TWEAK/Fn14 Signaling Is Required for Liver Regeneration after Partial Hepatectomy in Mice

Background & Aims: Pro-inflammatory cytokines are important for liver regeneration after partial hepatectomy (PH). Expression of Fibroblast growth factor-inducible 14 (Fn14), the receptor for TNF-like weak inducer of apoptosis (TWEAK), is induced rapidly after PH and remains elevated throughout the period of peak hepatocyte replication. The role of Fn14 in post-PH liver regeneration is uncertain because Fn14 is expressed by liver progenitors and TWEAK-Fn14 interactions stimulate progenitor growth, but replication of mature hepatocytes is thought to drive liver regeneration after PH. Methods: To clarify the role of TWEAK-Fn14 after PH, we compared post-PH regenerative responses in wild type (WT) mice, Fn14 knockout (KO) mice, TWEAK KO mice, and WT mice treated with anti-TWEAK antibodies. Results: In WT mice, rare Fn14(+) cells localized with other progenitor markers in peri-portal areas before PH. PH rapidly increased proliferation of Fn14(+) cells; hepatocytic cells that expressed Fn14 and other progenitor markers, such as Lgr5, progressively accumulated from 12-8 h post-PH and then declined to baseline by 96 h. When TWEAK/Fn14 signaling was disrupted, progenitor accumulation, induction of pro-regenerative cytokines, hepatocyte and cholangiocyte proliferation, and over-all survival were inhibited, while post-PH liver damage and bilirubin levels were increased. TWEAK stimulated proliferation and increased Lgr5 expression in cultured liver progenitors, but had no effect on either parameter in cultured primary hepatocytes. Conclusions: TWEAK-FN14 signaling is necessary for the healthy adult liver to regenerate normally after acute partial hepatectomy.

As Recordações de Itália (1852-1853), de A. P. Lopes de Mendonça: uma obra política: edição e estudo crítico

António Pedro Lopes de Mendonça, escritor romântico de postura liberal radical, que fez da literatura seu meio de subsistência, produziu uma escrita que flertou com muitos gêneros, da crônica-folhetim ao romance porém sempre permeada pelo viés político. Defendeu o Romantismo como um movimento extraliterário que ajudou a impulsionar transformações cruciais na sociedade portuguesa e, filiado à política jacobina, foi um dos precursores dos ideais socialistas em Portugal. Fez oposição à Regeneração, por entender que os esforços deste governo eram insuficientes às necessidades do país, e soube reconhecer, posteriormente, as mudanças promovidas por ele, defendendo os regeneradores em comparação com os absolutistas. Foi considerado ultrarromântico por muitos autores, o que consideramos uma classificação reducionista, por não ter em conta um aspecto fulcral da obra deste autor: o objetivo de formar leitores críticos, o compromisso civilizacional, de conscientizar e de ser combativo às injustiças de sua época. Usou a ironia a seu favor, como uma arma de pensamento, para acomodar, nas entrelinhas de seus romances, suas críticas à sociedade que se apresentava. Tendo percorrido uma Itália ainda não unificada, na viagem que inspirou as Recordações de Itália, pôde perceber como a falta de unidade dos grupos revolucionários em torno de um mesmo ideal era empecilho à unificação daquele país e convocou, por meio de seu jornal Eco dos Operários, as classes menos favorecidas à busca por justiça social, dando espaço a textos dos próprios trabalhadores e incutindo neles a importância da soma de forças por uma causa única. Morreu como louco, certamente não por não aceitar e por não se adequar às hipocrisias e injustiças que lhe eram impostas por aquela sociedade

Influence of Extracellular Matrix Components on the Expression of Integrins and Regeneration of Adult Retinal Ganglion Cells

Purpose Retinal ganglion cells (RGCs) are exposed to injury in a variety of optic nerve diseases including glaucoma. However, not all cells respond in the same way to damage and the capacity of individual RGCs to survive or regenerate is variable. In order to elucidate factors that may be important for RGC survival and regeneration we have focussed on the extracellular matrix (ECM) and RGC integrin expression. Our specific questions were: (1) Do adult RGCs express particular sets of integrins in vitro and in vivo? (2) Can the nature of the ECM influence the expression of different integrins? (3) Can the nature of the ECM affect the survival of the cells and the length or branching complexity of their neurites? Methods Primary RGC cultures from adult rat retina were placed on glass coverslips treated with different substrates: Poly-L-Lysine (PL), or PL plus laminin (L), collagen I (CI), collagen IV (CIV) or fibronectin (F). After 10 days in culture, we performed double immunostaining with an antibody against beta III-Tubulin to identify the RGCs, and antibodies against the integrin subunits: alpha V, alpha 1, alpha 3, alpha 5, beta 1 or beta 3. The number of adhering and surviving cells, the number and length of the neurites and the expression of the integrin subunits on the different substrates were analysed. Results PL and L were associated with the greatest survival of RGCs while CI provided the least favourable conditions. The type of substrate affected the number and length of neurites. L stimulated the longest growth. We found at least three different types of RGCs in terms of their capacity to regenerate and extend neurites. The different combinations of integrins expressed by the cells growing on different substrata suggest that RGCs expressed predominantly alpha 1 beta 1 or alpha 3 beta 1 on L, alpha 1 beta 1 on CI and CIV, and alpha 5 beta 3 on F. The activity of the integrins was demonstrated by the phosphorylation of focal adhesion kinase (FAK). Conclusions Adult rat RGCs can survive and grow in the presence of different ECM tested. Further studies should be done to elucidate the different molecular characteristics of the RGCs subtypes in order to understand the possible different sensitivity of different RGCs to damage in diseases like glaucoma in which not all RGCs die at the same time.

Strategy on International Fisheries Research: an update

The Strategy on International Fisheries Research's activities on information and aquaculture in Asia, SubSaharan Africa, Latin and North America are presented.

Investing in Africa: the WorldFish Center's African strategy in summary

Across much of Africa, freshwater and coastal fisheries provide an important source of food and livelihood for many millions of people. In addition, the aquaculture potential of the continent has only recently begun to be developed. To help sustain these capture fisheries, support the emergence of aquaculture and foster the contribution of both to sustainable livelihoods and improved food security, the WorldFish Center is increasing its investment in Africa. The framework for this investment is provided by a new Strategy for Africa and West Asia 2002-2006 that identifies priorities for the Center’s work in rivers and floodplains, lakes and reservoirs, coastal fisheries, aquaculture, policy research and capacity building. The present article summarizes the issues being addressed by the Center and describes initial research priorities.