Miracle-dz/UniFAR-FTUs huggingface dataset:
Inflammatory cytokines, oxidative and antioxidative stress levels in patients with diabetic macular edema and hyperreflective spots

Purpose: To determine the levels of serum oxidative, antioxidative markers and inflammatory cytokines in patients diagnosed with diabetic macular edema (DME) whose hyperreflective spots (HRS) were detected by optical coherence tomography (OCT). Methods: In this prospective cross-sectional clinical study included a total of 88 patients; 31 patients (group-1) with DME and HRS detected by OCT, 29 patients (group-2) with DME without HRS, and 28 patients (group-3) diagnosed with diabetes mellitus (DM) without any diabetic retinopathy findings. The main outcomes were best-corrected visual acuity (BCVA), CMT (central macular thickness), CMV (central macular volume), TMV (total macular volume), CT (choroidal thickness), serum TAS (total antioxidant status), TOS (total oxidant status), VEGF (vascular endothelial growth factor), FGF (fibroblast growth factor) and IL-1b levels. OCT parameters and biochemical measurements were compared statistically between the three groups. Results: A total of 88 patients (43 females (48.9%) and 45 males (51.1%)) were included in the study. The mean age was 56.29 ± 9.23 years. There was no difference between the three groups in age-and-sex. In group-1 and 2, BCVA(LogMAR) was statistically higher than group 3. CMT, CMV, TMV, TAS, TOS, VEGF and FGF were significantly higher in group-1 than in group-3. CMT, CMV, TMV, VEGF and FGF were significantly higher in group-2 than group 3. TOS and VEGF were significantly higher in group-1 than group-2. Conclusions: This study demonstrates that in patients with DME and HRS, TOS and VEGF levels were higher than those without HRS. Hence, hyperreflective spots may be an inflammatory biomarker.
Increasing axial parenchyma fraction in the Malagasy Magnoliids facilitated the co-optimization of hydraulic efficiency and safety.

The evolution of angiosperms was accompanied by the segregation and specialization of their xylem tissues. This study aimed to determine whether the fraction and arrangement of parenchyma tissue influence the hydraulic efficiency-safety trade-off in the basal angiosperms. We examined xylem anatomical structure and hydraulic functioning of 28 woody species of Magnoliids in a tropical rainforest of Madagascar and reported, for the first time, quantitative measurements that support the relationship between vessel-to-xylem parenchyma connectivity and the hydraulic efficiency-safety trade-off. We also introduced a new measurement - the distance of species from the trade-off limit - to quantify the co-optimization of hydraulic efficiency and safety. Although the basal angiosperms in this study had low hydraulic conductivity and safety, species with higher axial parenchyma fraction (APf) had significantly higher hydraulic conductivity. Hydraulic efficiency-safety optimization was accompanied by higher APf and vessel-to-axial parenchyma connectivity. Conversely, species exhibiting high ray parenchyma fraction and high vessel-to-ray connectivity had lower Ks and were further away from the hydraulic trade-off limit line. Our results provide evidence that axial parenchyma fraction and paratracheal arrangement are associated with both enhanced hydraulic efficiency and safety.
Transcriptomic changes in green bean pods against grey mould and white rot diseases via field application of chemical elicitor nanoparticles.

The authors tested the efficacy of two salt nanoparticles (NPs), namely, copper dioxide (CuO) and tri-calcium phosphate [Ca3(PO4)2] to induce resistance in green bean pods against grey mould and white rot diseases caused by Botrytis cinerea and Sclerotinia sclerotiorum, respectively. High amounts of phytoalexins, kievitone, coumestrol, phaseollidin, 6-ά-hydroxyphaseollin, and phaseollin, were detected in naturally infected and artificially inoculated green bean pods in response to the tested NPs. Green bean plants treated in the field with CuO and Ca3(PO4)2 NPs had the highest mRNA quantity of all the studied defence genes, receptor-like kinase (PvRK20), pathogenesis-related protein (PR1), 1,3-β-D-glucanase (pvgluc), polygalacturonase inhibitor protein (PvGIP), and alpha-dioxygenase (a-DOX) than that of the control group. CuO NPs followed by Ca3(PO4)2 NPs at 0.15 mg ml-1 were the most potent in increasing the transcriptomic levels of pk20, DOX, PR1, PvGIP, and pvgluc. Field applications of both chemical elicitor NPs exhibited a non-genotoxic effect on the Paulista green bean DNA using eight ISSR primers. The field application of the studied NPs could effectively extend the shelf life of green bean pods by up to 21 days at 7 ± 1°C during marketing and export due to its potent effect against grey mould and white rot diseases.
Revisiting the proteolytic processing of cell adhesion molecule L1

The important functions of cell adhesion molecule L1 in the nervous system depend on diverse proteolytic enzymes which generate different L1 fragments. It has been reported that cleavage in the third fibronectin type III (FNIII) homologous domain generates the fragments L1‐80 and L1‐140, while cleavage in the first FNIII domain yields the fragments L1‐70 and L1‐135. These results raised questions concerning the L1 cleavage sites. We thus generated gene‐edited mice expressing L1 with mutations of the cleavage sites either in the first or third FNIII domain. By immunoprecipitations and immunoblot analyses using brain homogenates and different L1 antibodies, we show that L1‐70 and L1‐135 are generated in wild‐type mice, but not or only to a low extent in L1 mutant mice. L1‐80 and L1‐140 were not detected in wild‐type or mutant mice. Mass spectrometry confirmed the results from immunoprecipitations and immunoblot analyses. Based on these observations, we propose that L1‐70 and L1‐135 are the predominant fragments in the mouse nervous system and that the third FNIII domain is decisive for generating these fragments. Treatment of cultured cerebellar neurons with trypsin or plasmin, which were both proposed to generate L1‐80 and L1‐140 by cleaving in the third FNIII domain, showed by immunoprecipitations and immunoblot analyses that both proteases lead to the generation of L1‐70 and L1‐135, but not L1‐80 and L1‐140. We discuss previous observations on the basis of our new results and propose a novel view on the molecular features that render previous and present observations compatible.
Natural Variation in Plant Pluripotency and Regeneration

Plant regeneration is essential for survival upon wounding and is, hence, considered to be a strong natural selective trait. The capacity of plant tissues to regenerate in vitro, however, varies substantially between and within species and depends on the applied incubation conditions. Insight into the genetic factors underlying this variation may help to improve numerous biotechnological applications that exploit in vitro regeneration. Here, we review the state of the art on the molecular framework of de novo shoot organogenesis from root explants in Arabidopsis, which is a complex process controlled by multiple quantitative trait loci of various effect sizes. Two types of factors are distinguished that contribute to natural regenerative variation: master regulators that are conserved in all experimental systems (e.g., WUSCHEL and related homeobox genes) and conditional regulators whose relative role depends on the explant and the incubation settings. We further elaborate on epigenetic variation and protocol variables that likely contribute to differential explant responsivity within species and conclude that in vitro shoot organogenesis occurs at the intersection between (epi) genetics, endogenous hormone levels, and environmental influences.
Non-Local Meets Global: An Iterative Paradigm for Hyperspectral Image Restoration

Non-local low-rank tensor approximation has been developed as a state-of-the-art method for hyperspectral image (HSI) restoration, which includes the tasks of denoising, compressed HSI reconstruction and inpainting. Unfortunately, while its restoration performance benefits from more spectral bands, its runtime also substantially increases. In this paper, we claim that the HSI lies in a global spectral low-rank subspace, and the spectral subspaces of each full band patch group should lie in this global low-rank subspace. This motivates us to propose a unified paradigm combining the spatial and spectral properties for HSI restoration. The proposed paradigm enjoys performance superiority from the non-local spatial denoising and light computation complexity from the low-rank orthogonal basis exploration. An efficient alternating minimization algorithm with rank adaptation is developed. It is done by first solving a fidelity term-related problem for the update of a latent input image, and then learning a low-dimensional orthogonal basis and the related reduced image from the latent input image. Subsequently, non-local low-rank denoising is developed to refine the reduced image and orthogonal basis iteratively. Finally, the experiments on HSI denoising, compressed reconstruction, and inpainting tasks, with both simulated and real datasets, demonstrate its superiority with respect to state-of-the-art HSI restoration methods.
Cardiovascular risk and mortality in rheumatoid arthritis compared with diabetes mellitus and the general population.

OBJECTIVES To compare risk of cardiovascular disease and mortality in patients with incident RA, diabetes mellitus (DM) and the general population (GP). METHODS Patients diagnosed with incident RA were matched 1:5 by age, sex and year of RA diagnosis with the GP. In the same period, patients with incident DM were included. Outcomes were heart failure (HF), myocardial infarction (MI), coronary revascularization, stroke, major adverse cardiovascular events (MACE) and death up to 10 years after diagnosis. RESULTS We included 15 032 patients with incident RA, 301 246 patients with DM and 75 160 persons from the GP. RA patients had an increased risk of HF [hazard ratio (HR) 1.51, 95% CI: 1.38, 1.64], MI (HR 1.58, 95% CI: 1.43, 1.74), percutaneous coronary intervention (PCI; HR 1.44, 95% CI: 1.27, 1.62), coronary artery bypass grafting (CABG; HR 1.30, 95% CI: 1.05, 1.62) and stroke (HR 1.22, 95% CI: 1.12-1.33) compared with the GP. However, the 10-year all-cause mortality was at the same level as observed in the GP. Cardiac death and MACE were increased in RA compared with the GP. When compared with patients with DM, RA patients had a lower adjusted risk of HF (HR 0.79, 95% CI: 0.73, 0.85), CABG (HR 0.62, 95% CI: 0.51, 0.76) and stroke (HR 0.82, 95% CI: 0.76, 0.89), and similar risk of MI and PCI. DM patients had the highest risk of 10-year mortality, cardiac death and MACE. CONCLUSION This study demonstrates that RA is associated with an increased risk of HF, MI, stroke and coronary revascularization than found in the GP but without reaching the risk levels observed in DM patients.
Proteostasis Disturbances and Inflammation in Neurodegenerative Diseases

Protein homeostasis (proteostasis) disturbances and inflammation are evident in normal aging and some age-related neurodegenerative diseases. While the proteostasis network maintains the integrity of intracellular and extracellular functional proteins, inflammation is a biological response to harmful stimuli. Cellular stress conditions can cause protein damage, thus exacerbating protein misfolding and leading to an eventual overload of the degradation system. The regulation of proteostasis network is particularly important in postmitotic neurons due to their limited regenerative capacity. Therefore, maintaining balanced protein synthesis, handling unfolding, refolding, and degrading misfolded proteins are essential to preserve all cellular functions in the central nervous sysytem. Failing proteostasis may trigger inflammatory responses in glial cells, and the consequent release of inflammatory mediators may lead to disturbances in proteostasis. Here, we review the mechanisms of proteostasis and inflammatory response, emphasizing their role in the pathological hallmarks of neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Furthermore, we discuss the interplay between proteostatic stress and excessive immune response that activates inflammation and leads to dysfunctional proteostasis.
Respiration in an Air-Breathing Fish, the Climbing Perch, Anabas Testudineus : II. Respiratory Patterns and the Control of Breathing

1. A study has been made of the patterns of respiration in climbing perch ( Anabas testudineus ) living in water containing different concentrations of oxygen and carbon dioxide and also in air-exposed fish. 2. The fish breathes both water and air in normal tap water. The intervals between air-breaths are irregular and vary within the range 8-15 min. 3. Air-breathing increases in water of high CO 2 content. The time interval between air breaths falls with increasing CO 2 content. Gill ventilatory frequency increases when 5-10% CO 2 is bubbled into the water. Aquatic respiration stops and only aerial respiration occurs if more than 20% CO 2 is bubbled into the water. 4. Three factors, CO 2 content, pH and O 2 content of water, control the respiratory patterns in climbing perch. Of these CO 2 content appears to be most important for fish living in water. 5. The climbing perch can live for long periods (6-12 h during observations made) in water of very high CO 2 content (20-33 vols. %). In such hypercarbic water gases are only exchanged through the air-breathing organs. The mouth and opercula are closed tightly and gill ventilation stops completely. 6. Exposure to air increases air-breathing but the frequencies are irregular. Inhalation of hypoxic gas or pure nitrogen also evokes air-breathing.
Long noncoding RNA lnc-NAP sponges mmu-miR-139-5p to modulate Nanog functions in mouse ESCs and embryos

ABSTRACT The pluripotency of embryonic stem cells (ESCs) is controlled by a multilayer regulatory network, of which the key factors include core pluripotency genes Oct4, Sox2 and Nanog, and multiple microRNAs (miRNAs). Recently, long noncoding RNAs (lncRNAs) have been discovered as a class of new regulators for ESCs, and some lncRNAs could function as competing endogenous RNAs (ceRNAs) to regulate mRNAs by competitively binding to miRNAs. Here, we identify mmu-miR-139-5p as a new regulator for Nanog by targeting Nanog 3′ untranslated region (UTR) to repress Nanog expression in mouse ESCs and embryos. Such regulation could be released by an ESC-specifically expressed ceRNA named lnc-NAP. The expression of lnc-NAP is activated by OCT4, SOX2, as well as NANOG through promoter binding. Downregulation of lnc-NAP reduces Nanog abundance, which leads to decreased pluripotency of mouse ESCs and embryonic lethality. These results reveal lnc-NAP as a new regulator for Nanog in mouse ESCs, and uncover a feed-forward regulatory loop of Nanog through the participation of lnc-NAP.
JNK3 as Therapeutic Target and Biomarker in Neurodegenerative and Neurodevelopmental Brain Diseases

The c-Jun N-terminal kinase 3 (JNK3) is the JNK isoform mainly expressed in the brain. It is the most responsive to many stress stimuli in the central nervous system from ischemia to Aβ oligomers toxicity. JNK3 activity is spatial and temporal organized by its scaffold protein, in particular JIP-1 and β-arrestin-2, which play a crucial role in regulating different cellular functions in different cellular districts. Extensive evidence has highlighted the possibility of exploiting these adaptors to interfere with JNK3 signaling in order to block its action. JNK plays a key role in the first neurodegenerative event, the perturbation of physiological synapse structure and function, known as synaptic dysfunction. Importantly, this is a common mechanism in many different brain pathologies. Synaptic dysfunction and spine loss have been reported to be pharmacologically reversible, opening new therapeutic directions in brain diseases. Being JNK3-detectable at the peripheral level, it could be used as a disease biomarker with the ultimate aim of allowing an early diagnosis of neurodegenerative and neurodevelopment diseases in a still prodromal phase.
Is improvement of fatigue in rheumatoid arthritis a proper effect of biologics?

Abstract Background. The objective of our present study is to assess the relation between persistent fatigue and rheumatoid arthritis (RA) disease activity and its functional impact and to determine if the positive effect of biologics on fatigue is due to good disease response or to a different pathway. Methods. A study cohort of patients with established RA was conducted. We included patients who had been prescried a biologic after at least failure of one conventional synthetic Disease Modifying Anti-Rheumatic Drug synthetic (csDMARDs). At baseline, patients had a moderately to highly active disease. Demographic characteristics, disease activity and functional impact were assessed by disease activity score (DAS28CRP) and health assessment questionnaire (HAQ) scores. Fatigue was evaluated by the Functional Assessment of Chronic Illness Therapy–Fatigue scale questionnaire (FACIT-F). Patients were examined before initiating biotherapy, then after three months and six months. Results. Thirty women with RA, with a mean age of 52.5 years, were included. At baseline, 57% received anti-TNFα: Etanercept (n = 9), Adalimumab (n = 6), Infliximab (n = 2) and 43% received Rituximab. Good Eular response was obtained in 80% of patients at the third month and 97% of patients at the sixth month. In the analytic study, a significant amelioration after 3 months of biotherapy was found in both disease response (DAS28CRP) and fatigue (FACIT-F), respectively (p = 0.01, p<0.001 and p<0.001). The disease activity decreased significantly also after sixth month (p = 0.01, p<0.001 and p = 0.012). In the linear multivariate analysis, the regression of visual analogic pain (VAS pain) was the only predictors of the improvement of fatigue. Conclusion. Biologics contribute to improve fatigue in patients with established RA and this effect seems to be independent from the clinical efficacy of this treatment.
Resolution acuity across the visual field for mesopic and scotopic illumination

We investigated the classical question of why visual acuity decreases with decreasing retinal illuminance by holding retinal eccentricity fixed while illumination varied. Our results indicate that acuity is largely independent of illuminance at any given retinal location, which suggests that under classical free-viewing conditions acuity improves as illumination increases from rod threshold to rod saturation because the retinal location of the stimulus is permitted to migrate from a peripheral location of maximum sensitivity but poor acuity to the foveal location of maximum acuity but poor sensitivity. Comparison with anatomical sampling density of retinal neurons suggests that mesopic acuity at all eccentricities and scotopic acuity for eccentricities beyond about 20° is limited by the spacing of midget ganglion cells. In central retina, however, scotopic acuity is further limited by spatial filtering due to spatial summation within the large, overlapping receptive fields of the A-II class of amacrine cells interposed in the rod pathway between rod bipolars and midget ganglion cells. Our results offer a mechanistic interpretation of the clinical metrics for low-luminance visual dysfunction used to monitor progression of retinal disease.
In Vitro and In Vivo Models to Study the Zoonotic Mosquito-Borne Usutu Virus

Usutu virus (USUV), a mosquito-borne zoonotic flavivirus discovered in South Africa in 1959, has spread to many European countries over the last 20 years. The virus is currently a major concern for animal health due to its expanding host range and the growing number of avian mass mortality events. Although human infections with USUV are often asymptomatic, they are occasionally accompanied by neurological complications reminiscent of those due to West Nile virus (another flavivirus closely related to USUV). Whilst USUV actually appears less threatening than some other emergent arboviruses, the lessons learned from Chikungunya, Dengue, and Zika viruses during the past few years should not be ignored. Further, it would not be surprising if, with time, USUV disperses further eastwards towards Asia and possibly westwards to the Americas, which may result in more pathogenic USUV strains to humans and/or animals. These observations, inviting the scientific community to be more vigilant about the spread and genetic evolution of USUV, have prompted the use of experimental systems to understand USUV pathogenesis and to boost the development of vaccines and antivirals. This review is the first to provide comprehensive coverage of existing in vitro and in vivo models for USUV infection and to discuss their contribution in advancing data concerning this neurotropic virus. We believe that this paper is a helpful tool for scientists to identify gaps in the knowledge about USUV and to design their future experiments to study the virus.
Genetic Evidence for the Involvement of Mismatch Repair Proteins, PMS2 and MLH3, in a Late Step of Homologous Recombination.

Homologous recombination (HR) repairs DNA double-strand breaks using intact homologous sequences as template DNA. Broken DNA and intact homologous sequences form joint molecules (JMs), including Holliday junctions (HJs), as HR intermediates. HJs are resolved to form crossover and noncrossover products. A mismatch repair factor, MLH3 endonuclease produces the majority of crossovers during meiotic HR, but it remains elusive whether mismatch repair factors promote HR in non-meiotic cells. We disrupted genes encoding the MLH3 and PMS2 endonucleases in the human B cell line, TK6, generating null MLH3-/- and PMS2-/- mutant cells. We also inserted point mutations into the endonuclease motif of MLH3 and PMS2 genes, generating endonuclease death MLH3DN/DN and PMS2EK/EK cells. MLH3-/- and MLH3DN/DN cells showed a very similar phenotype, a 2.5 times decrease in the frequency of heteroallelic HR-dependent repair of a restriction-enzyme-induced double-strand breaks. PMS2-/- and PMS2EK/EK cells showed a phenotype very similar to that of the MLH3 mutants. These data indicate that MLH3 and PMS2 promote HR as an endonuclease. The MLH3DN/DN and PMS2EK/EK mutations had an additive effect on the heteroallelic HR. MLH3DN/DN/PMS2EK/EK cells showed normal kinetics of g-irradiation-induced Rad51 foci but a significant delay in the resolution of Rad51 foci and three times decrease in the number of cisplatin-induced sister chromatid exchange (SCE). The ectopic expression of the Gen1 HJ resolvase partially reversed the defective heteroallelic HR of MLH3DN/DN/PMS2EK/EK cells. Taken together, we propose that MLH3 and PMS2 promote HR as endonucleases, most likely by processing JMs in mammalian somatic cells.