Miracle-dz/UniFAR-FTUs huggingface dataset:
Hippocampal-Prefrontal Interactions during Spatial Decision-Making

The hippocampus has been linked to memory encoding and spatial navigation, while the prefrontal cortex is associated with cognitive functions such as decision-making. These regions are hypothesized to communicate in tasks that demand both spatial navigation and decision-making processes. However, the electrophysiological signatures underlying this communication remain to be better elucidated. To investigate the dynamics of the hippocampal-prefrontal interactions, we have analyzed their local field potentials and spiking activity recorded from rats performing an odor-cued spatial alternation task in an 8-shaped maze. We found that the phase coherence of theta peaked around the choice point area of the maze. Moreover, Granger causality revealed a hippocampus->prefrontal cortex directionality of information flow at theta frequency, peaking at starting areas of the maze, and on the reverse direction at delta frequency, peaking near the turn onset. Additionally, the patterns of phase-amplitude cross-frequency coupling within and between the regions also showed spatial selectivity, and a new method revealed that hippocampal theta and prefrontal delta modulated not only gamma amplitude but also inter-regional gamma synchrony. Lastly, we found that the theta rhythm dynamically modulated neurons in both regions, with the highest modulation at the choice area; interestingly, prefrontal cortex neurons were more strongly modulated by the hippocampal theta rhythm than by their local field rhythm. In all, our results reveal maximum electrophysiological interactions between the hippocampus and the prefrontal cortex near the decision-making period of the spatial alternation task. These results corroborate the hypothesis that a dynamic interplay between these regions takes place during spatial decisions.
13C Electron Nuclear Double Resonance Spectroscopy Shows Acetyl-CoA Synthase Binds Two Substrate CO in Multiple Binding Modes and Reveals the Importance of a CO-Binding ‘Alcove’

EPR and Electron Nuclear Double Resonance spectroscopies here characterize CO binding to the active-site A cluster of wild-type (WT) Acetyl-CoA Synthase (ACS) and two variants, F229W and F229A. The A-cluster binds CO to a proximal Ni (Nip) that bridges a [4Fe-4S] cluster and distal Nid. An alcove seen in the ACS crystal-structure near the A-cluster, defined by hydrophobic residues including F229, forms a cage surrounding a Xe mimic of CO and is suggested to ‘cradle’ this CO. Previously, we only knew WT ACS bound a single CO in the Ared-CO intermediate, here seen as forming Nip(I)-CO with CO on-axis of the dz2 odd-electron orbital (g⊥>g‖∼2). The two-dimensional field-frequency pattern of 2K-35 GHz 13C-ENDOR spectra collected across the Ared-CO EPR envelope now reveals a second CO bound in the dz2 orbital’s equatorial plane. This WT A-cluster conformer dominates the nearly-conservative F229W variant, but 13C-ENDOR reveals a minority “A” conformation with (g‖>g⊥∼2) characteristic of a ‘cloverleaf’ (eg. dx2-y2) odd-electron orbital, and with Nip binding two, apparently ‘in-plane’ CO. Disruption of the alcove through introduction of the smaller alanine residue in the F229A variant diminishes conversion to Ni(I) ∼tenfold and introduces extensive cluster flexibility. 13C-ENDOR shows the F229A cluster is mostly (60%) in the “A” conformation, but with ∼20% each of the WT conformer and an “O” state in which dz2 Nip(I) (g⊥>g‖∼2) surprisingly lacks CO. This paper thus demonstrates the importance of an intact alcove in forming and stabilizing the Ni(I)-CO intermediate in the Wood-Ljungdahl pathway of anaerobic CO and CO2 fixation.
Variability of dynamic patterns of cortical excitability in schizophrenia: A test-retest TMS-EEG study

Background Altered stimuli processing is a key feature of schizophrenia. Application of concurrent transcranial magnetic stimulation (TMS) with electroencephalography (TMS-EEG) is an effective stimulus which allows direct measurement of the cortical response within a millisecond time resolution. Test-retest TMS-EEG studies present evidence of high reproducibility in healthy controls (HC), however, this stability of response has not been examined in schizophrenia. Objective The current study maps TMS-evoked patterns of cortical excitability in schizophrenia and examine whether these cortical patterns are amenable to change as symptoms of schizophrenia improve. Methods One hundred single-pulse TMS and 100 sham pulses were applied to frontal regions of 19 schizophrenia in-patients and 26 HC while electroencephalography data were simultaneously acquired. Medication and schizophrenia symptoms were reported. This protocol was repeated across three sessions (1 week apart) for each participant. The TMS-evoked cortical response of each participant was averaged and compared between groups. Results Schizophrenia patients showed reduced cortical excitability at early time-windows and increased excitability at later time-windows. Increased excitability at later windows was associated with heightened symptom severity. Schizophrenia patients showed an increased variability in cortical response over sessions relative to HC. Increased change in cortical response from session 1 to session 3 correlated with symptom improvement. Conclusions Schizophrenia patients presented with abnormal patterns of cortical excitability when processing TMS stimuli. These dynamic patterns of cortical response were amenable to change as symptoms of schizophrenia improved. Further research into electrophysiological biomarkers of symptom improvement is hoped to improve current diagnosis and treatment models of schizophrenia.
Evidence Indicating That Argentine Populations of Anastrepha fraterculus (Diptera: Tephritidae) Belong to a Single Biological Species

Abstract Anastrepha fraterculus (Wiedmann), a South American fruit fly, is an economically important pest for fruit-bearing plants of the neotropical region. Some evidence indicates that the nominal A. fraterculus comprises multiple cryptic species. In the current work we analyzed genetic variability and structure in Argentine populations of A. fraterculus based on eight isoenzymatic loci and the restriction patterns of a fragment of ≈500 bp belonging to the 16 S mitochondrial ribosomal DNA. The isoenzymatic analysis indicated a significant excess of homozygotes (FIS > 0), due to the fact that sampling sites probably do not constitute stable Mendelian populations. Genetic similarities ranged within values expected for conspecific populations and gene flow, estimated indirectly from the FST value, was high. The phenogram obtained by unweighted pair-group method with arithmetic average among populations shows disagreements with the expected result based on geographic distribution. Populations located in the neighborhood of Buenos Aires City show high diversity probably due to a high migration rate from different regions. The polymerase chain reaction (PCR)+restriction fragment-length polymorphism (RFLP) analysis of the mtDNA fragment involved 11 Argentine and one south Brazilian populations. The PCR product was digested by three endonucleases: Ssp-I, Ase-I, and Mnl-I. The observed patterns showed no variation within nor among the populations studied here but differed from the expected results based on the sequences recorded by other researchers for populations of north Brazil, Venezuela, and Mexico. The results so far obtained indicate that, despite the occurrence of macrogeographical variation, the Argentine and south Brazilian populations studied here belong to a single biological species.
Thin Film Metallization Stacks Serve as Reliable Conductors on Ceramic-based Substrates for Active Implants

Hermetic and non-hermetic packages of active implantable medical devices are often fabricated of ceramics like alumina. Screen printed PtAu paste is the state of the art metallization for functional structures. Due to solid state and liquid diffusion of Au at thermal exposure, solder times are limited; otherwise metal structures tend to delaminate. Moreover, it was shown that PtAu with solder fails after 37.4 years. We established a thin film metallization on alumina process to overcome these disadvantages. The metallization consists of sputtered platinum with an underlying adhesion layer made of tungsten-titanium to increase the adhesion strength to the alumina substrate. We avoided using gold in this work due to its high diffusion tendency. Instead, the materials in use provide relatively low diffusion properties, which potentially increases the long term mechanical performance and usability during assembly and packaging. Utilizing the Design of Experiment (DoE) methodology, we derived an optimal Pt thickness of 500 nm with 43 nm of WTi as adhesion promoting layer. After accelerated aging at 150 °C, corresponding to 125 years at body temperature (37 °C), the contact pad adhesion strength was with 32.75 MPa ± 7.08 MPa still significantly higher than the safety limit of 17 MPa, following the recommendations for a robust screen-printing metallization process. Moreover, soldering times of up to 120 s did not influence the adhesive strength. The new process reduced the minimum track distance to 50% of screen printing values and is capable of rapid prototyping. It helps to make the assembly process independent of the manufacturing person, to increase the yield of device fabrication and -most important in implantable device manufacturing-to make it more robust and thereby more safe for the patient.
Exploring the evolution of GANs through quality diversity

Generative adversarial networks (GANs) achieved relevant advances in the field of generative algorithms, presenting high-quality results mainly in the context of images. However, GANs are hard to train, and several aspects of the model should be previously designed by hand to ensure training success. In this context, evolutionary algorithms such as COEGAN were proposed to solve the challenges in GAN training. Nevertheless, the lack of diversity and premature optimization can be found in some of these solutions. We propose in this paper the application of a quality-diversity algorithm in the evolution of GANs. The solution is based on the Novelty Search with Local Competition (NSLC) algorithm, adapting the concepts used in COEGAN to this new proposal. We compare our proposal with the original COEGAN model and with an alternative version using a global competition approach. The experimental results evidenced that our proposal increases the diversity of the discovered solutions and leverage the performance of the models found by the algorithm. Furthermore, the global competition approach was able to consistently find better models for GANs.
Distribution of Molecules Related to Neurotransmission in the Nervous System of the Mussel Crenomytilus grayanus

In bivalves neurotransmitters are involved in a variety of behaviors, but their diversity and distribution in the nervous system of these organisms remains somewhat unclear. Here, we first examined immunohistochemically the distributions of neurons containing different neurotransmitters, neuropeptides, and related enzymes, as well as the proliferative status of neurons in the ganglia of the mussel Crenomytilus grayanus. H-Phe-Met-Arg-Phe-NH2 (FMRFamide), choline acetyltransferase (ChAT), γ-aminobutyric acid (GABA) and tyrosine hydroxylase (TH) were found to be expressed by neurons in all the ganglia, whereas serotonin (5-HT) neurons were found only in the cerebropleural and pedal, but not visceral ganglia. Moreover, incubation of living mussels in the presence of a 5-HT precursor (5-HTP) confirmed the absence of 5-HT-containing neurons from the visceral ganglia, indicating that the “serotonin center” of the visceral nervous system is located in the cerebral ganglia. Furthermore, immunostaining of molecules related to neurotransmission together with α-acetylated tubulin demonstrated that this cytoskeletal protein may be a potential pan-neuronal marker in bivalves. Adult mussel neurons do not proliferate, but a population of proliferating PCNA-LIP cells which do not express any of the neurotransmitters examined, perhaps glia cells, was detected in the ganglia. These novel findings suggest that the nervous system of bivalves contains a broad variety of signal molecules most likely involved in the regulation of different physiological and behavioral processes. In addition, proliferating cells may maintain and renew glial cells and neurons throughout the lives of bivalves.
Upregulated TRAIL and Reduced DcR2 Mediate Apoptosis of Decidual PMN-MDSC in Unexplained Recurrent Pregnancy Loss

Myeloid-derived suppressor cells (MDSC), especially polymorphonuclear MDSC (PMN-MDSC), accumulate in maternal-fetal interface during pregnancy and are involved in the maintenance of immune tolerance. Decreased PMN-MDSC is associated with pregnancy complications such as unexplained recurrent pregnancy loss (URPL). In the present study we showed decreased PMN-MDSC in the URPL group compared with the normal pregnancy (NP) group, and PMN-MDSC was the major subset of MDSC in human decidua with potent immune suppression activity. We then performed gene expression profile and found that human decidual PMN-MDSC in the NP and URPL groups showed different gene and pathway signature, including apoptosis. Apoptosis of decidual PMN-MDSC was mediated by TNF-related apoptosis–induced ligand (TRAIL) in a Caspase 3 dependent manner. TRAIL was expressed in decidua and upregulated in decidua of the URPL group. Notably, of all the membrane TRAIL receptors, only DcR2 was down-regulated in PMN-MDSC in the URPL group. In vitro experiment demonstrated that DcR2 blockade sensitized PMN-MDSC to TRAIL-mediated apoptosis. Together, these data indicate that increased TRAIL and reduced DcR2 on PMN-MDSC sensitize PMN-MDSC response to TRAIL-induced apoptosis in the URPL group, which is responsible for decreased accumulation of PMN-MDSC in URPL.
Dopamine-related striatal neurophysiology is associated with specialization of frontostriatal reward circuitry through adolescence

Characterizing developmental changes in frontostriatal circuitry is critical to our understanding of adolescent development and can clarify neurobiological mechanisms underlying increased reward sensitivity and sensation seeking, and the emergence of psychopathology during this period. However, the role of striatal neurobiology in the development of frontostriatal circuitry through human adolescence remains largely unknown. We combine longitudinal MR-based assessments of striatal tissue-iron as a correlate of dopamine-related neurobiology with functional magnetic resonance imaging indices of resting-state and reward-state connectivity to investigate the contribution of dopaminergic processes to developmental changes in frontostriatal circuitry. Connectivity between the nucleus accumbens and ventral anterior cingulate, subgenual cingulate, and orbitofrontal cortices decreased through adolescence into adulthood. Nucleus accumbens tissue-iron mediated age-related changes and was associated with variability in connectivity. Our results provide evidence that developmental changes in dopamine-related striatal properties contribute to specialization of frontostriatal circuitry, potentially underlying changes in sensation seeking and reward sensitivity into adulthood.
The effects of season and age of stand on the nutritive value of heather (Calluna vulgaris, L. Hull) to sheep

SUMMARY In two experiments frozen heather (Calluna vulgaris, L. Hull), which contained 85–90% of the current season's shoots, was offered ad libitum to castrated male sheep. In one experiment, heather harvested in July, September, November and March was offered to six sheep per harvest, D.M. digestibility fell from 55.9% in July to 41.9% in March, with the greatest decline occurring after flower development in August. There were no significant changes with season in voluntary intakes, which were low, ranging from 29 to 39 g D.M. /kg W0.75/day. Apart from the July harvest, intakes of digestible D.M. were insufficient to maintain the sheep. The apparent digestibility of N(14·3–42·2%) and plasma urea N values (5–6 mg/100 ml) were low and undigested N of dietary origin in the faeces was high (25–45%). Sheep offered the September, November and March harvests were in considerable negative apparent balances of N and it was calculated that the sheep were in a negative balance of truly digested N. In a second ex-periment, heather harvested in August from pioneer, building and mature stands was offered to six sheep per harvest. There were no significant differences between stands in voluntary intake and digestibility.
Desenvolvimento de uma prova de imunoadsorção enzimática para detecção de anticorpos contra Babesia bovis

An enzyme-linked immunosorbent assay (ELISA) for antibodies to Babesia bovis was developed and evaluated in comparison with the indirect fluorescent antibody test (IFAT). The ELISA sensitivity and specificity, estimated with 100 positive sera from cattle experimentally infected with B. bovis and 108 negative sera collected from B. bovis-free herds, were 98.0% and 98.1%, respectively. Positive and negative predictive values were, respectively, 98.0% and 98.1%, and precision was 98.1%. No cross-reactions were detected with 80 sera from calves experimentally inoculated with Babesia bigemina. The ELISA was compared with IFAT using 110 cattle sera from an enzootically stable area and with 168 cattle sera from an enzootically unstable area. In both cases, there was a significant agreement between results of both tests (P=0.631 and 0.4725, respectively). In an epidemiological study performed with ELISA in the Pantanal region of the State of Mato Grosso do Sul with 1,365 cattle sera, 83.9% were positive for antibodies against B. bovis, characterizing this region as enzootically stable.
The Role of the P1 and P2 Promoter-Driven HNF4a Isoforms in Cellular Proliferation and Differentiation in Human Colon Cancer and Mouse Embryonic Stem Cells

Cellular proliferation and differentiation are critical events in normal development and cancer. Despite decades of research, much remains to be learned about how cells transition between the two states. To decipher one aspect of this switch, we focused on the transcription factor, Hepatocyte Nuclear Factor (HNF) 4 alpha. HNF4a is a nuclear receptor that is important in development and in maintaining the homoeostasis of the adult liver and colon. There are multiple isoforms of the HNF4a that are generated by alterative promoter (P1 and P2) usage and 3' splicing events in different tissues. Both P1 and P2-HNF4a isoforms are expressed in the adult colon, while the P1-HNF4a is expressed in the adult liver. Others have shown that P1-HNF4a is downregulated in cancer, whereas P2-HNF4a is upregulated in hepatocellular carcinoma and colorectal cancer. This would suggest that P1-HNF4a is tumor suppressive, while P2-HNF4a may act as an oncogene although a mechanism has not been elucidated. One potential mechanism could be through a differential interplay with the Wnt/beta-catenin/TCF pathway, which is activated in many cancers including liver and colon. To determine whether HNF4a and TCF4 cross-talk to control the switch between proliferation and differentiation and to elucidate the role of the HNF4a isoforms in early development and cancer, we generated Tet-On inducible systems that express either HNF4a2 (P1) or HNF4a8 (P2) under the control of doxycycline in human colon cancer and mouse embryonic stem cells. We characterized the lines to look for morphological and functional differences between the isoforms. We performed RNA-Seq and ChIP-Seq on the HCT116 inducible lines to identify any changes in gene expression and regulation and compared the HNF4a2 and HNF4a8 lines to determine functional differences. Although we found some functional redundancy, there are discrete differences. HNF4a2 suppresses tumor growth, inhibits cellular proliferation, and competes with TCF4 for regulation of target genes more effectively than HNF4a8. Similarly, we also found that HNF4a2 decreases cell numbers more than HNF4a8 in the mES inducible lines. Our findings provide insight into the distinct role of the P1- and P2-HNF4a in cancer and normal development.
The influence of a 15-hydroxy group on the rearrangement reactions of steviol and its 16,17-epoxide

A 15-hydroxy group prevents the steviol/isosteviol rearrangement taking place. In the presence of hydrobromic acid, the 15α-alcohol undergoes rearrangement to a 17-alcohol whilst the 15β-alcohol gives the 15-ketones. Treatment of a 15α-hydroxy-16,17-epoxide gives the 15α,16α-dihydroxy-17-bromide, the structure of which was confirmed by X-ray analysis.
Gene Set Analysis: Challenges, Opportunities, and Future Research

Gene set analysis methods are widely used to provide insight into high-throughput gene expression data. There are many gene set analysis methods available. These methods rely on various assumptions and have different requirements, strengths and weaknesses. In this paper, we classify gene set analysis methods based on their components, describe the underlying requirements and assumptions for each class, and provide directions for future research in developing and evaluating gene set analysis methods.
Lateralized learning for robustness against adversarial attacks in a visual classification system

Deep learning is an important field of machine learning. It is playing a critical role in a variety of applications ranging from self-driving cars to security and surveillance. However, deep networks have deep flaws. For example, they are highly vulnerable to adversarial attacks. One reason may be the homogeneous nature of their knowledge representation, which allows a single disruptive pattern to cause miss-classification. Biological intelligence has lateral asymmetry, which allows heterogeneous, modular learning at different levels of abstraction, enabling different representations of the same object. This work aims to incorporate lateralization and modular learning at different levels of abstraction in an evolutionary machine learning system. The results of image classification tasks show that the lateralized system efficiently learns hierarchical distributions of knowledge, demonstrating performance that is similar to (or better than) other state-of-the-art deep systems as it reasons using multiple representations. Crucially, the novel system outperformed all the state-of-the-art deep models for the classification of normal and adversarial images by 0.43% -- 2.56% and 2.15% -- 25.84%, respectively. Lateralisation enabled the system to exhibit robustness beyond previous work, which advocates for the creation of data sets that enable components of objects and the objects themselves to be learned specifically or in an end-to-end manner.
GLP-1 Receptor Agonists in Diabetic Kidney Disease: From Clinical Outcomes to Mechanisms

Diabetic Kidney Disease (DKD) is the leading cause of end stage renal disease (ESRD) worldwide. Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are now widely used in the treatment of patients with type 2 diabetes (T2D). A series of clinical and experimental studies demonstrated that GLP-1RAs have beneficial effects on DKD, independent of their glucose-lowering abilities, which are mediated by natriuresis, anti-inflammatory and anti-oxidative stress properties. Furthermore, GLP-1RAs have been shown to suppress renal fibrosis. Recent clinical trials have demonstrated that GLP-1RAs have beneficial effects on renal outcomes, especially in patients with T2D who are at high risk for CVD. These findings suggest that GLP-1RAs hold great promise in preventing the onset and progression of DKD. However, GLP-1RAs have only been shown to reduce albuminuria, and their ability to reduce progression to ESRD remains to be elucidated. In this review article, we highlight the current understanding of the clinical efficacy and the mechanisms underlying the effects of GLP-1RAs in DKD.