Adipokines as New Biomarkers of Immune Recovery: Apelin Receptor,RBP4 and ZAG Are Related to CD4+ T-Cell Reconstitution in PLHIV on Suppressive Antiretroviral Therapy

A significant proportion of people living with HIV (PLHIV) who successfully achieve virological suppression fail to recover CD4⁺ T-cell counts. Since adipose tissue has been discovered as a key immune organ, this study aimed to assess the role of adipokines in the HIV immunodiscordant response. This is a multicenter prospective study including 221 PLHIV starting the first antiretroviral therapy (ART) and classified according to baseline CD4⁺ T-cell counts/µL (controls > 200 cells/µL and cases ≤ 200 cells/µL). Immune failure recovery was considered when cases did not reach more than 250 CD4⁺ T cells/µL at 144 weeks (immunological nonresponders, INR). Circulating adipokine concentrations were longitudinally measured using enzyme-linked immunosorbent assays. At baseline, apelin receptor (APLNR) and zinc-alpha-2-glycoprotein (ZAG) concentrations were significantly lower in INRs than in immunological responders (p = 0.043 and p = 0.034), and they remained lower during all ART follow-up visits (p = 0.044 and p = 0.028 for APLNR, p = 0.038 and p = 0.010 for ZAG, at 48 and 144 weeks, respectively). ZAG levels positively correlated with retinol-binding protein 4 (RBP4) levels (p < 0.01), and low circulating RBP4 concentrations were related to a low CD4⁺ T-cell gain (p = 0.018 and p = 0.039 at 48 and 144 weeks, respectively). Multiple regression adjusted for clinical variables and adipokine concentrations confirmed both low APLNR and RBP4 as independent predictors for CD4⁺ T cells at 144 weeks (p < 0.001). In conclusion, low APLNR and RBP4 concentrations were associated with poor immune recovery in treated PLHIV and could be considered predictive biomarkers of a discordant immunological response.     

Upregulated Apelin Signaling in Pancreatic Cancer Activates Oncogenic Signaling Pathways to Promote Tumor Development

Despite decades of effort in understanding pancreatic ductal adenocarcinoma (PDAC), there is still a lack of innovative targeted therapies for this devastating disease. Herein, we report the expression of apelin and its receptor, APJ, in human pancreatic adenocarcinoma and its protumoral function. Apelin and APJ protein expression in tumor tissues from patients with PDAC and their spatiotemporal pattern of expression in engineered mouse models of PDAC were investigated by immunohistochemistry. Apelin signaling function in tumor cells was characterized in pancreatic tumor cell lines by Western blot as well as proliferation, migration assays and in murine orthotopic xenograft experiments. In premalignant lesions, apelin was expressed in epithelial lesions whereas APJ was found in isolated cells tightly attached to premalignant lesions. However, in the invasive stage, apelin and APJ were co-expressed by tumor cells. In human tumor cells, apelin induced a long-lasting activation of PI3K/Akt, upregulated β-catenin and the oncogenes c-myc and cyclin D1 and promoted proliferation, migration and glucose uptake. Apelin receptor blockades reduced cancer cell proliferation along with a reduction in pancreatic tumor burden. These findings identify the apelin signaling pathway as a new actor for PDAC development and a novel therapeutic target for this incurable disease.     

H4K5 Butyrylation Coexist with Acetylation during Human Spermiogenesis and Are Retained in the Mature Sperm Chromatin

Male germ cells experience a drastic chromatin remodeling through the nucleo-histone to nucleo-protamine (NH-NP) transition necessary for proper sperm functionality. Post-translational modifications (PTMs) of H4 Lys5, such as acetylation (H4K5ac), play a crucial role in epigenetic control of nucleosome disassembly facilitating protamine incorporation into paternal DNA. It has been shown that butyrylation on the same residue (H4K5bu) participates in temporal regulation of NH-NP transition in mice, delaying the bromodomain testis specific protein (BRDT)-dependent nucleosome disassembly and potentially marking retained nucleosomes. However, no information was available so far on this modification in human sperm. Here, we report a dual behavior of H4K5bu and H4K5ac in human normal spermatogenesis, suggesting a specific role of H4K5bu during spermatid elongation, coexisting with H4K5ac although with different starting points. This pattern is stable under different testicular pathologies, suggesting a highly conserved function of these modifications. Despite a drastic decrease of both PTMs in condensed spermatids, they are retained in ejaculated sperm, with 30% of non-colocalizing nucleosome clusters, which could reflect differential paternal genome retention. Whereas no apparent effect of these PTMs was observed associated with sperm quality, their presence in mature sperm could entail a potential role in the zygote.     

Self-linking and self-linked rates of academic institutions on the Web

In this paper we introduce two measures self-linked and self-linkingthat are the analogues of self-citing and self-cited rates for scientific journals. These rates are calculated for a sample of sites to assess their meaning and utility. Self-linked is the more meaningful measure for the sample sites. As a first step towards a better understanding of self-linking (linking within a site), a sample of pages from an academic site was characterized using the method of content analysis. Even though most of the links serve navigational or other technical purposes, the percentage of content-bearing links among the self-links is significant, and even the portion of research oriented links is non-negligible.     

The sources used by bibliometrics-scientometrics as reflected in references

The aim of this study was to examine the extent to which the field of bibliometrics and scientometrics makes use of sources outside the field. The research was carried out by examining the references of articles published in Scientometrics in the course of two calendar years, 1990, 2000. The results show that in 2000, 56.9% (and 47.3% in 1990) of the references originated from three fields: scientometrics and bibliometrics; library and information science; and the sociology, history and philosophy of science. When comparing the two periods, there is also a considerable increase in journal self-citation (i.e., references to the journal Scientometrics) and in the percentage of references to journals. This revised version was published online in June 2006 with corrections to the Cover Date.     

The main features of suburbanization in the Great Hungarian Plain

Suburbanization, which took place through different mechanisms, and occured earlier in western European countries, is a relatively new phenomenon in Hungary. The Great Plain was only affected by industrial decentralization in the 1960s.The housing shortage is a serious problem in Hungary, thus the cheaper sites for sale in the suburds are especially attractive. Moreover, demands for space in the Great Plain compared with other regions of the country are greater here for people used to living in the large agrarian towns. The fact that they can do household and supplementary farming around their homes is an important incentive. This only means self-provision for many of them, but others carry out market gardening. Agriculture is the only survival strategy for numbers of people in the Great Plain, given the present dismal state of the Hungarian economy. Therefore, suburbs here are of unmistakably rural character and their population is not homogenous. Infrastructural investment has not kept up with the increase in population. Very often it is the commuting villages which have turned into suburbs, and with spatial relationships becoming more intense, they generally lose their administrative independence.     

Ultrasound as a probe of dislocation density in aluminum

Dislocations are at the heart of the plastic behavior of crystalline materials yet it is notoriously difficult to perform quantitative, non-intrusive measurements of their single or collective properties. Dislocation density is a critical variable that determines dislocation mobility, strength and ductility. On the one hand, individual dislocations can be probed in detail with transmission electron microscopy. On the other hand, their collective properties must be simulated numerically. Here we show that ultrasound technology can be used to measure dislocation density. This development rests on theory—a generalization of the Granato–Lücke theory for the interaction of elastic waves with dislocations—and resonant ultrasound spectroscopy (RUS) measurements. The chosen material is aluminum, to which different dislocation contents were induced through annealing and cold-rolling processes. The dislocation densities obtained with RUS compare favorably with those inferred from X-ray diffraction, using the modified Williamson–Hall method.     

Charting a path for innovative toilet technology using multicriteria decision analysis

Practical and theoretically sound methods for analyzing innovative environmental technologies are needed to inform public and private decisions regarding research and development, risk management, and stakeholder communication. By integrating scientific assessments with a characterization of values, multicriteria decision analysis (MCDA) supports the ranking of alternative technology pathways on the basis of technical, financial, and social concerns. We applied MCDAto evaluate the use of NoMix urine separating toilets for managing environmental risk and postponing expensive upgrades to a large wastewater treatment plant near Zürich, Switzerland. Results indicate that, given current priorities, no single, fixed course of action (including the status quo) will be desirable to all stakeholders over the considered time horizon. However, a path forward is suggested that is not significantly disadvantageous to any stakeholder now and leaves open future options, allowing society to achieve overall greater benefits if priorities change, new environmental risks are revealed, or technology improves. While our analysis focuses on a particular catchment in Switzerland, many communities worldwide are faced with an aging and inefficient wastewater treatment infrastructure while also experiencing growth and development. Our framework can help these communities balance the conflicting objectives of diverse stakeholders and gain insight into the role that urine separation can play in transitioning to a more comprehensive and sustainable urban water management system.     

Analysis of Molecular Networks in the Cerebellum in Chronic Schizophrenia: Modulation by Early Postnatal Life Stressors in Murine Models

Despite the growing importance of the cerebellum as a region highly vulnerable to accumulating molecular errors in schizophrenia, limited information is available regarding altered molecular networks with potential therapeutic targets. To identify altered networks, we conducted one-shot liquid chromatography–tandem mass spectrometry in postmortem cerebellar cortex in schizophrenia and healthy individuals followed by bioinformatic analysis (PXD024937 identifier in ProteomeXchange repository). A total of 108 up-regulated proteins were enriched in stress-related proteins, half of which were also enriched in axonal cytoskeletal organization and vesicle-mediated transport. A total of 142 down-regulated proteins showed an enrichment in proteins involved in mitochondrial disease, most of which were also enriched in energy-related biological functions. Network analysis identified a mixed module of mainly axonal-related pathways for up-regulated proteins with a high number of interactions for stress-related proteins. Energy metabolism and neutrophil degranulation modules were found for down-regulated proteins. Further, two double-hit postnatal stress murine models based on maternal deprivation combined with social isolation or chronic restraint stress were used to investigate the most robust candidates of generated networks. CLASP1 from the axonal module in the model of maternal deprivation was combined with social isolation, while YWHAZ was not altered in either model. METTL7A from the degranulation pathway was reduced in both models and was identified as altered also in previous gene expression studies, while NDUFB9 from the energy network was reduced only in the model of maternal deprivation combined with social isolation. This work provides altered stress- and mitochondrial disease-related proteins involved in energy, immune and axonal networks in the cerebellum in schizophrenia as possible novel targets for therapeutic interventions and suggests that METTL7A is a possible relevant altered stress-related protein in this context.