Miracle-dz/UniFAR-FTUs huggingface dataset:
HRM Practices and Organizational Performance: Mediation Effect of Innovation

Abstract The main aim of this study is to explore the mediating effect of innovation in the relationship between human resource management (HRM) practices and organizational performance. HRM practices are observed through selective hiring, training, participative decision-making, and rewarding. Innovation is conceptualized over behavioral, product, process, and market innovation. The study relies upon the principles of social exchange theory and resource-based theory. Data were collected from 408 managers in an emerging economy context. The proposed conceptual model is evaluated with structural equation modeling using Lisrel 8.8 and SPSS 22. Study findings suggest that innovation influences the relationship between selective hiring, training, and participative decision-making and organizational performance. However, no mediating effect of innovation was found in a relationship between rewarding and organizational business performances. Since human resources and innovation are among the leading sources for building competitive advantage for companies, the study findings contribute to HRM and innovation.
A Comparative Assessment of the Urbanization – Fertility Nexus in Most Urbanized Countries of Sub-Saharan Africa

Abstract There is a near-consensus in the literature that urbanization is incompatible with large family size owing to factors such as high cost of urban living, opportunity cost of having children in urban centers and increasing awareness of benefits of small family size. However, a cursory glance at the data on sub-Saharan Africa cast doubt on the incompatibility of urbanization with high fertility rate. Hence, this paper investigates the urbanization-fertility nexus in the two most urbanized countries of SSA – Nigeria and South Africa. Exploiting time series data for both countries within a Fully Modified Ordinary Least Square (FMOLS) framework, the incompatibility hypothesis is refuted in both countries. Specifically, the analysis suggests that in Nigeria and South Africa, increasing degree of urbanization is positively related with fertility rate with the magnitude of the relationship being higher in Nigeria than South Africa. These findings imply that policies aimed at improving urbanization process and reducing fertility rates are crucial in both countries.
Vinorelbine causes a neuropathic pain-like state in mice via STING and MNK1 signaling associated with type I interferon induction

Type I interferons (IFNs) increase the excitability of dorsal root ganglion (DRG) neurons via activation of MNK-eIF4E translation signaling to promote pain sensitization in mice. Activation of STING signaling is a key component of type I IFN induction. Manipulation of STING signaling is an active area of investigation in cancer and other therapeutic areas. Vinorelbine is a chemotherapeutic that activates STING and has been shown to cause pain and neuropathy in oncology clinical trials in patients. There are conflicting reports on whether STING signaling promotes or inhibits pain in mice. We hypothesized that vinorelbine would cause a neuropathic pain-like state in mice via STING and signaling pathways in DRG neurons associated with type I IFN induction. Vinorelbine (10 mg/kg, i.v.) induced tactile allodynia and grimacing in WT male and female mice and increased p-IRF3 and type I IFN protein in peripheral nerves. In support of our hypothesis, vinorelbine-mediated pain was absent in male and female StingGt/Gt mice. Vinorelbine also failed to induce IRF3 and type I IFN signaling in these mice. Since type I IFNs engage translational control via MNK1-eIF4E in DRG nociceptors, we assessed vinorelbine-mediated p-eIF4E changes. Vinorelbine increased p-eIF4E in DRG in WT animals but not in StingGt/Gtor Mknk1-/- (MNK1 KO) mice. Consistent with these biochemical findings, vinorelbine had an attenuated pro-nociceptive effect in male and female MNK1 KO mice. Our findings support the conclusion that activation of STING signaling in the peripheral nervous system causes a neuropathic pain-like state that is mediated by type I IFN signaling to DRG nociceptors.
Study of auxin metabolism using stable isotope labeling and LCMS; evidence for in planta auxin decarboxylation pathway

The natural plant hormone auxin indole-3-acetic acid (IAA) influences many physiological processes in plants. Here, the metabolism of IAA was studied in detail using tobacco BY-2 cells as a model and compared with the in planta metabolism in several plant species. A combination of labeled/unlabeled substrate feeding, global untargeted mass spectrometric (MS) scanning, and selective MS filtering allowed the detection of 17 auxin metabolites, 15 of which were identified. Subsequent study of intermediate metabolism and dynamics revealed eight major pathways: three amino acid conjugation pathways with aspartate, glutamate, and glutamine, followed by their 2-oxidation with the help of the DAO enzyme; side-chain glucosyl ester formation; direct 2-oxidation; two decarboxylation pathways; and a pathway producing an unidentified metabolite. Interestingly, the first intermediates of the two decarboxylation pathways, indole-3-carbinol and oxoindole-3-carbinol, were formed outside the cells. We found that the majority of the detected auxin metabolites occur naturally in several plant species and that IAA is their precursor, indicating that the auxin metabolic pathways observed in BY-2 cells also occur in planta. Our finding that the IAA decarboxylation pathway occurs in planta, and the previous reports of auxin activity of some metabolites of this pathway, suggest that at least some of the biological effects of IAA may be explained by its conversion to decarboxylative metabolites.
Stable Structures or poly(A)-binding protein loading protect cellular and viral RNAs against ISG20-mediated decay

ISG20 is an interferon-induced 3’-to-5’ RNA exonuclease that acts as a broad antiviral factor. At present, the features that expose RNA to ISG20 remain unclear, although recent studies have pointed to the modulatory role of epitranscriptomic modifications in the susceptibility of target RNAs to ISG20. These findings raise the question as to how cellular RNAs, on which these modifications are abundant, cope with ISG20. To obtain an unbiased perspective on this topic, we used RNAseq and biochemical assays to identify elements that regulate the behavior of RNAs against ISG20. The results we have obtained indicate that poly(A)-binding protein (PABP1) loading on the RNA 3’ tail provides a primal protection against ISG20, easily explaining the overall protection of cellular mRNAs observed by RNAseq. The second element we uncovered is provided by terminal stem-loop RNA structures, that have been associated to ISG20 protection before, but that we re-examine here systematically to define the stabilities that tilt the balance between resistance and susceptibility to ISG20. Given that these elements are present on cellular mRNAs, but can be co-opted by viruses as well, these results shed new light on the complex interplay that regulates the susceptibility of different classes of viruses against ISG20.
Human Rhinoviruses: a novel class of oncolytic virus

While continuing to develop new and improved OVs, researchers have been vigilant in optimizing their ability to safely infect, replicate, and induce an immune response within tumors. There are currently two crucial limitations in OV development, however: modification of viruses often negatively impact their ability to infect, and induction of strong immune responses also promotes rapid viral clearance. In this study, we investigate wild-type HRVs as a novel class of OV. Multiple HRV serotypes were propagated in human melanoma cell lines to produce highly oncolytic populations of virus. A large panel of cancer types were infected, with cytotoxicity evaluated using flow cytometry and real time live imaging. Pro-inflammatory signaling was assessed by cytokine multiplexing. Tumor responses to HRV were assessed in human xenograft and in syngeneic, immune-competent mouse tumor models. We find that HRVs are capable of infecting and killing a wide variety of human cancer cell lines in vitro and in vivo, inducing pro-inflammatory responses and, ultimately, tumor regression. We propose that the natural safety profile of these viruses, coupled with their anti-tumor efficacy and multivalent potential seen in our preclinical model systems, make HRVs ideal candidates for development as oncolytic viruses for clinical testing. Simple Summary The idea of utilizing viruses to combat cancer has been around for over a century, yet in practice has seen relatively modest therapeutic success following decades of strategic design to improve safety, efficacy, and tumor selectivity. Engagement of an immune response is critical to have lasting tumor regression upon treatment, but many patients are unable to mount a sufficient response to standard-of-care immunotherapy alone. Oncolytic viruses (OVs) have been shown to synergize with such therapies to accomplish this goal to varying degrees. The purpose of this study is to investigate human rhinoviruses (HRVs) to establish their efficacy as a novel class of anti-cancer agents. We aim to use HRVs to promote longer lasting and more effective immune responses to tumors by fostering viral persistence and immune evasion, in addition to developing multivalent treatment strategies that enhance tumor regression by preventing tumor escape from viral infection.
Oatmeal and wheat flour as the sources of thyroid peroxidase (TPO), lipoxygenase (LOX) and xanthine oxidase (XO) modulators potentially applicable in the prevention of inflammatory thyroid diseases

Despite the widespread potential pro-health effects of ferulic acid (FA), their interference in the progression of thyroid dysfunction has mainly remained unresolved. Here, we combined in vitro enzyme studies with the in vitro cellular approach to investigate the potential of main dietary sources of FA - the oatmeal (OM) and wheat flour (WF) compounds for the prophylactics of inflammatory thyroid diseases. Potentially bioaccessible OM and WF compounds activated thyroid peroxidase (TPO), while inhibiting the activity of lipoxygenase (LOX) and xanthine oxidase (XO). Isobolographic studies revealed cooperation between them. Relatively strong inhibitory activity of bioaccessible OM compounds on LOX activity correlated with their cytostatic and pro-invasive effects in thyroid cancer model in vitro. These data indicate the potential of OM and WF products for the prophylactics of inflammatory thyroid diseases (incl. hypothyroidism). However, it should be considered with care, especially in the context of the oncological status of the patient.
Temporally specific gene expression and chromatin remodeling programs regulate a conserved Pdyn enhancer

Neuronal and behavioral adaptations to novel stimuli are regulated by temporally dynamic waves of transcriptional activity, which shape neuronal function and guide enduring plasticity. Neuronal activation promotes expression of an immediate early gene (IEG) program comprised primarily of activity-dependent transcription factors, which are thought to regulate a second set of late response genes (LRGs). However, while the mechanisms governing IEG activation have been well studied, the molecular interplay between IEGs and LRGs remain poorly characterized. Here, we used transcriptomic and chromatin accessibility profiling to define activity-driven responses in rat striatal neurons. As expected, neuronal depolarization generated robust changes in gene expression, with early changes (1 h) enriched for inducible transcription factors and later changes (4 h) enriched for neuropeptides, synaptic proteins, and ion channels. Remarkably, while depolarization did not induce chromatin remodeling after 1 h, we found broad increases in chromatin accessibility at thousands of sites in the genome at 4 h after neuronal stimulation. These putative regulatory elements were found almost exclusively at non-coding regions of the genome, and harbored consensus motifs for numerous activity-dependent transcription factors such as AP-1. Furthermore, blocking protein synthesis prevented activity-dependent chromatin remodeling, suggesting that IEG proteins are required for this process. Targeted analysis of LRG loci identified a putative enhancer upstream of Pdyn (prodynorphin), a gene encoding an opioid neuropeptide implicated in motivated behavior and neuro-psychiatric disease states. CRISPR-based functional assays demonstrated that this enhancer is both necessary and sufficient for Pdyn transcription. This regulatory element is also conserved at the human PDYN locus, where its activation is sufficient to drive PDYN transcription in human cells. These results suggest that IEGs participate in chromatin remodeling at enhancers and identify a conserved enhancer that may act as a therapeutic target for brain disorders involving dysregulation of Pdyn.
The G protein biased serotonin 5-HT2A receptor agonist lisuride exerts anti-depressant drug-like activities in mice

There is now evidence from multiple Phase II clinical trials that psychedelic drugs can exert long-lasting anxiolytic, anti-depressant, and anti-drug abuse (nicotine and ethanol) effects in patients. Despite these benefits, the hallucinogenic actions of these drugs at the serotonin 2A receptor (5-HT2AR) limit their clinical use in diverse settings. Activation of the 5-HT2AR can stimulate both G protein and β-arrestin (βArr) -mediated signaling. Lisuride is a G protein biased agonist at the 5-HT2AR and, unlike the structurally-related LSD, the drug does not typically produce hallucinations in normal subjects at routine doses. Here, we examined behavioral responses to lisuride, in wild-type (WT), βArr1-KO, and βArr2-KO mice. In the open field, lisuride reduced locomotor and rearing activities, but produced a U-shaped function for stereotypies in both βArr lines of mice. Locomotion was decreased overall in βArr1-KOs and βArr2-KOs, relative to WT controls. Incidences of head twitches and retrograde walking to lisuride were low in all genotypes. Grooming was depressed in βArr1 mice, but was increased then decreased in βArr2 animals with lisuride. Prepulse inhibition (PPI) was unaffected in βArr2 mice, whereas 0.5 mg/kg lisuride disrupted PPI in βArr1 animals. The 5-HT2AR antagonist MDL100907 failed to restore PPI in βArr1 mice, whereas the dopamine D2/D3 antagonist raclopride normalized PPI in WTs but not in βArr1-KOs. Using vesicular monoamine transporter 2 mice, lisuride reduced immobility times in tail suspension and promoted a preference for sucrose that lasted up to 2 days. Together, it appears βArr1 and βArr2 play minor roles in lisuride’s actions on many behaviors, while this drug exerts anti-depressant drug-like responses without hallucinogenic-like activities.
Statistical Analysis of Genetic Counseling Impacts

A double-pronged statistical approach to retrospective data is used to test and develop hypotheses about some impacts of genetic counseling. Both log-linear and discriminant analyses suggest that education and burden centered explanations of postcounseling pregnancies should be modified in favor of a hypothesis based on an interaction of past reproductive experiences and parental desire for children. Log-linear and best subsets regression analyses converge on risk level and socioeconomic status as the key factors accounting for variance in couples' feelings about genetic counseling. Risk level is found to have a questionable effect on postcounseling reproductive behavior while providing the primary impact of all variables explaining couples' feelings about genetic counseling.
Functional ultrasound imaging of stroke in awake rats

Anesthesia is a major confounding factor in preclinical stroke research as stroke rarely occurs in sedated patients. Moreover, anesthesia affects both brain functions and the stroke outcome acting as neurotoxic or protective agent. So far, no approaches were well suited to induce stroke while imaging hemodynamics along with simultaneous large-scale recording of brain functions in awake animals. For this reason, the first critical hours following the stroke insult and associated functional alteration remain poorly understood. Here, we present a strategy to investigate both stroke hemodynamics and stroke-induced functional alterations without the confounding effect of anesthesia, i.e., under awake condition. Functional ultrasound (fUS) imaging was used to continuously monitor variations in cerebral blood volume (CBV) in +65 brain regions/hemisphere for up to 3hrs after stroke onset. The focal cortical ischemia was induced using a chemo-thrombotic agent suited for permanent middle cerebral artery occlusion in awake rats, and followed by ipsi- and contralesional whiskers stimulation to investigate on the dynamic of the thalamo-cortical functions. Early (0-3hrs) and delayed (day 5) fUS recording enabled to characterize the features of the ischemia (location, CBV loss), spreading depolarizations (occurrence, amplitude) and functional alteration of the somatosensory thalamo-cortical circuits. Post-stroke thalamo-cortical functions were affected not only early after the stroke onset but were also altered secondarly and remotely from the initial insult. Overall, our procedure enables early, continuous, and chronic evaluations of hemodynamics and brain functions which, combined to stroke or other pathologies, aims to better understand physiopathologies toward the development of clinically relevant therapeutic strategies.
DNA methylation signatures of early life adversity are exposure-dependent in wild baboons

The early life environment can profoundly shape the trajectory of an animal’s life, even years or decades later. One mechanism proposed to contribute to these early life effects is DNA methylation. However, the frequency and functional importance of DNA methylation in shaping early life effects on adult outcomes is poorly understood, especially in natural populations. Here, we integrate prospectively collected data on fitness-associated variation in the early environment with DNA methylation estimates at 477,270 CpG sites in 256 wild baboons. We find highly heterogeneous relationships between the early life environment and DNA methylation in adulthood: aspects of the environment linked to resource limitation (e.g., low-quality habitat, early life drought) are associated with many more CpG sites than other types of environmental stressors (e.g., low maternal social status). Sites associated with early resource limitation are enriched in gene bodies and putative enhancers, suggesting they are functionally relevant. Indeed, by deploying a baboon-specific, massively parallel reporter assay, we show that a subset of windows containing these sites are capable of regulatory activity, and that, for 88% of early drought-associated sites in these regulatory windows, enhancer activity is DNA methylation-dependent. Together, our results support the idea that DNA methylation patterns contain a persistent signature of the early life environment. However, they also indicate that not all environmental exposures leave an equivalent mark and suggest that socioenvironmental variation at the time of sampling is more likely to be functionally important. Thus, multiple mechanisms must converge to explain early life effects on fitness-related traits. Significance statement The environment animals face when young can affect how they function throughout life. Long-lasting changes in DNA methylation—a chemical mark deposited on DNA that can affect gene activity—have been hypothesized to contribute to early life effects. But evidence for persistent, early environment-associated differences in DNA methylation is lacking in wild animals. Here, we show that early life adversity in wild baboons predicts DNA methylation levels in adulthood, especially for animals born in low resource environments and drought conditions. We also show that some of the changes we observe in DNA methylation have the capacity to influence gene activity levels. Together, our results support the idea that early experiences can become biologically embedded in the genomes of wild animals.
FATORES INTERFERENTES NA REALIZAÇÃO DO CATETERISMO VESICAL INTERMITENTE EM CRIANÇAS COM MIELOMENINGOCELE NA PERCEPÇÃO DO CUIDADOR

Trata-se de uma pesquisa de carater descritivo e exploratorio, com o objetivo central de analisar os fatores interferentes na realizacao do cateterismo vesical intermitente limpo na crianca portadora de bexiga neurogenica, secundaria a mielomeningocele, sob a percepcao do cuidador. Participaram do estudo 55 cuidadores de criancas de 29 dias de vida a 11 anos e 11 meses, vinculadas a um hospital geral infantil do Municipio de Fortaleza-CE, que estivessem realizando o cateterismo vesical intermitente limpo (CIL) assistido e que tenham cumprido programa de reabilitacao. A maioria das criancas era de escolares (74,5%) e pertencia ao sexo feminino (58,2%), possuia beneficio de renda continuada (78,2%) e a renda familiar era de ate 2 salarios minimos. Quanto aos cuidadores, a maioria tinha entre 32 e 39 anos (38,2%), era de mulheres (96,4%), maes (94,5%), casadas (69,1%), as quais haviam estudado ate o Ensino Medio (58,2%) e nao possuia ocupacao fora do domicilio (89,1%). Em relacao a infra-estrutura da casa, a maioria das residencias possuia agua encanada (90,9%), saneamento basico (69,1%), banheiro (100%), de 4 a 5 comodos (50,9%), porta no local onde o CIL era realizado (63,6%) e de 4 a 5 pessoas coabitando no mesmo ambiente (47,3%). Quanto aos fatores que interferem na realizacao do CIL, os que apresentaram interferencia positiva foram: idade da crianca (p=0,047); cuidador sem ocupacao fora do domicilio (p=0,038); recebimento de beneficio de renda continuada (p=0,0001); recebimento do material utilizado no CIL do Municipio ou do Estado (p=0,0001); presenca de agua encanada (p=0,0001), saneamento basico (p=0,0001) e porta no local onde o CIL e realizado (p=0,0001); boa acuidade visual (p=0,0001) e destreza do cuidador (p=0,0001); aceitacao da crianca (p=0,0001) e do cuidador em relacao ao procedimento (p=0,0001); ausencia de intercorrencia durante a realizacao do CIL (p=0,0001). Quanto aos que apresentaram interferencia negativa, tem-se: a presenca de sensibilidade uretral (p=0,002), as perdas urinarias nos intervalos do CIL e o uso continuo de fraldas (p=0,0001) nessas criancas. Dois fatores investigados nao interferiram nem positiva nem negativamente: a quantidade de comodos da casa e o numero de pessoas coabitando com a crianca: p=0,0001. Esses resultados sugerem que o numero de variaveis que interferiram positivamente na realizacao do CIL foi superior ao dos que exerceram interferencia negativa. Os achados sao de extrema relevância, visto que possibilitam a inferencia de que a adesao ao CIL e facilitada pela presenca desses fatores.
ACES characterization of damping in micro-beam resonators

This study develops a preliminary model of Q-factor of MEMS resonators by using Analytical, Computational, and Experimental Solutions (ACES) methodology to investigate the effects of various damping mechanisms on the Q-factor of microelectromechanical resonators. Focus was made on the contributions of air damping, thermoelastic damping (TED), and surface damping to the Q-factor. Laser Doppler Vibrometry (LDV) and Michelson Interferometry were used to characterize the damping of tipless atomic force microscopy (AFM) probes through ring down tests. Tests were performed at various levels of vacuum with different beam geometries and coatings. COMSOL was used to model the TED as well as resonance characteristics of the beams and the computational results were compared to analytical and experimental results. It was found that as surface area to volume ratio increases beyond approximately 1 μm−1, surface damping becomes the dominant damping mechanism. Additionally air damping was significant at a vacuum level gr.