Miracle-dz/UniFAR-FTUs huggingface dataset:
Corticothalamic Projections Deliver Enhanced-Responses to Medial Geniculate Body as a Function of the Temporal Reliability of the Stimulus

Aging and challenging signal-in-noise conditions are known to engage use of cortical resources to help maintain speech understanding. Extensive corticothalamic projections are thought to provide attentional, mnemonic and cognitive-related inputs in support of sensory inferior colliculus (IC) inputs to the medial geniculate body (MGB). Here we show that a decrease in modulation depth, a temporally less distinct periodic acoustic signal, leads to a jittered ascending temporal code, changing MGB unit responses from adapting responses to responses showing repetition-enhancement, posited to aid identification of important communication and environmental sounds. Young-adult male Fischer Brown Norway rats, injected with the inhibitory opsin archaerhodopsin T (ArchT) into the primary auditory cortex (A1), were subsequently studied using optetrodes to record single-units in MGB. Decreasing the modulation depth of acoustic stimuli significantly increased repetition-enhancement. Repetition-enhancement was blocked by optical inactivation of corticothalamic terminals in MGB. These data support a role for corticothalamic projections in repetition-enhancement, implying that predictive anticipation could be used to improve neural representation of weakly modulated sounds. Key points Aging has been shown to increase temporal jitter in the ascending acoustic code prompting use of cognitive/attentional mechanisms to help better understand communication-like signals. Auditory thalamus receives extensive projections from cortex that are implicated in delivering higher-order cortical computations to enhance thalamic responses. The present study modeled aging in young rats by using temporally less distinct stimuli shown to alter the pattern of MGB unit responses from response adaptation to repetition-enhancement. Enhanced responses to repeating less temporally distinct modulated stimuli were reversed when inputs from cortex to auditory thalamus were blocked. Collectively, these data argue that low salience temporal signals engage cortical processes to enhance coding of weakly modulated signals in auditory thalamus.
Heme oxygenase limits mycobacterial infection-induced ferroptosis

Iron homeostasis is essential for both sides of the host-pathogen interface. Restricting access of iron slows bacterial growth while iron is also a necessary co-factor for host immunity. Heme oxygenase 1 (HMOX1) is a critical regulator of iron homeostasis that catalyses the liberation of iron during degradation of heme. It is also a stress-responsive protein that can be rapidly upregulated and confers protection to the host. Although a protective role of HMOX1 has been demonstrated in a variety of diseases, the role of HMOX1 in Mycobacterium tuberculosis infection is equivocal across experiments with different host-pathogen combinations. Here we use the natural host-pathogen pairing of the zebrafish-Mycobacterium marinum infection platform to study the role of zebrafish heme oxygenase in mycobacterial infection. We identify zebrafish Hmox1a as the relevant functional paralog of mammalian HMOX1 and demonstrate a conserved role for Hmox1a in protecting the host from mycobacterial infection. Using genetic and chemical tools, we show zebrafish Hmox1a protects the host against mycobacterial infection by reducing infection-induced iron accumulation and ferroptosis.
Young adults recruit similar motor modules across walking, turning, and chair transfers

Moving about in the world during daily life requires executing and successfully shifting between a variety of functional tasks, such as arising from a chair or bed, walking, turning, and navigating stairs, etc. Moreover, moving about during daily life requires not only navigating between different functional tasks but also performing these tasks in the presence of mental distractions. However, little is known about underlying neuromuscular control for executing and shifting between these different tasks. In this study, we investigated muscle coordination across walking, turning, and chair transfers by applying motor module (aka muscle synergy) analysis to the Timed-Up-and-Go (TUG) test with and without a secondary cognitive dual task. We found that healthy young adults recruit a small set of common motor modules across the subtasks of the TUG test and that their composition is robust to cognitive distraction. Instead, cognitive distraction impacted motor module activation timings such that they became more consistent. This work is the first to demonstrate motor module generalization across multiple tasks that are both functionally different and crucial for healthy mobility. Overall, our results suggest that the central nervous system may draw from a “library” of modular control strategies to navigate the variety of movements and cognitive demands required of daily life. New & Noteworthy We demonstrated that healthy young adults recruit a small set of motor modules across subtasks of the Timed-Up-and-Go test (i.e., walking, turning, and chair transfers). Moreover, we showed that motor module composition, but not activation timing, is robust to cognitive distractions. These results support the hypothesis that healthy young adults recruit from a “library” of motor modules and modulate their activation timing to meet the different mechanical and cognitive demands required to navigate daily life.
Water damages in HVAC, tap water and sewage systems in cold climates

Water damages in buildings in the Nordic countries results in costs amounting to several billion Euros each year as well as a great deal of unpleasantness. The vast majority of the water damages cost in Sweden is caused by leaks from buildings services in the form of piping such as tap water, sewage, drainage and heating, as well as through insufficiently waterproof layers in wet rooms. The economic potential for making measures to prevent water damages on building services and wet rooms is enormous and savings could be used for other sustainability measures in the built environment. The aim of this paper is to review statistics of damages caused in cold outdoor climates. This is done by an analyse of empirical damage statistics by a literature review of both scientific literature and in retrievable cases from practical experience. The result will be a help to focus on the right damage types in colder climate and will make a foundation for future research on how to prevent water damages. The cold climate in the Nordic countries seems to be a factor for the number of water damages due to freezing that are described in the statistics and it could be established that the impact of the climate should be considered and that it need to be constructed and designed for in a larger extent.
PENGARUH PENGGANTIAN RUMPUT GAJAH DENGAN JERAMI PADI AMONIASI TERHADAP KUALITAS SUSU SAPI PERAH

The Effect of Napier Grass Substitution with Ammoniated Rice Straw in Quality Cow’s Milk Lactation The study aimed at evaluating the extent to which the dairy cow milk quality appearance resulting from the substitution of Napier grass with ammoniated rice straw. The materials used in the study were: 16 dairy cows at 1 st , 2 nd , 3 rd and 4 th month lactations, Napier grass, concentrate, ammoniated rice straw, cassava leaves and bypass protein of the brand name Soyxyl. The paramof varians eters observed consisted of dry matter consumption, milk production, fat content, protein content, milk lactose content, glucose concentration, and blood triglyceride. The data was analyzed statistically using analysis and when there was a significant impact it was then analyzed using Duncan’s multiple range test. The results of the study showed that there was not significant difference (P > 0.05) between T0, T1, T2 and T3 treatments on the dry matter consumption, fat content, protein content, lactose content, and milk specific weight. Key words: Ammoniated Rice Straw, Cassava Leaves, Napier grass and Protein Supplement.
The Time for Chronotherapy in Radiation Oncology

Five decades ago, Franz Halberg conceived the idea of a circadian-based therapy for cancer, given the differential tolerance to treatment derived from the intrinsic host rhythms. Nowadays, different experimental models have demonstrated that both the toxicity and efficacy of several anticancer drugs vary by more than 50% as a function of dosing time. Accordingly, it has been shown that chemotherapeutic regimens optimally timed with the circadian cycle have jointly improved patient outcomes both at the preclinical and clinical levels. Along with chemotherapy, radiation therapy is widely used for cancer treatment, but its effectiveness relies mainly on its ability to damage DNA. Notably, the DNA damage response including DNA repair, DNA damage checkpoints, and apoptosis is gated by the circadian clock. Thus, the therapeutic potential of circadian-based radiotherapy against cancer is mainly dependent upon the control that the molecular clock exerts on DNA repair enzymes across the cell cycle. Unfortunately, the time of treatment administration is not usually considered in clinical practice as it varies along the daytime working hours. Currently, only a few studies have evaluated whether the timing of radiotherapy affects the treatment outcome. Several of these studies show that it is possible to reduce the toxicity of the treatment if it is applied at a specific time range, although with some inconsistencies. In this Perspective, we review the main advances in the field of chronoradiotherapy, the possible causes of the inconsistencies observed in the studies so far and provide some recommendations for future trials.
Genomic Surveillance of Vancomycin-Resistant Enterococcus faecium Reveals Spread of a Linear Plasmid Conferring a Nutrient Utilization Advantage

Sequencing microbial pathogens causing outbreaks has become a common practice to characterize transmission networks. In addition to the signal provided by vertical evolution, bacterial genomes harbor mobile genetic elements shared horizontally between clones. ABSTRACT Healthcare-associated outbreaks of vancomycin-resistant Enterococcus faecium (VREfm) are a worldwide problem with increasing prevalence. The genomic plasticity of this hospital-adapted pathogen contributes to its efficient spread despite infection control measures. Here, we aimed to identify the genomic and phenotypic determinants of health care-associated transmission of VREfm. We assessed the VREfm transmission networks at the tertiary-care University Hospital of Zurich (USZ) between October 2014 and February 2018 and investigated microevolutionary dynamics of this pathogen. We performed whole-genome sequencing for the 69 VREfm isolates collected during this time frame and assessed the population structure and variability of the vancomycin resistance transposon. Phylogenomic analysis allowed us to reconstruct transmission networks and to unveil external or wider transmission networks undetectable by routine surveillance. Notably, it unveiled a persistent clone, sampled 31 times over a 29-month period. Exploring the evolutionary dynamics of this clone and characterizing the phenotypic consequences revealed the spread of a variant with decreased daptomycin susceptibility and the acquired ability to utilize N-acetyl-galactosamine (GalNAc), one of the primary constituents of the human gut mucins. This nutrient utilization advantage was conferred by a novel plasmid, termed pELF_USZ, which exhibited a linear topology. This plasmid, which was harbored by two distinct clones, was transferable by conjugation. Overall, this work highlights the potential of combining epidemiological, functional genomic, and evolutionary perspectives to unveil adaptation strategies of VREfm. IMPORTANCE Sequencing microbial pathogens causing outbreaks has become a common practice to characterize transmission networks. In addition to the signal provided by vertical evolution, bacterial genomes harbor mobile genetic elements shared horizontally between clones. While macroevolutionary studies have revealed an important role of plasmids and genes encoding carbohydrate utilization systems in the adaptation of Enterococcus faecium to the hospital environment, mechanisms of dissemination and the specific function of many of these genetic determinants remain to be elucidated. Here, we characterize a plasmid providing a nutrient utilization advantage and show evidence for its clonal and horizontal spread at a local scale. Further studies integrating epidemiological, functional genomics, and evolutionary perspectives will be critical to identify changes shaping the success of this pathogen.
QoS-Guaranteed Resource Allocation for Full-Duplex Networks With M2M/H2H Co-Existence Under Imperfect CSI

To enhance spectrum efficiency for the future Internet-of-Things, in this paper, we investigate the joint subcarrier and power allocation problem for a full-duplex network with machine-to-machine nodes and cellular nodes. We aim to maximize the network spectral efficiency while achieving individual quality-of-service (QoS) requirements, considering imperfect and partial channel state information. The spectral efficiency maximization problem is formulated as a mixed-integer nonlinear programming problem and proved to be NP-hard. To make it more tractable, we first solve the coupling between subcarrier assignment and power allocation variables by replacing the product of two variables with one auxiliary variable. We then relax the binary subcarrier assignment variables to integer variables and introduce penalty terms to penalize the objective function. Majorization minimization method is adopted to further handle the coupling between uplink and downlink due to full-duplex transmission. We prove that the proposed joint resource allocation scheme converges to local optimal solution. Simulation results demonstrate the impact of channel estimation error on spectral efficiency and the superiority of the proposed algorithm.
Population analysis of Vibrio cholerae in aquatic reservoirs reveals a novel sister species (Vibrio paracholerae sp. nov.) with a history of association with human infections

Most efforts to understand the biology of Vibrio cholerae have focused on a single group, the pandemic-generating lineage harbouring the strains responsible for all known cholera pandemics. Consequently, little is known about the diversity of this species in its native aquatic environment. To understand the differences in the V. cholerae populations inhabiting in regions with varying history of cholera cases and how that might influence the abundance of pandemic strains, a comparative analysis of population composition was performed. Little overlap was found in lineage compositions between those in Dhaka (cholera endemic) located in the Ganges delta, and of Falmouth (no known history of cholera), a small coastal town on the US East Coast. The most striking difference was the presence of a group of related lineages at high abundance in Dhaka which was completely absent from Falmouth. Phylogenomic analysis revealed that these lineages form a cluster at the base of the phylogeny of V. cholerae species, sufficiently differentiated genetically and phenotypically to form a novel species. Strains from this species have been anecdotally isolated from around the world and were isolated as early as 1916 from a British soldier in Egypt suffering from choleraic diarrhoea. In 1935 Gardner and Venkatraman unofficially referred to a member of this group as Vibrio paracholerae. In recognition of this earlier designation, we propose the name Vibrio paracholerae, sp. nov. for this bacterium. Genomic analysis suggests a link with human populations for this novel species and substantial interaction with its better-known sister species. Importance Cholera continues to remain a major public health threat around the globe. Understanding the ecology, evolution and environmental adaptation of the causative agent Vibrio cholerae and tracking the emergence of novel lineages with pathogenic potential are essential to combat the problem. In this study, we investigated the population dynamics of Vibrio cholerae in an inland locality which is known as endemic for cholera and compared with that of a cholera free coastal location. We found the consistent presence of the pandemic generating V. cholerae in cholera-endemic Dhaka and an exclusive presence of a lineage phylogenetically distinct from other V. cholerae. Our study suggests that this lineage represents a novel species having pathogenic potential and a human link to its environmental abundance. The possible association with human population, co-existence and interaction with toxigenic V. cholerae in the natural environment make this potential human pathogen an important subject for future studies.
AMPK: Potential Therapeutic Target for Vascular Calcification

Vascular calcification (VC) is an urgent worldwide health issue with no available medical treatment. It is an active cell-driven process by osteogenic differentiation of vascular cells with complex mechanisms. The AMP-activated protein kinase (AMPK) serves as the master sensor of cellular energy status. Accumulating evidence reveals the vital role of AMPK in VC progression. AMPK is involved in VC in various ways, including inhibiting runt-related transcription factor 2 signaling pathways, triggering autophagy, attenuating endoplasmic reticulum stress and dynamic-related protein 1-mediated mitochondrial fission, and activating endothelial nitric oxide synthase. AMPK activators, like metformin, are associated with reduced calcification deposits in certain groups of patients, indicating that AMPK is a potential therapeutic target for VC.
Impact of Nematode Infections on Non-specific and Vaccine-Induced Humoral Immunity in Dual-Purpose or Layer-Type Chicken Genotypes

Nematode infections may induce immune-modulatory effects and influence host-immune responses to other pathogens. The aim of the study was to investigate whether a mixed nematode-infection influences non-specific and vaccine-induced humoral immunity against Newcastle Disease Virus (NDV), Infectious Bronchitis Virus (IBV), and Avian Metapneumovirus (AMPV) in already vaccinated hens of a dual-purpose (Lohmann Dual, LD) or a layer genotype (Lohmann Brown Plus; LB). Until 17 weeks-of-age, LD (n = 70) and LB (n = 109) hens were vaccinated against major bacterial and viral diseases and coccidiosis. At 24 weeks-of-age, the hens received either a placebo or an oral inoculation of 1,000 infectious eggs of A. galli and H. gallinarum. Plasma total immunoglobulin (Ig) isotypes (IgY, IgM, IgA) levels and vaccine-induced antibody titers against NDV, IBV, and AMPV were determined from 2 to 18 weeks post-infection (wpi). Infections had no suppressing effect on total Ig isotypes IgY, IgM, and IgA as well as on vaccine-induced antibody titers against NDV, IBV, and AMPV (P > 0.05). Overall, LB hens had higher levels of IgY, IgM, and IgA than those of LD hens (P < 0.05). There were no differences between IBV titers of the two genotypes (P > 0.05). Independent of infection status of the hens, NDV titers were higher in LB hens than in LD hens at wpi 2 (P < 0.05), but not in following weeks (P > 0.05). Uninfected LD hens had lower AMPV titers than their infected counterparts at 6 and 14 wpi (P < 0.05). Regardless of nematode infection, LD hens revealed a higher risk of responding weak to vaccination against NDV (odds ratio = 5.45; P = 0.021) and AMPV (odds ratio = 13.99, P < 0.001) than did LB hens (P > 0.05). We conclude that nematode infections have no adverse effects on non-specific and vaccine-induced humoral immunity in either genotype. LB hens have higher levels of total immunoglobulin isotypes than LD hens. Except for IBV, vaccine-induced humoral immune responses show a dependency on genotype. Dual-purpose hens show lower responsiveness to vaccinations against NDV and AMPV, possibly due to factors associated with increased body fat reserves in this genotype.
Histone marks are drivers of the splicing changes necessary for an epithelial-to-mesenchymal transition

Cell differentiation and reprogramming depend on coordinated changes in specific alternative splicing events. How these cell type-specific splicing patterns are dynamically modified in response to a stimulus remains elusive. Taking advantage of the epithelial-to-mesenchymal transition (EMT), a reversible cell reprogramming intimately involved in cancer cell invasiveness and metastasis, we found a strong correlation between changes in the alternative splicing of key exons for EMT, such as at the Fgfr2 and Cnntd1 loci, and changes in the enrichment levels of specific histone modifications, namely H3K27ac and H3K27me3. Localised CRISPR epigenome editing of these exon-specific histone marks was sufficient to induce changes in splicing capable of recapitulating important aspects of EMT, such as a motile and invasive cell phenotype. Whereas, impairment of the changes in H3K27 marks observed during EMT, using histone deacetylase inhibitors, repressed inclusion of the mesenchymal isoform despite an EMT induction, supporting a driving effect for H3K27 modifications in establishing the new cell type-specific splicing patterns necessary for EMT cell reprogramming. Finally, H3K27 marks were shown to impact splicing by modulating recruitment of the splicing factor PTB to its RNA binding sites, suggesting a direct link between chromatin modifications and the splicing machinery. Taken together, these results prove the causal role of H3K27 marks in driving the dynamic splicing changes necessary for induction of important aspects of EMT. They also prove that chromatin-mediated splicing changes are sufficient to impact the cell’s phenotype, which expands the cell’s toolkit to adapt and respond to diverse stimuli, such as EMT induction.
AZBA: A 3D Adult Zebrafish Brain Atlas for the Digital Age

Zebrafish have made significant contributions to our understanding of the vertebrate brain and the neural basis of behavior, earning a place as one of the most widely used model organisms in neuroscience. Their appeal arises from the marriage of low cost, early life transparency, and ease of genetic manipulation with a behavioral repertoire that becomes more sophisticated as animals transition from larvae to adults. To further enhance the use of adult zebrafish, we created the first fully segmented three-dimensional digital adult zebrafish brain atlas (AZBA). AZBA was built by combining tissue clearing, light-sheet fluorescence microscopy, and three-dimensional image registration of nuclear and antibody stains. These images were used to guide segmentation of the atlas into over 200 neuroanatomical regions comprising the entirety of the adult zebrafish brain. As an open source, online azba.wayne. edu), updatable digital resource, AZBA will significantly enhance the use of adult zebrafish in furthering our understanding of vertebrate brain function in both health and disease.
Growth-dependent heterogeneity in the DNA damage response in Escherichia coli

In natural environments bacteria are frequently exposed to sub-lethal levels of DNA damage which leads to the induction of a stress response (the SOS response in Escherichia coli). Natural environments also vary in nutrient availability, resulting in distinct physiological changes in bacteria which may have direct implications on their capacity to repair their chromosomes. Here, we evaluated the impact of varying the nutrient availability on the expression of the SOS response induced by chronic sub-lethal DNA damage in E. coli. The expression of the SOS regulon was found to be highly heterogeneous at the single-cell level in all growth conditions. Surprisingly, we observed a larger fraction of high SOS-induced cells in slow growth as compared with fast growth, despite a higher rate of SOS induction in fast growth. This counter-intuitive result can be explained by the dynamic balance between the rate of SOS induction and the division rates of cells exposed to DNA damage. Taken together, our data illustrates how cell division and physiology come together to produce growth-dependent heterogeneity in the DNA damage response.