Miracle-dz/UniFAR-FTUs huggingface dataset:
Experimental heatwaves facilitate invasion and alter species interactions and composition in a tropical host‐parasitoid community

As mean temperatures increase and heatwaves become more frequent, species are expanding their distributions to colonise new habitats. The resulting novel species interactions will simultaneously shape the temperature‐driven reorganization of resident communities. The interactive effects of climate change and climate change‐facilitated invasion have rarely been studied in multi‐trophic communities, and are likely to differ depending on the nature of the climatic driver (i.e., climate extremes or constant warming). We re‐created under laboratory conditions a host‐parasitoid community typical of high‐elevation rainforest sites in Queensland, Australia, comprising four Drosophila species and two associated parasitoid species. We subjected these communities to an equivalent increase in average temperature in the form of periodic heatwaves or constant warming, in combination with an invasion treatment involving a novel host species from lower‐elevation habitats. The two parasitoid species were sensitive to both warming and heatwaves, while the demographic responses of Drosophila species were highly idiosyncratic, reflecting the combined effects of thermal tolerance, parasitism, competition, and facilitation. After multiple generations, our heatwave treatment promoted the establishment of low‐elevation species in upland communities. Invasion of the low‐elevation species correlated negatively with the abundance of one of the parasitoid species, leading to cascading effects on its hosts and their competitors. Our study, therefore, reveals differing, sometimes contrasting, impacts of extreme temperatures and constant warming on community composition. It also highlights how the scale and direction of climate impacts could be further modified by invading species within a bi‐trophic community network.
CDC7 kinase inhibitors: a survey of recent patent literature (2017–2022)

ABSTRACT Introduction CDC7 is a serine/threonine kinase which plays an important role in DNA replication. Inhibition of CDC7 in cancer cells causes lethal S phase or M phase progression, whereas inhibition of CDC7 in normal cells does not cause cell death and only leads to cell cycle arrest at the DNA replication checkpoint. Therefore, CDC7 has been recognized as a potential target for novel therapeutic interventions in cancers. Areas covered Patent literature claiming novel small molecule compounds inhibiting CDC7 disclosed from 2017 to 2022. Expert opinion Despite the indisputable positive impact of CDC7 as a drug target, there have been reported only a handful of chemical scaffolds as CDC7 inhibitors. Several CDC7 inhibitors have been progressed into clinical trials for cancer treatments, but they did not result in satisfactory efficacies in those trials. One possible reason for the failure might be due to the dose-limiting toxicities, and some of the observed toxicities were thought to be not related to CDC7 inhibition, suggesting it should be important to identify novel chemical scaffolds to eliminate unwanted toxicities. Another important factor is the patient stratification that would enable greater response, and the identification of such predictive biomarkers should be the key to success for the development of CDC7 inhibitors.
The plant noncoding transcriptome: a versatile environmental sensor

Plant noncoding RNA transcripts have gained increasing attention in recent years due to growing evidence that they can regulate developmental plasticity. In this review article, we comprehensively analyze the relationship between noncoding RNA transcripts in plants and their response to environmental cues. We first provide an overview of the various noncoding transcript types, including long and small RNAs, and how the environment modulates their performance. We then highlight the importance of noncoding RNA secondary structure for their molecular and biological functions. Finally, we discuss recent studies that have unveiled the functional significance of specific long noncoding transcripts and their molecular partners within ribonucleoprotein complexes during development and in response to biotic and abiotic stress. Overall, this review sheds light on the fascinating and complex relationship between dynamic noncoding transcription and plant environmental responses, and highlights the need for further research to uncover the underlying molecular mechanisms and exploit the potential of noncoding transcripts for crop resilience in the context of global warming.
Public Perception towards Punjab Emergency Service (Rescue 1122): A Case Study of Lahore City, Punjab, Pakistan

This research aims at to know the perception of Punjab Emergency Service (Rescue 1122) among general public of Punjab, Pakistan. Rescue 1122 was launched from Lahore dating back 2004 and later on, it expanded to all districts of Punjab and other provinces of the country including Khyber Pakhtunkhaw; Gilgit Baltistan and Azad Jamu & Kashmir. The researchers adopted Survey as methodology to analyze the perception of Rescue 1122 in the minds of citizens of Punjab. Lahore, widely considered as a heart of Pakistan because having people belonging to all areas of the country, was selected for survey study. A questionnaire was developed, which carried 25 open ended questions and the population of 500 respondents were chosen on nonrandom sampling basis. Total 491 respondents replied, and majority of the respondents gave positive opinion about provision of emergency services to the victims of various emergencies. The youth gave more positive opinion about the Service as compared to senior citizens, whereas the people belonging to urban areas especially the females were more aware of about the functioning of Rescue 1122 as compared to the same age group living in rural areas. They, however, recommended that more females should be encouraged in the department. Majority of the respondents also opinionated about minimum corruption chances in Rescue 1122 as compared to other departments. Overall, the satisfaction level was observed up to the mark. Also, the hypothesis set by the researchers proved true.
Construction of an artificial phosphoketolase pathway that efficiently catabolizes multiple carbon sources to acetyl-CoA

The canonical glycolysis pathway is responsible for converting glucose into 2 molecules of acetyl-coenzyme A (acetyl-CoA) through a cascade of 11 biochemical reactions. Here, we have designed and constructed an artificial phosphoketolase (APK) pathway, which consists of only 3 types of biochemical reactions. The core enzyme in this pathway is phosphoketolase, while phosphatase and isomerase act as auxiliary enzymes. The APK pathway has the potential to achieve a 100% carbon yield to acetyl-CoA from any monosaccharide by integrating a one-carbon condensation reaction. We tested the APK pathway in vitro, demonstrating that it could efficiently catabolize typical C1-C6 carbohydrates to acetyl-CoA with yields ranging from 83% to 95%. Furthermore, we engineered Escherichia coli stain capable of growth utilizing APK pathway when glycerol act as a carbon source. This novel catabolic pathway holds promising route for future biomanufacturing and offering a stoichiometric production platform using multiple carbon sources.
Highly Electrophilic Intermediates in the Bypass Mechanism of Glutathione Peroxidase: Synthesis, Reactivity, and Structures of Selenocysteine-Derived Cyclic Selenenyl Amides.

Selenocysteine (Sec)-derived cyclic selenenyl amides, formed by the intramolecular cyclization of Sec selenenic acids (Sec-SeOHs), have been postulated to function as protective forms in the bypass mechanism of glutathione peroxidase (GPx). However, their chemical properties have not been experimentally elucidated in proteins or small-molecule systems. Recently, we reported the first nuclear magnetic resonance observation of Sec-SeOHs and their cyclization to the corresponding cyclic selenenyl amides using selenopeptide model systems incorporated in a molecular cradle. Herein, we elucidate the structures and reactivities of Sec-derived cyclic selenenyl amides. The crystal structures and reactions toward a cysteine thiol or a 1,3-diketone-type chemical probe indicated the highly electrophilic character of cyclic selenenyl amides. This suggests that they can serve not only as protective forms to suppress the inactivation of Sec-SeOHs in GPx but also as highly electrophilic intermediates in the reactions of selenoproteins.
IκB kinase‐α coordinates BRD4 and JAK/STAT signaling to subvert DNA damage‐based anticancer therapy

Activation of the IκB kinase (IKK) complex has recurrently been linked to colorectal cancer (CRC) initiation and progression. However, identification of downstream effectors other than NF‐κB has remained elusive. Here, analysis of IKK‐dependent substrates in CRC cells after UV treatment revealed that phosphorylation of BRD4 by IKK‐α is required for its chromatin‐binding at target genes upon DNA damage. Moreover, IKK‐α induces the NF‐κB‐dependent transcription of the cytokine LIF, leading to STAT3 activation, association with BRD4 and recruitment to specific target genes. IKK‐α abrogation results in defective BRD4 and STAT3 functions and consequently irreparable DNA damage and apoptotic cell death upon different stimuli. Simultaneous inhibition of BRAF‐dependent IKK‐α activity, BRD4, and the JAK/STAT pathway enhanced the therapeutic potential of 5‐fluorouracil combined with irinotecan in CRC cells and is curative in a chemotherapy‐resistant xenograft model. Finally, coordinated expression of LIF and IKK‐α is a poor prognosis marker for CRC patients. Our data uncover a functional link between IKK‐α, BRD4, and JAK/STAT signaling with clinical relevance.
Dupilumab leads to better-controlled asthma and quality of life in children: the VOYAGE study

Background Dupilumab has shown long-term treatment benefits in children with uncontrolled asthma. We assessed in more detail the impact of dupilumab on asthma control and health-related quality of life (HRQoL) in children and their caregivers. Methods Children aged 6–11 years with uncontrolled moderate-to-severe type 2 asthma (baseline blood eosinophils ≥150 cells·µL−1 or fractional exhaled nitric oxide ≥20 ppb; n=350) were treated with dupilumab or placebo for 52 weeks in the VOYAGE study. Primary outcomes of these analyses were asthma control (change from baseline in Asthma Control Questionnaire 7 Interviewer-Administered (ACQ-7-IA) and achieving a clinically meaningful response of ≥0.5 points); proportion of patients achieving well-controlled asthma or better (ACQ-7-IA ≤0.75 points); effect on patients’ (Standardised Paediatric Asthma Quality of Life Questionnaire Interviewer-Administered (PAQLQ(S)-IA)) and caregivers’ (Paediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ)) HRQoL; and allergic rhinitis-related QoL. Results Dupilumab versus placebo significantly improved children's ACQ-7-IA scores by week 4 with sustained improvements through week 52 (least squares mean difference at week 52: −0.44, 95% CI −0.59– −0.30; p<0.0001); a higher proportion achieved a clinically meaningful response (week 52: 86% versus 75%; p=0.0051). At weeks 24 and 52, more children who received dupilumab achieved well-controlled asthma (ACQ-7-IA ≤0.75 points: 61% versus 43%; p=0.0001 and 70% versus 46%; p<0.0001, respectively). Significant improvements in PAQLQ(S)-IA and PACQLQ scores were observed by week 52. Conclusions In children aged 6–11 years with moderate-to-severe type 2 asthma, dupilumab treatment was associated with rapid, sustained improvements in asthma control. HRQoL was significantly improved for children and their caregivers. Tweetable abstract This novel analysis of VOYAGE demonstrates that dupilumab significantly improves asthma control and health-related quality of life in children 6–11 years old with moderate-to-severe type 2 asthma, as well as the quality of life of their caregivers https://bit.ly/3RrLpyJ
Subcutaneous Bacillus Calmette–Guérin Administration Induces Innate Training in Monocytes in Preweaned Holstein Calves

Abstract The bacillus Calmette–Guérin (BCG) vaccine, administered to prevent tuberculosis, is a well-studied inducer of trained immunity in human and mouse monocytes. We have previously demonstrated that aerosol BCG administration induces innate training in calves. The current study aimed to determine whether s.c. BCG administration could induce innate training, identify the cell type involved, and determine whether innate training promoted resistance to bovine respiratory syncytial virus (BRSV) infection, a major cause of bovine respiratory disease in preweaned calves. A total of 24 calves were enrolled at 1–3 d of age and blocked by age into two treatment groups (BCG, n = 12; control, n = 12). BCG was given s.c. to preweaned calves. The control calves received PBS. We observed a trained phenotype, demonstrated by enhanced cytokine production in response to in vitro stimulation with LPS (TLR-4 agonist) in PBMCs and CD14+ monocytes from the BCG group 2 wk (IL-1β, p = 0.002) and 4 wk (IL-1β, p = 0.005; IL-6, p = 0.013) after BCG administration, respectively. Calves were experimentally infected via aerosol inoculation with BRSV strain 375 at 5 wk after BCG administration and necropsied on day 8 postinfection. There were no differences in disease manifestation between the treatment groups. Restimulation of bronchoalveolar lavage fluid cells isolated on day 8 after BRSV infection revealed enhanced IL-1β (p = 0.014) and IL-6 (p = 0.010) production by the BCG group compared with controls. In conclusion, results from our study show that s.c. administration of the BCG vaccine can induce trained immunity in bovine monocytes and influence cytokine production in the lung environment after BRSV infection.
The combined effects of treated sewage discharge and land use on rivers

Freshwater ecosystems are increasingly threatened by multiple anthropogenic stressors. Release of treated sewage effluent and pollution from agricultural or urban sources can independently reduce water quality with implications for ecological communities. However, our knowledge of the combined effects of these stressors is limited. We performed a field study to quantify the combined effect of treated sewage discharge and land use on nutrient concentrations, sewage fungus presence and communities of macroinvertebrates and benthic algae. Over three seasons in four rivers we found that a model which included an interaction between sewage pollution and time of the year (i.e. months) was the best predictor of nutrient concentrations and the abundance of algae and sewage fungus. Both macroinvertebrate and algae communities shifted downstream of sewage input. Specifically, more tolerant groups, such as cyanobacteria and oligochaetes, were more abundant. The EPT (Ephemeroptera, Plecoptera and Tricoptera) water quality score was best explained by an interaction between month and agriculture in the surrounding landscape. Overall, our results show that sewage discharge has a significant impact on water quality and benthic riverine communities, regardless of the surrounding land uses. Agricultural inputs, however, could be more important than treated sewage discharge in reducing the abundance of sensitive invertebrate taxa. We need both improvements to wastewater treatment processes and reductions in agricultural pollution to reduce threats to vulnerable freshwater communities.
Emerging Mechanisms in the Pathogenesis of Menière’s Disease: Evidence for the Involvement of Ion Homeostatic or Blood–Labyrinthine Barrier Dysfunction in Human Temporal Bones

Hypothesis Analysis of human temporal bone specimens of patients with Menière’s disease (MD) may demonstrate altered expression of gene products related to barrier formation and ionic homeostasis within cochlear structures compared with control specimens Background MD represents a challenging otologic disorder for investigation. Despite attempts to define the pathogenesis of MD, there remain many gaps in our understanding, including differences in protein expression within the inner ear. Understanding these changes may facilitate the identification of more targeted therapies for MD. Methods Human temporal bones from patients with MD (n = 8) and age-matched control patients (n = 8) were processed with immunohistochemistry stains to detect known protein expression related to ionic homeostasis and barrier function in the cochlea, including CLDN11, CLU, KCNJ10, and SLC12A2. Immunofluorescence intensity analysis was performed to quantify protein expression in the stria vascularis, organ of Corti, and spiral ganglion neuron (SGN). Results Expression of KCNJ10 was significantly reduced in all cochlear regions, including the stria vascularis (9.23 vs 17.52, p = 0.011), OC (14.93 vs 29.16, p = 0.014), and SGN (7.69 vs 18.85, p = 0.0048) in human temporal bone specimens from patients with MD compared with control, respectively. CLDN11 (7.40 vs 10.88, p = 0.049) and CLU (7.80 vs 17.51, p = 0.0051) expression was significantly reduced in the SGN. Conclusion The results of this study support that there may be differences in the expression of proteins related to ionic homeostasis and barrier function within the cochlea, potentially supporting the role of targeted therapies to treat MD.
Prospects and Pitfalls of Plasma Complement C4 in Schizophrenia: Building a Better Biomarker

Complex brain disorders like schizophrenia may have multifactorial origins related to mis-timed heritable and environmental factors interacting during neurodevelopment. Infections, inflammation, and autoimmune diseases are over-represented in schizophrenia leading to immune system-centered hypotheses. Complement component C4 is genetically and neurobiologically associated with schizophrenia, and its dual activity peripherally and in the brain makes it an exceptional target for biomarker development. Studies to evaluate the biomarker potential of plasma or serum C4 in schizophrenia do so to understand how peripheral C4 might reflect central nervous system-derived neuroinflammation, synapse pruning, and other mechanisms. This effort, however, has produced mostly conflicting results, with peripheral C4 sometimes elevated, reduced, or unchanged between comparison groups. We undertook a pilot biomarker development study to systematically identify sociodemographic, genetic, and immune-related variables (autoimmune, infection-related, gastrointestinal, inflammatory), which may be associated with plasma C4 levels in schizophrenia (SCH; n = 335) and/or in nonpsychiatric comparison subjects (NCs; n = 233). As with previously inconclusive studies, we detected no differences in plasma C4 levels between SCH and NCs. In contrast, levels of general inflammation, C-reactive protein (CRP), were significantly elevated in SCH compared to NCs (ANOVA, F = 20.74, p < 0.0001), suggestive that plasma C4 and CRP may reflect different sources or causes of inflammation. In multivariate regressions of C4 gene copy number variants, plasma C4 levels were correlated only for C4A (not C4B, C4L, C4S) and only in NCs (R Coeff = 0.39, CI = 0.01–0.77, R2 = 0.18, p < 0.01; not SCH). Other variables associated with plasma C4 levels only in NCs included sex, double-stranded DNA IgG, tissue-transglutaminase (TTG) IgG, and cytomegalovirus IgG. Toxoplasma gondii IgG was the only variable significantly correlated with plasma C4 in SCH but not in NCs. Many variables were associated with plasma C4 in both groups (body mass index, race, CRP, N-methyl-D-aspartate receptor (NMDAR) NR2 subunit IgG, TTG IgA, lipopolysaccharide-binding protein (LBP), and soluble CD14 (sCD14). While the direction of most C4 associations was positive, autoimmune markers tended to be inverse, and associated with reduced plasma C4 levels. When NMDAR-NR2 autoantibody-positive individuals were removed, plasma C4 was elevated in SCH versus NCs (ANOVA, F = 5.16, p < 0.02). Our study was exploratory and confirmation of the many variables associated with peripheral C4 requires replication. Our preliminary results point toward autoimmune factors and exposure to the pathogen, T. gondii, as possibly significant contributors to variability of total C4 protein levels in plasma of individuals with schizophrenia.
Click Chemistry and Radiochemistry: An Update

The term “click chemistry” describes a class of organic transformations that were developed to make chemical synthesis simpler and easier, in essence allowing chemists to combine molecular subunits as if they were puzzle pieces. Over the last 25 years, the click chemistry toolbox has swelled from the canonical copper-catalyzed azide–alkyne cycloaddition to encompass an array of ligations, including bioorthogonal variants, such as the strain-promoted azide–alkyne cycloaddition and the inverse electron-demand Diels–Alder reaction. Without question, the rise of click chemistry has impacted all areas of chemical and biological science. Yet the unique traits of radiopharmaceutical chemistry have made it particularly fertile ground for this technology. In this update, we seek to provide a comprehensive guide to recent developments at the intersection of click chemistry and radiopharmaceutical chemistry and to illuminate several exciting trends in the field, including the use of emergent click transformations in radiosynthesis, the clinical translation of novel probes synthesized using click chemistry, and the advent of click-based in vivo pretargeting.
Evaluating Dual Task Neurological Costs with Functional Near-Infrared Spectroscopy: A Preliminary Report in Healthy Athletes.

BACKGROUND Dual task assessments, which simultaneously challenge and assess cognitive and motor performance, have been used to improve the assessment of athletes with sports-related concussions (SRC). Our lab created a Dual Task Screen (DTS) to evaluate athletes with SRCs, and we have established that it is a valid behavioral measure, as it consistently elicits poorer behavioral performance under dual, compared to single, task conditions. Here, we used a Neuroimaging-Compatible (NC) version of the DTS, named the NC-DTS, which uses portable functional near-infrared spectroscopy (fNIRS) to assess behavioral performance and neural recruitment during single and dual tasks. Our study objective was to evaluate healthy athletes and establish whether the NC-DTS is a valid dual task neurological assessment that can elicit different patterns of neural recruitment during dual versus single task conditions. METHODS Twenty-five healthy collegiate athletes completed the NC-DTS in a single laboratory visit. The NC-DTS includes a lower and upper extremity subtask; both include single motor, single cognitive, and dual task conditions. The NC-DTS was administered in a block design, where conditions (i.e., single motor, single cognitive, and dual task) were repeated five times to generate average behavioral performance and task-dependent neural recruitment in superficial cortical regions including: prefrontal cortex, bilateral primary motor and sensory cortices, and posterior parietal cortex. Neural recruitment was measured with fNIRS and quantified using oxygenated hemoglobin (HbO) and deoxygenated hemoglobin (HbR) metrics. A single-tailed, within subject t-test was used to compare average dual task behavioral performance to average single task behavioral performance. Pairwise comparisons, that were family-wise-error (FWE) corrected, were used to compare localized neural recruitment during dual versus single task conditions. RESULTS As observed in previous studies, the NC-DTS elicited significantly poorer behavioral performance under dual, compared to single, task conditions. Additionally, dual task conditions of the NC-DTS elicited significantly greater neural recruitment in regions of the brain associated with attention allocation and task-specific demands in three of four comparisons. CONCLUSIONS These preliminary results suggest that the NC-DTS is a valid dual task neurological assessment which warrants future work using the NC-DTS to evaluate athletes with SRCs.