Miracle-dz/UniFAR-FTUs huggingface dataset:
Apoptosis induced by exposure to a low steady-state concentration of H2O2 is a consequence of lysosomal rupture

We have re-examined the lysosomal hypothesis of oxidative-stress-induced apoptosis using a new technique for exposing cells in culture to a low steady-state concentration of H 2 O 2 . This steady-state technique mimics the situation in vivo better than the bolus-administration method. A key aspect of H 2 O 2 -induced apoptosis is that the apoptosis is evident only after several hours, although cells may become committed within a few minutes of exposure to this particular reactive oxygen species. In the present work, we were able to show, for the first time, several correlative links between the triggering effect of H 2 O 2 and the later onset of apoptosis: (i) a short (15min) exposure to H 2 O 2 caused almost immediate, albeit limited, lysosomal rupture; (ii) early lysosomal damage, and later apoptosis, showed a similar dose-related response to H 2 O 2 ; (iii) both events were inhibited by pre-treatment with iron chelators, including desferrioxamine. This compound is known to be taken up by endocytosis only and thus to become localized in the lysosomal compartment. After exposure to oxidative stress, when cells were again in standard culture conditions, a time-dependent continuous increase in lysosomal rupture was observed, resulting in a considerably lowered number of intact lysosomes in apoptotic cells, whereas non-apoptotic cells from the same batch of oxidative-stress-exposed cells showed mainly intact lysosomes. Taken together, our results reinforce earlier findings and strongly suggest that lysosomal rupture is an early upstream initiating event, and a consequence of intralysosomal iron-catalysed oxidative processes, when apoptosis is induced by oxidative stress.
Phlebotomine sandflies in Venezuela. V. Review of the genus Brumptomyia (Diptera: Psychodidae), with description of the female of Brumptomyia devenanzii, re-description of the male and isozymatic profile

Recently collected data on the Venezuelan species of the genus Brumptomyia are used to produce an updated review of these sandflies. At present, four species are recognized in Venezuela: B. devenanzii, B. beaupertuyi, B. avellari and B. pintoi. A key for the males is given and the geographical distribution of each of these species is outlined. The previously unknown female of B. devenanzii is described, the male is re-described, and the genetic variability (based on 11 enzymatic loci) of this species and of B. beaupertuyi (a sympatric species in Rancho Grande, the type locality of B. devenanzii) are reported. Fixed allelic differences in one diagnostic locus (adenylate kinase; Ak), between sympatric and allopatric populations, allowed for the unequivocal separation of both sexes of B. beaupertuyi from those of B. devenanzii. Significant inter-specific differences were also detected in the allele frequencies of malate dehydrogenase (Mdh-2) and decarboxylating malate dehydrogenase (Me). For B. devenanzii, mean heterozygosity and mean number of alleles per locus ranged from 2.0%–3.1% and 1.1–1.5, respectively. The corresponding values for B. beaupertuyi were 3.8% and 1.2.
Progress report on radiation dosimetry at NPL.

Many of the radiation dosimetry facilities at NPL moved into new purpose built laboratories during 2001. This involved the dismantling and re-installation of the 50 kV and 300 kV x-ray sets and the movement of three self-shielded Co irradiators. An extensive program of work was also necessary both before and after the move to demonstrate that the realisation of air kerma from the associated primary standards had not changed as a result of the relocation.
Evolutionary History, Selective Sweeps, and Deleterious Variation in the Dog

The dog is our oldest domesticate and has experienced a wide variety of demographic histories, including a bottleneck associated with domestication and individual bottlenecks associated with the formation of modern breeds. Admixture with gray wolves, and among dog breeds and populations, has also occurred throughout its history. Likewise, the intensity and focus of selection have varied, from an initial focus on traits enhancing cohabitation with humans, to more directed selection on specific phenotypic characteristics and behaviors. In this review, we summarize and synthesize genetic findings from genome-wide and complete genome studies that document the genomic consequences of demography and selection, including the effects on adaptive and deleterious variation. Consistent with the evolutionary history of the dog, signals of natural and artificial selection are evident in the dog genome. However, conclusions from studies of positive selection are fraught with the problem of false positives given that de.
BET inhibition increases βIII-tubulin expression and sensitizes metastatic breast cancer in the brain to vinorelbine

Combination of BET inhibitor and vinorelbine improves survival in preclinical models of brain metastases. BETting against brain metastases Brain metastases are a dreaded complication of many cancer types. Even for malignancies that are relatively treatable, such as breast cancer, brain metastases are difficult to reach and often are not susceptible to the same therapies as peripheral tumors. By comparing primary and metastatic breast cancers, Kanojia et al. identified differences in the expression of cytoskeletal protein βIII-tubulin, which was increased in tumors that metastasized to the brain and sensitized them to vinorelbine, a chemotherapy drug. Another drug type, called a BET inhibitor, promoted βIII-tubulin expression and further sensitized breast cancer metastases to vinorelbine in mouse models, demonstrating a promising therapeutic combination. Metastases from primary breast cancer result in poor survival. βIII-tubulin (TUBB3) has been established as a therapeutic target for breast cancer metastases specifically to the brain. In this study, we conducted a systematic analysis to determine the regulation of TUBB3 expression in breast cancer metastases to the brain and strategically target these metastases using vinorelbine (VRB), a drug approved by the U.S. Food and Drug Administration (FDA). We found that human epidermal growth factor receptor 2 (HER2) signaling regulates TUBB3 expression in both trastuzumab-sensitive and trastuzumab-resistant neoplastic cells. We further discovered that bromodomain and extra-terminal domain (BET) inhibition increases TUBB3 expression, rendering neoplastic cells more susceptible to apoptosis by VRB. Orthotopic xenograft assays using two different breast cancer cell models revealed a reduction in tumor volume with BET inhibition and VRB treatment. In addition, in vivo studies using a model of multiple brain metastasis (BM) showed improved survival with the combination of radiation + BET inhibitor (iBET-762) + VRB (75% long-term survivors, P < 0.05). Using in silico analysis and BET inhibition, we found that the transcription factor myeloid zinc finger-1 (MZF-1) protein binds to the TUBB3 promoter. BET inhibition decreases MZF-1 expression and subsequently increases TUBB3 expression. Overexpression of MZF-1 decreases TUBB3 expression and reduces BM in vivo, whereas its knockdown increases TUBB3 expression in breast cancer cells. In summary, this study demonstrates a regulatory mechanism of TUBB3 and provides support for an application of BET inhibition to sensitize breast cancer metastases to VRB-mediated therapy.
Shell Mass, Biomass, Condition, and Reproductive State of the Invasive Bivalve Mytilopsis leucophaeata (Conrad, 1831) (Dreissenidae)

ABSTRACT Basic information on shell dimensions, calcimass and periostracum mass, biomass, and the relation between the condition and reproduction of Mytilopsis leucophaeata was analyzed for a population in the North Sea Canal, the Netherlands. The mean dry flesh weight of individuals with a mean shell length of 12.5 mm showed a peak at the end of June. The mussel reached the highest mean dry flesh weight in the month before the spatfall started. The gonad index (GI) was high in June, followed by a period of decrease until September and a period of increase until November. The condition index (CI) peaked in June and decreased during the remainder part of the year. The range of CI was highest in May when the gonadal development progressed and was smallest in June when the gonadal development was complete. The CI decreased during the rest of the year. Quantile regressions showed a highly significant relation between CI and shell length. Based on the regression coefficients, the CI was maximal at a shell length of 11.4 mm and minimal at 12.5 mm. Condition index variation was highest within a shell length range of 10–15 mm.
A Data Cleansing System for Musical Expression Analysis

A new data cleansing system for musical expression analysis is introduced. In order to analyze musical expression and to create musical rendition models, it is necessary to develop this new system since the database used in this study is no longer available and it is impossible to collect any more data without the new system. Inputs of this system are actual musical performance data of classic piano music in WAV format, and additionally musical information, i.e. chords, musical symbols, etc., obtained from analysis of the corresponding music score. The harmonic tension values and melodic attraction values are also used as inputs, which are obtained from the prolongational reduction tree expressing the cognitional and hierarchical tension-relaxation structure obtained from the score. From the WAV data, the system extracts physical onset times and calculates local tempos as its musical expression. Using multiple regression analysis, music expression of each performance is analyzed and some interesting features are obtained, that are useful to create musical rendition models.
To Remember or to Forget: The Role of Good and Bad Memories in Adoptive T Cell Therapy for Tumors

The generation of immunological memory is a hallmark of adaptive immunity by which the immune system “remembers” a previous encounter with an antigen expressed by pathogens, tumors, or normal tissues; and, upon secondary encounters, mounts faster and more effective recall responses. The establishment of T cell memory is influenced by both cell-intrinsic and cell-extrinsic factors, including genetic, epigenetic and environmental triggers. Our current knowledge of the mechanisms involved in memory T cell differentiation has instructed new opportunities to engineer T cells with enhanced anti-tumor activity. The development of adoptive T cell therapy has emerged as a powerful approach to cure a subset of patients with advanced cancers. Efficacy of this approach often requires long-term persistence of transferred T cell products, which can vary according to their origin and manufacturing conditions. Host preconditioning and post-transfer supporting strategies have shown to promote their engraftment and survival by limiting the competition with a hostile tumor microenvironment and between pre-existing immune cell subsets. Although in the general view pre-existing memory can confer a selective advantage to adoptive T cell therapy, here we propose that also “bad memories”—in the form of antigen-experienced T cell subsets—co-evolve with consequences on newly transferred lymphocytes. In this review, we will first provide an overview of selected features of memory T cell subsets and, then, discuss their putative implications for adoptive T cell therapy.
Effects of Autonomous Sensory Meridian Response on the Functional Connectivity as Measured by Functional Magnetic Resonance Imaging

Autonomous sensory meridian response (ASMR) is a sensory phenomenon in which audio-visual stimuli evoke a tingling sensation and is accompanied by a feeling of calm and relaxation. Therefore, there has been an increasing interest in using stimuli that elicit ASMR in cognitive and clinical neuroscience studies. However, neurophysiological basis of sensory-emotional experiences evoked by ASMR remain largely unexplored. In this study, we investigated how functional connectivity is changed while watching ASMR video, compared to resting state, and assessed its potential association with affective state induced by ASMR. 28 subjects participated in fMRI experiment consisting of 2 sessions (resting-state and task of viewing ASMR-eliciting video). Using a seed-based correlation analysis, we found that functional connections between the posterior cingulate cortex, and superior/middle temporal gyri, cuneus, and lingual gyrus were significantly increased during ASMR compared to resting state. In addition, we found that with the pregenual anterior cingulate cortex seed region, functional connectivity of the medial prefrontal cortex was increased during ASMR condition, relative to resting state. These results imply that ASMR can be elicited and maintained by ongoing interaction between regional activity that are mainly involved in the mentalizing and self-referential processing. We also found that ASMR-induced affective state changes (high activation negative and high activation positive state) were negatively correlated with functional connectivity involved in visual information processing, suggesting that visual information processing in response to high arousal states can be weakened by ASMR-eliciting stimuli.
Breeding performance in the western gull : effects of parental age, timing of breeding and year in relation to food availability

(1) We studied age-specific breeding success of western gulls (Larus occidentalis) on south-east Farallon Island, California in relation to annual variation in food abundance, 1983-89. We assessed yearly reproductive performance on the basis of clutch initiation date, clutch size, hatching and fledging success, and the number of chicks raised to independence. We categorized age of parent into three groups: young, middle-aged and old. (2) Mature birds initiated breeding earlier and laid larger clutches; they fledged more chicks than younger birds as a result of hatching a greater proportion of their eggs and fledging a greater proportion of their hatched chicks. The oldest birds generally did not differ from middle-aged in breeding performance. The difference in reproductive performance between young and mature birds was most apparent during years when food availability was reduced. (3) Timing of breeding influenced reproductive performance independently of parental age; reproductive performance decreased throughout the breeding season. Within-season reductions in reproductive performance were most apparent for young breeders and individuals with small clutches or broods. (4) Breeding performance varied significantly among years independently of age of the study animals. Food availability accounted for part of the yearly variation in breeding success. (5) We suggest that clutch/brood size reflects individual quality. Age-specific breeding success in western gulls is best explained by previous breeding experience and individual quality.
Auditory function at 14 years of age of very‐low‐birthweight children

The aim of the study was to determine audiological function at 14 years of age of very‐low‐birthweight (VLBW 1500g) children compared with a cohort of normal birthweight (NBW >2499g) children. Participants were consecutive surviving preterm children of birthweight <1000 g born between 1977 and 1982 (n=86) and of birthweight 1000 to 1500g born between 1980 and 1982 (n=124) and randomly selected NBW children born between 1981 and 1982 (n=60). Audiometric tests included pure tone audiometry, tympanometry, stapedius muscle reflexes, and measures of central auditory processing. Psychometric tests included measures of IQ, academic achievement, and behaviour. There were no significant differences in rates of hearing impairment, abnormal tympanograms, figure‐ground problems, or digit recall between VLBW children and NBW control children. VLBW children had higher rates of some central auditory processing problems, which in turn were associated with poorer intellectual, academic, and behavioural progress.
Sequestration of Voriconazole and Vancomycin Into Contemporary Extracorporeal Membrane Oxygenation Circuits: An in vitro Study

Background: Bacterial and fungal infections are common and often contribute to death in patients undergoing extracorporeal membrane oxygenation (ECMO). Drug disposition is altered during ECMO, and adsorption in the circuit is an established causative factor. Vancomycin and voriconazole are widely used, despite the lack of evidence-based prescription guidelines. Objective: The objective of this study was to determine the extraction of voriconazole and vancomycin by the Xenios/Novalung ECMO circuits. Methods: We have set up nine closed-loop ECMO circuits, consisting of four different iLAActivve® kits for neonatal, pediatric, and adult support: three iLA-ActivveMiniLung® petite kits, two iLA-ActivveMiniLung® kits, two iLA-ActivveiLA® kits, and two iLA-Activve X-lung® kits. The circuits were primed with whole blood and maintained at physiologic conditions for 24 h. Voriconazole and vancomycin were injected as a single-bolus age-related dose into the circuits. Pre-membrane (P2) blood samples were obtained at baseline and after drug injection at 2, 10, 30, 180, 360 min, and 24 h. A control sample at 2 min was collected for spontaneous drug degradation testing at 24 h. Results: Seventy-two samples were analyzed in triplicate. The mean percentage of drug recovery at 24 h was 20% for voriconazole and 62% for vancomycin. Conclusions: The extraction of voriconazole and vancomycin by contemporary ECMO circuits is clinically relevant across all age-related circuit sizes and may result in reduced drug exposure in vivo.
Biochar Administration to San Marzano Tomato Plants Cultivated Under Low-Input Farming Increases Growth, Fruit Yield, and Affects Gene Expression

Biochar is a rich-carbon charcoal obtained by pyrolysis of biomasses, which was used since antiquity as soil amendant. Its storage in soils was demonstrated contributing to abate the effects of climate changes by sequestering carbon, also providing bioenergy, and improving soil characteristics and crop yields. Despite interest in this amendant, there is still poor information on its effects on soil fertility and plant growth. Considerable variation in the plant response has been reported, depending on biomass source, pyrolysis conditions, crop species, and cultivation practices. Due to these conflicting evidences, this work was aimed at studying the effects of biochar from pyrolyzed wood at 550°C, containing 81.1% carbon and 0.91% nitrogen, on growth and yield of tomato plants experiencing low-input farming conditions. San Marzano ecotype from Southern Italy was investigated, due to its renowned quality and adaptability to sustainable farming practices. Biochar administration improved vegetative growth and berry yield, while affecting gene expression and protein repertoire in berries. Different enzymes of carbon metabolism and photosynthesis were over-represented, whereas various stress-responsive and defense proteins were down-represented. Molecular results are here discussed in relation to estimated agronomic parameters to provide a rationale justifying the growth-promoting effect of this soil amendant.
Fostering Innovation in the Treatment of Chronic Polymicrobial Cystic Fibrosis-Associated Infections Exploring Aspartic Acid and Succinic Acid as Ciprofloxacin Adjuvants

Cystic fibrosis (CF) disease provokes the accumulation of thick and viscous sputum in the lungs, favoring the development of chronic and polymicrobial infections. Pseudomonas aeruginosa is the main bacterium responsible for these chronic infections, and much of the difficulty involved in eradicating it is due to biofilm formation. However, this could be mitigated using adjuvant compounds that help or potentiate the antibiotic action. Therefore, the main goal of this study was to search for substances that function as adjuvants and also as biofilm-controlling compounds, preventing or dismantling P. aeruginosa biofilms formed in an in vitro CF airway environment. Dual combinations of compounds with subinhibitory (1 and 2 mg/L) and inhibitory concentrations (4 mg/L) of ciprofloxacin were tested to inhibit the bacterial growth and biofilm formation (prophylactic approach) and to eradicate 24-h-old P. aeruginosa populations, including planktonic cells and biofilms (treatment approach). Our results revealed that aspartic acid (Asp) and succinic acid (Suc) restored ciprofloxacin action against P. aeruginosa. Suc combined with 2 mg/L of ciprofloxacin (Suc-Cip) was able to eradicate bacteria, and Asp combined with 4 mg/L of ciprofloxacin (Asp–Cip) seemed to eradicate the whole 24-h-old populations, including planktonic cells and biofilms. Based on biomass depletion data, we noted that Asp induced cell death and Suc seemed somehow to block or reduce the expression of ciprofloxacin resistance. As far as we know, this kind of action had not been reported up till now. The presence of Staphylococcus aureus and Burkholderia cenocepacia did not affect the efficacy of the Asp–Cip and Suc–Cip therapies against P. aeruginosa and, also important, P. aeruginosa depletion from polymicrobial communities did not create a window of opportunity for these species to thrive. Rather the contrary, Asp and Suc also improved ciprofloxacin action against B. cenocepacia. Further studies on the cytotoxicity using lung epithelial cells indicated toxicity of Suc–Cip caused by the Suc. In conclusion, we provided evidences that Asp and Suc could be potential ciprofloxacin adjuvants to eradicate P. aeruginosa living within polymicrobial communities. Asp–Cip and Suc–Cip could be promising therapeutic options to cope with CF treatment failures.
Regular ArticleThe evolution of pelvic osteology and soft tissues on the line to extant birds (Neornithes)

Substantial differences in pelvic osteology and soft tissues separate crown group crocodylians (Crocodylia) and birds (Neornithes). A phylogenetic perspective including fossils reveals that these disparities arose in a stepwise pattern along the line to extant birds, with major changes occurring both within and outside Aves. Some character states that preceded the origin of Neornithes are only observable or inferable in extinct taxa. These transitional states are important for recognizing the derived traits of neornithines. Palaeontological and neontological data are vital for reconstructing the sequence of pelvic changes along the line to Neornithes. Soft tissue correlation with osteological structures allows changes in soft tissue anatomy to be traced along a phylogenetic framework, and adds anatomical significance to systematic characters from osteology. Explicitly addressing homologies of bone surfaces reveals many subtleties in pelvic evolution that were previously unrecognized or implicit. I advocate that many anatomical features often treated as independent characters should be interpreted as different character states of the same character. Relatively few pelvic character states are unique to Neornithes. Indeed, many features evolved quite early along the line to Neornithes, blurring the distinction between «avian» and «non-avian» anatomy.