Miracle-dz/UniFAR-FTUs huggingface dataset:
Reformulating Pro-Oxidant Microglia in Neurodegeneration

In neurodegenerative diseases, microglia-mediated neuroinflammation and oxidative stress are central events. Recent genome-wide transcriptomic analyses of microglial cells under different disease conditions have uncovered a new subpopulation named disease-associated microglia (DAM). These studies have challenged the classical view of the microglia polarization state’s proinflammatory M1 (classical activation) and immunosuppressive M2 (alternative activation). Molecular signatures of DAM and proinflammatory microglia (highly pro-oxidant) have shown clear differences, yet a partial overlapping gene profile is evident between both phenotypes. The switch activation of homeostatic microglia into reactive microglia relies on the selective activation of key surface receptors involved in the maintenance of brain homeostasis (a.k.a. pattern recognition receptors, PRRs). Two relevant PRRs are toll-like receptors (TLRs) and triggering receptors expressed on myeloid cells-2 (TREM2), whose selective activation is believed to generate either a proinflammatory or a DAM phenotype, respectively. However, the recent identification of endogenous disease-related ligands, which bind to and activate both TLRs and TREM2, anticipates the existence of rather complex microglia responses. Examples of potential endogenous dual ligands include amyloid β, galectin-3, and apolipoprotein E. These pleiotropic ligands induce a microglia polarization that is more complicated than initially expected, suggesting the possibility that different microglia subtypes may coexist. This review highlights the main microglia polarization states under disease conditions and their leading role orchestrating oxidative stress.
Genetic and genomic studies of pathogenic EXOSC2 mutations in the newly described disease SHRF implicate the autophagy pathway in disease pathogenesis.

Missense mutations in the RNA exosome component Exosome Component 2 (EXOSC2), also known as Ribosomal RNA-processing Protein 4 (RRP4), were recently identified in two unrelated families with a novel syndrome known as Short stature, Hearing loss, Retinitis pigmentosa, and distinctive Facies (SHRF, #OMIM 617763). Little is known about the mechanism of SHRF pathogenesis. Here we have studied the effect of mutations in EXOSC2/RRP4 in patient-derived lymphoblasts, clustered regularly interspaced short palindromic repeats (CRISPR)-generated mutant fetal keratinocytes, and Drosophila. We determined that human EXOSC2 is an essential gene, and that the pathogenic G198D mutation prevents binding to other RNA exosome components, resulting in protein and complex instability and altered expression and/or activities of critical genes, including those in the autophagy pathway. In parallel, we generated multiple CRISPR knockouts of the fly rrp4 gene. Using these flies, as well as rrp4 mutants with Piggy Bac (PBac) transposon insertion in the 3'UTR and RNAi flies, we determined that fly rrp4 was also essential, that fly rrp4 phenotypes could be rescued by wild-type human EXOSC2 but not the pathogenic form, and that fly rrp4 is critical for eye development and maintenance, muscle ultrastructure, and wing vein development. We found that overexpression of the transcription factor MITF was sufficient to rescue the small eye and adult lethal phenotypes caused by rrp4 inhibition. The autophagy genes ATG1 and ATG17, which are regulated by MITF, had similar effect. Pharmacological stimulation of autophagy with rapamycin also rescued the lethality caused by rrp4 inactivation. Our results implicate defective autophagy in SHRF pathogenesis and suggest therapeutic strategies.
Fucoidan-Rich Substances from Ecklonia cava Improve Trimethyltin-Induced Cognitive Dysfunction via Down-Regulation of Amyloid β Production/Tau Hyperphosphorylation

Ecklonia cava (E. cava) was investigated to compare the effect of polyphenol and fucoidan extract and mixture (polyphenol:fucoidan = 4:6) on cognitive function. The ameliorating effect of E. cava was evaluated using the Y-maze, passive avoidance and Morris water maze tests with a trimethyltin (TMT)-induced cognitive dysfunction model, and the results showed that the fucoidan extract and mixture (4:6) had relatively higher learning and memory function effects than the polyphenol extract. After a behavioral test, the inhibitory effect of lipid peroxidation and cholinergic system activity were examined in mouse brain tissue, and the fucoidan extract and mixture (4:6) also showed greater improvements than the polyphenol extract. Mitochondrial activity was evaluated using mitochondrial reactive oxygen species (ROS) content, mitochondrial membrane potential (MMP, ΔΨm), adenosine triphosphate (ATP) content, and mitochondria-mediated protein (BAX, cytochrome C) analysis, and these results were similar to the results of the behavioral tests. Finally, to confirm the cognitive function-related mechanism of E. cava, the amyloid-β production and tau hyperphosphorylation-medicated proteins were analyzed. Based on these results, the improvement effect of E. cava was more influenced by fucoidan than polyphenol. Therefore, our study suggests that the fucoidan-rich substances in E. cava could be a potential material for improving cognitive function by down-regulating amyloid-β production and tau hyperphosphorylation.
Ultrasensitive Electrical Detection of Hemagglutinin for Point-of-Care Detection of Influenza Virus Based on a CMP-NANA Probe and Top-Down Processed Silicon Nanowire Field-Effect Transistors

Rather than the internal genome nucleic acids, the biomolecules on the surface of the influenza virus itself should be detected for a more exact and rapid point-of-care yes/no decision for influenza virus-induced infectious diseases. This work demonstrates the ultrasensitive electrical detection of the HA1 domain of hemagglutinin (HA), a representative viral surface protein of the influenza virus, using the top-down complementary metal oxide semiconductor (CMOS) processed silicon nanowire (SiNW) field-effect transistor (FET) configuration. Cytidine-5′-monophospho-N-acetylneuraminic acid (CMP-NANA) was employed as a probe that specifically binds both to the aldehyde self-aligned monolayer on the SiNWs and to HA1 simultaneously. CMP-NANA was serially combined with two kinds of linkers, namely 3-aminopropyltriethoxysilane and glutaraldehyde. The surface functionalization used was verified using the purification of glutathione S-transferase-tagged HA1, contact angle measurement, enzyme-linked immunosorbent assay test, and isoelectric focusing analysis. The proposed functionalized SiNW FET showed high sensitivities of the threshold voltage shift (ΔVT) ~51 mV/pH and the ΔVT = 112 mV (63 mV/decade) with an ultralow detectable range of 1 fM of target protein HA1.
A Meta-Review of Indoor Positioning Systems

An accurate and reliable Indoor Positioning System (IPS) applicable to most indoor scenarios has been sought for many years. The number of technologies, techniques, and approaches in general used in IPS proposals is remarkable. Such diversity, coupled with the lack of strict and verifiable evaluations, leads to difficulties for appreciating the true value of most proposals. This paper provides a meta-review that performed a comprehensive compilation of 62 survey papers in the area of indoor positioning. The paper provides the reader with an introduction to IPS and the different technologies, techniques, and some methods commonly employed. The introduction is supported by consensus found in the selected surveys and referenced using them. Thus, the meta-review allows the reader to inspect the IPS current state at a glance and serve as a guide for the reader to easily find further details on each technology used in IPS. The analyses of the meta-review contributed with insights on the abundance and academic significance of published IPS proposals using the criterion of the number of citations. Moreover, 75 works are identified as relevant works in the research topic from a selection of about 4000 works cited in the analyzed surveys.
Glutamatergic Neurons in the Piriform Cortex Influence the Activity of D1- and D2-Type Receptor-Expressing Olfactory Tubercle Neurons

Sensory cortices process stimuli in manners essential for perception. Very little is known regarding interactions between olfactory cortices. The piriform “primary” olfactory cortex, especially its anterior division (aPCX), extends dense association fibers into the ventral striatum's olfactory tubercle (OT), yet whether this corticostriatal pathway is capable of shaping OT activity, including odor-evoked activity, is unknown. Sensory cortices process stimuli in manners essential for perception. Very little is known regarding interactions between olfactory cortices. The piriform “primary” olfactory cortex, especially its anterior division (aPCX), extends dense association fibers into the ventral striatum's olfactory tubercle (OT), yet whether this corticostriatal pathway is capable of shaping OT activity, including odor-evoked activity, is unknown. Further unresolved is the synaptic circuitry and the spatial localization of OT-innervating PCX neurons. Here we build upon standing literature to provide some answers to these questions through studies in mice of both sexes. First, we recorded the activity of OT neurons in awake mice while optically stimulating principal neurons in the aPCX and/or their association fibers in the OT while the mice were delivered odors. This uncovered evidence that PCX input indeed influences OT unit activity. We then used patch-clamp recordings and viral tracing to determine the connectivity of aPCX neurons upon OT neurons expressing dopamine receptor types D1 or D2, two prominent cell populations in the OT. These investigations uncovered that both populations of neurons receive monosynaptic inputs from aPCX glutamatergic neurons. Interestingly, this input originates largely from the ventrocaudal aPCX. These results shed light on some of the basic physiological properties of this pathway and the cell-types involved and provide a foundation for future studies to identify, among other things, whether this pathway has implications for perception. SIGNIFICANCE STATEMENT Sensory cortices interact to process stimuli in manners considered essential for perception. Very little is known regarding interactions between olfactory cortices. The present study sheds light on some of the basic physiological properties of a particular intercortical pathway in the olfactory system and provides a foundation for future studies to identify, among other things, whether this pathway has implications for perception.
Status of Plant Protein-Based Green Scaffolds for Regenerative Medicine Applications

In recent decades, regenerative medicine has merited substantial attention from scientific and research communities. One of the essential requirements for this new strategy in medicine is the production of biocompatible and biodegradable scaffolds with desirable geometric structures and mechanical properties. Despite such promise, it appears that regenerative medicine is the last field to embrace green, or environmentally-friendly, processes, as many traditional tissue engineering materials employ toxic solvents and polymers that are clearly not environmentally friendly. Scaffolds fabricated from plant proteins (for example, zein, soy protein, and wheat gluten), possess proper mechanical properties, remarkable biocompatibility and aqueous stability which make them appropriate green biomaterials for regenerative medicine applications. The use of plant-derived proteins in regenerative medicine has been especially inspired by green medicine, which is the use of environmentally friendly materials in medicine. In the current review paper, the literature is reviewed and summarized for the applicability of plant proteins as biopolymer materials for several green regenerative medicine and tissue engineering applications.
Trends of Two Epidemic Multidrug-Resistant Strains of Mycobacterium tuberculosis in Argentina Disclosed by Tailored Molecular Strategy.

Two Mycobacterium tuberculosis strains-M (sublineage 4.1) and Ra (sublineage 4.3)-have long prevailed in Argentina among patients with multidrug-resistant tuberculosis (MDR-TB). Recently, budget constraints have hampered the surveillance of MDR-TB transmission. Based on whole-genome sequence analysis, we used M- and Ra-specific single nucleotide polymorphisms to tailor two multiplex allele-specific PCRs, which we applied to 252 stored isolates (95% of all newly diagnosed MDR-TB cases countrywide), during 2015-2017. Compared with the latest data available (2007-2009), the M strain has receded (80/324 to 20/252, P < 0.0001), particularly among cross-border migrants (12/58 to 0/53, P = 0.0003) and HIV-infected people (30/97 to 7/74, P = 0.0007), but it still accounts for 4/12 new cases of extensively drug-resistant TB. Differently, the Ra strain remained stable in frequency (39/324 to 33/252) and contributed marginally to the extensive drug-resistance load (1/12). Our novel strategy disclosed recent trends of the two major MDR-TB strains, providing meaningful data to allocate control interventions more efficiently.
Comparison of cancer prevalence between patients with glomerulonephritis and the general population at the time of kidney biopsy

Glomerulonephritis (GN) has been associated with many solid and hematologic malignancies. However, cancer prevalence at the time of GN diagnosis has been rarely examined. We aimed to evaluate the cancer prevalence in patients with GN at the time of kidney biopsy and to compare the results to those of the general population. A total of 1,155 patients who underwent kidney biopsy between 2003 and 2017 were included. We investigated patients diagnosed with cancer within one month of kidney biopsy. The occurrence of cancer was compared with that of the Korean general population using the observed-to-expected rates (O/E ratio). Twenty-nine patients with GN had cancer. The mean age of patients with and without cancer was 49 and 66 years old, respectively. The proportion of male patients with and without cancer was 49.4% and 58.6%, respectively. The glomerular filtration rate was different between the groups (78.1 ± 37.0, 58.0 ± 43.6 ml/min/1.73 m2, p = 0.006), but the urine protein/creatinine ratio was not (3.21 ± 4.01, 5.38 ± 7.47 g/gCr, p = 0.172). Immunoglobulin A nephropathy (IgAN) was the most common GN (37.9%), followed by membranous GN (13.5%), focal segmental glomerulosclerosis (9.7%), minimal change disease (9.2%), amyloidosis (1.2%). Amyloidosis was the most common GN associated with malignancy (20.7%). In patients with amyloidosis, cancer was observed almost 28 times more than expected and these patients showed higher cancer occurrence than patients with other GN (Relative Risk [RR]: 15.73; 95% confidence interval [CI]: 4.82–51.30; p < 0.01). Cancer occurrence was three times greater in GN patients aged > 50 years compared to the general population (O/E ratio: 3.42; 95% CI: 1.37–5.46; p = 0.027). Patients with GN, especially amyloidosis, have higher risk of cancer than the general population at the time of GN diagnosis. Older age (> 50 years) was one of the major determinants of the presence of cancer in GN patients.
Long noncoding MIAT acting as a ceRNA to sponge microRNA‐204‐5p to participate in cerebral microvascular endothelial cell injury after cerebral ischemia through regulating HMGB1

This study is applied to the investigation of the long noncoding RNA myocardial infarction associated transcript's (MIAT's) role in regulating the expression of high‐mobility group box 1 (HMGB1) in cerebral microvascular endothelial cell (CMEC) injury after cerebral ischemia by serving as a competitive endogenous RNA (ceRNA) to sponge microRNA‐204‐5p (miR‐204‐5p). The cerebral ischemia model of middle cerebral artery occlusion (MCAO) in rats was established by the suture method, in which rats were injected with empty plasmids and MIAT siRNA plasmids. The cerebral ischemia injury model in vitro was established through oxygen glucose deprivation (OGD) in primary cultured CMECs in rats. The cells were transfected with empty plasmids and MIAT siRNA plasmids. The MIAT/miR‐204‐5p/HMGB1 axis’ function in damage and angiogenesis of CMECs were explored. The binding site between MIAT and miR‐204‐5p along with that between miR‐204‐5p and HMGB1 was determined. MIAT was overexpressed in MCAO rats’ brain tissue and inhibited MIAT attenuated the injury of brain tissue in MCAO rats. Inhibition of MIAT promoted angiogenesis, promoted miR‐204‐5p expression and inhibited HMGB1 expression in brain tissue of MCAO rats. Inhibition of MIAT reduced CMEC damage, induced angiogenesis of CMECs, increased the number of surviving neurons, promoted miR‐204‐5p expression and inhibited HMGB1 expression in CMECs treated with OGD. MIAT promoted HMGB1 expression by competitive binding to miR‐204‐5p to regulate the injury of CMECs after cerebral ischemia. Our study showed that MIAT promoted HMGB1 expression by competitively binding to miR‐204‐5p to regulate the injury of CMECs after cerebral ischemia.
Nitrate-responsive OBP4-XTH9 regulatory module controls lateral root development in Arabidopsis thaliana

Plant root system architecture in response to nitrate availability represents a notable example to study developmental plasticity, but the underlying mechanism remains largely unknown. Xyloglucan endotransglucosylases (XTHs) play a critical role in cell wall biosynthesis. Here we assessed the gene expression of XTH1-11 belonging to group I of XTHs in lateral root (LR) primordia and found that XTH9 was highly expressed. Correspondingly, an xth9 mutant displayed less LR, while overexpressing XTH9 presented more LR, suggesting the potential function of XTH9 in controlling LR development. XTH9 gene mutation obviously alters the properties of the cell wall. Furthermore, nitrogen signals stimulated the expression of XTH9 to promote LRs. Genetic analysis revealed that the function of XTH9 was dependent on auxin-mediated ARF7/19 and downstream AFB3 in response to nitrogen signals. In addition, we identified another transcription factor, OBP4, that was also induced by nitrogen treatment, but the induction was much slower than that of XTH9. In contrast to XTH9, overexpressing OBP4 caused fewer LRs while OBP4 knockdown with OBP4-RNAi or an artificial miRNA silenced amiOBP4 line produced more LR. We further found OBP4 bound to the promoter of XTH9 to suppress XTH9 expression. In agreement with this, both OBP4-RNAi and crossed OBP4-RNAi & 35S::XTH9 lines led to more LR, but OBP4-RNAi & xth9 produced less LR, similar to xth9. Based on these findings we propose a novel mechanism by which OBP4 antagonistically controls XTH9 expression and the OBP4-XTH9 module elaborately sustains LR development in response to nitrate treatment.
Effect of Temperatures Used in Food Storage on Duration of Heat Stress Induced Invasiveness of L. monocytogenes

The unpropitious conditions of the food processing environment trigger in Listeria monocytogenes stress response mechanisms that may affect the pathogen’s virulence. To date, many studies have revealed that acid, osmotic, heat, cold and oxidative stress modify invasiveness of L. monocytogenes. Nonetheless, there is limited data on the duration of the stress effect on bacterial invasiveness. Since most food is stored at low or room temperatures we studied the impact of these temperatures on the duration of heat stress effect on invasiveness of 8 L. monocytogenes strains. Bacteria were heat-treated for 20 min at 54 °C and then incubated at 5 and 20 °C up to 14 days. A decrease in invasiveness over time was observed for bacteria not exposed to heating. It was found that heat shock significantly reduced the invasion capacity of all strains and the effect lasted between 7 and 14 days at both 5 and 20 °C. In conclusion, 20-min heating reduces invasion capacity of all L. monocytogenes strains; however, the stress effect is temporary and lasts between 7 and 14 days in the food storage conditions. The invasiveness of bacteria changes along with the incubation time and is temperature-dependent.
Análise ecocardiográfica da função diastólica do ventrículo esquerdo após infarto do miocárdio em ratos

OBJECTIVE: To evaluate the diastolic left ventricular function by echocardiography one and three weeks after acute myocardial infarction (AMI). METHOD: Nineteen Wistar rats (mean 209 g) were utilized. After anesthesia with ketamine (50mg/kg) and xylazine (10mg/kg), the left coronary artery was ligated after left thoracotomy to cause myocardial infarction. The animals were divided in two groups: group A (control, n=7) and group B (n=9). Echocardiographic evaluation was undertaken in the control group and one week (B1, n=9) and three weeks (B3, n=8) post-AMI in group B animals. The cardiac function was evaluated using a 21275 A HP Sonos 1500 Echocardiography equipped with 7.5/5.5 MHz transducer. Diastolic function was evaluated by transmitral flow, by analysis of the A wave, E wave and atrial left volume (LAV). Histological specimens were evaluated on third week. RESULTS: There were no differences on E wave analyses (A=62cm/s, B1=65cm/s, B3=69cm/s) or A wave analyses (A=43cm/s, B1=40cm/s, B3=41cm/s) between the groups. There was an increase in LAV; A vs B1 and A vs B3 (A=0.05mL vs B1=0.15mL, p=0.04 e A vs B3=0.14mL, p=0.01). Histological examination confirmed AMI in all animals. CONCLUSIONS: The LAV may be useful to assess the diastolic function in rats with AMI. LAV could reflect increases in left ventricular end-diastolic pressure secondary to systolic or diastolic dysfunction.
CAF-1 Subunits Levels Suggest Combined Treatments with PARP-Inhibitors and Ionizing Radiation in Advanced HNSCC

Oral (OSCC) and oropharyngeal (OPSCC) squamous cell carcinomas show high morbidity and mortality rates. We aimed to investigate the role of the “Chromatin Assembly Factor-1” (CAF-1) p60 and p150 subunits, involved in DNA repair and replication, in OSCC and OPSCC progression and in response to Poly(ADP-ribose) polymerase (PARP)-inhibitors and exposure to ionizing radiation (IR). We immunostained tissue microarrays (TMAs), including 112 OSCC and 42 OPSCC, with anti-CAF-1/p60 and anti-CAF-1/p150 specific antibodies, correlating their expression with prognosis. Moreover, we assessed the sensitivity to PARP inhibitors and the double-strand breaks repair proficiency by cell viability and HR reporter assays, respectively, in HPV-positive and HPV-negative cell lines upon CAF-1/p60 and CAF-1/p150 depletion. The immunohistochemical analysis revealed a significant prognostic value of both tissue biomarkers combined expression in OSCC but not in OPSCC. In in vitro studies, the p60/150 CAF-1 subunits’ depletion impaired the proficiency of Homologous Recombination DNA damage repair, inducing sensitivity to the PARP-inhibitors, able to sensitize both the cell lines to IR. These results indicate that regardless of the prognostic meaning of p60/p150 tissue expression, the pharmacological depletion of CAF-1 complex’s function, combined to PARP-inhibitors and/or IR treatment, could represent a valid therapeutic strategy for squamous cell carcinomas of head and neck region.