Miracle-dz/UniFAR-FTUs huggingface dataset:
Synuclein Deficiency Results in Age-Related Respiratory and Cardiovascular Dysfunctions in Mice

Synuclein (α, β, and γ) proteins are highly expressed in presynaptic terminals, and significant data exist supporting their role in regulating neurotransmitter release. Targeting the gene encoding α-synuclein is the basis of many animal models of Parkinson’s disease (PD). However, the physiological role of this family of proteins in not well understood and could be especially relevant as interfering with accumulation of α-synuclein level has therapeutic potential in limiting PD progression. The long-term effects of their removal are unknown and given the complex pathophysiology of PD, could exacerbate other clinical features of the disease, for example dysautonomia. In the present study, we sought to characterize the autonomic phenotypes of mice lacking all synucleins (α, β, and γ; αβγ−/−) in order to better understand the role of synuclein-family proteins in autonomic function. We probed respiratory and cardiovascular reflexes in conscious and anesthetized, young (4 months) and aged (18–20 months) αβγ−/− male mice. Aged mice displayed impaired respiratory responses to both hypoxia and hypercapnia when breathing activities were recorded in conscious animals using whole-body plethysmography. These animals were also found to be hypertensive from conscious blood pressure recordings, to have reduced pressor baroreflex gain under anesthesia, and showed reduced termination of both pressor and depressor reflexes. The present data demonstrate the importance of synuclein in the normal function of respiratory and cardiovascular reflexes during aging.
A retrospective physiological noise correction method for oscillating steady‐state imaging

Oscillating steady‐state imaging (OSSI) is an SNR‐efficient steady‐state sequence with T2∗ sensitivity suitable for FMRI. Due to the frequency sensitivity of the signal, respiration‐ and drift‐induced field changes can create unwanted signal fluctuations. This study aims to address this issue by developing retrospective signal correction methods that utilize OSSI signal properties to denoise task‐based OSSI FMRI experiments.
Targeting Multiple EGFR-expressing Tumors with a Highly Potent Tumor-selective Antibody–Drug Conjugate

ABBV-321 (serclutamab talirine), a next-generation EGFR-targeted antibody–drug conjugate (ADC) incorporates a potent pyrrolobenzodiazepine (PBD) dimer toxin conjugated to the EGFR-targeting ABT-806 affinity-matured AM1 antibody. ABBV-321 follows the development of related EGFR-targeted ADCs including depatuxizumab mafodotin (depatux-m, ABT-414), ABT-806 conjugated to monomethyl auristatin F (MMAF), and ABBV-221 (losatuxizumab vedotin), AM1 antibody conjugated to monomethyl auristatin E (MMAE). The distinct tumor selectivity of ABBV-321 differentiates it from many previous highly active antibody PBD conjugates that lack a therapeutic window. Potency of the PBD dimer, combined with increased binding of AM1 to EGFR-positive tumor cells, opens the possibility to target a wide array of tumors beyond those with high levels of EGFR overexpression or amplification, including those insensitive to auristatin-based ADCs. ABBV-321 exhibits potent antitumor activity in cellular and in vivo studies including xenograft cell line and patient-derived xenograft glioblastoma, colorectal, lung, head and neck, and malignant mesothelioma tumor models that are less sensitive to depatux-m or ABBV-221. Combination studies with ABBV-321 and depatux-m suggest a promising treatment option permitting suboptimal, and potentially better tolerated, doses of both ADCs while providing improved potency. Collectively, these data suggest that ABBV-321 may offer an extended breadth of efficacy relative to other EGFR ADCs while extending utility to multiple EGFR-expressing tumor indications. Despite its highly potent PBD dimer payload, the tumor selectivity of ABBV-321, coupled with its pharmacology, toxicology, and pharmacokinetic profiles, support continuation of ongoing phase I clinical trials in patients with advanced EGFR-expressing malignancies.
Modulation of gut microbiota in healthy rats after exposure to nutritional supplements

ABSTRACT Introduction Rats are experimental animals, frequently used as model organisms in the biomedical studies, and increasingly used to study the gut microbiota. Specifically, the aim of latter studies is either the elucidation of relationship between intestinal dysbiosis and diseases or the determination of nutrients or pharmaceutical agents which can cause the modulation in the presence or abundance of gut microbiota. Aim Herein, the research studies conducted on the gut microbiota of healthy rats are presented in a summarized and concise overview. The focus is on studies aimed to reveal the shifts in microbial composition and functional changes after exposure to various types of nutritional supplements. Methods We performed the search of PubMed database using the term “rat gut microbiome microbiota” and examined studies aimed to assess the composition of gut microbiota in physiological homeostasis as well as the effect of various nutritional supplements on the gut microbiota of healthy rats.
The genetic Ca2+ sensor GCaMP3 reveals multiple Ca2+ stores differentially coupled to Ca2+ entry in the human malaria parasite Plasmodium falciparum

Cytosolic Ca2+ regulates multiple steps in the host-cell invasion, growth, proliferation, and egress of blood-stage Plasmodium falciparum, yet our understanding of Ca2+ signaling in this endemic malaria parasite is incomplete. By using a newly generated transgenic line of P. falciparum (PfGCaMP3) that expresses constitutively the genetically encoded Ca2+ indicator GCaMP3, we have investigated the dynamics of Ca2+ release and influx elicited by inhibitors of the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase pumps, cyclopiazonic acid (CPA), and thapsigargin (Thg). Here we show that in isolated trophozoite phase parasites: (i) both CPA and Thg release Ca2+ from intracellular stores in P. falciparum parasites; (ii) Thg is able to induce Ca2+ release from an intracellular compartment insensitive to CPA; (iii) only Thg is able to activate Ca2+ influx from extracellular media, through a mechanism resembling store-operated Ca2+ entry, typical of mammalian cells; and (iv) the Thg-sensitive Ca2+ pool is unaffected by collapsing the mitochondria membrane potential with the uncoupler carbonyl cyanide m-chlorophenyl hydrazone or the release of acidic Ca2+ stores with nigericin. These data suggest the presence of two Ca2+ pools in P. falciparum with differential sensitivity to the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase pump inhibitors, and only the release of the Thg-sensitive Ca2+ store induces Ca2+ influx. Activation of the store-operated Ca2+ entry–like Ca2+ influx may be relevant for controlling processes such as parasite invasion, egress, and development mediated by kinases, phosphatases, and proteases that rely on Ca2+ levels for their activation.
Systematic review and meta-analysis of the epidemiology of Lassa virus in humans, rodents and other mammals in sub-Saharan Africa

Accurate data on the Lassa virus (LASV) human case fatality rate (CFR) and the prevalence of LASV in humans, rodents and other mammals are needed for better planning of actions that will ultimately reduce the burden of LASV infection in sub-Saharan Africa. In this systematic review with meta-analysis, we searched PubMed, Scopus, Africa Journal Online, and African Index Medicus from 1969 to 2020 to obtain studies that reported enough data to calculate LASV infection CFR or prevalence. Study selection, data extraction, and risk of bias assessment were conducted independently. We extracted all measures of current, recent, and past infections with LASV. Prevalence and CFR estimates were pooled using a random-effect meta-analysis. Factors associated with CFR, prevalence, and sources of between-study heterogeneity were determined using subgroup and metaregression analyses. This review was registered with PROSPERO, CRD42020166465. We initially identified 1,399 records and finally retained 109 reports that contributed to 291 prevalence records from 25 countries. The overall CFR was 29.7% (22.3–37.5) in humans. Pooled prevalence of LASV infection was 8.7% (95% confidence interval: 6.8–10.8) in humans, 3.2% (1.9–4.6) in rodents, and 0.7% (0.0–2.3) in other mammals. Subgroup and metaregression analyses revealed a substantial statistical heterogeneity explained by higher prevalence in tissue organs, in case-control, in hospital outbreak, and surveys, in retrospective studies, in urban and hospital setting, in hospitalized patients, and in West African countries. This study suggests that LASV infections is an important cause of death in humans and that LASV are common in humans, rodents and other mammals in sub-Saharan Africa. These estimates highlight disparities between sub-regions, and population risk profiles. Western Africa, and specific key populations were identified as having higher LASV CFR and prevalence, hence, deserving more attention for cost-effective preventive interventions.
Recognition of Power Transformer Fault Based on Dissolved Gas Analysis using Fuzzy Logic Approach

The primary goal of the proposed study is to identify the fault type in the high voltage transformer using a fuzzy logic technique with tuned hyperparameters based on pattern search optimization. Based on the dissolved gas analysis results, fault types in the transformer are identified (DGA). For DGA analysis, this suggested study employs the conventional methodology, the International Electrotechnical Commission ratio (IEC), and the Duval triangle technique. There are transformer faults utilized. The fuzzy logic approach's hyperparameters are optimized using the pattern search optimization technique to improve the performance of the proposed work. In addition, four different fuzzy inference systems are used in this proposed work for further investigation. An intelligent maintenance approach is advised for efficient planning to prevent significant damage to the power transformer.
High Resolution Spectral Analysis and Signal Segregation Using the Polyphase Channelizer

The windowed fast Fourier transform (FFT) is the ubiquitous tool for spectral analysis because it is fast and easy to use. In this paper we will show how the polyphase channelizer can replace the FFT for spectral analysis and produce estimates of the power spectral density (PSD) and the short-time Fourier transform (STFT) spectrogram. We refer to the polyphase channelizer equivalents of these estimates respectively as the channelizer power spectral density (cPSD) and the channogram. It will be shown that the spectral resolution of the cPSD and channogram improves upon the well-established FFT-based estimators for a given FFT length while introducing minimal processing overhead. We will then discuss Parseval's theorem equivalent for the polyphase channelizer. Finally, we will show how the polyphase channelizer leads to straightforward signal segregation and inversion back to time domain when signals of random and unknown center frequencies and bandwidth are encountered. This is an important enabler for real-time radio frequency (RF) signal classification using machine learning algorithms.
Development of a Mobile Health Intervention with Personal Experiments for Smokers Who Are Ambivalent About Quitting: Formative Design and Testing

Background The majority of cigarette smokers want to quit someday but are not ready to commit to long-term abstinence. However, available smoking cessation treatments are not well-suited to meet the needs of these ambivalent smokers. Low-cost, high-reach mobile health (mHealth) interventions may be a cost-efficient means of offering assistance to ambivalent smokers, yet there are currently no evidence-based options available for this group. Objective The aim of this study was to develop and preliminarily evaluate the core content for an mHealth program targeting adult smokers who are ambivalent about quitting. The core content consisted of a series of “personal experiments” similar to those tested as part of a counseling intervention in prior work, including brief cognitive or behavioral tasks designed to boost readiness for changing smoking behavior. Methods We conducted individual user interviews (N=3) to refine program content, and then conducted a one-arm pilot study (N=25) to assess user receptivity and the potential impact of the experiments on motivation and self-efficacy to quit or reduce smoking. Results In user interviews, participants liked the concept of the personal experiments. Participants in the pilot study found a medium-fidelity prototype to be highly acceptable. After watching a brief orientation video that explained how the program works, most participants (80%, 20/25) indicated that it sounded interesting, primarily because it did not require any commitment to quit. All participants (100%, 25/25) completed all 7 experiments, including a 24-hour quit attempt, although not all were able to refrain from smoking for a full day based on qualitative feedback on the experiment. The mean rating of usefulness of the overall program was 4.12 (SD 1.09) out of 5, and the average rating of the difficulty of the experiments was 2.16 (SD 1.18) out of 5. At the last assessment point, 92% (23/25) of the participants indicated that they were more interested in either quitting or cutting back than when they began the program, and 72% (18/25) said that if the program had included a free trial of nicotine replacement therapy, they would have used it to try to quit smoking. Conclusions This formative work confirmed that ambivalent smokers are willing to use and will remain engaged with an mHealth intervention that employs the novel concept of personal experiments to enhance their motivation for and ability to quit smoking. The addition of action-oriented treatment (self-help and free nicotine replacement therapy, quitline referral) could further support users’ efforts to stop smoking and remain quit.
Into the tropics: phylogenomics and evolutionary dynamics of a contrarian clade of ants

Aim The standard latitudinal diversity gradient (LDG), in which species richness decreases from equator to pole, is a pervasive pattern observed in most groups of organisms. Despite its commonness, an increasing number of non-conforming lineages have been identified, presenting a challenge for general explanations of the standard LDG. Although problematic, documenting and studying these contrarian groups can help us to better understand LDGs generally. To that end we identify the ant tribe Stenammini, a diverse lineage with over 400 species, as a contrarian clade, and we attempt to explain the group’s atypical diversity pattern using a historical approach. We evaluate the following alternative hypotheses: time-for-speciation/center-of-origin (TFS/COO), niche conservatism, and differences in diversification rate. Location Global. Methods We examine the shape of the LDG in Stenammini by plotting latitudinal midpoints for all extant species. We then infer a robust phylogeny using a phylogenomic approach that employs ultraconserved element loci and we use the phylogeny to estimate divergence dates, biogeographic history, and ancestral habitats. We also test for diversification rate heterogeneity across the tree and among lineages within the tribe. Results Stenammini has a skewed inverse latitudinal diversity gradient with an extratropical richness peak in the northern temperate zone. Our phylogenomic approach resulted in a robust phylogeny revealing five major clades and several instances of non-monophyly among genera (Goniomma, Aphaenogaster). The tribe and most major lineages originated in the temperate zone and inhabited temperate niches. Crown Stenammini dates to 52 Ma (Eocene Climatic Optimum) and most major lineages appeared soon after during a period of global cooling. Despite its temperate origin, the group invaded the tropics at least six times, but failed to diversify greatly there. Across the tree diversification increased from 17.2-1.9 Ma following the Mid-Miocene Climatic Optimum, and among lineages there was a rate increase in Holarctic Aphaenogaster + Messor just prior to 17.2 Ma. Main Conclusions Our results suggest that time, niche conservatism, and increased diversification have all contributed to the inverse latitudinal gradient in Stenammini. Among these processes, niche conservatism may be less important given that the tribe has dispersed to the tropics multiple times.
Defining Positive Outcomes in More and Less Cognitively Able Autistic Adults

Identifying positive outcomes for a wide range of intellectual abilities in autism spectrum disorder (ASD) remains a challenge. Several past studies of autistic adults have used outcome definitions that do not reflect the experiences of less cognitively able adults. The aim of the current study was to (1) define three domains of outcomes: autonomy, social relationships, and purpose, and (2) examine how these outcomes relate to concurrent aspects of adult functioning. Using data from a longitudinal sample of 126 adults (85% diagnosed with ASD at some point), mean age 26, who first entered the study in early childhood, we generated distinct outcomes for less (daily living skills above an 8‐year‐old level, having regular activities outside the home, and social contacts outside the family) and more cognitively able adults (living independently, having paid employment, and at least one true friend). Verbal IQ, assessed in adulthood, was a significant predictor of more outcomes achieved for individuals within more and less cognitively able groups. For less cognitively able adults, having ever received a formal ASD diagnosis (in contrast to current Autism Diagnostic Observation Schedule [ADOS] CSS scores) was associated with lower odds of positive outcomes. For more cognitively able adults, living skills and happiness measures were positively associated with number of outcomes met; higher ADOS CSS, internalizing and externalizing symptoms, being racially diverse, and having caregiver education below college graduation were all negatively associated with the number of positive outcomes. Tailoring outcomes to ability levels may lead to better identification of goals and service needs.
A Traditional Korean Diet Alters the Expression of Circulating MicroRNAs Linked to Diabetes Mellitus in a Pilot Trial

The traditional Korean diet (K-diet) is considered to be healthy and circulating microRNAs (miRs) have been proposed as useful markers or targets in diet therapy. We, therefore, investigated the metabolic influence of the K-diet by evaluating the expression of plasma and salivary miRs. Ten women aged 50 to 60 years were divided into either a K-diet or control diet (a Westernized Korean diet) group. Subjects were housed in a metabolic unit-like condition during the two-week dietary intervention. Blood and saliva samples were collected before and after the intervention, and changes in circulating miRs were screened by an miR array and validated by individual RT-qPCRs. In the K-diet group, eight plasma miRs were down-regulated by array (p < 0.05), out of which two miRs linked to diabetes mellitus, hsa-miR26a-5p and hsa-miR126-3p, were validated (p < 0.05). Among five down-regulated salivary miRs, hsa-miR-92-3p and hsa-miR-122a-5p were validated, which are associated with diabetes mellitus, acute coronary syndrome and non-alcoholic fatty liver disease. In the control diet group, validated were down-regulated plasma hsa-miR-25-3p and salivary hsa-miR-31-5p, which are associated with diabetes mellitus, adipogenesis and obesity. The K-diet may influence the metabolic conditions associated with diabetes mellitus, as evidenced by changes in circulating miRs, putative biomarkers for K-diet.
Auditory cortex reflects goal-directed movement but is not necessary for behavioral adaptation in sound-cued reward tracking.

Mounting evidence suggests that the role of sensory cortices in perceptual decision making goes beyond the mere representation of the discriminative stimuli, and additionally involves the representation of non-sensory variables such as reward expectation. However, the relevance of these representations for behavior is not clear. To address this issue, we trained rats to discriminate sounds in a single-interval forced choice task, and then confronted animals with unsignaled blockwise changes of reward probabilities. We found that unequal reward probabilities for the two choice options led to substantial shifts in response bias without concomitant reduction in stimulus discrimination. Although decisional biases were on average less extreme than required to maximize overall reinforcement, a model-based analysis revealed that rats managed to harvest >97% of rewards. Neurons in auditory cortex recorded during task performance weakly differentiated the discriminative stimuli but more strongly the subsequent goal-directed movement. While 10-20% of units exhibited significantly different firing rates between task epochs with different response biases, control experiments showed this to result from inflated false-positive rates resulting from unspecific temporal correlations of spiking activity, rather than changing reinforcement contingencies. Transient pharmacological inactivation of auditory cortex reduced sound discriminability without affecting other measures of performance, whereas inactivation of medial prefrontal cortex affected both discriminability and bias. Together, these results suggest that auditory cortex activity only weakly reflects decisional variables during flexible updating of stimulus-response-outcome contingencies and does not play a crucial role in sound-cued adaptive behavior, beyond the representation of the discriminative stimuli.
Cloning of the Endoglucanase Gene from Actinomyces sp. 40 in Escherichia coli and Some Properties of the Gene Products

The -1,4-endoglucanase gene from Actinomyces sp. 40 was cloned into Escherichia coli DH5 with pUC19. Chromosomal DNA from Actinomyces sp. 40 was cleaved with the restriction enzyme Sau3AI and ligated into pUC19 for the transformation of Escherichia coli DH5. Positive clones of -1,4-endoglucanase gene were detected as the clear zones on a medium supplemented with carboxymethylcellulose (CMC). This transformant possessed a single plasmid, designated pDS1, which contained the vector DNA and a 3.5 kilobase (kb) Sau3AI insertion fragment encoding endoglucanase. The size of the cloned fragment was reduced to 2.0 kb. The endoglucanase activity produced by the E. coli DH5 (pDS6) was higher than that of Actinomyces sp. 40 strain. The optimum pH and temperature of the cloned enzyme were pH 4.05. 0 and 55, respectively. The cloned enzyme was stable at 55 or below and in buffer ranging from pH 4.0 to 7.0. The enzyme degraded CMC but did not degrade xylan, cellobiose, and methyl-umbelliferylcellobiopyranoside (MUC).