Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel Combination of a Long-Acting GLP-1/GIP/Glucagon Triple Agonist (HM15211) and Once-Weekly Basal Insulin (HM12460a) Offers Improved Glucose Lowering and Weight Loss in a Diabetic Animal Model

Obesity is an established risk factor for prediabetes, diabetes and the aggravation of preexisting diabetes by negatively affecting lipid metabolism, insulin response, and β-cell function. Thus, effective body weight loss not only prevents or delays the onset of T2DM, but also enhances the response to diabetes drugs including basal insulin in T2DM patients. Recently, we have developed a novel long-acting GLP-1/GIP/Glucagon triple agonist, HM15211, which showed potent weight loss in obese animal models. When combined with basal insulin, HM15211 might maximize the insulin response and provide additional weight loss. Here, we investigated the PK/PD properties of HM15211 and HM12460A (once weekly basal insulin developing in clinical stage) combination in animal models to evaluate the therapeutic benefits of this novel combination in diabetes. Firstly, drug-to-drug interaction (DDI) was evaluated to assess the changes in intrinsic activity and PK of the individual components. In vitro human insulin receptor phosphorylation by HM12460A was not affected by concomitant HM15211 treatment. Similarly, cAMP accumulation by HM15211 was unaffected. Analysis of PK demonstrated that the administration of HM15211 and HM12460A, either alone or in combination, did not change their extended half-lives in SD rats. Secondly, the glucose lowering and body weight loss by HM15211 in combination with HM12460A was evaluated in db/db mice. After 4 weeks treatment, a combination of HM15211 and HM12460A reduced the HbA1c more than the mono-treatment. Moreover, potent weight loss by HM15211 was well maintained even when combined with HM12460A. Based on these observation, we propose that HM15211 might be an additional combination partner for long-acting basal insulin such as HM12460A providing improved glycemic control and more favorable weight loss. Disclosure J. Kim: Employee; Self; Hanmi Pharmaceutical. Stock/Shareholder; Self; Hanmi Pharmaceutical. J. Lee: Employee; Self; Hanmi Pharmaceutical. Stock/Shareholder; Self; Hanmi Pharmaceutical. J. Choi: Employee; Self; Hanmi Pharmaceutical. Stock/Shareholder; Self; Hanmi Pharmaceutical. S. Jung: None. S. Lee: Employee; Self; Hanmi Pharmaceutical. I. Choi: Employee; Self; Hanmi Pharmaceutical. Stock/Shareholder; Self; Hanmi Pharmaceutical. S. Kim: Employee; Self; Hanmi Pharmaceutical. Stock/Shareholder; Self; Hanmi Pharmaceutical.
The indirect role of species‐level factors in biological invasions

Aim Biological invasions are driven by factors related to species, locations and events. Species-level factors (namely functional traits) often distinguish successful invaders from other groups of species in trait-only analyses. However, traits are routinely found to be much less important than event-level (e.g. propagule pressure) or location-level (e.g. abiotic or congeneric effects) factors when included in the same model. We hypothesized that this rift exists largely because traits have (often overlooked) indirect effects that affect invasion success by influencing other mechanisms. Location Global. Methods We developed a conceptual path diagram hypothesizing indirect effects on invasion success of species traits directly affecting (1) native range size, (2) propagule pressure, and (3) climate matching between native and non-native ranges. We used structural equation modelling to evaluate our hypothesis using open-access datasets on: (1) the naturalization success of non-native Pinus in New Zealand (McGregor et al., 2012, Diversity and Distributions, 18, 1013–1023), and (2) the global establishment success of non-native reptiles (Mahoney et al., 2015, Diversity and Distributions, 21, 64–74). Both these studies found little to no direct importance of traits on invasion success. Results Our analyses revealed indirect effects of species traits and native range size on invasion success. Traits indirectly affected Pinus naturalization success and reptile establishment success by affecting introduction effort and native range size. Consistent with the original analyses, traits had little measurable direct effect on invasion success. Main conclusions Species-level factors have both direct and indirect roles in biological invasions. Consideration of the indirect effects of functional traits may help to reconcile disparities in findings on the relative role of traits versus other contributors to the invasion process.
Brief Communication Reduced expression of PSA-NCAM in the hippocampus and piriform cortex of the R6/1 and R6/2 mouse models of Huntington's disease

Cognitive deficits and impaired olfactory function are observed in early stages of Huntington's disease (HD). The polysialylated form of the neural cell adhesion molecule (PSA-NCAM) is strongly associated with plastic events in the brain. During adulthood, it is most abundantly expressed in the hippocampus and the piriform cortex, which are involved in cognition and olfaction, respectively. We show that the numbers of PSA-NCAM-positive cells in the hippocampus and piriform cortex are dramatically reduced in the R6/1 and the R6/2 mouse models of HD. We hypothesize that the decrease in NCAM polysialylation reflects an impaired plasticity and might underlie some of the early symptoms in HD.
RESERVAS EXTRATIVISTAS NA AMAZÔNIA: UMA VISÃO DOS ATORES POR MEIO DO DISCURSO DO SUJEITO COLETIVO

Este artigo teve como objetivo analisar como grupos de atores sociais distintos interpretam a institucionalizacao de Reservas Extrativistas (RESEX) apreciada do ponto de vista de uma politica publica de conservacao da biodiversidade. Foram considerados os extrativistas e os representantes de organizacoes que giram em torno das RESEX, diferenciadas em governamentais e nao governamentais. Como referencial teorico, considerou-se a abordagem institucional e da sociologia organizacional. Metodologicamente, utilizou-se o Discurso do Sujeito Coletivo (DSC) como forma de compreender o discurso de ambos os grupos no que se refere a definicao de extrativismo, desenvolvimento e sustentabilidade. Os resultados apontam para discursos bastante distintos, sendo que os extrativistas relacionam suas atividades como meio de sobrevivencia, com pouca conotacao ambiental. Por outro lado, os representantes das organizacoes governamentais demonstram ter um discurso politicamente correto, mas com pouca eficacia na gestao ou apoio as RESEX. As organizacoes nao governamentais, por sua vez, encontram-se em uma posicao intermediaria, ora aproximando-se dos extrativistas ora das organizacoes publicas. Conclui-se que esse descompasso reflete negativamente na gestao destas Unidades de Conservacao e que a sustentabilidade ainda nao tem sido atingida nessas areas, vez que a baixa renda tem feito extrativistas optarem por manejos florestais, cada vez mais frequentes.
Manganese-Based Targeted Nanoparticles for Postoperative Gastric Cancer Monitoring via Magnetic Resonance Imaging

Postoperative recurrence is a common and severe problem in the treatment of gastric cancer; consequently, a prolonged course of chemotherapy treatment is inevitable. Monitoring by imaging could provide an accurate evaluation of the therapeutic effects, which would be beneficial to guide a treatment strategy adjustment over time. However, current imaging technologies remain insufficient for the continuous postoperative monitoring of gastric cancer. In this case, molecular imaging offers an efficient strategy. Targetable contrast agents are an essential part of molecular imaging, which could greatly enhance the accuracy and quality of monitoring. Herein, we synthesized a Mn-based contrast agent for magnetic resonance imaging (MRI) of gastric cancer monitoring. Initially, small-sized Mn3O4 nanoparticles (NPs) were synthesized. Then, a functionalized polyethylene glycol (PEG) lipid was attached to the surface of the Mn3O4 NPs, to improve biocompatibility. The targetable MRI contrast agent (Mn3O4@PEG-RGD NPs) was further prepared by the conjugation of the arginine-glycine-aspartic acid (RGD) peptides. The completed Mn3O4@PEG-RGD NPs had the small size of 7.3 ± 2.7 nm and exhibited superior colloidal stability in different solution environments. In addition, Mn3O4@PEG-RGD NPs exhibited reliable biotolerance and low toxicity both in vitro and in vivo. Imaging experiments amply demonstrated that Mn3O4@PEG-RGD NPs could efficiently accumulate in gastric cancer tissues and cells via RGD mediation, and immediately significantly increased the MRI effects. Through this study, we can conclude that Mn3O4@PEG-RGD NPs have the potential to be a novel MRI contrast agent for the postoperative monitoring of gastric cancer.
The use of naturally occurring minerals in animal feed

The term usually applied to food prepared for domesticated livestock is 'fodder,' which is primarily composed of natural organic ingredients such as hay, straw, silage, pelleted foods, oils, grains, legumes and molasses as well as spent grain from breweries and distilleries and DDGS (distiller's dried grains with solubles), from bio-ethanol production. Frank Hart* looks into the use of naturally-occurring minerals in animal feed. Economically, fusarium derived mycotoxins such as zearalenone are very important as they are oestrogenic and lead to poor fertility and potentially miscarriages in breeding livestock.Simple, cost effective and safe processes by which animals may be detoxified and decontaminated are in great demand. There is intense competition from non-mineral substances. Bacteria and enzymes are commonly used. These break down the mycotoxin structure into non-toxic metabolites. Esterified glucomannan, which is obtained from the cell walls of yeast, work in a similar manner to clays by absorption. However, these ingredients are almost always combined with a clay mineral, for example 'Mycosorb', one of Alltech's best selling products, which is a blend of yeast cell wall and mineral(s). Radionuclide containment Clinoptilite/zeolite is micro-porous with a very high surface area of approximately 500 metres squared per gram (m[superscript]2 /g). It can selectively absorb molecules depending on their size. The maximum size is determined by the dimension of channels in the crystal structure, hence its description as a 'molecular sieve'. It is sold into the aquaculture industry, to shrimp and fish farms and to pet aquariums, due to its ability to absorb ammonia from water. It is also used in animal feed to absorb mycotoxins, particularly aflatoxin as well as in poultry feed to bulk excrement and absorb ammonia. Globally, China and South Korea are the biggest producers.
Effect of Cucumber mosaic virus (CMV) infection on antineoplastic alkaloids from periwinkle (Catharanthus roseus L.) cultured in the Mecca region and resistance induction by plant-growth-promoting rhizobacteria (PGPR)

ABSTRACT More than 100 alkaloids have been found in periwinkle, of which vincristine and vinblastine are the most notable for the treatment of diseases such as leukaemia. In this study, characterization of naturally occurring Cucumber mosaic virus (CMV) infection showed mosaic, leaf deformation and stunting of plants. Viral identification was confirmed by double-antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) with a specific CMV polyclonal antibody and reverse transcription PCR with a specific primer for the CMV-RdRp-gene, which yielded a 513 base pair DNA fragment. The effect of CMV infection on the antineoplastic alkaloids in periwinkle leaves was determined. We also studied the effect of using plant-growth-promoting rhizobacteria (PGPR) isolates against virus infection to stimulate resistance induction in host plants. Bacillus subtilis 281 and B. pumilus 293 were examined individually (B1 and B2) and in a mixture (B1&B2) for their effectiveness against infection with CMV. The results of greenhouse experiments were confirmed by artificial mechanical inoculation. The PGPR strain treatments and results were reinforced by analysing the protein patterns as well as determining the total phenol, total flavonoid and total alkaloid contents. PGPR treatment evidently lowered the virus concentrations, the percentage of infected plants and the disease severity compared with healthy and infected controls. Seedlings treated with the B1&B2 strain mixture yielded significantly lower levels of virus infection than B1 or B2 individually in all experiments compared to controls. Our findings demonstrate the possibility of using selected Bacillus spp. strains to induce systemic resistance for CMV infection control.
The role of gene expression in the recent evolution of resistance in a model host parasite system

Damage by parasites is a perpetual challenge for hosts, often leading to the evolution of elaborate mechanisms of avoidance, immunity, or tolerance. Host resistance can evolve via changes in immune protein coding and/or expression. Heritable population differences in gene expression following infection can reveal mechanisms of immune evolution. We compared gene expression in infected and uninfected threespine stickleback (Gasterosteus aculeatus) from two natural populations that differ in their resistance to a native cestode parasite, Schistocephalus solidus. Genes in both the innate and adaptive immune system were differentially expressed as a function of host population, infection status, and their interaction. These genes were enriched for loci controlling immune functions that we independently verified differ between host populations, or in response to infection. For instance, populations differ strongly in reactive oxygen (ROS) production, and we observed corresponding differences in expression of ROS-affecting loci. Differentially expressed genes also were involved in fibroblast activation, B-cell activation, and leukocyte trafficking. Coexpression network analysis identified two distinct immune processes contributing to stickleback resistance; several modules of genes are correlated with parasite survival while a different set of modules are correlated with suppression of cestode growth. Comparison of networks between populations showed resistant fish have a dynamic expression profile while susceptible fish are static. In summary, recent evolutionary divergence between two vertebrate populations has generated population-specific gene expression responses to parasite infection, which reveal a few immune modules likely to separately affect cestode establishment, and growth.
A phylogenetic and chemotaxonomic view of microbial diversity and natural community structure

The application of molecular methods to phylogenetic studies of microorganisms has significandy expanded our knowledge of the extent of microbial diversiry and the pattern of microbial evolution. The most extensive molecular studies in this research field have been performed based on small subunit ribosomal RNA (165 and 165-like rRNA) sequences, and these studies have led to the proposal of classifying prokaryotes into rwo distinct monophyletic groups, designated archaebacteria and eubacteria, which are now recognized as the domains Archaea and Bacteria, respectively (WOESE er al. 1990). 165 rRNA sequence data in the databases are logarithmically increasing, and taxonomic systems for bacterial species and genera are being constructed and rearranged along the rRNA-based phylogenetic lines.
Synaptonemal complex architecture facilitates the chromosome-specific regulation of recombination in Drosophila

Synaptonemal complex architecture facilitates the chromosome-specific regulation of 1 recombination in Drosophila 2 Cori K. Cahoon*, G. Matthew Heenan*, Zulin Yu*, Jay R. Unruh*, Sean McKinney*, and R. Scott 3 Hawley* 4 5 * Stowers Institute for Medical Research, Kansas City, MO, United States of America 6 ‡ Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 7 Kansas City, KS, United States of America 8 9 Corresponding Author: 10 R. Scott Hawley 11 Stowers Institute for Medical Research 12 Kansas City, MO 64110 13 Phone (816) 926-4427 14 Fax (816) 926-2060 15 rsh@stowers.org 16 17 18
A 6 years follow-up comparison of two dental implants: bioactive vs DAE surface, a clinical case report

Introduction: The aim of the present study is to describe a case report of lower molars substitution with 2 different dental implants. One with a DAE surface and one with a type 1 collagen coated surface. Case presentation: In the present study, a 54-year-old man presented the absence of the first and second molars both on the left and on the right mandible. After clinical and radiographic evaluation, implant therapy was chosen to substitute the missing teeth. On the right mandible, a DAE surface implant was placed while on the left mandible, a bovine Type 1 collagen of dermal origin (custom made medical device) surface implant was placed. A radiographic 6 years follow up was performed. Discussion: The Type 1 collagen coated surface dental implant did not show any marginal bone loss after 6 years, moreover, it showed a bone gain after 3 months from its placement and kept it for 6 years while the traditional surface implant showed an immediate marginal bone loss.
Human sensory Long-Term Potentiation (LTP) predicts visual memory performance and is modulated by the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism

Background Long-Term Potentiation (LTP) is recognised as a core neuronal process underlying long-term memory. However, a direct relationship between LTP and human memory performance is yet to be demonstrated. The first aim of the current study was thus to assess the relationship between LTP and human long-term memory performance. With this also comes an opportunity to explore factors thought to mediate the relationship between LTP and long-term memory, and to gain additional insight into variations in memory function and memory decline. The second aim of the current study was to explore the relationship between LTP and memory in groups differing with respect to BDNF Val66Met; a single nucleotide polymorphism implicated in memory function. Methods 28 participants (15 female) were split into three genotype groups (Val/Val, Val/Met, Met/Met) and were presented with both an EEG paradigm for inducing LTP-like enhancements of the visually-evoked response, and a test of visual memory. Results The magnitude of LTP 40 minutes after induction was predictive of long-term memory performance. Additionally, the BDNF Met allele was associated with both reduced LTP and reduced memory performance. Conclusions The current study not only presents the first evidence for a relationship between sensory LTP and human memory performance, but also demonstrates how targeting this relationship can provide insight into factors implicated in variation in human memory performance. It is anticipated that this will be of utility to future clinical studies of disrupted memory function.
Rap2 and TNIK control Plexin-dependent synaptic tiling in C. elegans

During development, neurons form synapses with their fate-determined targets. While we begin to elucidate the mechanisms by which extracellular ligand-receptor interactions enhance synapse specificity by inhibiting synaptogenesis, our knowledge about their intracellular mechanisms remains limited. Here we show that Rap2 GTPase (rap-2) and its effector, TNIK (mig-15), act downstream of Plexin (plx-1) to restrict presynaptic assembly and to form tiled synaptic innervation in C. elegans. Both constitutively GTP- and GDP-forms of rap-2 mutants exhibit synaptic tiling defects as plx-1 mutants, suggesting that cycling of the RAP-2 nucleotide state is critical for synapse inhibition. Consistently, RAP-2 activity is locally suppressed by PLX-1. Excessive ectopic synapse formation in mig-15 mutants causes a severe synaptic tiling defect. Conversely, overexpression of mig-15 strongly inhibited synapse formation, suggesting that mig-15 is a negative regulator of synapse formation. These results reveal that subcellular regulation of small GTPase activity by Plexin shapes proper synapse patterning in vivo.
Genome-Guided Transcriptomics, DNA-Protein Interactions, and Variant Calling

Nowadays, molecular biology has definitely become an interdisciplinary science. Toward the study of the functions and the interactions of the biological molecules, such as nucleic acids and proteins, computer science and engineering, along with chemistry and statistics, are routinely engaged. In molecular biology, techniques and methods are constantly developed, and new techniques emerge. Next-generation sequencing and bioinformatics have become the cornerstones of molecular biology. The developing technologies have led to a decrease of the cost per molecular unit analyzed, but at the cost of computer integra- tion and intensification. Many research methods require a reference nucleic acid sequence. Considering the necessary integration of sequencing data and methodology, combining the “ omics ” approaches can help to elucidate more complex null hypotheses. Here, data processing basics, with an emphasis to commonly used techniques, are summarized. The knowledge gaps are discussed as well as further prospective for integrating next-generation sequencing data.
ArcA and FNR regulate bioluminescence in the light-organ symbiont Vibrio fischeri

Despite years of intense study of bioluminescence in Vibrio fischeri, much remains unanswered regarding its benefit to the cell and the environmental factors affecting its regulation. In this dissertation, I show that bioluminescence leads to a growth rate reduction under some culture conditions, yet it contributes to this bacterium’s ability to colonize one of its symbiotic hosts, the squid Euprymna scolopes. Based on the reaction catalyzed by the light-producing enzyme luciferase, two conflicting hypotheses have been suggested to explain the benefit that bioluminescence provides symbiotic V. fischeri. One proposal is that luminescence provides an advantage by consuming oxygen and thus serving as an antioxidant to protect the cell from toxic oxygen radicals. Conversely, a second proposal suggests that by consuming excess reductant luminescence acts as an electron sink. I examined the regulation of luminescence to help distinguish between these two hypotheses, assuming that luminescence would be maximally expressed when it is most beneficial. I examined luminescence of mutants lacking the redoxresponsive and oxygen-sensitive regulators ArcA and FNR, respectively. This was performed in the well-studied and naturally visibly luminescent strain MJ1 as well as in the relatively dim strain ES114, which is a natural symbiont of E. scolopes. ArcA is most active under reducing conditions, and I found that it represses luminescence in both strains due to a conserved ArcA binding site in the PluxI promoter, which controls the expression of the proteins necessary for light production. Similar to ArcA, FNR is active under anaerobic conditions and represses luminescence in MJ1, although no such effect is apparent in ES114. These results demonstrate that luminescence is repressed under reduced conditions and therefore my data is consistent with the antioxidant model explaining the benefits of luminescence, but are inconsistent with the electron sink model. This work is the first to use defined mutants in V. fischeri to elucidate a mechanism by which specific environmental factors alter the regulation of luminescence. INDEX WORDS: Photobacterium, Symbiosis, Quorum sensing, Lux ARCA AND FNR REGULATE BIOLUMINESCENCE IN THE LIGHT-ORGAN SYMBIONT