Miracle-dz/UniFAR-FTUs huggingface dataset:
Separate But Interactive Parallel Olfactory Processing Streams Governed by Different Types of GABAergic Feedback Neurons in the Mushroom Body of a Basal Insect

The basic organization of the olfactory system has been the subject of extensive studies in vertebrates and invertebrates. In many animals, GABA-ergic neurons inhibit spike activities of higher-order olfactory neurons and help sparsening of their odor representations. In the cockroach, two different types of GABA-immunoreactive interneurons (calyceal giants [CGs]) mainly project to the base and lip regions of the calyces (input areas) of the mushroom body (MB), a second-order olfactory center. The base and lip regions receive axon terminals of two different types of projection neurons, which receive synapses from different classes of olfactory sensory neurons (OSNs), and receive dendrites of different classes of Kenyon cells, MB intrinsic neurons. We performed intracellular recordings from pairs of CGs and MB output neurons (MBONs) of male American cockroaches, the latter receiving synapses from Kenyon cells, and we found that a CG receives excitatory synapses from an MBON and that odor responses of the MBON are changed by current injection into the CG. Such feedback effects, however, were often weak or absent in pairs of neurons that belong to different streams, suggesting parallel organization of the recurrent pathways, although interactions between different streams were also evident. Cross-covariance analysis of the spike activities of CGs and MBONs suggested that odor stimulation produces synchronized spike activities in MBONs and then in CGs. We suggest that there are separate but interactive parallel streams to process odors detected by different OSNs throughout the olfactory processing system in cockroaches. SIGNIFICANCE STATEMENT Organizational principles of the olfactory system have been the subject of extensive studies. In cockroaches, signals from olfactory sensory neurons (OSNs) in two different classes of sensilla are sent to two different classes of projection neurons, which terminate in different areas of the mushroom body (MB), each area having dendrites of different classes of MB intrinsic neurons (Kenyon cells) and terminations of different classes of GABAergic neurons. Physiological and morphological assessments derived from simultaneous intracellular recordings/stainings from GABAergic neurons and MB output neurons suggested that GABAergic neurons play feedback roles and that odors detected by OSNs are processed in separate but interactive processing streams throughout the central olfactory system.
DETERMINANTS OF THE MAGNITUDE OF TRAINING MEDIATED MUSCLE HYPERTROPHY

iv Acknowledgements . vi Table of contents . vii List of tables . ix Format and organization of this thesis . xii Contribution to papers with multiple authors . xiii CHAPTER 1: Introduction . 16 1.1 Historical background. 16 1.2 Measurement of muscle hypertrophy . 17 1.3 Variability in hypertrophic response . 19 1.4 Resistance training load . 24 1.5 Resistance training volume . 27 1.6 Protein turnover and hypertrophy . 28 1.7 Anabolic signaling pathways . 32 1.8 References . 35 CHAPTER 2: Resistance Exercise Load does not Determine Training-Mediated Hypertrophic Gains in Young Men . 42 Abstract . 43 Methods . 44 Results . 45 Discussion . 46 References . 47 CHAPTER 3: Muscular and Systemic Correlates of Resistance Training-Induced Muscle Hypertrophy . 46. 43 Methods . 44 Results . 45 Discussion . 46 References . 47 CHAPTER 3: Muscular and Systemic Correlates of Resistance Training-Induced Muscle Hypertrophy . 46
The frequency limit of outer hair cell motility measured in vivo

Outer hair cells (OHCs) in the mammalian ear exhibit electromotility, electrically driven somatic length changes that are thought to mechanically amplify sound-evoked vibrations. For this amplification to work, OHCs must respond to sounds on a cycle-by-cycle basis even at frequencies that exceed the low-pass corner frequency of their cell membranes. Using in vivo optical vibrometry we tested this theory by measuring sound-evoked motility in the 13–25 kHz region of the gerbil cochlea. OHC vibrations were strongly rectified, and motility exhibited first-order low-pass characteristics with corner frequencies around 3 kHz– more than 2.5 octaves below the frequencies the OHCs are expected to amplify. These observations lead us to suggest that the OHCs operate more like the envelope detectors in a classical gain-control scheme than like high-frequency sound amplifiers. These findings call for a fundamental reconsideration of the role of the OHCs in cochlear function and the causes of cochlear hearing loss.
MUR1‐mediated cell‐wall fucosylation is required for freezing tolerance in Arabidopsis thaliana

Summary Forward genetic screens play a key role in the identification of genes contributing to plant stress tolerance. Using a screen for freezing sensitivity, we have identified a novel freezing tolerance gene, SENSITIVE‐TO‐FREEZING8, in Arabidopsis thaliana. We identified SFR8 using recombination‐based mapping and whole‐genome sequencing. As SFR8 was predicted to have an effect on cell wall composition, we used GC‐MS and polyacrylamide gel electrophoresis to measure cell‐wall fucose and boron (B)‐dependent dimerization of the cell‐wall pectic domain rhamnogalacturonan II (RGII) in planta. After treatments to promote borate‐bridging of RGII, we assessed freeze‐induced damage in wild‐type and sfr8 plants by measuring electrolyte leakage from freeze‐thawed leaf discs. We mapped the sfr8 mutation to MUR1, a gene encoding the fucose biosynthetic enzyme GDP‐d‐mannose‐4,6‐dehydratase. sfr8 cell walls exhibited low cell‐wall fucose levels and reduced RGII bridging. Freezing sensitivity of sfr8 mutants was ameliorated by B supplementation, which can restore RGII dimerization. B transport mutants with reduced RGII dimerization were also freezing‐sensitive. Our research identifies a role for the structure and composition of the plant primary cell wall in determining basal plant freezing tolerance and highlights the specific importance of fucosylation, most likely through its effect on the ability of RGII pectin to dimerize.
K+ Channel-SEC11 Binding Exchange Regulates SNARE Assembly for Secretory Traffic

K+ channels initiate a binding exchange with the SNARE SYP121 to trigger SNARE complex assembly and drive secretory vesicle fusion at the plant plasma membrane. Cell expansion requires that ion transport and secretory membrane traffic operate in concert. Evidence from Arabidopsis (Arabidopsis thaliana) indicates that such coordination is mediated by physical interactions between subsets of so-called SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins, which drive the final stages of vesicle fusion, and K+ channels, which facilitate uptake of the cation to maintain cell turgor pressure as the cell expands. However, the sequence of SNARE binding with the K+ channels and its interweaving within the events of SNARE complex assembly for exocytosis remains unclear. We have combined protein-protein interaction and electrophysiological analyses to resolve the binding interactions of the hetero-oligomeric associations. We find that the RYxxWE motif, located within the voltage sensor of the K+ channels, is a nexus for multiple SNARE interactions. Of these, K+ channel binding and its displacement of the regulatory protein SEC11 is critical to prime the Qa-SNARE SYP121. Our results indicate a stabilizing role for the Qbc-SNARE SNAP33 in the Qa-SNARE transition to SNARE complex assembly with the R-SNARE VAMP721. They also suggest that, on its own, the R-SNARE enters an anomalous binding mode with the channels, possibly as a fail-safe measure to ensure a correct binding sequence. Thus, we suggest that SYP121 binding to the K+ channels serves the role of a primary trigger to initiate assembly of the secretory machinery for exocytosis.
Low‐dose‐rate brachytherapy for prostate cancer: A 15‐year experience in Japan

The history of prostate brachytherapy has passed one century. In 1983, modern low‐dose‐rate prostate brachytherapy using a transrectal ultrasound‐guided procedure was introduced. In the early 1990s, low‐dose‐rate brachytherapy was introduced and rapidly spread across the USA due to its excellent oncological control, cost‐effectiveness and technically easy procedure. Since low‐dose‐rate brachytherapy was introduced in Japan (2003), over 15 years have passed. More than 43 000 patients have undergone low‐dose‐rate brachytherapy. Japanese urologists and radiation oncologists are on course with leading brachytherapists in the USA. A nationwide prospective cohort study, J‐POPS, was initiated in 2005. The J‐POPS group also provides educational programs including an annual novel training course in low‐dose‐rate brachytherapy to familiarize urologists, radiation oncologists and pathologists with the procedure. Important information on Japanese patients has accumulated, especially by the J‐POPS study group. The Japanese investigators reported excellent oncological outcomes of low‐dose‐rate brachytherapy, showing equivalent or superior efficacy to surgery in low‐ to intermediate‐risk patients, and superior efficacy in high‐risk patients using the surgery biochemical recurrence definition (prostate‐specific antigen cut‐off value of 0.2 ng/mL). Two randomized controlled studies (SHIP study: intermediate risk, and TRIP study: high risk) carried out by the J‐POPS group are ongoing, and an additional follow‐up study (J‐POPS 2 study) has been started to evaluate survival outcomes over longer follow‐up periods. Low‐dose‐rate brachytherapy is expected to provide a survival benefit, which must be confirmed by further studies with longer follow‐up periods in the future.
Cost-Effective Cosmetic-Grade Hyaluronan Hydrogels for ReNcell VM Human Neural Stem Cell Culture

Hyaluronic acid (HA) is a polysaccharide polymer frequently used as a starting material to fabricate hydrogels, especially for recapitulating the brain’s extracellular matrix (ECM) for in vitro neural stem cell (NSC) cultures. Here, we report the successful synthesis of a methacrylated HA (MeHA) polymer from an inexpensive cosmetic-grade hyaluronan starting material. The MeHA polymers synthesized from cosmetic-grade HA yielded similar chemical purity to those from pharmaceutical/research-grade HA reported in the literature. Crosslinked MeHA (x-MeHA) hydrogels were formed using radical polymerization which resulted in mechanical properties matching previously reported mechanical property ranges for enhanced neuronal differentiation of NSCs. We assessed cellular adhesion, spreading, proliferation, and stiffness-dependent neuronal differentiation properties of ReNcell VM human neural stem cells (hNSCs) and compared our results to studies reported in the literature (that utilized non-human and human pluripotent cell-derived NSCs).
How chimpanzees (Pan troglodytes) share the spoils with collaborators and bystanders

Chimpanzees hunt cooperatively in the wild, but the factors influencing food sharing after the hunt are not well understood. In an experimental study, groups of three captive chimpanzees obtained a monopolizable food resource, either via two individuals cooperating (with the third as bystander) or via one individual acting alone alongside two bystanders. The individual that obtained the resource first retained most of the food but the other two individuals attempted to obtain food from the "captor" by begging. We found the main predictor of the overall amount of food obtained by bystanders was proximity to the food at the moment it was obtained by the captor. Whether or not an individual had cooperated to obtain the food had no effect. Interestingly, however, cooperators begged more from captors than did bystanders, suggesting that they were more motivated or had a greater expectation to obtain food. These results suggest that while chimpanzee captors in cooperative hunting may not reward cooperative participation directly, cooperators may influence sharing behavior through increased begging.
Relationship Between Troponin on Presentation and In‐Hospital Mortality in Patients With ST‐Segment–Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

Background Troponin release in ST‐segment–elevation myocardial infarction (STEMI) has predictable kinetics with early levels reflective of ischemia duration. Little research has examined the value of admission troponin levels in STEMI patients undergoing primary percutaneous coronary intervention. We investigated the relationship between troponin on presentation and mortality in a large, real‐world cohort of STEMI patients undergoing primary percutaneous coronary intervention. Methods and Results We used multivariable adaptive regression modeling to examine the association between admission troponin levels and in‐hospital mortality for patients who underwent primary percutaneous coronary intervention for STEMI. We adjusted for known clinical risk factors using a validated mortality risk model derived from the NCDR (National Cardiovascular Data Registry) CathPCI database, and this same model was used to calculate patients’ predicted mortality based on clinical and demographic factors. Patients were then stratified by troponin groups to compare predicted versus observed mortality. Of the 14 061 patients included in the cohort, 47.2% had initial troponin levels that were undetectable or within the reference range. Admission troponin was an independent predictor of in‐hospital mortality, and any value above the reference range was associated with increased mortality (1.8% versus 5.1%, [standardized difference, 18.2%]). Patients with the highest predicted risk for mortality (13% predicted) in the highest admission troponin grouping experienced an observed mortality of 19.5%. Patients in low troponin groupings consistently demonstrated lower than predicted mortality based on their clinical and demographic risk profile. Conclusions Nearly half of patients undergoing primary percutaneous coronary intervention had normal troponin on presentation and had a relatively good outcome. Mortality increases with elevated admission troponin levels, regardless of baseline clinical risk. The substantial number of patients who present with markedly elevated troponin and their relatively worse outcomes highlights the need for continued improvement in prehospital STEMI detection and care.
Translation, Cross-Cultural Adaptation, and Psychometric Properties of the Polish Version of the Hip Disability and Osteoarthritis Outcome Score (HOOS)

Background and Objectives: This study aimed to translate the Hip disability and Osteoarthritis Outcome Score (HOOS) into the Polish language, to determine its validity and reliability, and to assess its main psychometric properties. Materials and Methods: A total of 332 hip osteoarthritis (OA) subjects were recruited to the study group and 90 healthy subjects to the control group. The study consisted of the HOOS translation and the assessment of the discriminative power, internal consistency, and the potential floor and ceiling effects followed by the determination of the construct validity and test-retest reliability. The analysis was performed using Western Ontario and McMaster Universities osteoarthritis index (WOMAC) and SF-36 questionnaires. Results: The translation process consisted of forward translation, reconciliation, backward translation, review, harmonization, and proofreading. The hip OA patients reported a reduced HOOS score when compared to the control subjects. The discriminant validity of the questionnaire was confirmed. A Cronbach’s alpha of 0.97 was found, indicating a high internal consistency. The HOOS showed a significant correlation with the SF-36 and WOMAC, which ranged from r = −0.93, p-value < 0.05 for WOMAC total score to r = 0.92, and p-value < 0.05 for WOMAC daily living. No floor or ceiling effects were found. A very high intraclass correlation coefficient (ICC) was found (0.93–0.97) for the total score and the individual domains of the HOOS. Conclusions: The Polish HOOS is valid and reliable for evaluating the outcomes of hip OA patients in Poland. This questionnaire may be used with confidence for clinical and research purposes.
The Role of Lipopolysaccharide-Induced Extracellular Vesicles in Cardiac Cell Death

Exosomes play a crucial role in the progression of infectious diseases, as exosome release and biogenesis are affected by external factors, such as pathogenic infections. Pyrogens may aide in the progression of diseases by triggering inflammation, endothelial cell injury, and arterial plaque rupture, all of which can lead to acute coronary disease, resulting in cardiac tissue death and the onset of a cardiac event (CE). To better understand the effects of Gram-negative bacterial infections on exosome composition and biogenesis, we examined exosome characteristics after treatment of AC16 human cardiomyocytes with lipopolysaccharide (LPS), which served as a model system for Gram-negative bacterial infection. Using increasing doses (0, 0.1, 1, or 10 µg) of LPS, we showed that treatment with LPS substantially altered the composition of AC16-derived exosomes. Both the relative size and the quantity (particles/mL) of exosomes were decreased significantly at all tested concentrations of LPS treatment compared to the untreated group. In addition, LPS administration reduced the expression of exosomal proteins that are related to exosomal biogenesis. Conversely, we observed an increase in immunomodulators present after LPS administration. This evaluation of the impact of LPS on cardiac cell death and exosome composition will yield new insight into the importance of exosomes in a variety of physiological and pathological processes as it relates to disease progression, diagnosis, and treatment.
Osteoclast-Like Cells in Aneurysmal Disease Exhibit an Enhanced Proteolytic Phenotype

Abdominal aortic aneurysm (AAA) is among the top 20 causes of death in the United States. Surgical repair is the gold standard for AAA treatment, therefore, there is a need for non-invasive therapeutic interventions. Aneurysms are more closely associated with the osteoclast-like catabolic degradation of the artery, rather than the osteoblast-like anabolic processes of arterial calcification. We have reported the presence of osteoclast-like cells (OLCs) in human and mouse aneurysmal tissues. The aim of this study was to examine OLCs from aneurysmal tissues as a source of degenerative proteases. Aneurysmal and control tissues from humans, and from the mouse CaPO4 and angiotensin II (AngII) disease models, were analyzed via flow cytometry and immunofluorescence for the expression of osteoclast markers. We found higher expression of the osteoclast markers tartrate-resistant acid phosphatase (TRAP), matrix metalloproteinase-9 (MMP-9), and cathepsin K, and the signaling molecule, hypoxia-inducible factor-1α (HIF-1α), in aneurysmal tissue compared to controls. Aneurysmal tissues also contained more OLCs than controls. Additionally, more OLCs from aneurysms express HIF-1α, and produce more MMP-9 and cathepsin K, than myeloid cells from the same tissue. These data indicate that OLCs are a significant source of proteases known to be involved in aortic degradation, in which the HIF-1α signaling pathway may play an important role. Our findings suggest that OLCs may be an attractive target for non-surgical suppression of aneurysm formation due to their expression of degradative proteases.
RNA-seq as a tool for evaluating human embryo competence

The majority of embryos created through in vitro fertilization (IVF) do not implant. It seems plausible that rates of implantation would improve if we had a better understanding of molecular factors affecting embryo competence. Currently, the process of selecting an embryo for uterine transfer uses an ad hoc combination of morphological criteria, the kinetics of development, and genetic testing for aneuploidy. However, no single criterion can ensure selection of a viable embryo. In contrast, RNA-sequencing (RNA-seq) of embryos could yield high-dimensional data, which may provide additional insight and illuminate the discrepancies among current selection criteria. Recent advances enabling the production of RNA-seq libraries from single cells have facilitated the application of this technique to the study of transcriptional events in early human development. However, these studies have not assessed the quality of their constituent embryos relative to commonly used embryological criteria. Here, we perform proof-of-principle advancement to embryo selection procedures by generating RNA-seq libraries from a trophectoderm biopsy as well as the remaining whole embryo. We combine state-of-the-art embryological methods with low-input RNA-seq to develop the first transcriptome-wide approach for assessing embryo competence. Specifically, we show the capacity of RNA-seq as a promising tool in preimplantation screening by showing that biopsies of an embryo can capture valuable information available in the whole embryo from which they are derived. Furthermore, we show that this technique can be used to generate a RNA-based digital karyotype and to identify candidate competence-associated genes. Together, these data establish the foundation for a future RNA-based diagnostic in IVF.
Behavioral adjustment in children with life threatening illness A qualitative study

Behavioral Adjustment of Children with Life Threatening Illness By E. Joseph Becher, Jr. This study investigated factors that affect adjustment in children with life-threatening illness from the viewpoint of the parents/caregivers. The data were collected from parents/caregivers whose children have a life threatening diagnosis. Parents/caregivers were interviewed and asked to complete the Parent Request Questionnaire (PRQ) which was given to them after the in-person interview. This newly developed PRQ was utilized into prior research to predict the levels of adjustment in children. It includes age, whether the child has been informed of the diagnosis, whether the child engages in ageappropriate activities, the child's prior experience with death, the child's family's involvement in treatment, and the child's belief in an after-life. Prior literature suggests associations between these factors and the child's ability to adjust to the diagnosis. This study examined these factors revealed by the parents/caregivers and any similarities were noted. There has been limited research conducted on behavioral adjustment in children with life threatening illness. This qualitative study utilized an open-ended interview process to gather information about the factors that promote behavioral adjustment and whether or not the factors already researched in quantitative studies applied. The interviewees were participants in independent support groups benefiting the caregivers/parents of the children with life threatening illness. Participants were also recruited by word-of-mouth after calling such groups and individuals in California. The PRQ was distributed after the interview as an additional measure. The interview revealed factors as noted by the caregivers and indicated the emergent themes of: isolation, fear, inquisitiveness, age-appropriate activities, diagnoses shared, and support systems. The interview and the PRQ were used to analyze child adjustment reported during the interview sessions. The participants in this study were all parents/caregivers. Instrumentation was a structured interview and a demographic questionnaire (PRQ). The texts were transcribed and analyzed using Thematic Analysis. Narratives of their life experience with the child having life-threatening illness were examined. Emergent themes, previously mentioned, were elicited from the interview material in hopes of providing additional support services needed as voiced by the parents/caregivers. “The electronic version of the dissertation is accessible at the Ohiolink ETD center http://www.ohiolink. edu/etd/ “.