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Defensins are natural endogenous antimicrobial peptides with potent anti-HIV activity and immuno-modulatory effects. We recently demonstrated that immature dendritic cells (DC) produce alpha-defensins1-3 and that alpha-defensins1-3 modulate DC generation and maturation. Since DC-HIV interaction plays a critical role during the first steps of HIV infection, we investigated the possible impact of alpha-defensins1-3 production by DC on disease progression. Monocyte-derived DC (MDDC) were analyzed comparatively in healthy controls (HC) and HIV-infected patients, including untreated \"elite\" and \"viremic\" controllers, untreated viremic non-controllers and antiretroviral-treated patients. We found that production of alpha-defensins1-3 was significantly increased in MDDC from HIV-infected patients versus HC, and this increase was mainly due to that observed in controllers, while in non-controllers the increase was not statistically significant (controllers vs. HC, p<0.005; controllers vs. non-controllers p<0.05). Secreted alpha-defensins1-3 by immature MDDC positively correlated with CD4 T cell counts in controllers, but not in non-controllers. Moreover, independently of their clinical classification, HIV-infected patients with higher alpha-defensins1-3 secretion by immature MDDC showed slower disease progression, measured as no decrease in the number of CD4+ T-cells below 350 cell/mm(3), lower increase of plasma viral load and no initiation of treatment over time. Plasma alpha-defensins1-3 levels lacked any relationship with immunologic and virologic parameters. High production of alpha-defensins1-3 by immature DCs appears as a host protective factor against progression of HIV-1 infection, suggesting potential diagnostic, therapeutic and preventive implications. This protective effect may arise from the activity of alpha-defensins1-3 to damage the virions prior and/or after their internalization by immature DC, and hence favoring a more efficient viral processing and presentation to HIV-specific CD4+ T cells, without or with a minor rate of transmission of infectious HIV-1 virions.

APOBEC3G (apolipoprotein B mRNA editing enzyme catalytic polypeptide‐like 3G; A3G) is an innate defense protein showing activity against retroviruses and retrotransposons. Activated CD4+ T cells are highly permissive for HIV‐1 replication, whereas resting CD4+ T cells are refractory. Dendritic cells (DCs), especially mature DCs, are also refractory. We investigated whether these differences could be related to a differential A3G expression and/or subcellular distribution. We found that A3G mRNA and protein expression is very low in resting CD4+ T cells and immature DCs, but increases strongly following T‐cell activation and DC maturation. The Apo‐7 anti‐A3G monoclonal antibody (mAb), which was specifically developed, confirmed these differences at the protein level and disclosed that A3G is mainly cytoplasmic in resting CD4+ T cells and immature DCs. Nevertheless, A3G translocates to the nucleus in activated‐proliferating CD4+ T cells, yet remaining cytoplasmic in matured DCs, a finding confirmed by immunoblotting analysis of cytoplasmic and nuclear fractions. Apo‐7 mAb was able to immunoprecipitate endogenous A3G allowing to detect complexes with numerous proteins in activated‐proliferating but not in resting CD4+ T cells. The results show for the first time the nuclear translocation of A3G in activated‐proliferating CD4+ T cells.

APOBEC3G (apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3G; A3G) is an innate defense protein showing activity against retroviruses and retrotransposons. Activated CD4 super(+) T cells are highly permissive for HIV-1 replication, whereas resting CD4 super(+) T cells are refractory. Dendritic cells (DCs), especially mature DCs, are also refractory. We investigated whether these differences could be related to a differential A3G expression and/or subcellular distribution. We found that A3G mRNA and protein expression is very low in resting CD4 super(+) T cells and immature DCs, but increases strongly following T-cell activation and DC maturation. The Apo-7 anti-A3G monoclonal antibody (mAb), which was specifically developed, confirmed these differences at the protein level and disclosed that A3G is mainly cytoplasmic in resting CD4 super(+) T cells and immature DCs. Nevertheless, A3G translocates to the nucleus in activated-proliferating CD4 super(+) T cells, yet remaining cytoplasmic in matured DCs, a finding confirmed by immunoblotting analysis of cytoplasmic and nuclear fractions. Apo-7 mAb was able to immunoprecipitate endogenous A3G allowing to detect complexes with numerous proteins in activated-proliferating but not in resting CD4 super(+) T cells. The results show for the first time the nuclear translocation of A3G in activated-proliferating CD4 super(+) T cells.

Defensins are natural endogenous antimicrobial peptides with potent anti-HIV activity and immuno-modulatory effects. We recently demonstrated that immature dendritic cells (DC) produce [alpha]-defensins1-3 and that [alpha]-defensins1-3 modulate DC generation and maturation. Since DC-HIV interaction plays a critical role during the first steps of HIV infection, we investigated the possible impact of [alpha]-defensins1-3 production by DC on disease progression. Monocyte-derived DC (MDDC) were analyzed comparatively in healthy controls (HC) and HIV-infected patients, including untreated \"elite\" and \"viremic\" controllers, untreated viremic non-controllers and antiretroviral-treated patients. We found that production of [alpha]-defensins1-3 was significantly increased in MDDC from HIV-infected patients versus HC, and this increase was mainly due to that observed in controllers, while in non-controllers the increase was not statistically significant (controllers vs. HC, p<0.005; controllers vs. non-controllers p<0.05). Secreted [alpha]-defensins1-3 by immature MDDC positively correlated with CD4 T cell counts in controllers, but not in non-controllers. Moreover, independently of their clinical classification, HIV-infected patients with higher [alpha]-defensins1-3 secretion by immature MDDC showed slower disease progression, measured as no decrease in the number of CD4+ T-cells below 350 cell/mm.sup.3, lower increase of plasma viral load and no initiation of treatment over time. Plasma alpha-defensins1-3 levels lacked any relationship with immunologic and virologic parameters. High production of [alpha]-defensins1-3 by immature DCs appears as a host protective factor against progression of HIV-1infection, suggesting potential diagnostic, therapeutic and preventive implications. This protective effect may arise from the activity of [alpha]-defensins1-3 to damage the virions prior and/or after their internalization by immature DC, and hence favoring a more efficient viral processing and presentation to HIV-specific CD4+ T cells, without or with a minor rate of transmission of infectious HIV-1 virions.

Interleukin (IL) 4 is a key T helper-2 cytokine that downregulates and upregulates CCR5 and CXCR4, respectively, the main coreceptors for HIV. Our objective is to investigate whether single-nucleotide polymorphisms (SNPs) in the IL-4 receptor α chain gene (IL4RA) affect HIV infection and its progression to AIDS. The I50V SNP in exon 5 and the haplotypes of six SNPs in exon 12 (E375A, C406R, S411L, S478P, Q551R, and V554I) were studied by polymerase chain reaction and sequencing in 30 HIV⁺ long-term nonprogressors (LTNP), 36 HIV⁺ typical progressors (TP), 55 highly exposed but uninfected individuals (EU), 25 EU-sexuals (EU-Sex; mostly women) and 30 EU-hemophiliacs (EU-Hem; hepatitis C virus⁺), and 97 healthy controls (HC), all Caucasians and lacking CCR5Δ32 homozygosity. V50 homozygosity was increased in LTNP (44%) compared with the other groups [p=0.005; relative risk ratio=3.4, 95% confidence interval (CI)=1.12-10.6, p=0.03]. The most common (C) exon 12 haplotype, ECSSQV, predominated in all groups, but uncommon (U) haplotypes were increased in HIV⁺ individuals (n=64), especially in those (51 of 64) infected via parenteral exposure (35.3%) compared with HC (20.4%) and EU-Hem (18.4%) [p=0.01; odds ratio (OR)=2.14, 95% CI=1.25-3.67, p=0.01]. EU-Sex also had an increased frequency of U-haplotypes (34.8%) (OR=2.10, 95% CI=1.03-4.21, p=0.01) as well as an increased frequency of CU + UU genotypes (60.9%) compared with HC (38.2%) and EU-Hem (26.6%) (p=0.043). Distributions of genotypes fitted Hardy-Weinberg equilibrium. Data suggest that V50 homozygosity associates with slow progression and that exon 12 U-haplotypes might be associated with both susceptibility to infection via parenteral route and resistance to infection via sexual exposure. Further studies are required to confirm these findings.

Interleukin (IL) 4 is a key T helper-2 cytokine that downregulates and upregulates CCR5 and CXCR4, respectively, the main coreceptors for HIV. Our objective is to investigate whether single-nucleotide polymorphisms (SNPs) in the IL-4 receptor α chain gene (IL4RA) affect HIV infection and its progression to AIDS. The I50V SNP in exon 5 and the haplotypes of six SNPs in exon 12 (E375A, C406R, S411L, S478P, Q551R, and V554I) were studied by polymerase chain reaction and sequencing in 30 HIV^sup +^ long-term nonprogressors (LTNP), 36 HIV^sup +^ typical progressors (TP), 55 highly exposed but uninfected individuals (EU), 25 EU-sexuals (EU-Sex; mostly women) and 30 EU-hemophiliacs (EU-Hem; hepatitis C virus^sup +^), and 97 healthy controls (HC), all Caucasians and lacking CCR5Δ32 homozygosity. V50 homozygosity was increased in LTNP (44%) compared with the other groups [p=0.005; relative risk ratio=3.4, 95% confidence interval (CI)=1.12-10.6, p=0.03]. The most common (C) exon 12 haplotype, ECSSQV, predominated in all groups, but uncommon (U) haplotypes were increased in HIV^sup +^ individuals (n=64), especially in those (51 of 64) infected via parenteral exposure (35.3%) compared with HC (20.4%) and EU-Hem (18.4%) [p=0.01; odds ratio (OR)=2.14, 95% CI=1.25-3.67, p=0.01]. EU-Sex also had an increased frequency of U-haplotypes (34.8%) (OR=2.10, 95% CI=1.03-4.21, p=0.01) as well as an increased frequency of CU + UU genotypes (60.9%) compared with HC (38.2%) and EU-Hem (26.6%) (p=0.043). Distributions of genotypes fitted Hardy-Weinberg equilibrium. Data suggest that V50 homozygosity associates with slow progression and that exon 12 U-haplotypes might be associated with both susceptibility to infection via parenteral route and resistance to infection via sexual exposure. Further studies are required to confirm these findings.[PUBLICATION ABSTRACT]

In the search for an integrated understanding of the relationships among productive activities, human well-being, and ecosystem functioning, we evaluated the services delivered by a tropical dry forest (TDF) ecosystem in the Chamela Region, on the Pacific Coast of Mexico. We synthesized information gathered for the past two decades as part of a long-term ecosystem research study and included social data collected in the past four years using the Millennium Ecosystem Assessment (MA) conceptual framework as a guide. Here we identify the four nested spatial scales at which information has been obtained and emphasize one of them through a basin conceptual model. We then articulate the biophysical and socioeconomic constraints and drivers determining the delivery of ecosystem services in the Region. We describe the nine most important services, the stakeholders who benefit from those services, and their degree of awareness of such services. We characterize spatial and temporal patterns of the services’ delivery as well as trade-offs among services and stakeholders. Finally, we contrast three alternative future scenarios on the delivery of ecosystem services and human well-being. Biophysical and socioeconomic features of the study site strongly influence human–ecosystem interactions, the ecosystem services delivered, the possible future trajectories of the ecosystem, and the effect on human well-being. We discuss future research approaches that will set the basis for an integrated understanding of human–ecosystem interactions and for constructing sustainable management strategies for the TDF.

We present here a two-step strategy for micropatterning proteins on a substrate to control neurite growth in culture. First, conventional microcontact printing is used to prepare a micropattern of protein A, which binds the Fc fragment of immunoglobulins. Then, a chimeric protein, consisting of the extracellular domain of a guidance protein recombinantly linked to the Fc fragment of IgG (prepared using conventional molecular techniques), is applied from solution. The chimeric protein binds to the patterned protein A, taking on its geometric pattern. Using this method, we have micropatterned the extracellular domain of the cell adhesion molecule, L1 (as an L1-Fc chimera) and demonstrated that it retains its ability to selectively guide axonal growth. L1-Fc micropatterned on a background of poly-L-lysine resulted in selective growth of the axons on the micropattern, whereas the somata and dendrites were unresponsive. Substrates bearing simultaneous micropatterns of L1-Fc and poly-L-lysine on a background of untreated glass were also created. Using this approach, cell body position was controlled by manipulating the dimensions of the poly-L-lysine pattern, and the dendrites were constrained to the poly-L-lysine pattern, while the axons grew preferentially on L1-Fc. The two-step microcontact printing method allows preparation of substrates that contain guidance proteins in geometric patterns with resolution of approximately 1 microm. This method should be broadly applicable to many classes of proteins.

Background Mild cognitive impairment (MCI) and Alzheimer's disease (AD) are progressive neurodegenerative conditions affecting cognition and daily functioning. In Peru, this is the first multi‐site study conducted across Lima, Arequipa, Puno, Chiclayo, and Loreto to evaluate cognitive performance using standardized neuropsychological instruments. The objective was to characterize participants with MCI and AD through a comprehensive neuropsychological assessment. Method A total of 267 patients were evaluated, including 145 controls, 41 individuals with MCI, and 81 with AD. Standardized assessments included PHQ‐9, Pfeffer, RUDAS, and INECO. RUDAS and INECO scores were compared between groups using appropriate statistical tests (T‐Student or Mann‐Whitney U). Result AD patients exhibited significant cognitive and executive impairments compared to controls. RUDAS Total Score: AD (11.26 ± 8.3) vs. Controls (26.61 ± 3.1, p < 0.001). INECO Total Score: AD (1.01 ± 3.29) vs. Controls (1.32 ± 4.93, p =  0.363, Mann‐Whitney U). The most affected INECO subtests in AD patients included Instrucciones Conflictivas (p < 0.001) and Meses Atrás (p = 0.018). Conclusion These findings confirm the severe cognitive and executive impairments in AD patients compared to MCI and controls. The significant differences in RUDAS and INECO scores highlight their potential role in differentiating neurocognitive conditions. Impairments in control inhibitory functions and working memory were evident in AD patients. This study provides novel insights into dementia evaluation in Peru and underscores the importance of standardized neuropsychological assessments for early identification of cognitive decline. Future research should expand sample sizes and refine assessment tools to improve early detection strategies.

Mild cognitive impairment (MCI) and Alzheimer's disease (AD) are progressive neurodegenerative conditions affecting cognition and daily functioning. In Peru, this is the first multi-site study conducted across Lima, Arequipa, Puno, Chiclayo, and Loreto to evaluate cognitive performance using standardized neuropsychological instruments. The objective was to characterize participants with MCI and AD through a comprehensive neuropsychological assessment. A total of 267 patients were evaluated, including 145 controls, 41 individuals with MCI, and 81 with AD. Standardized assessments included PHQ-9, Pfeffer, RUDAS, and INECO. RUDAS and INECO scores were compared between groups using appropriate statistical tests (T-Student or Mann-Whitney U). AD patients exhibited significant cognitive and executive impairments compared to controls. RUDAS Total Score: AD (11.26 ± 8.3) vs. Controls (26.61 ± 3.1, p < 0.001). INECO Total Score: AD (1.01 ± 3.29) vs. Controls (1.32 ± 4.93, p =  0.363, Mann-Whitney U). The most affected INECO subtests in AD patients included Instrucciones Conflictivas (p < 0.001) and Meses Atrás (p = 0.018). These findings confirm the severe cognitive and executive impairments in AD patients compared to MCI and controls. The significant differences in RUDAS and INECO scores highlight their potential role in differentiating neurocognitive conditions. Impairments in control inhibitory functions and working memory were evident in AD patients. This study provides novel insights into dementia evaluation in Peru and underscores the importance of standardized neuropsychological assessments for early identification of cognitive decline. Future research should expand sample sizes and refine assessment tools to improve early detection strategies.