Miracle-dz/UniFAR-FTUs huggingface dataset:
Serum Vitamin D Metabolites and CXCL10 Concentrations Associate With Survival in Dogs With Immune Mediated Disease

Background: Low vitamin D increases the risk of immune-mediated disease (IMD) in human beings and rodent models. Vitamin D metabolites, particularly 1,25(OH)2D3, modulate gene expression of immune cells and may attenuate immune pathways that drive IMD. Hypothesis/objectives: Our primary hypothesis was that serum 25(OH)D3 and 1,25(OH)2D3, are reduced in patients with IMD and associate with poorer outcomes. We secondarily hypothesized serum 24,25(OH)2D3 would not be associated with disease or outcome. We also measured serum CXCL10 concentrations to determine if an increase occurs in dogs with IMD and in association with poorer survival. Animals: We enrolled dogs diagnosed with IMD (n = 29) and healthy control dogs (n = 9) in the study with informed client consent. Methods: Serum was collected and stored at −80°C until analyses. Serum vitamin D metabolites were measured by LC-MS/MS by an accredited laboratory. A commercially available canine-specific ELISA kit measured serum CXCL10. Results: Serum 25(OH)D3 and 1,25(OH)2D3 were significantly reduced in dogs (n = 25) with IMD. Serum CXCL10 concentrations undetectable in all controls, and were 30 times higher overall in IMD dogs (n = 25; P = 0.004). CXL10 was, however, undetectable in 40% of dogs with IMD. Of the 60% of IMD dogs with increased CXCL10 concentrations, 5/25 had concentrations at the upper limit of quantification. The survival of those five dogs was significantly (P = 0.049) shorter (72 days) than all other dogs with IMD with measured CXCL10 concentrations. The median survival time (MST) for dogs with 25(OH)D3 concentrations ≤ the median was 106 days, while dogs with concentrations of 25(OH)D3 > the median did not achieve an MST. Conclusions and clinical importance: Serum 25(OH)D3 and 1,25(OH)2D3, but not 24,25(OH)2D3 levels are reduced dogs with IMD. Vitamin D metabolites and CXCL10 may be useful prognostic markers and may be targets for adjunct therapy in canine IMD. These data support the future investigation of vitamin D analogs in the treatment of canine IMD.
Comparative Analysis of Microfluidics Thrombus Formation in Multiple Genetically Modified Mice: Link to Thrombosis and Hemostasis

Genetically modified mice are indispensable for establishing the roles of platelets in arterial thrombosis and hemostasis. Microfluidics assays using anticoagulated whole blood are commonly used as integrative proxy tests for platelet function in mice. In the present study, we quantified the changes in collagen-dependent thrombus formation for 38 different strains of (genetically) modified mice, all measured with the same microfluidics chamber. The mice included were deficient in platelet receptors, protein kinases or phosphatases, small GTPases or other signaling or scaffold proteins. By standardized re-analysis of high-resolution microscopic images, detailed information was obtained on altered platelet adhesion, aggregation and/or activation. For a subset of 11 mouse strains, these platelet functions were further evaluated in rhodocytin- and laminin-dependent thrombus formation, thus allowing a comparison of glycoprotein VI (GPVI), C-type lectin-like receptor 2 (CLEC2) and integrin α6β1 pathways. High homogeneity was found between wild-type mice datasets concerning adhesion and aggregation parameters. Quantitative comparison for the 38 modified mouse strains resulted in a matrix visualizing the impact of the respective (genetic) deficiency on thrombus formation with detailed insight into the type and extent of altered thrombus signatures. Network analysis revealed strong clusters of genes involved in GPVI signaling and Ca2+ homeostasis. The majority of mice demonstrating an antithrombotic phenotype in vivo displayed with a larger or smaller reduction in multi-parameter analysis of collagen-dependent thrombus formation in vitro. Remarkably, in only approximately half of the mouse strains that displayed reduced arterial thrombosis in vivo, this was accompanied by impaired hemostasis. This was also reflected by comparing in vitro thrombus formation (by microfluidics) with alterations in in vivo bleeding time. In conclusion, the presently developed multi-parameter analysis of thrombus formation using microfluidics can be used to: (i) determine the severity of platelet abnormalities; (ii) distinguish between altered platelet adhesion, aggregation and activation; and (iii) elucidate both collagen and non-collagen dependent alterations of thrombus formation. This approach may thereby aid in the better understanding and better assessment of genetic variation that affect in vivo arterial thrombosis and hemostasis.
Resuscitation of Dormant “Non-culturable” Mycobacterium tuberculosis Is Characterized by Immediate Transcriptional Burst

Under unfavorable conditions such as host immune responses and environmental stresses, human pathogen Mycobacterium tuberculosis may acquire the dormancy phenotype characterized by “non-culturability” and a substantial decrease of metabolic activity and global transcription rates. Here, we found that the transition of M. tuberculosis from the dormant “non-culturable” (NC) cells to fully replicating population in vitro occurred not earlier than 7 days after the start of the resuscitation process, with predominant resuscitation over this time interval evidenced by shortening apparent generation time up to 2.8 h at the beginning of resuscitation. The early resuscitation phase was characterized by constant, albeit low, incorporation of radioactive uracil, indicating de novo transcription immediately after the removal of the stress factor, which resulted in significant changes of the M. tuberculosis transcriptional profile already after the first 24 h of resuscitation. This early response included transcriptional upregulation of genes encoding enzymes of fatty acid synthase system type I (FASI) and type II (FASII) responsible for fatty acid/mycolic acid biosynthesis, and regulatory genes, including whiB6 encoding a redox-sensing transcription factor. The second resuscitation phase took place 4 days after the resuscitation onset, i.e., still before the start of active cell division, and included activation of central metabolism genes encoding NADH dehydrogenases, ATP-synthases, and ribosomal proteins. Our results demonstrate, for the first time, that the resuscitation of dormant NC M. tuberculosis is characterized by immediate activation of de novo transcription followed by the upregulation of genes controlling key metabolic pathways and then, cell multiplication.
Identify the Alteration of Balance Control and Risk of Falling in Stroke Survivors During Obstacle Crossing Based on Kinematic Analysis

This study aims to compare the differences in the kinematic characteristics of crossing obstacles of different heights between stroke survivors and age-matched healthy controls and to identify the changes of balance control strategy and risk of falling. Twelve stroke survivors and twelve aged-matched healthy controls were recruited. A three-dimensional motion analysis system and two force plates were used to measure the kinematic and kinetic data during crossing obstacles with heights of 10, 20, and 30% leg length. The results showed that during leading and trailing limb clearance, (AP) center of mass (COM) velocities of the stroke group were smaller than those of the healthy controls for all heights. The decreased distances between COM and center of pressure (COP) in the AP direction during the both trailing and leading limb support period were also found between stroke survivors and healthy controls for all heights. The COM velocity and COM-COP distance significantly correlated with the lower limb muscle strength. In addition, stroke survivors showed greater lateral pelvic tilt, greater hip abduction, and larger peak velocity in the medio-lateral (ML) direction. There was a positive correlation between the COM-COP distance in the AP direction and the clinical scales. These results might identify that the stroke survivors used a conservative strategy to negotiate the obstacles and control balance due to a lack of muscle strength. However, the abnormal patterns during obstacle crossing might increase the risk of falling. The findings could be used to design specific rehabilitation training programs to enhance body stability, reduce energy cost, and improve motion efficiency.
Autophagic Control of Skin Aging

The skin forms the barrier to the environment. Maintenance of this barrier during aging requires orchestrated responses to variable types of stress, the continuous renewal of the epithelial compartment, and the homeostasis of long-lived cell types. Recent experimental evidence suggests that autophagy is critically involved in skin homeostasis and skin aging is associated with and partially caused by defects of autophagy. In the outer skin epithelium, autophagy is constitutively active during cornification of keratinocytes and increases the resistance to environmental stress. Experimental suppression of autophagy in the absence of stress is tolerated by the rapidly renewing epidermal epithelium, whereas long-lived skin cells such as melanocytes, Merkel cells and secretory cells of sweat glands depend on autophagy for cellular homeostasis and normal execution of their functions during aging. Yet other important roles of autophagy have been identified in the dermis where senescence of mesenchymal cells and alterations of the extracellular matrix (ECM) are hallmarks of aging. Here, we review the evidence for cell type-specific roles of autophagy in the skin and their differential contributions to aging.
Pleiotropy Complicates Human Gene Editing: CCR5Δ32 and Beyond

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Segmented Iba1-Positive Processes of Microglia in Autism Model Marmosets

Autism spectrum disorder (ASD) is one of the most widespread neurodevelopmental disorders, characterized by impairment in social interactions, and restricted stereotyped behaviors. Using immunohistochemistry and positron emission tomography (PET), several studies have provided evidence of the existence of activated microglia in ASD patients. Recently, we developed an animal model of ASD using the new world monkey common marmoset (Callithrix jacchus) and demonstrated ASD-like social impairment after the in utero administration of valproic acid (VPA). To characterize microglia in this marmoset model of ASD from early toddler to adult, morphological analyses of microglia in VPA marmosets and age-matched unexposed (UE) marmosets were performed using immunohistochemistry for microglia-specific markers, Iba1, and P2RY12. The most robust morphological difference between VPA marmosets and UE marmosets throughout the life span evaluated were the microglia processes in VPA marmosets being frequently segmented by thin and faintly Iba1-positive structures. The segmentation of microglial processes was only rarely observed in UE marmosets. This feature of segmentation of microglial processes in VPA marmosets can also be observed in images from previous studies on ASD conducted in humans and animal models. Apoptotic cells have been shown to have segmented processes. Therefore, our results might suggest that microglia in patients and animals with ASD symptoms could frequently be in the apoptotic phase with high turnover rates of microglia found in some pathological conditions.
Doctor Drone: Non-invasive Measurement of Humpback Whale Vital Signs Using Unoccupied Aerial System Infrared Thermography

Measuring and monitoring the behavior and biomedical condition of free-ranging whales remains a fundamental challenge in cetacean science and conservation. Advances in unoccupied aerial systems (UAS) and infrared thermography (IRT) create unprecedented opportunities to fill these knowledge gaps and advance our understanding of how cetaceans interact with the environment. Here, we show that non-invasive UAS-IRT systems, deployed from shore-based positions in a humpback whale (Megaptera novaeangliae) calving ground, can be used to document rarely observed whale behaviors and quantify biomedical vital signs. Our findings demonstrate: 1) prolonged (>3 h) logging behavior by a mother-calf pair located ~550 m offshore; 2) that the calf’s respiration rate (~3 breaths per minute) was 6 times higher than its mother’s (~0.5 breaths per minute); 3) that the calf’s blowholes were ~1.55° C warmer than adjacent ocean water and that the mother’s blowholes were ~2.16° C warmer than adjacent ocean water; 4) that the mother’s dorsal fin included four infrared hot-spots, each separated by ~20 cm in horizontal distance, that ranged between 1° C and 2° C warmer than adjacent ocean water; 5) a significant (p<<0.05; wavelet analysis) temporal cyclicity in the hottest of the mother’s dorsal fin hot-spots consistent with cardiovascular blood flow pumped at an apneic heart rate of 9.3 beats per minute. Wider deployment and development of UAS-IRT technologies should help to both overcome current challenges, including cost and data processing, and provide unique perspectives and data that will inform our understanding of whale behavior and biomedical condition in rapidly changing marine systems.
Malocclusion Generates Anxiety-Like Behavior Through a Putative Lateral Habenula–Mesencephalic Trigeminal Nucleus Pathway

Malocclusion is an important risk factor for temporomandibular disorder (TMD), a series of disorders characterized by dysfunction in the orofacial region involving the temporomandibular joint (TMJ) and jaw muscles. We recently showed that experimental unilateral anterior crossbite (UAC) produced masseter hyperactivity through a circuit involving the periodontal proprioception, trigeminal mesencephalic nucleus (Vme), and trigeminal motor nucleus (Vmo). Anxiety is a common complication in patients with TMD. The lateral habenula (LHb) is involved in emotional modulation and has direct projections to the Vme. Therefore, the present research examined whether UAC facilitates excitatory input from the LHb to the Vme and, subsequently, anxiety-like behaviors in rats. The LHb activation was evaluated by the electrophysiological recording, assessment of vesicular glutamate transporter-2 (VGLUT2) mRNA expression, and measurement of anxiety-like behaviors. The effects of LHb activity on Vme were evaluated by electrophysiological recording from Vme neurons and local changes in VGLUT2 protein density. UAC produced anxiety in modeled rats and increased neuronal activity in the LHb. VGLUT2 mRNA expression was also increased in the LHb. Further, VGLUT2-positive boutons were observed in close apposite upon parvalbumin (PV)-labeled Vme neurons. VGLUT2 protein expression was also increased in the Vme. Significantly, injection of VGLUT2-targeted shRNA into the LHb reduced the expression of VGLUT2 protein in the Vme, attenuated UAC-associated anxiety-like behaviors, and attenuated electrophysiological changes in the Vme neurons. In conclusion, we show that UAC activates the LHb neurons as well as the periodontal proprioceptive pathway to provide excitatory input to the Vme and produce anxiety in rats. These findings provide a rationale for suppressing activity of the LHb to attenuate both the physical and psychological effects of TMD.
Iron and Nickel Mixed Oxides Derived From NiIIFeII-PBA for Oxygen Evolution Electrocatalysis

The sluggish kinetics of oxygen evolution reaction (OER) on anode hinders the efficiency of electrochemical water splitting. Electrocatalysts for OER based on non-precious transition metals are highly desirable. Herein, iron and nickel mixed oxides with surface oxygen vacancies were fabricated using NiIIFeII-Prussian blue analog as the precursors by a facile two-step thermal-assisted method. The precursor compositions and calcination temperatures exert great impact on the structure and morphology of the derivatives, as well as the electrocatalytic performances for OER. Both the higher content of Ni ions during the synthesis of precursors and lower calcination temperature favor the electrocatalytic performance of the corresponding derivatives. The porous metal oxides consisting of nickel oxide and nickel ferrite exhibited the remarkable electrocatalytic property toward OER in an alkaline solution, which can be attributed to the nanosized and porous structure, the co-existence of spinel NiFe2O4 and cubic NiO, the high content of surface oxygen vacancies, and the low charge transfer resistance. This study will provide new inspiration for the facile design of low-cost active catalysts for OER in the future.
Comparative Analyses of Fecal Microbiota in European Mouflon (Ovis orientalis musimon) and Blue Sheep (Pseudois nayaur) Living at Low or High Altitudes

The gut microbiota is a complex and essential system organ that plays an integrative role in balancing key vital functions in the host. Knowledge of the impact of altitude on the gut microbiota of European mouflon (Ovis orientalis musimon) and blue sheep (Pseudois nayaur) is currently limited. In this study, we compared the characteristics of gut microbiota in 5 mouflon at low altitude (K group), 4 mouflon at high altitude (L group), 4 blue sheep at low altitude (M group), and 4 blue sheep at high altitude (N group). The V3–V4 region of the 16S rRNA gene was analyzed using high-throughput sequencing. Analyses based on the operational taxonomic units showed significant changes in the gut microbial communities between groups at different altitudes. At the phylum level, groups at the high altitudes had a higher relative abundance of Firmicutes and a lower relative abundance of Bacteroidetes than those at the low altitudes. A higher Firmicutes:Bacteroidetes ratio is beneficial to animals in terms of the gut microbiota-mediated energy harvest. The relative abundance of Proteobacteria was significantly higher in the gut microbiota of mouflon sheep at high altitudes. At the genus level, the Bacteroides:Prevotella ratio was significantly higher in the low-altitude group (than the high-altitude group) of mouflon sheep and the ratio was significantly higher in the high-altitude group (than the low-altitude group) in blue sheep. In addition, the Ruminococcaceae_UCG-005 related to cellulose and starch digestion was the predominant genus in blue sheep and the relative abundance of the genus was significant higher in the high-altitude group than the low-altitude group of blue sheep (P < 0.01). In conclusion, our results suggested that the gut microbiota of high-altitude groups of sheep had stronger abilities related to energy metabolism and the decomposition of substances, e.g., fiber and cellulose, and that such abilities are associated with high-altitude adaptation.
Ecological Conditions and Molecular Determinants Involved in Agrobacterium Lifestyle in Tumors

The study of pathogenic agents in their natural niches allows for a better understanding of disease persistence and dissemination. Bacteria belonging to the Agrobacterium genus are soil-borne and can colonize the rhizosphere. These bacteria are also well known as phytopathogens as they can cause tumors (crown gall disease) by transferring a DNA region (T-DNA) into a wide range of plants. Most reviews on Agrobacterium are focused on virulence determinants, T-DNA integration, bacterial and plant factors influencing the efficiency of genetic transformation. Recent research papers have focused on the plant tumor environment on the one hand, and genetic traits potentially involved in bacterium-plant interactions on the other hand. The present review gathers current knowledge about the special conditions encountered in the tumor environment along with the Agrobacterium genetic determinants putatively involved in bacterial persistence inside a tumor. By integrating recent metabolomic and transcriptomic studies, we describe how tumors develop and how Agrobacterium can maintain itself in this nutrient-rich but stressful and competitive environment.
Efficient Data-Parallel Primitives on Heterogeneous Systems

Data-parallel primitives, such as gather, scatter, scan, and split, are widely used in data-intensive applications. However, it is challenging to optimize them on a system consisting of heterogeneous processors. In this paper, we study and compare the existing implementations and optimization strategies for a set of data-parallel primitives on three processors: GPU, CPU and Xeon Phi co-processor. Our goal is to identify the key performance factors in the implementations of data-parallel primitive operations on different architectures and develop general strategies for implementing these primitives efficiently on various platforms. We introduce a portable and efficient sequential memory access pattern, which eliminates the cost of adjusting the memory access pattern for individual device. With proper tuning, our optimized primitive implementations can achieve comparable performance to the native versions. Moreover, our profiling results show that the CPU and the Phi co-processor share most optimization strategies whereas the GPU differs from them significantly, due to the hardware differences among these devices, such as efficiency of vectorization, data and TLB caching, and data prefetching. We summarize these factors and deliver common primitive optimization strategies for heterogeneous systems.
Perception of virtual characters

This course will introduce students, researchers and digital artists to the recent results in perceptual research on virtual characters. It covers both how technical and artistic aspects that constitute the appearance of a virtual character influence human perception. We will report results of studies that addressed the influence of low-level cues like facial proportions, shading or level of detail and higher-level cues such as behavior or artistic stylization. We will place emphasis on aspects that are encountered during character development, animation, and achieving consistency between the visuals and storytelling. The insights that we present in this course will serve as an additional toolset to anticipate the effect of certain design decisions and to create more convincing characters, especially in the case where budgets or time are limited.
Near-Data Processing-Enabled and Time-Aware Compaction Optimization for LSM-tree-based Key-Value Stores

With the growing volume of storage systems, the traditional relational databases cannot reach the high performance required by big-data applications. As high-throughput alternatives to relational databases, LSM-tree-based key-value stores (KV stores in short) are confronted with degraded write performance during compaction under update-intensive workloads. To address this issue, we design and implement a time-aware compaction optimization framework for KV stores called TStore. TStore explores the near-data processing (i.e., NDP) model. It dynamically partitions compaction tasks into both host and NDP-enabled device to minimize the total time of compaction. The partitioned compaction tasks are conducted by the host and the device in parallel. The NDP-based devices exhibit low-latency, high-performance and high-bandwidth capability, thus facilitating key-value stores. TStore can not only accomplish compaction for KV stores, but also improve overall performance by removing bottleneck in compaction. Results show that the TStore with an NDP framework can achieve 3.8x and 1.9x performance improvement over LevelDB and Co-KV under the db_bench workload. In addition, the TStore-enabled KV store outperforms LevelDB and Co-KV by a factor of 3.6x and 1.9x in throughput and 72.0% and 48.9% in latency, respectively, under realistic workloads generated by YCSB.