Miracle-dz/UniFAR-FTUs huggingface dataset:
F-Type Bacteriocins of Listeria monocytogenes: a New Class of Phage Tail-Like Structures Reveals Broad Parallel Coevolution between Tailed Bacteriophages and High-Molecular-Weight Bacteriocins

ABSTRACT Listeria monocytogenes is a significant foodborne human pathogen that can cause severe disease in certain high-risk individuals. L. monocytogenes is known to produce high-molecular-weight, phage tail-like bacteriocins, or “monocins,” upon induction of the SOS system. In this work, we purified and characterized monocins and found them to be a new class of F-type bacteriocins. The L. monocytogenes monocin genetic locus was cloned and expressed in Bacillus subtilis, producing specifically targeted bactericidal particles. The receptor binding protein, which determines target cell specificity, was identified and engineered to change the bactericidal spectrum. Unlike the F-type pyocins of Pseudomonas aeruginosa, which are related to lambda-like phage tails, monocins are more closely related to TP901-1-like phage tails, structures not previously known to function as bacteriocins. Monocins therefore represent a new class of phage tail-like bacteriocins. It appears that multiple classes of phage tails and their related bacteriocins have coevolved separately in parallel. IMPORTANCE Phage tail-like bacteriocins (PTLBs) are structures widespread among the members of the bacterial kingdom that are evolutionarily related to the DNA delivery organelles of phages (tails). We identified and characterized “monocins” of Listeria monocytogenes and showed that they are related to the tail structures of TP901-1-like phages, structures not previously known to function as bacteriocins. Our results show that multiple types of envelope-penetrating machines have coevolved in parallel to function either for DNA delivery (phages) or as membrane-disrupting bacteriocins. While it has commonly been assumed that these structures were coopted from phages, we cannot rule out the opposite possibility, that ancient phages coopted complex bacteriocins from the cell, which then underwent adaptations to become efficient at translocating DNA.
Cloud K-SVD: A Collaborative Dictionary Learning Algorithm for Big, Distributed Data

This paper studies the problem of data-adaptive representations for big, distributed data. It is assumed that a number of geographically-distributed, interconnected sites have massive local data and they are interested in collaboratively learning a low-dimensional geometric structure underlying these data. In contrast with previous works on subspace-based data representations, this paper focuses on the geometric structure of a union of subspaces (UoS). In this regard, it proposes a distributed algorithm-termed cloud K-SVD-for collaborative learning of a UoS structure underlying distributed data of interest. The goal of cloud K-SVD is to learn a common overcomplete dictionary at each individual site such that every sample in the distributed data can be represented through a small number of atoms of the learned dictionary. Cloud K-SVD accomplishes this goal without requiring exchange of individual samples between sites. This makes it suitable for applications where sharing of raw data is discouraged due to either privacy concerns or large volumes of data. This paper also provides an analysis of cloud K-SVD that gives insights into its properties as well as deviations of the dictionaries learned at individual sites from a centralized solution in terms of different measures of local/global data and topology of interconnections. Finally, the paper numerically illustrates the efficacy of cloud K-SVD on real and synthetic distributed data.
Online learning over a finite action set with limited switching

This paper studies the value of switching actions in the Prediction From Experts problem (PFE) and Adversarial Multiarmed Bandits problem (MAB). First, we revisit the well-studied and practically motivated setting of PFE with switching costs. Many algorithms achieve the minimax optimal order for both regret and switches in expectation; however, high probability guarantees are an open problem. We present the first algorithms that achieve this optimal order for both quantities with high probability. This also implies the first high probability guarantees for several other problems, and, in particular, is efficiently adaptable to online combinatorial optimization with limited switching. Next, to investigate the value of switching actions more granularly, we introduce the switching budget setting, which limits algorithms to a fixed number of (costless) switches. Using this result and several reductions, we unify previous work and completely characterize the complexity of this switching budget setting up to small polylogarithmic factors: for both PFE and MAB, for all switching budgets, and for both expectation and high probability guarantees. Interestingly, as the switching budget decreases, the minimax regret rate admits a phase transition for PFE but not for MAB. These results recover and generalize the known minimax rates for the (arbitrary) switching cost setting.
Ultra High-Speed SM2 ASIC Implementation

In this paper, we present a high-performance elliptic curve cryptographic architecture over SCA-256 prime field by introducing a one-cycle full-precision multiplier. Based on the multiplier, we give a thorough bottom-up optimization in algorithm level. The performance of the architecture is boosted by the use of a two-stage pipeline scheme, and our pipeline utilization reaches 100%. It takes only 8 cycles to perform point doubling and 12 cycles to perform point addition. Using NAF recoding of scalar k, it takes about 3333 cycles to complete the point multiplication operation. In the hardware evaluation using a 0.13 mum CMOS standard cell library, our high-performance SM2 architecture executes one point multiplication operation in 20.36 mus, which translates into more than 49000 point multiplications per second. To the best of our knowledge, our architecture offers the highest single-core performance over prime fields reported in literature up to now.
Pathways of Prion Spread during Early Chronic Wasting Disease in Deer

ABSTRACT Among prion infections, two scenarios of prion spread are generally observed: (i) early lymphoid tissue replication or (ii) direct neuroinvasion without substantial antecedent lymphoid amplification. In nature, cervids are infected with chronic wasting disease (CWD) prions by oral and nasal mucosal exposure, and studies of early CWD pathogenesis have implicated pharyngeal lymphoid tissue as the earliest sites of prion accumulation. However, knowledge of chronological events in prion spread during early infection remains incomplete. To investigate this knowledge gap in early CWD pathogenesis, we exposed white-tailed deer to CWD prions by mucosal routes and performed serial necropsies to assess PrPCWD tissue distribution by real-time quaking-induced conversion (RT-QuIC) and tyramide signal amplification immunohistochemistry (TSA-IHC). Although PrPCWD was not detected by either method in the initial days (1 and 3) postexposure, we observed PrPCWD seeding activity and follicular immunoreactivity in oropharyngeal lymphoid tissues at 1 and 2 months postexposure (MPE). At 3 MPE, PrPCWD replication had expanded to all systemic lymphoid tissues. By 4 MPE, the PrPCWD burden in all lymphoid tissues had increased and approached levels observed in terminal disease, yet there was no evidence of nervous system invasion. These results indicate the first site of CWD prion entry is in the oropharynx, and the initial phase of prion amplification occurs in the oropharyngeal lymphoid tissues followed by rapid dissemination to systemic lymphoid tissues. This lymphoid replication phase appears to precede neuroinvasion. IMPORTANCE Chronic wasting disease (CWD) is a universally fatal transmissible spongiform encephalopathy affecting cervids, and natural infection occurs through oral and nasal mucosal exposure to infectious prions. Terminal disease is characterized by PrPCWD accumulation in the brain and lymphoid tissues of affected animals. However, the initial sites of prion accumulation and pathways of prion spread during early CWD infection remain unknown. To investigate the chronological events of early prion pathogenesis, we exposed deer to CWD prions and monitored the tissue distribution of PrPCWD over the first 4 months of infection. We show CWD uptake occurs in the oropharynx with initial prion replication in the draining oropharyngeal lymphoid tissues, rapidly followed by dissemination to systemic lymphoid tissues without evidence of neuroinvasion. These data highlight the two phases of CWD infection: a robust prion amplification in systemic lymphoid tissues prior to neuroinvasion and establishment of a carrier state.
A Xhosa language translation of the CORE-OM using South African university student samples

The translation of well established psychometric tools from English into Xhosa may assist in improving access to psychological services for Xhosa speakers. The aim of this study was to translate the Clinical Outcomes in Routine Evaluation – Outcome Measure (CORE-OM), a measure of general distress and dysfunction developed in the UK, into Xhosa for use at South African university student counselling centres. The CORE-OM and embedded CORE-10 were translated into Xhosa using a five-stage translation design. This design included (a) forward-translation, (b) back-translation, (c) committee approach, (d) qualitative piloting, and (e) quantitative piloting on South African university students. Clinical and general samples were drawn from English-medium South African universities. Clinical samples were generated from university student counselling centres. General student samples were generated through random stratified cluster sampling of full-time university students. Qualitative feedback from the translation process and results from quantitative piloting of the 34-item CORE-OM English and Xhosa versions supported the reduction of the scale to 10 items. This reduced scale is referred to as the South African CORE-10 (SA CORE-10). A measurement and structural model of the SA CORE-10 English version was developed and cross-validated using an English-speaking university student sample. Equivalence of this model with the SA CORE-10 Xhosa version was investigated using a first-language Xhosa-speaking university sample. Partial measurement equivalence was achieved at the metric level. The resultant SA CORE-10 Xhosa and English versions provide core measures of distress and dysfunction. Additional, culture- and language-specific domains could be added to increase sensitivity and specificity.
The burden of loss: unexpected death of a loved one and psychiatric disorders across the life course in a national study.

OBJECTIVE Unexpected death of a loved one is common and associated with subsequent elevations in symptoms of multiple forms of psychopathology. Determining whether this experience predicts novel onset of psychiatric disorders and whether these associations vary across the life course has important clinical implications. The authors examined associations of a loved one's unexpected death with first onset of common anxiety, mood, and substance use disorders in a population-based sample. METHOD The relation between unexpected death of a loved one and first onset of lifetime DSM-IV disorders was estimated by using a structured interview of adults in the U.S. general population (analytic sample size=27,534). Models controlled for prior occurrence of any disorder, other traumatic experiences, and demographic variables. RESULTS Unexpected death of a loved one was the most common traumatic experience and most likely to be rated as the respondent's worst, regardless of other traumatic experiences. Increased incidence after unexpected death was observed at nearly every point across the life course for major depressive episode, panic disorder, and posttraumatic stress disorder. Increased incidence was clustered in later adult age groups for manic episode, phobias, alcohol use disorders, and generalized anxiety disorder. CONCLUSIONS The bereavement period is associated with elevated risk for the onset of multiple psychiatric disorders, consistently across the life course and coincident with the experience of the loved one's death. Novel associations between unexpected death and onset of several disorders, including mania, confirm multiple case reports and results of small studies and suggest an important emerging area for clinical research and practice.
Experimental Treatment Options in Absence Epilepsy.

BACKGROUND The benign character of absence epilepsy compared to other genetic generalized epilepsy syndromes has often hampered the search for new treatment options. Absence epilepsy is most often treated with ethosuximide or valproic acid. However, both drugs are not always well tolerated or fail, and seizure freedom for a larger proportion of patients remains to be achieved. The availability of genuine animal models of epilepsy does allow to search for new treatment options not only for absence epilepsy per se but also for other genetic - previously called idiopathic - forms of epilepsy. The recent discovery of a highly excitable cortical zone in these models is considered as a new therapeutic target area. METHODS Here, we provide an overview regarding the search for new therapeutical options as has been investigated in the genetic rodent models (mainly WAG/Rij and GAERS) including drugs and whether antiepileptogenesis can be achieved, various types of electrical and optogenetical invasive stimulations, different types of noninvasive stimulation and finally whether absence seizures can be predicted and prevented. RESULTS Many factors determine either the cortical and or thalamic excitability or the interaction between cortex and thalamus and offer new possibilities for new anti-absence drugs, among others metabotropic glutamatergic positive and negative allosteric modulators. The inhibition of epileptogenesis by various drugs with its widespread consequences seems feasible, although its mechanisms remain obscure and seems different from the antiabsence action. Surgical intervention on the cortical zone initiating seizures, either with radiosurgery using synchrotron- generated microbeams, or ablation techniques might reduce spike-and-wave discharges in the rodent models. High frequency electrical subcortical or cortical stimulation might be a good way to abort ongoing spikeand- wave discharges. In addition, possibilities for prevention with real-time EEG analyses in combination with electrical stimulation could also be a way to fully control these seizures. CONCLUSION Although it is obvious that some of these treatment possibilities will not be used for absence epilepsy and/or need to be further developed, all can be considered as proof of principle and provide clear directives for further developments.
A large gene family in fission yeast encodes spore killers that subvert Mendel’s law

Spore killers in fungi are selfish genetic elements that distort Mendelian segregation in their favor. It remains unclear how many species harbor them and how diverse their mechanisms are. Here, we discover two spore killers from a natural isolate of the fission yeast Schizosaccharomyces pombe. Both killers belong to the previously uncharacterized wtf gene family with 25 members in the reference genome. These two killers act in strain-background-independent and genome-location-independent manners to perturb the maturation of spores not inheriting them. Spores carrying one killer are protected from its killing effect but not that of the other killer. The killing and protecting activities can be uncoupled by mutation. The numbers and sequences of wtf genes vary considerably between S. pombe isolates, indicating rapid divergence. We propose that wtf genes contribute to the extensive intraspecific reproductive isolation in S. pombe, and represent ideal models for understanding how segregation-distorting elements act and evolve. DOI: http://dx.doi. org/10.7554/eLife.26057. 001
Cushing’s sign and severe traumatic brain injury in children after blunt trauma: a nationwide retrospective cohort study in Japan

Objective We tested whether Cushing’s sign could predict severe traumatic brain injury (TBI) requiring immediate neurosurgical intervention (BI-NSI) in children after blunt trauma. Design Retrospective cohort study using Japan Trauma Data Bank. Setting Emergency and critical care centres in secondary and tertiary hospitals in Japan. Participants Children between the ages of 2 and 15 years with Glasgow Coma Scale motor scores of 5 or less at presentation after blunt trauma from 2004 to 2015 were included. A total of 1480 paediatric patients were analysed. Primary outcome measures Patients requiring neurosurgical intervention within 24 hours of hospital arrival and patients who died due to isolated severe TBI were defined as BI-NSI. The combination of systolic blood pressure (SBP) and heart rate (HR) on arrival, which were respectively divided into tertiles, and its correlation with BI-NSI were investigated using a multiple logistic regression model. Results In the study cohort, 297 (20.1%) exhibited BI-NSI. After adjusting for sex, age category and with or without haemorrhage shock, groups with higher SBP and lower HR (SBP ≥135 mm Hg; HR ≤92 bpm) were significantly associated with BI-NSI (OR 2.84, 95% CI 1.68 to 4.80, P<0.001) compared with the patients with normal vital signs. In age-specific analysis, hypertension and bradycardia were significantly associated with BI-NSI in a group of 7–10 and 11–15 years of age; however, no significant association was observed in a group of 2–6 years of age. Conclusions Cushing’s sign after blunt trauma was significantly associated with BI-NSI in school-age children and young adolescents.
Developmental Trajectories of Maladaptive Perfectionism in Middle Childhood.

The developmental trajectories of maladaptive perfectionism, along with their consequences and origins, were examined in middle childhood. A sample of Singaporean children and their parents (N = 302) were recruited for a longitudinal study when the children were 7 years old. Subsequent follow-up assessments were made at ages 8, 9, and 11. A multimethod approach was adopted where parent reports, child reports, and observational data on a dyadic interaction task were obtained. Using latent class growth modeling, four distinct classes were obtained for critical self-oriented perfectionism (SOP-C), whereas two classes emerged for socially prescribed perfectionism (SPP). Children with high and/or increasing SOP-C and SPP trajectories constituted 60% and 78% of the sample, respectively. For both SOP-C and SPP, trajectories with high initial status were associated with higher internalizing and externalizing symptoms. Parental intrusiveness and negative parenting predicted high and/or increasing SOP-C trajectories, whereas the child temperament dimension of surgency predicted high SPP trajectory. Both SOP-C and SPP trajectories tended to co-occur, suggesting a mutually reinforcing process. This study yields important findings that help advance current understanding of the emergence and developmental pathways of maladaptive perfectionism in children.
Astronomical tunings of the Oligocene-Miocene transition from Pacific Ocean Site U1334 and implications for the carbon cycle

Abstract. Astronomical tuning of sediment sequences requires both unambiguous cycle pattern recognition in climate proxy records and astronomical solutions, as well as independent information about the phase relationship between these two. Here we present two different astronomically tuned age models for the Oligocene–Miocene transition (OMT) from Integrated Ocean Drilling Program Site U1334 (equatorial Pacific Ocean) to assess the effect tuning has on astronomically calibrated ages and the geologic timescale. These alternative age models (roughly from ∼ 22 to ∼ 24 Ma) are based on different tunings between proxy records and eccentricity: the first age model is based on an aligning CaCO3 weight (wt%) to Earth's orbital eccentricity, and the second age model is based on a direct age calibration of benthic foraminiferal stable carbon isotope ratios (δ13C) to eccentricity. To independently test which tuned age model and associated tuning assumptions are in best agreement with independent ages based on tectonic plate-pair spreading rates, we assign the tuned ages to magnetostratigraphic reversals identified in deep-marine magnetic anomaly profiles. Subsequently, we compute tectonic plate-pair spreading rates based on the tuned ages. The resultant alternative spreading-rate histories indicate that the CaCO3 tuned age model is most consistent with a conservative assumption of constant, or linearly changing, spreading rates. The CaCO3 tuned age model thus provides robust ages and durations for polarity chrons C6Bn.1n–C7n.1r, which are not based on astronomical tuning in the latest iteration of the geologic timescale. Furthermore, it provides independent evidence that the relatively large (several 10 000 years) time lags documented in the benthic foraminiferal isotope records relative to orbital eccentricity constitute a real feature of the Oligocene–Miocene climate system and carbon cycle. The age constraints from Site U1334 thus indicate that the delayed responses of the Oligocene–Miocene climate–cryosphere system and (marine) carbon cycle resulted from highly non-linear feedbacks to astronomical forcing.
Holistic protocol for callus culture optimization using statistical modelling

Abstract Plants endue a key role against illnesses caused by oxidative stress. These attributes are frequently associated with polyphenolic compounds. However, presence and concentration of secondary metabolites are affected by abiotic factors. The in vitro culture techniques can solve these drawbacks. Peppers can be a suitable alternative to obtain polyphenols. Aiming to optimise the callus culture stage from Capsicum baccatum to produce polyphenols, this work evaluated systemically the effects of the explant’s origin (root, hypocotyl and cotyledon), growth hormone type (2,4-dichlorophenoxyacetic acid (2,4-D), benzylaminopurine (BAP) and a combination of 2,4-D/BAP at five-to-one ratio) and concentration (0.023–10.000 mg L−1) on callus culture efficiency parameters using a multilevel factorial design. The root explant in combination with BAP at 1.138 mg L−1 ensured the optimal values of the assessed responses; callus mass (225.03 mg), antioxidant activity (35.95%), total phenols (11.48 mg of GAE/g DE) and flavonoids (15.92 mg of RU/g DE) production.