Miracle-dz/UniFAR-FTUs huggingface dataset:
Live-cell fluorescence imaging of microgametogenesis in the human malaria parasite Plasmodium falciparum

Formation of gametes in the malaria parasite occurs in the midgut of the mosquito and is critical to onward parasite transmission. Transformation of the male gametocyte into microgametes, called microgametogenesis, is an explosive cellular event and one of the fastest eukaryotic DNA replication events known. The transformation of one microgametocyte into eight flagellated microgametes requires reorganisation of the parasite cytoskeleton, replication of the 22.9 Mb genome, axoneme formation and host erythrocyte egress, all of which occur simultaneously in <20 minutes. Whilst high-resolution imaging has been a powerful tool for defining stages of microgametogenesis, it has largely been limited to fixed parasite samples, given the speed of the process and parasite photosensitivity. Here, we have developed a live-cell fluorescence imaging workflow that captures the entirety of microgametogenesis. Using the most virulent human malaria parasite, Plasmodium falciparum, our live-cell approach captured early microgametogenesis with three-dimensional imaging through time (4D imaging) and microgamete release with two-dimensional (2D) fluorescence microscopy. To minimise the phototoxic impact to parasites, acquisition was alternated between 4D fluorescence, brightfield and 2D fluorescence microscopy. Combining live-cell dyes specific for DNA, tubulin and the host erythrocyte membrane, 4D and 2D imaging together enables definition of the positioning of newly replicated and segregated DNA. This combined approach also shows the microtubular cytoskeleton, location of newly formed basal bodies, elongation of axonemes and morphological changes to the erythrocyte membrane, the latter including potential echinocytosis of the erythrocyte membrane prior to microgamete egress. Extending the utility of this approach, the phenotypic effects of known transmission-blocking inhibitors on microgametogenesis were confirmed. Additionally, the effects of bortezomib, an untested proteasomal inhibitor, revealed a clear block of DNA replication, full axoneme nucleation and elongation. Thus, as well as defining a framework for broadly investigating microgametogenesis, these data demonstrate the utility of using live imaging to validate potential targets for transmission-blocking antimalarial drug development.
Cancer Treatment During COVID-19: Resilience of Individuals With Advanced Non-Small Cell Lung Cancer Versus Community Controls.

BACKGROUND Among all patients with cancer, those with advanced non-small cell lung cancer (NSCLC) experience the most distress. Although new therapies are improving survival, it is unknown whether receiving immunotherapy or targeted therapy during the COVID-19 pandemic increases patients' psychological vulnerability. To meet clinical needs, knowledge of patients' COVID-19 perceptions and safety behaviors is essential. Thus, this study compared patients' psychological responses at diagnosis and during COVID-19 and compared patients with similar individuals without cancer during the same period. PATIENTS AND METHODS Patients with advanced NSCLC enrolled at diagnosis for cohort study participated (ClinicalTrials.gov identifier: NCT03199651). Those with follow-ups from April 28, 2020, through July 14, 2020 (n=76), were assessed again including COVID-19 measures. Simultaneously, community controls with similar sociodemographics and smoking histories were solicited (n=67). Measures were COVID-19 perceptions (Brief Illness Perception Questionnaire), social distancing, and depressive (Patient Health Questionnaire-9) and anxiety (Generalized Anxiety Disorder-7) symptoms. First, analyses evaluated differences in the psychological responses of patients with NSCLC at diagnosis and during COVID-19. Second, patients and controls were contrasted on COVID-19 perceptions, social distancing, and psychological symptoms. RESULTS The depressive and anxious symptoms of patients with NSCLC were greater at diagnosis (P<.02) than during COVID-19, approximately 1 year later. Patients with NSCLC and controls did not differ in terms of sociodemographics, except those with NSCLC were more racially diverse and older, and had greater smoking history (P<.03). Groups did not differ regarding concern, understanding, or perceived control over COVID-19 (P>.406). Notably, controls anticipated the COVID threat would last longer, practiced more social distancing, were more concerned about family (P<.04), and reported worse psychological symptoms (P<.023). With less depression and anxiety, patients with NSCLC viewed COVID-19 as a shorter-term threat and had fewer COVID-19-related worries than did controls. For controls, COVID-19 was more salient, heightening worries and psychological symptoms. CONCLUSIONS Despite multiple health stressors, patients with NSCLC demonstrated resilience when receiving cancer treatment during COVID-19. Nonetheless, this population remains psychologically vulnerable, requiring support at diagnosis and thereafter.
Intercellular adhesive molecule 1(ICAM-1) and acute ischaemic stroke: Role of statins.

Objectives To demonstrate the differential effect of atorvastatin and rosuvastatin on the Intercellular adhesive molecule 1(ICAM-1) in acute ischaemic stroke (AIS) patients. METHODS The case-control study was done in the Department of Clinical Pharmacology and Therapeutic, Mustansiriyah University, Baghdad, from May to July, 2020 and involved sixty-six patients with AIS compared with twenty-two healthy controls. They were divided into four groups; Group I: Patients with AIS on atorvastatin therapy (n=22). Group II: Patients with AIS on rosuvastatin therapy (n=22), Group III: Patients with AIS not on statin therapy (n=22), Group IV: Healthy controls (n=22). Anthropometric, lipid, and pressure profiles were evaluated. As well, ICAM-1 serum level was estimated in different treatment groups. SPSS version 20.00 was used for data analysis. RESULTS ICAM-1 levels were increased in patients with AIS compared to the controls. ICAM-1 serum levels were higher in patients with AIS not on statins therapy compared to the controls (P=0.0001), and it was lower in patients with AIS on statins therapy (77.41±16.46) as compared with patients with AIS not on statin therapy (118.71±10.38), (P=0.001). Besides, there was differential effect of statin therapy on the ICAM-1 serum level, which was higher in patients with AIS on rosuvastatin (72.93±9.03) as compared with patients with AIS on atorvastatin (70.61±10.94), (P=0.44). Stroke risk score (SRS) was lower in patients with AIS on atorvastatin therapy (7.60±2.05) as compared with patients with AIS on rosuvastatin therapy (9.11±2.72), (P=0.04). CONCLUSIONS ICAM-1 is regarded as a surrogate biomarker of AIS in patients with underlying poor cardio-metabolic profile. Both atorvastatin and rosuvastatin are effective in attenuation of AIS measured by lowering of ICAM-1 serum levels.
Single-cell genomics for resolution of conserved bacterial genes and mobile genetic elements of the human intestinal microbiota using flow cytometry

ABSTRACT As our understanding of the importance of the human microbiota in health and disease grows, so does our need to carefully resolve and delineate its genomic content. 16S rRNA gene-based analyses yield important insights into taxonomic composition, and metagenomics-based approaches reveal the functional potential of microbial communities. However, these methods generally fail to directly link genetic features, including bacterial genes and mobile genetic elements, to each other and to their source bacterial genomes. Further, they are inadequate to capture the microdiversity present within a genus, species, or strain of bacteria within these complex communities. Here, we present a method utilizing fluorescence-activated cell sorting for isolation of single bacterial cells, amplifying their genomes, screening them by 16S rRNA gene analysis, and selecting cells for genomic sequencing. We apply this method to both a cultured laboratory strain of Escherichia coli and human stool samples. Our analyses reveal the capacity of this method to provide nearly complete coverage of bacterial genomes when applied to isolates and partial genomes of bacterial species recovered from complex communities. Additionally, this method permits exploration and comparison of conserved and variable genomic features between individual cells. We generate assemblies of novel genomes within the Ruminococcaceae family and the Holdemanella genus by combining several 16S rRNA gene-matched single cells, and report novel prophages and conjugative transposons for both Bifidobacterium and Ruminococcaceae. Thus, we demonstrate an approach for flow cytometric separation and sequencing of single bacterial cells from the human microbiota, which yields a variety of critical insights into both the functional potential of individual microbes and the variation among those microbes. This method definitively links a variety of conserved and mobile genomic features, and can be extended to further resolve diverse elements present in the human microbiota.
Spiritual over physical formidability determines willingness to fight and sacrifice through loyalty in cross-cultural populations

Significance Despite intermittent interest in and evidence of the importance of nonmaterial factors in war and other extreme forms of intergroup conflict, material factors such as optimal use of physical strength, manpower, and firepower remain the dominant concerns of US and allied military training, decision-making, and related academic literature. In this work, we demonstrate the cross-cultural primacy of personal spiritual over physical formidability on the will to fight in populations from the Middle East, Europe, and North America, including US cadets in whom stronger group loyalty mediates the effect. This empirical examination of spiritual formidability and its link between self and group in willingness to self-sacrifice aims to extend understanding of interpersonal and intergroup conflict and inform considerations of policy. Across 11 studies involving six countries from four continents (n = 3,285), we extend insights from field investigations in conflict zones to offline and online surveys to show that personal spiritual formidability—the conviction and immaterial resources (values, strengths of beliefs, character) of a person to fight—is positively associated with the will to fight and sacrifice for others. The physical formidability of groups in conflict has long been promoted as the primary factor in human decisions to fight or flee in times of conflict. Here, studies in Spain, Iraq, Lebanon, Palestine, and Morocco reveal that personal spiritual formidability, a construct distinct from religiosity, is more strongly associated with the willingness to fight and make costly self-sacrifices for the group than physical formidability. A follow-on study among cadets of the US Air Force Academy further indicates that this effect is mediated by a stronger loyalty to the group, a finding replicated in a separate study with a European sample. The results demonstrate that personal spiritual formidability is a primary determinant of the will to fight across cultures, and this individual-level factor, propelled by loyal bonds made with others, disposes citizens and combatants to fight at great personal risk.
Shame proneness is associated with individual differences in temporal pole white matter structure

ABSTRACT Shame and guilt are distinct negative moral emotions, although they are usually regarded as overlapping affective experiences. Of these two emotions, shame is more closely related to concerns about other people’s judgment, whereas guilt is more related to concerns about one’s own judgment. Although some studies have tried to identify the psychological process underlying shame as opposed to guilt, there is no clear evidence of brain regions that are specifically relevant to the experience of shame rather than guilt and, more generally, self-blame. We therefore investigated associations between individual differences in shame- and guilt-proneness and the gray and white matter structures of the brain using magnetic resonance imaging and voxel-based morphometry while controlling for associations with guilt- or shame-proneness. To accomplish this goal, we enrolled 590 healthy, right-handed individuals (338 men and 252 women; age, 20.6 ± 1.8 years). We administered a questionnaire to assess shame proneness and guilt proneness. Based on our hypothesis, we found that high shame proneness was associated with decreased regional white matter density only in the right inferior temporal pole, whereas no significant region was associated with guilt. The function of this area may be important for the underlying processes differentiating shame from guilt.
N, P, O-codoped biochar from phytoremediation residues: a promising cathode material for Li–S batteries

Environment and energy are two key issues in today’s society. In terms of environmental protection, the treatment of phytoremediation residues has become a key problem to be solved urgently, while for energy storage, it tends to utilize low-cost and high specific energy storage materials (i.e. porous carbon). In this study, the phytoremediation residues is applied to the storage materials with low-cost and high specific capacity. Firstly, the phosphorous acid assisted pyrolysis of oilseed rape stems from phytoremediation is effective in the removal of Zn, Cu, Cd and Cr from the derived biochar. Moreover, the derived biochar from phytoremediation residues shows abundant porous structure and polar groups (–O/–P/–N), and it can deliver 650 mAh g−1 with 3.0 mg cm−2 sulfur, and keeps 80% capacity after 200 cycles when employing it as a sulfur host for lithium–sulfur (Li–S) batteries. Hence, phosphorous acid assisted pyrolysis and application in Li–S battery is a promising approach for the disposal of phytoremediation residues, which is contributed to the environmental protection as well as energy storage.
Association between the Estimated Glomerular Filtration Rate and Brain Atrophy in Older Adults

End-stage kidney disease has been associated with cognitive impairment and brain atrophy. It remains unclear if mild to moderate kidney dysfunction is associated with brain atrophy, especially in older adults. We used cross-sectional data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), an NIH-funded multicenter longitudinal cohort study, to better understand the association between estimated glomerular filtration rate (eGFR) and brain volumes. We included all ADNI participants with both baseline serum creatinine values and MRI brain volume assessments. We used multiple linear regression modeling to assess cross-sectional associations between eGFR and whole-brain gray matter, hippocampus, entorhinal, fusiform, and middle temporal brain volumes. Participants (n = 1,596) were 74 ± 7 years old with a mean eGFR of 69.4 ± 14.8 mL/min/1.73 m2; 53% had mild cognitive impairment, and 19% had dementia. Unadjusted analysis showed an association between lower eGFR and smaller brain volumes. After adjusting for age, sex, and education, there was no association between eGFR brain volumes (p > 0.05 for all). These results remained consistent after subgroup analysis by age stratification and baseline cognitive status. Age was a confounding variable in the unadjusted association between the eGFR and brain volumes. Thus, a mild to moderately reduced eGFR was not associated with brain atrophy in ADNI participants.
24. A Box Model to Quantify Groundwater Discharge Along the Kona Coast of Hawaii Using Natural Tracers

Major islands such as Hawaii typically exhibit conditions favorable for high submarine groundwater discharge (SGD) to the ocean. Quantitative aerial thermal imaging along the leeward Kona coast of Hawaii reveals plumes of relatively cold groundwater discharging from distinct portals along the coastline. Many of these plumes are thought to represent substantial volumes of groundwater discharge. The goal of our tracer work is to quantify groundwater fluxes to the coastal ocean from some of these plumes as a means of calibrating the aerial imaging. We employed coincident mass equations for two tracers (salinity and randon) and water fluxes to develop a mass balance box model for quantifying groundwater discharge. Our results indicate that a small SGD discharge plume emanating from Kahualoa Bay represents water fluxes on the order of thousands of m3/day to the coastal ocean.
What does desmin do: A bibliometric assessment of the functions of the muscle intermediate filament

Intermediate filaments were first described in muscle in 1968, and desmin was biochemically identified about 10 years afterwards. Its importance grew after the identification of desminopathies and desmin mutations that cause mostly cardiopathies. Since its characterization until recently, different functions have been attributed to desmin. Here, we use bibliometric tools to evaluate the articles published about desmin and to assess its several putative functions. We identified the most productive authors and the relationships between research groups. We studied the more frequent words among 9734 articles (September 2021) containing “desmin” on the title and abstract, to identify the major research focus. We generated an interactive spreadsheet with the 934 papers that contain “desmin” only on the title that can be used to search and quantify terms in the abstract. We further selected the articles that contained the terms “function” or “role” from the spreadsheet, which we then classified according to type of function, organelle, or tissue involved. Based on the bibliographic analysis, we assess comparatively the putative functions, and we propose an alternative explanation for the desmin function.
RNA sequencing on muscle biopsy from a 5‐week bed rest study reveals the effect of exercise and potential interactions with dorsal root ganglion neurons

Sedentary lifestyle, chronic disease, or microgravity can cause muscle deconditioning that then has an impact on other physiological systems. An example is the nervous system, which is adversely affected by decreased physical activity resulting in increased incidence of neurological problems such as chronic pain. We sought to better understand how this might occur by conducting RNA sequencing experiments on muscle biopsies from human volunteers in a 5‐week bed‐rest study with an exercise intervention arm. We also used a computational method for examining ligand–receptor interactions between muscle and human dorsal root ganglion (DRG) neurons, the latter of which play a key role in nociception and are generators of signals responsible for chronic pain. We identified 1352 differentially expressed genes (DEGs) in bed rest subjects without an exercise intervention but only 132 DEGs in subjects with the intervention. Among 591 upregulated muscle genes in the no intervention arm, 26 of these were ligands that have receptors that are expressed by human DRG neurons. We detected a specific splice variant of one of these ligands, placental growth factor (PGF), in deconditioned muscle that binds to neuropilin 1, a receptor that is highly expressed in DRG neurons and known to promote neuropathic pain. We conclude that exercise intervention protects muscle from deconditioning transcriptomic changes, and prevents changes in the expression of ligands that might sensitize DRG neurons, or act on other cell types throughout the body. Our work creates a set of actionable hypotheses to better understand how deconditioned muscle may influence the function of sensory neurons that innervate the entire body.
Prevention of measles, mumps and rubella: 40 years of global experience with M-M-RII

ABSTRACT Measles, mumps, and rubella are highly contagious diseases that caused significant global mortality and morbidity in the pre-vaccine era. Since its first approval in the United States over 40 years ago, M-M-RII has been used in >75 countries for prevention of these diseases. The vaccine has been part of immunization programs that have achieved dramatic global reductions in case numbers and mortality rates, as well as the elimination of measles and rubella in several countries and regions. This report summarizes over four decades of global safety, immunogenicity, efficacy, and effectiveness data for the vaccine. We include studies on the use of M-M-RII in different age groups, concomitant use with other routine childhood vaccines, administration via different routes, persistence of immunity, and vaccine effectiveness during outbreaks of measles and mumps. We conclude that M-M-RII is well tolerated and has shown consistently high performance during routine use in multiple countries, in randomized controlled trials with diverse designs, and in outbreak settings, including use as measles postexposure prophylaxis. Physicians, parents, and the public can continue to have a high degree of confidence in the use of M-M-RII as a vital part of global public health programs.
Lactate Maintains BCR/Abl Expression and Signaling in Chronic Myeloid Leukemia Cells Under Nutrient Restriction

This study was directed to deepen the effects of nutrient shortage on BCR/Ablprotein expression and signaling in chronic myeloid leukemia (CML) cells. The backbone of the study was cell culture in medium lacking glucose, the consumption of which we had previously shown to drive BCR/Ablprotein suppression, and glutamine, the other main nutrient besides glucose. In this context, we focused on the role of lactate, the main by-product of glucose metabolism under conditions of rapid cell growth, in particular as a modulator of the maintenance of CML stem/progenitor cell potential, a crucial determinant of disease course and relapse of disease. The results obtained indicated that lactate is a powerful surrogate of glucose to prevent the suppression of BCR/Abl signaling and is therefore capable to maintain BCR/Abl-dependent CML stem/progenitor cell potential. A number of metabolism-related functional and phenotypical features of CML cells were also determined. Among these, we focused on the effect of lactate on oxygen consumption rate, the dependence of this effect on the cell surface lactate carrier MCT-1, and the relationship of the lactate effect to pyruvate and to the activity of mitochondrial pyruvate carrier.