Miracle-dz/UniFAR-FTUs huggingface dataset:
The Braak hypothesis in prion disease with a focus on Creutzfeldt–Jakob disease

This review considers whether the Braak hypothesis on protein propagation could account for prion disease, particularly Creutzfeldt–Jakob disease (CJD). In CJD, we can speculate on the pathological onset region to some degree in reference to the clinical symptoms and magnetic resonance imaging findings. Although relating the Braak hypothesis to prion disease is not straightforward, the following could be proposed based on experimental and previously reported case observations. Pathogenic abnormal prion protein (PrP) deposition in the central nervous system (CNS) probably begins several months or years before clinical symptom onset, signifying the potentiality of a preclinical stage, similar to α‐synuclein deposition in Parkinson's disease (PD) and amyloid‐β/tau deposition in Alzheimer's disease (AD). Unlike in PD and AD, the initial clinical symptoms of CJD vary by case, and thus the onset lesions must also be various and multiple in the CNS. Based on the pathological findings, particularly of PrP deposition extensively observed in the CNS gray matter of autopsy cases, it could be speculated that in the early disease stage, including the preclinical stage, abnormal PrP spreads from the onset region without directionality or hierarchy. Because each CNS region shows either vulnerability to or resistance against PrP deposition and pathological progression in prion disease, the lesion distribution shows system degeneration. Although pathologically combined cases of type 1 and type 2 PrP patterns are often recognized, type 1 and type 2 PrP patterns must never shift toward each other during the disease course; in other words, the original type of PrP deposition in each region presumably remains unchanged in each case. According to the several observations and corresponding speculations, there are at least partial similarities between prion disease and protein propagation, as explained by the Braak hypothesis, in terms of pathological lesion progression, but several noted contradictions preclude the hypothesis from comprehensively accounting for prion disease.
Purification and Characterization of endo‐ and exo‐lnulinase 1

A crude inulinase preparation, from Aspergillus, was fractioned in a sequence of operations, including ion exchange chromatography on CM‐Sepharose and high‐performance gel permeation chromatography. Two highly purified inulin‐degrading enzymes were thus obtained and some of their characteristics were established. The first enzyme had an endo‐type activity, a Mr of 53,000, and Km = 570 mm (in terms of glycosidic bonds). The second was of the exo‐type, and has a Mr of 81,000 and Km = 60 mm (in terms of inulin chains). The two enzymes are highly activated (up to 20‐fold) by Fe3+ and partially inhibited by Mn2+ and Mg2+. Both enzymes also exhibit invertase activity.
Light and electron microscope observations of a vacuolar structure associated with the floral apex of Nigella damascena

Both light and electron microscope observations were recorded of a vacuolar structure which is associated with the onset of flowering in Nigella damascena. This structure has been observed in both chemically fixed and fresh-frozen sections. It is a spherical, occasionally lobed, rough-surfaced structure found in both dividing and non-dividing cells of the corpus and pith – rib meristem of the prefloral and floral apex. Less frequently these structures were located in the cells of the floral organs and occasionally at the tips of young bracts and leaves. The slight differential staining response of these structures suggests some internal differentiation and this is supported by electron micrographs. At least three regions of differing electron density can be recognized. While small pieces of unit membrane can be found attached to the outer surface, this structure is not membrane bound. We suggest that this vacuolar structure represents an accumulation, in the cells of the floral apex, of some synthetic pro.
Néoformation de boutons floraux sur culture in vitro de feuilles et de racines de Cichorium intybus L.—Existence d'un état vernalisé en l'absence de bourgeons

SummaryFlower buds can be produced on tissues excised from the veins of leaves and the central core of roots of Cichorium intybus L. cultivar « Witloof », provided the plants have been vernalized beforehand. The flower buds were obtained in sterile culture on media devoid of added auxin, but containing coumarin (1 mg/1), the cultures being kept under long days. Uridylic acid (2 × 10−5)M did not cause flower-bud formation on unvernalized tissues. Experiments done in the Phytotron showed that most of the chicory plants are vernalized after 5 weeks at 5°C with 9-hour days of about 2,000 ft.c. light intensity. There is a physiological variability among plants grown from seed, as far as vernalization requirements are concerned. The formation of flower buds, produced adventitiously on tissues after the cold treatment demonstrates that, in order to become vernalized, a bud does not necessarily have to be subjected itself to low temperatures or to derive from a vernalized bud. Rather, it points out to the existen.
Ventilation and dive patterns of humpback whales, Megaptera novaeangliae, on their Alaskan feeding grounds

Noncalf humpback whales in Frederick Sound, Alaska, were tracked for periods of up to 12.5 h during July through September 1982, 1983, and 1984. Ventilation and dive patterns in presumably undisturbed humpback whales were characterized for six behaviors. Humpbacks appeared to restrict their dives to 150 m and rarely exceeded depths of 120 m, as determined by echo sounder tracings. Duration of dives and surfacings, number of blows per surfacing, and mean blow interval were positively correlated with the depth to which whales dived. Ventilation and dive variable values were significantly elevated in 1983 relative to 1982 and 1984. This was likely due to an increase in the depth of available prey during the 1983 season. The depth to which a feeding whale dove could be related to the depth of the target prey patch with greater than 84% accuracy based upon ventilation and dive variables.
The effect of type of concentrate and level of concentrate feeding on milk production

Twenty-four British Friesian dairy cows in early lactation were used in a change-over design experiment with three periods, each of 4 weeks duration. The aim of the experiment was to assess the effects of both the type of concentrate and the level of concentrate supplementation on the utilization of grass silage for milk production. Four treatments consisted of offering 10 kg/day of either a barley (10B) or a sugar beet pulp-based concentrate (10S), each concentrate being offered at two crude protein concentrations of 175 (low) and 245 (high) g/kg dry matter. In a further two treatments the barley-based concentrates containing the low and high protein concentrations were offered at 7 kg/day (7B). All concentrates were offered in addition to the cows having ad libitum access to grass silage containing a dry-matter concentration of 213 g/kg and a digestible organic matter concentration of 668 g/kg dry matter. Silage dry-matter intakes (kg/day) for cows given the low- and high-protein concentrates respectively were: 9·06 and 9·28 for the 7B treatments; 8·21 and 8·33 for the 10B treatments; and 8·04 and 7·97 for the 10S treatments (pooled s.e. 0·11). Fat-corrected milk yields for cows given the low- and high-protein concentrates respectively were: 24·0 and 24·1 for the 7B treatments; 25·9 and 27·0 for the 10B treatments; and 25·7 and 26·2 for the 10S treatments (pooled s.e. 0·57). The higher level of concentrate feeding significantly increased milk yield ( P P > 0·05). There was a trend towards a greater response to increased protein concentration at the higher level of feeding.
Effects of military training on plasma amino acid concentrations and their associations with overreaching

Amino acids are thought to have a key role in the processes contributing to overreaching development through their metabolic properties and neuronal functions. In the present study, the effects of 10-week military training on the concentrations of 19 amino acids were investigated. Plasma amino acid concentrations were measured at rest from 53 healthy male conscripts on weeks 1, 4, 7, and 9 of their military service. Conscripts were classified as overreached and non-overreached. Overreaching classification was based on fulfilling at least three of five criteria: greater than 5% decrease in maximal oxygen uptake, increased rating perceived exertion (RPE), and decreased lactate-RPE ratio in submaximal marching test, admitting feeling overloaded and both increased scores in fatigue and decreased scores in vigor in the Profile of Mood States Adolescents. Eight conscripts (15%) were classified as overreached; their glutamine–glutamate ratio and alanine and arginine levels were significantly lower (P < 0.05) and glutamate concentration significantly higher (P < 0.05) in comparison to their non-overreached counterparts. The levels of arginine increased (P < 0.05) and tryptophan (P < 0.001) decreased in both groups throughout the study. The tyrosine concentration increased in non-overreached but, in contrast, remained at the same level in overreached individuals (P < 0.05). The results suggest that alterations in the levels of three metabolically important amino acids, alanine, glutamate and arginine, and the possibly neuroactive tyrosine and tryptophan might explain some of the physical and psychological symptoms of overreaching. The present study also confirms the potential use of glutamine–glutamate ratio as a tool for detecting overreaching. Impact statement The diagnosis of overtraining syndrome and overreaching poses a great challenge. Military training aims at improving the physical performance of the conscripts, but an excessive training load could also lead to overreaching. This study of Finnish conscripts provides new insights into the pathophysiology of overreaching and overtraining through amino acids concentrations. In addition to confirming the possible use of plasma glutamine/glutamate concentration to indicate and predict overreaching, we made a novel finding, i.e. low alanine and arginine concentrations might have a role in performance decrement and fatigue related to overreaching. Moreover, this study is the first to show the possible association between amino acids with putative neuronal properties and overreaching. Thus, the present findings might help to detect and prevent overreaching and offer a reliable diagnostic approach. In order to avoid overreaching, military training should be planned more periodically and individually, especially during the first four weeks of military service.
A transdiagnostic perspective of constructs underlying obsessive-compulsive and related disorders: An international Delphi consensus study

Background: The Research Domain Criteria seeks to bridge knowledge from neuroscience with clinical practice by promoting research into valid neurocognitive phenotypes and dimensions, irrespective of symptoms and diagnoses as currently conceptualized. While the Research Domain Criteria offers a vision of future research and practice, its 39 functional constructs need refinement to better target new phenotyping efforts. This study aimed to determine which Research Domain Criteria constructs are most relevant to understanding obsessive-compulsive and related disorders, based on a consensus between experts in the field of obsessive-compulsive and related disorders. Methods: Based on a modified Delphi method, 46 experts were recruited from Australia, Africa, Asia, Europe and the Americas. Over three rounds, experts had the opportunity to review their opinion in light of feedback from the previous round, which included how their response compared to other experts and a summary of comments given. Results: Thirty-four experts completed round one, of whom 28 (82%) completed round two and 24 (71%) completed round three. At the final round, four constructs were endorsed by ⩾75% of experts as ‘primary constructs’ and therefore central to understanding obsessive-compulsive and related disorders. Of these constructs, one came from the Positive Valence System (Habit), two from the Cognitive Control System (Response Selection/Inhibition and Performance Monitoring) and the final construct was an additional item suggested by experts (Compulsivity). Conclusion: This study identified four Research Domain Criteria constructs that, according to experts, cut across different obsessive-compulsive and related disorders. These constructs represent key areas for future investigation, and may have potential implications for clinical practice in terms of diagnostic processes and therapeutic management of obsessive-compulsive and related disorders.
Competitive Coexistence in a Seasonally Fluctuating Environment II. Multiple Stable States and Invasion Success

Abstract Effects of seasonal environmental variation on coexistence of two competing species are investigated using the Lotka-Volterra competition system with periodically varying coefficients. In a symmetric case, there may appear triple stable periodic solutions and either coexistence or competitive exclusion can result depending on the initial abundances. It is also revealed that the timing of an invasion influences the outcome. In an asymmetric case in which the intrinsic growth rates and the competition coefficients of the two species are out of phase, a pair of stable coexistent periodic solutions are found. In each of four qualitatively different cases in the classical Lotka-Volterra system, an alternative possibility appears in a seasonal environment. Therefore, invasibility or stability of a boundary solution is insufficient to forecast the outcome of competition, and coexistence may be possible even when an invasion by a small number of individuals ends in failure.
Cephalic Homologies. A Contribution to the Determination of the Ancestry of Vertebrates

That Amphioxus has affinities both with Tunicates and with Vertebrates is, with our present knowledge, quite clear; but the relative degree of affinity on the two sides has not been settled. Amphioxus was originally classed with the fishes, but is now universally separated from them. Perhaps the most usual opinion is, that which clashes Amphioxus with the Vertebrata, and divides the Vertebrata into two groups: I. CEPHALOCHORDA, (Amphioxus). II. VERTEBRATA PROPER, (Oraniota). This division recognizes the fact that Amphioxus differs fundamentally from all the true vertebrates, but holds that the concept " Vertebrata " must be greatly extended and essentially modified, so as to admit the lancelet. The first writer known to me to deny that the Branchiostoma could be classed as a vertebrate was Carl Semper in 1875. This position has
Hemodynamic principles of prosthetic aortic valve evaluation in the transcatheter aortic valve replacement era

Evaluating the hemodynamic performance of aortic valve prostheses has relied primarily on echocardiography. This involves calculating the trans‐prosthetic valve mean gradient (MG) and aortic valve area (AVA), and assessing for valvular and paravalvular regurgitation in a fashion similar to the native aortic valve. In conjunction with other echocardiographic and nonechocardiographic parameters, MG and AVA are used to distinguish between prosthesis stenosis, prosthesis patient mismatch, pressure recovery, increased flow, and measurement errors. This review will discuss the principles and limitations of echocardiographic evaluation of aortic valve prosthesis following surgical, and transcatheter aortic valve replacement and in comparison to invasive hemodynamics through illustrative clinical cases.
Location detection of key areas in medical images based on Haar-like fusion contour feature learning

BACKGROUND: Key area location is an important content of medical image processing and an important detail of auxiliary medical diagnosis. OBJECTIVE: In this paper, a prior knowledge fusion method based on Haar-like feature and contour feature is proposed to locate and detect key areas in medical images. METHOD: For the image to be processed, six Haar-like features and five contour features are extracted respectively. The improvement of Haar-like feature extraction template better adapts to the complexity of regional structure of medical images. The design of the contour feature extraction process fully reflects the consideration of feature invariance. The two features, together with prior knowledge, are fed into their respective decision makers and final fusers as the basis for determining and locating key regions. RESULTS: The experimental results show that the proposed method has excellent performance in locating key regions of medical images on MRI. When the capacity of the database increases from 10 to 200, the accuracy of locating the key areas of the image to be processed still reaches more than 90%. CONCLUSION: The proposed method realizes the accurate location of the key areas of medical images, which is of great significance for the auxiliary medical diagnosis.
Signaling from G Protein-coupled Receptors to c-Jun Kinase Involves Subunits of Heterotrimeric G Proteins Acting on a Ras and Rac1-dependent Pathway (*)

Stimulation of a variety of cell surface receptors enhances the enzymatic activity of mitogen-activated protein kinases (MAPKs). MAPKs have been classified in three subfamilies: extracellular signal-regulated kinases (ERKs), stress-activated protein kinases or c-Jun NH-terminal kinases (SAPKs/JNKs), and p38 kinase. Whereas the pathway linking cell surface receptors to ERKs has been partially elucidated, the mechanism of activation of JNKs is still poorly understood. Recently, we have shown that stimulation of G protein-coupled receptors can effectively induce JNK in NIH 3T3 cells (Coso, O. A., Chiariello, M., Kalinec, G., Kyriakis, J. M., Woodgett, J., and Gutkind, J. S.(1995) J. Biol. Chem. 270, 5620-5624). In the present study, we have used the transient expression in COS-7 cells of m1 and m2 muscarinic receptors (mAChRs) as a model system to study the signaling pathway linking G protein-coupled receptors to JNK. We show that stimulation of either muscarinic receptor subtype leads to JNK activation; however, this effect was not mimicked by expression of activated forms of α, α, α, or α G protein α subunits. In contrast, overexpression of Gβ subunits potently induced JNK activity. Furthermore, we show that signaling from m1 and m2 mAChRs to JNK involves β subunits of heterotrimeric G proteins, acting on a Ras and Rac1-dependent pathway.
COYOTE PREDATION AND HABITAT SEGREGATION OF WHITE-TAILED DEER AND MULE DEER

Predation has been proposed as a major factor maintaining segregation among species of ungulates, but predator–prey interactions have not been observed to test this idea directly. Here, observations of coyote (Canis latrans) packs hunting deer are used to show that mule deer (Odocoileus hemionus), which typically stand high on slopes and on rugged terrain, increased both their risk of being encountered and attacked by coyotes by standing low rather than high on slopes. The risk incurred at certain heights was not fixed: a mule deer's risk of being approached by coyotes was also affected by the height of other mule deer groups present during the same hunt. White-tailed deer (O. virginianus), which typically use gentle terrain, were not similarly disadvantaged by remaining low on slopes or on flat terrain. When confronted by coyotes, mule deer moved to and up slopes, whereas white-tails moved down and away from slopes. Species differences in behavior were independent of starting position and were observed f.
Bone Morphogenetic Protein-9 Is a Potent Chondrogenic and Morphogenic Factor for Articular Cartilage Chondroprogenitors

Articular cartilage contains a subpopulation of tissue-specific progenitors that are an ideal cell type for cell therapies and generating neocartilage for tissue engineering applications. However, it is unclear whether the standard chondrogenic medium using transforming growth factor beta (TGFβ) isoforms is optimal to differentiate these cells. We therefore used pellet culture to screen progenitors from immature bovine articular cartilage with a number of chondrogenic factors and discovered that bone morphogenetic protein-9 (BMP9) precociously induces their differentiation. This difference was apparent with toluidine blue staining and confirmed by biochemical and transcriptional analyses with BMP9-treated progenitors exhibiting 11-fold and 5-fold greater aggrecan and collagen type II (COL2A1) gene expression than TGFβ1-treated progenitors. Quantitative gene expression analysis over 14 days highlighted the rapid and phased nature of BMP9-induced chondrogenesis with sequential activation of aggrecan then collagen type II, and negligible collagen type X gene expression. The extracellular matrix of TGFβ1-treated progenitors analyzed using atomic force microscopy was fibrillar and stiff whist BMP9-induced matrix of cells more compliant and correspondingly less fibrillar. Polarized light microscopy revealed an annular pattern of collagen fibril deposition typified by TGFβ1-treated pellets, whereas BMP9-treated pellets displayed a birefringence pattern that was more anisotropic. Remarkably, differentiated immature chondrocytes incubated as high-density cultures in vitro with BMP9 generated a pronounced anisotropic organization of collagen fibrils indistinguishable from mature adult articular cartilage, with cells in deeper zones arranged in columnar manner. This contrasted with cells grown with TGFβ1, where a concentric pattern of collagen fibrils was visualized within tissue pellets. In summary, BMP9 is a potent chondrogenic factor for articular cartilage progenitors and is also capable of inducing morphogenesis of adult-like cartilage, a highly desirable attribute for in vitro tissue-engineered cartilage.
Harmonizing antibiotic regimens with renal replacement therapy

ABSTRACT Introduction: Critically ill patients with acute kidney injury often require renal replacement therapy and antibiotic therapy. Mortality rates are high in these patients, possibly due to ineffective dosing due to altered pharmacokinetic profiles and drug removal by renal replacement therapy. Areas covered: The main types of renal replacement therapies are intermittent hemodialysis, prolonged intermittent renal replacement therapy and continuous renal replacement therapy. Each of these renal replacement therapies may have drastic, yet different, effects on antibiotic serum concentration profiles. Moreover, three antibiotic administration strategies are often used: (1) standard infusion; (2) extended infusion; and (3) continuous infusion. A literature review was conducted on Medline in December 2019 to identify pertinent research. Expert opinion: Renal replacement therapies used in the treatment of acute kidney injury in critically ill patients usually complicates antibiotic use. Although antibiotic toxicity can be seen, most studies find that these patients do not receive sufficient antibiotic doses to achieve desired pharmacodynamic targets. Clinicians should dose antibiotics to match renal replacement therapy drug clearance characteristics to antibiotic pharmacodynamic profiles.