julilili42/papers huggingface dataset:
A strategy to design protein-based antagonists against type I cytokine receptors
2024-11-26

Excessive cytokine signaling resulting from dysregulation of a cytokine or its receptor can be a main driver of cancer, autoimmune, or hematopoietic disorders. Here, we leverage protein design to create tailored cytokine receptor blockers with idealized properties. Specifically, we aimed to tackle the granulocyte-colony stimulating factor receptor (G-CSFR), a mediator of different types of leukemia and autoinflammatory diseases. By modifying designed G-CSFR binders, we engineered hyper-stable proteins that function as nanomolar signaling antagonists. X-ray crystallography showed atomic-level agreement with the experimental structure of an exemplary design. Furthermore, the most potent design blocks G-CSFR in acute myeloid leukemia cells and primary human hematopoietic stem cells. Thus, the resulting designs can be used for inhibiting or homing to G-CSFR-expressing cells. Our results also demonstrate that similarly designed cytokine mimics can be used to derive antagonists to tackle other type I cytokine receptors.
Continuity of Short-Time Dynamics Crossing the Liquid–Liquid Phase Separation in Charge-Tuned Protein Solutions
2024-11-26

Liquid-liquid phase separation (LLPS) constitutes a crucial phenomenon in biological self-organization, not only intervening in the formation of membraneless organelles but also triggering pathological protein aggregation, which is a hallmark in neurodegenerative diseases. Employing incoherent quasi-elastic neutron spectroscopy (QENS), we examine the short-time self-diffusion of a model protein undergoing LLPS as a function of phase splitting and temperature to access information on the nanosecond hydrodynamic response to the cluster formation both within and outside the LLPS regime. We investigate the samples as they dissociate into microdroplets of a dense protein phase dispersed in a dilute phase as well as the separated dense and dilute phases obtained from centrifugation. By interpreting the QENS results in terms of the local concentrations in the two phases determined by UV-vis spectroscopy, we hypothesize that the short-time transient protein cluster size distribution is conserved at the transition point while the local volume fractions separate.
Applying the efficient coding principle to understand encoding of multisensory and multimodality sensory signals
2024-11-26

Sensory neurons often encode multisensory or multimodal signals. For example, many medial superior temporal (MST) neurons are tuned to heading direction of self-motion based on visual (optic flow) signals and vestibular signals. Middle temporal (MT) cortical neurons are tuned to object depth from signals of two visual modalities: motion parallax and binocular disparity. A MST neuron's preferred heading directions from different senses can be congruent (matched) or opposite from each other. Similarly, the preferred depths of a MT neuron from the two modalities are congruent in some neurons and opposite in other neurons. While the congruent tuning appears natural for cue integration, the functions of the opposite tuning have been puzzling. This paper explains these tunings from the efficient coding principle that sensory encoding extracts as much sensory information as possible while minimizing neural cost. It extends the previous applications of this principle to understand neural receptive fields in retina and the primary visual cortex, particularly multimodal encoding of cone signals or binocular signals. Congruent and opposite sensory signals that excite the congruent and opposite neurons, respectively, are the decorrelated sensory components that provide a general purpose, efficient, representation of sensory inputs before task specific object segmentation and recognition. It can be extended to encoding signals from more than two sensory sources, e.g., from three cone types. This framework also predicts a wider tuning width for the opposite than congruent neurons, neurons that are neither congruent nor opposite, and how neural receptive fields adapt to statistical changes of sensory environments.
Intact protein barcoding enables one-shot identification of CRISPRi strains and their metabolic state
2024-11-26

Detecting strain-specific barcodes with mass spectrometry can facilitate the screening of genetically engineered bacterial libraries. Here, we introduce intact protein barcoding, a method to measure protein-based library barcodes and metabolites using flow injection mass spectrometry (FI-MS). Protein barcodes are based on ubiquitin with N-terminal tags of six amino acids. We demonstrate that FI-MS detects intact ubiquitin proteins and identifies the mass of N-terminal barcodes. In the same analysis, we measured relative concentrations of primary metabolites. We constructed six ubiquitin-barcoded CRISPR interference (CRISPRi) strains targeting metabolic enzymes and analyzed their metabolic profiles and ubiquitin barcodes. FI-MS detected barcodes and distinct metabolome changes in CRISPRi-targeted pathways. We demonstrate the scalability of intact protein barcoding by measuring 132 ubiquitin barcodes in microtiter plates. These results show that intact protein barcoding enables fast and simultaneous detection of library barcodes and intracellular metabolites, opening up new possibilities for mass spectrometry-based barcoding.
Coincidence of Concentric Vessel-Wall Contrast Enhancement in Moyamoya Disease and Acute Postoperative Ischemic Stroke During Revascularization Procedures
2024-11-26

Background: Concentric vessel-wall contrast enhancement (VW-CE) of the terminal carotid artery and its proximal branches may be linked to ischemic strokes, disease activity and progression in Moyamoya disease (MMD). The objective of this retrospective cohort study is to analyze the association between VW-CE and perioperative acute ischemic stroke (PAIS) occurring within 24 h after revascularization. Methods: All previously untreated MMD patients who required revascularization and who had undergone preoperative MRI with VW-CE-sequences were included. PAIS was detected by CT and/or diffusion-weighted MRI sequences within 24 h postoperatively. Results: Of the 110 patients included (female-to-male ratio: 2.7:1, median age: 45.1 (16.6–69.2); n = 247 revascularizations), a priori VW-CE was present in 67.3% (mean time from MRI to first surgery: 86 days ± 82 days). PAIS occurred in five patients undergoing primary revascularization (PAIS rate per revascularization: 2.1%), all of whom had a preoperative pathological VW-CE in the vascular segment corresponding to the stroke area. Two (40%) incidents of PAIS occurred in revascularized territory, while three (60%) occurred in non-revascularized vascular territory. In each case, the supplying artery exhibited VW-CE, indicating disease activity. No additional PAIS occurred during subsequent revascularizations in cases of multistage procedures (n = 38), such as ACA or PCA revascularization as a second step. Conclusions: Preoperative VW-CE in one or more vascular segments may be a marker for postoperative stroke in the respective vascular territory at the time of revascularization. VW-CE imaging should be routinely performed when planning revascularization in MMD. If VW-CE is found, strict perioperative monitoring of these high-risk patients should be performed to achieve the best results possible.
Non-invasive cerebral autoregulation monitoring during paediatric cardiac surgery without cardiopulmonary bypass requiring intraoperative cross-clamping of one of the carotid arteries
2024-11-26

Introduction Neurologic complications remain one of the major risks after pediatric cardiac surgery. Cerebral autoregulation (CA) is a physiologic mechanism regulating cerebral perfusion. A dynamic intraoperative evaluation can possibly detect the impairment of the cerebral regulatory function during surgery. The aim of the present study was to evaluate the utility of dynamic cerebral blood perfusion monitoring using cerebral oxygenation index (COx) as CA parameter during pediatric cardiac surgery without cardiopulmonary bypass (CPB) requiring intraoperative cross-clamping of one carotid artery to perform the procedure. Materials and methods Prospective intraoperative autoregulation monitoring was performed in 14 children under the age of 1 year requiring elective cardiac surgery with intraoperative cross-clamping of one of carotid artery. Procedures requiring the use of CPB and redo surgeries were excluded. Results Impaired CA could be measured during 33.8% of cross-clamping time on the ipsilateral side and 30.1% on the contralateral side. The difference in COx was not significant before ( p = 0.7), during ( p = 0.29) and after cross clamping ( p = 0.63), but a significant difference in COx levels throughout the entire cohort was noted individually. The mean ABP during normal (COx &lt;0.4) CA was 61.8 mmHg (95% CI 60.7 – 62.9) and 62.9 mmHg (95% CI 61.9 – 63.9) for cross clamped and opposite side. During impaired (COx &gt;0.4) CA the ABP values were 58.9 mmHg (95% CI 57.7 – 60.1, p &lt; 0.05) and 56 mmHg (95% CI 54.8 – 57.3, p &lt; 0.05) respectively. Conclusions A dynamic intraoperative monitoring of CA during pediatric cardiac surgery is possible and allows to confirm the impairment of autoregulation during cross-clamping of one of the carotid arteries.
Young rat microbiota extracts strongly inhibit fibrillation of α-synuclein and protect neuroblastoma cells and zebrafish against α-synuclein toxicity
2024-11-26

The clinical manifestations of Parkinson's disease (PD) are driven by aggregation of α-Synuclein (α-Syn) in the brain. However, there is increasing evidence that PD may be initiated in the gut and thence spread to the brain, eg, via the vagus nerve. Many studies link PD to changes in the gut microbiome, and bacterial amyloid has been shown to stimulate α-Syn aggregation. Yet, we are not aware of any studies reporting on a direct connection between microbiome components and α-Syn aggregation. Here, we report that soluble extract from the gut microbiome of the rats, particularly young rats transgenic for PD, shows a remarkably strong ability to inhibit in vitro α-Syn aggregation and keep it natively unfolded and monomeric. The active component(s) are heat-labile molecule(s) of around 30- to 100-kDa size, which are neither nucleic acid nor lipid. Proteomic analysis identified several proteins whose concentrations in different rat samples correlated with the samples' anti-inhibitory activity, while a subsequent pull-down assay linked the protein chaperone DnaK with the inhibitory activity of young rat's microbiome, confirmed in subsequent in vitro assays. Remarkably, the microbiome extracts also protected neuroblastoma SH-SY5Y cells and zebrafish embryos against α-Syn toxicity. Our study sheds new light on the gut microbiome as a potential source of protection against PD and opens up for new microbiome-based therapeutic strategies.
Warehouse-based, immunopeptidome-guided design of personalised peptide vaccines shows feasibility in clinical trial evaluation in CLL patients
2024-11-26

Cancer peptide vaccination represents a promising therapeutic approach, but has been hampered by lack of suitable antigens and restricted applicability due to different HLA backgrounds of individual patients. We here introduce a novel warehouse-based concept for composition of personalized peptide vaccines and report on its successful application in a Phase II clinical trial in patients with chronic lymphocytic leukemia (CLL) after first-line therapy. 26 CLL patients in at least partial remission (PR) after 6 months of immuno-chemotherapy were vaccinated with a personalized vaccine compiled from a premanufactured peptide warehouse comprising immunopeptidome-defined CLL-associated peptides. Primary objective was evaluation of immunogenicity, secondary objectives were safety and minimal residual disease (MRD) response. Immunopeptidome-guided vaccine composition was throughout successful, proving the feasibility of warehouse-based vaccine design. Vaccination was well tolerated, with local injection site reactions being the most common adverse event. Only few patients showed vaccine-induced T cell responses, attributable to their inability to mount strong immune responses due to immune-chemotherapy and lack of potent adjuvant formulations. Both issues are addressed within a follow-up trial (NCT04688385), combining the immunopeptidome-guided warehouse-based vaccine design reported here with a potent novel adjuvant evaluating personalized multi- peptide vaccination in CLL patients under T cell supportive BTK inhibitor therapies. Clinical trial registration www.clinicaltrialsregister.eu , identifier NCT02802943.
Ovarian tissue cryopreservation for an 8 year old girl after hematopoietic stem cell transplantation in China: case report and literature review
2024-11-26

Patients who miss fertility preservation before HSCT should consult fertility preservation and gynecological endocrinology experts as early as possible after HSCT and undergo regular follow-up. If clinical evidence indicates residual ovarian function, fertility protection measures should be discussed promptly. OTC should be assessed as a successful option for women after HSCT.
First record of Metriorhynchidae (Crocodylomorpha, Thalattosuchia) from the Lower Cretaceous of northeastern Italy: high-resolution biostratigraphy, morphological description and comparative pelagic taphonomy
2024-11-26

The Italian record of Metriorhynchoidea, a Mesozoic clade of marine crocodylomorphs, is represented by fossils from the Veneto, Lombardy and Sicily regions. A new specimen (FMCR FOS03817) from the Lower Cretaceous of Asiago area (Veneto region, northeastern Italy) is here described for the first time and comparatively studied with a Middle Jurassic specimen (FMCR FOS03839) coming from the same locality. A petrographic and micropalaeontological analysis was performed in order to assess the stratigraphic position of both specimens. The newly described specimen is herein ascribed to the basal Berriasian (Lower Cretaceous) and referred to Metriorhynchidae incertae sedis after a comparative assessment of its morphology with coeval longirostrine crocodylomorphs. A taphonomic and petrographic comparative analysis between FMCR FOS03817 and FMCR FOS03839 is presented to compare their preservational status, being the two specimens coming from similar pelagic settings. While the Cretaceous specim...
MnCl2(C6N10H6): Insights into a Luminescent Transition Metal–Melem Complex
2024-11-27

In this work, the (MnCl2(C6N10H6) complex has been synthesized via solid-state reaction between manganese (II) chloride and melamine in the molar ratio of 1:2. A similar synthesis has been repeated with CoCl2, and FeCl2, resulting in two new metal–melam complexes (FeCl2(C6N11H9) and CoCl2(C6N11H9)). MnCl2(C6N10H6) crystallizes in the monoclinic crystal system with the space group I2/a. The crystalline powder of MnCl2(C6N10H6) was studied by X-ray diffraction, infrared spectroscopy, and thermogravimetric analysis to examine its structure and properties. MnCl2(C6N10H6) also shows good thermal stability up to 370 °C; however, the complete decomposition occurred at 900 °C, yielding Mn7C3. This paper presents an easy synthesis of the first luminescent transition metal–melem complex, providing new insights into the reactivity of melamine at elevated temperatures in the presence of transition metal chlorides.
A head-mounted Tilted Reality Device for the treatment of pusher syndrome: a usability study in healthy young and older adults
2024-11-27

Abstract Pusher syndrome is a disorder of postural control after stroke. Patients show a mismatch in their perception of (almost preserved) visual and (pathologically tilted) postural verticality. In order to reduce this mismatch, we developed a novel head-mounted Tilted Reality Device (TRD). It presents patients visual footage of their actual surroundings but tilted to one side rather than upright. We investigated its usability and possible limitations in its use for the treatment of pusher patients in two samples of healthy participants with an average age of 26.4 years and 63.9 years respectively. Individuals from both age groups showed similar levels of tolerance to prolonged exposure to the tilted visual environment for an average of 40.4 min while walking around in the hospital. The TRD was found to be comfortable and not frustrating whilst wearing, but somewhat challenging in terms of technical handling, particularly for older participants. At the end of the maximally tolerated exposure time participants of both groups experienced some feelings of discomfort, like dizziness or increased stomach awareness, which disappeared rapidly after terminating TRD exposure. Our TRD appears to be a practical device especially for an older population, like pusher patients. While users must be aware of the possibility of side effects, these should be balanced against the benefits of future use for rehabilitation purposes.
Deployment of power-to-protein technology in Ethiopia to provide drought-related emergency relief and mitigate food insecurity
2024-11-27

Food insecurity in Ethiopia is an immediate humanitarian crisis that is expected to worsen due to population growth and climate change. This study applied GIS-based approaches to evaluate the feasibility of deploying an emergent type of single-cell protein (SCP) technology to supplement the nutritional needs of Ethiopian citizens who are most vulnerable to drought. The technology—power-to-protein (PtP)—uses H 2 and O 2 from water electrolysis and CO 2 from woody biomass combustion in a two-stage bioprocess to produce nutrient-rich protein powder for human consumption. Population density, land use, and other geographical data were used to identify optimal site locations for these PtP systems based on two deployment strategies: large centralized plants vs. small decentralized units. The model also accounted for biomass availability, collection, and distribution logistics. The analysis revealed three sites that are both (highly) vulnerable/food-insecure and accessible within walking distance. The identified sites are proximate to the urban areas of Mekele in northern Ethiopia, Addis Ababa in central Ethiopia, and Hawasa south of Addis Ababa. If centralized PtP were deployed, the protein requirements of these populations could be sustained for several months, assuming a modest biomass collection radius of 35 km. Decentralized PtP deployment was similarly effective, requiring a distribution density of 5.4–11.0 PtP units per km 2 under conservative estimates and 0.76–1.1 units per km 2 under optimistic estimates. Lastly, a theoretical comparison showed that PtP is more efficient than conventional agricultural food production regarding biomass-to-protein conversion yields. Overall, our study suggests that PtP technology would be a feasible approach to supplement the nutritional needs of Ethiopian people in times of drought-related emergencies. However, given logistical limitations and considering social preference factors, it would be more practical to implement PtP in conjunction with standard emergency food aid measures.
Intermittent theta burst stimulation over the left prefrontal cortex: no additional effect for virtual reality exposure therapy in acrophobia—a randomized trial
2024-11-27

Abstract Anxiety disorders are the most prevalent mental health conditions. Besides psycho-pharmacotherapy, cognitive behavioral therapy with an exposure-based approach is considered the gold standard. However, not all patients benefit from this approach. Here, we aimed to translate laboratory findings on enhanced fear extinction with repetitive transcranial magnetic stimulation (TMS) to the clinic. In this double-blind, randomized, placebo-controlled clinical trial, 76 participants with acrophobia received an activating intermittent theta burst stimulation (iTBS) targeting the left posterior prefrontal cortex immediately before two virtual reality exposure therapy sessions. Phobic symptoms were assessed at baseline, post-intervention, and a 6-month follow-up. Results revealed a significant reduction in phobic symptoms from baseline to post-assessment and follow-up and confirmed the efficacy of virtual reality exposure therapy as a treatment for specific phobias. Interestingly, no additional effect was observed for active iTBS compared to sham iTBS. Our post-hoc analyses argue for an individualized TMS application. Further research is needed to determine optimal TMS parameters and validate these results in clinical trials, accounting for methodological and inter- and intra-individual variability, as well as alternative therapeutic processes.
Dyadic Psychopathology and Adjustment to Parenthood in Families With and Without Eating Disorder History—Findings From a Longitudinal Study
2024-11-27

ABSTRACT Objective Transition to parenthood is a vulnerable period for individual health and partnership quality. This study investigated parental health and partnership after childbirth in families with and without maternal eating disorder (ED) history. We report longitudinal data on parental ED psychopathology, depressive symptoms, and adjustment, including dyadic associations. Method Data derived from the prospective multi‐method cohort study EMKIE. Women with ( n = 24) and without ( n = 33) ED history and their partners took part from late pregnancy to 10 months postpartum and completed the Eating Disorder Examination Questionnaire, the Patient Health Questionnaire, and the Maternal Adjustment and Maternal Attitudes Questionnaire or the paternal equivalent. Results ED psychopathology increased in mothers in both groups. Mothers in the ED group had more severe ED psychopathology, higher depression scores, and lower levels of adjustment to motherhood compared to the control group across all measurement points. No group differences emerged between partners, but ED psychopathology increased in partners of women with ED history over time. A negative correlation between maternal ED severity and paternal adjustment was observed in the ED group. Discussion After childbirth, mothers with ED history experienced mental health deterioration and adjustment difficulties and fathers struggled with paternal adjustment if their partner was affected by severe ED symptoms. These results emphasize the need for close monitoring and consistent care of women with ED during this vulnerable period and highlight adjustment needs of partners of severely affected women. Further qualitative approaches are needed to deepen the knowledge of paternal experiences during this period.