Facultative secondary lecithotrophy in the megalopa of the shrimp Lysmata seticaudata (Risso, 1816) (Decapoda : Hippolytidae) under laboratory conditions

Certain decapod crustaceans can catabolize internal reserves to undergo partial or full larval development. This feature is termed secondary lecithotrophy, if energy used results from plankton derived organic matter accumulated Ig earlier larval stages. The present work reports the ability of Lysmata seticaudata megalopa to moll to the first juvenile stage in the absence of food. Unlike previous records of secondary lecithotrophy displayed by nonfeeding last larval stages of hermit crabs and spiny lobsters, the megalopa of L. seticaudata retains its feeding capacity. This is the first time such a feature has been reported in decapods, and the term facultative secondary lecithotrophy is proposed. The build up of energy reserves continues during the last zoeal stage of L. seticaudata, with starved zoea IX failing to molt to megalopa. Energy reserves that enable starved megalopa to molt to juvenile seem to be partially depleted, with starved juveniles produced either from, starved or fed megalopae being unable to molt to the next juvenile stage. The longer resistance of starved juveniles produced from fed megalopae (nine days), compared to that of starved juveniles produced from starved megalopae (five days), indicates that some energy reserves may pass to juvenile, not being totally depleted at metamorphosis.info:eu-repo/semantics/publishedVersio

Decapod crustaceans associated with the snakelock anemone Anemonia sulcata. Living there or just passing by?

The present work identifies the decapod crustaceans that associate with Anemonia sulcata on the southwestern Atlantic coast of Portugal and characterises their host use pattern. It determines whether the anemone is monopolised by any species, resulting in the exclusion of conspecifics or other decapods and, under laboratory conditions, it evaluates the degree of association between each species and A. sulcata. From all sampled anemones, 79% harboured at least I decapod crustacean, with the majority displaying either one or two specimens (32 and 24%, respectively). The most abundant species were the shrimp Periclimenes sagittifer and the crab Inochus pholangium (representing 36 and 3 1 % of collected specimens, respectively), which displayed lasting associations and were commonly recorded among the tentacles of the host. The species Eualus occultus, E. complex cranchii, Clibanarius erythropus, Maja brachydactyla, Pilummus hirtellus and Polybius (Necora) puber displayed short-term associations, were mainly present on the substratum near the base, and avoided the tentacles of A. sulcata. Periclimenes sagittifr and I. phalangium were only recorded alone or in heterosexual pairs, appearing to efficiently defend their host against conspecifics. The majority of recorded species only seem to temporarily associate with A. sulcata, in order to seek protection from predators when other shelters are unavailable.info:eu-repo/semantics/publishedVersio

MYC is essential for the formation and maintenance of germinal centers

Germinal centers (GC) are sites of intense B cell proliferation, central for T cell dependent antibody responses. However, the role of MYC, a key cell cycle regulator, in this process has been questioned. Here, we identified MYC positive B cell subpopulations in immature and mature GCs, and show through genetic ablation of Myc that they play indispensable roles in GC formation and maintenance. The identification of these functionally critical cellular subsets has important implications for human B cell lymphomagenesis, which mostly originates from GC B cells and frequently involves MYC chromosomal translocations. As these translocations are generally dependent on transcription of the recombining partner loci, the MYC positive GC subpopulations may be at a particularly high risk for malignant transformation

Immature B cells preferentially switch to IgE with increased direct Sμ to Sε recombination

Immunoglobulin heavy chain (IgH) class-switch recombination (CSR) replaces initially expressed Cμ (IgM) constant regions (C(H)) exons with downstream C(H) exons. Stimulation of B cells with anti-CD40 plus interleukin-4 induces CSR from Cμ to Cγ1 (IgG1) and Cε (IgE), the latter of which contributes to the pathogenesis of atopic diseases. Although Cε CSR can occur directly from Cμ, most mature peripheral B cells undergo CSR to Cε indirectly, namely from Cμ to Cγ1, and subsequently to Cε. Physiological mechanisms that influence CSR to Cγ1 versus Cε are incompletely understood. In this study, we report a role for B cell developmental maturity in IgE CSR. Based in part on a novel flow cytometric IgE CSR assay, we show that immature B cells preferentially switch to IgE versus IgG1 through a mechanism involving increased direct CSR from Cμ to Cε. Our findings suggest that IgE dysregulation in certain immunodeficiencies may be related to impaired B cell maturation

Matrix stiffness controls lymphatic vessel formation through regulation of a GATA2-dependent transcriptional program

Tissue and vessel wall stiffening alters endothelial cell properties and contributes to vascular dysfunction. However, whether extracellular matrix (ECM) stiffness impacts vascular development is not known. Here we show that matrix stiffness controls lymphatic vascular morphogenesis. Atomic force microscopy measurements in mouse embryos reveal that venous lymphatic endothelial cell (LEC) progenitors experience a decrease in substrate stiffness upon migration out of the cardinal vein, which induces a GATA2-dependent transcriptional program required to form the first lymphatic vessels. Transcriptome analysis shows that LECs grown on a soft matrix exhibit increased GATA2 expression and a GATA2-dependent upregulation of genes involved in cell migration and lymphangiogenesis, including VEGFR3. Analyses of mouse models demonstrate a cell-autonomous function of GATA2 in regulating LEC responsiveness to VEGF-C and in controlling LEC migration and sprouting in vivo. Our study thus uncovers a mechanism by which ECM stiffness dictates the migratory behavior of LECs during early lymphatic development.Peer reviewe

RAC1(P29S) Induces a Mesenchymal Phenotypic Switch via Serum Response Factor to Promote Melanoma Development and Therapy Resistance

RAC1 P29 is the third most commonly mutated codon in human cutaneous melanoma, after BRAF V600 and NRAS Q61. Here, we study the role of RAC1P29S in melanoma development and reveal that RAC1P29S activates PAK, AKT, and a gene expression program initiated by the SRF/MRTF transcriptional pathway, which results in a melanocytic to mesenchymal phenotypic switch. Mice with ubiquitous expression of RAC1P29S from the endogenous locus develop lymphoma. When expressed only in melanocytes, RAC1P29S cooperates with oncogenic BRAF or with NF1-loss to promote tumorigenesis. RAC1P29S also drives resistance to BRAF inhibitors, which is reversed by SRF/MRTF inhibitors. These findings establish RAC1P29S as a promoter of melanoma initiation and mediator of therapy resistance, while identifying SRF/MRTF as a potential therapeutic target

Tumor-activated lymph node fibroblasts suppress T cell function in diffuse large B cell lymphoma

Recent transcriptomic-based analysis of diffuse large B cell lymphoma (DLBCL) has highlighted the clinical relevance of LN fibroblast and tumor-infiltrating lymphocyte (TIL) signatures within the tumor microenvironment (TME). However, the immunomodulatory role of fibroblasts in lymphoma remains unclear. Here, by studying human and mouse DLBCL-LNs, we identified the presence of an aberrantly remodeled fibroblastic reticular cell (FRC) network expressing elevated fibroblast-activated protein (FAP). RNA-Seq analyses revealed that exposure to DLBCL reprogrammed key immunoregulatory pathways in FRCs, including a switch from homeostatic to inflammatory chemokine expression and elevated antigen-presentation molecules. Functional assays showed that DLBCL-activated FRCs (DLBCL-FRCs) hindered optimal TIL and chimeric antigen receptor (CAR) T cell migration. Moreover, DLBCL-FRCs inhibited CD8+ TIL cytotoxicity in an antigen-specific manner. Notably, the interrogation of patient LNs with imaging mass cytometry identified distinct environments differing in their CD8+ TIL-FRC composition and spatial organization that associated with survival outcomes. We further demonstrated the potential to target inhibitory FRCs to rejuvenate interacting TILs. Cotreating organotypic cultures with FAP-targeted immunostimulatory drugs and a bispecific antibody (glofitamab) augmented antilymphoma TIL cytotoxicity. Our study reveals an immunosuppressive role of FRCs in DLBCL, with implications for immune evasion, disease pathogenesis, and optimizing immunotherapy for patients

Análise de Viabilidade do Transporte Público Coletivo Ferroviário na Linha do Oeste

Dissertação de Mestrado em Engenharia Civil na especialidade de Urbanismo, Transportes e Vias de Comunicação, apresentada à Faculdade de Ciências e Tecnologia da Universidade de Coimbra.Este trabalho pretende analisar o serviço ferroviário de passageiros na Linha do Oeste, o qual tem vindo ao longo dos últimos anos a registar acentuados decréscimos na procura de passageiros e que se revela incapaz de ser economicamente sustentável. Apesar destas dificuldades, e sendo a motivação desta Dissertação a deteção de potencialidades da zona do Oeste para a utilização deste modo de transporte, foi efetuado um estudo socioeconómico da região e foram traçados dois cenários de intervenção que considerassem essas potencialidades. Além destes cenários foi também analisado o cenário atual, tendo-se chegado à conclusão que do ponto de vista económico, não é viável a manutenção deste serviço sem alterações substanciais na sua eficiência e qualidade. O cenário atual traduz-se em procura reduzida e custos de exploração que superam largamente as receitas, contudo, investimentos na sua beneficiação incrementarão a procura de forma bastante acentuada, facto confirmado pela análise dos dois cenários acima referidos. Estes dois cenários distinguem-se essencialmente pelo nível de investimento aplicado, sendo que no cenário que implica um maior esforço financeiro, foi onde se observaram os melhores resultados económicos, com as receitas a serem superiores aos custos de exploração, apesar do investimento inicial nunca ser possível recuperar. No cenário em que o investimento foi menor, concluiu-se que, ao grande aumento de procura, não estão associados resultados económicos que ofereçam sustentabilidade ao serviço ferroviário.This document analyzes the passenger rail service in Western Line, which has been over the past years to register sharp declines in passenger demand and that is unable to be economically sustainable. Despite these difficulties, and being the motivation of this Dissertation the detection of the potential of the West area for using this mode of transport, it was conducted a socioeconomic study of the region and were set two intervention scenarios that consider this potential. In addition to these scenarios was also analyzed the current scenario, having come to the conclusion that from an economic point of view, it is not feasible to maintain this service without substantial changes in their efficiency and quality. The current scenario translates into reduced demand and operating costs that far outweigh the revenues, however, investments in its improvement will increase the demand for quite sharply, confirmed by the analysis of the two scenarios above. These two scenarios are distinguished primarily by the applied level of investment, and in the scenario that implies a greater financial effort, was where we found the best economic results, with revenues to be higher than operation costs, despite the initial investment will never be able to recover. In the scenario in which the investment was lower, it was concluded that the large increase in demand, are not associated with economic results that provide sustainability to rail service

Bopyrid isopods do not castrate the simultaneously hermaphroditic shrimp Lysmata amboinensis (Decapoda : Hippolytidae)

This study evaluates possible parasitic castration induced by a bopyrid isopod of the genus Parabopyrella, which parasitizes the branchial chamber of the simultaneously hermaphroditic shrimp Lysmata amboinensis. Parasitized shrimp (PS) carried embryos and produced significantly fewer larvae (mean +/- SD: 363 +/- 102; p = 0.002) than formerly parasitized shrimp (FPS) (1297 +/- 143) and unparasitized shrimp (US) paired with other US (1409 +/- 102), with PS (1362 +/- 234) or with FPS (1384 +/- 157). Starvation trials revealed no significant differences in the quality of larvae produced by PS, FPS and US paired with other US, PS and FPS. Host embryo production is only quantitatively, not qualitatively, affected, probably due to nutritional drain and/or endocrine disruption caused by the parasite. The host male sexual system remains fully functional and 'reproductive death' does not occur. The feminization of pleopods that prevents parasitized males of gonochoric species from successfully copulating seems to have no effect on L. seticaudata: pleopods are always feminized during their transition from male to simultaneous hermaphrodite phase, with adults being able to successfully fertilize broods. Parabopyrella sp. significantly affects the female sexual system of its host, but does not cause castration, as recorded for L. seticaudata parasitized by the bopyrid isopod Eophryxus lysmatae (an abdominal parasite)

Immune Crosstalk Between Lymph Nodes and Breast Carcinomas, With a Focus on B Cells

Lymph nodes (LNs) are highly organized secondary lymphoid organs, and reflective of immune responses to infection, injuries, or the presence of cancer. Extensive molecular and morphological analyses of immune and stromal features in tumors and LNs of breast cancer patients have revealed novel patterns indicative of disease progression. Within LNs, there are dynamic structures called germinal centers (GCs), that act as the immunological hubs for B cell development and generation of affinity matured memory B and antibody-producing plasma cells. Acting as a bridge between systemic and local immunity, associations are observed between the frequency of GCs within cancer-free LNs, the levels of stromal tumor infiltrating lymphocytes, and cancer progression. Scattered throughout the tumor microenvironment (TME) or aggregated in clusters forming tertiary lymphoid structures (TLS), the occurrence of tumor infiltrating B cells (TIL-Bs) has been linked mostly to superior disease trajectories in solid cancers. Recent TIL-Bs profiling studies have revealed a plethora of different TIL-B populations, their functional roles, and whether they are derived from GC reactions in the LN, and/or locally from GC-like structures within the TME remains to be investigated. However, parallels between the immunogenic nature of LNs as a pre-metastatic niche, TIL-B populations within the TME, and the presence of TLS will help to decipher local and widespread TIL-Bs responses and their influence on cancer progression to the lymphatics. Therapies that enhance TIL-Bs responses in the LN GC and/or in GC-like structures in the TME are thus emerging management strategies for breast and other cancer patients