Miracle-dz/UniFAR-FTUs huggingface dataset:
Estimating Age-Dependent Extinction: Contrasting Evidence from Fossils and Phylogenies

&NA; The estimation of diversification rates is one of the most vividly debated topics in modern systematics, with considerable controversy surrounding the power of phylogenetic and fossil‐based approaches in estimating extinction. Van Valen's seminal work from 1973 proposed the “Law of constant extinction,” which states that the probability of extinction of taxa is not dependent on their age. This assumption of age‐independent extinction has prevailed for decades with its assessment based on survivorship curves, which, however, do not directly account for the incompleteness of the fossil record, and have rarely been applied at the species level. Here, we present a Bayesian framework to estimate extinction rates from the fossil record accounting for age‐dependent extinction (ADE). Our approach, unlike previous implementations, explicitly models unobserved species and accounts for the effects of fossil preservation on the observed longevity of sampled lineages. We assess the performance and robustness of our method through extensive simulations and apply it to a fossil data set of terrestrial Carnivora spanning the past 40 myr. We find strong evidence of ADE, as we detect the extinction rate to be highest in young species and declining with increasing species age. For comparison, we apply a recently developed analogous ADE model to a dated phylogeny of extant Carnivora. Although the phylogeny‐based analysis also infers ADE, it indicates that the extinction rate, instead, increases with increasing taxon age. The estimated mean species longevity also differs substantially, with the fossil‐based analyses estimating 2.0 myr, in contrast to 9.8 myr derived from the phylogeny‐based inference. Scrutinizing these discrepancies, we find that both fossil and phylogeny‐based ADE models are prone to high error rates when speciation and extinction rates increase or decrease through time. However, analyses of simulated and empirical data show that fossil‐based inferences are more robust. This study shows that an accurate estimation of ADE from incomplete fossil data is possible when the effects of preservation are jointly modeled, thus allowing for a reassessment of Van Valen's model as a general rule in macroevolution.
Downstream effects of hippocampal sharp wave ripple oscillations on medial entorhinal cortex layer V neurons in vitro

The entorhinal cortex (EC) is a critical component of the medial temporal lobe (MTL) memory system. Local networks within the MTL express a variety of state‐dependent network oscillations that are believed to organize neuronal activity during memory formation. The peculiar pattern of sharp wave‐ripple complexes (SPW‐R) entrains neurons by a very fast oscillation at ∼200 Hz in the hippocampal areas CA3 and CA1 and then propagates through the “output loop” into the EC. The precise mechanisms of SPW‐R propagation and the resulting cellular input patterns in the mEC are, however, largely unknown. We therefore investigated the activity of layer V (LV) principal neurons of the medial EC (mEC) during SPW‐R oscillations in horizontal mouse brain slices. Intracellular recordings in the mEC were combined with extracellular monitoring of propagating network activity. SPW‐R in CA1 were regularly followed by negative field potential deflections in the mEC. Propagation of SPW‐R activity from CA1 to the mEC was mostly monosynaptic and excitatory, such that synaptic input to mEC LV neurons directly reflected unit activity in CA1. Comparison with propagating network activity from CA3 to CA1 revealed a similar role of excitatory long‐range connections for both regions. However, SPW‐R‐induced activity in CA1 involved strong recruitment of rhythmic synaptic inhibition and corresponding fast field oscillations, in contrast to the mEC. These differences between features of propagating SPW‐R emphasize the differential processing of network activity by each local network of the hippocampal output loop. © 2016 Wiley Periodicals, Inc.
Production of Chitin from Penaeus vannamei By-Products to Pilot Plant Scale Using a Combination of Enzymatic and Chemical Processes and Subsequent Optimization of the Chemical Production of Chitosan by Response Surface Methodology

The waste generated from shrimp processing contains valuable materials such as protein, carotenoids, and chitin. The present study describes a process at pilot plant scale to recover chitin from the cephalothorax of Penaeus vannamei using mild conditions. The application of a sequential enzymatic–acid–alkaline treatment yields 30% chitin of comparable purity to commercial sources. Effluents from the process are rich in protein and astaxanthin, and represent inputs for further by-product recovery. As a last step, chitin is deacetylated to produce chitosan; the optimal conditions are established by applying a response surface methodology (RSM). Under these conditions, deacetylation reaches 92% as determined by Proton Nuclear Magnetic Resonance (1H-NMR), and the molecular weight (Mw) of chitosan is estimated at 82 KDa by gel permeation chromatography (GPC). Chitin and chitosan microstructures are characterized by Scanning Electron Microscopy (SEM).
APOE, MAPT, and COMT and Parkinson's Disease Susceptibility and Cognitive Symptom Progression.

BACKGROUND Cognitive decline is well recognized in Parkinson's disease (PD) and a major concern for patients and caregivers. Apolipoprotein E (APOE), catechol-O-methyl transferase (COMT), and microtubule-associated protein tau (MAPT) are of interest related to their contributions to cognitive decline or dementia in PD. OBJECTIVE Here, we investigate whether APOE, COMT, or MAPT influence the rate of cognitive decline in PD patients. METHODS We relied on 634 PD patients and 879 controls to examine gene-PD susceptibility associations, and nested longitudinal cohort of 246 patients from the case-control study, which followed patients on average 5 years and 7.5 years into disease. We repeatedly assessed cognitive symptom progression with the MMSE and conducted a full neuropsychological battery on a subset of 183 cognitively normal patients. We used repeated-measures regression analyses to assess longitudinal associations between genotypes and cognitive progression scores. RESULTS The MAPT H1 haplotype was associated with PD susceptibility. APOE 4 carriers (ɛ4+) (p = 0.03) and possibly COMT Met/Met (p = 0.06) carriers exhibited faster annual decline on the MMSE. Additionally, APOEɛ4+ carriers showed faster decline in many of the neuropsychological test scores. No such differences in neuropsychological outcomes were seen for the COMT genotypes. CONCLUSION This work supports a growing set of research identifying overlapping etiology and pathology between synucleinopathies, such as PD, Alzheimer's disease, and tauopathies, especially in the context of cognitive dysfunction in PD. We provide support for the argument that APOE ɛ4+ and COMT Met/Met genotypes can be used as predictors of faster cognitive decline in PD.
Waterpipe Promotion and Use on Instagram: #Hookah

Introduction Waterpipe (hookah) use is becoming more prevalent in the United States and abroad with potential implications for public health. As waterpipe use rapidly grows in popularity, novel data streams are needed that can help capture and document the social and environmental context in which individuals use, and are marketed, this emerging tobacco product. This study characterized waterpipe-related posts on Instagram in order to inform regulatory and policy activities in the United States. Methods Data were collected from Instagram, an image-based social media site. Inclusion criteria for this study comprised an Instagram post with the hashtag "#hookah" that was accompanied by geo-location metadata demonstrating that the post was inside the contiguous United States. Rules were established for coding themes of images (n = 1705). Results Seven percent of images depicted a single person using a waterpipe and/or blowing smoke, 25% depicted two or more persons lounging and/or using a waterpipe, 6% depicted waterpipes, coals or flavored tobacco without people, 18% of images were promotional material for hookah lounges and restaurant/bars/nightclubs referencing hookah in the text or depicting a waterpipe, 25% were non-waterpipe-related promotional material, 1% were sexually explicit material, and 18% other. 31% of all images depicted or referenced alcohol. 30% of posts provided geo-location from a hookah lounge, 56% from a restaurant/bar/nightclub, and 14% from other types of locations. Conclusions The cross promotion of waterpipe and alcohol use by hookah lounges, and restaurants/bars/nightclubs suggests that poly-substance use is regularly depicted, and promoted, in nightlife entertainment as well as normalized on Instagram in the United States. Implications In the US Instagram posts with the hashtag #hookah regularly depicted waterpipe use in conjunction with alcohol use. Instagram's focus on images facilitates picture-based advertising where hookah lounges promote drink specials at the same time nightclubs promote waterpipe specials. Instagram users often document the variety of shapes, sizes, and styles, of waterpipes, suggesting users take pride in their purchases and like to show their customized, and often times elaborate, waterpipes to their followers. Instagram has been underutilized in understanding tobacco related-behaviors and identifying tobacco-related promotional material.
Anticoagulation knowledge in patients with atrial fibrillation: An Australian survey

Atrial fibrillation (AF) is the most commonly diagnosed arrhythmia in clinical practice, and is associated with a significant medical and economic burden. Anticoagulants reduce the risk of stroke and systemic embolism by approximately two‐thirds compared with no therapy. Knowledge regarding anticoagulant therapy can influence treatment outcomes in patients with AF.
The effects of a topical gel containing chitosan, 0,2% chlorhexidine, allantoin and despanthenol on the wound healing process subsequent to impacted lower third molar extraction

Background Despite efforts to prevent postoperative discomfort, there are still many immediate side effects associated with the surgical extraction of impacted lower third molars. Cicatrization is a physiological process through which the loss of integrity of oral mucosa is recovered and damaged tissues are repaired. Bexident Post (ISDIN, Spain) is a topical gel that contains chitosan, 0.2% chlorhexidine, allantoin and dexpanthenol. While this gel has many clinical indications, there are no published clinical trials evaluating its use in impacted mandibular third molar surgery. This study aims to clinically evaluate the efficacy of a gel containing chitosan, 0.2% chlorhexidine, allantoin and dexpanthenol on wound healing and reduction of postoperative side effects and complications after extraction of an impacted mandibular third molar. Material and Methods A split-mouth design study was carried out on a total of 50 bilaterally and symmetrically impacted third molar extractions, which were randomly placed into either a control group (CG=25) or an experimental group (EG=25). Patients were all informed of the purpose of the study and provided written consent. All procedures were carried out by the same dental practitioner, in accordance with standard surgical protocol. A different dental practitioner, unaware of which treatment had been applied, provided follow-up care. The EG applied 10 ml of topical gel composed of chitosan, 0.2% chlorhexidine, allantoin and dexpanthenol to the surgical wound three times a day for 10 days, patients in the CG did not apply any gel. Results The groups were homogeneous insofar as potentially confounding variables. No significant findings were found regarding postoperative swelling and pain. Neither of the groups displayed poor healing or infectious complications of the wound during the postoperative period. In all the recorded follow-ups (Day 7 p=0.001, and Day 14 p=0.01), the wound’s aesthetic appearance was better in the EG. Overall treatment tolerance was satisfactory and similar in both groups. Conclusions The gel composed of chitosan, 0.2% chlorhexidine, allantoin and dexpanthenol did not aid in patients’ postoperative comfort; however, improved wound healing was observed. Key words:Impacted lower third molar, postoperative wound healing, chitosan, chlorhexidine, allantoin, dexpanthenol, postoperative period.
Impact of Long-Term Exposure to the Tyrosine Kinase Inhibitor Imatinib on the Skeleton of Growing Rats

The tyrosine kinase (TK) inhibitor imatinib provides a highly effective therapy for chronic myeloid leukemia (CML) via inhibition of the oncogenic TK BCR-ABL1. However, off-target TKs like platelet-derived growth factor receptors (PDGF-R) and colony-stimulating factor-1 receptor (c-fms), involved in bone remodeling, are also inhibited. Thus, pediatric patients with CML on imatinib exhibit altered bone metabolism, leading to linear growth failure. As TKI treatment might be necessary for a lifetime, long-term effects exerted on bone in children are of major concern. Therefore, we studied the skeletal long-term effects of continuous and intermittent imatinib exposure in a juvenile rat model. Four-weeks-old male Wistar rats were chronically exposed to imatinib via drinking water over a period of 10 weeks. Animals were exposed to a standard and high imatinib dosage continuously and to the high imatinib dose intermittently. Bone mass and strength were assessed using pQCT, micro-computed tomography (μCT), and biomechanical testing at the prepubertal, pubertal, and postpubertal age. Bone length and vertebral height as well as biochemical markers of bone turnover were analyzed. Femoral and tibial bone length were dose-dependently reduced by up to 24% (p<0.0001), femoral and tibial trabecular bone mass density (BMD) were reduced by up to 25% (p<0.01), and femoral breaking strength was lowered by up to 20% (p<0.05). Intermittent exposure mitigated these skeletal effects. Long-term exposure resulted in reduced vertebral height by 15% and lower trabecular BMD by 5%. Skeletal changes were associated with suppressed serum osteocalcin (p<0.01) and non-significantly elevated serum CTX-I and PINP levels. In conclusion, imatinib mainly impaired longitudinal growth of long bones rather than the vertebrae of growing rats. Interestingly, intermittent imatinib exposure has less skeletal side effects, which may be beneficial in pediatric patients taking imatinib.
Gain Control in the Auditory Cortex Evoked by Changing Temporal Correlation of Sounds

Abstract Natural sounds exhibit statistical variation in their spectrotemporal structure. This variation is central to identification of unique environmental sounds and to vocal communication. Using limited resources, the auditory system must create a faithful representation of sounds across the full range of variation in temporal statistics. Imaging studies in humans demonstrated that the auditory cortex is sensitive to temporal correlations. However, the mechanisms by which the auditory cortex represents the spectrotemporal structure of sounds and how neuronal activity adjusts to vastly different statistics remain poorly understood. In this study, we recorded responses of neurons in the primary auditory cortex of awake rats to sounds with systematically varied temporal correlation, to determine whether and how this feature alters sound encoding. Neuronal responses adapted to changing stimulus temporal correlation. This adaptation was mediated by a change in the firing rate gain of neuronal responses rather than their spectrotemporal properties. This gain adaptation allowed neurons to maintain similar firing rates across stimuli with different statistics, preserving their ability to efficiently encode temporal modulation. This dynamic gain control mechanism may underlie comprehension of vocalizations and other natural sounds under different contexts, subject to distortions in temporal correlation structure via stretching or compression.
Regulation of Neurotransmitter Reuptake by Nitric Oxide

NO (nitric oxide) is a novel, gaseous biological messenger molecule in the CNS which is enzymatically formed from L-arginine by nitric oxide synthase, a Ca2+ calmodulin requiring enzyme; citrulline is the coproduct.I4 Activation of calmodulin is caused by calcium influx, at least partly derived from the stimulation of glutamate receptor^. ^-^^ NO has been proposed to mediate in the neurotoxic actions of g l ~ t a m a t e , ~ ~ J ~ to promote long term p o t e n t i a t i ~ n I ~ ~ ~ and long term depression,21 and to modulate neurotransmitter release.22-E Uptake of neurotransmitters like glutamate and dopamine by nerve endings is a mechanism to terminate the synaptic actions of released glutamate or d o p a ~ n i n e . ~ ” ~ ~ While the regulation of these uptake transporters are not fully understood, factors such as depolari~ation,~~ inhibition by endogenous ~ubs tances ,~~ phosphorylation (Kitayama et al., in preparation), and changes in t ran~cr ip t ion~~ (Cerutti et al., in preparation) have been suggested as possibilities. We have shown that NO inhibits transporters for some neurotransmitters in brain; this may be a new type of transynaptic retrograde regulation mechanism for uptake regulation.
Placing memories in context: Hippocampal representations promote retrieval of appropriate memories

Returning to a familiar context triggers retrieval of relevant memories, making memories from other contexts less likely to intrude and cause interference. We investigated the physiology that underlies the use of context to prevent interference by recording hippocampal neurons while rats learned two conflicting sets of discrimination problems, either in the same context or in two distinct contexts. Rats that learned the conflicting problem sets in the same context maintained similar neural representations, and performed poorly because conflicting memories interfered with new learning. In contrast, rats that learned in different contexts formed distinct ensemble representations and performed significantly better. We also measured trial‐to‐trial variation in representations and found that hippocampal activity was directly linked with performance: on trials where an old representation was active, rats were far more likely to make errors. These results show that the formation of distinct hippocampal representations is critical for contextually appropriate memory retrieval. © 2016 Wiley Periodicals, Inc.
SPABox: Safeguarding Privacy During Deep Packet Inspection at a MiddleBox

Widely used over the Internet to encrypt traffic, HTTPS provides secure and private data communication between clients and servers. However, to cope with rapidly changing and sophisticated security attacks, network operators often deploy middleboxes to perform deep packet inspection (DPI) to detect attacks and potential security breaches, using techniques ranging from simple keyword matching to more advanced machine learning and data mining analysis. But this creates a problem: how can middleboxes, which employ DPI, work over HTTPS connections with encrypted traffic while preserving privacy? In this paper, we present SPABox, a middlebox-based system that supports both keyword-based and data analysis-based DPI functions over encrypted traffic. SPABox preserves privacy by using a novel protocol with a limited connection setup overhead. We implement SPABox on a standard server and show that SPABox is practical for both long-lived and short-lived connection. Compared with the state-of-the-art Blindbox system, SPABox is more than five orders of magnitude faster and requires seven orders of magnitude less bandwidth for connection setup while SPABox can achieve a higher security level.
Executive Function in Adolescents With Type 1 Diabetes: Relationship to Adherence, Glycemic Control, and Psychosocial Outcomes

Objective Impairments in executive function (EF) skills have been observed in youth with type 1 diabetes (T1D), and these skills are critical for following the complex treatment regimen. This study examines parent reports of EF in relation to measures of adherence, glycemic control (A1c), and psychosocial outcomes (depression and quality of life) in adolescents with T1D. A total of 120 adolescents (aged 13-17 years, 52.5% female, 87.5% White) with T1D and their parents completed questionnaires. Glucometers were downloaded and A1c was obtained during clinical visits at the time of enrollment. The prevalence of clinically significant elevated scores on specific EF skills ranged from 11 to 18.6%. In multivariate analyses, parent-reported EF deficits were associated with poorer adherence and lower quality of life, explaining 13 and 12% of the variance, respectively. Adolescents with T1D exhibit specific EF deficits that may negatively impact their quality of life and their ability to engage in self-management activities.
A Novel Human CAMK2A Mutation Disrupts Dendritic Morphology and Synaptic Transmission, and Causes ASD-Related Behaviors

Characterizing the functional impact of novel mutations linked to autism spectrum disorder (ASD) provides a deeper mechanistic understanding of the underlying pathophysiological mechanisms. Here we show that a de novo Glu183 to Val (E183V) mutation in the CaMKIIα catalytic domain, identified in a proband diagnosed with ASD, decreases both CaMKIIα substrate phosphorylation and regulatory autophosphorylation, and that the mutated kinase acts in a dominant-negative manner to reduce CaMKIIα-WT autophosphorylation. The E183V mutation also reduces CaMKIIα binding to established ASD-linked proteins, such as Shank3 and subunits of l-type calcium channels and NMDA receptors, and increases CaMKIIα turnover in intact cells. In cultured neurons, the E183V mutation reduces CaMKIIα targeting to dendritic spines. Moreover, neuronal expression of CaMKIIα-E183V increases dendritic arborization and decreases both dendritic spine density and excitatory synaptic transmission. Mice with a knock-in CaMKIIα-E183V mutation have lower total forebrain CaMKIIα levels, with reduced targeting to synaptic subcellular fractions. The CaMKIIα-E183V mice also display aberrant behavioral phenotypes, including hyperactivity, social interaction deficits, and increased repetitive behaviors. Together, these data suggest that CaMKIIα plays a previously unappreciated role in ASD-related synaptic and behavioral phenotypes. SIGNIFICANCE STATEMENT Many autism spectrum disorder (ASD)-linked mutations disrupt the function of synaptic proteins, but no single gene accounts for >1% of total ASD cases. The molecular networks and mechanisms that couple the primary deficits caused by these individual mutations to core behavioral symptoms of ASD remain poorly understood. Here, we provide the first characterization of a mutation in the gene encoding CaMKIIα linked to a specific neuropsychiatric disorder. Our findings demonstrate that this ASD-linked de novo CAMK2A mutation disrupts multiple CaMKII functions, induces synaptic deficits, and causes ASD-related behavioral alterations, providing novel insights into the synaptic mechanisms contributing to ASD.