The mechanism by which piR-000699 targets SLC39A14 regulates ferroptosis in aging myocardial ischemia/reperfusion injury.

Myocardial ischemia/reperfusion (I/R) injury is a classic type of cardiovascular disease characterized by injury to cardiomyocytes leading to different types of cell death. The degree of irreversible myocardial damage is closely related to age, and ferroptosis is involved in cardiomyocyte damage. However, the mechanisms underlying ferroptosis regulation in aging myocardial I/R injury are still unclear. The present study aims to explore the underlying mechanism of piRNA regulation in ferroptosis. Using left anterior descending coronary artery ligation in an aging rat model and a D-galactose-induced rat cardiomyocyte line (H9C2) to construct an aging cardiomyocyte model, we investigate whether ferroptosis occurs after reperfusion injury in vitro and in vivo. This study focuses on the upregulation of piR-000699 after hypoxia/reoxygenation treatment in aging cardiomyocytes by observing hypoxia/reoxygenation (H/R) injury indicators and ferroptosis-related indicators and clarifying the role of piR-000699 in H/R injury caused by ferroptosis in aging cardiomyocytes. Bioinformatics analysis reveals that SLC39A14 is a gene that binds to piR-000699. Our data show that ferroptosis plays an important role in I/R injury both in vivo and in vitro. Furthermore, the results show the potential role of piR-000699 in regulating SLC39A14 in ferroptosis in aging cardiomyocytes under hypoxia/reoxygenation conditions. Together, our results reveal that the mechanism by which piR-000699 binds to SLC39A14 regulates ferroptosis in aging myocardial I/R injury.

Passive Infrared Sensor-Based Occupancy Monitoring in Smart Buildings: A Review of Methodologies and Machine Learning Approaches.

Buildings are rapidly becoming more digitized, largely due to developments in the internet of things (IoT). This provides both opportunities and challenges. One of the central challenges in the process of digitizing buildings is the ability to monitor these buildings' status effectively. This monitoring is essential for services that rely on information about the presence and activities of individuals within different areas of these buildings. Occupancy information (including people counting, occupancy detection, location tracking, and activity detection) plays a vital role in the management of smart buildings. In this article, we primarily focus on the use of passive infrared (PIR) sensors for gathering occupancy information. PIR sensors are among the most widely used sensors for this purpose due to their consideration of privacy concerns, cost-effectiveness, and low processing complexity compared to other sensors. Despite numerous literature reviews in the field of occupancy information, there is currently no literature review dedicated to occupancy information derived specifically from PIR sensors. Therefore, this review analyzes articles that specifically explore the application of PIR sensors for obtaining occupancy information. It provides a comprehensive literature review of PIR sensor technology from 2015 to 2023, focusing on applications in people counting, activity detection, and localization (tracking and location). It consolidates findings from articles that have explored and enhanced the capabilities of PIR sensors in these interconnected domains. This review thoroughly examines the application of various techniques, machine learning algorithms, and configurations for PIR sensors in indoor building environments, emphasizing not only the data processing aspects but also their advantages, limitations, and efficacy in producing accurate occupancy information. These developments are crucial for improving building management systems in terms of energy efficiency, security, and user comfort, among other operational aspects. The article seeks to offer a thorough analysis of the present state and potential future advancements of PIR sensor technology in efficiently monitoring and understanding occupancy information by classifying and analyzing improvements in these domains.

A new glutamine synthetase index to evaluate hepatic lobular restoration in advanced fibrosis during anti-HBV therapy.

Hepatic lobular architecture distortion is a deleterious turning point and a crucial histological feature of advanced liver fibrosis in chronic liver diseases. Regression of fibrosis has been documented in chronic hepatitis B (CHB) patients. However, whether lobular architecture could be restored following fibrosis regression after antiviral therapy is still unclear. Glutamine synthetase (GS) is generally expressed by perivenular hepatocytes around hepatic veins (HV). In this study, we defined abnormal lobular architecture (GSPT ) as GS expressing in the vicinity of portal tracts (PT), which denotes parenchymal extinction and lobular collapse. We defined normal lobular architecture (GSHV ) as GS positivity area not approximating PTs. Therefore, we propose a new GS-index, defined as the percentage of GSHV /(GSHV + GSPT ), to evaluate the extent of architectural disruption and restoration. We evaluated 43 CHB patients with advanced fibrosis (Ishak stage ≥4). Posttreatment liver biopsy was performed after 78 weeks of anti-HBV therapy. The median GS-index improved from 7% (interquartile range [IQR]: 0%-23%) at baseline to 36% (IQR: 20%-57%) at Week 78 (p < 0.001). Totals of 22 patients (51%) had significant GS-index improvement from 0% (IQR: 0%-13%) to 55% (IQR: 44%-81%), while the other half had almost no change between 17% (IQR: 0%-33%) to 20% (IQR: 12%-31%). When GS-index78w ≥ 50% was used to define hepatic lobular restoration, 37% of patients (16/43) achieved lobular restoration, with much improvement in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (median value of ∆/Baseline in ALT: restored vs. nonrestored was 79.1% vs. 48.8%, p = 0.018; median value of ∆/Baseline in AST: restored vs. nonrestored was 69.1% vs. 32.5%, p = 0.005). More importantly, lobular restoration correlated with fibrosis regression (median value of ∆/Baseline in Ishak stage: restored vs. nonrestored was 25.0% vs. 0%, p = 0.008). Therefore, in the era of antiviral therapy for CHB, restoration of hepatic lobular architecture is achievable in patients with advanced fibrosis. GS-index provides additional insight into fibrosis regression that goes beyond collagen degradation.

piRNA-823 is a novel potential therapeutic target in aortic dissection.

Aortic dissection (AD) presents a medical challenge for clinicians. Here, to determine the role of a novel small non-coding piRNA-823 (piR-823) in AD, murine and human aorta from patients with AD were used. A high expression levels of piR-823 were found in patients with AD. Using performed loss- and gain-of-function assays in vitro and in vivo, we explore the regulatory effect of piR-823 on vascular smooth muscle cells (VSMCs) and AD. piR-823 obviously facilitates the proliferation, migration, and phenotypic transformation of VSMCs with or without nicotine treatment. piR-823 directly binds and suppresses histone deacetylase 1 (HDAC1) expression, and regulates the acetylation of histone 3 (H3) via H3K9ac and H3K27ac, eventually, VSMC functions and AD. To consolidate our findings, AD murine model was performed, and we observed that piR-823 antagomir strongly inhibited the pathogenesis of AD through regulating vascular remodeling. Thus, our study finds a potential target for the prevention and treatment strategy for nicotine-induced AD.

Streamlining N-terminally anchored yeast surface display via structural insights into S. cerevisiae Pir proteins.

Surface display co-opts yeast's innate ability to embellish its cell wall with mannoproteins, thus converting the yeast's outer surface into a growing and self-sustaining catalyst. However, the efficient toolbox for converting the enzyme of interest into its surface-displayed isoform is currently lacking, especially if the isoform needs to be anchored to the cell wall near the isoform's N-terminus, e.g., through a short GPI-independent protein anchor. Aiming to advance such N-terminally anchored surface display, we employed in silico and machine-learning strategies to study the 3D structure, function, genomic organisation, and evolution of the Pir protein family, whose members evolved to covalently attach themselves near their N-terminus to the ß-1,3-glucan of the cell wall. Through the newly-gained insights, we rationally engineered 14 S. cerevisiae Hsp150 (Pir2)-based fusion proteins. We quantified their performance, uncovering guidelines for efficient yeast surface display while developing a construct that promoted a 2.5-fold more efficient display of a reporter protein than the full-length Hsp150. Moreover, we developed a Pir-tag, i.e., a peptide spanning only 4.5 kDa but promoting as efficient surface display of a reporter protein as the full-length Hsp150. These constructs fortify the existing surface display toolbox, allowing for a prompt and routine refitting of intracellular proteins into their N-terminally anchored isoforms.

A Multi-Sensor Fusion Approach Based on PIR and Ultrasonic Sensors Installed on a Robot to Localise People in Indoor Environments.

This work illustrates an innovative localisation sensor network that uses multiple PIR and ultrasonic sensors installed on a mobile social robot to localise occupants in indoor environments. The system presented aims to measure movement direction and distance to reconstruct the movement of a person in an indoor environment by using sensor activation strategies and data processing techniques. The data collected are then analysed using both a supervised (Decision Tree) and an unsupervised (K-Means) machine learning algorithm to extract the direction and distance of occupant movement from the measurement system, respectively. Tests in a controlled environment have been conducted to assess the accuracy of the methodology when multiple PIR and ultrasonic sensor systems are used. In addition, a qualitative evaluation of the system's ability to reconstruct the movement of the occupant has been performed. The system proposed can reconstruct the direction of an occupant with an accuracy of 70.7% and uncertainty in distance measurement of 6.7%.

Exploiting the PIR Sensor Analog Behavior as Thermoreceptor: Movement Direction Classification Based on Spiking Neurons.

Pyroelectric infrared sensors (PIR) are widely used as infrared (IR) detectors due to their basic implementation, low cost, low power, and performance. Combined with a Fresnel lens, they can be used as a binary detector in applications of presence and motion control. Furthermore, due to their features, they can be used in autonomous intelligent devices or included in robotics applications or sensor networks. In this work, two neural processing architectures are presented: (1) an analog processing approach to achieve the behavior of a presynaptic neuron from a PIR sensor. An analog circuit similar to the leaky integrate and fire model is implemented to be able to generate spiking rates proportional to the IR stimuli received at a PIR sensor. (2) An embedded postsynaptic neuron where a spiking neural network matrix together with an algorithm based on digital processing techniques is introduced. This structure allows connecting a set of sensors to the post-synaptic circuit emulating an optic nerve. As a case study, the entire neural processing approach presented in this paper is applied to optical flow detection considering a four-PIR array as input. The results validate both the spiking approach for an analog sensor presented and the ability to retrieve the analog information sent as spike trains in a simulated optic nerve.

'Personality and bipolar disorder: personality profiles of patients with remitted bipolar disorder and matched controls in a Danish sample'.

BACKGROUND: The aim of the study was to investigate whether patients with bipolar disorder (BD) in remission differ in personality traits compared with a healthy control group. METHODS: A sample of patients with BD (n = 44) was compared with an individually matched control group (n = 44) using the Danish version of the Revised NEO Personality Inventory (NEO PI-R). Paired t-tests were used to analyze differences between the two groups and multiple regression models to evaluate predictors of NEO scores in the patient group. RESULTS: Patients with BD reported significantly higher scores on both Neuroticism and Openness to Experience and lower scores on Conscientiousness. No differences were found on Extraversion and Agreeableness. The effect size for Neuroticism and its facets had a range from 0.77 to 1.45 SD.Statistically significant group differences were seen on 15 of 30 lower-level traits within all five high-order dimensions. There were large effect sizes for Trust (0.77) and Self-discipline (0.85), while the other statistically significant group differences were smaller with effect sizes in the range from 0.43 to 0.74 SD.However, patients with BD showed a profile with high-order dimensions and lower-level traits within one standard deviation from the mean score except for the lower-level trait Depression. CONCLUSIONS: Our findings suggest that patients with BD differ from healthy control persons with respect to higher levels of Neuroticism, Openness to Experience and lower scores on Agreeableness and on Conscientiousness, but prospective studies are needed to evaluate the implications of this finding.

A Receptor Story: Insulin Resistance Pathophysiology and Physiologic Insulin Resensitization's Role as a Treatment Modality.

Physiologic insulin secretion consists of an oscillating pattern of secretion followed by distinct trough periods that stimulate ligand and receptor activation. Apart from the large postprandial bolus release of insulin, ß cells also secrete small amounts of insulin every 4-8 min independent of a meal. Insulin resistance is associated with a disruption in the normal cyclical pattern of insulin secretion. In the case of type-2 diabetes, ß-cell mass is reduced due to apoptosis and ß cells secrete insulin asynchronously. When ligand/receptors are constantly exposed to insulin, a negative feedback loop down regulates insulin receptor availability to insulin, creating a relative hyperinsulinemia. The relative excess of insulin leads to insulin resistance (IR) due to decreased receptor availability. Over time, progressive insulin resistance compromises carbohydrate metabolism, and may progress to type-2 diabetes (T2D). In this review, we discuss insulin resistance pathophysiology and the use of dynamic exogenous insulin administration in a manner consistent with more normal insulin secretion periodicity to reverse insulin resistance. Administration of insulin in such a physiologic manner appears to improve insulin sensitivity, lower HgbA1c, and, in some instances, has been associated with the reversal of end-organ damage that leads to complications of diabetes. This review outlines the rationale for how the physiologic secretion of insulin orchestrates glucose metabolism, and how mimicking this secretion profile may serve to improve glycemic control, reduce cellular inflammation, and potentially improve outcomes in patients with diabetes.

The Problem of Monitoring Activities of Older People in Multi-Resident Scenarios: An Innovative and Non-Invasive Measurement System Based on Wearables and PIR Sensors.

This paper presents an innovative multi-resident activity detection sensor network that uses the Bluetooth Low Energy (BLE) signal emitted by tags worn by residents and passive infrared (PIR) motion sensors deployed in the house to locate residents and monitor their activities. This measurement system solves the problem of monitoring older people and measuring their activities in multi-resident scenarios. Metrics are defined to analyze and interpret the collected data to understand daily habits and measure the activity level (AL) of older people. The accuracy of the system in detecting movements and discriminating residents is measured. As the sensor-to-person distance increases, the system decreases its ability to detect small movements, while still being able to detect large ones. The accuracy in discriminating the identity of residents can be improved by up to 96% using the Decision Tree (DT) classifier. The effectiveness of the measurement system is demonstrated in a real multi-resident scenario where two older people are monitored during their daily life. The collected data are processed, obtaining the AL and habits of the older people to assess their behavior.

Expression of the AHPND Toxins PirAvp and PirBvp Is Regulated by Components of the Vibrio parahaemolyticus Quorum Sensing (QS) System.

Acute hepatopancreatic necrosis disease (AHPND) in shrimp is caused by Vibrio strains that harbor a pVA1-like plasmid containing the pirA and pirB genes. It is also known that the production of the PirA and PirB proteins, which are the key factors that drive the observed symptoms of AHPND, can be influenced by environmental conditions and that this leads to changes in the virulence of the bacteria. However, to our knowledge, the mechanisms involved in regulating the expression of the pirA/pirB genes have not previously been investigated. In this study, we show that in the AHPND-causing Vibrio parahaemolyticus 3HP strain, the pirAvp and pirBvp genes are highly expressed in the early log phase of the growth curve. Subsequently, the expression of the PirAvp and PirBvp proteins continues throughout the log phase. When we compared mutant strains with a deletion or substitution in two of the quorum sensing (QS) master regulators, luxO and/or opaR (luxOD47E, ΔopaR, ΔluxO, and ΔopaRΔluxO), our results suggested that expression of the pirAvp and pirBvp genes was related to the QS system, with luxO acting as a negative regulator of pirAvp and pirBvp without any mediation by opaRvp. In the promoter region of the pirAvp/pirBvp operon, we also identified a putative consensus binding site for the QS transcriptional regulator AphB. Real-time PCR further showed that aphBvp was negatively controlled by LuxOvp, and that its expression paralleled the expression patterns of pirAvp and pirBvp. An electrophoretic mobility shift assay (EMSA) showed that AphBvp could bind to this predicted region, even though another QS transcriptional regulator, AphAvp, could not. Taken together, these findings suggest that the QS system may regulate pirAvp/pirBvp expression through AphBvp.

Physiologic Insulin Resensitization as a Treatment Modality for Insulin Resistance Pathophysiology.

Prevalence of type 2 diabetes increased from 2.5% of the US population in 1990 to 10.5% in 2018. This creates a major public health problem, due to increases in long-term complications of diabetes, including neuropathy, retinopathy, nephropathy, skin ulcers, amputations, and atherosclerotic cardiovascular disease. In this review, we evaluated the scientific basis that supports the use of physiologic insulin resensitization. Insulin resistance is the primary cause of type 2 diabetes. Insulin resistance leads to increasing insulin secretion, leading to beta-cell exhaustion or burnout. This triggers a cascade leading to islet cell destruction and the long-term complications of type 2 diabetes. Concurrent with insulin resistance, the regular bursts of insulin from the pancreas become irregular. This has been treated by the precise administration of insulin more physiologically. There is consistent evidence that this treatment modality can reverse the diabetes-associated complications of neuropathy, diabetic ulcers, nephropathy, and retinopathy, and that it lowers HbA1c. In conclusion, physiologic insulin resensitization has a persuasive scientific basis, significant treatment potential, and likely cost benefits.

Oil palm and gendered time use: A mixed-methods case study from West Kalimantan, Indonesia.

Measuring the social impact of oil palm requires the use of multiple metrics which capture different dimensions of well-being. To date, most studies have examined welfare outcomes at the household level, relying on a relatively narrow range of indicators. There is a need for a more diverse range of metrics to measure the social impacts of oil palm as well as more explicit accounting for study context and gendered effects. Here we demonstrate the utility of specialised time use methods used in combination with qualitative research to understand intra-household labour dynamics associated with oil palm adoption. We use a mixed-methods approach to investigate the role of smallholder oil palm plasma schemes on men and women's time use in Kapuas Hulu District, West Kalimantan. Time allocation is an important determinant of well-being as well as maternal and child nutrition and an indicator of women's empowerment and gender equality. We integrate the results from a fractional multinomial logistic regression of data from 603 individuals with qualitative findings on the subjective experience of time allocation, as well as, the causes, consequences and coping strategies to manage trade-offs in time allocation. We find that relative to non-oil-palm adopting swidden farmers, participation in oil palm plasma schemes is associated with more time spent in productive labour for both men and women, driven by off-farm labour on oil palm plantations. For women, increased time comes at the cost of reduced time spent in rest, leisure and sleep. Increased time spent in off-farm labour drives households to adapt agricultural production methods, changing cash crop production as well as accelerating swidden transitions. These changes alter gender dynamics and responsibilities within the household. Our results suggest that changes in time allocation may have significant consequences for women's well-being and gender equity. Women in the oil palm site experienced greater stress over time scarcity and employed coping strategies more frequently. Our findings indicate that time allocation could be used as an indicator of the effects of oil palm expansion and adoption on well-being and that potential effects of time scarcity on well-being, gender equity, and maternal and child nutrition should be considered by policy makers when making land use decisions.

New Bounds and a Generalization for Share Conversion for 3-Server PIR.

Private Information Retrieval (PIR) protocols, which allow the client to obtain data from servers without revealing its request, have many applications such as anonymous communication, media streaming, blockchain security, advertisement, etc. Multi-server PIR protocols, where the database is replicated among the non-colluding servers, provide high efficiency in the information-theoretic setting. Beimel et al. in CCC 12' (further referred to as BIKO) put forward a paradigm for constructing multi-server PIR, capturing several previous constructions for k≥3 servers, as well as improving the best-known share complexity for 3-server PIR. A key component there is a share conversion scheme from corresponding linear three-party secret sharing schemes with respect to a certain type of "modified universal" relation. In a useful particular instantiation of the paradigm, they used a share conversion from (2,3)-CNF over Zm to three-additive sharing over Zpß for primes p1,p2,p where p1≠p2 and m=p1·p2, and the relation is modified universal relation CSm. They reduced the question of the existence of the share conversion for a triple (p1,p2,p) to the (in)solvability of a certain linear system over Zp, and provided an efficient (in m,logp) construction of such a sharing scheme. Unfortunately, the size of the system is Θ(m2) which entails the infeasibility of a direct solution for big m's in practice. Paskin-Cherniavsky and Schmerler in 2019 proved the existence of the conversion for the case of odd p1, p2 when p=p1, obtaining in this way infinitely many parameters for which the conversion exists, but also for infinitely many of them it remained open. In this work, using some algebraic techniques from the work of Paskin-Cherniavsky and Schmerler, we prove the existence of the conversion for even m's in case p=2 (we computed ß in this case) and the absence of the conversion for even m's in case p>2. This does not improve the concrete efficiency of 3-server PIR; however, our result is promising in a broader context of constructing PIR through composition techniques with k≥3 servers, using the relation CSm where m has more than two prime divisors. Another our suggestion about 3-server PIR is that it's possible to achieve a shorter server's response using the relation CSm' for extended Sm'⊃Sm. By computer search, in BIKO framework we found several such sets for small m's which result in share conversion from (2,3)-CNF over Zm to 3-additive secret sharing over Zpß', where ß'>0 is several times less than ß, which implies several times shorter server's response. We also suggest that such extended sets Sm' can result in better PIR due to the potential existence of matching vector families with the higher Vapnik-Chervonenkis dimension.

ILT4 functions as a potential checkpoint molecule for tumor immunotherapy.

Immune checkpoint blockade therapy targeting CTLA4 and PD-1/PD-L1 is a promising strategy in the treatment of different types of cancers. However, the clinical success rates of these therapies are still moderate and varied among cancer types. Therefore, identification of alternative and novel checkpoint molecules or interrupting tolerogenic pathways is urgently needed for successful tumor immunotherapy. Immunoglobulin-like transcript 4 (ILT4) is as an immunosuppressive molecule predominantly expressed in myeloid cells, including monocytes, macrophages, dendritic cells and granulocytes. Recent studies revealed that ILT4 is also enriched in tumor cells and stroma cells in the tumor microenvironment of various malignancies, modulating the biological behaviors of tumor cells and promoting their immune escape. However, the underlying mechanisms responsible for ILT4-mediated tumor development and progression are still poorly understood. In this review, we explore the functional role of ILT4 as a novel checkpoint molecule in cancers. We specifically discuss the mechanisms mediated by ILT4 for controlling tumor malignant behaviors, impairing effector anti-tumor immune responses, and sustaining the tumor suppressive microenvironment. We also highlight the potential role of ILT4 as a novel immune checkpoint target for tumor immunotherapy. Improved understanding of these issues is critical for elucidation of the role of ILT4 in tumor pathogenesis and should open new avenues for cancer immunotherapy specifically targeting this novel and alternative checkpoint molecule.

Synthetic Generation of Passive Infrared Motion Sensor Data Using a Game Engine.

Quantifying the number of occupants in an indoor space is useful for a wide variety of applications. Attempts have been made at solving the task using passive infrared (PIR) motion sensor data together with supervised learning methods. Collecting a large labeled dataset containing both PIR motion sensor data and ground truth people count is however time-consuming, often requiring one hour of observation for each hour of data gathered. In this paper, a method is proposed for generating such data synthetically. A simulator is developed in the Unity game engine capable of producing synthetic PIR motion sensor data by detecting simulated occupants. The accuracy of the simulator is tested by replicating a real-world meeting room inside the simulator and conducting an experiment where a set of choreographed movements are performed in the simulated environment as well as the real room. In 34 out of 50 tested situations, the output from the simulated PIR sensors is comparable to the output from the real-world PIR sensors. The developed simulator is also used to study how a PIR sensor's output changes depending on where in a room a motion is carried out. Through this, the relationship between sensor output and spatial position of a motion is discovered to be highly non-linear, which highlights some of the difficulties associated with mapping PIR data to occupancy count.

A Setup for Measuring the Centering Error of a Dual-Element Pyroelectric Infrared Sensor Module.

This paper presents an experimental setup to measure the horizontal centering error of a pre-built pyroelectric infrared (PIR) sensor module, in which a dual-element PIR sensor is aligned at the focal point of a single-zone Fresnel Lens. In the setup, the sensor module was placed facing a modulated infrared radiating source and turned over a range of horizontal angles. The position of the optical axis of the sensor module was determined based on the analysis of the output response of the sensor at turned angles. Thus, the horizontal centering error of the module is defined as the difference between the mechanical axis of the housing and the found optical axis. For the prebuilt sensor module, with the specific available equipment, the measurement of the centering error of the module achieved a resolution of 0.02 degrees.

Motion Sensor-Based Detection of Outlier Days Supporting Continuous Health Assessment for Single Older Adults.

The aging population has resulted in interest in remote monitoring of elderly individuals' health and well being. This paper describes a simple unsupervised monitoring system that can automatically detect if an elderly individual's pattern of presence deviates substantially from the recent past. The proposed system uses a small set of low-cost motion sensors and analyzes the produced data to establish an individual's typical presence pattern. Then, the algorithm uses a distance function to determine whether the individual's observed presence for each day significantly deviates from their typical pattern. Empirically, the algorithm is validated on both synthetic data and data collected by installing our system in the residences of three older individuals. In the real-world setting, the system detected, respectively, five, four, and one deviating days in the three locations. The deviating days detected by the system could result from a health issue that requires attention. The information from the system can aid caregivers in assessing the subject's health status and allows for a targeted intervention. Although the system can be refined, we show that otherwise hidden but relevant events (e.g., fall incident and irregular sleep patterns) are detected and reported to the caregiver.

PIWI-interacting RNA 39980 promotes tumor progression and reduces drug sensitivity in neuroblastoma cells.

Neuroblastoma (NB) is the leading pediatric cancer known for its heterogeneity and clinical aggressiveness leading to chemoresistance. Recent evidence in small RNA research has led to the discovery of PIWI-interacting RNAs (piRNAs) which work in an orchestrated fashion to modulate gene expression both in homeostatic conditions and abnormalities like cancer including NB. This study aims to decipher the possible role of a repeat-derived piRNA, piR-39980 (identified from our previous piRNA profiling study in human NB cell lines) in tumorigenesis of NB cells. piR-39980, overexpressed in NB cells act as an oncopiR and promotes tumor progression, while its inhibition resulted in reduced viability, invasion as well as the migration of IMR-32 cells. Interestingly, we observed that inhibition of piRNA induces senescence of NB cells without affecting the classical apoptosis pathway by modulating the expression of JAK3 through target binding. In addition, piR-39980 was found to desensitize the effect of doxorubicin and inhibit drug-induced apoptosis. Overall, we report piR-39980, as the first oncopiR which might serve as a novel therapeutic target for this malignancy.

Conserved associations between G-quadruplex-forming DNA motifs and virulence gene families in malaria parasites.

BACKGROUND: The Plasmodium genus of malaria parasites encodes several families of antigen-encoding genes. These genes tend to be hyper-variable, highly recombinogenic and variantly expressed. The best-characterized family is the var genes, exclusively found in the Laveranian subgenus of malaria parasites infecting humans and great apes. Var genes encode major virulence factors involved in immune evasion and the maintenance of chronic infections. In the human parasite P. falciparum, var gene recombination and diversification appear to be promoted by G-quadruplex (G4) DNA motifs, which are strongly associated with var genes in P. falciparum. Here, we investigated how this association might have evolved across Plasmodium species - both Laverania and also more distantly related species which lack vars but encode other, more ancient variant gene families. RESULTS: The association between var genes and G4-forming motifs was conserved across Laverania, spanning ~ 1 million years of evolutionary time, with suggestive evidence for evolution of the association occurring within this subgenus. In rodent malaria species, G4-forming motifs were somewhat associated with pir genes, but this was not conserved in the Laverania, nor did we find a strong association of these motifs with any gene family in a second outgroup of avian malaria parasites. Secondly, we compared two different G4 prediction algorithms in their performance on extremely A/T-rich Plasmodium genomes, and also compared these predictions with experimental data from G4-seq, a DNA sequencing method for identifying G4-forming motifs. We found a surprising lack of concordance between the two algorithms and also between the algorithms and G4-seq data. CONCLUSIONS: G4-forming motifs are uniquely strongly associated with Plasmodium var genes, suggesting a particular role for G4s in recombination and diversification of these genes. Secondly, in the A/T-rich genomes of Plasmodium species, the choice of prediction algorithm may be particularly influential when studying G4s in these important protozoan pathogens.