Miracle-dz/UniFAR-FTUs huggingface dataset:
The c-Abl inhibitor IkT-148009 suppresses neurodegeneration in mouse models of heritable and sporadic Parkinson’s disease

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease of the central nervous system, with an estimated 5,000,000 cases worldwide. PD pathology is characterized by the accumulation of misfolded α-synuclein, which is thought to play a critical role in the pathogenesis of the disease. Animal models of PD suggest that activation of Abelson tyrosine kinase (c-Abl) plays an essential role in the initiation and progression of α-synuclein pathology and initiates processes leading to degeneration of dopaminergic and nondopaminergic neurons. Given the potential role of c-Abl in PD, a c-Abl inhibitor library was developed to identify orally bioavailable c-Abl inhibitors capable of crossing the blood-brain barrier based on predefined characteristics, leading to the discovery of IkT-148009. IkT-148009, a brain-penetrant c-Abl inhibitor with a favorable toxicology profile, was analyzed for therapeutic potential in animal models of slowly progressive, α-synuclein–dependent PD. In mouse models of both inherited and sporadic PD, IkT-148009 suppressed c-Abl activation to baseline and substantially protected dopaminergic neurons from degeneration when administered therapeutically by once daily oral gavage beginning 4 weeks after disease initiation. Recovery of motor function in PD mice occurred within 8 weeks of initiating treatment concomitantly with a reduction in α-synuclein pathology in the mouse brain. These findings suggest that IkT-148009 may have potential as a disease-modifying therapy in PD. Description Therapeutic administration of the c-Abl inhibitor, IkT-148009, abrogates loss of dopamine neurons leading to functional recovery in mouse models of Parkinson’s disease. Protecting dopamine neurons with a c-Abl inhibitor Neurodegeneration of dopaminergic neurons in Parkinson’s disease (PD) leads to activation of the non-receptor tyrosine kinase c-Abl. Karuppagounder et al. now report that IkT-148009, a c-Abl inhibitor that can cross the blood-brain barrier, rescued dopaminergic neuron deficits in mouse models of inherited and sporadic PD. Rescue of dopaminergic neurons occurred even when oral administration of IkT-148009 began 4 weeks after disease initiation. These results suggest that IkT-148009 should be investigated further as a disease-modifying therapy for PD. —OMS
Heritable defects in telomere and mitotic function selectively predispose to sarcomas

Cancer genetics has to date focused on epithelial malignancies, identifying multiple histotype-specific pathways underlying cancer susceptibility. Sarcomas are rare malignancies predominantly derived from embryonic mesoderm. To identify pathways specific to mesenchymal cancers, we performed whole-genome germline sequencing on 1644 sporadic cases and 3205 matched healthy elderly controls. Using an extreme phenotype design, a combined rare-variant burden and ontologic analysis identified two sarcoma-specific pathways involved in mitotic and telomere functions. Variants in centrosome genes are linked to malignant peripheral nerve sheath and gastrointestinal stromal tumors, whereas heritable defects in the shelterin complex link susceptibility to sarcoma, melanoma, and thyroid cancers. These studies indicate a specific role for heritable defects in mitotic and telomere biology in risk of sarcomas. Description Sarcoma genes in the limelight Sarcomas are cancers of muscles, bones, and other connective tissues that tend to develop in younger patients and are often aggressive and difficult to treat. Because of their relative rarity, the biology of sarcomas is not nearly as well understood as that of more common cancers. In a massive, multinational genomic study involving thousands of patients, their families, and controls, Ballinger et al. identified distinct biological pathways where mutations increase the inherited risk for developing sarcoma through alterations of telomere biology and mitotic function (see the Perspective by Mandelker and Ladanyi). More work is needed before these findings can lead to therapeutic advances, but the study provides much needed biological insight into a deadly disease. —YN Human genome germline sequencing reveals that defects in centrosome and shelterin pathways may specifically increase risk for sarcomas.
Drone-assisted collection of environmental DNA from tree branches for biodiversity monitoring

The protection and restoration of the biosphere is crucial for human resilience and well-being, but the scarcity of data on the status and distribution of biodiversity puts these efforts at risk. DNA released into the environment by organisms, i.e., environmental DNA (eDNA), can be used to monitor biodiversity in a scalable manner if equipped with the appropriate tool. However, the collection of eDNA in terrestrial environments remains a challenge because of the many potential surfaces and sources that need to be surveyed and their limited accessibility. Here, we propose to survey biodiversity by sampling eDNA on the outer branches of tree canopies with an aerial robot. The drone combines a force-sensing cage with a haptic-based control strategy to establish and maintain contact with the upper surface of the branches. Surface eDNA is then collected using an adhesive surface integrated in the cage of the drone. We show that the drone can autonomously land on a variety of branches with stiffnesses between 1 and 103 newton/meter without prior knowledge of their structural stiffness and with robustness to linear and angular misalignments. Validation in the natural environment demonstrates that our method is successful in detecting animal species, including arthropods and vertebrates. Combining robotics with eDNA sampling from a variety of unreachable aboveground substrates can offer a solution for broad-scale monitoring of biodiversity. Description A drone incorporating a force-sensing cage with adhesive surfaces enables environmental DNA to be collected from tree branches.
Tryptanthrin Reduces Campylobacter jejuni Colonization in the Chicken Gut by a Bactericidal Mechanism

Campylobacter is a widespread pathogen in the food chain of chickens. Once chickens become infected, large numbers of Campylobacter cells are excreted in their feces. ABSTRACT Campylobacter jejuni is a leading cause of foodborne bacterial gastroenteritis worldwide, and raw or undercooked chicken meat is considered the major source of human campylobacteriosis. In this study, we identified 36 compounds that showed inhibitory effects on C. jejuni growth at low concentrations by screening a chemical compound library. Three of the 36 compounds were herbal compounds, including tryptanthrin (TRP), an indoloquinazoline alkaloid. TRP has been reported to have a variety of biological properties, such as antimicrobial, anti-inflammatory, and antitumor activities, but there was previously no information about its anti-C. jejuni activity. We further conducted in vitro and in vivo experiments to evaluate the potential of TRP for the control of C. jejuni in chicken farms. The MIC of TRP for C. jejuni was much lower than that of 13 other herbal compounds that were previously reported to have anti-C. jejuni activities. Time-kill assays under growing and nongrowing conditions demonstrated that TRP has bactericidal activity against C. jejuni. In addition, TRP showed a narrow-spectrum antimicrobial effect against C. jejuni, and there was little potential for the development of TRP-resistant C. jejuni during serially passaged culture. In chick infection experiments, the administration of TRP in drinking water significantly reduced the cecal colonization of C. jejuni when TRP was used either before or after C. jejuni infection. These data suggest that TRP is effective for the control of C. jejuni in chicken farms. IMPORTANCE Campylobacter is a widespread pathogen in the food chain of chickens. Once chickens become infected, large numbers of Campylobacter cells are excreted in their feces. The development of an effective material for reducing the amount of Campylobacter in the chicken intestinal tract will make it possible to reduce the contamination of the food chain with Campylobacter and to produce safe and secure chicken meat. In the present study, in vivo experiments revealed that the use of an herbal compound, tryptanthrin, significantly reduced the number of Campylobacter cells in the chicken gut by a bactericidal mechanism. Furthermore, our in vitro experiments demonstrated that, compared with the other herbal compounds, tryptanthrin achieved antimicrobial activity against C. jejuni at the lowest concentration. The use of tryptanthrin may lead to the development of a novel control measure for reducing the colonization of C. jejuni in the food chain.
De Novo Genome Sequencing and Assembly of Rhodosporidium toruloides Strain Δdao1e

Rhodosporidium toruloides is an important industrial strain with high oil production. Here, we report the de novo sequencing of R. toruloides strain Δdao1e, which was derived from R. toruloides strain ATCC 10657, by combining sequencing results from the Illumina and PacBio Sequel platforms. ABSTRACT Rhodosporidium toruloides is an important industrial strain with high oil production. Here, we report the de novo sequencing of R. toruloides strain Δdao1e, which was derived from R. toruloides strain ATCC 10657, by combining sequencing results from the Illumina and PacBio Sequel platforms.
What Lies Beneath? Taking the Plunge into the Murky Waters of Phage Biology

The sequence revolution revealed that bacteria-infecting viruses, known as phages, are Earth’s most abundant biological entities. Phages have far-reaching impacts on the form and function of microbial communities and play a fundamental role in ecological processes. ABSTRACT The sequence revolution revealed that bacteria-infecting viruses, known as phages, are Earth’s most abundant biological entities. Phages have far-reaching impacts on the form and function of microbial communities and play a fundamental role in ecological processes. However, even well into the sequencing revolution, we have only just begun to explore the murky waters around the phage biology iceberg. Many viral reads cannot be assigned to a culturable isolate, and reference databases are biased toward more easily collectible samples, which likely distorts our conclusions. This minireview points out alternatives to mapping reads to reference databases and highlights innovative bioinformatic and experimental approaches that can help us overcome some of the challenges in phage research and better decipher the impact of phages on microbial communities. Moving beyond the identification of novel phages, we highlight phage metabolomics as an important influencer of bacterial host cell physiology and hope to inspire the reader to consider the effects of phages on host metabolism and ecosystems at large. We encourage researchers to report unassigned/unknown sequencing reads and contigs and to continue developing alternative methods to investigate phages within sequence data.
Elongation Factor P Is Important for Sporulation Initiation

Elongation factor P (EF-P) is a universally conserved translation factor that prevents ribosome stalling at amino acids that form peptide bonds with low efficiency, particularly polyproline tracts. Phenotypes associated with EF-P deletion are pleiotropic, and the mechanistic basis underlying many of these phenotypes is unclear. ABSTRACT The universally conserved protein elongation factor P (EF-P) facilitates translation at amino acids that form peptide bonds with low efficiency, particularly polyproline tracts. Despite its wide conservation, it is not essential in most bacteria and its physiological role remains unclear. Here, we show that EF-P affects the process of sporulation initiation in the bacterium Bacillus subtilis. We observe that the lack of EF-P delays expression of sporulation-specific genes. Using ribosome profiling, we observe that expression of spo0A, encoding a transcription factor that functions as the master regulator of sporulation, is lower in a Δefp strain than the wild type. Ectopic expression of Spo0A rescues the sporulation initiation phenotype, indicating that reduced spo0A expression explains the sporulation defect in Δefp cells. Since Spo0A is the earliest sporulation transcription factor, these data suggest that sporulation initiation can be delayed when protein synthesis is impaired. IMPORTANCE Elongation factor P (EF-P) is a universally conserved translation factor that prevents ribosome stalling at amino acids that form peptide bonds with low efficiency, particularly polyproline tracts. Phenotypes associated with EF-P deletion are pleiotropic, and the mechanistic basis underlying many of these phenotypes is unclear. Here, we show that the absence of EF-P affects the ability of B. subtilis to initiate sporulation by preventing normal expression of Spo0A, the key transcriptional regulator of this process. These data illustrate a mechanism that accounts for the sporulation delay and further suggest that cells are capable of sensing translation stress before committing to sporulation.
Ear Development in Select Coral Reef Fishes: Clues for the Role of Hearing in Larval Orientation Behavior?

The pelagic larvae of coral reef fishes can detect and discriminate among different types of sounds suggesting that they may be able to localize acoustic cues and thus identify suitable settlement sites on reefs. It has been suggested that a description of ear development may provide clues about the importance of sound in larval behavior. Here we provide the first description of the ontogeny of the ear in the pelagic larvae and juveniles of representatives of three important families of coral reef fishes: Gobiidae (Elacatinus lori, E. colini), Apogonidae (Cheilodipterus quinquelineatus), and Pomacentridae (Amblyglyphidodon leucogaster, Amphiprion polymnus). Histological analysis revealed that the ear of the larvae and juveniles of the five study species lack any of the morphological specializations known in percomorph fishes. However, it showed that the ears of the two gobies are quite similar with respect to size and shape of the three otolithic organs, but that ears of the cardinalfish and damselfishes are different with respect to the absolute and relative sizes and position of the otolithic organs, as well as the timing of the appearance of the lagena; however, the functional significance of these features are unknown. It is concluded that if hearing plays a role in orientation behavior in the pelagic larvae of coral reef fishes then their “unremarkable” ears are sufficient to allow these diminutive fishes to carry out the extraordinary feat of navigating the open ocean and successfully locating coral reefs on which to settle.
Floristic Patterns and Conservation Values of Mojave and Sonoran Desert Springs in California

ABSTRACT In the face of a rapidly changing climate, spring-fed habitats are increasingly vulnerable to numerous threats. Botanical inventories provide valuable information to assess the conservation value of desert springs, and can serve as indicators to document changing conditions, including the proportion of native vs. nonnative taxa, diversity of life forms present that influence structure and function of ecosystems, species persistence and longevity, and the proportion of taxa that are rare and sensitive to land use change. Here we evaluate plant species composition and richness within and between springs, and evaluate botanical diversity with respect to physical parameters including hydrology and geography. We find that desert springs collectively support a large proportion of plant diversity, or nearly 22% of the total vascular plant diversity known within the California desert in only 0.000005% of the total land area. The springs we sampled are highly dissimilar in plant species composition, thus, restoration and management activities likely need to be highly individualized and site specific. Monitoring and inventory programs can increase opportunities for restoration and protection by providing information to assess warning signs of habitat degradation, such as changing species composition and local extirpation of wetland-dependent species.
Inverse Problems in Engineering

Presented here are 11 noteworthy papers selected from the Fifth International Conference on Inverse Problems in Engineering: Theory and Practice held in Cambridge, UK during 11–15 July 2005. The papers have been peer-reviewed to the usual high standards of this journal and the contributions of reviewers are much appreciated. The conference featured a good balance of the fundamental mathematical concepts of inverse problems with a diverse range of important and interesting applications, which are represented here by the selected papers. Aspects of finite-element modelling and the performance of inverse algorithms are investigated by Autrique et al and Leduc et al. Statistical aspects are considered by Emery et al and Watzenig et al with regard to Bayesian parameter estimation and inversion using particle filters. Electrostatic applications are demonstrated by van Berkel and Lionheart and also Nakatani et al. Contributions to the applications of electrical techniques and specifically electrical tomographies are provided by Wakatsuki and Kagawa, Kim et al and Kortschak et al. Aspects of inversion in optical tomography are investigated by Wright et al and Douiri et al. The authors are representative of the worldwide interest in inverse problems relating to engineering applications and their efforts in producing these excellent papers will be appreciated by many readers of this journal.
Sampling in shift-invariant spaces of functions with polynomial growth

Under suitable conditions, a function f(t) in a principal shift-invariant space can be recovered from its uniform samples { f(n)} n∈ℤ with a simple sampling formula. Provided that the generator ϕ has compact support, we consider the sampling problem in the bigger space V ϕ ≔ {∑a n ϕ(t − n) : a n ∈ ℂℤ}. In this space, there exist infinite functions with the same samples y n = f(n). We show that polynomial growth conditions give the uniqueness: if y n has polynomial growth, there is a unique function of polynomial growth f ∈ V ϕ, satisfying f(n) = y n , n ∈ ℤ. This function is given by the known sampling formula. The same result is proved also when we consider average samples y n = f ∗ h(n).
The audio features of sleep music: Universal and subgroup characteristics

Throughout history, lullabies have been used to help children sleep, and today, with the increasing accessibility of recorded music, many people report listening to music as a tool to improve sleep. Nevertheless, we know very little about this common human habit. In this study, we elucidated the characteristics of music associated with sleep by extracting audio features from a large number of tracks (N = 225,626) retrieved from sleep playlists at the global streaming platform Spotify. Compared to music in general, we found that sleep music was softer and slower; it was more often instrumental (i.e. without lyrics) and played on acoustic instruments. Yet, a large amount of variation was present in sleep music, which clustered into six distinct subgroups. Strikingly, three of the subgroups included popular tracks that were faster, louder, and more energetic than average sleep music. The findings reveal previously unknown aspects of the audio features of sleep music and highlight the individual variation in the choice of music used for sleep. By using digital traces, we were able to determine the universal and subgroup characteristics of sleep music in a unique, global dataset, advancing our understanding of how humans use music to regulate their behaviour in everyday life.
When is the probability ranking principle suboptimal

The probability ranking principle retrieves documents in decreasing order of their predictive probabilities of relevance. Gordon and Lenk (1991) demonstrated that this principal is optimal within a signal detection—decision theory framework, and it maximizes the inquirer's expected utility for relevant documents. These results hold under three conditions: calibration, independent assessment of relevance by the inquirer, and certainty about the computed probabilities of relevance. We demonstrate that the probability ranking principle can be suboptimal with respect to expected utility when one of these conditions fails to hold. © 1992 John Wiley & Sons, Inc.
On the data privacy practices of Android OEMs

In this paper we present the first in-depth measurement study looking at the data privacy practices of the proprietary variants of the Android OS produced by Samsung, Xiaomi, Huawei and Realme. We address two questions: how are identifiers used in network connections and what types of data are transmitted. To answer these, we decrypt and decode the network traffic transmitted by a range of Android handsets. We find that all of the OEMs make undue use of long-lived hardware identifiers such as the hardware serial number, handset IMEI and so fail to follow best privacy practice. Hardware identifiers are also linked to the handset user’s real identity when they sign in to an OEM account on the handset. All of the OEMs collect the list of apps installed in a handset. This is a privacy concern since the list of installed apps can be used to profile user traits and preferences. All of the OEMs collect analytics/telemetry data, raising obvious privacy concerns.
A framework to quantify flow through coral reefs of varying coral cover and morphology

Flow velocities within coral reefs are greatly reduced relative to those at the water surface. The in-reef flow controls key processes that flush heat, cycle nutrients and transport sediment from the reef to adjacent beaches, all key considerations in assessments of reef resilience and restoration interventions. An analytical framework is proposed and tested with a suite of high-resolution numerical experiments. We demonstrate a single parameter that describes the total coral frontal area explains variation of horizontally averaged velocity within a reef canopy across morphologies, densities, and flow depths. With the integration of existing data of coral cover and geometry, this framework is a practical step towards the prediction of near-bed flows in diverse reef environments.
The Phoenix spectrograph at Gemini South

Phoenix, a high resolution near-infrared spectrograph build by NOAO, was first used on the Gemini South telescope in December 2001. Previously on the Kitt Peak 2.1 and 4 meter telescopes, Phoenix received a new detector, as well as modified refrigeration, mounting, and handling equipment, prior to being sent to Gemini South. Using a two-pixel slit the resolution is ~75,000, making Phoenix the highest resolution infrared spectrograph available on a 6-10 meter class telescope at the current time. Modifications to and performance of the instrument are discussed. Some results on Magellanic cloud stars, brown dwarf stars, premain-sequence objects, and stellar exotica are reviewed briefly.
Stereophonic Listening and Speech Intelligibility against Voice Babble

The utilization of a particular form of stereophonic information was studied with respect to the intelligibility of a single speech source heard in the presence of a voice babble of other speakers. The reception of monosyllabic words, presented against a babble of 1, 2, 4, or 7 talkers, was compared under two listening conditions: (1) In the stereophonic listening condition, one set of background talkers was presented to one earphone, another set of background talkers was presented to the other earphone, and the test words were presented binaurally, in phase; (2) In the control listening condition, only a single set of background talkers, and the test words, were presented to a single ear. The stereophonic advantage, for 50% word intelligibility, ranged from 12 db with 1 background voice per channel to 5.5 db with 7 background voices per channel.