Miracle-dz/UniFAR-FTUs huggingface dataset:
Dual Role of Autophagy in Diseases of the Central Nervous System

Autophagy is a vital lysosomal degradation and recycling pathway in the eukaryotic cell, responsible for maintaining an intricate balance between cell survival and cell death, necessary for neuronal survival and function. This dual role played by autophagy raises the question whether this process is a protective or a destructive pathway, the contributor of neuronal cell death or a failed attempt to repair aberrant processes? Deregulated autophagy at different steps of the pathway, whether excessive or downregulated, has been proposed to be associated with neurodegenerative disorders such as Alzheimer’s-, Huntington’s-, and Parkinson’s-disease, known for their intracellular accumulation of protein aggregates. Recent observations of impaired autophagy also appeared in psychiatric disorders such as schizophrenia and bipolar disorder suggesting an additional contribution to the pathophysiology of mental illness. Here we review the current understanding of autophagy’s role in various neuropsychiatric disorders and, hitherto, the prevailing new potential autophagy-related therapeutic strategies for their treatment.
Total and Potentially Active Bacterial Communities Entrapped in a Late Glacial Through Holocene Ice Core From Scarisoara Ice Cave, Romania

Our understanding of the icy-habitat microbiome is likely limited by a lack of reliable data on microorganisms inhabiting underground ice that has accumulated inside caves. To characterize how environmental variation impacts cave ice microbial community structure, we determined the composition of total and potentially active bacterial communities along a 13,000-year-old ice core from Scarisoara cave (Romania) through 16S rRNA gene Illumina sequencing. An average of 2,546 prokaryotic gDNA operational taxonomic units (OTUs) and 585 cDNA OTUs were identified across the perennial cave ice block and analyzed in relation to the geochemical composition of ice layers. The total microbial community and the putative active fraction displayed dissimilar taxa profiles. The ice-contained microbiome was dominated by Actinobacteria with a variable representation of Proteobacteria, while the putative active microbial community was equally shared between Proteobacteria and Firmicutes. Accordingly, a major presence of Cryobacterium, Lysinomonas, Pedobacter, and Aeromicrobium phylotypes homologous to psychrotrophic and psychrophilic bacteria from various cold environments were noted in the total community, while the prevalent putative active bacteria belonged to Clostridium, Pseudomonas, Janthinobacterium, Stenotrophomonas, and Massilia genera. Variation in the microbial cell density of ice strata with the dissolved organic carbon (DOC) content and the strong correlation of DOC and silicon concentrations revealed a major impact of depositional processes on microbial abundance throughout the ice block. Post-depositional processes appeared to occur mostly during the 4,000–7,000 years BP interval. A major bacterial composition shift was observed in 4,500–5,000-year-old ice, leading to a high representation of Beta- and Deltaproteobacteria in the potentially active community in response to the increased concentrations of DOC and major chemical elements. Estimated metabolic rates suggested the presence of a viable microbial community within the cave ice block, characterized by a maintenance metabolism in most strata and growth capacity in those ice deposits with high microbial abundance and DOC content. This first survey of microbial distribution in perennial cave ice formed since the Last Glacial period revealed a complex potentially active community, highlighting major shifts in community composition associated with geochemical changes that took place during climatic events that occurred about 5,000 years ago, with putative formation of photosynthetic biofilms.
Alternative bait trials in the Barents Sea snow crab fishery

Commercial harvesting of snow crab (Chionoecetes opilio) in the Barents Sea started in 2012 by Norwegian fishing vessels. This new fishery has significant bait requirements, representing an emerging conservation challenge. In this study, we evaluate the performance of five alternative (natural) baits manufactured from the waste stream of existing and sustainably managed harp seal (Pagophilus groenlandicus) and minke whale (Balaenoptera acutorostrata) capture. Five different types of new bait were evaluated, including seal fat (SF), seal fat with skin (SFS), seal meat with bone (SMB), whale fat with skin (WFS), and whale meat with fat (WMF). A comparative fishing experiment was conducted onboard a commercial snow crab fishing vessel in the Barents Sea (May–June, 2016) to evaluate the performance of traditional bait (squid, Illexs spp.) and alternative baits at catching snow crabs. Performance of the different baits were compared on the basis of the number of commercial crab caught per trap haul catch per unit effort (CPUE) and carapace width (CW). Our results showed that SF and SFS performed equally well to traditional bait, with no statistical difference in CPUE (p-value = 0.325 and 0.069, respectively). All of the other experimental baits significantly decreased CPUE, when compared to squid. No significant effect of bait treatment on CW was detected and the cumulative distribution of CW was the same between control traps and each of the bait treatments. Overall the results indicated that SF and SFS represent a viable alternative to replace traditional bait, addressing a key conservation challenge in this bait intensive snow crab fishery.
Bacteroides thetaiotaomicron Starch Utilization Promotes Quercetin Degradation and Butyrate Production by Eubacterium ramulus

Consumption of flavonoids has been associated with protection against cardiovascular and neurodegenerative diseases. Most dietary flavonoids are subjected to bacterial transformations in the gut where they are converted into biologically active metabolites that are more bioavailable and have distinct effects relative to the parent compounds. While some of the pathways involved in the breakdown of flavonoids are emerging, little it is known about the impact of carbon source availability and community dynamics on flavonoid metabolism. This is relevant in the gut where there is a fierce competition for nutrients. In this study, we show that metabolism of one of the most commonly consumed flavonoids, quercetin, by the gut-associated bacterium Eubacterium ramulus is dependent on interspecies cross-feeding interactions when starch is the only energy source available. E. ramulus can degrade quercetin in the presence of glucose but is unable to use starch for growth or quercetin degradation. However, the starch-metabolizing bacterium Bacteroides thetaiotaomicron, which does not metabolize quercetin, stimulates degradation of quercetin and butyrate production by E. ramulus via cross-feeding of glucose and maltose molecules released from starch. These results suggest that dietary substrates and interactions between species modulate the degradation of flavonoids and production of butyrate, thus shaping their bioavailability and bioactivity, and likely impacting their health-promoting effects in humans.
Long-Term Spatiotemporal Variation in the Juvenile Fish Assemblage of the Tramandaí River Estuary (29°S) and Adjacent Coast in Southern Brazil

Based on a set of intermittent and seasonal data, covering a discontinuous 21-year period (1995 to 2016) and using a standard beach seine with replicates at several collection points inside the Tramandai River estuary (TRE) and outside in the marine adjacent coastal area (MACA), we evaluated connectivity between TRE and MACA and the spatiotemporal variations of fish associations. In the TRE (405 samples; 42,987 individuals) 55 species were captured. In the MACA (297 samples; 54,295 individuals) 41 species were captured. After data standardization the expected richness of the TRE [E(S) = 18.2] was significantly greater (p <0.05) than that of the MACA [E(S) = 14.4]. The fish association structure and distribution patterns in TRE and MACA are dynamic and interconnected but quite different in terms of species composition, especially due to the influence of local salinity. The TRE association is richer in a number of species but numerically dominated by marine estuarine-dependent juveniles. Freshwater species may eventually be carried in by heavy rains, bringing pulses of species richness. The MACA association is represented by a few typical marine species in addition to a couple of estuarine-related transient species who uses the surf-zone as a passageway to enter the estuaries. Even if there is a higher percentage of common species reported (30 out of 66), the monthly average Jaccard Index of similarity (JI = 28%) and the monthly average Percent Similarity Index (PSI=30%) was low, suggesting that the shallow water functional connectivity between MACA and TRE are represented by few species that occur equally in abundance in both environments. Juvenile of two species of mullets (Mugil liza and Mugil curema) add up to more than 70% of the total catches in both environments. The hypothesized signal of decadal diversity and abundance reduction seems to be muffled by seasonal environmental fluctuation revealing that fish assemblage of MACA and TRE are highly resilient through the years. The only observed interdecadal trend was the reduction in abundance of juvenile M. liza that seems to parallel the reduction in abundance of the adults fishing stocks in southern Brazil.
Interleukin-1β Inhibition for Chronic Kidney Disease in Obese Mice With Type 2 Diabetes

Inflammasome-driven release of interleukin(IL)-1β is a central element of many forms of sterile inflammation and has been evident to promote the onset and progression of diabetic kidney disease. We microdissected glomerular and tubulointerstitial samples from kidney biopsies of patients with diabetic kidney disease and found expression of IL-1β mRNA. Immunostaining of such kidney biopsies across a broad spectrum of diabetic kidney disease stages revealed IL-1β positivity in a small subset of infiltrating immune cell. Thus, we speculated on a potential of IL-1β as a therapeutic target and neutralizing the biological effects of murine IL-1β with a novel monoclonal antibody in uninephrectomized diabetic db/db mice with progressive type 2 diabetes- and obesity-related single nephron hyperfiltration, podocyte loss, proteinuria, and progressive decline of total glomerular filtration rate (GFR). At 18 weeks albuminuric mice were randomized to intraperitoneal injections with either anti-IL-1β or control IgG once weekly for 8 weeks. During this period, anti-IL-1β IgG had no effect on food or fluid intake, body weight, and fasting glucose levels. At week 26, anti-IL-1β IgG had reduced renal mRNA expression of kidney injury markers (Ngal) and fibrosis (Col1, a-Sma), significantly attenuated the progressive decline of GFR in hyperfiltrating diabetic mice, and preserved podocyte number without affecting albuminuria or indicators of single nephron hyperfiltration. No adverse effect were observed. Thus, IL-1β contributes to the progression of chronic kidney disease in type 2 diabetes and might therefore be a valuable therapeutic target, potentially in combination with drugs with different mechanisms-of-action such as RAS and SGLT2 inhibitors.
Transfer Free Energies of Test Proteins Into Crowded Protein Solutions Have Simple Dependence on Crowder Concentration

The effects of macromolecular crowding on the thermodynamic properties of test proteins are determined by the latter's transfer free energies from a dilute solution to a crowded solution. The transfer free energies in turn are determined by effective protein-crowder interactions. When these interactions are modeled at the all-atom level, the transfer free energies may defy simple predictions. Here we investigated the dependence of the transfer free energy (Δμ) on crowder concentration. We represented both the test protein and the crowder proteins atomistically, and used a general interaction potential consisting of hard-core repulsion, non-polar attraction, and solvent-screened electrostatic terms. The chemical potential was rigorously calculated by FMAP (Qin and Zhou, 2014), which entails expressing the protein-crowder interaction terms as correlation functions and evaluating them via fast Fourier transform (FFT). To high accuracy, the transfer free energy can be decomposed into an excluded-volume component (Δμe−v), arising from the hard-core repulsion, and a soft-attraction component (Δμs−a), arising from non-polar and electrostatic interactions. The decomposition provides physical insight into crowding effects, in particular why such effects are very modest on protein folding stability. Further decomposition of Δμs−a into non-polar and electrostatic components does not work, because these two types of interactions are highly correlated in contributing to Δμs−a. We found that Δμe−v fits well to the generalized fundamental measure theory (Qin and Zhou, 2010), which accounts for atomic details of the test protein but approximates the crowder proteins as spherical particles. Most interestingly, Δμs−a has a nearly linear dependence on crowder concentration. The latter result can be understood within a perturbed virial expansion of Δμ (in powers of crowder concentration), with Δμe−v as reference. Whereas the second virial coefficient deviates strongly from that of the reference system, higher virial coefficients are close to their reference counterparts, thus leaving the linear term to make the dominant contribution to Δμs−a.
Breast Metastasis of Serous Ovarian Papillary Carcinoma: A Report of Two Cases Diagnosed by Fine-Needle Aspiration

Breast metastases from gynecologic cancer are infrequent and are mainly from the ovary. They usually appear in advanced stages and have poor survival rates after diagnosis. Two cases of breast metastasis of serous ovarian carcinoma are presented. In both cases fine-needle aspiration (FNA) study of breast revealed a lesion with morphologic characteristics of serous carcinoma, while one of them was with immunocytochemical study. Origin was confirmed by histological examination of this lesion.
Asenapine for the treatment of bipolar disorder

ABSTRACT Introduction: Bipolar I disorder (BDI) is amongst the most debilitating psychiatric conditions with a great impact on both patients and their families. A class of drugs commonly used in this condition is second-generation antipsychotics (SGAs) including asenapine, one of the latest to be introduced into the clinical practice worldwide to treat manic episodes in BDI. Areas covered: The aim of this paper is to critically review the literature on the pharmacological characteristics, tolerability, and safety data of asenapine, as well as on its short- and long-term clinical trials in manic episodes as both a monotherapy and as an add-on treatment. Expert opinion: The available data indicate that asenapine is an effective antimanic agent in both adult and pediatric patients and that it might also improve depressive symptoms and recurrences in BDI patients. Its tolerability profile is good, and its most common side effects are somnolence, light extrapyramidal symptoms, dizziness, weight gain, and oral (but reversible) hypoesthesia. Taken together, the published studies indicate that asenapine might be an effective therapeutic agent in BDI with a broad spectrum of clinical activities. Further double-blind, short- and long-term studies are, however, necessary to clarify its precise role in the treatment of BD.
Binding Modes and Metabolism of Caffeine

A correct estimate of ligand binding modes and a ratio of their occupancies is crucial for calculations of binding free energies. The newly developed method BLUES combines molecular dynamics with nonequilibrium candidate Monte Carlo. Nonequilibrium candidate Monte Carlo generates a plethora of possible binding modes and molecular dynamics enables the system to relax. We used BLUES to investigate binding modes of caffeine in the active site of its metabolizing enzyme Cytochrome P450 1A2 with the aim of elucidating metabolite-formation profiles at different concentrations. Because the activation energies of all sites of metabolism do not show a clear preference for one metabolite over the others, the orientations in the active site must play a key role. In simulations with caffeine located in a spacious pocket above the I-helix, it points N3 and N1 to the heme iron, whereas in simulations where caffeine is in close proximity to the heme N7 and C8 are preferably oriented toward the heme iron. We propose a mechanism where at low caffeine concentrations caffeine binds to the upper part of the active site, leading to formation of the main metabolite paraxanthine. On the other hand, at high concentrations two molecules are located in the active site, forcing one molecule into close proximity to the heme and yielding metabolites theophylline and trimethyluretic acid. Our results offer an explanation of previously published experimental results.
Using semantic web and service oriented technologies to build loosely coupled systems: SWOAT - a service and semantic web oriented architecture technology

The creation of loosely coupled and flexible applications has been a challenge faced by most organizations. This has been important because organization systems need to quickly respond and adapt to changes that occur in the business environment. In order to address these key issues, we implemented SWOAT, a ‘Service and Semantic Web Oriented Architecture Technology’ based middleware. Our system uses ontologies to semantically describe and formalize the information model of the organization, providing a global and integrated view over a set of database systems. It also allows interoperability with several systems using Web Services. Using ontologies and Web services, clients remain loosely coupled from data sources. As a result, data structures can be changed and moved without having to change all clients, internal or external to the organization.
Crosslinker co-polymerisation for property control in inverse vulcanisation.

Sulfur is an underused by-product of the petrochemicals industry. Recent research into inverse vulcanisation has shown how this excess sulfur can be transformed into functional polymers, by stabilization with organic crosslinkers. For these interesting new materials to realise their potential for applications, more understanding and control of their physical properties is needed. Here we report four new terpolymers prepared from sulfur and two distinct alkene monomers that can be predictively tuned in glass transition, molecular weight, solubility, mechanical properties, and colour.
Harvesting Energy from Vibrations by a Micromachined Electret Generator

The development of low power autonomous systems has triggered the research for waste energy recuperation. A micromachined generator has been designed to extract energy from vibrations in the ambient. It consists of an electrostatic transducer which is continuously polarized by an electret. The design of the generator has been optimized towards miniaturization. A prototype has been fabricated.
2 . Case management : problems and possibilities

We are now in a period of changing structures, organisations and vocabularies. Hence, it is probably helpful to begin with a definition of terms. Care Management and Case Management are phrases which are currently assuming such currency that their meaning may be lost in a blur of positive value as has happened in recent years to words such as ‘community’ or ‘decentralisation’. Within the Griffiths report (1988) and the prior influential Report of the Audit Commission (1986) are two potentially distinct definitions of the organisational position of those who could be seen as care managers or case managers. The Audit Commission (1986) recommended (para. 174): ‘A single budget under the control of a single manager who will purchase from whichever public or private agency he sees fit the appropriate services for elderly people in the community’. It would be easy to understand this as that of a resource manager at a relatively high tier in an organisation rather than that of a case manager in the sense of being a key worker and close to the client. On the other hand Griffiths (1988) recommended (para. 6.6): ‘In cases where a significant level of resources are involved a "care manager" should be nominated from within the social service authority’s staff to oversee the assessment and reassessment function and manage the resulting action. ’ To provide a distinction between care management and case management I take the definition of case management to be the
Characterization of the developmental dynamics of the elongation of a bamboo internode during the fast growth stage.

Previous studies on the fast growth of bamboo shoots mainly focused on the entire culm. No work about the fast elongation of a single internode, which is the basic unit for the fast growth of bamboo shoots, has been reported so far according to our knowledge. In this study, we have systematically investigated the regulating mechanisms underlying the fast growth of a single bamboo internode of Bambusa multiplex. We discover that the growth of the internode displays a logistic pattern, and the two parts located in the bottom of the internode, one for cell division, another for cell elongation and each with a ~ 1-cm length, comprise the effective zones for the internode growth. RNA-Seq analysis reveals a number of key candidate genes potentially involved in regulating the fast growth of bamboo shoots, including those in the hormone pathway such as auxin as well as the downstream target genes involved in cell wall development and cell division, were identified. Further analysis discovers that sugar plays an important role in promoting the fast growth of bamboo internodes through inhibition of BmSnf1. Mechanical stress is found to be involved in the triggering of the internode growth decrease through activation of the generation of reactive oxygen species (ROS) by upregulating CaMs. Those results provide systematic insight into the biological mechanisms underlying the fast growth of bamboo shoots based on a single internode behavior.
Virtual Network Embedding Algorithm Considering Resource Fragmentation in Virtualized Industrial Fiber-Wireless (FiWi) Access Network

As the traditional networks cannot meet the growing bandwidth and flexibility requirements of industry users, the big data transmission from end devices to the cloud server is becoming the bottleneck to the development of industry Internet. Fiber-Wireless (FiWi) access network which combines the advantages of optical and wireless networks has caught a wide attention and become a promising solution. However, different protocols as well as resource scheduling mechanisms between optical and wireless subnetworks of FiWi access network pose a huge challenge to its seamless integration and resource optimization. Network virtualization, which allows several Virtual Networks (VNs) running independently on the common Substrate Network (SN) and provides customized services to end users, becomes an effective solution for the network ossification problem of industry FiWi access network. However, due to the diverse needs for node and link resources of industrial VNs, the residual resources of nodes and links in SN may easily become unbalanced during the Virtual Network Embedding (VNE), which impairs the resource utilization of SN. Considering the resource fragmentation problem in VNE approaches, an online VNE algorithm is proposed in this paper. Our work aims to improve the VN acceptance ratio and SN resource utilization through minimizing the resource occupied by VNs and reducing the resource fragmentation degree of SN.