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Summary: Deep‐water access is arguably the most effective, but under‐studied, mechanism that plants employ to survive during drought. Vulnerability to embolism and hydraulic safety margins can predict mortality risk at given levels of dehydration, but deep‐water access may delay plant dehydration. Here, we tested the role of deep‐water access in enabling survival within a diverse tropical forest community in Panama using a novel data‐model approach.We inversely estimated the effective rooting depth (ERD, as the average depth of water extraction), for 29 canopy species by linking diameter growth dynamics (1990–2015) to vapor pressure deficit, water potentials in the whole‐soil column, and leaf hydraulic vulnerability curves. We validated ERD estimates against existing isotopic data of potential water‐access depths.Across species, deeper ERD was associated with higher maximum stem hydraulic conductivity, greater vulnerability to xylem embolism, narrower safety margins, and lower mortality rates during extreme droughts over 35 years (1981–2015) among evergreen species. Species exposure to water stress declined with deeper ERD indicating that trees compensate for water stress‐related mortality risk through deep‐water access.The role of deep‐water access in mitigating mortality of hydraulically‐vulnerable trees has important implications for our predictive understanding of forest dynamics under current and future climates. [ABSTRACT FROM AUTHOR]

Summary: The effects of climate change on tropical forests will depend on how diverse tropical tree species respond to drought. Current distributions of evergreen and deciduous tree species across local and regional moisture gradients reflect their ability to tolerate drought stress, and might be explained by functional traits.We measured leaf water potential at turgor loss (i.e. 'wilting point'; πtlp), wood density (WD) and leaf mass per area (LMA) on 50 of the most abundant tree species in central Panama. We then tested their ability to explain distributions of evergreen and deciduous species within a 50 ha plot on Barro Colorado Island and across a 70 km rainfall gradient spanning the Isthmus of Panama.Among evergreen trees, species with lower πtlp were associated with drier habitats, with πtlp explaining 28% and 32% of habitat association on local and regional scales, respectively, greatly exceeding the predictive power of WD and LMA. In contrast, πtlp did not predict habitat associations among deciduous species.Across spatial scales, πtlp is a useful indicator of habitat preference for tropical tree species that retain their leaves during periods of water stress, and holds the potential to predict vegetation responses to climate change. [ABSTRACT FROM AUTHOR]

Tropical forests are well known for their high woody plant diversity. Processes occurring at early life stages are thought to play a critical role in maintaining this high diversity and shaping the composition of tropical tree communities. To evaluate hypothesized mechanisms promoting tropical tree species coexistence and influencing composition, we initiated a census of woody seedlings and small saplings in the permanent 50 ha Forest Dynamics Plot (FDP) on Barro Colorado Island (BCI), Panama. Situated in old‐growth, lowland tropical moist forest, the BCI FDP was originally established in 1980 to monitor trees and shrubs ≥1 cm diameter at 1.3 m above ground (dbh) at ca. 5‐year intervals. However, critical data on the dynamics occurring at earlier life stages were initially lacking. Therefore, in 2001 we established a 1‐m2 seedling plot in the center of every 5 × 5 m section of the BCI FDP. All freestanding woody individuals ≥20 cm tall and <1 cm dbh (hereafter referred to as seedlings) were tagged, mapped, measured, and identified to species in 19,313 1‐m2 seedling plots. Because seedling dynamics are rapid, we censused these seedling plots every 1–2 years. Here, we present data from the 14 censuses of these seedling plots conducted between the initial census in 2001 to the most recent census, in 2018. This data set includes nearly 1 M observations of ~185,000 individuals of >400 tree, shrub, and liana species. These data will permit spatially‐explicit analyses of seedling distributions, recruitment, growth, and survival for hundreds of woody plant species. In addition, the data presented here can be linked to openly‐available, long‐term data on the dynamics of trees and shrubs ≥1 cm dbh in the BCI FDP, as well as existing data sets from the site on climate, canopy structure, phylogenetic relatedness, functional traits, soil nutrients, and topography. This data set can be freely used for non‐commercial purposes; we request that users of these data cite this data paper in all publications resulting from the use of this data set. [ABSTRACT FROM AUTHOR]

Abstract: Macrophages respond to endogenous and non-self stimuli acquiring the M1 or M2 phenotypes, corresponding to classical or alternative activation, respectively. The role of B-1 cells in the regulation of macrophage polarization through the secretion of interleukin (IL)-10 has been demonstrated. However, the influence of B-1 cells on macrophage phenotype induction by an immunogen that suppress their ability to secrete IL-10 has not been explored. Here, we studied the peritoneal macrophage pattern induced by liposomes comprised of dipalmitoylphosphatidylcholine (DPPC) and cholesterol (Chol) carrying ovalbumin (OVA) (Lp DPPC/OVA), and the involvement of B-1 cells in macrophage polarization. Peritoneal cells from BALB/c, B-1 cells-deficient BALB/xid and C57BL/6 mice immunized with Lp DPPC/OVA and OVA in soluble form (PBS/OVA) were analyzed and stimulated or not in vitro with lipopolysaccharide (LPS). Peritoneal macrophages from BALB/c and C57BL/6 mice immunized with Lp DPPC/OVA showed an M2-like phenotype as evidenced by their high arginase activity without LPS stimulation. Upon stimulation, these macrophages were reprogrammable toward the M1 phenotype with the upregulation of nitric oxide (NO) and a decrease in IL-10 secretion. In addition, high IFN-γ levels were detected in the culture supernatant of peritoneal cells from BALB/c and C57BL/6 mice immunized with Lp DPPC/OVA. Nevertheless, still high levels of arginase activity and undetectable levels of IL-12 were found, indicating that the switch to a classical activation state was not complete. In the peritoneal cells from liposomes-immunized BALB/xid mice, levels of arginase activity, NO, and IL-6 were below those from wild type animals, but the last two products were restored upon adoptive transfer of B-1 cells, together with an increase in IFN-γ secretion. Summarizing, we have demonstrated that Lp DPPC/OVA induce an M2-like pattern in peritoneal macrophages reprogrammable to M1 phenotype after LPS stimulation, with the involvement of B-1 cells. [Copyright &y& Elsevier]

Epidermal Growth Factor Receptor (EGFR or HER1) is considered a tumor associated antigen. HER1 is overexpressed in many human epithelial tumors and involved in crucial cellular functions for tumor development. For this reason HER1 is considered a good target for cancer immunotherapy and some passive agents are being evaluated in clinical trials. However , HER1-based active immunotherapy has not been clinically explored. To develop an active immunotherapy approach based on HER1 for the treatment of HER1+ cancer patients, we cloned and expressed in mammalian cells the HER1 extracellular domain protein (HER1-ECD), which was specifically recognized by an anti- EGFR monoclonal antibody. HER1-ECD was purified by affinity chromatography and adjuvated in Very Small Size Proteoliposomes (VSSP) or Complete Freund adjuvant to immunize C57BL/6 mice. Immunization elicited specific humoral and cellular immune response. The polyclonal antibodies induced by immunization recognized the full length HER1 on the surface of a lung tumor cell line. These results suggest that HER1-ECD could be an appropriated antigen to induce specific immune response in patients with HER1+ tumors. [ABSTRACT FROM AUTHOR]

Abstract: P3 mAb is an IgM monoclonal antibody specific for N-glycolyl-containing gangliosides. The immunogenicity of the P3 idiotype has been previously described by immunizing syngeneic BALB/c mice with the purified murine IgM or the mouse-human chimeric IgG antibody. In the present work we study the antibody response against the idiotype of P3 mAb through immunization with DNA. We used small immune proteins (SIP) consisting on the idiotype in the scFv format, covalently linked to γ1CH3, the self-dimerizing domain of murine IgG1. SIPs were previously shown to be appropriate to induce specific anti-idiotypic responses. By gene gun immunization, a polyspecific response was occasionally generated, particularly with the P3 idiotype. A single shot of DNA was sufficient to induce a strong and long-lasting anti-P3 idiotype response. In addition, by delivery of the same DNA construct with a recombinant adeno-associated virus the unique immunogenicity of the P3 idiotype was demonstrated. The requirement of T cells in the anti-P3 idiotype response was indicated by the lack of P3-specific anti-idiotypic antibodies following immunization of both, allogeneic C57BL/6 and athymic BALB/c mice. [Copyright &y& Elsevier]

Abstract: The heavy-chain variable regions (VH) from 14F7 MAb, an IgG1 antibody specific for GM3(NeuGc) ganglioside, and its anti-idiotype, the 4G9 MAb, were cloned and sequenced. Comparison with previously reported sequences showed that VH 14F7 belongs to the J558(VHI) gene family and that it is highly mutated. VH 4G9 belongs to the Q52(VHII) gene family. The HCDR3 14F7 sequence contains three basic residues that could be involved in the binding to 4G9 MAb, which bears acidic residues in its HCDR3. Studies performed in the syngeneic model showed that 14F7 MAb requires both coupling to KLH and the use of Freund''s adjuvant to induce an effective anti-idiotypic IgG (Ab2) response. In contrast, P3 MAb, a germline gene-encoded Ab1 that also recognizes the GM3(NeuGc) ganglioside through a basic motif in its H-CDRs, has been reported to be immunogenic in syngeneic mice, even when injected in saline. In addition, when Leghorn chickens were immunized with 14F7 or P3 MAbs emulsified in Freund′s adjuvant, only P3-immunized animals were able to develop antibodies that recognized NeuGc-containing gangliosides, antigens which are not present in the normal tissues of this animal species. This phenomenon could be due to the lack of idiotypic connectivity of 14F7MAb. [Copyright &y& Elsevier]

Within a short period of time, the teaching and popularization of Biotechnology has become a need not only for the academic world, but for society as well. The advances in this field have repercussions within the scientific community, as well as politicians, businessmen, manufacturers, lawyers, journalists and the general population alike. At the same time, Biotechnology as a discipline is not stagnant, but evolves with the findings of related disciplines such as Biology, Biochemistry, Genetics, Microbiology, process-related engineering specialties (chemical, biochemical or industrial) and other sciences such as Physics, Mathematics and Information Technology. Given its importance for society and its multidisciplinary nature, designing a method for the popularized teaching of Biotechnology that gives a general approach to this field and not resulting overly complex is a considerable challenge. Such a design, therefore, must take into account the methodological complexity, resulting in courses with very specific objectives and targeted to a certain audience, or conceived with a general structure offering an overall knowledge of this discipline in varying degrees, depending on the cultural and educational level of the learner. The present paper shows our experience in the design of a Biotechnology course, following a methodological conception for the adaptation of the contents to the specific goals of the course for the targeted audience while following a train of thought and a relationship with the facts of everyday life. [ABSTRACT FROM AUTHOR]

La enseñanza de la Biotecnología se ha convertido en pocos años en una necesidad, no solo del mundo académico, sino también de la sociedad en su conjunto. Los científicos y también los políticos, los comerciales, los productores, los abogados, los periodistas, los economistas y la población en general están relacionados de una forma u otra con los avances en esta rama, y a la vez la Biotecnología continúa en desarrollo con los avances de otras ciencias como la Biología, la Bioquímica, la Genética, la Microbiología, las ingenierías vinculadas a procesos (química, bioquímica o industrial), y con otras ciencias como la Física, las Matemáticas y las Ciencias de la Computación. La Biotecnología requiere de todas estas ciencias y tecnologías particulares, pero el problema fundamental consiste en diseñar un método para su estudio que posibilite su enfoque de manera integral de manera que no resulte tan compleja. El diseño de un programa de estudio sobre Biotecnología debe entonces tener en cuenta esta complejidad metodológica y su concepción. El curso debe estar dirigido a objetivos específicos, sectores determinados, o concebido de forma general para que posibilite apropiarse del conocimiento global en diferentes grados en dependencia del nivel educacional y cultural del receptor. En el presente artículo se muestra la experiencia de diseño de un programa sobre Biotecnología, siguiendo una concepción metodológica que permite adaptar los contenidos y los objetivos específicos que se persiguen según el público al que va dirigido, manteniendo siempre un hilo conductor y una relación con la vida cotidiana. [ABSTRACT FROM AUTHOR]

The article provides information on the highlights of "Immunotherapy for the New Century," the continuation of a series of international workshops organized by the Center of Molecular Immunology (CIM), in Havana, Cuba in 2004. The event was focused on the impact of the complexity of the Immune System (IS) in the development of new cancer immunotherapeutic agents. The instructive role of the Innate Immune System (IIS) on the Adaptive Immune System (AIS) is one major concept of the regulation of the IS.

The Epidermal Growth Factor Receptor (EGFR) plays an essential role in regulating neoplastic processes. EGFR over-expression in many human epithelial tumors has been correlated with disease progression and bad prognosis. Passive EGFR-directed immunotherapy has been introduced in medical oncology practice, but no active specific approaches have been used. We designed a vaccine candidate based on the extracellular domain (ECD) of human EGFR (HER1), and the homologous vaccine for mice based on murine EGFR. This vaccine candidate uses the Very Small-Sized Proteoliposomes from Neisseria meningitidis (VSSP) and Montanide ISA 51 -VG as adjuvants. The autologous vaccine circumvents the tolerance to self EGFR by inducing a specific immune response with an anti-metastatic effect on EGFR+ tumors. The vaccine candidate based on HER1 -ECD induced anti-EGFR polyclonal antibodies (PAb) that bind EGFR+ human tumor cell lines from different tissues. These anti-EGFR PAb abrogate ligand-dependent EGFR phosphorylation, provoking the inhibition of tumor cell growth and apoptosis. Preclinical results further encouraged the evaluation of the HER1 vaccine candidate in phase I clinical trials. [ABSTRACT FROM AUTHOR]

The epidermal growth factor receptor (EGFR) is considered one of the main targets for the treatment of epithelial tumors. Growing evidence shows the essential role of this receptor in disseminating metastasis. The Center of Molecular Immunology (CIM) has pioneered the development of this new therapeutic concept, generating different anti-EGFR agents that are currently under preclinical and clinical evaluation. One of these agents is the h-R3 monoclonal antibody (MAb h-R3), used to treat patients with metastatic tumors. The mechanisms by which the anti-EGFR MAbs exert their anti-metastatic effect is not yet clear, since studies have been made in athymic mice transplanted with human tumors, where the role of T cells cannot be characterized. We obtained here for the first time a MAb that can recognize the extracellular domain of the murine EGFR, named 7A7. It allowed us to confirm the potent anti-metastatic effect of anti-EGFR MAbs in immunocompetent mice. The EGFR signaling inhibition, mediated by anti-proliferative, anti-migratory and pro-apoptotic effects contributes to its anti-metastatic effect. Also, these results suggest the induction of cytotoxic responses through the Fc region of 7A7 could increase its antitumor effect. This was also the first report of a MAb that depends on CD4+ and CD8+ T cell functions to exert its anti-metastatic effects. [ABSTRACT FROM AUTHOR]

El receptor del factor de crecimiento epidérmico (EGFR, del inglés epidermal growth factor receptor) es considerado uno de los blancos principales para el tratamiento de los tumores de origen epitelial. Se han acumulado evidencias de que este receptor puede desempeñar un papel importante en la diseminación metastásica. El Centro de Inmunología Molecular (CIM) ha sido pionero en el desarrollo de este nuevo concepto terapéutico, y ha generado diferentes agentes anti-EGFR que se encuentran en fases de evaluación preclínica y clínica. Un ejemplo de ello es el anticuerpo monoclonal (AcM) h R3, utilizado para el tratamiento de pacientes con tumores metastásicos. Los mecanismos asociados al efecto antimetastásico de los AcM anti-EGFR no se han dilucidado totalmente, ya que los estudios han sido en ratones atímicos trasplantados con tumores humanos, donde no se puede analizar la participación de las células T. Tras esta investigación se obtuvo por primera vez un AcM capaz de reconocer el dominio extracelular del EGFR murino. Este AcM nos permitió confirmar el potente efecto antimetastásico de los AcMs anti-EGFR en ratones inmunocompetentes. Se demostró que la inhibición de la señalización por el EGFR contribuye a este fenómeno, mediante efectos antiproliferativos, antimigratorios y proapoptóticos, y sugiere que la inducción de respuestas citotóxicas por la región constante de este AcM es un mecanismo que puede incrementar su potencial antitumoral. Este estudio constituye el primer reporte sobre la dependencia de un AcM anti-EGFR de la función de las células T-CD4+ y CD8+ para ejercer su efecto antimetastásico. [ABSTRACT FROM AUTHOR]

Immune escape is one of the essential properties of tumors. However, there are no evidences discriminating if the establishment of the immune suppressor phenotype is exclusively determined by the immune system pressure on tumor progression, or intrinsically supported by the events leading to neoplastic transformation. To unravel this dichotomy, we used two in vitro models based on the sequential transformation of mesenchymal stem cells (MSC). Malignant transformation reinforces the natural immune escape properties of MSC, mediated by the reduction of membrane HLA class I levels and the increasing inhibitory capacity on T cells. It was evidenced that as a consequence of transformation, there is a transition in the natural inhibitory effect of MSC on T-cell proliferation from an inducible mechanism depending on IFN-γ signaling and mediated by indoleamine 2,3-dioxygenase towards a constitutive mechanism involving TGF-β, HGF, COX-2 and PDL-1. It was found that the increased expression of the inflammatory mediators IL-1β and PGE2 caused by the neoplastic transformation of MSC supports the immune suppressor properties of these cells. Our results indicate that oncogenic signals are able to concert intrinsic inflammation and immune escape, independently of the selective pressure of the immune system. This research granted the 2015 Award of the Cuban National Academy of Sciences. [ABSTRACT FROM AUTHOR]

The epidermal growth factor receptor (EGFR) plays a central role in the development and progression of many tumors and its overexpression is associated with decreased survival, being an attractive target for cancer treatment. We introduce here a new therapeutic cancer vaccine based in the extracellular domain of human EGFR (EGFR-ECD). Vaccination of mice with EGFR-ECD induced both specific IgG secreting B cells and CD4+ T cells. Besides, sera from immunized mice reacted with antigen-positive cell lines and inhibited the EGF/EGFR binding. Furthermore immunization of mice with murine EGFR ECD (mEGFR-ECD) in appropriated adjuvants, produced specific high titer antibody response with a TH1 isotype profile. No toxicity associated to vaccine administration was detected. [ABSTRACT FROM AUTHOR]

P3 mAb is a murine IgM that specifically recognizes N-glycolyl (NeuGc)-gangliosides and sulfatides. It also reacts with antigens expressed in human breast tumors and melanoma. In syngeneic model, P3 mAb is able to elicit a strong anti-idiotypic (Ab2) antibody response, even in absence of adjuvants or carrier proteins. Here we reported the construction of the human IgG1 chimeric P3 antibody, and the evaluation of the maintenance of the main properties of the murine P3 mAb. Chimeric P3 antibody specifically reacted with GM3(NeuGc) and GM2(NeuGc) gangliosides, and not with their acetylated variants. Also, it recognized the anti-idiotypic 1E10 mAb. Upon immunization of Balb/c mice with chimeric P3 antibody, we were able to demonstrate the immunodominance of its variable region. The anti-idiotypic response induced by this antibody was very strong and in three out of four mice was even significantly higher than the anti-isotypic response, despite the fact that 70% of the chimeric molecule is xenogenic with respect to the animal model. In chickens, the immunogenicity of chimeric P3 antibody idiotype was also evaluated. [ABSTRACT FROM AUTHOR]

We developed a phase I clinical trial for patients with stage III/IV breast carcinoma treated with the anti-idiotype mAb 1E10 (Ab2) specific to an Ab1 mAb (P3) able to react specifically with N-glycolyl-containing gangliosides and with antigens expressed on human melanoma and breast carcinoma cells. In animal models this Ab2 mAb induced Ab3 antibody responses sharing immunochemically-defined idiotopes with the Ab1, but unable to recognize N-glycolyl-containing gangliosides. The treatment of tumor-bearing mice with 1E10 mAb induced a strong antitumor activity. In a previous clinical trial carried out with anti-id mAb 1E10 in patie nts with advanced malignant melanoma, the vaccine proved to be safe and immunologically effective, with most patients being able to generate a specific immune response against 1E10 and NeuGc-GM3 ganglioside. The purpose of the present study was to evaluate the toxicity, the immune response to 1E10 anti- id vaccine and to test two levels of doses of the vaccine preparation. Ten patients of breast carcinoma, distributed in two groups of five, received six doses of 1 and 2 mg respectively, of aluminum hydroxide precipitated 1E10 anti-id mAb, intradermally into multiple sites at two weeks intervals. In eight of the nine patients who received at least four doses of the anti- id vaccine strong specific responses were observed both against 1E10 mAb and the NeuGc-GM3 ganglioside (Ab3Id+Ag+). Non-classical Ab1' antibodies (Id-Ag+) were also elicited by 1E10 mAb vaccine treatment. The comparative analyses of the responses indicated that there were not differences between the two levels of dose tested in relation to toxic ity and immunogenicity. No evidences of serious or unexpected effects were observed. The results of this clinical trial showed that 1E10 anti-id vaccine was well tolerated and immunologically active, capable of inducing a specific immune response against 1E10 and NeuGc-GM3 ganglioside in most breast cancer patients. [ABSTRACT FROM AUTHOR]

Transforming Growth Factor alpha (TGFα) is an endogenous growth factor that is associated with the loss of growth regulation of the transformed phenotype and its action is by the interaction with the epidermal growth factor (EGF) receptor. Also this molecule is over-expressed by carcinomas as a tumor-associated antigen. In this regard the principal goal of this work is to development an active immunoteraphy capable to block the autocrine loop TGFα-EGFR and/or to elicit a specific cellular response against tumor that over-expressed this growth factor. To our knowledge TGFα has not been used in active specific cancer immunotherapy. A new vaccine containing a fusion protein between human TGFα (hTGFα) and P64k from Neisseria meningitidis, was generated and characterized in a mouse model using different adjuvants. Interestingly a good correlation between anti-hTGFα serum antibody titers, mainly IgG, and antibody secreting B cells in the lymph nodes of immunized mice was seen. The isotype profile of hTGFα-specific antibody responses was similar when Freund adjuvant complete or incomplete was used showing increase levels of IgG2a and IgG2b immunoglobulins respect to aluminum hydroxide. Noteworthy, those anti-hTGFα antibodies recognize the hTGFα precursor in cell line expressing this growth factor. For 4 peptide represent the different loops of hTGFα tested, serum from immunized mice mainly recognize the C-loop and C-terminal region. That region is important in the TGFα/EGF-R binding. Not crossreactivity against human or murine epidermal growth factor (EGF) was found. [ABSTRACT FROM AUTHOR]

An heterophilic ganglioside cancer vaccine, obtained by combining NeuGcGM3 with the outer membrane protein complex of Neisseria meningitidis to form very small size proteoliposomes (VSSP), and incomplete Freund's adjuvant (Montanide ISA 51) was developed. A phase I clinical trial was performed to determine safety and immunogenicity of this vaccine. Stage III- IV breast cancer patients received up to fifteen (200 (g) doses of the vaccine by intramuscular injection. The first 5 doses (induction phase) were given at two weeks intervals, while in the remaining of the treatment (maintenance) monthly administrations were given. Patients (21), 11 of whom had metastatic disease, were included. Main toxicity's included erythema and induration at the injection site, sometimes associated with mild pain, and low-grade fever (WHO grades I, II). All treated patients, who completed the induction phase, developed anti-NeuGcGM3 antibody titers between 1: 1,280 to 1:164,000 (IgG) and 1:640 to 1:160,000 (IgM). Noteworthy specific IgA antibodies were induced by vaccination in all stage III patients and in 3 stage IV patients. Serum antibody levels were higher in the stage III patients, with the larger increases being observed after week 32. Hyper-immune sera marked IgG differential reactivity against human mammary ductal carcinoma samples. NeuGcGM3/VSSP/Montanide ISA 51 is the highly immunogenic ganglioside vaccine and is also safe. Post-immune serum specific IgA, and IgG reactivity vs human mammary ductal carcinoma, warrants further exploration. [ABSTRACT FROM AUTHOR]

Mycorrhizae, a form of plant-fungal symbioses, mediate vegetation impacts on ecosystem functioning. Climatic effects on decomposition and soil quality are suggested to drive mycorrhizal distributions, with arbuscular mycorrhizal plants prevailing in low-latitude/high-soil-quality areas and ectomycorrhizal (EcM) plants in high-latitude/low-soil-quality areas. However, these generalizations, based on coarse-resolution data, obscure finer-scale variations and result in high uncertainties in the predicted distributions of mycorrhizal types and their drivers. Using data from 31 lowland tropical forests, both at a coarse scale (mean-plot-level data) and fine scale (20 × 20 metres from a subset of 16 sites), we demonstrate that the distribution and abundance of EcM-associated trees are independent of soil quality. Resource exchange differences among mycorrhizal partners, stemming from diverse evolutionary origins of mycorrhizal fungi, may decouple soil fertility from the advantage provided by mycorrhizal associations. Additionally, distinct historical biogeographies and diversification patterns have led to differences in forest composition and nutrient-acquisition strategies across three major tropical regions. Notably, Africa and Asia's lowland tropical forests have abundant EcM trees, whereas they are relatively scarce in lowland neotropical forests. A greater understanding of the functional biology of mycorrhizal symbiosis is required, especially in the lowland tropics, to overcome biases from assuming similarity to temperate and boreal regions., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

One mechanism proposed to explain high species diversity in tropical systems is strong negative conspecific density dependence (CDD), which reduces recruitment of juveniles in proximity to conspecific adult plants. Although evidence shows that plant-specific soil pathogens can drive negative CDD, trees also form key mutualisms with mycorrhizal fungi, which may counteract these effects. Across 43 large-scale forest plots worldwide, we tested whether ectomycorrhizal tree species exhibit weaker negative CDD than arbuscular mycorrhizal tree species. We further tested for conmycorrhizal density dependence (CMDD) to test for benefit from shared mutualists. We found that the strength of CDD varies systematically with mycorrhizal type, with ectomycorrhizal tree species exhibiting higher sapling densities with increasing adult densities than arbuscular mycorrhizal tree species. Moreover, we found evidence of positive CMDD for tree species of both mycorrhizal types. Collectively, these findings indicate that mycorrhizal interactions likely play a foundational role in global forest diversity patterns and structure., (© 2023. Springer Nature Limited.)

Purpose: The F3II cell line is a highly invasive variant of mammary carcinoma. Although it is frequently used as a model to evaluate the efficacy of immunotherapy, its impact on the immune system remains poorly understood. The main objectives of this study were to evaluate the effects of F3II tumors on the development of chronic inflammation and to characterize tumor-associated immunosuppression., Methods: Following the experimental implantation of F3II tumors in BALB/c mice, alterations in the liver and spleen anatomy and the numbers of circulating leukocytes, myeloid-derived suppressor cells (MDSCs), and regulatory T cells were measured using hematological techniques, histopathological analysis, and flow cytometry. The capacity of the F3II tumor-bearing mice to reject MB16F10 allogeneic tumor transplantation was also evaluated. In addition, the restoration of immune parameters in tumor-bearing mice was evaluated after standard breast cancer chemotherapy and surgical tumor excision., Results: F3II tumor implantation increased the levels of chronic inflammatory markers, such as the neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios, and caused myeloid alterations, including extramedullary granulopoiesis and megakaryopoiesis, along with the recruitment of MDSCs to the spleen. Chemotherapy or surgical F3II tumor removal completely rescued the tumor-associated extramedullary granulopoiesis and megakaryopoiesis. Notably, the presence of F3II tumors reduced the capacity of BALB/c mice to reject MB16F10 allogeneic tumor transplantation., Conclusion: These results support the occurrence of F3II tumor-mediated immune cell dysfunction, which mimics the immune alterations characterized by chronic systemic inflammation and immunosuppression observed in breast cancer in clinical settings. Thus, the F3II tumor model is relevant for evaluating novel breast cancer immunotherapies and combinations in preclinical studies. This model could also be useful for identifying appropriate therapeutic targets and developing proof-of-concept experiments in the future., Competing Interests: The authors declare that they have no competing interests., (© 2022 Korean Breast Cancer Society.)

Tree size shapes forest carbon dynamics and determines how trees interact with their environment, including a changing climate. Here, we conduct the first global analysis of among-site differences in how aboveground biomass stocks and fluxes are distributed with tree size. We analyzed repeat tree censuses from 25 large-scale (4-52 ha) forest plots spanning a broad climatic range over five continents to characterize how aboveground biomass, woody productivity, and woody mortality vary with tree diameter. We examined how the median, dispersion, and skewness of these size-related distributions vary with mean annual temperature and precipitation. In warmer forests, aboveground biomass, woody productivity, and woody mortality were more broadly distributed with respect to tree size. In warmer and wetter forests, aboveground biomass and woody productivity were more right skewed, with a long tail towards large trees. Small trees (1-10 cm diameter) contributed more to productivity and mortality than to biomass, highlighting the importance of including these trees in analyses of forest dynamics. Our findings provide an improved characterization of climate-driven forest differences in the size structure of aboveground biomass and dynamics of that biomass, as well as refined benchmarks for capturing climate influences in vegetation demographic models., (© 2022 The Authors. New Phytologist © 2022 New Phytologist Foundation.)

Introduction: Skin and soft tissue infections caused by nontuberculous mycobacteria (NMT) are reported to be associated with injections, liposuction, plastic surgery, and acupuncture. Herein, we describe an outbreak of soft tissue infection due to NMT following mesotherapy, a cosmetic procedure involving injection of poorly defined mixtures alleged to reduce local adiposity., Methods: Patients with skin lesions and a history of mesotherapy treatment, who visited the dermatology department of the public hospital in Barinas, Venezuela, from November 2004 to February 2005 were interviewed. Clinical and environmental samples were taken for mycobacteria isolation., Results: The interviews revealed that 68 patients who had been treated for cosmetic purposes at the same clinic by the same therapist had received injections with the same product and were infected with NMT. Clinical specimens from 5 patients grew Mycobacterium abscessus. No mesotherapy solution was available for analysis but M. abscessus was isolated from an environmental sample in the clinic. PCR-based strain typing techniques (ERIC-PCR, BOXA1R and RAPD) showed that the patient's isolates were undistinguishable from each other but different from the environmental isolate., Conclusions: This outbreak was likely caused by a contaminated injectable mesotherapy product and not by mycobacteria from the clinic environment. We emphasize the importance of better microbiological control of these products. To our knowledge, this outbreak, which affected at least 68 patients, appears to be the largest ever associated with mesotherapy and described in the literature., (Copyright © 2009 Elsevier España, S.L. All rights reserved.)

Trichotillomania represents a chronic disorder in which patients traumatically remove their own hair in a bizarre pattern. Like obsessive-compulsive disorder, the hair-pulling behavior is recognized as senseless and undesirable, but is performed in response to several emotions and affects, such as increasing anxiety, or unconscious conflicts with a resultant tension relief. The condition may be episodic, but is usually chronic and difficult to treat. We present three cases of trichotillomania and review common clinical and pathologic findings of this, often chronic and socially debilitating, disorder. In addition, we discuss treatment options for dermatologists and how the collaboration with psychiatrists is the most effective management for these difficult-to-treat patients.

1E10 is an anti-idiotype murine monoclonal antibody (Ab2 MAb) specific to an Ab1 MAb which reacts with NeuGc-containing gangliosides, sulfatides and with antigens expressed in some human tumors. Preparations containing this Ab2 were capable to induce a strong anti-metastatic effect in tumor-bearing mice. We conducted a Phase I clinical trial to evaluate the toxicity and humoral immune response elicited by 1E10 vaccine in patients with small cell lung cancer (SCLC). Eligible patients were those who after received chemotherapy and/or radiotherapy had partial or complete response to treatment. Patients received four biweekly injections with 2 mg of aluminum hydroxide-precipitated 1E10 MAb, then other six doses at 28-day intervals, and later the patients who maintained a good performance status were reimmunized. Six patients with limited-stage disease and three with extensive-stage disease were enrolled in the study. Most of the patients who received at least four doses of 1E10 vaccine developed strong specific antibody responses against 1E10 MAb and NeuGc-GM3 ganglioside. Antibodies able to react with lung carcinoma tissue sections were detected in sera from vaccinated patients. A prolonged survival was observed in several patients treated with the anti-idiotype vaccine. No evidence of serious adverse effects was found.

The 1H and 13C NMR spectroscopic data for alkyl and polyamine-linked bis(2-thioxo-[1,3,5]thiadiazinan-3-yl) carboxylic acids, prepared from alkyl diamines and N4-(benzyl) spermidine have been fully assigned by combination of one- and two-dimensional experiments (DEPT, HMBC, HMQC, COSY)., (Copyright (c) 2007 John Wiley & Sons, Ltd.)

The poor prognosis of patients with high-grade glioma has led to the search for new therapeutic strategies. More than half of these tumors overexpress Epidermal Growth factor Receptor (EGFR). h-R3 is a humanized monoclonal antibody that recognize the EGFR external domain with high affinity, inhibiting tyrosine kinase activation. In order to evaluate safety, immunogenicity and preliminary efficacy of h-R3 in newly diagnosed high-grade glioma patients, we conducted a Phase I/II trial. Patients received six weekly infusions of h-R3 at the dose of 200 mg in combination with external beam radiotherapy. Twenty-nine patients (mean age, 45 years and median KPS 80) were entered into the study. Tumor types were: glioblastoma (GB) (16 patients), anaplastic astrocytoma (AA) (12 patients) and anaplastic oligodendroglioma (AO) (1 patient). All patients underwent debulking surgery or biopsy before entering the trial. The antibody was very well tolerated. No evidences of grade 3/4 adverse events were detected. None of the patients developed acneiform rash or allergic reactions. One patient developed a positive anti-idiotypic response. Objective response-rate was 37.9% (17.2% complete response, 20.7% partial response) while stable disease occurred in 41.4% of the patients. With a median follow up time of 29 months, the median survival is 22.17 months for all subjects. Median survival time (MST) is 17.47 months for GB, whereas MST is not reached for AA patients.

Purpose: The recently defined molar-refractivity-partition index was applied to a family of 1,3,5- thiadiazin-2-thione derivatives in order to establish quantitative structure-antitumoral models. The goal of this effort is to establish the relationships between the structure and biological response of these compounds., Method: After the splitting of the sample in two sets, their indices were correlated against the measured biological activity. The combined use of our index with others had been able to describe not only the topologic but also the London dispersive forces of any fragment in relation to the biological response of the sets., Results: The obtained models showed correlation coefficients of 0.87 and 0.81 respectively linking structural and biological features of the molecules. The mean relative error values were less than 7%. According to the models, the activity of the first sample is related mostly to molecular topology and dispersive forces. Sample two activity was associated to the size and branching of the substituents, and also to the London forces., Conclusion: The index was able to discriminate between pure topological features and those related to dispersive forces.

We have previously generated a murine anti-idiotype (Ab2) monoclonal antibody (mAb) to a murine Ab1 mAb, named P3, which selectively binds Neu-glycolyl (NeuGc)-sialic acid on several monosialo- and disialogangliosides, and also reacts with sulfatides and antigens expressed in human melanoma and breast tumors. This Ab2 mAb, designated as 1E10, induced anti-anti-idiotype antibodies (Ab3) in mice and cancer patients. These Ab3 generated by 1E10 mAb were characterized by bearing P3 mAb idiotopes (Ab3, Id +). But when the specificity of these Ab3 antibodies was tested, no specific humoral response against NeuGc-containing gangliosides was detected in sera from immunized mice. However, hyperimmune sera from melanoma and breast cancer patients vaccinated with this Ab2 mAb were able to react specifically with these gangliosides. The different expression of NeuGc-containing gangliosides in the normal tissues of mice and humans could explain these results. In order to demonstrate these findings in other animal species with a different NeuGc-sialic acid expression, we performed similar studies in monkeys and chickens. In monkeys, as in most mammals, NeuGc-containing gangliosides are self-antigens. In contrast, chickens, like humans, lack the expression of these antigens in normal tissues. Here we report that the antibody response against NeuGc-containing gangliosides induced by immunization with 1E10 mAb was completely different in both species. No specific antibody response against these gangliosides was detected in hyperimmune monkey sera. In contrast, a strong and specific Ab3 response against GM3(NeuGc) and GM2(NeuGc) gangliosides (Ab3, Ag+) was generated in chickens due to the administration of 1E10 mAb.

Ten thiadiazine derivatives were tested in vitro for antiparasitic effects against both extracellular promastigotes and intracellular amastigotes of Leishmania amazonensis. The results showed that the evaluated compounds exhibited a strong antiproliferative activity on all developmental stages of the parasite. The minimal inhibitory concentration and the 50 % effective concentration values against the promastigote were 2.1-5.1 microg/ml and 0.6-1.8 microg/ml, respectively. The tested compounds caused an irreversible inhibition of the promastigote growth either after 1 h of treatment with 10 microg/ml or after 24 h with 1 microg/ml. Also, the thiadiazine derivatives were active against amastigotes producing between 12 and 89 % of reduction of infection at 100 ng/ml. However, the compounds exhibited high toxicity and provoked inhibition of the phagocytosis in the murine host cell.