Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic dissection of stress-induced reproductive arrest in Drosophila melanogaster females

By genetic manipulations, we study the roles played by insulin-producing cells (IPCs) in the brain and their target, the corpora allata (CA), for reproductive dormancy in female Drosophila melanogaster, which is induced by exposing them to a combination of low temperature (11°C), short-day photoperiod (10L:14D) and starvation (water only) for 7 days immediately after eclosion (dormancy-inducing conditions). Artificial inactivation of IPCs promotes, whereas artificial activation impedes, the induction of reproductive dormancy. A transcriptional reporter assay reveals that the IPC activity is reduced when the female flies are exposed to dormancy-inducing conditions. The photoperiod sensitivity of reproductive dormancy is lost in pigment-dispersing factor (pdf), but not cry, mutants, suggesting that light input to IPCs is mediated by pdf-expressing neurons. Genetic manipulations to upregulate and downregulate insulin signaling in the CA, a pair of endocrine organs that synthesize the juvenile hormone (JH), decrease and increase the incidence of reproductive dormancy, respectively. These results demonstrate that the IPC-CA axis constitutes a key regulatory pathway for reproductive dormancy.
The Collaborative Role of North American Departments of Pediatrics in Global Child Health

In this review, we describe the collaborative role of NA pediatrics departments in GCH education, and clinical practice and research summarizing challenges and best practices. Appeals for health equity call for departments of pediatrics to improve the health of all children including those from underserved communities in North America and around the world. Consequently, North American (NA) departments of pediatrics have a role in global child health (GCH) which focuses on providing health care to underserved children worldwide. In this review, we describe how NA departments of pediatrics can collaboratively engage in GCH education, clinical practice, research, and advocacy and summarize best practices, challenges, and next steps for engaging in GCH in each of these areas. For GCH in low- and middle-income countries (LMICs), best practices start with the establishment of ethical, equitable, and collaborative partnerships with LMIC communities, organizations, and institutions engaged in GCH who are responsible for the vast majority of work done in GCH. Other best practices include adequate preparation of trainees and clinicians for GCH experiences; alignment with local clinical and research priorities; contributions to local professional development and ongoing monitoring and evaluation. Challenges for departments include generating funding for GCH activities; recruitment and retention of GCH-focused faculty members; and challenges meeting best practices, particularly adequate preparation of trainees and clinicians and ensuring mutual benefit and reciprocity in NA–LMIC collaborations. We provide examples of how departments have overcome these challenges and suggest next steps for development of the role of NA departments of pediatrics in GCH. Collaborative implementation of best practices in GCH by LMIC–NA partnerships can contribute to reductions of child mortality and morbidity globally.
The Roles of p53 in Mitochondrial Dynamics and Cancer Metabolism: The Pendulum between Survival and Death in Breast Cancer?

Cancer research has been heavily geared towards genomic events in the development and progression of cancer. In contrast, metabolic regulation, such as aberrant metabolism in cancer, is poorly understood. Alteration in cellular metabolism was once regarded simply as a consequence of cancer rather than as playing a primary role in cancer promotion and maintenance. Resurgence of cancer metabolism research has identified critical metabolic reprogramming events within biosynthetic and bioenergetic pathways needed to fulfill the requirements of cancer cell growth and maintenance. The tumor suppressor protein p53 is emerging as a key regulator of metabolic processes and metabolic reprogramming in cancer cells—balancing the pendulum between cell death and survival. This review provides an overview of the classical and emerging non-classical tumor suppressor roles of p53 in regulating mitochondrial dynamics: mitochondrial engagement in cell death processes in the prevention of cancer. On the other hand, we discuss p53 as a key metabolic switch in cellular function and survival. The focus is then on the conceivable roles of p53 in breast cancer metabolism. Understanding the metabolic functions of p53 within breast cancer metabolism will, in due course, reveal critical metabolic hotspots that cancers advantageously re-engineer for sustenance. Illustration of these events will pave the way for finding novel therapeutics that target cancer metabolism and serve to overcome the breast cancer burden.
A perceptual-based approach to bit allocation for H.264 encoder

Since the ultimate receivers of encoded video are human eyes, the characteristics of human visual system should be taken into consideration in the design of bit allocation to improve the perceptual video quality. In this paper, we incorporate the structural similarity index as a distortion metric and propose a novel rate-distortion model to characterize the relationship between rate and the structural similarity index. Based on the model, we develop an optimum bit allocation and rate control scheme for H.264 encoders. Experimental results show that up to 25% bitrate reduction over the JM reference software can be achieved. Subjective evaluation further confirms that the proposed scheme preserves more structural information and improves the perceptual quality of the encoded video.
On-demand release of Candida albicans biofilms from urinary catheters by mechanical surface deformation

Abstract Candida albicans is a leading cause of catheter-associated urinary tract infections and elimination of these biofilm-based infections without antifungal agents would constitute a significant medical advance. A novel urinary catheter prototype that utilizes on-demand surface deformation is effective at eliminating bacterial biofilms and here the broader applicability of this prototype to remove fungal biofilms has been demonstrated. C. albicans biofilms were debonded from prototypes by selectively inflating four additional intralumens surrounding the main lumen of the catheters to provide the necessary surface strain to remove the adhered biofilm. Deformable catheters eliminated significantly more biofilm than the controls (>90% eliminated vs 10% control; p < 0.001). Mechanical testing revealed that fungal biofilms have an elastic modulus of 45 ± 6.7 kPa with a fracture energy of 0.4–2 J m−2. This study underscores the potential of mechanical disruption as a materials design strategy to combat fungal device-associated infections.
Regional Variation of /r/ in Swiss German Dialects

German-speaking Europe is known to feature substantial regional variation in the articulation of /r/. According to historical surveys, this is particularly true for the most southwestern fringe of the region, i.e. German-speaking Switzerland. Large-scale, multilocality studies that show an updated picture of regional variation in this region are lacking, however. To this end, we coded /r/s of almost 3,000 speakers from 438 localities on a predominantly auditory basis, using data crowdsourced through a smartphone app. We report substantial regional variation, with uvular articulations especially dominant in the Northwest and the Northeast and alveolar – particularly tapped – articulations prevalent in the Midlands. We further provide exemplary evidence of an urban ([ ʁ ]) vs. rural stratification ([ ɾ ]) in the Northwest. This contribution further discusses (a) issues related to the coding of /r/, given the volatile articulatory and acoustic properties of /r/s and (b) the benefits and pitfalls of the crowdsourcing methodology applied more generally.
An object detection strategy for uncooled infrared imagery

Abstract An overall strategy for the very difficult problem of object detection using uncooled infrared (UCIR) sensors is discussed. The UCIR sensors are based on micro-bolometer technology and thus differ significantly from cooled infrared sensors that employ photon-counting detectors. As such, UCIR imagery tends to be very low contrast, since the sensor operates over a broad spectral band; and blurry, because of the long integration times. Ideally, the UCIR imagery would be preprocessed using an appropriate image reconstruction/restoration algorithm. If the sources of image degradation are understood and lend themselves to accurate modelling, the image reconstruction can be solved as an inverse problem. Most often this is not the case and the problem is solved using minimization approaches, such as blind deconvolution. Because image reconstruction/restoration approaches tend to be very throughput intensive, they are rarely performed in a tactical environment. More typically, a detection algorithm is applied directly to the UCIR imagery. In this paper, Local Singular Value Decomposition (LSVD) is evaluated for anomaly detection. LSVD uses local statistics to identify anomalous regions and is very good at identifying local texture differences; it appears to work quite well on UCIR imagery. Target detection results are presented for a simulated data set.
[Effect of serum estradiol level before progesterone administration on pregnancy outcomes of frozen-thawed embryo transfer cycles].

OBJECTIVE To explore whether a high serum estradiol (E2) level before progesterone administration adversely affects the pregnancy outcomes of frozen-thawed embryo transfer (FET) cycles. METHODS We retrospectively analyzed 205 hormone replacement therapy (HRT)-FET cycles in our Center between February, 2017 and August, 2017. With a cutoff value of serum E2 level of 600 pg/mL before progesterone administration, the cases were divided into high E2 level group and control group with normal E2 level, and the clinical characteristics and pregnancy outcomes were compared between the two groups. RESULTS No significant difference was found between the two groups in the patients'age during IVF/ICSI cycle, body mass index (BMI) or endometrial thickness at the time of FET (P>0.05). The patients with high E2 levels had a significantly younger age (P<0.05) and a significantly longer duration of estradiol administration than those in the control group (P<0.05). The clinical pregnancy rates, ongoing pregnancy rates, early miscarriage rates, late abortion rates and live birth rates were all comparable between the two groups (P>0.05). After controlling for the compounding factors including the age at FET cycle and the duration of estradiol administration, all these pregnancy outcomes were still comparable between the two groups. CONCLUSION A high serum E2 level before progesterone administration does not adversely affect the pregnancy outcomes of HRT-FET cycles.
Inhibition of prostaglandin E2 protects abdominal aortic aneurysm from expansion through regulating miR-29b-mediated fibrotic ECM expression

The risk of rupture, the most feared clinical consequence of abdominal aortic aneurysm, increases with the enlargement of aorta. MicroRNA-29b (miR-29b) has emerged as a key modulator of extracellular matrix (ECM) homeostasis and thereby is proposed to play a crucial role in vascular remodeling. However, agents that alter miR-29b expression are relatively inefficient in the aorta, likely due to inferior uptake. Herein we found that miR-29b was upregulated in aortic smooth muscle cells upon prostaglandin E2 (PGE2) stimulation whereas indomethacin treatment downregulated miR-29b expression. In order to obtain insight into the pathological processes associated with the vascular remodeling that accompanies aortic dilatation, we compared expression profiles of several representative ECM components in aortic walls. Notably, PGE2 induced a dramatic decline in these ECM components, which was rescued by introduction of indomethacin. In addition, COL1A1 was validated as a direct target gene of miR-29b by dual-luciferase reporter assay. In aggregate, our study suggests that PGE2 may accelerate ECM degradation through decreasing miR-29b expression. Thus those anti-inflammatory drugs that inhibit PGE2 synthesis represent an effective means of inducing an augmented profibrotic response in the aortic walls and thereby inhibiting aneurysmal expansion.
Evaluating Domain-Specific Metric Thresholds: An Empirical Study

Software metrics and thresholds provide means to quantify several quality attributes of software systems. Indeed, they have been used in a wide variety of methods and tools for detecting different sorts of technical debts, such as code smells. Unfortunately, these methods and tools do not take into account characteristics of software domains, as the intrinsic complexity of geo-localization and scientific software systems or the simple protocols employed by messaging applications. Instead, they rely on generic thresholds that are derived from heterogeneous systems. Although derivation of reliable thresholds has long been a concern, we still lack empirical evidence about threshold variation across distinct software domains. To tackle this limitation, this paper investigates whether and how thresholds vary across domains by presenting a large-scale study on 3,107 software systems from 15 domains. We analyzed the derivation and distribution of thresholds based on 8 well-known source code metrics. As a result, we observed that software domain and size are relevant factors to be considered when building benchmarks for threshold derivation. Moreover, we also observed that domain-specific metric thresholds are more appropriated than generic ones for code smell detection.
IGF1R Gene Alterations in Small for Gestational Age (SGA) Children

BACKGROUND: Small for gestational age children (SGA) is born on term with BW and or BL of -2.0 standard deviation score (SDS). SGA children have an increased risk of being short, developing DM, and cardiovascular and cerebrovascular disease. Often defects of IGF1R are the cause of SGA. Most frequently affected part of the IGF1R gene is the exon 2. AIM: To investigate whether the exon 2 of the IGF1R gene is affected in the SGA children. PATIENTS AND METHODS: A cohort of 100 SGA children born in term was evaluated for alterations in IG1R gene. Their anthropometric parameters, IGF1 serum concentrations and IGF1 SDS values were analysed. The molecular analysis of IGF1R gene was performed by PCR restriction-site analysis and followed by direct sequencing of conspicuous fragments. RESULTS: Within our cohort, 64 SGA children were with short stature (height SDS -3.25 ± 0.90 SDS), and 36 were with normal height for their age and sex, (H SDS was 0.20 ± 1.1 SDS). None of these children had microcephaly (occipitofrontal circumference -0.70 ± 1.01 SDS vs 0.06 ± 0.56 SDS in SGA children with normal height) or dysmorphic features. The IGF1 serum concentrations and IGF1 SDS values of all children were within normal range. Only one child had lower normal serum IGF1 concentration. No alterations in exon 2 of IGF1R gene were detected. CONCLUSIONS: The genetic analysis of the exon 2 of the IGF1R gene did not detect any gene defects in the analysed patients. The putative genetic defect in those children affects other parts of the IGF1R gene or another gene (s), or yet unidentified factors.
The Effects of Beta-Hydroxy-Beta-Methylbutyrate-Free Acid Supplementation and Resistance Training on Oxidative Stress Markers: A Randomized, Double-Blind, Placebo-Controlled Study

The aim of this study was to investigate the effects of 6-week beta-hydroxy-beta methylbutyrate-free acid (HMB-FA) supplementation on oxidative stress and biochemical variables in responses to resistance training. Sixteen healthy young males participated in this study and were randomly assigned to a HMB-FA supplementation group (n = 8) or a placebo supplementation group (n = 8). The resistance training program was applied for 6 weeks with two sessions per week. Blood samples were collected before and after training, and 8-hydroxy-2-deoxyguanosine (8-OHdG), malondialdehyde (MDA), protein carbonyl (PC), and biochemical variables, such as alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and the numbers of total white blood cells (WBC), neutrophils, lymphocytes, and monocytes were analyzed. Following intervention, both the HMB-FA and placebo supplementation groups showed significant decreases in MDA (effect size [ES]; −0.39, −0.33) and PC (ES; −1.37, −1.41), respectively. However, 8-OHdG did not change after 6 weeks of training in any of the groups. In addition, both groups showed similar training effects on biochemical variables after 6 weeks of intervention. It was concluded that HMB-FA supplementation during resistance training did not add further adaptive changes related to oxidative stress markers.
The stress hormone norepinephrine increases the growth and virulence of Aeromonas hydrophila

Stress is an important contributing factor in the outbreak of infectious fish diseases. To comprehensively understand the impact of catecholamine stress hormone norepinephrine (NE) on the pathogenicity of Aeromonas hydrophila, we assessed variations in bacterial growth, virulence‐related genes expression and virulence factors activity after NE addition in serum‐SAPI medium. Further, we assessed the effects of NE on A. hydrophila virulence in vivo by challenging fish with pathogenic strain AH196 and following with or without NE injection. The NE‐associated stimulation of A. hydrophila strain growth was not linear‐dose‐dependent, and only 100 μM, or higher concentrations, could stimulate growth. Real‐time PCR analyses revealed that NE notably changed 13 out of the 16 virulence‐associated genes (e.g. ompW, ahp, aha, ela, ahyR, ompA, and fur) expression, which were all significantly upregulated in A. hydrophila AH196 (p < 0.01). NE could enhance the protease activity, but not affect the lipase activity, hemolysis, and motility. Further, the mortality of crucian carp challenged with A. hydrophila AH196 was significantly higher in the group treated with NE (p < 0.01). Collectively, our results showed that NE enhanced the growth and virulence of pathogenic bacterium A. hydrophila.
Streptozotocin-induced diabetes mellitus affects the NMDA receptors: Role of caffeine administration in enhancing learning, memory and locomotor deficits

Objective: To investigate the deterioration of the brain functions by diabetes mellitus (DM) and the beneficial effect of caffeine. Materials and Methods: First, the component of N-methyl-D-aspartate receptors (NMDA) of the field excitatory postsynaptic potential (fEPSP) were recorded in streptozotocin (STZ)-induced DM and compared with control animals. Later, 40 mice were divided randomly into five groups (8 mice in each): (1) Normal control (Cont), (2) diabetic group (DM), (3) animals pretreated with i.p. caffeine before the induction of DM (Pre Caf), (4) acute caffeine-treated group (Ac Caf), and (5) chronic caffeine group (Ch Caf). Learning and memory were assessed in Morris-Water maze, and motor coordination was tested by rotarod. Results: A significant reduction in the NMDA-component of the fEPSPs responses was recorded in the hippocampus of the diabetic animals. All the DM-groups demonstrated defects in learning and memory tasks; only the Ac Caf group could reverse the deteriorating effect of DM. This group showed a significantly lower latency values to reach their target (submerged platform) in the water maze in comparison to the DM, Pre Caf, and Ch Caf groups. Their performance was not significantly different from the control animals. Rotarod testing showed significant role of acute, but not chronic, caffeine administration in enhancing the motor skills. Conclusion: STZ -induced DM resulted into defects in memory tasks which are associated with a reduction in the hippocampal NMDA-receptor component of the fEPSP. Acute, but not chronic administration of caffeine could reverse the deteriorating effect of DM on learning and memory.
14-3-3: A Case Study in PPI Modulation

In recent years, targeting the complex network of protein–protein interactions (PPIs) has been identified as a promising drug-discovery approach to develop new therapeutic strategies. 14-3-3 is a family of eukaryotic conserved regulatory proteins which are of high interest as potential targets for pharmacological intervention in human diseases, such as cancer and neurodegenerative and metabolic disorders. This viewpoint is built on the “hub” nature of the 14-3-3 proteins, binding to several hundred identified partners, consequently implicating them in a multitude of different cellular mechanisms. In this review, we provide an overview of the structural and biological features of 14-3-3 and the modulation of 14-3-3 PPIs for discovering small molecular inhibitors and stabilizers of 14-3-3 PPIs.
[Interaction between glycogen synthase kinase-3β and endoplasmic reticulum stress is involved in high glucose-induced injury in human umbilical vein endothelial cells].

OBJECTIVE To explore the role of the interaction between glycogen synthase kinase-3β (GSK-3β) and endoplasmic reticulum stress (ERS) in the high glucose (HG)-induced injury in human umbilical vein endothelial cells (HUVECs). METHODS HUVECs treated with 40 mmol/L glucose for 24 h were examined for expression levels of GSK-3β, GRP78, CHOP and cleaved caspase-3 protein using Western blotting. The cell viability was examined using CCK-8 assay and cell apoptosis was detected with Hoechst 33258 nuclear staining and photofluorography. The intracellular level of reactive oxygen species (ROS) was measured with dichlorfluoresein staining and photofluorography. Mitochondrial membrane potential (MMP) was tested by rhodamine 123 (Rh123) staining and photofluorography. RESULTS Treatment of HUVECs with 40 µmol/L glucose for 3-24 h activated GSK-3β in a time-dependent manner, leading to significantly down-regulated expression of phosphorylated (p)-GSK-3β (P<0.05). HG exposure of the cells for 1-24 h induced ERS, evidenced by time-dependently up-regulated expression of GRP78 and CHOP (P<0.05). LiCl, an inhibitor of GSK-3β, attenuated HG-induced ERS and significantly lowered the expression levels of GRP78 and CHOP (P<0.01). 4-PBA, an inhibitor of ERS, obviously ameliorated the activation of GSK-3β by HG as shown by the increase in p-GSK-3β expression level (P<0.01). HG exposure for 24 h induced obvious injuries in HUVECs, which exhibited decreased cell viability, increased cell apoptosis, increased expression of cleaved caspase-3 and ROS generation, and loss of MMP. Pretreatment of the cells with LiCl or 4-PBA for 60 min before HG exposure significantly lessened the cell injuries (P<0.01). CONCLUSION Interactions between GSK-3β and ERS occur in HUVECs exposed to HG and participate in HG-induced cell injuries.
Cellular and Molecular Mediators of Bone Metastatic Lesions

Bone is the preferential site of metastasis for breast and prostate tumor. Cancer cells establish a tight relationship with the host tissue, secreting factors that stimulate or inhibit bone cells, receiving signals generated from the bone remodeling activity, and displaying some features of bone cells. This interplay between tumor and bone cells alters the physiological bone remodeling, leading to the generation of a vicious cycle that promotes bone metastasis growth. To prevent the skeletal-related events (SRE) associated with bone metastasis, approaches to inhibit osteoclast bone resorption are reported. The bisphosphonates and Denosumab are currently used in the treatment of patients affected by bone lesions. They act to prevent or counteract the SRE, including pathologic fractures, spinal cord compression, and pain associated with bone metastasis. However, their primary effects on tumor cells still remain controversial. In this review, a description of the mechanisms leading to the onset of bone metastasis and clinical approaches to treat them are described.