Miracle-dz/UniFAR-FTUs huggingface dataset:
MAGNETICALLY-DRIVEN HYDROGEL SURFACES FOR DYNAMIC STIFFNESS MODULATION FOR MODULATING MACROPHAGE BEHAVIOR

During the host response towards implanted biomaterials, macrophages can shift phenotype rapidly upon changes in their microenvironment within the host tissue. Exploration of this phenomenon can gain significantly from the development of adequate tools. Creating dynamic surface alterations on classical hydrogel substrates presents challenges, particularly when integrating them with cell cultivation and monitoring processes. However, having the capability to dynamically manipulate the stiffness of biomaterial surfaces holds significant potential. We introduce magnetically actuated dynamic surfaces (MadSurface) tailored to induce reversible stiffness changes on polyacrylamide hydrogel substrates with embedded magnetic microparticles in a time-controllable manner. Our investigation focused on exploring the potential of MadSurface in dynamically modulating macrophage behavior in a programmable manner. We achieved a consistent modulation by subjecting the MadSurface to a pulsed magnetic field with a frequency of 0.1 Hz and a magnetic field flux density of 50 mT and analyzed exposed cells using flow cytometry and ELISA. At the single cell level, we identified a sub-population for which the dynamic stiffness conditions in conjunction with the pulsed magnetic field increased the expression of CD206 in M1-activated THP-1 cells, indicating a consistent shift toward M2 anti-inflammatory phenotype on MadSurface. At the population level, this effect was mostly hindered in the first 24 hours. MadSurface approach can create controlled environments to advance our understanding of the interplay between dynamic surface mechanics and macrophage behavior.
Thoracic epidural blockade after myocardial infarction benefits from anti-arrhythmic pathways mediated in part by parasympathetic modulation

Background Thoracic epidural anesthesia (TEA) has been shown to reduce the burden of ventricular tachyarrhythmias (VT) in small case-series of patients with refractory VT and cardiomyopathy. However, its electrophysiological and autonomic effects in diseased hearts remain unclear and its use after myocardial infarction (MI) is limited by concerns for potential RV dysfunction. Methods MI was created in Yorkshire pigs (N=22) by LAD occlusion. Six weeks post-MI, an epidural catheter was placed at the C7-T1 vertebral level for injection of 2% lidocaine. RV and LV hemodynamics were recorded using Millar pressure-conductance catheters, and ventricular activation-recovery intervals (ARIs), a surrogate of action potential durations, by a 56-electrode sock and 64-electrode basket catheter. Hemodynamics and ARIs, baroreflex sensitivity (BRS) and intrinsic cardiac neural activity, and ventricular effective refractory periods (ERP) and slope of restitution (Smax) were assessed before and after TEA. VT/VF inducibility was assessed by programmed electrical stimulation. Results TEA reduced inducibility of VT/VF by 70%. TEA did not affect RV-systolic pressure or contractility, although LV-systolic pressure and contractility decreased modestly. Global and regional ventricular ARIs increased, including in scar and border zone regions post-TEA. TEA reduced ARI dispersion specifically in border zone regions. Ventricular ERPs prolonged significantly at critical sites of arrhythmogenesis, and Smax was reduced. Interestingly, TEA significantly improved cardiac vagal function, as measured by both BRS and intrinsic cardiac neural activity. Conclusion TEA does not compromise RV function in infarcted hearts. Its anti-arrhythmic mechanisms are mediated by increases in ventricular ERP and ARIs, decreases in Smax, and reductions in border zone heterogeneity. TEA improves parasympathetic function, which may independently underlie some of its observed anti-arrhythmic mechanisms. This study provides novel insights into the anti-arrhythmic mechanisms of TEA, while highlighting its applicability to the clinical setting. Abstract Illustration Myocardial infarction is known to cause cardiac autonomic dysfunction characterized by sympathoexcitation coupled with reduced vagal tone. This pathological remodeling collectively predisposes to ventricular arrhythmia. Thoracic epidural anesthesia not only blocks central efferent sympathetic outflow, but by also blocking ascending projections of sympathetic afferents, relieving central inhibition of vagal function. These complementary autonomic effects of thoracic epidural anesthesia may thus restore autonomic balance, thereby improving ventricular electrical stability and suppressing arrhythmogenesis. DRG=dorsal root ganglion, SG=stellate ganglion.
Convergent origin and accelerated evolution of vesicle-associated RhoGAP proteins in two unrelated parasitoid wasps

Animal venoms and other protein-based secretions that perform a variety of functions, from predation to defense, are highly complex cocktails of bioactive compounds. Gene duplication, accompanied by modification of the expression and/or function of one of the duplicates under the action of positive selection, followed by further duplication to produce multigene families of toxins is a well-documented process in venomous animals. This evolutionary model has been less described in parasitoid wasps, which use maternal fluids, including venom, to protect their eggs from encapsulation by the host immune system. Here, we evidence the convergent recruitment and accelerated evolution of two multigene families of RhoGAPs presumably involved in virulence in two unrelated parasitoid wasp species, Leptopilina boulardi (Figitidae) and Venturia canescens (Icheumonidae). In both species, these RhoGAPs are associated with vesicles that act as transport systems to deliver virulence factors, but are produced in different tissues: the venom gland in Leptopilina sp. and the ovarian calyx in V. canescens. We show that the gene encoding the cellular RacGAP1 is at the origin of the virulent RhoGAP families found in Leptopilina sp. and V. canescens. We also show that both RhoGAP families have undergone evolution under positive selection and that almost all of these RhoGAPs lost their GAP activity and GTPase binding ability due to substitutions in key amino acids. These results suggest an accelerated evolution and functional diversification of these vesicle-associated RhoGAPs in the two phylogenetically distant parasitoid species. The potential new function(s) and the exact mechanism of action of these proteins in host cells remain to be elucidated.
Modeling interpretable correspondence between cell state and perturbation response with CellCap

Single-cell transcriptomics, in conjunction with genetic and compound perturbations, offers a robust approach for exploring cellular behaviors in diverse contexts. Such experiments allow un-covering cell-state-specific responses to perturbations, a crucial aspect in unraveling the intricate molecular mechanisms governing cellular behavior and potentially discovering novel regulatory pathways and therapeutic targets. However, prevailing computational methods predominantly focus on predicting average cellular responses, disregarding the inherent response heterogeneity associated with cell state diversity. In this study, we present CellCap, a deep generative model designed for the end-to-end analysis of single-cell perturbation experiments. CellCap employs sparse dictionary learning in a latent space to deconstruct cell-state-specific perturbation responses into a set of transcriptional response programs. These programs are then utilized by each perturbation condition and each cell at varying degrees. The incorporation of specific model design choices, such as dot-product cross-attention between cell states and response programs, along with a linearly-decoded latent space, underlay the interpretation power of CellCap. We evaluate CellCap’s model interpretability through multiple simulated scenarios and apply it to two real single-cell perturbation datasets. These datasets feature either heterogeneous cellular populations or a complex experimental setup. Our results demonstrate that CellCap successfully uncovers the relationship between cell state and perturbation response, unveiling novel insights overlooked in previous analyses. The model’s interpretability, coupled with its effectiveness in capturing heterogeneous responses, positions CellCap as a valuable tool for advancing our understanding of cellular behaviors in the context of perturbation experiments.
Handedness is modulated by sex and self-perception

The distribution of handedness is different for men and women. Less pronounced right- or left-handedness in men is well established and often attributed to direct effects of genetic factors. Many studies observing this sex difference assessed handedness via questionnaire. It may therefore be influenced by a sex-specific bias in self-perception. Permanent inadequate self-perceptions are key characteristics of hypochondriasis. The study therefore tested 1017 participants (614 females) on two standard questionnaires to assess handedness and hypochondriasis: the Edinburgh Inventory and the Whiteley Index. Effects of sex, hypochondriac traits and the direction of handedness (left-handers; right-handers) on the degree of handedness (DH; the strength of lateralisation) were tested with multivariate linear regression. In confirmation of previous results, the DH is lower (less pronounced) in right-handed males than right-handed females, but is similar across sexes in left-handers. Regression analyses showed that for right-handers, male sex and higher hypochondriac traits are independent predictors of lower DH. For left-handers, main effects of sex and hypochondriac traits are not significant whereas a significant interaction of these two factors indicates that in left-handed men higher hypochondriac traits are associated with a differentially stronger shift towards lower DH compared to left-handed women. In conclusion, the DH is modulated by sex-specific effects of self-perception for left-handers but not right-handers. The implications of this finding on current theories of the inheritance of handedness are discussed. The assessment of hypochondriac traits might be useful to control response bias in questionnaire-based studies of human handedness.
Climate Change and U.S. Water Resources: Results from a Study by the American Association for Advancement of Science

The time horizon of the changes that might occur is similar to the time required for planning, approval, funding, construction and economic life of such major water facilities as dams, irrigation canals, treatment plants and drainage systems. The report of the AAAS study considers the prospects for climate change, the relationships between climate and hydrology, and the possible effects of climate change on floods, droughts, irrigated agriculture, water supply, water quality, recreation and wildlife, urban water systems, and hydro-power. Economic and political implications are discussed. The study concludes that the consequences of global warming on water systems throughout the United States will be significant, widespread, and expensive to mitigate.
Control-flow analysis of functional programs

We present a survey of control-flow analysis of functional programs, which has been the subject of extensive investigation throughout the past 30 years. Analyses of the control flow of functional programs have been formulated in multiple settings and have led to many different approximations, starting with the seminal works of Jones, Shivers, and Sestoft. In this article, we survey control-flow analysis of functional programs by structuring the multitude of formulations and approximations and comparing them.
A Major Species of Mouse μ-opioid Receptor mRNA and Its Promoter-Dependent Functional Polyadenylation Signal

The pharmacological effects of opioid drugs are mediated mainly by the μ-opioid receptor (MOR), which is encoded by an mRNA transcript named MOR1. Although several MOR mRNA splice variants have been reported, their biological relevance has been debated. In this study, we found that probes of regions essential for the production of functional MOR, as well as that of the 3′-downstream region of the MOR gene coding region, detected by Northern blot analyses, a major species of mature transcript MOR1 from mouse brain of ∼11.5 kilobases (kb). Although exon 3 probe detected an additional 3.7-kb transcript, this transcript was not detected by other probes, ruling out its ability to produce functional MOR. The 3′-untranslated region (UTR) of MOR1 is contiguously extended from the end of the coding region, and uses a single polyadenylation [poly (A)] signal (located 10,179 bp downstream of the MOR1 stop codon). The poly (A) signal (AAUAAA) is located 26 bp upstream of the poly (A) site. Transient transfection using luciferase reporters verified the functionality of this poly (A) signal, in particular on a reporter driven by the MOR promoter. This poly (A) is much less effective for a heterologous promoter, such as simian virus 40, indicating a functional coupling of MOR promoter and its own poly (A). This report verifies MOR1 as the major mature MOR gene transcript that has the full capacity to produce functional MOR protein, identifies the 3′-UTR of MOR1 transcript, and uncovers functional coupling of the MOR gene promoter and its polyadenylation signal.
Characterisation of livestock biochars and their effect on selected soil properties and maize early growth stage in soils of Eastern Cape province, South Africa

Few studies have evaluated biochar application rates that would make economic sense using feedstocks readily available to subsistence farmers. Biochar from livestock manures were examined in Oakleaf and Tukulu soils. Pyrolysis had the most effect on poultry manure where it increased pH (7.8%), electrical conductivity (19.8%), total phosphorus (31%) and zinc (23.9%). Maize germination percentage in Oakleaf soil was enhanced more under cattle manure biochar (CMB) at 100 kg C ha−1, which differed from the control by 14.29%. In Tukulu soil, CMB at 400 kg C ha−1 enhanced germination percentage more and this increase was 22.50% higher than that of the control. In Oakleaf soil, 100 kg C ha−1 was optimal to increase plant height under sheep manure biochar (SMB), goat manure biochar (GMB), and poultry manure biochar (PMB), whereas 400 kg C ha−1 was optimal under CMB; however, in Tukulu soil 100 kg C ha−1 was optimum under GMB and CMB. The difference from the control in plant biomass was highest (28.06%) under SMB at 400 kg C ha−1 in the Oakleaf soil, whereas in Tukulu soil SMB at 300 kg C ha−1 produced the highest (19.03%) plant biomass. Overall, CMB provided a better alternative for use in Tukulu and Oakleaf soils, but field trials need to be conducted.
Perfusion with the olfactomedin domain of myocilin does not affect outflow facility.

PURPOSE Mutations in the MYOC gene coding for myocilin are associated with elevated intraocular pressure (IOP), and recombinant myocilin, produced in a prokaryotic expression system, has been reported to affect aqueous outflow facility. This study was conducted to test whether perfusion with a fragment of recombinant myocilin (containing the full-length olfactomedin domain), produced in a eukaryotic expression system, affects facility. METHODS 293 EBNA cells were transfected by a vector containing the BM40 signal peptide, a human cDNA coding for myocilin, and a polyhistidine tag (HisTag) sequence. Recombinant protein was isolated by Ni-chelate chromatography, and characterized, and perfused into cultured anterior segments of human and porcine eyes. RESULTS Recombinant myocilin was secreted as a approximately 55-kDa intact protein and two fragments arising from cleavage of the recombinant protein at amino acid 215. The C-terminal fragment, containing the entire olfactomedin domain, was successfully isolated. When perfused into human and porcine eyes, this C-terminal fragment did not appreciably affect outflow facility. CONCLUSIONS Although the olfactomedin domain appears to be important for the function of myocilin, perfusion with a recombinant myocilin fragment containing this domain does not change outflow facility. It is possible that both the olfactomedin and N-terminal domains (including the leucine zipper) must be present for myocilin to have full function. Alternatively, posttranslational modifications of myocilin may have a major impact on protein function.
Clinical Emergence of Entecavir-Resistant Hepatitis B Virus Requires Additional Substitutions in Virus Already Resistant to Lamivudine

ABSTRACT Entecavir (ETV) exhibits potent antiviral activity in patients chronically infected with wild-type or lamivudine (3TC)-resistant (3TCr) hepatitis B virus (HBV). Among the patients treated in phase II ETV clinical trials, two patients for whom previous therapies had failed exhibited virologic breakthrough while on ETV. Isolates from these patients (arbitrarily designated patients A and B) were analyzed genotypically for emergent substitutions in HBV reverse transcriptase (RT) and phenotypically for reduced susceptibility in cultures and in HBV polymerase assays. After 54 weeks of 3TC therapy, patient A (AI463901-A) received 0.5 mg of ETV for 52 weeks followed by a combination of ETV and 100 mg of 3TC for 89 weeks. Viral rebound occurred at 133 weeks after ETV was started. The 3TCr RT substitutions rtV173L, rtL180M, and rtM204V were present at study entry, and the additional substitutions rtI169T and rtM250V emerged during ETV-3TC combination treatment. Reduced ETV susceptibility in vitro required the rtM250V substitution in addition to the 3TCr substitutions. For liver transplant patient B (AI463015-B), previous famciclovir, ganciclovir, foscarnet, and 3TC therapies had failed, and RT changes rtS78S/T, rtV173L, rtL180M, rtT184S, and rtM204V were present at study entry. Viral rebound occurred after 76 weeks of therapy with ETV at 1.0 mg, with the emergence of rtT184G, rtI169T, and rtS202I substitutions within the preexisting 3TCr background. Reduced susceptibility in vitro was highest when both the rtT184G and the rtS202I changes were combined with the 3TCr substitutions. In summary, infrequent ETV resistance can emerge during prolonged therapy, with selection of additional RT substitutions within a 3TCr HBV background, leading to reduced ETV susceptibility and treatment failure.
CONTRIBUTIONS OF PROCESSING FLUENCY TO REPETITION EFFECTS IN MASKED WORD IDENTIFICATION

Prior exposure to a word is shown to improve its later identification in a brief, masked display when a free report task is used, but not in two-alternati ve forced choice or single-probe matching tasks that eliminate certain bias effects and provide an assessment of discriminability. Modified forced choice and single-probe tasks were also used, in which subjects attempted to identify the target before presentation of the probe(s). This modification produced a discriminabili ty advantage for old words, but only in the single-probe task. We argue that prior exposure does not enhance sensory processing of a target word; rather, it increases the fluency with which the target comes to mind when presented under difficult viewing conditions. In forced choice and single-probe tasks, fluency associated with processing the target may be ignored in deference to discriminatin g among or evaluating the processing of the probe(s).
Arteriopathy Diagnosis in Childhood Arterial Ischemic Stroke: Results of the Vascular Effects of Infection in Pediatric Stroke Study

Background and Purpose— Although arteriopathies are the most common cause of childhood arterial ischemic stroke, and the strongest predictor of recurrent stroke, they are difficult to diagnose. We studied the role of clinical data and follow-up imaging in diagnosing cerebral and cervical arteriopathy in children with arterial ischemic stroke. Methods— Vascular effects of infection in pediatric stroke, an international prospective study, enrolled 355 cases of arterial ischemic stroke (age, 29 days to 18 years) at 39 centers. A neuroradiologist and stroke neurologist independently reviewed vascular imaging of the brain (mandatory for inclusion) and neck to establish a diagnosis of arteriopathy (definite, possible, or absent) in 3 steps: (1) baseline imaging alone; (2) plus clinical data; (3) plus follow-up imaging. A 4-person committee, including a second neuroradiologist and stroke neurologist, adjudicated disagreements. Using the final diagnosis as the gold standard, we calculated the sensitivity and specificity of each step. Results— Cases were aged median 7.6 years (interquartile range, 2.8–14 years); 56% boys. The majority (52%) was previously healthy; 41% had follow-up vascular imaging. Only 56 (16%) required adjudication. The gold standard diagnosis was definite arteriopathy in 127 (36%), possible in 34 (9.6%), and absent in 194 (55%). Sensitivity was 79% at step 1, 90% at step 2, and 94% at step 3; specificity was high throughout (99%, 100%, and 100%), as was agreement between reviewers (&kgr;=0.77, 0.81, and 0.78). Conclusions— Clinical data and follow-up imaging help, yet uncertainty in the diagnosis of childhood arteriopathy remains. This presents a challenge to better understanding the mechanisms underlying these arteriopathies and designing strategies for prevention of childhood arterial ischemic stroke.
Serum prolactin stress values in patients with systemic lupus erythematosus

Over the past decade we have seen a gradual increase in reports giving more support to the hypothesis that mildly or moderately increased values of serum prolactin have a role in the pathogenesis and clinical activity of systemic lupus erythematosus (SLE). Jara et al summed up this information in an article published in a special edition of the international journal Lupus . 1 “Idiopathic hyperprolactinaemia” (hyperprolactin) has been confirmed under a variety of conditions by several authors, including us,2 in 20–30% of patients with SLE investigated; nevertheless, opinion continues to vary about its connection with greatly increased clinical activity of the disease.3,4 Prolactin is a hormone with a very wide range of action, and its effect on the immune response has been proved in both animal experiments5 and in humans.6 It is also one of the stress hormones, and the physiological 24 hour curve of its serum concentrations is similar to that of the growth hormone, a near relation, but not to those of the hormones along the line connecting the hypothalamus-pituitary-adrenocortex. In our first experiments designed to reproduce the study of hyperprolactin in patients with SLE or even rheumatoid arthritis (RA), we took account of the fact, emphasised by endocrinologists, that prolactin as a stress hormone is released in repeated pulses rather than continually; this is true at least, for the prolactin of pituitary origin, though not prolactin secreted in lymphoid paracrine tissue.7 The secretion of prolactin in the adenohypophysis …