Miracle-dz/UniFAR-FTUs huggingface dataset:
A Testis-Derived Hydrogel as an Efficient Feeder-Free Culture Platform to Promote Mouse Spermatogonial Stem Cell Proliferation and Differentiation

Fertility preservation and assisted reproductive medicine require effective culture systems for the successful proliferation and differentiation of spermatogonial stem cells (SSCs). Many SSC culture systems require the addition of feeder cells at each subculture, which is tedious and inefficient. Here, we prepared decellularized testicular matrix (DTM) from testicular tissue, which preserved essential structural proteins of testis. The DTM was then solubilized and induced to form a porous hydrogel scaffold with randomly oriented fibrillar structures that exhibited good cytocompatibility. The viability of SSCs inoculated onto DTM hydrogel scaffolds was significantly higher than those inoculated on Matrigel or laminin, and intracellular gene expression and DNA imprinting patterns were similar to that of native SSCs. Additionally, DTM promoted SSC differentiation into round spermatids. More importantly, the DTM hydrogel supported SSC proliferation and differentiation without requiring additional somatic cells. The DTM hydrogel scaffold culture system provided an alternative and simple method for culturing SSCs that eliminates potential variability and contamination caused by feeder cells. It might be a valuable tool for reproductive medicine.
A Novel MAX Gene Mutation Variant in a Patient With Multiple and “Composite” Neuroendocrine–Neuroblastic Tumors

Introduction: Pheochromocytomas (PCCs), paragangliomas (PGLs), ganglioneuroblastomas (GNBs), and ganglioneuromas (GNs) are neuroendocrine neoplasms (NENs) that were thought to share a common embryologic origin from neural crest cells. However, they rarely occur concurrently and recurrently. We describe the case of a 40-years-old woman with “composite PCC-GN” and multiple NENs and neuroblastic tumors. Case presentation: The patient was first referred to our department at the age of 15 years for paroxysmal hypertension, headache, sweating, and watery diarrhea. Her personal history included the diagnosis of a pelvic GNB with lumbar–aortic lymph node metastases at 11 months. Her family history was positive for cerebral glioblastoma multiforme (father). An abdominal ultrasound showed a right adrenal mass that histologically was a “composite adrenal PCC-GN. ” The symptoms disappeared after surgery. At the age of 20 years, the symptoms returned: computed tomography (CT) and 131I-metaiodobenzylguanidine (MIBG) scintigraphy showed an inter-aortocaval mass, found histologically to be an inter-aortocaval PGL. Her symptoms reappeared again at 28 years: CT and magnetic resonance imaging revealed four left adrenal gland nodules, found histologically to be multifocal PCCs with some atypia. Genetic screening for VHL, RET, NF1, Tp53, SDHD, SDHB, SDHC, SDHAF2, SDHAF3, SDHA, and TMEM127 was negative. Mutational analysis of the MAX gene revealed the presence of a novel heterozygous variant, c299G>C (p.Arg100Pro, NM_002382.5) that the bioinformatics prediction programs defined as noxious and causative of pathology. Conclusion: This report represents the first description of a co-occurrence of multiple composite PCC-GN and neuroblastic tumors. The long timeline of the presentation of the NENs/neuroblastic tumors from infancy to adulthood requires a lifelong follow-up for this patient. Moreover, the importance of this case lies in the presence of a novel MAX gene variant deleterious, harmful, and causative of pathology, confirmed by Sanger sequencing and never been associated before with multiple composite PCC-GN. The present case underlines the importance of precision medicine and molecular diagnoses for hereditary pheochromocytomas and paragangliomas, suggesting that when they occur in early childhood, it is necessary to perform an extensive genetic investigation and a lifelong follow-up.
Discrimination of alternative male phenotypes in Scapanes australis (Boisduval) (Coleoptera: Scarabaeidae: Dynastinae)

The palm pest Scapanes australis has been the object of considerable recent research to develop control measures that target male reproductive behaviour. This study investigated horn size scaling relationships and frequency distributions in two subspecies of S. australis for evidence of alternative male reproductive strategies. Indeed, a sigmoidal horn size allometry in both populations was detected as a significant vertical discontinuity by a piece-wise regression model, which indicates that distinct minor and major male phenotypes are expressed in both taxa. A non-linear regression algorithm showed that these subspecies differ significantly in two modelled parameters of horn allometry. A likelihood model was used for probabilistic discrimination of the alternative male phenotypes by estimating their ratios across the bimodal frequency distribution. The latter is intended to aid field investigation of the reproductive biology of S. australis by statistically discriminating the alternative male phenotypes on the basis of easily measured parameters in live samples. (Resume d'auteur)
Event-Based Computation for Touch Localization Based on Precise Spike Timing

Precise spike timing and temporal coding are used extensively within the nervous system of insects and in the sensory periphery of higher order animals. However, conventional Artificial Neural Networks (ANNs) and machine learning algorithms cannot take advantage of this coding strategy, due to their rate-based representation of signals. Even in the case of artificial Spiking Neural Networks (SNNs), identifying applications where temporal coding outperforms the rate coding strategies of ANNs is still an open challenge. Neuromorphic sensory-processing systems provide an ideal context for exploring the potential advantages of temporal coding, as they are able to efficiently extract the information required to cluster or classify spatio-temporal activity patterns from relative spike timing. Here we propose a neuromorphic model inspired by the sand scorpion to explore the benefits of temporal coding, and validate it in an event-based sensory-processing task. The task consists in localizing a target using only the relative spike timing of eight spatially-separated vibration sensors. We propose two different approaches in which the SNNs learns to cluster spatio-temporal patterns in an unsupervised manner and we demonstrate how the task can be solved both analytically and through numerical simulation of multiple SNN models. We argue that the models presented are optimal for spatio-temporal pattern classification using precise spike timing in a task that could be used as a standard benchmark for evaluating event-based sensory processing models based on temporal coding.
Nitroxyl: A Novel Strategy to Circumvent Diabetes Associated Impairments in Nitric Oxide Signaling

Diabetes is associated with an increased mortality risk due to cardiovascular complications. Hyperglycemia-induced oxidative stress underlies these complications, leading to an impairment in endogenous nitric oxide (NO•) generation, together with reductions in NO• bioavailability and NO• responsiveness in the vasculature, platelets and myocardium. The latter impairment of responsiveness to NO•, termed NO• resistance, compromises the ability of traditional NO•-based therapeutics to improve hemodynamic status during diabetes-associated cardiovascular emergencies, such as acute myocardial infarction. Whilst a number of agents can ameliorate (e.g. angiotensin converting enzyme [ACE] inhibitors, perhexiline, statins and insulin) or circumvent (e.g. nitrite and sGC activators) NO• resistance, nitroxyl (HNO) donors offer a novel opportunity to circumvent NO• resistance in diabetes. With a suite of vasoprotective properties and an ability to enhance cardiac inotropic and lusitropic responses, coupled with preserved efficacy in the setting of oxidative stress, HNO donors have intact therapeutic potential in the face of diminished NO• signaling. This review explores the major mechanisms by which hyperglycemia-induced oxidative stress drives NO• resistance, and the therapeutic potential of HNO donors to circumvent this to treat cardiovascular complications in type 2 diabetes mellitus.
Predictive Model for Ambulatory Hypertension Based on Office Blood Pressure in Obese Children

Background: The epidemic of obesity, along with hypertension (HT) and cardiovascular disease, is a growing contributor to global disease burden. It is postulated that obese children are predisposed to hypertension and subsequent cardiovascular disease in adulthood. Early detection and management of hypertension in these children can significantly modify the course of the disease. However, there is a paucity of studies for the characterization of blood pressure in obese children through ambulatory blood pressure monitoring (ABPM), especially in the developing world. This study aims to characterize ambulatory blood pressure in obese children and to explore feasibility of using office BP that will predict ambulatory hypertension. Methods:In the present study, 55 children with a body mass index (BMI) in the ≥95th percentile for age and sex were enrolled in a tertiary care hospital and underwent 24 h of ABPM and detailed biochemical investigations. Results:Ambulatory hypertension was recorded in 14/55 (25.5%; white coat hypertension in 17/29 (58.6%) and masked hypertension in 2/26 (7.69%). For office SBP percentile the area under curve (AUC) was 0.773 (95% CI: 0.619–0.926, p = 0.005) and for office DBP percentile the AUC was 0.802 (95% CI: 0.638–0.966, p = 0.002). The estimated cut offs (Youden's index) for office blood pressure which predicts ambulatory hypertension in obese children were the 93rd percentile for systolic BP (sensitivity-67% and specificity−78%) and the 88th percentile for diastolic BP (sensitivity-83% and specificity-62%). Conclusion:Ambulatory blood pressure abnormalities are highly prevalent among children with obesity. Office blood pressure did not accurately predict ambulatory hypertension. More than half of the children labeled as “hypertension” on office blood pressure measurement in the study were diagnosed to have white coat hypertension (WCH), thus emphasizing the role of ABPM for evaluation of WCH before the child is subjected to detailed investigations or started on pharmacotherapy.
Localization Preference of Antimicrobial Peptides on Liquid-Disordered Membrane Domains

We performed coarse-grained simulations of the antimicrobial peptides Magainin-2, BP100, MSI-103, and MSI-78 on a phase-separated membrane to study their preference for the different domains. All the peptides displayed a clear preference for the liquid-disordered (Ld) phase over the liquid-ordered (Lo) one. For BP100, MSI-103, and MSI-78 there was a further preference of the peptides for the domain interface. The peptides’ preference toward the disordered phase was shown to reflect a penalization of lipid–lipid interaction enthalpy in the Lo phase, when in the vicinity of peptides. Similar results were observed at the two studied concentrations, although Ld phase saturation at the higher concentration drove some of the peptide excess to the Lo phase. Magainin-2 and MSI-103 were found to dimerize, in agreement with available experimental data. Interestingly, at high concentrations of Magainin-2 toroidal pores spontaneously formed in the Ld phase. We performed additional simulations to characterize this phenomenon, which is likely related to Magainin-2’s membranolytic action.
Towards an Individual Differences Perspective in Mindfulness Training Research: Theoretical and Empirical Considerations

A growing body of research indicates that mindfulness training can have beneficial effects on critical aspects of psychological well-being, cognitive function, and brain health. Although these benefits have been generalized to the population level, individual variability in observed effects of mindfulness training has not been systematically investigated. Research on other similar forms of psychological intervention demonstrates that individual differences are prominent in terms of intervention responsiveness and outcomes. Furthermore, individual characteristics such as personality traits have been shown to play a crucial role in influencing the effects of intervention. In light of these lines of evidence, we review representative work on individual differences in mindfulness training and advocate for an individual difference perspective in mindfulness training research. We discuss relevant empirical evidence of individual differences potentially influencing behavioral outcomes of mindfulness training, focusing on both cognitive function and psychological well-being. Finally, theoretical considerations and potentially fruitful research strategies and directions for studying individual differences in mindfulness training are discussed, including those involving cognitive neuroscience methods.
Hierarchical Micro-Nano Topography Promotes Cell Adhesion and Osteogenic Differentiation via Integrin α2-PI3K-AKT Signaling Axis

Surface topography dictates important aspects of cell biological behaviors. In our study, hierarchical micro-nano topography (SLM-AHT) with micro-scale grooves and nano-scale pores was fabricated and compared with smooth topography (S) and irregular micro-scale topography (SLA) surfaces to investigate mechanism involved in cell-surface interactions. Integrin α2 had a higher expression level on SLM-AHT surface compared with S and SLA surfaces, and the expression levels of osteogenic markers icluding Runx2, Col1a1, and Ocn were concomitantly upregulated on SLM-AHT surface. Moreover, formation of mature focal adhesions were significantly enhanced in SLM-AHT group. Noticablely, silencing integrin α2 could wipe out the difference of osteogenic gene expression among surfaces with different topography, indicating a crucial role of integrin α2 in topography induced osteogenic differentiation. In addition, PI3K-AKT signaling was proved to be regulated by integrin α2 and consequently participate in this process. Taken together, our findings illustrated that integrin α2-PI3K-AKT signaling axis plays a key role in hierarchical micro-nano topography promoting cell adhesion and osteogenic differentiation.
Green Pathway for Processing Non-mulberry Antheraea pernyi Silk Fibroin/Chitin-Based Sponges: Biophysical and Biochemical Characterization

Silk protein fibroin (SF)-based matrices from non-mulberry, and mulberry silkworms are used for different applications in regenerative medicine. Silk fiber spun by the wild non-mulberry silkworm Antheraea pernyi (Ap) is also a promising biomedical material, due to the presence of the inherent tripeptide sequence of Arginine-Glycine-Aspartic acid (RGD) on the protein fibroin sequences. However, SF derived from the Ap cocoons still lacks exploitation in the healthcare field due to its poor solubility in the conventional solvents. This work addresses the application of green chemistry principles, namely the use of ionic liquids (ILs, 1-butyl-imidazolium acetate) and renewable resources such as Antheraea pernyi silk fibroin (ApSF) and chitin (Ch), for the fabrication of sponges from the blends of ApSF and Ch (APC). The formation of β-sheet in different contents during ApSF/Ch/IL was acquired by exposing gels to methanol/water and ethanol/water. The sponges were then obtained by freeze-drying. This approach promotes the formation of both stable and ordered ApSF/Ch-based sponges. The developed sponges show the suitable porosity and interconnectivity, appreciable swelling degree, and tuneable viscoelastic compressive properties for tissue engineering applications. Collectively, the structural properties of these ApSF/Ch-based sponges make them promising candidates for biomedical applications, namely cartilage regeneration.
Impact of Microbiota Transplant on Resistome of Gut Microbiota in Gnotobiotic Piglets and Human Subjects

Microbiota transplant is becoming a popular process to restore or initiate “healthy” gut microbiota and immunity. But, the potential risks of the related practices need to be carefully evaluated. This study retrospectively examined the resistomes of donated fecal microbiota for treating intestinal disorders, vaginal microbiota of pregnant women, and infant fecal microbiota from rural and urban communities, as well as the impact of transplants on the fecal resistome of human and animal recipients. Antibiotic resistance (AR) genes were found to be abundant in all donor microbiota. An overall surge of resistomes with higher prevalence and abundance of AR genes was observed in the feces of all transplanted gnotobiotic pigs as well as in the feces of infant subjects, compared to those in donor fecal and maternal vaginal microbiota. Surprisingly, transplants using rural Amish microbiota led to more instead of less AR genes in the fecal microbiota of gnotobiotic pigs than did transplants using urban microbiota. New AR gene subtypes undetected originally also appeared in gnotobiotic pigs, in Crohn’s Disease (CD) patients after transplant, and in feces of infant subjects. The data illustrated the key role of the host gastrointestinal tract system in amplifying the ever-increasing AR gene pool, even without antibiotic exposure. The data further suggest that the current approaches of microbiota transplant can introduce significant health risk factor(s) to the recipients, and newborn human and animal hosts with naïve gut microbiota were especially susceptible. Given the illustrated public health risks of microbiota transplant, minimizing massive and unnecessary damages to gut microbiota by oral antibiotics and other gut impacting drugs becomes important. Since eliminating risk factors including AR bacteria and opportunistic pathogens directly from donor microbiota is still difficult to achieve, developing microbial cocktails with defined organisms and functions has further become an urgent need, should microbiota transplantation become necessary.
Epigenetic Regulation of Kaposi’s Sarcoma-Associated Herpesvirus Latency

Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic γ-herpesvirus that infects humans and exhibits a biphasic life cycle consisting of latent and lytic phases. Following entry into host cells, the KSHV genome undergoes circularization and chromatinization into an extrachromosomal episome ultimately leading to the establishment of latency. The KSHV episome is organized into distinct chromatin domains marked by variations in repressive or activating epigenetic modifications, including DNA methylation, histone methylation, and histone acetylation. Thus, the development of KSHV latency is believed to be governed by epigenetic regulation. In the past decade, interrogation of the KSHV epitome by genome-wide approaches has revealed a complex epigenetic mark landscape across KSHV genome and has uncovered the important regulatory roles of epigenetic modifications in governing the development of KSHV latency. Here, we highlight many of the findings regarding the role of DNA methylation, histone modification, post-translational modification (PTM) of chromatin remodeling proteins, the contribution of long non-coding RNAs (lncRNAs) in regulating KSHV latency development, and the role of higher-order episomal chromatin architecture in the maintenance of latency and the latent-to-lytic switch.
Light in the Dark: Retrieving Underwater Irradiance in Shallow Eutrophic Waters From AC-S Measurements

Light is essential for primary production and, therefore, its attenuation controls the vertical distribution of plants and phytoplankton over the water column. The diffuse attenuation of irradiance (K) is mainly governed by the attenuation by the water itself and the concentrations of optically active substances (e.g., phytoplankton, inorganic particles and colored dissolved molecules), which makes it an important parameter for eutrophication monitoring. Over the past century, Denmark has had recurrent eutrophication events, with extreme episodic cases where anoxic conditions were observed. Since the 1980’s, eutrophication in Danish waters has been monitored with regards to the diffuse attenuation coefficient of scalar irradiance (Ko) of photosynthetically active radiation (PAR, 400–700 nm), Ko(PAR). However, radiometric measurements in Denmark are difficult in winter due to low solar zenith angle and only few light hours. On top of that, radiometric measurements in the first meters of the water column are highly affected by light refraction influenced by waves, compromising the monitoring of shallow turbid waters as in Denmark. Therefore, we developed a semi-analytical model based on data to from a spectral AC instrument (AC-S, Sea-Bird Scientific) that can estimate the underwater light field and the diffuse attenuation coefficient of downwelling irradiance, Kd(PAR). We tested two distinct approaches based on equations from the literature for estimation of Kd(PAR). The results show that modeled PAR profiles follow the overall shape of in situ radiometric profiles but with smoother profiles, especially in the surface layer (2–5 m). Along with that, the method provided robust Kd(PAR) estimates, that were strongly correlated to the reference Ko(PAR) values from in situ profiles and with low root mean square error (RMSE). Thus, AC-S data can be used to estimate the underwater light field and Ko(PAR). This will make possible to retrieve Ko(PAR) in the absence of daylight and, therefore, allow for environmental monitoring outside the daylight hours, making environmental monitoring more efficient. In addition, the method provides valuable insights into the factors controlling light attenuation.
Structural Covariance Changes of Anterior and Posterior Hippocampus During Musical Training in Young Adults

Musical training can induce the functional and structural changes of the hippocampus. The hippocampus is not a homogeneous structure which can be divided into anterior and posterior parts along its longitudinal axis, and the whole-brain structural covariances of anterior (aHC) and posterior hippocampus (pHC) show distinct patterns in young adults. However, little is known about whether the anterior and posterior hippocampal structural covariances change after long-term musical training. Here, we investigated the musical training-induced changes of the whole-brain structural covariances of bilateral aHC and pHC in a longitudinal designed experiment with two groups (training group and control group) across three time points [the beginning (TP1) and the end (TP2) of 24 weeks of training, and 12 weeks after training (TP3)]. Using seed partial least square, we identified two significant patterns of structural covariance of the aHC and pHC. The first showed common structural covariance of the aHC and pHC. The second pattern revealed distinct structural covariance of the two regions and reflected the changes of structural covariance of the left pHC in the training group across three time points: the left pHC showed significant structural covariance with bilateral hippocampus and parahippocampal gyrus, left calcarine sulcus only at TP1 and TP3. Furthermore, the integrity of distinct structural networks of aHC and pHC in the second pattern significantly increased in the training group. Our findings suggest that musical training could change the organization of structural whole-brain covariance for left pHC and enhance the degree of the structural covariance network differentiation of the aHC and pHC in young adults.