Miracle-dz/UniFAR-FTUs huggingface dataset:
Case Report: Viral Shedding for 60 Days in a Woman with COVID-19

Abstract. Novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has become a public health emergency of international concern. This was first noted in Wuhan, Hubei Province, China, and since then has become widespread globally. We report a 71-year-old woman with documented viral shedding (based on reverse transcription–polymerase chain reaction (RT-PCR) testing) of SARS-CoV-2 for 60 days from the onset of symptoms (55 days from her first positive test and 36 days after complete resolution of symptoms). This is to our knowledge the longest duration of viral shedding reported to date. This case demonstrates that viral shedding after COVID-19 diagnosis can be prolonged.
p27 as a Transcriptional Regulator: New Roles in Development and Cancer

p27 binds and inhibits cyclin-CDK to arrest the cell cycle. p27 also regulates other processes including cell migration and development independent of its cyclin-dependent kinase (CDK) inhibitory action. p27 is an atypical tumor suppressor–deletion or mutational inactivation of the gene encoding p27, CDKN1B, is rare in human cancers. p27 is rarely fully lost in cancers because it can play both tumor suppressive and oncogenic roles. Until recently, the paradigm was that oncogenic deregulation results from either loss of growth restraint due to excess p27 proteolysis or from an oncogenic gain of function through PI3K-mediated C-terminal p27 phosphorylation, which disrupts the cytoskeleton to increase cell motility and metastasis. In cancers, C-terminal phosphorylation alters p27 protein–protein interactions and shifts p27 from CDK inhibitor to oncogene. Recent data indicate p27 regulates transcription and acts as a transcriptional coregulator of cJun. C-terminal p27 phosphorylation increases p27-cJun recruitment to and action on target genes to drive oncogenic pathways and repress differentiation programs. This review focuses on noncanonical, CDK-independent functions of p27 in migration, invasion, development, and gene expression, with emphasis on how transcriptional regulation by p27 illuminates its actions in cancer. A better understanding of how p27-associated transcriptional complexes are regulated might identify new therapeutic targets at the interface between differentiation and growth control.
Circulating microRNA as biomarkers of canine mammary carcinoma in dogs

Abstract Background Differentiating benign from canine malignant mammary tumors requires invasive surgical biopsy. Circulating microRNAs (miRNA) may represent promising minimally invasive cancer biomarkers in people and animals. Objectives To evaluate the serum mRNA profile between dogs with and without mammary carcinoma, and to determine if any of these markers have prognostic significance. Animals Ten healthy client‐owned female dogs (5 intact, 5 spayed) and 10 dogs with histologically confirmed mammary carcinoma were included; 9 were client‐owned, whereas 1 was a research colony dog. Methods Retrospective study. Serum miRNA was evaluated by RNA deep‐sequencing (RNAseq) and digital droplet PCR (dPCR). Expression of candidate biomarkers miR‐18a, miR‐19b, miR‐29b, miR‐34c, miR‐122, miR‐125a, and miR‐181a was compared with clinical characteristics, including grade, metastasis, and survival. Results 452 unique serum miRNAs were detected by RNAseq. Sixty‐five individual miRNAs were differentially expressed (>±1.5‐fold) and statistically significant between groups. Serum miR‐19b (P = .003) and miR‐125a (P < .001) were significantly higher in the mammary carcinoma group by dPCR. Both had high accuracy based on receiver operator characteristic area under the curve (0.930 for miR‐125a; 0.880 for miR‐19b). Circulating miR‐18a by RNAseq was significantly higher in mammary carcinoma dogs with histologic evidence of lymphatic invasion (P = 0.03). There was no significant association with any miRNA and survival or inflammatory status. Conclusions and Clinical Importance Circulating miRNAs are differentially expressed in dogs with mammary carcinoma. Serum miR‐19b and miR‐18a represent candidate biomarkers for diagnosis and prognosis, respectively.
Drosophila Synaptotagmin 7 negatively regulates synaptic vesicle release and replenishment in a dosage-dependent manner

Synchronous neurotransmitter release is triggered by Ca2+ binding to the synaptic vesicle protein Synaptotagmin 1, while asynchronous fusion and short-term facilitation is hypothesized to be mediated by plasma membrane-localized Synaptotagmin 7 (SYT7). We generated mutations in Drosophila Syt7 to determine if it plays a conserved role as the Ca2+ sensor for these processes. Electrophysiology and quantal imaging revealed evoked release was elevated 2-fold. Syt7 mutants also had a larger pool of readily-releasable vesicles, faster recovery following stimulation, and intact facilitation. Syt1/Syt7 double mutants displayed more release than Syt1 mutants alone, indicating SYT7 does not mediate the residual asynchronous release remaining in the absence of SYT1. SYT7 localizes to an internal membrane tubular network within the peri-active zone, but does not enrich at active zones. These findings indicate the two Ca2+ sensor model of SYT1 and SYT7 mediating all phases of neurotransmitter release and facilitation is not applicable at Drosophila synapses.
Trait mindfulness and intrinsic exercise motivation uniquely contribute to exercise self-efficacy

Abstract Objective: Traditional views of exercise motivation emphasize the long-term health benefits of exercise. We investigated whether mindfulness, present-moment awareness, is associated with greater exercise motivation and exercise self-efficacy in college students. Exercise self-efficacy reflects how confident individuals are that they can persist in exercising despite obstacles. Participants: Undergraduate students (N = 188) were recruited from the psychology participant pool in Fall 2017. Methods: Participants completed an online survey assessing trait mindfulness, exercise motivation, exercise self-efficacy, and demographic information. Results: Hierarchical regression analyses revealed positive associations between intrinsic and extrinsic exercise motivation and exercise self-efficacy, mindfulness and intrinsic exercise motivation, and mindfulness and exercise self-efficacy. The latter relationship was partially mediated by intrinsic exercise motivation. Extrinsic exercise motivation was not associated with mindfulness. Conclusions: Both mindfulness and intrinsic exercise motivation independently predict exercise self-efficacy, suggesting that mindfulness may uniquely contribute to positive health behaviors in college students.
A-kinase interacting protein 1, a potential biomarker associated with advanced tumor features and CXCL1/2 in prostate cancer

Objective: This study aimed to investigate the correlation of A-kinase interacting protein 1 (AKIP1) with chemokine (C-X-C motif) ligand 1 (CXCL1) and CXCL2, as well as their associations with clinical characteristics and prognosis in prostate cancer patients. Methods: A total of 248 eligible prostate cancer patients who underwent surgery were consecutively recruited, and tumor tissues were collected during the surgery. AKIP1, CXCL1, and CXCL2 expression in tumor tissues were assessed by immunohistochemistry. Disease-free survival and overall survival were recorded, and the median follow-up time was 27 months. Results: The proportion of patients with AKIP1, CXCL1, and CXCL2 high expression was 56.5%, 63.7%, and 56.9%, respectively. Additionally, AKIP1 expression positively correlated with CXCL1 expression (P<0.001) and CXCL2 expression (P<0.001), and CXCL1 expression was positively associated with CXCL2 expression (P<0.001). Furthermore, AKIP1 expression positively correlated with pathological T stage (P<0.001) and pathological N stage (P=0.003). CXCL1 expression was positively associated with pathological T stage (P<0.001) and pathological N stage (P<0.001) as well. However, the CXCL2 expression only positively correlated with pathological T stage (P=0.002). Also, AKIP1 high expression correlated with worse disease-free survival (P=0.049) and OS (P=0.013), and CXCL1 high expression was associated with unfavorable disease-free survival (P=0.023) but not overall survival (P=0.052). CXCL2 expression was not correlated with disease-free survival (P=0.083) or overall survival (P=0.065). Multivariate Cox’s regression disclosed that AKIP1 high expression independently predicted worse overall survival (P=0.009). Conclusion: AKIP1 positively associates with CXCL1/2 and is a potential biomarker for disease monitoring as well as prognosis in prostate cancer.
Isolation of infectious SARS-CoV-2 from urine of a COVID-19 patient

ABSTRACT SARS-CoV-2 caused a major outbreak of severe pneumonia (COVID-19) in humans. Viral RNA was detected in multiple organs in COVID-19 patients. However, infectious SARS-CoV-2 was only isolated from respiratory specimens. Here, infectious SARS-CoV-2 was successfully isolated from urine of a COVID-19 patient. The virus isolated could infect new susceptible cells and was recognized by its’ own patient sera. Appropriate precautions should be taken to avoid transmission from urine.
Quantification of native mRNA dynamics in living neurons using fluorescence correlation spectroscopy and reduction-triggered fluorescent probes

RNA localization in subcellular compartments is essential for spatial and temporal regulation of protein expression in neurons. Several techniques have been developed to visualize mRNAs inside cells, but the study of the behavior of endogenous and nonengineered mRNAs in living neurons has just started. In this study, we combined reduction-triggered fluorescent (RETF) probes and fluorescence correlation spectroscopy (FCS) to investigate the diffusion properties of activity-regulated cytoskeleton-associated protein (Arc) and inositol 1,4,5-trisphosphate receptor type 1 (Ip3r1) mRNAs. This approach enabled us to discriminate between RNA-bound and unbound fluorescent probes and to quantify mRNA diffusion parameters and concentrations in living rat primary hippocampal neurons. Specifically, we detected the induction of Arc mRNA production after neuronal activation in real time. Results from computer simulations with mRNA diffusion coefficients obtained in these analyses supported the idea that free diffusion is incapable of transporting mRNA of sizes close to those of Arc or Ip3r1 to distal dendrites. In conclusion, the combined RETF-FCS approach reported here enables analyses of the dynamics of endogenous, unmodified mRNAs in living neurons, affording a glimpse into the intracellular dynamics of RNA in live cells.
Additions to the phylogeny of colubrine snakes in Southwestern Asia, with description of a new genus and species (Serpentes: Colubridae: Colubrinae)

Reptiles are still being described worldwide at a pace of hundreds of species a year. While many discoveries are from remote tropical areas, biodiverse arid regions still harbor many novel taxa. Here, we present an updated phylogeny of colubrid snakes from the Western Palearctic by analyzing a supermatrix of all available global snake species with molecular data and report on the discovery of a new genus and species of colubrine snake from southeastern Iran. The new taxon, named Persiophis fahimii Gen. et sp. nov., is nested within a clade containing Middle Eastern and South Asian ground racers (Lytorhynchus, Rhynchocalamus, Wallaceophis, and Wallophis). This species has a derived morphology including an edentulous pterygoid and occurrence of short and blunt teeth on the palatine, maxillae and dentary bones, an elongated snout and a relatively trihedral first supralabial scale that is slightly bigger than the second, and elongated toward the tip of rostral. We also report on the osteology and phylogenetic placement of several poorly studied colubrines: Hierophis andreanus (reassigned to Dolichophis) and Muhtarophis barani.
A Bioorthogonal Click Chemistry Toolbox for Targeted Synthesis of Branched and Well‐Defined Protein–Protein Conjugates

Abstract Bioorthogonal chemistry holds great potential to generate difficult‐to‐access protein–protein conjugate architectures. Current applications are hampered by challenging protein expression systems, slow conjugation chemistry, use of undesirable catalysts, or often do not result in quantitative product formation. Here we present a highly efficient technology for protein functionalization with commonly used bioorthogonal motifs for Diels–Alder cycloaddition with inverse electron demand (DAinv). With the aim of precisely generating branched protein chimeras, we systematically assessed the reactivity, stability and side product formation of various bioorthogonal chemistries directly at the protein level. We demonstrate the efficiency and versatility of our conjugation platform using different functional proteins and the therapeutic antibody trastuzumab. This technology enables fast and routine access to tailored and hitherto inaccessible protein chimeras useful for a variety of scientific disciplines. We expect our work to substantially enhance antibody applications such as immunodetection and protein toxin‐based targeted cancer therapies.
Icariin Promotes Fracture Healing in Ovariectomized Rats

Background Osteoporotic fractures are common in postmenopausal women and associated with complications. Numerous studies have demonstrated that icariin can be used to treat fractures and osteoporosis. Herein, we evaluated the efficacy of gavage-administered icariin to promote fracture healing in postmenopausal osteoporotic fracture (POF) rats. Material/Methods In this study, ovariectomy-induced POF rats were treated with 600 mg/kg icariin. Micro-computed tomography (micro-CT) was used to assess fracture healing; besides, serum APK, TRACP-5b, and E2 expression levels were detected by commercial kits, and the uterine index was calculated. In addition, the expression of osteogenesis-related proteins (Runx 2 and COL1A2) in the callus was measured by western blot, whereas the expression of OPG/RANKL pathway proteins was measured by western blot and immunohistochemical analysis. Results Our data revealed that icariin promoted the expression level of Runx 2 and COL1A2 and suppressed the expression level of serum bone turn over biomarkers via the OPG/RANKL pathway. Besides, a more mature callus was observed in the POF rats receiving icariin than in the untreated POF rats, while serum E2 and uterine index were unaffected by icariin treatment. Conclusions These results revealed that icariin could promote fracture healing in ovariectomized rats via OPG/RANKL signaling, and that serum E2 and uterine index were not affected by icariin treatment.
Differential requirements of the hindbrain and mesenchyme on inner ear patterning

Title of Document: DIFFERENTIAL REQUIREMENTS OF THE HINDBRAIN AND MESENCHYME ON INNER EAR PATTERNING Jennifer Kimiko Liang Master of Science 2009 Directed By: Dr. Hey-Kyoung Lee, Department of Biology Microsurgical manipulations were performed in ovo to identify the tissues tha t are required for conferring inner ear patterning. Our results show that the hindbrai n, namely rhombomeres 5 and 6, are required for the formation and patterning of the cochlear duct (basilar papilla). Rhombomere 5 and its underlying notochord appear to be important for the growth of the cochlear duct, whereas rhomobomere 6 and its respective notochord ar e required for cochlear patterning. Rotating the segment of hindbrain from rhombomere 5 to rhombomere 6 along the anteroposterior axis affects cochlear duct formati on but has no effect on the development of vestibular structures. The signaling molecules intr insic to these tissues are distinct from Sonic Hedgehog, which has been shown to be required f or cochlear duct outgrowth. In contrast, otic mesenchyme adjacent to the developing i nner ear provides anteroposterior axial information to pattern the anterior and poste rior canals and ampullae. DIFFERENTIAL REQUIREMENTS OF THE HINDBRAIN AND MESENCHYME ON INNER EAR PATTERNING
Kinetic Studies on Radical Scavenging Activity of Kaempferol Decreased by Sn(II) Binding

Sn(II) binds to kaempferol (HKaem, 3,4′,5,7-tetrahydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) at the 3,4-site forming [Sn(II)(Kaem)2] complex in ethanol. DPPH• scavenging efficiency of HKaem is dramatically decreased by SnCl2 coordination due to formation of acid inhibiting deprotonation of HKaem as ligands and thus reduces the radical scavenging activity of the complex via a sequential proton-loss electron transfer (SPLET) mechanism. Moderate decreases in the radical scavenging of HKaem are observed by Sn(CH3COO)2 coordination and by contact between Sn and HKaem, in agreement with the increase in the oxidation potential of the complex compared to HKaem, leading to a decrease in antioxidant efficiency for fruits and vegetables with Sn as package materials.
The natural course of pregnancies in women with primary atypical haemolytic uraemic syndrome and asymptomatic relatives

Pregnancy has been linked to various microangiopathies, including primary atypical haemolytic uraemic syndrome (aHUS). Complement dysregulation, often linked to rare variants in complement genes, is key for primary aHUS to manifest and may play a role in pregnancy complications of the mother and fetus. The burden of such complications is unknown, making counselling of women with primary aHUS and asymptomatic relatives difficult. We analyzed the maternal and fetal outcomes of 39 pregnancies from 17 women with primary aHUS and two asymptomatic relatives. Seven out of 39 pregnancies were complicated by pregnancy‐associated aHUS. Five out of 32 pregnancies not linked to pregnancy‐associated aHUS were complicated by pre‐eclampsia or HELLP. Rare genetic variants were identified in 10 women (asymptomatic relatives, n = 2) who had a total of 14 pregnancies, including 10 uncomplicated pregnancies. Thirty‐five out of 39 pregnancies resulted in live birth. Eight out of 19 women had progressed to end‐stage kidney disease, with an incidence of 2·95 (95% confidence interval, 1·37–5·61) per 100 person‐years after the first pregnancy. Thus, we emphasized the frequency of successful pregnancies in women with primary aHUS and asymptomatic relatives. Pregnancies should be monitored closely. Rare genetic variants cannot predict the risk of a given pregnancy.
A SURVEY OF FALL ARMYWORM (LEPIDOPTERA: NOCTUIDAE) PARASITOIDS IN THE MEXICAN STATES OF MICHOACÁN, COLIMA, JALISCO, AND TAMAULIPAS

Fall armyworm larvae, Spodoptera frugiperda (J. E. Smith) were collected from whorl stage corn or sorghum in the states of Michoacan, Colima, and Jalisco in August, and Tamaulipas, Mexico in September 1998. Eleven species of hymenopteran parasitoids were recovered representing 3 families: Ichneumonidae (Ophion flavidus Brulle, Campoletis flavicincta Ashmead, and Pristomerus spinator F.); Braconidae (Aleiodes laphygmae Viereck, Cotesia marginiventris Cresson, Meteorus laphygmae Viereck, Meteorus sp., Chelonus insularis Cresson, Chelonus sp. probably cautus Cresson, and Chelonus sp.); and Eulophidae (Euplectrus platyhypenae Howard). The overall rate of parasitism was 11.3%, based on 2219 larvae collected. The highest rate of parasitism from a single collection was 26.5%, representing 6 species of parasitoids in Michoacan. The next highest rate of parasitism, 23%, was by a single species, C. flavicincta, in Michoacan. The most widely distributed species was P. spinator, occurring in 12 collections from 3 states. Chelonus sp. was collected from all four states in only 6 collections. The greater diversity of parasitoids and higher rates of parasitism in Michoacan may be related to the more diverse habitat with more forests, orchards, and pastures near the cornfields in that state.
Attenuation of the Diffuse Noxious Inhibitory Controls in Chronic Joint Inflammatory Pain Is Accompanied by Anxiodepressive-Like Behaviors and Impairment of the Descending Noradrenergic Modulation

The noradrenergic system is paramount for controlling pain and emotions. We aimed at understanding the descending noradrenergic modulatory mechanisms in joint inflammatory pain and its correlation with the diffuse noxious inhibitory controls (DNICs) and with the onset of anxiodepressive behaviours. In the complete Freund’s adjuvant rat model of Monoarthritis, nociceptive behaviors, DNICs, and anxiodepressive-like behaviors were evaluated. Spinal alpha2-adrenergic receptors (a2-AR), dopamine beta-hydroxylase (DBH), and noradrenaline were quantified concomitantly with a2-AR pharmacologic studies. The phosphorylated extracellular signal–regulated kinases 1 and 2 (pERK1/2) were quantified in the Locus coeruleus (LC), amygdala, and anterior cingulate cortex (ACC). DNIC was attenuated at 42 days of monoarthritis while present on days 7 and 28. On day 42, in contrast to day 28, noradrenaline was reduced and DBH labelling was increased. Moreover, spinal a2-AR were potentiated and no changes in a2-AR levels were observed. Additionally, at 42 days, the activation of ERKs1/2 was increased in the LC, ACC, and basolateral amygdala. This was accompanied by anxiety- and depressive-like behaviors, while at 28 days, only anxiety-like behaviors were observed. The data suggest DNIC is attenuated in prolonged chronic joint inflammatory pain, and this is accompanied by impairment of the descending noradrenergic modulation and anxiodepressive-like behaviors.
Changes in cerebral perfusion following a 12-month exercise and diet intervention.

Overweight and obesity may damage the cerebrovascular architecture, resulting in a significant reduction in cerebral blood flow. To date, there have been few randomized clinical trials (RCT) examining whether obesity-related reductions in cerebral blood flow could be modified by weight loss. Further, it is unknown whether the behavioral intervention strategy for weight loss (i.e., diet alone or diet combined with exercise) differentially influences cerebral blood flow in adults with overweight or obesity. The primary aim of this study was to determine whether a 12-month RCT of exercise and diet increases cerebral blood flow in 125 midlife (Mean age ± SD = 44.63 ± 8.36 years) adults with overweight and obesity. Further, we evaluated whether weight loss via diet combined with aerobic exercise has an added effect on changes in cerebral blood flow compared to weight loss via diet alone and whether there were regionally specific effects of the type of behavioral intervention on cerebral blood flow patterns. Consistent with our predictions, a 12-month diet and exercise program resulting in 10% weight loss increased cerebral blood flow. These effects were widespread and extended throughout frontal, parietal, and subcortical regions. Further, there was some regional specificity of effects for both diet-only and diet combined with exercise. Our results demonstrate that weight-related reductions in cerebral blood flow can be modified by 10% weight loss over the course of 12 months and that interventions involving exercise exposure may provide unique effects on cerebral blood flow compared to interventions involving only diet.