Miracle-dz/UniFAR-FTUs huggingface dataset:
Eukaryotic SNARE VAMP3 Dynamically Interacts with Multiple Chlamydial Inclusion Membrane Proteins

Chlamydia trachomatis, an obligate intracellular pathogen, undergoes a biphasic developmental cycle within a membrane-bound vacuole called the chlamydial inclusion. To facilitate interactions with the host cell, Chlamydia modifies the inclusion membrane with type III secreted proteins, called Incs. ABSTRACT Chlamydia trachomatis, an obligate intracellular pathogen, undergoes a biphasic developmental cycle within a membrane-bound vacuole called the chlamydial inclusion. To facilitate interactions with the host cell, Chlamydia modifies the inclusion membrane with type III secreted proteins, called Incs. As with all chlamydial proteins, Incs are temporally expressed, modifying the chlamydial inclusion during the early and mid-developmental cycle. VAMP3 and VAMP4 are eukaryotic SNARE proteins that mediate membrane fusion and are recruited to the inclusion to facilitate inclusion expansion. Their recruitment requires de novo chlamydial protein synthesis during the mid-developmental cycle. Thus, we hypothesize that VAMP3 and VAMP4 are recruited by Incs. In chlamydia-infected cells, identifying Inc binding partners for SNARE proteins specifically has been elusive. To date, most studies examining chlamydial Inc and eukaryotic proteins have benefitted from stable interacting partners or a robust interaction at a specific time postinfection. While these types of interactions are the predominant class that have been identified, they are likely the exception to chlamydia-host interactions. Therefore, we applied two separate but complementary experimental systems to identify candidate chlamydial Inc binding partners for VAMPs. Based on these results, we created transformed strains of C. trachomatis serovar L2 to inducibly express a candidate Inc-FLAG protein. In chlamydia-infected cells, we found that five Incs temporally and transiently interact with VAMP3. Further, loss of incA or ct813 expression altered VAMP3 localization to the inclusion. For the first time, our studies demonstrate the transient nature of certain host protein-Inc interactions that contribute to the chlamydial developmental cycle.
Comparison of consumer-based methodologies for optimizing the development of new products: A case study with probiotic chocolate flavored milk

Several studies have reported that most new products do not achieve satisfactory results when launched on the market. There is a need to increase the efficiency of the methodologies used in the development of new products to increase success rates. Rapid sensory methodologies named Polarized Sensory Positioning (PSP), Check-all-that-apply (CATA), Projective mapping (PM) or Napping were applied to obtain sensory and hedonic information of a new product, probiotic-added chocolate flavored milk, aiming at determining preference guides that can be used to obtain a high overall liking level. It was possible to develop a probiotic chocolate flavored milk with general positive overall liking. The preferred sample was formulated with high content of sugar and chocolate, concluding that these characteristics are preference guides. The results supplied by the consumers using different methodologies were consistent, although the methodologies differed in their ability for sample differentiation. CATA methodology allowed better discrimination between samples than the other methodologies, followed by Projective Mapping, PSP with scales and triadic PSP. We could confirm that those rapid methodologies of sensory characterization are efficient when applied to product development. Practical applications Using those methodologies, it was possible to develop a probiotic chocolate flavored milk that meets both, consumer’s expectations in relation to nutrition and taste and functionality. The methodologies proved to be efficient in characterizing consumer preference guides, and therefore fundamental to the development of a product with higher overall liking.
Association of adverse outcomes of intrahepatic cholestasis of pregnancy with zonulin levels

Abstract Our aim was to investigate serum zonulin levels in intrahepatic cholestasis of pregnancy (ICP) and to determine the usefulness of zonulin in ICP follow-up. A prospective case-control study was carried out which included 88 pregnant women (44 patients with ICP and 44 controls). Maternal serum samples obtained from all participants and zonulin levels were determined by enzyme-linked immunosorbent assay (ELISA). Compared with controls, women with ICP had significantly higher zonulin levels (mean 0.728 ± 0.520 ng/mL vs. 1.303 ± 0.63 ng/mL, p <.001). According to the receiver operating characteristic (ROC) analysis performed for the predictive value of zonulin levels for ICP, the area under the curve (AUC) was 0.761 (95% CI: 0.661–0.860). Multivariable logistic regression analysis revealed serum zonulin levels was independently associated with adverse perinatal outcomes (OR = 1.278, 95% CI: 0.232–7.041), severity ICP (OR: 7.535, 95% CI: 1.597–13.553) and also unresponsiveness to treatment in ICP (OR: 4.178, 95% CI: 0.929–8.784). IMPACT STATEMENT What is already known on this subject? Zonulin is a regulator protein that increases the intestinal permeability by modulating the intercellular tight junctions (TJ). It is the only physiological protein known to control intestinal permeability and damage of the intestinal barrier is one of the causes of absorption disorders, inflammation and autoimmunity. ICP is a relatively non-threatening condition to women but is linked with a higher risk of preterm delivery, foetal distress and foetal death. What do the results of this study add? This study showed that increased levels of zonulin are associated with adverse perinatal outcomes, severity of ICP and unresponsiveness to treatment in ICP. What are the implications of these findings for clinical practice and/or further research? Focussing on preservation of intestinal permeability may be an alternative preventive strategy to reduce the adverse perinatal outcomes and severity of ICP. Further longitudinal studies are needed to verify the relationships among zonulin levels and pregnancy-related diseases.
Usability of Remote Assessment of Exercise Capacity for Pulmonary Telerehabilitation Program

Pulmonary rehabilitation [PR] has been successfully carried out via telemedicine however initial patient assessment has been traditionally conducted in PR centers. The first step in PR is assessment of patient's exercise capacity which allows individualized prescription of safe and effective exercise program. With COVID-19 pandemics assessment of patients in PR centers has been limited resulting in significant reduction of patients undergoing life-saving PR. The goal of this pilot study was to introduce approaches for remote assessment of exercise capacity using videoconferencing platforms and provide initial usability assessment of this approach by conducing cognitive walkthrough testing. We developed a remote assessment system that supports comprehensive physical therapy assessment necessary for prescription of a personalized exercise program tailored to individual fitness level and limitations in gait and balance of the patient under evaluation. Usability was assessed by conducting cognitive walkthrough and system usability surveys. The usability inspection of the remote exercise assessment demonstrated overall high acceptance by all study participants. Our next steps in developing user-centered interface should include usability evaluation in different subgroups of patients with varying socio-economic background, different age groups, computer skills, literacy and numeracy.
Effect of Fillers on the Recovery of Rubber Foam: From Theory to Applications

Natural rubber foam (NRF) can be prepared from concentrated natural latex, providing specific characteristics such as density, compression strength, compression set, and so on, suitable for making shape-memory products. However, many customers require NRF products with a low compression set. This study aims to develop and prepare NRF to investigate its recoverability and other related characteristics by the addition of charcoal and silica fillers. The results showed that increasing filler loading increases physical and mechanical properties. The recoverability of NRF improves as silica increases, contrary to charcoal loading, due to the higher specific surface area of silica. Thermodynamic aspects showed that increasing filler loading increases the compression force (F) as well as the proportion of internal energy to the compression force (Fu/F). The entropy (S) also increases with increasing filler loading, which is favorable for thermodynamic systems. The activation enthalpy (∆Ha) of the NRF with silica is higher than the control NRF, which is due to rubber–filler interactions created within the NRF. A thermodynamic concept of crosslinked rubber foam with filler is proposed. From theory to application, in this study, the NRF has better recoverability with silica loading.
Computer Methods and Programs in Biomedicine

problem, in order to enhance realism of surgical tools with respect to the background. Re-sults Quantitative and qualitative (i.e., human-based) evaluations of generated images have been carried out in order to assess the e ﬀ ectiveness of the method. Conclusions Experimental results show that the proposed method is actually able to translate MIS segmentations to realistic MIS images, which can in turn be used to augment existing data sets and help at overcoming the lack of useful images; this allows physicians and algorithms to take advantage from new annotated instances for their training.
Disruption of Conscious Access in Psychosis Is Associated with Altered Structural Brain Connectivity

According to global neuronal workspace (GNW) theory, conscious access relies on long-distance cerebral connectivity to allow a global neuronal ignition coding for conscious content. In patients with schizophrenia and bipolar disorder, both alterations in cerebral connectivity and an increased threshold for conscious perception have been reported. The implications of abnormal structural connectivity for disrupted conscious access and the relationship between these two deficits and psychopathology remain unclear. The aim of this study was to determine the extent to which structural connectivity is correlated with consciousness threshold, particularly in psychosis. We used a visual masking paradigm to measure consciousness threshold, and diffusion MRI tractography to assess structural connectivity in 97 humans of either sex with varying degrees of psychosis: healthy control subjects (n = 46), schizophrenia patients (n = 25), and bipolar disorder patients with (n = 17) and without (n = 9) a history of psychosis. Patients with psychosis (schizophrenia and bipolar disorder with psychotic features) had an elevated masking threshold compared with control subjects and bipolar disorder patients without psychotic features. Masking threshold correlated negatively with the mean general fractional anisotropy of white matter tracts exclusively within the GNW network (inferior frontal-occipital fasciculus, cingulum, and corpus callosum). Mediation analysis demonstrated that alterations in long-distance connectivity were associated with an increased masking threshold, which in turn was linked to psychotic symptoms. Our findings support the hypothesis that long-distance structural connectivity within the GNW plays a crucial role in conscious access, and that conscious access may mediate the association between impaired structural connectivity and psychosis.
PWD-3DNet: A Deep Learning-Based Fully-Automated Segmentation of Multiple Structures on Temporal Bone CT Scans

The temporal bone is a part of the lateral skull surface that contains organs responsible for hearing and balance. Mastering surgery of the temporal bone is challenging because of this complex and microscopic three-dimensional anatomy. Segmentation of intra-temporal anatomy based on computed tomography (CT) images is necessary for applications such as surgical training and rehearsal, amongst others. However, temporal bone segmentation is challenging due to the similar intensities and complicated anatomical relationships among critical structures, undetectable small structures on standard clinical CT, and the amount of time required for manual segmentation. This paper describes a single multi-class deep learning-based pipeline as the first fully automated algorithm for segmenting multiple temporal bone structures from CT volumes, including the sigmoid sinus, facial nerve, inner ear, malleus, incus, stapes, internal carotid artery and internal auditory canal. The proposed fully convolutional network, PWD-3DNet, is a patch-wise densely connected (PWD) three-dimensional (3D) network. The accuracy and speed of the proposed algorithm was shown to surpass current manual and semi-automated segmentation techniques. The experimental results yielded significantly high Dice similarity scores and low Hausdorff distances for all temporal bone structures with an average of 86% and 0.755 millimeter (mm), respectively. We illustrated that overlapping in the inference sub-volumes improves the segmentation performance. Moreover, we proposed augmentation layers by using samples with various transformations and image artefacts to increase the robustness of PWD-3DNet against image acquisition protocols, such as smoothing caused by soft tissue scanner settings and larger voxel sizes used for radiation reduction. The proposed algorithm was tested on low-resolution CTs acquired by another center with different scanner parameters than the ones used to create the algorithm and shows potential for application beyond the particular training data used in the study.
Decreased mechanotransduction prevents nuclear collapse in a Caenorhabditis elegans laminopathy

Significance Nuclear envelopathies are a complex group of human diseases caused by mutations in nuclear envelope proteins, including progeria, myopathy, and dystonia. Here, we used the Caenorhabditis elegans germline as a model system to investigate the function of the OOC-5/torsinA AAA+ ATPase, which localizes to the nuclear envelope and is mutated in early-onset DYT1 dystonia in humans. We show that OOC-5/torsinA promotes the function of the LINC complex, which spans the nuclear envelope and transmits forces to the nuclear lamina. Remarkably, decreasing the function of OOC-5/torsinA or the LINC complex prevents nuclear collapse in the absence of a functional nuclear lamina. Therapeutics targeting torsinA or the LINC complex might prevent nuclear damage from endogenous forces in certain nuclear envelopathies. The function of the nucleus depends on the integrity of the nuclear lamina, an intermediate filament network associated with the linker of nucleoskeleton and cytoskeleton (LINC) complex. The LINC complex spans the nuclear envelope and mediates nuclear mechanotransduction, the process by which mechanical signals and forces are transmitted across the nuclear envelope. In turn, the AAA+ ATPase torsinA is thought to regulate force transmission from the cytoskeleton to the nucleus. In humans, mutations affecting nuclear envelope-associated proteins cause laminopathies, including progeria, myopathy, and dystonia, though the extent to which endogenous mechanical stresses contribute to these pathologies is unclear. Here, we use the Caenorhabditis elegans germline as a model to investigate mechanisms that maintain nuclear integrity as germ cell nuclei progress through meiotic development and migrate for gametogenesis—processes that require LINC complex function. We report that decreasing the function of the C. elegans torsinA homolog, OOC-5, rescues the sterility and premature aging caused by a null mutation in the single worm lamin homolog. We show that decreasing OOC-5/torsinA activity prevents nuclear collapse in lamin mutants by disrupting the function of the LINC complex. At a mechanistic level, OOC-5/torsinA promotes the assembly or maintenance of the lamin-associated LINC complex and this activity is also important for interphase nuclear pore complex insertion into growing germline nuclei. These results demonstrate that LINC complex-transmitted forces damage nuclei with a compromised nuclear lamina. Thus, the torsinA–LINC complex nexus might comprise a therapeutic target for certain laminopathies by preventing damage from endogenous cellular forces.
Volatile organic compounds in a headspace sampling system and asthmatics sputum samples

The headspace of a biological sample contains exogenous volatile organic compounds (VOCs) present within the sampling environment which represent the background signal. This study aimed to characterise the background signal generated from a headspace sampling system in a clinical site, to evaluate intra- and inter-day variation of background VOC and to understand the impact of a sample itself upon commonly reported background VOC using sputum headspace samples from severe asthmatics. The headspace, in absence of a biological sample, was collected hourly from 11am to 3pm within a day (time of clinical samples acquisition), and from Monday to Friday in a week, and analysed by thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS). Chemometric analysis identified 1120 features, 37 of which were present in at least the 80% of all the samples. The analyses of intra- and inter-day background variations were performed on 13 of the most abundant features, ubiquitously present in headspace samples. The concentration ratios relative to background were reported for the selected abundant VOC in 36 asthmatic sputum samples, acquired from 36 stable severe asthma patients recruited at Glenfield Hospital, Leicester, UK. The results identified no significant intra- or inter-day variations in compounds levels and no systematic bias of z-scores, with the exclusion of benzothiazole, whose abundance increased linearly between 11am and 3pm with a maximal intra-day fold change of 2.13. Many of the identified background features are reported in literature as components of headspace of biological samples and are considered potential biomarkers for several diseases. The selected background features were identified in headspace of all severe asthma sputum samples, albeit with varying levels of enrichment relative to background. Our observations support the need to consider the background signal derived from the headspace sampling system when developing and validating headspace biomarker signatures using clinical samples.
DNA methylomic homogeneity and heterogeneity in muscles and testes throughout pig adulthood

DNA methylome pattern is significantly different among tissues, ages, breeds, and genders. We assessed 20 methylome and transcriptome data in longissimus dorsi (LD) or testicles from Bamaxiang (BMX) and Large White pigs (LW) by deep sequencing technology. We identified ~55.7M CpGs and 5.30M, 0.20M, 1.20M, and 0.16M differential CpGs (P<0.01) between tissues, ages, breeds, and genders, respectively. Interestingly, 7.54% of differentially methylated regions (DMRs) are co-localized with promoters, which potentially regulate gene expression. RNA-seq analysis revealed that 23.42% CpGs are significantly correlated with gene expression (mean |r|=0.58, P<0.01), most of which are enriched in tissue-specific functions. Specially, we also found that the methylation levels in promoters of 655 genes were strongly associated with their expression levels (mean |r|=0.66, P<0.01). In addition, differentially methylated CpGs (DMCpGs) between breeds in HOXC gene cluster imply important regulatory roles in myocytes hypertrophy and intermuscular fat (IMF) deposition. Dramatically, higher similarity of methylation pattern was observed within pedigree than across pedigrees, which indicates the existence of heritable methylation regions. In summary, a part of CpGs in promoter can change its methylation pattern and play a marked regulatory function in different physiological or natural environments.
Single cell RNA-seq reveals developmental plasticity with coexisting oncogenic and immune evasion programs in ETP-ALL.

Lineage plasticity and stemness have been invoked as the cause of therapy resistance in cancer, as these flexible states allow cancer cells to de-differentiate and alter their dependencies. We investigated such resistance mechanisms in relapsed / refractory early T-cell progenitor acute lymphoblastic leukemia carrying activating NOTCH1 mutations, by full-length single cell RNA sequencing of malignant and microenvironmental cells. We identified two highly distinct stem-like states that critically differ in their cell-cycle and oncogenic signaling. Fast-cycling stem-like leukemia cells demonstrate Notch activation and are effectively eliminated in patients by Notch inhibition, while slow cycling stem-like cells are Notch-independent but rather rely on PI3K signaling, likely explaining the poor efficacy of Notch inhibition in this disease. Remarkably, we find that both stem-like states can differentiate into a more mature leukemia state with prominent immune-modulatory functions, including high expression of the LGALS9 checkpoint molecule. These cells promote an immunosuppressive leukemia ecosystem with clonal accumulation of dysfunctional CD8+ T cells that express HAVCR2, the cognate receptor for LGALS9. Our study identifies complex interactions between signaling programs, cellular plasticity and immune programs that characterize T-ALL and illustrates the multi-dimensionality of tumor heterogeneity. In this scenario, combination therapies targeting diverse oncogenic states and the immune ecosystem appear most promising to successfully eliminate tumor cells that escape treatment through co-existing transcriptional programs.
Bilateral Vein Compression by Popliteal Artery Aneurisms Mimicking Post-Thrombotic Syndrome

Purpose: To report a case of a 79-year-old man who presented a bilateral popliteal artery aneurysm compressing both popliteal veins mimicking signs and symptoms of post-thrombotic syndrome. Case Report: A 79-year-old male patient, was seen in the ambulatory clinic with a 2-year history of bilateral leg swelling, calf pain, chronic ulceration, and hyperpigmentation. Upon physical examination, lower extremities were edematous, with a 3 cm suppurative ulcer on each leg. Image studies showed a popliteal right arterial aneurysm of maximum diameter of 41.7 mm, extrinsically compressing the ipsilateral popliteal vein. Likewise, on the left leg, a popliteal arterial aneurysm of maximum diameter of 47.9 mm was encountered triggering the same phenomenon. Bilateral endovascular treatment deploying stent grafts was auspiciously performed. At 36-months follow up, his symptoms are completely resolved, and his ulcers healed. US follow up showed exclusion of the aneurysms with progressive shrinkage of both residual sacs. Conclusion: Popliteal artery aneurysm compressing and constraining flow in the popliteal vein must be included as a differential diagnosis among the causes of chronic venous syndromes. Prompt diagnosis with its appropriate treatment is needed for reducing severe complications caused by PAA, such as the venous disorder our patient had.