Miracle-dz/UniFAR-FTUs huggingface dataset:
Broad and thematic remodeling of the surfaceome and glycoproteome on isogenic cells transformed with driving proliferative oncogenes

Significance The cell surface proteome (surfaceome) mediates interactions between the cell and the extracellular environment and is a major target for immunotherapy in cancer. Here, we compared how six neighboring proliferative oncogenes cause large and bidirectional change in expression of some 700 surface proteins. These large changes converge to common functional consequences that are reversed by small-molecule inhibition of the MAPK pathway. We further complemented the surfaceome analysis with bottom-up glycoproteomics enabled by activated ion electron transfer dissociation and found a dynamic regulation of the glycoproteome. This large-scale comparative study provides important insights for how oncogenes remodel isogenic cells in a cell autologous fashion and suggests opportunities for antibody drug discovery in cancer. The cell surface proteome, the surfaceome, is the interface for engaging the extracellular space in normal and cancer cells. Here we apply quantitative proteomics of N-linked glycoproteins to reveal how a collection of some 700 surface proteins is dramatically remodeled in an isogenic breast epithelial cell line stably expressing any of six of the most prominent proliferative oncogenes, including the receptor tyrosine kinases, EGFR and HER2, and downstream signaling partners such as KRAS, BRAF, MEK, and AKT. We find that each oncogene has somewhat different surfaceomes, but the functions of these proteins are harmonized by common biological themes including up-regulation of nutrient transporters, down-regulation of adhesion molecules and tumor suppressing phosphatases, and alteration in immune modulators. Addition of a potent MEK inhibitor that blocks MAPK signaling brings each oncogene-induced surfaceome back to a common state reflecting the strong dependence of the oncogene on the MAPK pathway to propagate signaling. Cell surface protein capture is mediated by covalent tagging of surface glycans, yet current methods do not afford sequencing of intact glycopeptides. Thus, we complement the surfaceome data with whole cell glycoproteomics enabled by a recently developed technique called activated ion electron transfer dissociation (AI-ETD). We found massive oncogene-induced changes to the glycoproteome and differential increases in complex hybrid glycans, especially for KRAS and HER2 oncogenes. Overall, these studies provide a broad systems-level view of how specific driver oncogenes remodel the surfaceome and the glycoproteome in a cell autologous fashion, and suggest possible surface targets, and combinations thereof, for drug and biomarker discovery.
Effects of Lonicera japonica extract on performance, blood biomarkers of inflammation and oxidative stress during perinatal period in dairy cows

Objective An experiment was conducted to evaluate the effects of Lonicera japonica extract (LJE) on milk production, rumen fermentation and blood biomarkers of energy metabolism, inflammation and oxidative stress during the perinatal period of Holstein dairy cows. Methods Eighteen Holstein dairy cows were used in a complete randomized design experiment with 3 dietary treatments and 6 cows per treatment. All cows received the same basal total mixed ration (TMR) including a prepartal diet (1.35 Mcal of net energy for lactation [NEL]/kg of dry matter [DM], 13.23% crude protein [CP]) from −60 d to calving and a postpartal diet (1.61 Mcal of NEL/kg of DM, 17.39% CP) from calving to 30 days in milk (DIM). The 3 dietary treatments were TMR supplemented with LJE at 0 (control), 1 and 2 g/kg DM, respectively. LJE was offered from 21 d before calving to 30 DIM. Dry matter intake (DMI) and milk production were measured daily after calving. Milk and rumen fluid samples were collected on 29 and 30 d after calving. On −10, 4, 14, and 30 d relative to calving, blood samples were collected to analyze the biomarkers of energy metabolism, inflammation and oxidative stress. Results Compared with control diet, LJE supplementation at 1 and 2 g/kg DM increased DMI, milk yield and reduced milk somatic cell count. LJE supplementation also decreased the concentrations of blood biomarkers of pro-inflammation (interleukin-1β [IL-1β], IL-6, and haptoglobin), energy metabolism (nonesterified fatty acid and β-hydroxybutyric acid) and oxidative stress (reactive oxygen metabolites), meanwhile increased the total antioxidant capacity and superoxide dismutase concentrations in blood. No differences were observed in rumen pH, volatile fatty acid, and ammonia-N (NH3-N) concentrations between LJE supplemented diets and the control diet. Conclusion Supplementation with 1 and 2 g LJE/kg DM could increase DMI, improve lactation performance, and enhance anti-inflammatory and antioxidant capacities of dairy cows during perinatal period.
A machine learning approach to scenario analysis and forecasting of mixed migration

The development of MM4SIGHT, a machine learning system that enables annual forecasts of mixed-migration flows, is presented. Mixed migration refers to cross-border movements of people that are motivated by a multiplicity of factors to move including refugees fleeing persecution and conflict, victims of trafficking, and people seeking better lives and opportunity. Such populations have a range of legal status, some of which are not reflected in official government statistics. The system combines institutional estimates of migration along with in-person monitoring surveys to establish a migration volume baseline. The surveys reveal clusters of migratory drivers of populations on the move. Given macrolevel indicators that reflect migratory drivers found in the surveys, we develop an ensemble model to determine the volume of migration between source and host country along with uncertainty bounds. Using more than 80 macroindicators, we present results from a case study of migratory flows from Ethiopia to six countries. Our evaluations show error rates for annual forecasts to be within a few thousand persons per year for most destinations.
Structuring Opportunity for Immigration Origin Children

Immigrant origin children are the fastest growing sector of public schools in many post-industrial countries. In this chapter we begin by reviewing key challenges that these students bring with them as they enter schools in their new lands. We draw on two studies to address how well schools are prepared to address the needs of recently arrived immigrant students. The first mixed-methods study followed 400 diverse re cently arrived students for 5 years as they transitioned to their new land considering school, family, and individual factors. The findings from that study illuminated the cumulative challenges these youth encounter as well as the ways in which their edu cational environments often fail to meet their socio-emotional and educational needs. As not all schools are created equal, the other study used a multiple case study design of 4 promising schools in New York and Sweden, delineating practices that served immigrant students well.
Rapid redistribution of agricultural land alters avian richness, abundance, and functional diversity

Abstract The conversion of natural, or seminatural, habitats to agricultural land and changes in agricultural land use are significant drivers of biodiversity loss. Within the context of land‐sharing versus land‐sparing debates, large‐scale commercial agriculture is known to be detrimental to biodiversity, but the effects of small‐scale subsistence farming on biodiversity are disputed. This poses a problem for sustainable land‐use management in the Global South, where approximately 30% of farmland is small‐scale. Following a rapid land redistribution program in Zimbabwe, we evaluated changes in avian biodiversity by examining richness, abundance, and functional diversity. Rapid land redistribution has, in the near term, resulted in increased avian abundance in newly farmed areas containing miombo woodland and open habitat. Conversion of seminatural ranched land to small‐scale farms had a negative impact on larger‐bodied birds, but species richness increased, and birds in some feeding guilds maintained or increased abundance. We found evidence that land‐use change caused a shift in the functional traits of the communities present. However, functional analyses may not have adequately reflected the trait filtering effect of land redistribution on large species. Whether newly farmed landscapes in Zimbabwe can deliver multiple benefits in terms of food production and habitat for biodiversity in the longer term is an open question. When managing agricultural land transitions, relying on taxonomic measures of diversity, or abundance‐weighted measures of function diversity, may obscure important information. If the value of smallholder‐farmed land for birds is to be maintained or improved, it will be essential to ensure that a wide array of habitat types is retained alongside efforts to reduce hunting and persecution of large bird species.
Evaluating the Performance of Malaria Genetics for Inferring Changes in Transmission Intensity Using Transmission Modeling

Advances in genetic sequencing and accompanying methodological approaches have resulted in pathogen genetics being used in the control of infectious diseases. To utilise these methodologies for malaria we first need to extend the methods to capture the complex interactions between parasites, human and vector hosts, and environment. Here we develop an individual-based transmission model to simulate malaria parasite genetics parameterised using estimated relationships between complexity of infection and age from 5 regions in Uganda and Kenya. We predict that cotransmission and superinfection contribute equally to within-host parasite genetic diversity at 11.5% PCR prevalence, above which superinfections dominate. Finally, we characterise the predictive power of six metrics of parasite genetics for detecting changes in transmission intensity, before grouping them in an ensemble statistical model. The best performing model successfully predicted malaria prevalence with mean absolute error of 0.055, suggesting genetic tools could be used for monitoring the impact of malaria interventions.
Coral bioerosion on the marginal reefs of northeastern Arabia

The maintenance of coral reef framework results from a balance between skeletal accretion and bioerosion, and this balance can be disrupted by environmental stress and disturbance. Coral reefs in northeastern Arabia exist in extreme environmental conditions and have experienced severe disturbances in recent years. This study assessed the intensity of macrobioerosion in two regionally common species, Platygyra daedalea and Cyphastrea microphthalma, at three sites within the southern Persian/Arabian Gulf and at one site in the Sea of Oman. On average, bioeroders removed 9.2±1.6% of the skeletal surface area in P. daedalea and 26.4±1.6% in C. microphthalma, with variation between species attributed to differences in colony morphology. Bioerosion intensity varied among sites in each species. Within the southern Arabian Gulf, both P. daedalea and C. microphthalma showed the highest bioerosion intensity at Delma, in the western region, compared with that of Saadiyat or Ras Ghanada to the east, with the elevated bioerosion at Delma consistent with a history of more extreme environmental conditions and bleaching-related disturbances. The highest bioerosion in P. daedalea occurred at Fujairah in the Sea of Oman, and this site was amongst the highest in C. microphthalma. Although this site is characterized by more benign environmental conditions, reefs in this area experienced mass coral mortality due to anoxia during a large-scale harmful algal bloom in 2008/9 and the high bioerosion in Fujairah likely represents a long-term signature of this disturbance. The intensity of macrobioerosion observed here is high compared with other regions, suggesting that that chronic exposure to long-term environmental stress and a history of disturbance may lead enhanced loss of reef framework.
Connecting genetic incompatibilities with natural selection on additive genetic variation during adaptive radiation

Evolutionary biologists have long sought to identify the links between micro and macroevolution to better understand how biodiversity is created. Despite this pursuit, it remains a challenge to understand how allele frequency changes correlate with the evolution of morphological diversity, and the build-up of reproductive isolation amongst taxa. To connect mechanisms of microevolution with patterns of diversification, we tested the adaptive importance of alleles underlying genetic incompatibilities, and the consequences for predicting evolutionary trajectories of multiple ecotypes of an Australian wildflower. Using a quantitative genetics crossing design, we produced an F4 generation Advanced Recombinant Form (ARF) between four contrasting ecotypes, which we phenotyped in the glasshouse (N=770) and transplanted into the four natural habitats (N=14,265 seeds), alongside the parental ecotypes. F2 hybrid breakdown was associated with the loss of extreme phenotypes and habitat-specific genetic variation in field performance. Genetic trade-offs existed among habitats, but only in axes describing smaller amounts of genetic variance for fitness. Habitats that showed stronger patterns of adaptive divergence for native versus foreign ecotypes, also showed lower genetic variance in fitness of the ARF. Integrating data from the field and glasshouse predicted patterns of selection on morphological traits in a similar direction to the parental ecotypes. Overall, our results provide strong empirical evidence linking ecotype specific alleles with phenotypic divergence, fitness trade-offs, rapid adaptation and the accumulation of genetic incompatibilities among recently derived ecotypes. Our data connects microevolutionary change with macroevolution through adaptive radiation, where selection for environment specific alleles creates rapid adaptive divergence leading to speciation.
The complete mitochondrial genome of Hemerobius simulans Walker (Neuroptera, Hemerobiidae)

Abstract The complete mitochondrial (mt) genome of Hemerobius simulans Walker (Neuroptera, Hemerobiidae) is reported in this work. The whole mt genome is 17,985 bp long and contains 37canonical genes and an A + T-rich region, which is the same with insect ancestral mt genome arrangement. All 13 PCGs used the typical ATN as initiation codons. The control region of H. simulans mt genome is 1,416 bp long and the base composition is 90.0% of A + T. The phylogenetic analysis revealed that Hemerobiidae was monophyletic and was the sister group to Chrysopidae.
The complete chloroplast genome of Cymbidium floribundum var. pumilum (Orchidaceae)

Abstract Cymbidium floribundum var. pumilum is an epiphytic orchid distributed in the southern China. It has a high ornamental value and always be used as a hybrid parent. In this study, we obtained a complete chloroplast genome of C. floribundum var. pumilum from BGISEQ-500 sequencing data. The total chloroplast genome was 155,291 bp in length, consisting of a large single copy region (LSC 84,415 bp), a small single copy region (SSC 17,484 bp), and two inverted repeat regions (IRA and IRB 26,696 bp). The complete chloroplast genome contains 139 genes, including 80 protein-coding genes, 38 transfer RNA (tRNA) genes, and 8 ribosomal RNA (rRNA) genes. In addition, the phylogenetic analysis indicates that C. floribundum var. pumilum was sister to section Geocymbidium, section Pachyrhizanthe and section Jensoa. The chloroplast genome will contribute to establish an effective conservation strategy for C. floribundum var. pumilum.
Plasmodial enzymes in metabolic pathways as therapeutic targets and contemporary strategies to discover new antimalarial drugs: a review

Malaria continues to pose imminent threat to the world population, as the mortality rate associated with this disease remains high. Current treatment relies on antimalarial drugs such as Artemisinin Combination Therapy (ACT) are still effective throughout the world except in some places, where ACT-resistance has been reported, thus necessitating novel approaches to develop new anti-malarial therapy. In the light of emerging translational research, several plasmodial targets, mostly proteins or enzymes located in the parasite’s unique organelles, have been extensively explored as potential candidates for the development of novel antimalarial drugs. By targeting the metabolic pathways in mitochondrion, apicoplast or cytoplasm of Plasmodium, the possibility to discover new drugs is tremendous, as they have potentials as antimalarial therapeutic targets. This literature review summarizes pertinent information on plasmodial targets, especially enzymes involved in specific metabolic pathways, and the strategies used to discover new antimalarial drugs.
An activity-guided map of electrophile-cysteine interactions in primary human immune cells

Electrophilic compounds originating from nature or chemical synthesis have profound effects on immune cells. These compounds are thought to act by cysteine modification to alter the functions of immune-relevant proteins; however, our understanding of electrophile-sensitive cysteines in the human immune proteome remains limited. Here, we present a global map of cysteines in primary human T cells that are susceptible to covalent modification by electrophilic small molecules. More than 3000 covalently liganded cysteines were found on functionally and structurally diverse proteins, including many that play fundamental roles in immunology. We further show that electrophilic compounds can impair T cell activation by distinct mechanisms involving direct functional perturbation and/or ligand-induced degradation of proteins. Our findings reveal a rich content of ligandable cysteines in human T cells, underscoring the potential of electrophilic small molecules as a fertile source for chemical probes and ultimately therapeutics that modulate immunological processes and their associated disorders.
Two new species of miniature psammophilic sarcoglanidine catfishes of the genus Microcambeva from the Atlantic Forest of eastern Brazil (Siluriformes: Trichomycteridae)

ABSTRACT Trichomycterid catfishes of the Sarcoglanidinae, which includes small-sized species living in sandy river substratum, have been poorly represented in collections. We herein describe two new species of the sarcoglanidine genus Microcambeva, endemic to river basins draining the Brazilian Atlantic Forest. The presence of a distal widening on the posterior process of the autopalatine and a rudimentary anterior autopalatine ossification shared by the two new species, M. mucuriensis sp. nov. from the Rio Mucuri and M. jucuensis sp. nov. from the Rio Jucu basin, and M. draco from the Rio Jucuruçu basin indicates that these three species are more closely related to each other than to other congeners. Microcambeva mucuriensis seems to be more closely related to M. draco than to M. jucuensis in that the first two species share the presence of a well-developed anterior process of the interopercle. The two new species are also distinguished from congeners by the number of opercular odontodes and premaxillary teeth, and the relative size of the sesamoid supraorbital. Available evidence taken from this study and previous reports indicates that different sarcoglanidine lineages have adapted to live in distinct riverine habitats, with species of Atlantic Forest Microcambeva inhabiting clearwater streams and Amazonian sarcoglanidines found in tea-stained acidic-water streams. http://www.zoobank.org/urn:lsid:zoobank.org:pub:8CFF9C88-1CEC-44AF-AD26-1D4A56F3D946
Dietary preferences and autecology of a basal Holarctic ground squirrel Spermophilinus (Rodentia: Sciuridae: Xerinae), inferred from dental microwear analysis

ABSTRACT Spermophilinus is a primitive marmotine ground squirrel from the early Miocene – early Pliocene of Eurasia. Despite the high abundance in small mammal communities, apparently indicating its important role in Neogene terrestrial ecosystems, an autecological study of this taxon based on direct methods has not yet been carried out. Herein, we report on a dental microwear analysis of S. bredai, the type species of the genus, based on the m3 specimens from the early late Miocene locality Grytsiv in western Ukraine. The results suggest that the diet of this ground squirrel has presumably consisted of hard fruit and seeds with no evidence of significant grass consumption or burrowing behaviour, thus suggesting feeding preferences most closely resembling those of the living tree squirrels of the genera Sciurus and Callosciurus. We also discuss the dental microwear of the extant ground and tree-dwelling Sciuridae in relation to their diet.
Targeted mental health in schools: outputs from a qualitative appraisal of the TaMHS Programme in Cumbria

In Cumbria, the year-long TaMHS project concluded at the end of March 2011 after formal work in schools had begun in September 2010, supported by a steering group including senior managers from Children’s Services and the NHS. Eighteen schools, in three clusters across the county itself, were supported. These clusters each included a secondary school and partner primary schools, plus one PRU. The appraisal is based on rigorous qualitative investigation of 30 semi-structured interviews, each between 20 and 30 minutes in length, using a purposive sample of participants composed of TaMHS leads at participating schools (n=13), involved members of staff at these schools (n=11) and mental health professionals seconded to TaMHS from Cumbrian mental health services (n=6). Thematic analysis of the collected evidence revealed eleven central issues, closely related to the priority concerns outlined by the commissioning body. Synthesis of the data revealed that the TaMHS project in Cumbria was, on the whole, very well received by professionals in education and mental health alike, and produced concrete positive impacts. Respondents involved in the appraisal identified many encouraging aspects. Only one of thirty respondents was broadly negative about the project, while the others reported a wide range of successes in a variety of structural, social and psychological domains, and tangible benefits for professional staff, students and students’ families.