donor CD4⁺ T-cells (AhR-Tregs). These AhR-Treg have a suppressive capacity greater than thymus-derived natural Treg. Therefore it is hypothesized that suppression of the CTL response is mediated by the AhR-Treg. The purpose of these studies was two-fold: 1) to identify mechanisms by which TCDD-activated AhR induces AhR-Tregs and 2) to determine the mechanism by which AhR-Tregs suppress the CTL response. To address the first aim, we hypothesized that the AhR, a transcription factor, may directly influence gene expression during CD4⁺ T-cell activation and differentiation, thereby driving their differentiation into AhR-Treg. T-cell differentiation is dependent upon expression of certain transcription factors and lineage-specific genes for proteins and cytokines. Therefore, gene expression associated with CD4⁺ T-cell activation and/or differentiation was evaluated in CD4⁺ T-cells cultured under different polarizing conditions. Unexpectedly, treatment with TCDD did not alter lineage-specific genes that drive CD4⁺ T-cell differentiation. Apart from the known AhR-regulated genes Cyp1a1, Cyp1b1 and Ahrr, only expression of Il22 was inappropriately up- regulated across all conditions tested. The increase in Il22 expression translated to increased IL-22 protein n. Of the 49 genes evaluated there were no other changes in gene expression consistent across polarizing conditions. This suggests that the role of AhR is superimposed upon the cytokine milieu, and therefore may have been obscured by the use of strongly polarizing cytokines. Ultimately, the results cast doubt on the use of in vitro conditions to recapitulate in vivo events, although the role of IL-22 in AhR biology remains of interest. To address the second part of my hypotheses, the suppressive mechanism(s) of the AhR-Treg were examined, focusing primarily on the increased expression of CTLA-4, CD25 and IL-10 seen on day 2 of the GVH response in previous studies. Expression of CTLA-4 induces the IFNγ - IDO tolerogenic pathway. Expression of CD25, the high-affinity subunit for the IL-2R is associated with regulatory function, through induction of tolerogenic cytokines and sequestration of IL-2. The immunosuppressive cytokine IL-10 is known to inhibit T-cell activation and expansion. Independent blockade of CTLA-4 and IDO function revealed that the AhR-Treg do not appear to use the IDO tolerogenic pathway to mediate suppression. Furthermore, antibody-mediated blockade of neither CD25 nor IL-10 were able to alleviate TCDD-mediated immunosuppression. During these studies we discovered that treatment with TCDD induced Foxp3, the transcription factor for Treg, in donor CD4⁺ and CD8⁺ T-cells 15 days after adoptive transfer. Interestingly, the up-regulation of Foxp3 was also seen in un-activated host cells, indicating non-specific regulation of Foxp3 by TCDD-activated AhR. Furthermore, concurrent blockade of CD25 and Foxp3 had no effect on TCDD's ability to suppress the GVH response. In sum, these studies suggest that the AhR-Treg is a novel regulatory cell, with characteristics of a Treg and increased IL-22 production. Regulatory T-cells have a wide repertoire of suppressive mechanisms, including production of TGFβ1 and TGFβ3, sequestration of IL-2 and granzyme B. Understanding the mechanism of suppression utilized by the AhR-Treg is crucial to develop the AhR as a novel therapeutic target. Future studies will continue to evaluate the potential for the AhR-Treg to use alternative mechanisms to suppress T-dependent immune diseases. Title: Investigations of the AhR-induced Treg : transcriptional regulation and suppressive mechanisms Author: Rohlman, Diana The aryl hydrocarbon receptor (AhR) has recently been described as a novel therapeutic target, given the potent suppression of multiple immune-mediated diseases following activation by the prototypic ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In the parent-into-F1 graft-versus-host (GVH) model, suppression of the cytotoxic T-lymphocyte (CTL) response is associated with the presence of CD25⁺CTLA-4⁺IL-10⁺Foxp3[superscript neg] regulatory donor CD4⁺ T-cells (AhR-Tregs). These AhR-Treg have a suppressive capacity greater than thymus-derived natural Treg. Therefore it is hypothesized that suppression of the CTL response is mediated by the AhR-Treg. The purpose of these studies was two-fold: 1) to identify mechanisms by which TCDD-activated AhR induces AhR-Tregs and 2) to determine the mechanism by which AhR-Tregs suppress the CTL response. To address the first aim, we hypothesized that the AhR, a transcription factor, may directly influence gene expression during CD4⁺ T-cell activation and differentiation, thereby driving their differentiation into AhR-Treg. T-cell differentiation is dependent upon expression of certain transcription factors and lineage-specific genes for proteins and cytokines. Therefore, gene expression associated with CD4⁺ T-cell activation and/or differentiation was evaluated in CD4⁺ T-cells cultured under different polarizing conditions. Unexpectedly, treatment with TCDD did not alter lineage-specific genes that drive CD4⁺ T-cell differentiation. Apart from the known AhR-regulated genes Cyp1a1, Cyp1b1 and Ahrr, only expression of Il22 was inappropriately up- regulated across all conditions tested. The increase in Il22 expression translated to increased IL-22 protein n. Of the 49 genes evaluated there were no other changes in gene expression consistent across polarizing conditions. This suggests that the role of AhR is superimposed upon the cytokine milieu, and therefore may have been obscured by the use of strongly polarizing cytokines. Ultimately, the results cast doubt on the use of in vitro conditions to recapitulate in vivo events, although the role of IL-22 in AhR biology remains of interest. To address the second part of my hypotheses, the suppressive mechanism(s) of the AhR-Treg were examined, focusing primarily on the increased expression of CTLA-4, CD25 and IL-10 seen on day 2 of the GVH response in previous studies. Expression of CTLA-4 induces the IFNγ - IDO tolerogenic pathway. Expression of CD25, the high-affinity subunit for the IL-2R is associated with regulatory function, through induction of tolerogenic cytokines and sequestration of IL-2. The immunosuppressive cytokine IL-10 is known to inhibit T-cell activation and expansion. Independent blockade of CTLA-4 and IDO function revealed that the AhR-Treg do not appear to use the IDO tolerogenic pathway to mediate suppression. Furthermore, antibody-mediated blockade of neither CD25 nor IL-10 were able to alleviate TCDD-mediated immunosuppression. During these studies we discovered that treatment with TCDD induced Foxp3, the transcription factor for Treg, in donor CD4⁺ and CD8⁺ T-cells 15 days after adoptive transfer. Interestingly, the up-regulation of Foxp3 was also seen in un-activated host cells, indicating non-specific regulation of Foxp3 by TCDD-activated AhR. Furthermore, concurrent blockade of CD25 and Foxp3 had no effect on TCDD's ability to suppress the GVH response. In sum, these studies suggest that the AhR-Treg is a novel regulatory cell, with characteristics of a Treg and increased IL-22 production. Regulatory T-cells have a wide repertoire of suppressive mechanisms, including production of TGFβ1 and TGFβ3, sequestration of IL-2 and granzyme B. Understanding the mechanism of suppression utilized by the AhR-Treg is crucial to develop the AhR as a novel therapeutic target. Future studies will continue to evaluate the potential for the AhR-Treg to use alternative mechanisms to suppress T-dependent immune diseases. Close

• 860. [Article] Transcription factor CTIP2 regulates hair follicle development, hair cycling and wound healing

  The integumentary system is the largest organ system of the body that comprises of skin and its appendages such as hair follicles, sebaceous and sweat glands. Skin is divided into three distinct structural ...

  Citation × Citation Citation Abstract Copy Title: Transcription factor CTIP2 regulates hair follicle development, hair cycling and wound healing Author: Bhattacharya, Shreya The integumentary system is the largest organ system of the body that comprises of skin and its appendages such as hair follicles, sebaceous and sweat glands. Skin is divided into three distinct structural layers: the epidermis, dermis and hypodermis. The epidermis originates from the ectoderm and is composed of four layers specified as basal, spinous, granular and corneal layer. The function of epidermis is to protect against all sources of environmental insults, prevent water loss and undergo re-epithelialization after wounding. For its normal functioning, the epidermis continually replenishes itself through a process of continuous proliferation and terminal differentiation of keratinocytes from the basal layer. The hair follicle is a complex appendage of skin, which give rise to the keratinized hair shaft. Hair follicle is formed during embryonic development and it goes through cycles of growth (anagen), regression (catagen) and quiescence (telogen). The bulge region of the hair follicle in the outer root sheath area contains slow-cycling stem cells which are responsible for normal hair cycling as well as cutaneous wound repair after injury. CTIP2 (COUP-TF interacting protein 2) is a C2H2 zinc finger transcription factor that is expressed in various organs and tissues. It has been shown to play an important role in the development of thymocyte, tooth and corticospinal motor neuron. Expression of CTIP2 is observed in the developing murine epidermis and dermis during skin organogenesis and predominantly in epidermal keratinocytes in adult mice skin. It is also expressed in the embryonic and mature adult hair follicles, especially in bulge region. CTIP2 regulates epidermal proliferation and terminal differentiation during embryogenesis and adulthood. Here we show that CTIP2 controls hair follicle development, hair cycling and cutaneous wound healing. To study the role of CTIP2 in hair morphogenesis and hair cycling, we have utilized two different genetically modified mouse strains. First, we studied the effect of CTIP2 during hair follicle formation using Ctip2-null mice containing a germline deletion of Ctip2. Ctip2-null mice exhibited reduced hair follicle density and downregulation of EGFR and NOTCH1 expression. To analyze the consequence of loss-of–funtion of CTIP2 on postnatal hair cycling, we selectively ablated Ctip2 in the epidermis and hair follicles using the Cre-LoxP strategy to generate Ctip2[superscript ep-/-] mice. Ctip2[superscript ep-/-] mice showed a defect in postnatal hair cycling marked by early exit from telogen and premature entry into anagen. The premature induction of anagen is a result of stem cell activation, increase in cell proliferation and decrease in apoptosis-driven cell death in the hair follicles. This early activation of follicular stem cells eventually leads to their depletion and therefore ultimate loss of hair follicles and hair coat. Reduced expression of LHX2 and NFATC1, which are two important regulators of hair cycling, was observed in the bulge area of Ctip2[superscript ep-/-] mice hair follicles. Furthermore, chromatin immunoprecipitation (ChIP) assay revealed that CTIP2 is recruited to the promoter region of both Lhx2 and Nfatc1 and possibly directly regulates their expression. Altogether, our results suggest that CTIP2 modulates expression of factors that regulate hair follicle morphogenesis and normal hair cycling as well as control stem cell fate and survival in the HFs. Considering CTIP2’s role in skin formation and homeostasis we hypothesized that CTIP2 is involved in the epidermal regeneration process during wound closure after injury. To test our hypothesis, we used Ctip2[superscript ep-/-] mouse model where Ctip2 is conditionally inactivated in epidermis and hair follicle. Selective ablation of Ctip2 in the epidermis and HFs lead to the delay in wound healing. The slower healing property was an outcome of impaired keratinocyte activation, proliferation, differentiation and migration. Moreover, defects in cell-cell adhesion and ECM development were also observed in the healing wounds of Ctip2ep-/- mice due to the lack of E-cadherin and insufficient expression of alpha smooth muscle actin. Hair follicle stem cell factors such as K15, CD34, CD133, NFATC1 and LRIG1 that are crucial for wound re-epithelialization were aberrantly expressed in wound adjacent region of Ctip2[superscript ep-/-] mice. Our results identify CTIP2 as a key regulator of epidermal stem cells during skin wound healing and an important player in efficient wound closure after injury. Title: Transcription factor CTIP2 regulates hair follicle development, hair cycling and wound healing Author: Bhattacharya, Shreya The integumentary system is the largest organ system of the body that comprises of skin and its appendages such as hair follicles, sebaceous and sweat glands. Skin is divided into three distinct structural layers: the epidermis, dermis and hypodermis. The epidermis originates from the ectoderm and is composed of four layers specified as basal, spinous, granular and corneal layer. The function of epidermis is to protect against all sources of environmental insults, prevent water loss and undergo re-epithelialization after wounding. For its normal functioning, the epidermis continually replenishes itself through a process of continuous proliferation and terminal differentiation of keratinocytes from the basal layer. The hair follicle is a complex appendage of skin, which give rise to the keratinized hair shaft. Hair follicle is formed during embryonic development and it goes through cycles of growth (anagen), regression (catagen) and quiescence (telogen). The bulge region of the hair follicle in the outer root sheath area contains slow-cycling stem cells which are responsible for normal hair cycling as well as cutaneous wound repair after injury. CTIP2 (COUP-TF interacting protein 2) is a C2H2 zinc finger transcription factor that is expressed in various organs and tissues. It has been shown to play an important role in the development of thymocyte, tooth and corticospinal motor neuron. Expression of CTIP2 is observed in the developing murine epidermis and dermis during skin organogenesis and predominantly in epidermal keratinocytes in adult mice skin. It is also expressed in the embryonic and mature adult hair follicles, especially in bulge region. CTIP2 regulates epidermal proliferation and terminal differentiation during embryogenesis and adulthood. Here we show that CTIP2 controls hair follicle development, hair cycling and cutaneous wound healing. To study the role of CTIP2 in hair morphogenesis and hair cycling, we have utilized two different genetically modified mouse strains. First, we studied the effect of CTIP2 during hair follicle formation using Ctip2-null mice containing a germline deletion of Ctip2. Ctip2-null mice exhibited reduced hair follicle density and downregulation of EGFR and NOTCH1 expression. To analyze the consequence of loss-of–funtion of CTIP2 on postnatal hair cycling, we selectively ablated Ctip2 in the epidermis and hair follicles using the Cre-LoxP strategy to generate Ctip2[superscript ep-/-] mice. Ctip2[superscript ep-/-] mice showed a defect in postnatal hair cycling marked by early exit from telogen and premature entry into anagen. The premature induction of anagen is a result of stem cell activation, increase in cell proliferation and decrease in apoptosis-driven cell death in the hair follicles. This early activation of follicular stem cells eventually leads to their depletion and therefore ultimate loss of hair follicles and hair coat. Reduced expression of LHX2 and NFATC1, which are two important regulators of hair cycling, was observed in the bulge area of Ctip2[superscript ep-/-] mice hair follicles. Furthermore, chromatin immunoprecipitation (ChIP) assay revealed that CTIP2 is recruited to the promoter region of both Lhx2 and Nfatc1 and possibly directly regulates their expression. Altogether, our results suggest that CTIP2 modulates expression of factors that regulate hair follicle morphogenesis and normal hair cycling as well as control stem cell fate and survival in the HFs. Considering CTIP2’s role in skin formation and homeostasis we hypothesized that CTIP2 is involved in the epidermal regeneration process during wound closure after injury. To test our hypothesis, we used Ctip2[superscript ep-/-] mouse model where Ctip2 is conditionally inactivated in epidermis and hair follicle. Selective ablation of Ctip2 in the epidermis and HFs lead to the delay in wound healing. The slower healing property was an outcome of impaired keratinocyte activation, proliferation, differentiation and migration. Moreover, defects in cell-cell adhesion and ECM development were also observed in the healing wounds of Ctip2ep-/- mice due to the lack of E-cadherin and insufficient expression of alpha smooth muscle actin. Hair follicle stem cell factors such as K15, CD34, CD133, NFATC1 and LRIG1 that are crucial for wound re-epithelialization were aberrantly expressed in wound adjacent region of Ctip2[superscript ep-/-] mice. Our results identify CTIP2 as a key regulator of epidermal stem cells during skin wound healing and an important player in efficient wound closure after injury. Close