Miracle-dz/UniFAR-FTUs huggingface dataset:
Neuronal Nitric Oxide Synthase in Nucleus Accumbens Specifically Mediates Susceptibility to Social Defeat Stress through Cyclin-Dependent Kinase 5

Stress-induced depression is common worldwide. NAc, a “reward” center, is recently reported to be critical to confer the susceptibility to chronic social defeat stress (CSDS) and the depression-related outcome. However, the underlying molecular mechanisms have not been well characterized. Stress-induced depression is common worldwide. NAc, a “reward” center, is recently reported to be critical to confer the susceptibility to chronic social defeat stress (CSDS) and the depression-related outcome. However, the underlying molecular mechanisms have not been well characterized. In this study, we induced depression-like behaviors with CSDS and chronic mild stress in male mice to mimic social and environmental factors, respectively, and observed animal behaviors with social interaction test, tail suspension test, and sucrose preference test. To determine the role of neuronal nitric oxide synthase (nNOS) and its product nitric oxide (NO), we used brain region-specifically nNOS overexpression and stereotaxic injection of NO inhibitor or donor. Moreover, the downstream molecular cyclin-dependent kinase 5 (CDK5) was explored by conditional KO and gene mutation. We demonstrate that nNOS-implicated mechanisms in NAc shell (NAcSh), including increased cell number, increased protein expression levels, and increased specific enzyme activity, contribute the susceptibility to social defeat and the following depression-like behaviors. NAcSh nNOS does not directly respond to chronic mild stress but facilitates the depression-like behaviors. The increased NAcSh nNOS expression after CSDS leads to the social avoidance and depression-like behaviors in defeated mice, which is dependent on the nNOS enzyme activity and NO production. Moreover, we identify the downstream signal in NAcSh. S-nitrosylation of CDK5 by NO contributes to enhanced CDK5 activity, leading to depression-related behaviors in susceptible mice. Therefore, NAcSh nNOS mediates susceptibility to social defeat stress and the depression-like behaviors through CDK5. SIGNIFICANCE STATEMENT Stress-induced depression is common worldwide, and chronic exposure to social and psychological stressors is important cause of human depression. Our study conducted with chronic social defeat stress mice models demonstrates that nNOS in NAcSh is crucial to regulate the susceptibility to social defeat stress and the following depression-like behaviors, indicating NAcSh nNOS as the responding molecule to social factors of depression. Moreover, we discover the downstream mechanism of NAcSh nNOS in mediating the susceptibility is NO and S-nitrosylation of CDK5. Thus, NAcSh nNOS mediates susceptibility to social defeat stress through CDK5 is a potential mechanism for depression, which may interpret how the brain transduces social stress exposure into depression.
Methodological issues in assessing change in dietary intake and appetite following gastric bypass surgery: A systematic review

Gastric bypass surgery is an effective long‐term treatment for individuals with severe obesity. Changes in appetite, dietary intake, and food preferences have all been postulated to contribute to postoperative body weight regulation, however, findings are inconsistent. The aim of this systematic review was to evaluate the current literature on changes in dietary intake and appetite following gastric bypass surgery, in the context of the methodology used and the analysis, interpretation, and presentation of results. Four databases were systematically searched with terms related to “gastric bypass surgery,” “appetite,” and “dietary intake,” and 49 papers (n = 2384 patients after gastric bypass) were eligible for inclusion. The evidence indicated that only a reduction in overall energy intake and an increase in postprandial satiety are maintained beyond 6‐month post‐surgery, whereas relative macronutrient intake and premeal hunger remain unchanged. However, available data were limited by inconsistencies in the methods, analysis, presentation, and interpretation of results. In particular, there was a reliance on data collected by subjective methods with minimal acknowledgment of the limitations, such as misreporting of food intake. There is a need for further work employing objective measurement of appetite and dietary intake following gastric bypass surgery to determine how these mechanisms may contribute to weight regulation in the longer term.
Antimicrobial Activity of Zinc Oxide Nano/Microparticles and Their Combinations against Pathogenic Microorganisms for Biomedical Applications: From Physicochemical Characteristics to Pharmacological Aspects

Zinc oxide (ZnO) nano/microparticles (NPs/MPs) have been studied as antibiotics to enhance antimicrobial activity against pathogenic bacteria and viruses with or without antibiotic resistance. They have unique physicochemical characteristics that can affect biological and toxicological responses in microorganisms. Metal ion release, particle adsorption, and reactive oxygen species generation are the main mechanisms underlying their antimicrobial action. In this review, we describe the physicochemical characteristics of ZnO NPs/MPs related to biological and toxicological effects and discuss the recent findings of the antimicrobial activity of ZnO NPs/MPs and their combinations with other materials against pathogenic microorganisms. Current biomedical applications of ZnO NPs/MPs and combinations with other materials are also presented. This review will provide the better understanding of ZnO NPs/MPs as antibiotic alternatives and aid in further development of antibiotic agents for industrial and clinical applications.
Strategies to Get Drugs across Bladder Penetrating Barriers for Improving Bladder Cancer Therapy

Bladder cancer is a significant public health concern and social burden due to its high recurrence risk. Intravesical drug instillation is the primary therapy for bladder cancer to prevent recurrence. However, the intravesical drug therapeutic effect is limited by bladder penetrating barriers. The inadequate intravesical treatment might cause the low drug concentration in lesions, resulting in a high recurrence/progression rate of bladder cancer. Many strategies to get drugs across bladder penetrating barriers have been developed to improve intravesical treatment, including physical and chemical methods. This review summarizes the classical and updated literature and presents insights into great therapeutic potential strategies to overcome bladder penetrating barriers for improving the intravesical treatment of bladder cancer.
Exact short time dynamics for steeply repulsive potentials

The autocorrelation functions for the force on a particle, the velocity of a particle and the transverse momentum flux are studied for the power law potential v(r)=ε(σr)ν (soft spheres). The latter two correlation functions characterize the Green–Kubo expressions for the self-diffusion coefficient and shear viscosity. The short-time dynamics is calculated exactly as a function of ν. The dynamics is characterized by a universal scaling function S(τ), where τ=t/τν and τν is the mean time to traverse the core of the potential divided by ν. In the limit of asymptotically large ν this scaling function leads to delta function in time contributions in the correlation functions for the force and momentum flux. It is shown that this singular limit agrees with the special Green–Kubo representation for hard-sphere transport coefficients. The domain of the scaling law is investigated by comparison with recent results from molecular dynamics simulation for this potential.
Decoding and interpreting cortical signals with a compact convolutional neural network

Objective. Brain–computer interfaces (BCIs) decode information from neural activity and send it to external devices. The use of Deep Learning approaches for decoding allows for automatic feature engineering within the specific decoding task. Physiologically plausible interpretation of the network parameters ensures the robustness of the learned decision rules and opens the exciting opportunity for automatic knowledge discovery. Approach. We describe a compact convolutional network-based architecture for adaptive decoding of electrocorticographic (ECoG) data into finger kinematics. We also propose a novel theoretically justified approach to interpreting the spatial and temporal weights in the architectures that combine adaptation in both space and time. The obtained spatial and frequency patterns characterizing the neuronal populations pivotal to the specific decoding task can then be interpreted by fitting appropriate spatial and dynamical models. Main results. We first tested our solution using realistic Monte-Carlo simulations. Then, when applied to the ECoG data from Berlin BCI competition IV dataset, our architecture performed comparably to the competition winners without requiring explicit feature engineering. Using the proposed approach to the network weights interpretation we could unravel the spatial and the spectral patterns of the neuronal processes underlying the successful decoding of finger kinematics from an ECoG dataset. Finally we have also applied the entire pipeline to the analysis of a 32-channel EEG motor-imagery dataset and observed physiologically plausible patterns specific to the task. Significance. We described a compact and interpretable CNN architecture derived from the basic principles and encompassing the knowledge in the field of neural electrophysiology. For the first time in the context of such multibranch architectures with factorized spatial and temporal processing we presented theoretically justified weights interpretation rules. We verified our recipes using simulations and real data and demonstrated that the proposed solution offers a good decoder and a tool for investigating motor control neural mechanisms.
Aberrant Methylation of Tumour Suppressor Gene ADAM12 in Chronic Lympocytic Leukemia Patients: Application of Methylation Specific-PCR Technique

Objective: Chronic Lymphocytic Leukemia (CLL) is a common leukemia among Caucasians but rare in Asians population. We postulated that aberrant methylation either hypermethylation or partial methylation might be one of the silencing mechanisms that inactivates the tumour suppressor genes in CLL. This study aimed to compare the methylation status of tumour suppressor gene, ADAM12, among CLL patients and normal individuals. We also evaluated the association between methylation of ADAM12 and clinical and demographic characteristics of the participants. Methods: A total of 25 CLL patients and 25 normal individuals were recruited in this study. The methylation status of ADAM12 was determined using Methylation-Specific PCR (MSP); whereas, DNA sequencing method was applied for validation of the MSP results. Results: Among CLL patients, 12 (48%) were partially methylated and 13 (52%) were unmethylated. Meanwhile, 5 (20%) and 20 (80.6%) of healthy individuals were partially methylated and unmethylated, respectively. There was a statistically significant association between the status of methylation at ADAM12 and the presence of CLL (p=0.037). Conclusion: The aberrant methylation of ADAM12 found in this study using MSP assay may provide new exposure to CLL that may improve the gaps involved in genetic epigenetic study in CLL.
A tissue-engineered human trabecular meshwork hydrogel for advanced glaucoma disease modeling

Purpose Abnormal human trabecular meshwork (HTM) cell function and extracellular matrix (ECM) remodeling contribute to HTM stiffening in primary open-angle glaucoma (POAG). Most current cellular HTM model systems do not sufficiently replicate the complex native three dimensional (3D) cell-ECM interface, which makes them less than ideal to investigate POAG pathology. Tissue-engineered protein-based hydrogels are ideally positioned to overcome shortcomings of current models. Here, we report a novel biomimetic HTM hydrogel and test its utility as a POAG disease model. Methods HTM hydrogels were engineered by mixing normal donor-derived HTM cells with collagen type I, elastin-like polypeptide and hyaluronic acid, each containing photoactive functional groups, followed by UV light-activated free-radical crosslinking. Glaucomatous conditions were induced with dexamethasone (DEX), and therapeutic effects of the Rho-associated kinase (ROCK) inhibitor Y27632 on cytoskeletal organization and tissue-level function, contingent on HTM cell-ECM interactions, were assessed. Results DEX exposure increased HTM hydrogel contractility, f-actin and alpha smooth muscle actin abundance and rearrangement, ECM remodeling, and fibronectin and collagen type IV deposition, all contributing to HTM hydrogel condensation and stiffening consistent with recent data from normal vs. glaucomatous HTM tissue. Y27632 treatment produced precisely the opposite effects and attenuated the DEX-induced pathologic changes, resulting in HTM hydrogel relaxation and softening. Conclusions We have developed a biomimetic HTM hydrogel model for detailed investigation of 3D cell-ECM interactions under normal and simulated glaucomatous conditions. Its bidirectional responsiveness to pharmaceutical challenge and rescue suggests promising potential to serve as screening platform for new POAG treatments with focus on HTM biomechanics.
Identification of Key Pathways and Genes Related to the Development of Hair Follicle Cycle in Cashmere Goats

The development of hair follicle in cashmere goats shows significant periodic change, as with mice and humans. However, for cashmere goat with double-coat, the periodic change may be due to other regulatory molecules and signal pathways. To understand the mechanism of periodic development of hair follicle, we performed a weighted gene coexpression network analysis (WGCNA) to mine key genes and establish an interaction network by utilizing the NCBI public dataset. Ten coexpression modules, including 7689 protein-coding genes, were constructed by WGCNA, six of which are considered to be significantly related to the development of the hair follicle cycle. A functional enrichment analysis for each model showed that they are closely related to ECM- receptor interaction, focal adhesion, PI3K-Akt signaling pathway, estrogen signaling pathway, and so on. Combined with the analysis of differential expressed genes, 12 hub genes from coexpression modules were selected as candidate markers, i.e., COL1A1, C1QTNF6, COL1A2, AQP3, KRTAP3-1, KRTAP11-1, FA2H, NDUFS5, DERL2, MRPL14, ANTKMT and XAB2, which might be applied to improve cashmere production.
Nano-Hydroxyapatite Derived from Biogenic and Bioinspired Calcium Carbonates: Synthesis and In Vitro Bioactivity

Biogenic calcium carbonates naturally contain ions that can be beneficial for bone regeneration and therefore are attractive resources for the production of bioactive calcium phosphates. In the present work, cuttlefish bones, mussel shells, chicken eggshells and bioinspired amorphous calcium carbonate were used to synthesize hydroxyapatite nano-powders which were consolidated into cylindrical pellets by uniaxial pressing and sintering 800–1100 °C. Mineralogical, structural and chemical composition were studied by SEM, XRD, inductively coupled plasma/optical emission spectroscopy (ICP/OES). The results show that the phase composition of the sintered materials depends on the Ca/P molar ratio and on the specific CaCO3 source, very likely associated with the presence of some doping elements like Mg2+ in eggshell and Sr2+ in cuttlebone. Different CaCO3 sources also resulted in variable densification and sintering temperature. Preliminary in vitro tests were carried out (by the LDH assay) and they did not reveal any cytotoxic effects, while good cell adhesion and proliferation was observed at day 1, 3 and 5 after seeding through confocal microscopy. Among the different tested materials, those derived from eggshells and sintered at 900 °C promoted the best cell adhesion pattern, while those from cuttlebone and amorphous calcium carbonate showed round-shaped cells and poorer cell-to-cell interconnection.
MULTIFUNCTION AUTOMATIC RECORDING PHOTOMETRIC TITRATOR

A versatile automatic recording photometric titrator, suitable for colorimetric, nephelometric, and chemiluminescent indicator titrimetry, was assembled from a Precision-Dow recording potentiometric titrator, a modified Beckman Model B spectrophotometer, and necessary intermediate electronic components. The operation of the titrator is described and typical titration curves are shown. (auth)
Hierarchical Microstructure Informed Tractography

Background: Tractography uses diffusion magnetic resonance imaging to noninvasively infer the macroscopic pathways of white matter fibers and it is the only available technique to probe in vivo the structural connectivity of the brain. However, despite this unique and compelling ability and its wide range of possible neurological applications, tractography is still limited, lacks anatomical precision, and suffers from a serious sensitivity/specificity trade-off. For this reason, in the past few years, tractography postprocessing techniques have emerged and proved effective for improving the quality of the reconstructions. Among them, the Convex Optimization Modeling for Microstructure Informed Tractography formulation allows incorporating the anatomical prior that fibers are naturally organized in fascicles, and has obtained exceptional results in increasing the accuracy of the estimated tractograms. Methods: We propose an extension to this idea and introduce a multilevel grouping of the streamlines to capture the white matter arrangement in fascicles and subfascicles. We tested our proposed formulation in synthetic and in vivo data. Results: Our experiments show that using multiple levels allows considering information about the white matter organization more adequately and helps to improve further the accuracy of the resulting tractograms. Conclusion: This new formulation represents a further important step toward a more accurate structural connectivity estimation.
Changing Incidence and Survival of Primary Central Nervous System Lymphoma in Australia: A 33-Year National Population-Based Study

Simple Summary In Australia, all cancers are recorded in the Australian Cancer Database. We used pathological and anatomical classification codes to identify cases of brain lymphoma—termed primary central nervous system lymphoma or PCNSL—that had occurred in Australia during the past four decades. This allowed us to calculate the incidence of PCNSL, as well as the overall survival after diagnosis with this lymphoma. PCNSL is rare, recently affecting approximately 4 per one million adult Australians per year. However, the number of people diagnosed with this cancer is increasing. Survival of people diagnosed with PCNSL has been improving, but is still low, with only 33% of people alive at 5 years after receiving this diagnosis. As the first survey of the incidence of PCSNL in Australia and the survival of Australians diagnosed with this rare cancer, our research supports current efforts to understand risk factors and improve outcomes. Abstract Primary central nervous system lymphoma (PCNSL) is a rare brain cancer that remains challenging to study. Epidemiology of PCNSL in the Australian population, which is racially and ethnically diverse, has not been examined previously. Using ICD-O-3.1 Morphology and Topography Codes to identify cases, we analyzed complete datasets from the comprehensive Australian Cancer Database (1982–2014, adults aged ≥ 20 years) to establish incidence rates and trends of PCNSL, and to define survival outcomes of individuals diagnosed with PCNSL, including the predominant diffuse large B-cell lymphoma (DLBCL) type. Age-standardized incidence of PCNSL increased by an average annual 6.8% percent over the study period, with current incidence of 0.43 (95% confidence interval, 0.41–0.46) per 100,000 person-years, in comparison to 21.89 (21.41–22.38) per 100,000 person-years for non-CNS lymphoma. Increase in incidence was characterized by an acute rise between 1996 and 1999, was more pronounced with increasing age, and was driven by increasing incidence of DLBCL. Overall survival for persons diagnosed with PCNSL improved significantly across the study period, with 5-year survival probability increasing from 0.21 (95% confidence interval, 0.16–0.26) to 0.33 (0.30–0.36), and median survival increasing from 318 to 600 days, between 1982–1999 and 2000–2014. Increase in survival was significantly higher for persons with DLBCL versus non-DLBCL PCNSL, but substantially lower than that for persons with non-CNS lymphoma, who had a 5-year survival probability of 0.62 (0.62–0.62) and a median survival of 3388 days in 2000–2014. This study links increasing incidence of PCNSL in Australia to increasing incidence of DLCBL, including in younger adults, and highlights the improving, but low, survival outcome of this cancer.
Induction of Brain Tumors by the Archetype Strain of Human Neurotropic JCPyV in a Transgenic Mouse Model

JC Virus (JCPyV), a member of the Polyomaviridiæ family, is a human neurotropic virus with world-wide distribution. JCPyV is the established opportunistic infectious agent of progressive multifocal leukoencephalopathy, a fatal demyelinating disease, which results from the cytolytic infection of oligodendrocytes. Mutations in the regulatory region of JCPyV determine the different viral strains. Mad-1 the strain associated with PML contains two 98 base pair repeats, whereas the archetype strain (CY), which is the transmissible form of JCPyV, contains only one 98 tandem with two insertions of 62 and 23 base pairs respectively. The oncogenicity of JCPyV has been suspected since direct inoculation into the brain of rodents and primates resulted in the development of brain tumors and has been attributed to the viral protein, T-Antigen. To further understand the oncogenicity of JCPyV, a transgenic mouse colony containing the early region of the archetype strain (CY), under the regulation of its own promoter was generated. These transgenic animals developed tumors of neural crest origin, including: primitive neuroectodermal tumors, medulloblastomas, adrenal neuroblastomas, pituitary tumors, malignant peripheral nerve sheath tumors, and glioblastomas. Neoplastic cells from all different phenotypes express T-Antigen. The close parallels between the tumors developed by these transgenic animals and human CNS tumors make this animal model an excellent tool for the study of viral oncogenesis.
Positive factors related to graduate student mental health

Abstract Objective: Graduate students report high levels of distress, levels that professionals are calling a mental health crisis. Researchers have identified several factors that may exacerbate student distress, but our objective was to assess positive aspects that may attenuate distress. Methods: Over 3600 graduate students from 10 campuses responded to questionnaires assessing depressive symptoms as well as both positive and negative aspects of their current lives. Results: Both negative factors (financial concerns, poor mentorship, and perceived institutional discrimination) and positive factors (social support, departmental social climate, and optimism about their career prospects) are related to depressive symptoms in the expected directions, although the positive factors have stronger effects. Further, positive factors buffer the effects of the negative aspects on depressive symptoms. Conclusion: Although findings are correlational and do not imply causation, results suggest potentially modifiable factors that universities should consider when considering graduate student well-being.