Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential membrane binding of the human immunodeficiency virus type 1 matrix protein

The human immunodeficiency virus type 1 matrix protein (p17MA) plays a central role at both the early and late stages of the virus life cycle. During viral assembly, the p17MA domain of Pr55gag promotes membrane association, which is essential for the formation of viral particles. When viral infection occurs, the mature p17MA dissociates from the plasma membrane and participates in the nuclear targeting process. Thus, p17MA contains a reversible membrane binding signal to govern its differential subcellular localization and biological functions. We previously identified a membrane binding signal within the amino-terminal 31 amino acids of the matrix domain of human immunodeficiency virus type 1 Gag, consisting of myristate and a highly basic region (W. Zhou, L. J. Parent, J. W. Wills, and M. D. Resh, J. Virol. 68:2556-2569, 1994). Here we show that exposure of this membrane binding signal is regulated in different Gag protein contexts. Within full-length Pr55gag, the membrane targeting signal is exposed and can direct Pr55gag as well as heterologous proteins to the plasma membrane. However, in the context of p17MA alone, this signal is hidden and unable to confer plasma membrane binding. To investigate the molecular mechanism for regulation of membrane binding, a series of deletions within p17MA was generated by sequentially removing alpha-helical regions defined by the nuclear magnetic resonance structure. Removal of the last alpha helix (amino acids 97 to 109) of p17MA was associated with enhancement of binding to biological membranes in vitro and in vivo. Liposome binding experiments indicated that the C-terminal region of p17MA exerts a negative effect on the N-terminal MA membrane targeting domain by sequestering the myristate signal. We propose that mature p17MA adopts a conformation different from that of the p17MA domain within Pr55gag and present evidence to support this hypothesis. It is likely that such a conformational change results in an N-terminal myristyl switch which governs differential membrane binding.
Introducing insecticide‐treated nets in the Kilombero Valley, Tanzania: the relevance of local knowledge and practice for an Information, Education and Communication (IEC) campaign

Since 1997 the WHO has been recommending an integrative strategy to combat malaria including new medicines, vaccines, improvements of health care systems and insecticide‐treated nets (ITNs). After successful controlled trials with ITNs in the past decade, large‐scale interventions and research now focus on operational issues of distribution and financing. In developing a social marketing approach in the Kilombero Valley in south‐east Tanzania in 1996, a combination of qualitative and quantitative methods was employed to investigate local knowledge and practice relating to malaria. The findings show that the biomedical concept of malaria overlaps with several local illness concepts, one of which is called maleria and refers to mild malaria. Most respondents linked maleria to mosquitoes (76%) and already used mosquito nets (52%). But local understandings of severe malaria differed from the biomedical concept and were not linked to mosquitoes or malaria. A social marketing strategy to promote ITNs was developed on the basis of these findings, which reinforced public health messages and linked them with nets and insecticide. Although we did not directly evaluate the impact of promotional activities, the sharp rise in ownership and use of ITNs by the population (from 10 to > 50%) suggests that they contributed significantly to the success of the programme. Local knowledge and practice is highly relevant for social marketing strategies of ITNs.
Inhibition of amyloid fibrillation of lysozyme by indole derivatives − possible mechanism of action

Amyloid aggregation of polypeptides is related to a growing number of pathologic states known as amyloid disorders. There is a great deal of interest in developing small molecule inhibitors of the amyloidogenic processes. In the present article, the inhibitory effects of some indole derivatives on amyloid fibrillation of hen egg white lysozyme (HEWL) are reported. Acidic pH and high temperatures were used to drive HEWL towards amyloid formation. A variety of techniques, ranging from thioflavin T fluorescence and Congo red absorbance assays to far‐UV CD and transmission electron microscopy, were employed to characterize the HEWL fibrillation process. Among the indole derivatives tested, indole 3‐acetic acid, indole 3‐carbinol and tryptophol had the most inhibitory effects on amyloid formation, indole and indole 3‐propionic acid gave some inhibition, and indole aldehyde and tryptophan showed no significant inhibition. Although indoles did not protect the HEWL native state from conformational changes, they were effective in diminishing HEWL amyloid fibril formation, delaying both the nucleation and elongation phases. Disaggregation of previously formed HEWL amyloid fibrils was also enhanced by indole 3‐acetic acid. Various medium conditions, such as the presence of different anions and alcoholic cosolvents, were explored to gain an insight into possible mechanisms. These observations, taken together, suggest that the indole ring is likely to play the main role in inhibition and that the side chain hydroxyl group may contribute positively, in contrast to the side chain carbonyl and intervening methylene groups.
An Updated Survey on Statistical Thresholding and Sample Size of fMRI Studies

Background: Since the early 2010s, the neuroimaging field has paid more attention to the issue of false positives. Several journals have issued guidelines regarding statistical thresholds. Three papers have reported the statistical analysis of the thresholds used in fMRI literature, but they were published at least 3 years ago and surveyed papers published during 2007–2012. This study revisited this topic to evaluate the changes in this field. Methods: The PubMed database was searched to identify the task-based (not resting-state) fMRI papers published in 2017 and record their sample sizes, inferential methods (e.g., voxelwise or clusterwise), theoretical methods (e.g., parametric or non-parametric), significance level, cluster-defining primary threshold (CDT), volume of analysis (whole brain or region of interest) and software used. Results: The majority (95.6%) of the 388 analyzed articles reported statistics corrected for multiple comparisons. A large proportion (69.6%) of the 388 articles reported main results by clusterwise inference. The analyzed articles mostly used software Statistical Parametric Mapping (SPM), Analysis of Functional NeuroImages (AFNI), or FMRIB Software Library (FSL) to conduct statistical analysis. There were 70.9%, 37.6%, and 23.1% of SPM, AFNI, and FSL studies, respectively, that used a CDT of p ≤ 0.001. The statistical sample size across the articles ranged between 7 and 1,299 with a median of 33. Sample size did not significantly correlate with the level of statistical threshold. Conclusion: There were still around 53% (142/270) studies using clusterwise inference that chose a more liberal CDT than p = 0.001 (n = 121) or did not report their CDT (n = 21), down from around 61% reported by Woo et al. (2014). For FSL studies, it seemed that the CDT practice had no improvement since the survey by Woo et al. (2014). A few studies chose unconventional CDT such as p = 0.0125 or 0.004. Such practice might create an impression that the threshold alterations were attempted to show “desired” clusters. The median sample size used in the analyzed articles was similar to those reported in previous surveys. In conclusion, there seemed to be no change in the statistical practice compared to the early 2010s.
Integrins modulate Sog activity in the Drosophila wing

Morphogenesis of the Drosophila wing depends on a series of cell-cell and cell-extracellular matrix interactions. During pupal wing development, two secreted proteins, encoded by the short gastrulation (sog) and decapentaplegic (dpp) genes, vie to position wing veins in the center of broad provein territories. Expression of the Bmp4 homolog dpp in vein cells is counteracted by expression of the Bmp antagonist sog in intervein cells, which results in the formation of straight veins of precise width. We screened for genetic interactions between sog and genes encoding a variety of extracellular components and uncovered interactions between sog and myospheroid (mys), multiple edematous wing (mew) and scab (scb), which encode βPS,α PS1 and αPS3 integrin subunits, respectively. Clonal analysis reveals that integrin mutations affect the trajectory of veins inside the provein domain and/or their width and that misexpression of sog can alter the behavior of cells in such clones. In addition, we show that a low molecular weight form of Sog protein binds to αPS1βPS. We find that Sog can diffuse from its intervein site of production into adjacent provein domains, but only on the dorsal surface of the wing, where Sog interacts functionally with integrins. Finally, we show that Sog diffusion into provein regions and the reticular pattern of extracellular Sog distribution in wild-type wings requires mys and mew function. We propose that integrins act by binding and possibly regulating the activity/availability of different forms of Sog during pupal development through an adhesion independent mechanism.
Second-line therapy for NSCLC in clinical practice: baseline results of the European SELECTTION observational study

Abstract Objective: Although the efficacy of a number of drugs for the second-line treatment of non-small cell lung cancer (NSCLC) has been demonstrated in Phase III trials, very limited evidence exists on optimal duration of second-line treatment or the reasons why this treatment is stopped in standard clinical practice. SELECTTION (Survey in European Lung Cancer Evaluating Choice of Treatment and Tolerability In Observed NSCLC) was designed to assess the time from initiation of second-line treatment for NSCLC to treatment discontinuation for any reason, the reasons for discontinuation, and the impact of discontinuation on outcomes. Methods: From October 2006 to January 2008, 1012 patients with advanced/metastatic NSCLC who completed or discontinued first-line treatment were enrolled in a multi-national, prospective observational cohort study (SELECTTION). Treatment cohorts were constructed based on the patients’ distribution across second-line treatments that were assigned by physician decision (pemetrexed, docetaxel, erlotinib, other treatments). This report presents a descriptive analysis of the baseline data collected, including patient/disease characteristics, treatment history and planned second-line treatments. Factors that may have affected treatment choice, selected by physicians from a range of options, were also identified. Results: Overall, 468 patients (46.2%) were enrolled in the pemetrexed cohort, 232 (22.9%) in docetaxel cohort, 206 (20.4%) in erlotinib cohort and 106 (10.5%) received other treatments. The profile of patients enrolled in the erlotinib cohort differed from those of patients enrolled in the pemetrexed or docetaxel cohorts in that erlotinib was more frequently planned for women, never-smokers and patients with adenocarcinomas. The primary reasons physicians gave for selection of the second-line treatment were tolerance and efficacy for pemetrexed, and preferred regimen for the particular patient and efficacy for the other treatments. Conclusions: In this observational study, pemetrexed, then docetaxel and erlotinib were the most frequently prescribed second-line treatments, which is in line with international guidelines. Erlotinib was most commonly prescribed to that subset of patients expected to gain the greatest benefit (those with adenocarcinoma, never-smokers and females). Pemetrexed was more frequently prescribed than docetaxel, with physicians most commonly choosing to prescribe the former agent because of its tolerability profile.
Induction of hypoxia‐inducible factor‐1 (HIF‐1) and its target genes following focal ischaemia in rat brain

HIF‐1 is a heterodimeric transcription factor, induced by hypoxia, that is composed of HIF‐1α and HIF‐1β protein subunits. It binds to promoter/enhancer elements and stimulates the transcription of hypoxia‐inducible target genes, including glucose transporter‐1 and the glycolytic enzymes. Because HIF‐1 activation might promote cell survival in hypoxic tissues, we studied the effect of permanent middle cerebral artery occlusion on the expression of HIF‐1α, HIF‐1β and several HIF‐1 target genes in adult rat brain. After focal ischaemia, mRNAs encoding HIF‐1α, glucose transporter‐1 and several glycolytic enzymes were up‐regulated in the peri‐infarct penumbra. This was observed by 7.5 h after the onset of ischaemia and increased further at 19 and 24 h. Regional cerebral blood flow was moderately decreased at 1 and 24 h after the ischaemia in areas of HIF‐1 and HIF‐1 target gene induction. Because hypoxia induces HIF‐1 in other tissues, systemic hypoxia (6% O2 for 4.5 h) was also shown to increase HIF‐1α protein expression in the adult rat brain. It is proposed that decreased blood flow to the penumbra decreases the supply of oxygen and that this induces HIF‐1 and its target genes. This is the first study to show induction of HIF‐1 after focal ischaemia in brain. Increased expression of HIF‐1 target genes as a result of HIF‐1 activation by hypoxia may contribute to tissue viability in the hypoxic/ischaemic penumbra by increasing glucose transport and glycolysis.
Degree Distribution Based MIMO - LDPC Scheme

In this paper, an LDPC based MIMO scheme is proposed in which matrix modulation scheme of MIMO and unequal protection ability of irregular LDPC codes are employed. The new scheme named degree distribution based-MIMO (DDB-MIMO for short) combines the two schemes, in which the important bits with large degrees are transmitted in transmission diversity (TD) symbols and bits with small degrees are mapped to the spatial multiplexing (SM) mode symbols. Since the TD mode could offer more protection to the data streams by offering more transmission power, the important bits with large degrees which could contribute more to the decoding process would have more protection from TD mode and hence the system performance would be improved namely. The performance of the new scheme has also been evaluated by the Gaussian approximation (GA) scheme which is used to analyze the asymptotic performance of LDPC coded system. The analysis results provide us the optimal mapping fractions between the bits with different degrees and transmitted symbols in different modes which is almost the same as the DDB-MIMO scheme offering. The simulation results also proved the new scheme.
Bacterial DNA confers neuroprotection after optic nerve injury by suppressing CD4+CD25+ regulatory T-cell activity.

PURPOSE Protective autoimmunity attenuates secondary degeneration after central nervous system (CNS) injury. Such neuroprotection is achieved via activation of autoimmune CD4(+)CD25(-) effector T cells (Teffs) or suppression of naturally occurring CD4(+)CD25(+) regulatory T cells (Tregs). In this study the ability of bacterial DNA, characterized by unmethylated CpG islands, to downregulate Treg activity and therefore, to confer neuroprotection was investigated. METHODS The effects of CpG on suppressive activity of mouse Tregs were studied by coculturing Tregs with Teffs and measuring proliferation by radiolabeled thymidine. The neuroprotective effects of CpG-mediated Treg suppression was examined in rats after optic nerve crush. RESULTS Teff proliferation in response to T-cell receptor stimuli was significantly reduced when the Teffs were cocultured with Tregs, compared with Teff activation when cultured alone. Treating Tregs with CpG reduced their suppressive activity and restored Teff proliferation to baseline levels. CpG injection in rats with optic nerve crush conferred significant neuroprotection compared with that in untreated control rats (118 +/- 8 cells/mm(2) vs. 69 +/- 5 cells/mm(2), respectively; mean +/- SEM; P < 0.05). CpG-mediated neuroprotection was accompanied by significantly increased T-cell infiltration at the injury site. Similar CpG treatment of athymic nude rats yielded no neuroprotection, further suggesting a T-cell-dependent mechanism of CpG action. CONCLUSIONS These findings strongly support the notion that alleviation of Treg suppression after injury benefits neuronal survival. Bacterial DNA attenuation of Treg suppressive activity may represent an evolutionary adaptation that curbs the amplified infection risk after CNS trauma, due to blood-brain barrier breakdown. This study may prompt development of new neuroprotective therapies aimed at the immune system, to benefit the injured CNS.
Multicenter randomized controlled trial comparing the performance of 22 gauge versus 25 gauge EUS–FNA needles in solid masses

Abstract Background and aims. Few randomized studies have assessed the clinical performance of 25-gauge (25G) needles compared with 22-gauge (22G) needles during endoscopic ultrasound-guided fine needle aspiration (EUS–FNA) biopsy of intra-abdominal lesions. We aimed to compare the diagnostic yield, as well as performance characteristics of 22G versus 25G EUS biopsy needles by determining their diagnostic capabilities, the number of needle passes as well as cellularity of aspirated tissue specimen. Methods. The study is a prospective, randomized, multicenter study. Patients were referred between January 2009 and January 2010 for diagnostic EUS including EUS-guided FNA of different lesions adjacent to the upper GI tract. All patients were randomized to EUS–FNA performed with either a 22G or 25G aspiration needle. Results. EUS–FNA was performed in 135 patients (62 patients with a 22G needle). Sensitivity and specificity of the 22G needle was 94.1% and 95.8%, respectively, and for the 25G needle 94.1% and 100%, respectively. Investigators reported better visualization and performance for the 22G needle compared to the 25G (p < 0.0001). The number of tissue slides obtained was higher for the 22G needle during the second and third needle passes (p < 0.05). We did not observe significant differences between the number and preservation status of obtained cells (p > 0.05). Conclusions. A significant difference was found between the two types of needles in terms of reduced visualization of the 25G needle and suboptimal performance rating. However, this did not impact on overall results since both needles were equally successful in terms of a high diagnostic yield and overall accuracy.
An overview of the LASER-AD study: A longitudinal epidemiological study of people with Alzheimer's disease

Abstract Research into the epidemiological, clinical characteristics and economic impact of dementia is critical to increase understanding and better inform care and policy, and empower people with Alzheimer's disease (AD) and their families to make preparations and timely decisions about accommodation, care and treatment. The LASER-AD longitudinal study of people with AD and their carers has contributed to our understanding of the progression, characteristics and costs of the disease, and to developing tools that help detect dementia earlier, and screen and identify problems experienced by carers. Our work on quality of life shows that even those with severe dementia can report this meaningfully, although family proxy ratings of quality of life do not necessarily mirror the views of the individual. Despite the impact of the disease process, people with AD experience well-being in adversity and still live fulfilling lives. The study highlights the high prevalence and severity of neuropsychiatric symptoms, carer anxiety, depression and abusive behaviour. It informs future directions for possible interventions, in particular the central role of carer coping strategies in predicting carer mental illness. Current research is building on our findings, which have also been used to inform national and international plans for managing people with dementia and their carers.
High fairness reader anti-collision protocol in passive RFID systems

With the spread of passive Radio Frequency Identification (RFID) systems, new applications will see the coexistence of more and more RFID readers in the same area. As for wireless devices, also RFID readers experience collisions whenever sharing the same communication channel. In this paper, an anti-collision protocol has been proposed in order to solve the reader collision problem. The aims of the proposed solution are: (1) to prevent and avoid collisions among readers; and (2) to limit the access delay of the readers on the channel, while guaranteeing them fairness with respect to the channel contention. The reader anticollision here proposed, referred as to High Fairness Reader Anti-Collision Protocol (HF-RACP), has been designed taking into account passive tags and their limitations in terms of computational and frequency selectivity capabilities. In this paper, after presenting the reader collision problem and discussing the simulation models and the evaluation methodology used herein, the simulation results for several anti-collision algorithms are shown in terms of collision avoidance and access delay. The comparison with contention-based schemes, like Listen Before Talk (LBT), demonstrates that HF-RACP is more effective against collisions, improves the fairness among readers and considerably reduces the maximum access delay.
Biocompatibility of Platinum Nanoparticles in Brain ex vivo Models in Physiological and Pathological Conditions

Platinum nanoparticles (PtNPs) have unique physico-chemical properties that led to their use in many branches of medicine. Recently, PtNPs gathered growing interest as delivery vectors for drugs, biosensors and as surface coating on chronically implanted biomedical devices for improving electrochemical properties. However, there are contradictory statements about their biocompatibility and impact on target organs such as the brain tissue, where these NPs are finding many applications. Furthermore, many of the reported studies are conducted in homeostasis conditions and, consequently, neglect the impact of the pathologic conditions on the tissue response. To expand our knowledge on the effects of PtNPs on neuronal and glial cells, we investigated the acute effects of monodisperse sodium citrate-coated PtNPs on rat organotypic hippocampal cultures in physiological or neuronal excitotoxic conditions induced by kainic acid (KA). The cellular responses of the PtNPs were evaluated through cytotoxic assays and confocal microscopy analysis. To mimic a pathologic scenario, 7-day organotypic hippocampal cultures were exposed to KA for 24 h. Subsequently, PtNPs were added to each slice. We show that incubation of the slices with PtNPs for 24 h, does not severely impact cell viability in normal conditions, with no significant differences when comparing the dentate gyrus (DG), as well as CA3 and CA1 pyramidal cell layers. Such effects are not exacerbated in KA-treated slices, where the presence of PtNPs does not cause additional neuronal propidium iodide (PI) uptake in CA3 and CA1 pyramidal cell layers. However, PtNPs cause microglial cell activation and morphological alterations in CA3 and DG regions indicating the establishment of an inflammatory reaction. Morphological analysis revealed that microglia acquire activated ameboid morphology with loss of ramifications, as a result of their response to PtNPs contact. Surprisingly, this effect is not increased in pathological conditions. Taken together, these results show that PtNPs cause microglia alterations in short-term studies. Additionally, there is no worsening of the tissue response in a neuropathological induced scenario. This work highlights the need of further research to allow for the safe use of PtNPs. Also, it supports the demand of the development of novel and more biocompatible NPs to be applied in the brain.