In situ analysis of neuronal injury and neuroinflammation during HIV-1 infection.

BACKGROUND: Since the introduction of combination antiretroviral therapy (cART) the brain has become an important human immunodeficiency virus (HIV) reservoir due to the relatively low penetration of many drugs utilized in cART into the central nervous system (CNS). Given the inherent limitations of directly assessing acute HIV infection in the brains of people living with HIV (PLWH), animal models, such as humanized mouse models, offer the most effective means of studying the effects of different viral strains and their impact on HIV infection in the CNS. To evaluate CNS pathology during HIV-1 infection in the humanized bone marrow/liver/thymus (BLT) mouse model, a histological analysis was conducted on five CNS regions, including the frontal cortex, hippocampus, striatum, cerebellum, and spinal cord, to delineate the neuronal (MAP2ab, NeuN) and neuroinflammatory (GFAP, Iba-1) changes induced by two viral strains after 2 weeks and 8 weeks post-infection. RESULTS: Findings reveal HIV-infected human cells in the brain of HIV-infected BLT mice, demonstrating HIV neuroinvasion. Further, both viral strains, HIV-1JR-CSF and HIV-1CH040, induced neuronal injury and astrogliosis across all CNS regions following HIV infection at both time points, as demonstrated by decreases in MAP2ab and increases in GFAP fluorescence signal, respectively. Importantly, infection with HIV-1JR-CSF had more prominent effects on neuronal health in specific CNS regions compared to HIV-1CH040 infection, with decreasing number of NeuN+ neurons, specifically in the frontal cortex. On the other hand, infection with HIV-1CH040 demonstrated more prominent effects on neuroinflammation, assessed by an increase in GFAP signal and/or an increase in number of Iba-1+ microglia, across CNS regions. CONCLUSION: These findings demonstrate that CNS pathology is widespread during acute HIV infection. However, neuronal loss and the magnitude of neuroinflammation in the CNS is strain dependent indicating that strains of HIV cause differential CNS pathologies.

Transforming Growth Factor ß Signaling Promotes HIV-1 Infection in Activated and Resting Memory CD4+ T Cells.

Understanding the facilitator of HIV-1 infection and subsequent latency establishment may aid the discovery of potential therapeutic targets. Here, we report the elevation of plasma transforming growth factor ß (TGF-ß) during acute HIV-1 infection among men who have sex with men (MSM). Using a serum-free in vitro system, we further delineated the role of TGF-ß signaling in mediating HIV-1 infection of activated and resting memory CD4+ T cells. TGF-ß could upregulate both the frequency and expression of the HIV-1 coreceptor CCR5, thereby augmenting CCR5-tropic viral infection of resting and activated memory CD4+ T cells via Smad3 activation. The production of live HIV-1JR-FL upon infection and reactivation was increased in TGF-ß-treated resting memory CD4+ T cells without increasing CD4 expression or inducing T cell activation. The expression of CCR7, a central memory T cell marker that serves as a chemokine receptor to facilitate T cell trafficking into lymphoid organs, was also elevated on TGF-ß-treated resting and activated memory CD4+ T cells. Moreover, the expression of CXCR3, a chemokine receptor recently reported to facilitate CCR5-tropic HIV-1 infection, was increased on resting and activated memory CD4+ T cells upon TGF-ß treatment. These findings were coherent with the observation that ex vivo CCR5 and CXCR3 expression on total resting and resting memory CD4+ T cells in combination antiretroviral therapy (cART)-naive and cART-treated patients were higher than in healthy individuals. Overall, the study demonstrated that TGF-ß upregulation induced by acute HIV-1 infection might promote latency reservoir establishment by increasing infected resting memory CD4+ T cells and lymphoid organ homing of infected central memory CD4+ T cells. Therefore, TGF-ß blockade may serve as a potential supplementary regimen for HIV-1 functional cure by reducing viral latency. IMPORTANCE Incomplete eradication of HIV-1 latency reservoirs remains the major hurdle in achieving a complete HIV/AIDS cure. Dissecting the facilitator of latency reservoir establishment may aid the discovery of druggable targets for HIV-1 cure. This study showed that the T cell immunomodulatory cytokine TGF-ß was upregulated during the acute phase of infection. Using an in vitro serum-free system, we specifically delineated that TGF-ß promoted HIV-1 infection of both resting and activated memory CD4+ T cells via the induction of host CCR5 coreceptor. Moreover, TGF-ß-upregulated CCR7 or CXCR3 might promote HIV-1 latent infection by facilitating lymphoid homing or IP-10-mediated viral entry and DNA integration, respectively. Infected resting and central memory CD4+ T cells are important latency reservoirs. Increased infection of these cells mediated by TGF-ß will promote latency reservoir establishment during early infection. This study, therefore, highlighted the potential use of TGF-ß blockade as a supplementary regimen with cART in acute patients to reduce viral latency.

Too hot to handle? An urgent need to understand climate change impacts on the biogeochemistry of tropical coastal waters.

Tropical regions contain ecologically and socio-economically important habitats, and are home to about 3.8 billion people, many of which directly depend on tropical coastal waters for their well-being. At the basis of these ecosystems are biogeochemical processes. Climate change is expected to have a greater impact in the tropics compared to temperate regions because of the relatively stable environmental conditions found there. However, it was surprising to find only 660 research articles published focusing on the impact of climate change on the biogeochemistry of coastal tropical waters compared to 4823 for temperate waters. In this perspective, we highlight important topics in need of further research. Specifically, we suggest that in tropical regions compared to temperate counterparts climate change stressors will be experienced differently, that organisms have a lower acclimation capacity, and that long-term baseline biogeochemical datasets useful for quantifying future changes are lacking. The low number of research papers on the impacts of climate change in coastal tropical regions is likely due to a mix of reasons including limited resources for research and limited number of long time series in many developing tropical countries. Finally, we propose some action points that we hope will stimulate more studies in tropical coastal waters.

Zoom-in to molecular mechanisms underlying root growth and function under heterogeneous soil environment and abiotic stresses.

MAIN CONCLUSION: The review describes tissue-specific and non-cell autonomous molecular responses regulating the root system architecture and function in plants. Phenotypic plasticity of roots relies on specific molecular and tissue specific responses towards local and microscale heterogeneity in edaphic factors. Unlike gravitropism, hydrotropism in Arabidopsis is regulated by MIZU KUSSIE1 (MIZ1)-dependent asymmetric distribution of cytokinin and activation of Arabidopsis response regulators, ARR16 and ARR17 on the lower water potential side of the root leading to higher cell division and root bending. The cortex specific role of Abscisic acid (ABA)-activated SNF1-related protein kinase 2.2 (SnRK2.2) and MIZ1 in elongation zone is emerging for hydrotropic curvature. Halotropism involves clathrin-mediated internalization of PIN FORMED 2 (PIN2) proteins at the side facing higher salt concentration in the root tip, and ABA-activated SnRK2.6 mediated phosphorylation of cortical microtubule-associated protein Spiral2-like (SP2L) in the root transition zone, which results in anisotropic cell expansion and root bending away from higher salt. In hydropatterning, Indole-3-acetic acid 3 (IAA3) interacts with SUMOylated-ARF7 (Auxin response factor 7) and prevents expression of Lateral organ boundaries-domain 16 (LBD16) in air-side of the root, while on wet side of the root, IAA3 cannot repress the non-SUMOylated-ARF7 thereby leading to LBD16 expression and lateral root development. In root vasculature, ABA induces expression of microRNA165/microRNA166 in endodermis, which moves into the stele to target class III Homeodomain leucine zipper protein (HD-ZIP III) mRNA in non-cell autonomous manner. The bidirectional gradient of microRNA165/6 and HD-ZIP III mRNA regulates xylem patterning under stress. Understanding the tissue specific molecular mechanisms regulating the root responses under heterogeneous and stress environments will help in designing climate-resilient crops.

Phenotypic evaluation of pre-weaning growth traits of Akaushi- (Wagyu), Angus- and Brahman-sired calves in tropical conditions.

The objective was to assess the effect of sire breed on birth weight, average daily gain from birth to weaning, and actual weaning weight of calves. The calves were produced by AI using semen of five Akaushi (Wagyu), six Angus, and six Brahman bulls. Dams of calves were Beefmaster (n = 60) and Brown Swiss x Zebu (n = 21). The three sire breeds were used on both dam genetic types to produce the calves (45 males and 36 females). Each dam genetic type was raised in two ranches; therefore, all calves were born in four ranches, in the same calendar year. Average age at weaning weight m easurement was 186 days. The traits were analyzed with the MIXED procedure of SAS. The statistical model included the fixed effects of sire breed, dam genetic type, calf sex, ranch, and birth season within sire breed-ranch; sire within breed of sire was included as a random effect (except for weaning weight; P > 0.05). In addition, the model for weaning weight included calf age at weaning as a covariate. Birth weights and average daily gains of Akaushi-, Angus- and Brahman-sired calves were similar (P > 0.05). In contrast, Angus-sired calves were heavier (P < 0.05) at weaning than Akaushi- and Brahman-sired calves. Calves out of Brown Swiss x Zebu dams had higher (P < 0.05) pre-weaning average daily gains than calves out of Beefmaster dams. Angus-sired calves performed better at weaning.

Nonpharmacological interventions and outcomes in the management of complications of human T-cell lymphotropic virus type 1-related myelopathy/tropical spastic paraparesis: A systematic review.

Background: Human T-cell lymph tropic virus type 1 (HTLV-I)-related myelopathy/tropical spastic paraparesis (TSP) is a progressive inflammatory process affecting the spinal cord that occurs as a result of HTLV 1. The use of nonpharmacological approaches has always been one of the treatment strategies in these patients, but disagreement about these interventions and their results has led to their limited use. Therefore, this study aimed to identify nonpharmacological interventions and their consequences in these patients. Materials and Methods: We followed the Cochrane Handbook for systematic reviews of interventions. The present report is organized according to the preferred reporting items for systematic reviews and meta-analyses. This study was conducted at PubMed, Cochrane Library, Web of Science, and Scopus, among all published studies by December 30, 2021. Keywords were: HTLV-1, Human T-lymph tropic virus 1, HTLV-I-associated myelopathy, HAM/TSP, tropical spastic paraparesis, nonpharmacological intervention, nonpharmacological treatment, massage, physiotherapy, acupuncture, acupressure, and exercise. The quality of the studies was assessed using JADAD. Results: Of 288 articles, 11 were eligible for data extraction published between 2014 and 2021. 90/9% of studies were randomized clinical trials. 81/8% of articles were of high quality. The total sample size was 253 people, of which 137 (54/15%) were women. Approaches such as exercise and motion therapy, electrotherapy, behavioral therapy, and virtual reality can be used for these patients. With these interventions, results such as improved mobility and balance, physical condition, pain, quality of life, muscle spasticity, maximum inspiratory pressure, and urinary symptoms can be achieved. Conclusion: The most common physical therapy method used in studies was active and passive body movements, which are associated with positive results for patients. Due to the small sample size in this group of studies, it is necessary to conduct more clinical trials for more accurate conclusions. Furthermore, due to the limited number of studies that have used electrical stimulation or combined intervention packages, it is not possible to say with certainty what effect these methods have on patients. It is necessary to conduct more clinical trials.

miRNAs derived from plasma small extracellular vesicles predict organo-tropic metastasis of gastric cancer.

BACKGROUND: Peritoneum, liver and lymph node are the most common metastatic sites of gastric cancer (GC). Biomarkers for GC's organo-tropic metastasis remained largely unknown, which was investigated in this study from the perspective of small extracellular vesicle (sEV)-derived miRNAs. METHODS: Plasma from treatment-naïve GC patients including no metastasis (M0), peritoneal metastasis (PM), hepatic metastasis (HM) and distant lymph node metastasis (dLNM)) were divided into one discovery (N = 40), one training (N = 40) and one validating cohort (N = 86), then assessed by sEV-miRNA-sequencing and sEV-miRNA-qPCR. Functional explorations were also performed for verification. RESULTS: The expression profiles of sEV-miRNAs varied greatly across different metastatic patterns. Based on logistic regression models, we constructed signatures for M0 (hsa-miR-186-5p/hsa-miR-200c-3p/hsa-miR-429/hsa-miR-5187-5p/hsa-miR-548ae-5p), PM (hsa-miR-200c-3p/hsa-miR-429), HM (hsa-miR-200c-3p/hsa-miR-429) and dLNM (hsa-miR-324-5p/hsa-miR-374a-5p/hsa-miR-429/hsa-miR-548ae-5p). These signatures vigorously characterized organo-tropic metastasis (all displaying AUC > 0.8, consistency ≥ 75%), and effectively conjectured the risk of future metastasis within 5 years (accuracy 45.5% for occurrence, 70% for organotropism, P = 0.002 for prognostic diversity). Additionally, we explored these seven biomarker miRNAs' impact on GC's in vitro motility and discussed their potential involvement in cancer-related biological processes and pathways. CONCLUSIONS: Our work highlighted that plasma sEV-miRNAs powerfully characterized and predicted the organo-tropic metastasis of GC and provided new insight into the applications of sEV-based liquid biopsy in clinical practice.

Artificial stem cells mediated inflammation-tropic delivery of antiviral drugs for pneumonia treatment.

BACKGROUND: Cytomegalovirus (CMV) pneumonia is a major cause of morbidity and mortality in immunodeficiency individuals, including transplant recipients and Acquired Immune Deficiency Syndrome patients. Antiviral drugs ganciclovir (GCV) and phosphonoformate (PFA) are first-line agents for pneumonia caused by herpesvirus infection. However, the therapy suffers from various limitations such as low efficiency, drug resistance, toxicity, and lack of specificity. METHODS: The antiviral drugs GCV and PFA were loaded into the pH-responsive nanoparticles fabricated by poly(lactic-co-glycolic acid) (PLGA) and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), and further coated with cell membranes derived from bone marrow mesenchymal stem cells to form artificial stem cells, namely MPDGP. We evaluated the viral suppression effects of MPDGP in vitro and in vivo. RESULTS: MPDGP showed significant inflammation tropism and efficient suppression of viral replication and virus infection-associated inflammation in the CMV-induced pneumonia model. The synergistic effects of the combination of viral DNA elongation inhibitor GCV and viral DNA polymerase inhibitor PFA on suppressing the inflammation efficiently. CONCLUSION: The present study develops a novel therapeutic intervention using artificial stem cells to deliver antiviral drugs at inflammatory sites, which shows great potential for the targeted treatment of pneumonia. To our best knowledge, we are the first to fabricate this kind of artificial stem cell to deliver antiviral drugs for pneumonia treatment.

Searching for a Paradigm Shift in Auger-Electron Cancer Therapy with Tumor-Specific Radiopeptides Targeting the Mitochondria and/or the Cell Nucleus.

Although 99mTc is not an ideal Auger electron (AE) emitter for Targeted Radionuclide Therapy (TRT) due to its relatively low Auger electron yield, it can be considered a readily available "model" radionuclide useful to validate the design of new classes of AE-emitting radioconjugates. With this in mind, we performed a detailed study of the radiobiological effects and mechanisms of cell death induced by the dual-targeted radioconjugates 99mTc-TPP-BBN and 99mTc-AO-BBN (TPP = triphenylphosphonium; AO = acridine orange; BBN = bombesin derivative) in human prostate cancer PC3 cells. 99mTc-TPP-BBN and 99mTc-AO-BBN caused a remarkably high reduction of the survival of PC3 cells when compared with the single-targeted congener 99mTc-BBN, leading to an augmented formation of γH2AX foci and micronuclei. 99mTc-TPP-BBN also caused a reduction of the mtDNA copy number, although it enhanced the ATP production by PC3 cells. These differences can be attributed to the augmented uptake of 99mTc-TPP-BBN in the mitochondria and enhanced uptake of 99mTc-AO-BBN in the nucleus, allowing the irradiation of these radiosensitive organelles with the short path-length AEs emitted by 99mTc. In particular, the results obtained for 99mTc-TPP-BBN reinforce the relevance of targeting the mitochondria to promote stronger radiobiological effects by AE-emitting radioconjugates.

Addition of clinoptilolite in the diet reduces uterine PMN leukocytes and open days in multiparous lactating dairy cows managed in a mountain tropical pasture-based system.

This study aimed to assess the effect of adding clinoptilolite in the diet on uterine health and reproductive performance in multiparous lactating dairy cows managed in a tropical pasture-based system above 2500 m of altitude. Seventy-seven multiparous Holstein crossbred cows from two farms were allocated randomly into two groups: clinoptilolite supplemented cows (CLG, n = 42) and non-supplemented cows as control (CG, n = 35). Cows from CLG were supplemented with clinoptilolite from 30 days (50 g/cow/day) before to 60 days after calving (200 g/cow/day). In CLG cows, percentages of uterine PMN leukocytes (P < 0.0001) and proportion of subclinical endometritis (P = 0.0187) were lower than in CG. The interval calving to first corpus luteum was shorter (P = 0.0759) in CLG than CG, and calving to first service interval was similar between treatments. Cows from CLG became pregnant 35 days earlier than CG cows (P = 0.0224). On farm A, calving to conception interval was 18.1 days longer in CLG than in CG (P = 0.3750); in farm B, this interval was 86.2 days shorter in CLG than in CG (P = 0.0002). In conclusion, daily addition of clinoptilolite in the diet decreased the percentage of uterine PMN leukocytes, the proportion of cows with subclinical endometritis, and shortened the calving-conception interval in multiparous lactating dairy cows.

Plant thermotropism: an underexplored thermal engagement and avoidance strategy.

Various strategies evolved in plants to adjust the position of organs relative to the prevailing temperature condition, which allows optimal plant growth and performance. Such responses are classically separated into nastic and tropic responses. During plant thermotropic responses, organs move towards (engage) or away (avoid) from a directional temperature cue. Despite thermotropism being a classic botanical concept, the underlying ecological function and molecular and biophysical mechanisms remain poorly understood to this day. This contrasts to the relatively well-studied thermonastic movements (hyponasty) of e.g., rosette leaves. In this review, we provide an update on the current knowledge on plant thermotropisms and propose directions for future research and application.

Understanding the Intricate Web of Phytohormone Signalling in Modulating Root System Architecture.

Root system architecture (RSA) is an important developmental and agronomic trait that is regulated by various physical factors such as nutrients, water, microbes, gravity, and soil compaction as well as hormone-mediated pathways. Phytohormones act as internal mediators between soil and RSA to influence various events of root development, starting from organogenesis to the formation of higher order lateral roots (LRs) through diverse mechanisms. Apart from interaction with the external cues, root development also relies on the complex web of interaction among phytohormones to exhibit synergistic or antagonistic effects to improve crop performance. However, there are considerable gaps in understanding the interaction of these hormonal networks during various aspects of root development. In this review, we elucidate the role of different hormones to modulate a common phenotypic output, such as RSA in Arabidopsis and crop plants, and discuss future perspectives to channel vast information on root development to modulate RSA components.

Effect of parota (Enterolobium cyclocarpum) pod protein supplement on feed intake and digestibility and calf ruminal characteristics.

The objective of this study was to evaluate feed intake and digestibility and ruminal characteristics of development-stage calves fed mulatto II (Brachiaria sp.) grass hay (MGH) and a protein supplement (PS) consisting of increasing levels of the parota (Enterolobium cyclocarpum) pod (PP). We used eight Swiss-zebu calves in growth stage with an average age of 11 months and initial average weight of 157.6 ± 8.5 kg. They were distributed in a repeated 4 × 4 Latin square design with 4 treatments (period 30 days): 0% (PP0), 25% (PP25), 50% (PP50), and 75% (PP75) of the PP. Calves in the PP0 and PP25 treatments had higher intake of PS and MGH as dry matter (DM) than those in the PP50 and PP75 treatments (p < 0.05). Organic matter intake (OMI) of the PP75 calves was lower than that of PP0 and PP25 calves. Crude protein intakes (CPI) of PP0 and PP25 calves were higher than those of PP50 and PP75 calves (p < 0.05). Apparent digestibility of crude protein was higher in the PP0, PP25, and PP50 treatments compared with that in treatment PP75 (p < 0.05). The treatments did not affect total bacterial count, cellulolytic bacterial count, cellulase enzymatic activity, volatile fatty acids, or the acetate/propionate ratio (p > 0.05). Rumen pH in the PP0 calves was higher than that of the PP25 calves, whereas the protozoa count and ammonia content were higher in PP0 calves than in PP75 (p < 0.05). In conclusion, the inclusion of 25% PP in the PS for forage-fed calves is a feeding alternative.

Feasibility of selective anthelmintic therapy to horses in tropical conditions: the Cuban scenario.

For the past several decades, selective anthelmintic therapy (SAT) has been recommended in temperate climate countries for controlling gastrointestinal parasites in horses. However, the feasibility of this approach in tropical climates remains unknown, given the very different parasite transmission patterns and a larger representation of working equids. The aim of this study was to evaluate the bio-economic feasibility of SAT in horses kept under tropical conditions of Camagüey, Cuba. Fecal egg counts were determined from 794 adult horses and used for evaluating three different putative treatment thresholds; > 500 strongylid eggs per gram of feces (EPG); > 1000 EPG; and treatments yielding > 80% of the total herd egg output. These scenarios were evaluated under three treatment frequencies (every 2, 6, and 12 months). The bio-economic feasibility of these nine possible selective anthelmintic therapy scenarios was evaluated taking into account the cost of parasitological tests, and the mean cost of anthelmintic treatment in Camagüey. The majority (96.7%) of the samples tested were positive for strongyle eggs, with a mean of 1549 EPG. The percentage of horses exceeding the cut-off points at the nine scenarios varied between 40.1 and 93.8%. All owners surveyed used extra-label anthelmintic product in their horses on a routine basis. The economic analysis demonstrated that selective therapy generally was much more costly than deworming the entire herd without determining egg counts. However, we consider that the deworming every 6 months of the horses that expel 80% of the eggs in the herd allows a reduction of the treatment intensity without increasing costs, and it can be considered as a viable selective deworming scheme under similar conditions.

Use of unconventional agro-industrial by-products for supplementation of grazing dairy cattle in the Peruvian Amazon region.

The effect of supplementation of grazing cattle with unconventional agro-industrial by-products on milk production and economic performance was evaluated in the Amazon region of Peru. Ten lactating cows were used in a simple crossover design with two periods of 21 days (11 days of adaptation and 10 days of measurements), and two treatments: conventional supplementation (rice polishing) and a mixture of unconventional agro-industrial by-products-MUABP (rice polishing, rice middling, cocoa hull, and coconut meal). Cattle supplemented with MUABP produced more milk than those fed the conventional supplement (10.2 vs. 8.8 kg/cow/day, p <0.001). No differences were found between the two treatments in protein, fat, or lactose content of milk (3.9%, 3.17%, 4.54% on average respectively; p ≥0.05). Daily weight gain with the MUABP treatment was 0.09 kg/day, while with conventional supplementation cow lost -0.04 kg/day (p =0.01). Body condition did not differ between treatments (p ≥0.05). Income due to supplementation with unconventional agro-industrial by-product was US $0.2 in comparison with only rice polishing. Cattle supplemented with MUABP improved milk production and their economic profitability.

Schwann cell-derived CXCL1 contributes to human immunodeficiency virus type 1 gp120-induced neuropathic pain by modulating macrophage infiltration in mice.

The neuroinflammatory responses to human immunodeficiency virus type 1 (HIV-1) coat proteins, such as glycoprotein 120 (gp120), are considered to be responsible for the HIV-associated distal sensory neuropathy. Accumulating evidences suggest that T-cell line tropic X4 gp120 increases macrophage infiltration into the peripheral nerves, and thereby induces neuroinflammation leading to pain. However, the mechanisms underlying X4 gp120-induced macrophage recruitment to the peripheral nervous systems remain unclear. Here, we demonstrated that perineural application of X4 gp120 from HIV-1 strains IIIB and MN elicited mechanical hypersensitivity and spontaneous pain-like behaviors in mice. Furthermore, flow cytometry and immunohistochemical studies revealed increased infiltration of bone marrow-derived macrophages into the parenchyma of sciatic nerves and dorsal root ganglia (DRG) 7 days after gp120 IIIB or MN application. Chemical deletion of circulating macrophages using clodronate liposomes markedly suppressed gp120 IIIB-induced pain-like behaviors. In in vitro cell infiltration analysis, RAW 264.7 cell (a murine macrophage cell line) was chemoattracted to conditioned medium from gp120 IIIB- or MN-treated cultured Schwann cells, but not to conditioned medium from these gp120-treated DRG neurons, suggesting possible involvement of Schwann cell-derived soluble factors in macrophage infiltration. We identified using a gene expression array that CXCL1, a chemoattractant of macrophages and neutrophils, was increased in gp120 IIIB-treated cultured Schwann cells. Similar to gp120 IIIB or MN, perineural application of recombinant CXCL1 elicited pain-like behaviors accompanied by macrophage infiltration to the peripheral nerves. Furthermore, the repeated injection of CXCR2 (receptor for CXCL1) antagonist or CXCL1 neutralizing antibody prevented both pain-like behaviors and macrophage infiltration in gp120 IIIB-treated mice. Thus, the present study newly defines that Schwann cell-derived CXCL1, secreted in response to X4 gp120 exposure, is responsible for macrophage infiltration into peripheral nerves, and is thereby associated with pain-like behaviors in mice. We propose herein that communication between Schwann cells and macrophages may play a prominent role in the induction of X4 HIV-1-associated pain.

Epidemiologic studies about food allergy and food sensitization in tropical countries. Results and limitations.

The variety of foods and methods of preparation are part of the cultural identity of each population, and thus the main foods that cause symptoms vary among different regions. Due to their increasing frequency, Adverse Reactions to Food (AFR) have been the subject of extensive study, especially in North America and Europe but few studies have been conducted in other areas, especially in populations located in the tropics and subtropics. In this article, we review available information on the epidemiology of food sensitization and food allergies in tropical regions and explore the different epidemiological data considering the major food involved, the underlying immune mechanism and clinical symptoms partners. In addition, we identify the possible limitations and questions that arise from studies conducted in tropical countries, which helps to generate objectives for future research.

[Hyperpigmentation]. / Hyperpigmentations.

The key diagnostic tool for hyperpigmentation is histopathology, which may be accompanied by certain laboratory tests. Hyperpigmentation may result from excess melanin (hypermelanosis), cutaneous iron deposits (hemosiderosis), cutaneous carotene deposits (carotenoderma), or cutaneous deposits of a substance not normally found in the skin (dyschromia). The different types of hypermelanosis may be classified as either localised or generalised. The former generally correspond to skin tumours and may form a cutaneous expression of complex syndromes, which most notably include cardiac abnormalities, or to pigmented forms of inflammatory and/or infectious dermatoses. Diffuse hypermelanosis is frequently a sign of systemic disease, generally metabolic or endocrine disease, or else it may result from pharmaceutical therapy. Herein we review the various causes of hyperpigmentation and the corresponding therapy.

In vivo characterization of macrophage-tropic simian immunodeficiency virus molecular clones in rhesus macaques.

Macrophages are a major target of HIV/SIV infection and play an important role in pathogenesis by serving as viral reservoirs in the central nervous system. Previously, a unique early SIVmac251 envelope (Env) variant, deSIV147 was cloned from blood of a rhesus macaque with rapid disease progression and SIV-associated encephalitis. Here, we show that infectious molecular clone deSIV147 caused systemic infection in rhesus macaques following intravenous or intrarectal exposure. Next, we inoculated deSIV147 into macaques depleted of CD4+ T cells and found that animals were SIV-positive, with high plasma and CSF viral loads. These macaques also showed SIVp17-positive macrophages in brain, lymph nodes, colon, lung, and liver. Furthermore, accumulation of perivascular macrophages, multinucleated giant cells, and microgliosis was detected. These findings suggest that the neurotropic deSIV147 clone will be useful to study macrophage infection in HIV/SIV-associated neurocognitive disorders, gain insights into myeloid cell reservoirs in brain and other anatomical sites, as well as test strategies for eradication.

A Fluorescence Study on Binding Interaction of N-acetylated Dansylamide Conjugates with ß-cyclodextrin, Tween-20 and DPPC Lipid Bilayer Membrane.

The present work describes the photophysical behavior of a saturated fatty acid (palmitic acid) containing N-acetylated dansylamide derivative (DAN-PA) into biologically important organized assembly such as ß-cyclodextrin (ß-CD), Tween-20 (T-20) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipid bilayer membrane. The results were compared by using another N-acetylated dansylamide conjugate having a short hydrophobic tail, DAN-ACYL. Long hydrophobic tail (saturated fatty acid) containing dansylamide conjugate (DAN-PA) shows more efficient binding interactions with the ß-CD as compared to the short tail containing dansylamide derivative (DAN-ACYL). The calculated binding constants values of DAN-PA and DAN-ACYL probes are 1.35 × 102 M -1 and 0.31 × 102 M -1 respectively. The DAP-PA is a sensitive fluorophore for understanding the micellization process in T-20, as compared to the DAN-ACYL because it shows a significant change in fluorescent properties (steady-state and time-resolved both) with changing in T-20 concentrations. The calculated CMC value for T-20 surfactant is 0.07 mM. While the DAN-ACYL does not show any change in the fluorescent properties while changing the T-20 concentrations. Fluorescent parameters like steady-state and time-resolved of DAN-PA are quite sensitive towards the thermo-tropic phase transitional changes into lipid bilayer membrane properties. And the calculated thermo-tropic phase transition temperature by using DAN-PA fluorophore is 42 °C.