Miracle-dz/UniFAR-FTUs huggingface dataset:
Testing Local Adaptation in a Natural Great Tit-Malaria System: An Experimental Approach

Finding out whether Plasmodium spp. are coevolving with their vertebrate hosts is of both theoretical and applied interest and can influence our understanding of the effects and dynamics of malaria infection. In this study, we tested for local adaptation as a signature of coevolution between malaria blood parasites, Plasmodium spp. and its host, the great tit, Parus major. We conducted a reciprocal transplant experiment of birds in the field, where we exposed birds from two populations to Plasmodium parasites. This experimental set-up also provided a unique opportunity to study the natural history of malaria infection in the wild and to assess the effects of primary malaria infection on juvenile birds. We present three main findings: i) there was no support for local adaptation; ii) there was a male-biased infection rate; iii) infection occurred towards the end of the summer and differed between sites. There were also site-specific effects of malaria infection on the hosts. Taken together, we present one of the few experimental studies of parasite-host local adaptation in a natural malaria system, and our results shed light on the effects of avian malaria infection in the wild.
Systematic review of maternal voice interventions demonstrates increased stability in preterm infants

We systematically reviewed how effectively maternal voice interventions supported the clinical outcomes and development of preterm infants. A total of 512 preterm infants were included in 15 studies with different designs, from January 2000 to July 2015. Live and recorded maternal voice interventions were associated with the physiologic and behavioural stabilisation of preterm infants, with fewer cardiorespiratory events, but the evidence was insufficient to evaluate the long‐term effects. Well‐defined determinants and clear setting conditions are needed for such interventions.
Effects of Antioxidant Supplements on the Survival and Differentiation of Stem Cells

Although physiological levels of reactive oxygen species (ROS) are required to maintain the self-renewal capacity of stem cells, elevated ROS levels can induce chromosomal aberrations, mitochondrial DNA damage, and defective stem cell differentiation. Over the past decade, several studies have shown that antioxidants can not only mitigate oxidative stress and improve stem cell survival but also affect the potency and differentiation of these cells. Further beneficial effects of antioxidants include increasing genomic stability, improving the adhesion of stem cells to culture media, and enabling researchers to manipulate stem cell proliferation by using different doses of antioxidants. These findings can have several clinical implications, such as improving neurogenesis in patients with stroke and neurodegenerative diseases, as well as improving the regeneration of infarcted myocardial tissue and the banking of spermatogonial stem cells. This article reviews the cellular and molecular effects of antioxidant supplementation to cultured or transplanted stem cells and draws up recommendations for further research in this area.
Complex Permittivity and Permeability Studies Viewing Antenna Applications of NBR-Based Composites Comprising Conductive Fillers

The work presents studies on the complex permittivity and permeability of composites based on acrylonitrile butadiene rubber containing combinations of conductive fillers which include carbon black and nickel powder. The properties of those composites, containing each of the fillers at the same amount were compared. The permittivity and permeability values of the composites are influenced remarkably by their morphology and structure as well as by the morphological and structural specifics of both fillers. As electron scanning microscopy studies confirm, those parameters are predetermined by the nature of the composites studied—particle size, particles arrangement in the matrix and their tendency to clustering. Last but not least matrix-filler interface phenomena also impact the characteristics in question. The possibilities for applications of the composites in antennae have been studied, in particular, as substrates and insulating layers in flexible antennae for body centric communications (BCCs). The research results allow the conclusion that these materials can find such applications indeed. Composites of higher conductivity can be used where surface waves are generated to provide on-body communications, while composites of lower conductivity may be used for antennae that will be on the body of a person and will transmit to and receive from other antennas that are not on the body of the same person (off-body communications). It is clear that one can engineer the properties of antennae substrates at microwave frequencies by adjusting the filler content and the type of filler and thus control and tailor the antenna performance specific for a particular application.
Menopausal symptoms and physical activity in multiethnic groups of midlife women: a secondary analysis.

AIMS To explore the effect of diverse types of women's physical activity on menopausal symptoms among multiethnic groups of midlife women in the USA. BACKGROUND Although physical activity is one of the most widely used non-pharmacological methods for managing menopausal symptoms, there is a paucity of clinical guidelines for women and healthcare providers because the relationship between physical activity and menopausal symptoms has been found inconsistent in previous studies. DESIGN A secondary analysis of the data from a lager Internet survey study conducted in 2008-2010. METHODS A total of 481 midlife women among four ethnic groups were selected from the original study. The data were collected using the Kaiser Physical Activity Survey and the Midlife Women's Symptom Index. Bivariate correlation analyses and hierarchical multiple regression analyses were used to analyse the data. RESULTS/FINDINGS The household/caregiving activity index was positively associated with the prevalence scores of the psychological symptoms in both non-Hispanic Asians and non-Hispanic African Americans. The increased sports/exercise activity index was negatively associated with the severity scores of the physical symptoms in both Hispanics and non-Hispanic Whites. The occupational activity index and the active living activity index significantly predicted the severity scores of the psychosomatic symptoms in Hispanics and non-Hispanic African Americans, respectively. CONCLUSION Nurses who take care of multiethnic groups of midlife women who experience menopausal symptoms should be aware of diverse types of women's physical activities within the cultural context.
A Double-Blind, Randomized, Placebo-Controlled, Dose-Frequency Study of Intravenous Ketamine in Patients With Treatment-Resistant Depression.

OBJECTIVE Ketamine, an N-methyl-d-aspartate glutamate receptor antagonist, has demonstrated a rapid-onset antidepressant effect in patients with treatment-resistant depression. This study evaluated the efficacy of twice- and thrice-weekly intravenous administration of ketamine in sustaining initial antidepressant effects in patients with treatment-resistant depression. METHOD In a multicenter, double-blind study, adults (ages 18-64 years) with treatment-resistant depression were randomized to receive either intravenous ketamine (0.5 mg/kg of body weight) or intravenous placebo, administered over 40 minutes, either two or three times weekly, for up to 4 weeks. Patients who discontinued double-blind treatment after at least 2 weeks for lack of efficacy could enter an optional 2-week open-label phase to receive ketamine with the same frequency as in the double-blind phase. The primary outcome measure was change from baseline to day 15 in total score on the Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS In total, 67 (45 women) of 68 randomized patients received treatment. In the twice-weekly dosing groups, the mean change in MADRS score at day 15 was -18.4 (SD=12.0) for ketamine and -5.7 (SD=10.2) for placebo; in the thrice-weekly groups, it was -17.7 (SD=7.3) for ketamine and -3.1 (SD=5.7) for placebo. Similar observations were noted for ketamine during the open-label phase (twice-weekly, -12.2 [SD=12.8] on day 4; thrice-weekly, -14.0 [SD=12.5] on day 5). Both regimens were generally well tolerated. Headache, anxiety, dissociation, nausea, and dizziness were the most common (≥20%) treatment-emergent adverse events. Dissociative symptoms occurred transiently and attenuated with repeated dosing. CONCLUSIONS Twice-weekly and thrice-weekly administration of ketamine at 0.5 mg/kg similarly maintained antidepressant efficacy over 15 days.
Conditional Deletion of the L-Type Calcium Channel Cav1.2 in NG2-Positive Cells Impairs Remyelination in Mice

Exploring the molecular mechanisms that drive the maturation of oligodendrocyte progenitor cells (OPCs) during the remyelination process is essential to developing new therapeutic tools to intervene in demyelinating diseases such as multiple sclerosis. To determine whether L-type voltage-gated calcium channels (L-VGCCs) are required for OPC development during remyelination, we generated an inducible conditional knock-out mouse in which the L-VGCC isoform Cav1.2 was deleted in NG2-positive OPCs (Cav1.2KO). Using the cuprizone (CPZ) model of demyelination and mice of either sex, we establish that Cav1.2 deletion in OPCs leads to less efficient remyelination of the adult brain. Specifically, Cav1.2KO OPCs mature slower and produce less myelin than control oligodendrocytes during the recovery period after CPZ intoxication. This reduced remyelination was accompanied by an important decline in the number of myelinating oligodendrocytes and in the rate of OPC proliferation. Furthermore, during the remyelination phase of the CPZ model, the corpus callosum of Cav1.2KO animals presented a significant decrease in the percentage of myelinated axons and a substantial increase in the mean g-ratio of myelinated axons compared with controls. In addition, in a mouse line in which the Cav1.2KO OPCs were identified by a Cre reporter, we establish that Cav1.2KO OPCs display a reduced maturational rate through the entire remyelination process. These results suggest that Ca2+ influx mediated by L-VGCCs in oligodendroglial cells is necessary for normal remyelination and is an essential Ca2+ channel for OPC maturation during the remyelination of the adult brain. SIGNIFICANCE STATEMENT Ion channels implicated in oligodendrocyte differentiation and maturation may induce positive signals for myelin recovery. Voltage-gated Ca2+ channels (VGCCs) are important for normal myelination by acting at several critical steps during oligodendrocyte progenitor cell (OPC) development. To determine whether voltage Ca2+ entry is involved in oligodendrocyte differentiation and remyelination, we used a conditional knockout mouse for VGCCs in OPCs. Our results indicate that VGCCs can modulate oligodendrocyte maturation in the demyelinated brain and suggest that voltage-gated Ca2+ influx in OPCs is critical for remyelination. These findings could lead to novel approaches for obtaining a better understanding of the factors that control OPC maturation in order to stimulate this pool of progenitors to replace myelin in demyelinating diseases.
Electrical stimulation of adipose‐derived mesenchymal stem cells and endothelial cells co‐cultured in a conductive scaffold for potential orthopaedic applications

Electrical stimulation (ES) has emerged as a useful tool to regulate cell behaviour, but the effect of ES on mesenchymal stem cell (MSC)/vasculogenic cell co‐culture has not been investigated. Herein, human adipose‐derived MSCs (AD‐MSCs) and umbilical vein endothelial cells (HUVECs) were co‐cultured in an electrically conductive polypyrrole/chitosan scaffold. Compared with AD‐MSC monoculture, calcium deposition in the co‐culture without and with ES (200 μA for 4 h/day) was 139% and 346% higher, respectively, after 7 days. As the application of ES to AD‐MSC monoculture only increased calcium deposition by 56% compared with that without ES after 7 days, these results indicate that ES and co‐culture with HUVECs have synergistic effects on AD‐MSCs' osteogenic differentiation. ES application also significantly enhanced CD31 expression of HUVECs. In HUVEC monoculture, application of ES increased CD31 expression by 224%, whereas the corresponding increase in AD‐MSC/HUVEC co‐culture with ES application was 62%. The gene expression results indicate that ES enhanced the cellular functions in AD‐MSC and HUVEC monoculture via autocrine bone morphogenetic protein‐2 (BMP‐2) and vascular endothelial growth factor (VEGF), respectively. In co‐culture, crosstalk between AD‐MSCs and HUVECs due to paracrine BMP‐2 and VEGF enhanced the cellular functions compared with the respective monoculture. With application of ES to the AD‐MSC/HUVEC co‐culture, autocrine signalling was enhanced, resulting in further promotion of cellular functions. These findings illustrate that co‐culturing AD‐MSC/HUVEC in a conductive scaffold with ES offers potential benefits for bone defect therapy.
How will climate novelty influence ecological forecasts? Using the Quaternary to assess future reliability

Future climates are projected to be highly novel relative to recent climates. Climate novelty challenges models that correlate ecological patterns to climate variables and then use these relationships to forecast ecological responses to future climate change. Here, we quantify the magnitude and ecological significance of future climate novelty by comparing it to novel climates over the past 21,000 years in North America. We then use relationships between model performance and climate novelty derived from the fossil pollen record from eastern North America to estimate the expected decrease in predictive skill of ecological forecasting models as future climate novelty increases. We show that, in the high emissions scenario (RCP 8.5) and by late 21st century, future climate novelty is similar to or higher than peak levels of climate novelty over the last 21,000 years. The accuracy of ecological forecasting models is projected to decline steadily over the coming decades in response to increasing climate novelty, although models that incorporate co‐occurrences among species may retain somewhat higher predictive skill. In addition to quantifying future climate novelty in the context of late Quaternary climate change, this work underscores the challenges of making reliable forecasts to an increasingly novel future, while highlighting the need to assess potential avenues for improvement, such as increased reliance on geological analogs for future novel climates and improving existing models by pooling data through time and incorporating assemblage‐level information.
The Mycobacterium tuberculosis Drugome and Its Polypharmacological Implications

We report a computational approach that integrates structural bioinformatics, molecular modelling and systems biology to construct a drug-target network on a structural proteome-wide scale. The approach has been applied to the genome of Mycobacterium tuberculosis (M.tb), the causative agent of one of today's most widely spread infectious diseases. The resulting drug-target interaction network for all structurally characterized approved drugs bound to putative M.tb receptors, we refer to as the ‘TB-drugome’. The TB-drugome reveals that approximately one-third of the drugs examined have the potential to be repositioned to treat tuberculosis and that many currently unexploited M.tb receptors may be chemically druggable and could serve as novel anti-tubercular targets. Furthermore, a detailed analysis of the TB-drugome has shed new light on the controversial issues surrounding drug-target networks [1]–[3]. Indeed, our results support the idea that drug-target networks are inherently modular, and further that any observed randomness is mainly caused by biased target coverage. The TB-drugome (http://funsite.sdsc.edu/drugome/TB) has the potential to be a valuable resource in the development of safe and efficient anti-tubercular drugs. More generally the methodology may be applied to other pathogens of interest with results improving as more of their structural proteomes are determined through the continued efforts of structural biology/genomics.
IP3-mediated gating mechanism of the IP3 receptor revealed by mutagenesis and X-ray crystallography

Significance Cells use chemical signals for intracellular communication in our bodies. Inositol 1,4,5-trisphosphate (IP3) is a chemical signal that binds to the IP3 receptor (IP3R) to release calcium ions from the endoplasmic reticulum. The distance from ligand-binding sites to the channel within IP3R is the longest among known ligand-gated ion channels, and the fundamental question of how IP3-binding physically opens the channel remains unanswered. Here, we solved IP3-bound and unbound structures of large cytosolic domains of the IP3R by X-ray crystallography and clarified the IP3-dependent gating mechanism through a unique leaflet structure. These findings reveal a principle of long-range allosteric coupling in ligand-gated ion channels and provide drug targets for IP3R-regulated events, including autophagy, apoptosis, cancers, and brain disorders. The inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) is an IP3-gated ion channel that releases calcium ions (Ca2+) from the endoplasmic reticulum. The IP3-binding sites in the large cytosolic domain are distant from the Ca2+ conducting pore, and the allosteric mechanism of how IP3 opens the Ca2+ channel remains elusive. Here, we identify a long-range gating mechanism uncovered by channel mutagenesis and X-ray crystallography of the large cytosolic domain of mouse type 1 IP3R in the absence and presence of IP3. Analyses of two distinct space group crystals uncovered an IP3-dependent global translocation of the curvature α-helical domain interfacing with the cytosolic and channel domains. Mutagenesis of the IP3R channel revealed an essential role of a leaflet structure in the α-helical domain. These results suggest that the curvature α-helical domain relays IP3-controlled global conformational dynamics to the channel through the leaflet, conferring long-range allosteric coupling from IP3 binding to the Ca2+ channel.
The Emerging Pathogen Candida auris: Growth Phenotype, Virulence Factors, Activity of Antifungals, and Effect of SCY-078, a Novel Glucan Synthesis Inhibitor, on Growth Morphology and Biofilm Formation

ABSTRACT Candida auris, a new multidrug-resistant Candida spp. which is associated with invasive infection and high rates of mortality, has recently emerged. Here, we determined the virulence factors (germination, adherence, biofilm formation, phospholipase and proteinase production) of 16 C. auris isolates and their susceptibilities to 11 drugs belonging to different antifungal classes, including a novel orally bioavailable 1,3-β-d-glucan synthesis inhibitor (SCY-078). We also examined the effect of SCY-078 on the growth, ultrastructure, and biofilm-forming abilities of C. auris. Our data showed that while the tested strains did not germinate, they did produce phospholipase and proteinase in a strain-dependent manner and had a significantly reduced ability to adhere and form biofilms compared to that of Candida albicans (P = 0.01). C. auris isolates demonstrated reduced susceptibility to fluconazole and amphotericin B, while, in general, they were susceptible to the remaining drugs tested. SCY-078 had an MIC90 of 1 mg/liter against C. auris and caused complete inhibition of the growth of C. auris and C. albicans. Scanning electron microscopy analysis showed that SCY-078 interrupted C. auris cell division, with the organism forming abnormal fused fungal cells. Additionally, SCY-078 possessed potent antibiofilm activity, wherein treated biofilms demonstrated significantly reduced metabolic activity and a significantly reduced thickness compared to the untreated control (P < 0.05 for both comparisons). Our study shows that C. auris expresses several virulence determinants (albeit to a lesser extent than C. albicans) and is resistant to fluconazole and amphotericin B. SCY-078, the new orally bioavailable antifungal, had potent antifungal/antibiofilm activity against C. auris, indicating that further evaluation of this antifungal is warranted.
Fast and Space-optimal Low-rank Factorization in the Streaming Model With Application in Differential Privacy

In this paper, we consider the problem of computing a low-rank factorization of an $m \times n$ matrix in the general turnstile update model. We consider both the private and non-private setting. In the non-private setting, we give a space-optimal algorithm that computes a low-rank factorization. Our algorithm maintains three sketches of the matrix instead of five as in Boutsidis {\it et al.} (STOC 2016). Our algorithm takes $\widetilde{O}(1)$ time to update the sketch and computes the factorization in time linear in the sparsity and the dimensions of the matrix. In the private setting, we study low-rank factorization in the framework of differential privacy and under turnstile updates. We give two algorithms with respect to two levels of privacy. Both of our privacy levels are stronger than earlier studied privacy levels, namely that of Blocki {\it et al.} (FOCS 2012), Dwork {\it et al.} (STOC 2014), Hardt and Roth (STOC 2012, STOC 2013), and Hardt and Price (NIPS 2014).
Dietary planning, self-efficacy, and outcome expectancies play a role in an online intervention on fruit and vegetable consumption

Objective: An online intervention to improve fruit and vegetable (FV) intake examines the role of planning, outcome expectancies, self-efficacy and gender. Women are not only expected to eat more FV than men, but they are also expected to be more responsive to nutritional advice and benefit more from treatment. Method: A two-arm digital intervention with 269 men and 395 women (Mage = 41.2, SDage = 11.45; range: 19–66 years) was conducted in Italy, Spain and Greece, followed up at three and six months, comparing a static with a dynamic, feedback-intensive platform. Results: Linear mixed models yielded an increase in FV consumption in both the dynamic and the static intervention arms. In men, outcome expectancies were positively related to follow-up FV intake. Dietary planning interacted with self-efficacy on behavioural outcomes. Conclusion: FV intake increased overall, and being a woman and involvement in planning facilitated behaviour change. Women seemed to be more engaged in the dynamic platform resulting in a higher amount of planning. Initial motivation, as indicated by outcome expectancies, seemed to be beneficial for men. Self-efficacious individuals benefitted from their engagement in planning, but self-efficacy did not compensate for failing to plan.