Miracle-dz/UniFAR-FTUs huggingface dataset:
FK506-Binding Protein 12.6/1b, a Negative Regulator of [Ca2+], Rescues Memory and Restores Genomic Regulation in the Hippocampus of Aging Rats

Hippocampal overexpression of FK506-binding protein 12.6/1b (FKBP1b), a negative regulator of ryanodine receptor Ca2+ release, reverses aging-induced memory impairment and neuronal Ca2+ dysregulation. Here, we tested the hypothesis that FKBP1b also can protect downstream transcriptional networks from aging-induced dysregulation. We gave hippocampal microinjections of FKBP1b-expressing viral vector to male rats at either 13 months of age (long-term, LT) or 19 months of age (short-term, ST) and tested memory performance in the Morris water maze at 21 months of age. Aged rats treated ST or LT with FKBP1b substantially outperformed age-matched vector controls and performed similarly to each other and young controls (YCs). Transcriptional profiling in the same animals identified 2342 genes with hippocampal expression that was upregulated/downregulated in aged controls (ACs) compared with YCs (the aging effect). Of these aging-dependent genes, 876 (37%) also showed altered expression in aged FKBP1b-treated rats compared with ACs, with FKBP1b restoring expression of essentially all such genes (872/876, 99.5%) in the direction opposite the aging effect and closer to levels in YCs. This inverse relationship between the aging and FKBP1b effects suggests that the aging effects arise from FKBP1b deficiency. Functional category analysis revealed that genes downregulated with aging and restored by FKBP1b were associated predominantly with diverse brain structure categories, including cytoskeleton, membrane channels, and extracellular region. Conversely, genes upregulated with aging but not restored by FKBP1b associated primarily with glial–neuroinflammatory, ribosomal, and lysosomal categories. Immunohistochemistry confirmed aging-induced rarefaction and FKBP1b-mediated restoration of neuronal microtubular structure. Therefore, a previously unrecognized genomic network modulating diverse brain structural processes is dysregulated by aging and restored by FKBP1b overexpression. SIGNIFICANCE STATEMENT Previously, we found that hippocampal overexpression of FK506-binding protein 12.6/1b (FKBP1b), a negative regulator of intracellular Ca2+ responses, reverses both aging-related Ca2+ dysregulation and cognitive impairment. Here, we tested whether hippocampal FKBP1b overexpression also counteracts aging changes in gene transcriptional networks. In addition to reducing memory deficits in aged rats, FKBP1b selectively counteracted aging-induced expression changes in 37% of aging-dependent genes, with cytoskeletal and extracellular structure categories highly associated with the FKBP1b-rescued genes. Our results indicate that, in parallel with cognitive processes, a novel transcriptional network coordinating brain structural organization is dysregulated with aging and restored by FKBP1b.
HbzF Catalyzes Direct Hydrolysis of Maleylpyruvate in the Gentisate Pathway of Pseudomonas alcaligenes NCIMB 9867

ABSTRACT HbzF from Pseudomonas alcaligenes NCIMB 9867 was purified to homogeneity as a His-tagged protein and likely a dimer by SDS-PAGE and gel filtration. This protein was demonstrated to be a novel maleylpyruvate hydrolase, catalyzing direct hydrolysis of maleylpyruvate to maleate and pyruvate, and belongs to the fumarylacetoacetate hydrolase superfamily. This study reveals the genetic determinate for the direct maleylpyruvate hydrolysis in the gentisate pathway, complementary to the well-studied maleylpyruvate isomerization route.
Circadian Clock Proteins and Melatonin Receptors in Neurons and Glia of the Sapajus apella Cerebellum

Oscillations of brain proteins in circadian rhythms are important for determining several cellular and physiological processes in anticipation of daily and seasonal environmental rhythms. In addition to the suprachiasmatic nucleus, the primary central oscillator, the cerebellum shows oscillations in gene and protein expression. The variety of local circuit rhythms that the cerebellar cortex contains influences functions such as motivational processes, regulation of feeding, food anticipation, language, and working memory. The molecular basis of the cerebellar oscillator has been demonstrated by “clock gene” expression within cells of the cerebellar layers. Genetic and epidemiological evidence suggests that disruption of circadian rhythms in humans can lead to many pathological conditions. Despite this importance, data about clock gene and protein expression in the cerebellum of diurnal (day-active) species, specifically primates, is currently poorly explored, mainly in regard to cellular identity, as well as the relationship with other molecules also involved in cerebellar functions. These studies could contribute to clarification of the possible mechanisms behind cerebellar rhythmicity. Considering that calcium binding proteins (CaBPs) play crucial roles in preserving and modulating cerebellar functions and that clock gene expression can be controlled by afferent projections or paracrine circadian signals such as the hormone melatonin, the present study aimed to describe cellular identities, distribution patterns and day/night expression changes in PER1, PER2, CaBPs, and MT1 and MT2 melatonin receptors in the cerebellar cortex of a diurnal primate using conventional fluorescence and peroxidase-antiperoxidase immunocytochemical techniques. PER1 and PER2 immunoreactive (IR) cells were observed in the Purkinje cells of the cerebellum, and MT1 and MT2 receptors were localized around Purkinje cells in the Pj layer in Bergmann cells. This identity was confirmed by the S100β-IR of these cells. The highest expression of PER seen in the daytime analysis coincided with the highest expression of melatonin receptors. CaBPs showed day/night morphological and density changes in the cerebellar cortex. The presence of the same temporal variations in the expression of PER in the Pj neurons and in MT1 and MT2 receptors in Bergmann cells indicates a possible relation between these cells during the rhythmic processing of the cerebellum, in addition to the CaBP temporal morphological and density changes.
Systemic Immunomodulating Therapies for Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Systematic Review and Meta-analysis

Importance Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are rare but severe adverse reactions with high mortality. There is no evidence-based treatment, but various systemic immunomodulating therapies are used. Objectives To provide an overview on possible immunomodulating treatments for SJS/TEN and estimate their effects on mortality compared with supportive care. Data Sources A literature search was performed in December 2012 for articles published in MEDLINE, MEDLINE Daily, MEDLINE Inprocess, Web of Science, EMBASE, Scopus, and the Cochrane Library (Central) from January 1990 through December 2012, and updated in December 2015, in the English, French, Spanish, and German languages looking for treatment proposals for SJS/TEN. Other sources were screened manually. Study Selection Initially, 157 randomized and nonrandomized studies on therapies (systemic immunomodulating therapies or supportive care) for SJS/TEN were selected. Data Extraction and Synthesis Relevant data were extracted from articles. Authors were contacted for further information. Finally, 96 studies with sufficient information regarding eligibility and adequate quality scores were considered in the data synthesis. All steps were performed independently by 2 investigators. Meta-analyses on aggregated study data (random-effects model) and individual patient data (IPD) (logistic regression adjusted for confounders) were performed to assess therapeutic efficacy. In the analysis of IPD, 2 regression models, stratified and unstratified by study, were fitted. Main Outcomes and Measures Therapy effects on mortality were expressed in terms of odds ratios (ORs) with 95% CIs. Results Overall, 96 studies (3248 patients) were included. Applied therapies were supportive care or systemic immunomodulating therapies, including glucocorticosteroids, intravenous immunoglobulins, cyclosporine, plasmapheresis, thalidomide, cyclophosphamide, hemoperfusion, tumor necrosis factor inhibitors, and granulocyte colony-stimulating factors. Glucocorticosteroids were associated with a survival benefit for patients in all 3 analyses but were statistically significant in only one (aggregated data: OR, 0.5; 95%% CI, 0.3-1.01; IPD, unstratified: OR, 0.7; 95% CI, 0.5-0.97; IPD, stratified: OR, 0.8; 95% CI, 0.4-1.3). Despite the low patient size, cyclosporine was associated with a promising significant result in the only feasible analysis of IPD (unstratified model) (OR, 0.1; 95% CI, 0.0-0.4). No beneficial findings were observed for other therapies, including intravenous immunoglobulins. Conclusions and Relevance Although all analyses, including the unstratified model, had limitations, glucocorticosteroids and cyclosporine were the most promising systemic immunomodulating therapies for SJS/TEN. Further evaluation in prospective studies is required. However, this work provides a comprehensive overview on proposed systemic immunomodulating treatments for SJS/TEN, which is of great relevance for treating physicians.
Why Do Some Toddlers Help A Stranger ? Origins of Individual Di ff erences in Prosocial Behavior

This study investigated the influence of emotion on toddlers’ prosocial behavior in instrumental helping tasks with an unfamiliar adult. The goals were to examine whether early prosocial behavior was affected by (1) the adult’s expressions of sadness (in contrast to a neutral expression) as a cue of need and (2) toddlers’ emotion understanding. Thirty-five 18to 20-month-olds participated in eight trials in which an experimenter either indicated need for assistance (experimental condition) or did not (control). In addition, the experimenter expressed either sadness or neutral affect in each trial. Toddlers’ emotion understanding was assessed using maternal reports of children’s emotion words. The experimenter’s emotional expression alone was not associated with prosocial behavior, but toddlers helped more in experimental than control conditions. However, toddlers with larger emotion word vocabularies were marginally more prosocial when the experimenter expressed sadness, and girls provided more assistance than boys in experimental conditions. These findings highlight the complex influences of emotion on early prosocial motivation.
Does Evaluative Conditioning Depend on Awareness? Evidence From a Continuous Flash Suppression Paradigm

The role of awareness in evaluative learning has been thoroughly investigated with a variety of theoretical and methodological approaches. We investigated evaluative conditioning (EC) without awareness with an approach that conceptually provides optimal conditions for unaware learning - the Continuous Flash Suppression paradigm (CFS). In CFS, a stimulus presented to one eye can be rendered invisible for a prolonged duration by presenting a high-contrast dynamic pattern to the other eye. The suppressed stimulus is nevertheless processed. First, Experiment 1 established EC effects in a pseudo-CFS setup without suppression. Experiment 2 then employed CFS to suppress conditioned stimuli (CSs) from awareness while the unconditioned stimuli (USs) were visible. While Experiment 1 and 2 used a between-participants manipulation of CS suppression, Experiments 3 and 4 both manipulated suppression within participants. We observed EC effects when CSs were not suppressed, but found no EC effects when the CS was suppressed from awareness. We relate our finding to previous research and discuss theoretical implications for EC.
Relationship Between Change of Direction, Speed, and Power in Male and Female National Olympic Team Handball Athletes

Abstract Pereira, LA, Nimphius, S, Kobal, R, Kitamura, K, Turisco, LAL, Orsi, RC, Cal Abad, CC, and Loturco, I. Relationship between change of direction, speed, and power in male and female National Olympic Team handball athletes. J Strength Cond Res 32(10): 2987–2994, 2018—The aims of this study were to (a) assess the relationship between selected speed- and power-related abilities (determined by 20-m sprint, unloaded countermovement jump [CMJ] and squat jump [SJ], and loaded jump squat [JS]) and performance in 2 distinct change of direction (COD) protocols (Zigzag test and T-test) and (b) determine the magnitude of difference between female and male Brazilian National Olympic Team handball athletes. Fifteen male and 23 female elite handball athletes volunteered to perform the following assessments: SJ and CMJ; Zigzag test and T-test; 20-m sprint with 5-, 10-, and 20-m splits; and mean propulsive power in JS. Pearson's product-moment correlation (p ⩽ 0.05) was performed to determine the relationship between the COD tests (Zigzag test and T-test) and speed-power measures (sprint, SJ, CMJ, and JS). The differences between male and female performances were determined using the magnitude-based inference. Moderate to very large significant correlations were observed between both COD tests and the speed-power abilities. Furthermore, male athletes demonstrated likely to almost certainly higher performances than female athletes in all assessed variables. The results of the current study suggest that different speed-power qualities are strongly correlated to the performance obtained in various COD assessments (r values varying from 0.38 to 0.84 and from 0.34 to 0.84 for correlations between speed and power tests with Zigzag test and T-test, respectively). However, the level of these associations can vary greatly, according to the mechanical demands of each respective COD task. Although COD tests may be difficult to implement during competitive seasons, because of the strong correlations presented herein, the regular use of vertical jump tests with these athletes seems to be an effective and applied alternative. Furthermore, it might be inferred that the proper development of loaded and unloaded jump abilities has potential for improving the physical qualities related to COD performance in handball athletes.
Edge Dissimilarity Reduced-Reference Quality Metric with Low Overhead Bitrate

In multimedia transmission, it is important to rely on an objective quality metric which accurately represents the subjective quality of processed images and video sequences. Reduced-reference metrics make use of side-information that is transmitted to the receiver for estimating the quality of the received sequence with low complexity. In this paper, an Edge-based Dissimilarity Reduced-Reference video quality metric with low overhead bitrate is proposed. The metric is evaluated by finding the dissimilarity between the edge information of original and distorted sequences. The edge degradation can be detected in this manner as perceived video quality is highly associated with edge structural. Due to the high overhead using the Soergel distance, it is pertinent to find a way to reduce the overhead while maintaining the edge information that can convey the quality measure of the sequences. The effects of different edge detection operator, video resolution and file compressor are investigated. The aim of this paper is to significantly reduce the bitrate required in order to transmit the side information overhead as the reduced reference video quality metric. From the results obtained, the side information extracted using Sobel edge detector maintained consistency throughout the reduction of spatial and temporal down-sample.
Appropriate Child and Adolescent Mental Health Service (CAMHS): Māori Caregiver's Perspectives

The development of Child and Adolescent Mental Health Services (CAMHS) that meet the needs of Maori (indigenous people of Aotearoa/ New Zealand) is critical. This study, Te Tomokanga, investigated the acceptability of mainstream 1 , bicultural, 2 and kaupapa Māori 3 CAMHS access and delivery to young Māori and their whānau. 4 Detailed factors contributing to potential areas for improvement are identified in this examination. This includes, most specifically, a cultural framework based on the traditional Māori Pōwhiri process of access and engagement provided by a culturally relevant workforce. Method A kaupapa Māori (Māori driven) research paradigm, based on the traditional Pōwhiri process of engagement and participation guided this qualitative research approach, particularly the components of karanga, mihimihi, whaikōrero and koha. These components are discussed in more detail in this article. 1. Mainstream services in this study had no dedicated Māori positions available. 2. Bicultural services in this study had a/some dedicated Māori positions available. 3. Kaupapa Māori services in this study had dedicated Māori positions available. 4. Whānau, parents and caregivers are used interchangeably in this thesis.
Bioinspired Surface for Low Drag, Self-Cleaning, and Antifouling: Shark Skin, Butterfly and Rice Leaf Effects

ii DEDICATION . iv ACKNOWLEDGMENTS . v VITA . vi LIST OF TABLES . xiii LIST OF FIGURES . xiv CHAPTER 1: Introduction . 1 1.1. Fluid drag and antifouling overview . 3 1.2. Bioinspired low drag and antifouling. 8 1.3. The rice and butterfly wing effect . 10 1.4. Scope of the thesis . 12 CHAPTER 2: Biofouling: Lessons from Nature . 14 2.
Does laparoscopy still has a role in modern fertility practice?

Background: More than 3 decades after the introduction of in vitro fertilization (IVF) and despite the improved success rates of assisted reproductive technologies, the argument for performing laparoscopy as a part of the infertility workup still stands. Objective: To evaluate the role of laparoscopy±hysteroscopy in diagnosis and management of infertility in our setting in view of modern fertility practice. Materials and Methods: This case control study was carried out on 600 infertile women subjected to laparoscopy or combined laparoscopy and hysteroscopy at endoscopy unit in Minia University Hospital, Egypt during the period from January 2012 to December 2014. Results: The causes of infertility as identified by laparoscopy±hysteroscopy were polycystic ovary syndrome (25.1%), tubal factor (30%), uterine cause (4%), and endometriosis (2.7%). No cause was identified in 38.2% of cases. Based on operative findings, women were treated with different options. Expectant management was used in 92 cases (15.3%). Ovulation induction with anti-estrogens or gonadotropins was used in 372 cases (62%). Sixty cases (10%) had intrauterine insemination and sixty four cases (10.7%) underwent in vitro fertilization (IVF) / intracytoplasmic sperm injection (ICSI) treatment. Within 1 yr after laparoscopy, 180 cases achieved pregnancy (30%). The most favorable outcome was recorded in women with unexplained infertility (36.7% of cases got pregnant) followed by women with polycystic ovary syndrome (27.8%). Participants with uterine and tubal infertility factor achieved pregnancy in 25% and 22.8% of cases, respectively. The worst outcome was recorded in women with endometriosis. Conclusion: Laparoscopy still has an important role in the diagnosis and treatment of infertility.
Electrophysiological evidence of phonetic normalization across coarticulation in infants.

The auditory neural representations of infants can easily be studied with electroencephalography using mismatch experimental designs. We recorded high-density event-related potentials while 3-month-old infants were listening to trials consisting of CV syllables produced with different vowels (/bX/ or /gX/). The consonant remained the same for the first three syllables, followed (or not) by a change in the fourth position. A consonant change evoked a significant difference around the second auditory peak (400-600 ms) relative to control trials. This mismatch response demonstrates that the infants robustly categorized the consonant despite coarticulation that blurs the phonetic cues, and at an age at which they do not produce these consonants themselves. This response was obtained even when infants had no visual articulatory information to help them to track the consonant repetition. In combination with previous studies establishing categorical perception and normalization across speakers, this result demonstrates that preverbal infants already have abstract phonetic representation integrating over acoustical features in the first months of life.
The value of secure property rights : global evidence from fisheries ∗

Property rights are often touted as a solution to common pool resource problems. But in practice the strength and security of these property rights varies significantly; this variation is expected to affect asset value. In fisheries, the property rights underlying individual transferable quotas (ITQs) very substantially both within and across countries, though the implications of the security of these rights has not been carefully studied. We compile a unique dataset covering ITQ sales and lease prices for fisheries in several countries, and examine the relationship between property rights strength and the value of fishery assets. We find that stronger property rights are associated with substantially higher asset values and lower implied discount rates. This result confirms basic economic intuition, and informs current policy debate on the design of property rights institutions for natural resources.
RGD-conjugated albumin nanoparticles as a novel delivery vehicle in pancreatic cancer therapy

Integrin αvβ3 receptor is expressed on several types of cancer cells, including pancreatic cancer cells, and plays an important role in tumor growth and metastasis. The ability to target the integrin αvβ3 receptor on cancer cells increases the efficacy of targeted therapy and reduces the side effects. The aim of this study is to develop a novel arginine-glycine-aspartic acid (RGD) peptide-conjugated albumin nanoparticle to enhance the intracellular uptake of anticancer drug into the pancreatic cancer cells through receptor-mediated endocytosis. In cellular uptake studies, the fluorescent signal of RGD-conjugated BSANPs in BxPC3 cells was higher than that of BSANPs without RGD conjugation as determined by fluorescence spectrophotometer. We also found that BSANPs bound to BxPC3 cells in a time- and concentration-dependent manner. The uptake of RGD-conjugated BSANPs by pancreatic cancer cells was inhibited by an excess amount of free RGD peptide, indicating that the binding and/or uptake were mediated by the αvβ3 receptor. Furthermore, the nanoparticles were found to be located close to the nuclei by using laser scanning confocal microscopy. Besides, no significant in vitro cytotoxicity was observed as measured with MTT assay. Both in vitro and in vivo antitumor efficacy was improved by targeting gemcitabine-loaded nanoparticles to BxPC-3 cells using RGD peptides. Therefore, the RGD-conjugated BSANPs hold great potential as an effective drug delivery system to deliver therapeutic agents to pancreatic cancer.