Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular targets of honey bee’s products in cancer prevention and treatment

Chemotherapy and radiotherapy are currently the main treatments for cancer but their toxicities on the surrounding normal cells limit their use in cancer therapy. Moreover, many cancers have developed some resistance to the available anticancer chemicals and put in failure the chemotherapy currently used in the cancer treatment. This failure of the targeted monotherapy resulting from bypass mechanisms has obligated researchers to use agents that interfere with multiple cell-signaling pathways. Recently, researches focused on the use of natural products which can target cancer promoting factors genes expression. Of these natural products, honey has been extensively studied. The pharmacological properties of honey include antioxidant, anti-inflammatory, antibacterial, immunomodulatory, estrogenic and anti-cancer effects. The honey bee’s products are potent sources of nutritional components including sugar, amino-acids, water and minerals. Furthermore honey contains chemopreventive compounds such as flavonoids, phenol acids, tannins, vitamins that may interfere with multiple cell’s pathways and hereby reduce the incidence of many types of cancers. However, the molecular mechanisms of honey bee’s products in cancer prevention and treatment are less known. This review highlights the molecular mechanism of honey bioactive compounds in cancer prevention and treatment.
Feeding increases the number of offspring but decreases parental investment of Red Sea coral Stylophora pistillata

Abstract Successful reproductive output and recruitment is crucial to coral persistence and recovery following anthropogenic stress. Feeding is known to alter coral physiology and increase resilience to bleaching. The goal of the study was to address the knowledge gap of the influence of feeding on reproductive output and offspring phenotype. Colonies of Stylophora pistillata from the Northern Gulf of Aqaba (Red Sea) were fed an Artemia diet or unfed for 5 months during gametogenesis, fertilization, and brooding. In addition, time to settlement and mortality of planulae were assessed at water temperatures ranging from winter temperature (22°C) to three degrees above average peak summer temperature (31°C). A range of physiological parameters was measured in parents and offspring. In brooding parents, feeding significantly increased protein concentration and more than tripled the number of released planulae. Planulae from unfed colonies had higher chlorophyll per symbiont concentration and concomitantly higher photosynthetic efficiency compared to planulae from fed parents. In settlement assays, planulae showed a similar thermal resistance as known for this Red Sea adult population. Mortality was greater in planulae from unfed parents at ambient and 3°C above ambient temperature despite higher per offspring investment in terms of total fatty acid content. Fatty acid profiles and relative abundances were generally conserved between different fed and unfed colonies but planulae were enriched in monounsaturated fatty acids relative to adults, that is, 16:1, 18:1, 20:1, 22:1, and 24:1 isomers. Ultimately the availability of zooplankton could influence population physiology and recruitment in corals.
Shoulder function and activity limitations in patients with early rheumatoid arthritis

Patients with rheumatoid arthritis (RA) have impaired physical function which can lead to difficulties with daily activities. Despite improved pharmacological treatment, patients with early RA report difficulties with activities involving the shoulder. There is limited knowledge of the shoulder function and activity limitations related to the shoulder, arm and hand among patients with early RA. The overall aim of this thesis was to investigate shoulder function and activity limitations related to the shoulder, arm and hand, and the relationship between shoulder function, activity limitations and work ability in patients with early RA. A methodological study evaluated the reliability and validity for the Disability of the Shoulder, Arm and Hand (DASH) questionnaire which assess activity limitations related to the shoulder, arm and hand. A controlled cross-sectional study and a crosssectional study investigated shoulder function and activity limitations related to the shoulder, arm and hand and the relationship between shoulder function, activity limitations and work ability in patients with early RA. A randomized-controlled study evaluted moderately intensive pool exercise for patients with RA. Main findings. DASH was found to possess satisfactory reliability and validity to assess activity limitations in patients with early RA. The shoulder function was found to be impaired, in particular the shoulder muscle strength which was 65% of the muscle strength in the reference group.The majority of the patients reported some activity limitations related to the shoulder,arm and hand when compared with the reference group. Impaired work ability is common among patients with early RA and associated with impaired shoulder function, mechanical exposure and activity limitations related to the shoulder, arm and hand. Moderately intensive pool exercise improved muscle function in the upper and lower extremites, active range of motion of the shoulder, activity limitations and well-being in patients with RA, while the aerobic capacity did not improve. Long-term follow-up showed also improved physical and mental quality of life. Conclusion. Screening and monitoring of shoulder function from disease onset is warranted as the shoulder function is impaired, in particular the shoulder muscle strength. The majority of the patients with early RA report activity limitations related to the shoulder, arm and hand. DASH can be used to monitor the progress of the upper extremity function and activity limitations in patients with RA. Work ability in early RA is associated with shoulder function, mechanical exposure and activity limitations related to the shoulder, arm and hand. Moderately intensive pool exercise can be recommended for improvement of physical function, activity limitations and quality of life for patients with RA.
Complete chloroplast genome of the tiny marine diatom Nanofrustulum shiloi (Bacillariophyta) from the Adriatic Sea

Abstract We report the chloroplast genome sequence of Nanofrustulum shiloi, a tiny araphid pennate diatom collected from the Adriatic Sea. The 160,994-bp N. shiloi genome displays a quadripartite structure and its gene repertoire resembles those of other diatom chloroplast genomes. Besides the genes located in the inverted repeat, psbY is duplicated. A gene-poor region in the large single-copy region contains multiple ORFs sharing sequence similarities with plasmids and chloroplast ORFs found in other diatom species. The genome features a single intron, a group II intron in petB. Phylogenomic analysis identified N. shiloi at a basal position within the araphid 2 clade.
Lipid Chaperoning of a Thylakoid Protease Whose Stability is Modified by the Protonmotive Force

Protein folding is a complex cellular process often assisted by chaperones but can also be facilitated by interactions with lipids. Disulfide bond formation is a common mechanism to stabilize a protein. This can help maintain functionality amidst changes in the biochemical milieu which are especially common across energy-transducing membranes. Plastidic Type I Signal Peptidase 1 (Plsp1) is an integral thylakoid membrane signal peptidase which requires an intramolecular disulfide bond for in vitro activity. We have investigated the interplay between disulfide bond formation, lipids, and pH in the folding and activity of Plsp1. By combining biochemical approaches with a genetic complementation assay, we provide evidence that interactions with lipids in the thylakoid membrane have chaperoning activity towards Plsp1. Further, the disulfide bridge appears to prevent an inhibitory conformational change resulting from proton motive force-mimicking pH conditions. Broader implications related to the folding of proteins in energy-transducing membranes are discussed.
Single-cell analysis of human retina identifies evolutionarily conserved and species-specific mechanisms controlling development

The development of single-cell RNA-Sequencing (scRNA-Seq) has allowed high resolution analysis of cell type diversity and transcriptional networks controlling cell fate specification. To identify the transcriptional networks governing human retinal development, we performed scRNA-Seq over retinal organoid and in vivo retinal development, across 20 timepoints. Using both pseudotemporal and cross-species analyses, we examined the conservation of gene expression across retinal progenitor maturation and specification of all seven major retinal cell types. Furthermore, we examined gene expression differences between developing macula and periphery and between two distinct populations of horizontal cells. We also identify both shared and species-specific patterns of gene expression during human and mouse retinal development. Finally, we identify an unexpected role for ATOH7 expression in regulation of photoreceptor specification during late retinogenesis. These results provide a roadmap to future studies of human retinal development, and may help guide the design of cell-based therapies for treating retinal dystrophies.
A comparison of treatment choices when dental caries lesions are diagnosed with two visual-tactile systems the Nyvad and ICDAS II+LAA

Aim: The aim of this randomized cross-over study was to evaluate the reproducibility and differences in diagnostic outcomes by practicing dental clinicians previously inexperienced in using the Nyvad (NY) and the ICDAS II with LAA (IC+LAA) systems. Methods: Four volunteer dentists were randomly allocated to one of two groups. Both groups of dentists examined the same voluntary sample (n=140) of caries active young adults using the NY and the IC+LAA criteria in different sequences. The first group used the NY criteria during period I, followed by IC+LAA during period II; the second group did the examinations in the opposite sequence. Before the period 1 and 2 examinations, dentists from both groups were trained with the NY or the IC+LAA criteria, depending on the group in which they were assigned. Results: Inter-examiner agreement for the severity diagnostic threshold was high for both diagnostic instruments (Kappa 0.71-0.73). For the D1 (active) diagnostic threshold, the interexaminer Kappa values were 0.48-0.51 for the IC+LAA and 0.45-0.57 for the NY. The mean number of active non-cavitated carious lesions was significantly higher for the IC+LAA (6.14(SD±5.4)) than for the NY criteria (3.90(SD±3.9), 44 p<0.0001). Active cavitated/dentinal carious lesions were significantly higher for the IC+LAA (4.14, SD±4.1) than for the NY criteria (2.13, SD±3.1; p<0.0001). Conclusion: Both the NY and the IC+LAA diagnostic systems showed high reproducibility for the severity assessment. The mean number of active carious lesions was significantly higher using the IC+LAA criteria, which may subsequently lead to more caries treatment. Trial registration: ISRCTN65592532.
Exploring rain forest diversification using demographic model testing in the African foam‐nest treefrog Chiromantis rufescens

Species with wide distributions spanning the African Guinean and Congolian rain forests are often composed of genetically distinct populations or cryptic species with geographic distributions that mirror the locations of the remaining forest habitats. We used phylogeographic inference and demographic model testing to evaluate diversification models in a widespread rain forest species, the African foam‐nest treefrog Chiromantis rufescens.
Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma and vascular invasion or extrahepatic spread: A subanalysis from the SHARP trial

4584 Background: Liver cancer is the third leading cause of cancer death globally, with most deaths occurring within one year of diagnosis. The multi-kinase inhibitor sorafenib became the first treatment approved by the FDA and EMEA for the treatment of HCC based on data from the phase III Sorafenib HCC Assessment Randomized Protocol (SHARP) trial, which demonstrated that sorafenib 400mg bid increased overall survival (OS) vs placebo in patients with advanced HCC. The influence of risk factors such as macroscopic vascular invasion (MVI) and/or extrahepatic spread (EHS), on the safety and efficacy of sorafenib has not previously been reported. Here we compare sorafenib versus placebo in patients with and without MVI and/or EHS. Methods: Patients with advanced, measurable HCC, Eastern Cooperative Oncology Group performance status (ECOG PS) 0–2 and Child-Pugh status A received either sorafenib (400mg bid) or placebo. Endpoints included OS, time to progression (TTP; based on independent tumor assessment), and.
Molecular weight of condensed tannins of some tropical feed-leaves and their effect on in vitro gas and methane production

The concentration and molecular weights (MW) of condensed tannins (CT) of three locally available tropical plant species leaves which have potential to be used as ruminant feed, and their effects on in vitro gas, including methane, production were investigated. Leaves of three plant species, namely, leucaena (Leucaena leucocephala), cassava (Manihot esculenta, Cranzt), and Siamese neem (Azadirachta indica A.Juss. var. Siamensis Valeton) were used in the present study. CT contents ranged from 1.2% in the leucaena to 5.0% in Siamese neem. The weight-average molecular weights (Mw) of the purified CTs, determined using gel-permeation chromatography, were 3222, 3409 and 3612 Da for leucaena, cassava and Siamese neem respectively. The above values were within the range reported for CTs of various tropical plant species. We know of no published data on MW of CTs from leaves of cassava and Siamese neem and, thus, this research, for the first time, reported the MWs of the above two plant materials. Subsequently, two CT extracts with differing MWs, such as CTs extracted from leaves of Siamese neem and leaves of leucaena, were selected as the representative of high and low MWs of CT respectively, and used for investigation of the effect of the MW of CT on in vitro gas production and fermentation parameters. Supplementation of CTs of a higher MW extracted from leaves of Siamese neem (at 2–6 mg/100 mg DM) significantly inhibited in vitro total gas and methane production, while supplementation of CTs with a lower MW extracted from leaves of leucaena had no effect, except for total gas production at the highest level (6 mg/100 mg DM) of supplementation. Similarly, CT from Siamese neem leaves had a stronger inhibitory effect (P < 0.001) on in vitro volatile fatty acid, acetic acid and butyric acid production. The above results indicated that concentrations and the MW of CT varied among the plant species; in addition, the efficacy of CTs to inhibit ruminal CH4 emission are influenced by their MW.
The role of the preproglucagon neurons in cardiovascular control, energy homeostasis and glucose homeostasis

Glucagon-like peptide-1 (GLP-1) is produced in the gut and central nervous system. Microinjection of GLP-1 analogues into specific brain regions causes hypophagia, induces insulin release and tachycardia. GLP-1 is produced within the brain by preproglucagon (PPG) neurons, situated in the caudal brainstem. PPG neurons project to nuclei involved in cardiovascular control, glucose homeostasis, and food intake. I hypothesised that PPG neurons are the endogenous source of GLP-1 in the brain, and their activation should reproduce the effects seen upon injection of exogenous GLP-1 into the brain. I demonstrated that selective chemogenetic activation of PPG neurons increased heart rate, but, their inhibition did not reduce it. These results demonstrate that PPG neurons can modulate heart rate but are not doing so under resting conditions. Similarly, I showed that PPG neuron activation acutely but not chronically decreases food intake. To further understand under which circumstances PPG neurons are activated to control food intake, c-Fos- immunoreactivity (C-Fos-IR) was used to detect neuronal activity in response to stimuli. There were few C-Fos-IR positive PPG neurons with normal feeding, but intake of highly palatable Ensure (Vanilla milkshake) substantially increased the number of C-Fos-IR positive PPG neurons suggesting that they are activated when consuming a high calorific and/or a high-volume meal. This suggests that PPG neurons induce satiety only in response to large or palatable meals. Neither chemogenetic activation nor ablation of the PPG neurons affected glucose tolerance, arguing that PPG neurons do not modulate blood glucose levels. The results presented here provide evidence for the physiological role of PPG neurons in satiety, implicating them as a possible target for weight loss drugs. Additionally, PPG neurons are capable of raising heart rate, however further studies must define under which conditions PPG neurons induce tachycardia. As these results mimic the effects of exogenous GLP-1, it seems likely that PPG neurons induce satiety and tachycardia through the release of GLP-1.
Presynaptic α2δ subunits are key organizers of glutamatergic synapses

Significance Voltage-gated calcium channels are important regulators of neuronal functions, as for example synaptic transmission. Their auxiliary α2δ subunits are modulating the calcium currents. Beyond that they have emerged as modulators of synaptic functions. Here, we established a cellular triple knockout/knockdown model in cultured hippocampal neurons by knocking out or knocking down the expression of all three α2δ subunits expressed in brain. Our experiments demonstrate that the presynaptic loss of α2δ proteins leads to a severe defect in glutamatergic synapse formation, which could be rescued by reintroducing any of the three neuronal α2δ isoforms. Thus, our study suggests that α2δ proteins are critical regulators of excitatory synapse formation and thereby contributes to the understanding of basic nerve cell functions. In nerve cells the genes encoding for α2δ subunits of voltage-gated calcium channels have been linked to synaptic functions and neurological disease. Here we show that α2δ subunits are essential for the formation and organization of glutamatergic synapses. Using a cellular α2δ subunit triple-knockout/knockdown model, we demonstrate a failure in presynaptic differentiation evidenced by defective presynaptic calcium channel clustering and calcium influx, smaller presynaptic active zones, and a strongly reduced accumulation of presynaptic vesicle-associated proteins (synapsin and vGLUT). The presynaptic defect is associated with the downscaling of postsynaptic AMPA receptors and the postsynaptic density. The role of α2δ isoforms as synaptic organizers is highly redundant, as each individual α2δ isoform can rescue presynaptic calcium channel trafficking and expression of synaptic proteins. Moreover, α2δ-2 and α2δ-3 with mutated metal ion-dependent adhesion sites can fully rescue presynaptic synapsin expression but only partially calcium channel trafficking, suggesting that the regulatory role of α2δ subunits is independent from its role as a calcium channel subunit. Our findings influence the current view on excitatory synapse formation. First, our study suggests that postsynaptic differentiation is secondary to presynaptic differentiation. Second, the dependence of presynaptic differentiation on α2δ implicates α2δ subunits as potential nucleation points for the organization of synapses. Finally, our results suggest that α2δ subunits act as transsynaptic organizers of glutamatergic synapses, thereby aligning the synaptic active zone with the postsynaptic density.
LSU Digital Commons LSU Digital Commons Natively oxidized amino acid residues in the spinach PS I-LHC I Natively oxidized amino acid residues in the spinach PS I-LHC I supercomplex supercomplex

Reactive oxygen species (ROS) production is an unavoidable byproduct of electron transport under aerobic conditions. Photosystem II (PS II), the cytochrome b 6 / f complex and Photosystem I (PS I) are all demonstrated sources of ROS. It has been proposed that PS I produces substantial levels of a variety of ROS including O 2. − , 1 O 2 , H 2 O 2 and, possibly, •OH; however, the site(s) of ROS production within PS I has been the subject of significant debate. We hypothesize that amino acid residues close to the sites of ROS generation will be more susceptible to oxidative modification than distant residues. In this study, we have identified oxidized amino acid residues in spinach PS I which was isolated from field-grown spinach. The modified residues were identified by high-resolution tandem mass spectrometry. As expected, many of the modified residues lie on the surface of the complex. However, a well-defined group of oxidized residues, both buried and surface-exposed, lead from the chl a ’ of P 700 to the surface of PS I. These residues (PsaB: 609 F, 611 E, 617 M, 619 W, 620 L, and PsaF: 139 L, 142 A, 143 D) may identify a preferred route for ROS, probably 1 O 2 , to egress the complex from the vicinity of P 700 . Additionally, two buried residues located in close proximity to A 1B (PsaB: 712 H and 714 S) were modified, which appears consistent with A 1B being a source of O 2. − . Surprisingly, no oxidatively modified residues were identified in close proximity to the 4Fe–FS clusters F X , F A or F B . These cofactors had been identified as principal targets for ROS damage in the photosystem. Finally, a large number of residues located in the hydrophobic cores of Lhca1–Lhca4 are oxidatively modified. These appear to be the result of 1 O 2 production by the distal antennae for the photosystem.
The Use of CRISPR-Cas9 Genome Editing to Determine the Importance of Glycerol Uptake in Wine Yeast During Icewine Fermentation

The high concentration of sugars in Icewine juice causes formidable stress for the fermenting Saccharomyces cerevisiae, causing cells to lose water and shrink in size. Yeast can combat this stress by increasing the internal concentration of glycerol by activating the high osmolarity glycerol response to synthesize glycerol and by actively transporting glycerol into the cell from the environment. The H+/glycerol symporter, Stl1p, has been previously characterized as being glucose repressed and inactivated, despite osmotic stress induction. To further investigate the role of Stl1p in Icewine fermentations, we developed a rapid single plasmid CRISPR-Cas9-based genome editing method to construct a strain of the common Icewine yeast, S. cerevisiae K1-V1116, that lacks STL1. In an Icewine fermentation, the ∆STL1 strain had reduced fermentation performance, and elevated glycerol and acetic acid production compared to the parent. These results demonstrate that glycerol uptake by Stl1p has a significant role during osmotically challenging Icewine fermentations in K1-V1116 despite potential glucose downregulation.