Using a simple, environment friendly proteome extraction (TOP), we were able to optimize the analysis of clinical samples. Using our TOP method we analyzed a clinical cohort of microsatellite stable (MSS) and unstable (MSI-H) colorectal carcinoma (CRC). We identified a tumor cell specific, STAT1-centered, immune signature expressed by the MSI-H tumor cells. We then showed that long, but not short, exposure to Interferon- induces a similar signature in vitro. We identified 10 different temporal protein expression patterns, classifying the Interferon- protein temporal regulation in CRC. Our data sheds light on the changes that tumor cells undergo under long-term immunological pressure in vivo, the importance of STAT proteins in specific biological scenarios. The data generated could help find novel clinical biomarkers and therapeutic approaches.

The Discoidin, CUB, and LCCL domain-containing protein (DCBLD) family consists of two type-I transmembrane scaffolding receptors, DCBLD1 and DCBLD2, which play important roles in development and cancer. The nonreceptor tyrosine kinases FYN and ABL are known to drive phosphorylation of tyrosine residues in YXXP motifs within the intracellular domains of DCBLD family members, which leads to the recruitment of the Src homology 2 (SH2) domain of the adaptors CT10 regulator of kinase (CRK) and CRK-like (CRKL). We previously characterized the FYN- and ABL-driven phosphorylation of DCBLD family YXXP motifs. However, we have identified additional FYN- and ABL-dependent phosphorylation sites on DCBLD1 and DCBLD2. This suggests that beyond CRK and CRKL, additional DCBLD interactors may be regulated by FYN and ABL activity. Here, we report a quantitative proteomics approach in which we map the FYN- and ABL-regulated interactomes of DCBLD family members. We found FYN and ABL regulated the binding of several signaling molecules to DCBLD1 and DCBLD2, including members of the 14-3-3 family of adaptors. Biochemical investigation of the DCBLD2/14-3-3 interaction revealed ABL-induced binding of 14-3-3 family members directly to DCBLD2.

Co-fractionation MS (CF-MS) is a technique with potential to characterize endogenous and unmanipulated protein complexes on an unprecedented scale. However this potential has been offset by a lack of guidelines for best-practice CF-MS data collection and analysis. To obtain such guidelines, this study thoroughly evaluates novel and published Saccharomyces cerevisiae CF-MS data sets using very high proteome coverage libraries of yeast gold standard complexes. A new method for identifying gold standard complexes in CF-MS data, Reference Complex Profiling, and the Extending 'Guilt-by-Association' by Degree (EGAD) R package are used for these evaluations, which are verified with concurrent analyses of published human data. By evaluating data collection designs, which involve fractionation of cell lysates, it is found that near-maximum recall of complexes can be achieved with fewer samples than published studies. Distributing sample collection across orthogonal fractionation methods, rather than a single high resolution data set, leads to particularly efficient recall. By evaluating 17 different similarity scoring metrics, which are central to CF-MS data analysis, it is found that two metrics rarely used in past CF-MS studies – Spearman and Kendall correlations – and the recently introduced Co-apex metric frequently maximize recall, whereas a popular metric—Euclidean distance—delivers poor recall. The common practice of integrating external genomic data into CF-MS data analysis is also evaluated, revealing that this practice may improve the precision and recall of known complexes but is generally unsuitable for predicting novel complexes in model organisms. If studying nonmodel organisms using orthologous genomic data, it is found that particular subsets of fractionation profiles (e.g. the lowest abundance quartile) should be excluded to minimize false discovery. These assessments are summarized in a series of universally applicable guidelines for precise, sensitive and efficient CF-MS studies of known complexes, and effective predictions of novel complexes for orthogonal experimental validation.

Protein tyrosine kinases (PTKs) play key roles in cellular signal transduction, cell cycle regulation, cell division, and cell differentiation. Dysregulation of PTK-activated pathways, often by receptor overexpression, gene amplification, or genetic mutation, is a causal factor underlying numerous cancers. In this study, we have developed a parallel reaction monitoring (PRM)-based assay for quantitative profiling of 83 PTKs. The assay detects 308 proteotypic peptides from 54 receptor tyrosine kinases and 29 nonreceptor tyrosine kinases in a single run. Quantitative comparisons were based on the labeled reference peptide method. We implemented the assay in four cell models: 1) a comparison of proliferating versus epidermal growth factor (EGF)-stimulated A431 cells, 2) a comparison of SW480Null (mutant APC) and SW480APC (APC restored) colon tumor cell lines, and 3) a comparison of 10 colorectal cancer cell lines with different genomic abnormalities, and 4) lung cancer cell lines with either susceptibility (11-18) or acquired resistance (11-18R) to the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib. We observed distinct PTK expression changes that were induced by stimuli, genomic features or drug resistance, which were consistent with previous reports. However, most of the measured expression differences were novel observations. For example, acquired resistance to erlotinib in the 11-18 cell model was associated not only with previously reported upregulation of MET, but also with upregulation of FLK2 and downregulation of LYN and PTK7. Immunoblot analyses and shotgun proteomics data were highly consistent with PRM data. Multiplexed PRM assays provide a targeted, systems-level profiling approach to evaluate cancer-related proteotypes and adaptations. Data are available through Proteome eXchange Accession PXD002706.

Gonadal soma-derived factor (gsdf) has been demonstrated to be essential for testicular differentiation in medaka (Oryzias latipes). To understand the protein dynamics of Gsdf in spermatogenesis regulation, we used a His-tag "pull-down" assay coupled with shotgun LC-MS/MS to identify a group of potential interacting partners for Gsdf, which included cytoplasmic dynein light chain 2, eukaryotic polypeptide elongation factor 1 alpha (eEF1α), and actin filaments in mature medaka testis. As for the interaction with TGFβ-dynein being critical for spermatogonial division in Drosophila melanogaster, the physical interactions of Gsdf-dynein and Gsdf-eEF1α were identified through a yeast 2-hybrid (Y2H) screening of an adult testis cDNA library using Gsdf as bait, which were verified by a paired Y2H assay. Co-immunoprecipitation of Gsdf and eEF1α was defined in adult testes as supporting the requirement of a Gsdf and eEF1α interaction in testis development. Proteomics analysis (data are available via ProteomeXchange with identifier PXD022153) and ultrastrutural observations showed that Gsdf deficiency activated eEF1α-mediated protein synthesis and ribosomal biogenesis, which in turn led to the differentiation of undifferentiated germ cells. Thus, our results provide a framework and new insight into the coordination of a Gsdf (TGFβ and eEF1α complex in the basic processes of germ cell proliferation, transcriptional and translational control of sexual RNA which may be fundamentally conserved across phyla during sexual differentiation.

Sporozoites are a motile form of malaria-causing Plasmodium falciparum parasites that migrate from the site of transmission in the dermis through the bloodstream to invade hepatocytes. Sporozoites interact with many cells within the host, but the molecular identity of these interactions and their role in the pathology of malaria is poorly understood. Parasite proteins that are secreted and embedded within membranes are known to be important for these interactions, but our understanding of how they interact with each other to form functional complexes is largely unknown. Here, we compile a library of recombinant proteins representing the repertoire of cell surface and secreted proteins from the P. falciparum sporozoite and use an assay designed to detect extracellular interactions to systematically identify complexes. We identify three protein complexes including an interaction between two components of the p24 complex that is involved in the trafficking of glycosylphosphatidylinositol (GPI)-anchored proteins through the secretory pathway. Plasmodium parasites lacking either gene are strongly inhibited in the establishment of liver stage infections. These findings reveal an important role for the p24 complex in malaria pathogenesis and show that the library of recombinant proteins represents a valuable resource to investigate P. falciparum sporozoite biology.

Deep proteome coverage in bottom-up proteomics requires peptide-level fractionation to simplify the complex peptide mixture before analysis by tandem mass spectrometry. By decreasing the number of co-eluting precursor peptide ions, fractionation effectively reduces the complexity of the sample leading to higher sample coverage and reduced bias towards high abundance precursors that are preferentially identified in data-dependent acquisition strategies. To achieve this goal, we report a bead-based off-line peptide fractionation method termed CIF or Carboxylate modified magnetic bead-based isopropanol gradient peptide fractionation. CIF is an extension of the SP3 (single-pot solid-phase-enhanced sample preparation) strategy and provides an effective but complementary approach to other commonly used fractionation methods including strong cation exchange (SCX) and reversed phase (RP)-based chromatography. We demonstrate that CIF is an effective offline separation strategy capable of increasing the depth of peptide analyte coverage both when used alone or as a second dimension of peptide fractionation in conjunction with high pH RP. These features make it ideally suited for a wide range of proteomic applications including the affinity purification of low abundance bait proteins.

Mine Action in Angola: Clearing the Legacies of Conflict to Harness the Potential of Peace Other resource sysadmin 14 June 2019

This publication draws on and updates the briefing note published following a meeting of the All- Party Parliamentary Group (APPG) on Angola on 26 April 2017. It also incorporates insights from a Chatham House Africa Programme conference session on the legacies of the Angolan Civil War, held on 23 March 2018; and draws on the Africa Programme’s research into conservation-driven development models in Southern Africa.

Almost two decades after the end of its civil war, Angola remains one of the most heavily landmine-contaminated countries in the world. The Angolan government has committed to clearing its landmines by 2025, and there is constructive collaboration between the government and mine clearing agencies in this endeavour, but the target will be achievable only if a decline in funding from international donors is reversed. International funding for mine clearance in Angola fell by more than 80 per cent between 2005 and 2017, and this sharp drop in external support has compounded the impact on domestic funding for national clearance efforts as a result of the downturn in prices for Angola’s main export commodities.

The national mine action agency, the Comissão Nacional Intersectorial de Desminagem e Assistência Humanitária (CNIDAH), is supported by the Mines Advisory Group (MAG), Norwegian People’s Aid (NPA) and the HALO Trust. By 2017, 15 years after the end of the civil war, these organizations had collectively helped clear 56 per cent of known landmine-contaminated land. State-led demining has focused principally on clearing areas designated for infrastructure projects. Now, it is critical that humanitarian demining in largely agricultural and conservation areas is prioritized to bring to an end the daily threat to Angola’s rural poor – as well as to the country’s livestock and wildlife – of injury or death as a result of landmine accidents.

Angola has some of the world’s most important remaining wilderness, including the tributary system for the unique Okavango Delta, and the country has the potential to host one of the most diverse wildlife populations on the continent. However, the presence of landmines and other remnants of the civil war render large areas of the country unsafe both for wildlife and for the local people, whose ability to derive a sustainable livelihood from their natural environment is fundamental to its protection.

Wildlife and tourism provide important economic opportunities for diversification beyond an oil-dominated economy. Critically, Angola’s economic diversification and development objectives can only be achieved if the landmines that prohibit access to land for agriculture, mining, tourism and wildlife are cleared.

There are economic opportunities for released land in the most heavily mined provinces of Cuando Cubango and Moxico. Already, some new funding for mine action in Angola, if upscaled or matched by international donors, could be transformative for its people, and for the conservation of the region’s vital biodiversity.

Racing settles in for the winter season this weekend with the Breeders' Cup in the rearview mirror and the Dubai World Cup Carnival opening its tents Friday at Meydan Racecourse.

Best known in education circles for its performance assessment, New Hampshire is a hotbed of innovation around personalized learning, writes Adriana Martinez of the Innovation Lab Network.

Lindsay P. Cameron
Nov 8, 2023; 43:7472-7482
Symposium and Mini-Symposium

Aggression involves both sexually monomorphic and dimorphic actions. How the brain implements these two types of actions is poorly understood. We found that in Drosophila melanogaster, a set of neurons, which we call CL062, previously shown to mediate male aggression also mediate female aggression. These neurons elicit aggression acutely and without the presence of a target. Although the same set of actions is elicited in males and females, the overall behavior is sexually dimorphic. The CL062 neurons do not express fruitless, a gene required for sexual dimorphism in flies, and expressed by most other neurons important for controlling fly aggression. Connectomic analysis in a female electron microscopy dataset suggests that these neurons have limited connections with fruitless expressing neurons that have been shown to be important for aggression and signal to different descending neurons. Thus, CL062 is part of a monomorphic circuit for aggression that functions parallel to the known dimorphic circuits.

Plasticity in the subcortical motor basal ganglia–thalamo–cerebellar network plays a key role in the acquisition and control of long-term memory for new procedural skills, from the formation of population trajectories controlling trained motor skills in the striatum to the adaptation of sensorimotor maps in the cerebellum. However, recent findings demonstrate the involvement of a wider cortical and subcortical brain network in the consolidation and control of well-trained actions, including a brain region traditionally associated with declarative memory—the hippocampus. Here, we probe which role these subcortical areas play in skilled motor sequence control, from sequence feature selection during planning to their integration during sequence execution. An fMRI dataset (N = 24; 14 females) collected after participants learnt to produce four finger press sequences entirely from memory with high movement and timing accuracy over several days was examined for both changes in BOLD activity and their informational content in subcortical regions of interest. Although there was a widespread activity increase in effector-related striatal, thalamic, and cerebellar regions, in particular during sequence execution, the associated activity did not contain information on the motor sequence identity. In contrast, hippocampal activity increased during planning and predicted the order of the upcoming sequence of movements. Our findings suggest that the hippocampus preorders movements for skilled action sequences, thus contributing to the higher-order control of skilled movements that require flexible retrieval. These findings challenge the traditional taxonomy of episodic and procedural memory and carry implications for the rehabilitation of individuals with neurodegenerative disorders.

A valuable tool has been produced for decision makers responsible for integrating the Sustainable Development Goals into national policies and programmes. This publication, Transforming food and agriculture to achieve [...]

FAO is pleased to announce the release of the Global Plan of Action for the Conservation, Sustainable Use and Development of Aquatic Genetic Resources for Food [...]

Although we have made progress towards building a better world, too many people have been left behind. People who are unable to benefit from human development, innovation or economic growth.

In [...]

The Committee on Agriculture (COAG) is one of FAO’s Governing Bodies providing overall policy and regulatory guidance on issues relating to agriculture, livestock, food safety, nutrition, rural development and [...]

Over the course of 50 years, John Marshall filmed the African tribe, tracking how their nomadic culture slowly died out

This unmanned aerial vehicle can be launched from, and land on, a moving ship thanks to new technology Narrated by T.A. Frail Script by Brendan McCabe Video courtesy of Insitu

Connor McDavid retured from injury — well ahead of schedule. The Oilers captain re-entered the lineup when Edmonton hosted the Vegas Golden Knights on Wednesday.

Able to compact gallons of trash with a single gulp, BigBelly Solar trash compactor cuts public garbage collection emissions by up to 80 percent

Tampico, Mexico :: After a five-week maintenance period, Logos Hope resumes her schedule in a new port, to an enthusiastic reception.

Members of OM Costa Rica help a 90-year-old woman get to her doctor appointment at a hospital six hours away from her home.

Penn State’s Local Climate Action Program is making a valuable impact beyond Pennsylvania’s borders, thanks in part to Joe Thompson, a World Campus Energy and Sustainability Policy graduate. Thompson was recently honored at a ceremony hosted by the San Diego chapter of the Climate Action Campaign, for his help in creating the City of Orange climate action plan.

Voice assistants (VAs) like Alexa and Siri continue to gain popularity in households and on personal devices. According to digital trends research company Emarketer, the number of VA users will surpass 150 million in 2025. Despite the ubiquity, companies haven’t been able to work around users’ strong negative reactions to advertising on these applications. A research team, including scholars from Penn State, may have a solution.

A youth group from Lyon, France, participates in a summer 2012 TiM outreach to Southampton, UK.

A 5th grade teacher uses fractions to promote both language and math skills in her dual-language classroom.

Elementary math specialist Kristin Gray helps her 2nd graders understand different subtraction strategies by talking through their thought processes.

Reports of the outages spiked between midnight and 2 am EST, with the network receiving thousands of complaints during this time, according to Down Detector.

Several civil society groups and student organisations of the Kuki tribes have condemned what they call "barbaric actions" of the Central Reserve Police Force (CRPF), a day after 10 men from the Kuki tribes were killed in Manipur's Jiribam district.

Signal has been updated with Call Links, a feature that enables users to initiate a group call with multiple participants without the need to form a separate group chat. Additional updates include a "raise hand" button, emoji reactions, and a dedicated calls tab on Signal.

The film will release on November 14

The Great Indian Kapil Show episode featuring Navjot Singh Sidhu will premiere on Netflix on Saturday, November 16 

Shraddha dropped a string of sweaty face and head slamming emojis

Series of changes come after reports of Highmark premium notice errors Dozens of complaints have been registered with the Delaware Department of Insurance after Highmark Blue Cross Blue Shield processed hundreds of customer birthdates incorrectly, leading to notices of higher July 1 premiums for many Medicare Supplement participants, including those in the company’s Medigap Blue […]

Shilpa Shetty's unapologetic foodie side shines through in her latest Instagram reel. "My food is my food, and none of your food!" she declared.

Attorney General Kathy Jennings’ Consumer Protection Unit announced Monday that it filed an administrative lawsuit against Centerdon Group, Inc. n/k/a Hilvanim Group, Inc., a California corporation, for violating the Delaware Uniform Debt-Management Services Act, the Delaware Consumer Fraud Act and the Delaware Deceptive Trade Practices Act. “Delawareans who are struggling with debt deserve our help, […]

Prosecutors have secured three convictions against Camden Mayor Justin King over a physical confrontation he began with two victims, as well as his subsequent lack of candor with investigators. King, 41, was until recently the mayor of Camden, Delaware and owns several businesses in the area. On February 25, King confronted two male victims, both […]

The Delaware Forest Service is seeking public comment on its new 2020 "Forest Action Plan," comprised of an updated Delaware Forest Resource Assessment, Delaware Statewide Forest Strategy, and a new "Assessment of Need" for the U.S. Forest Legacy Program, which provides funding to conserve working forests.  The documents can be found at de.gov/forestactionplan and are available in both Flipbook versions and PDF format. The public is kindly asked to review and provide comments via email at delawareforests@gmail.com by Friday, September 4, 2020.

SAS Decision Builder is a decision intelligence solution, which means that it uses machine learning and automation to augment human decision-making for better and faster insights that drive tactical and strategic business decisions. It’s a cousin to business intelligence and the next step after data engineering and model training, completing the analytics lifecycle to help achieve business goals.

SAS Decision Builder in Microsoft Fabric: Helping you translate insights into action was published on SAS Users.

WILMINGTON, Del. — Community and state leaders highlighted the need for robust reentry supports to help returning citizens thrive during the first Delaware Day of Action, a special convening for criminal justice advocates and policymakers.      Hosted by Lt. Governor Bethany Hall-Long, Senator Darius Brown and Representative Melissa Minor-Brown in partnership with REFORM Alliance, the Delaware […]

DOVER, Del. — As the 152nd General Assembly comes to a close, Lt. Governor Bethany Hall-Long on Sunday highlighted historic investments in early education, protections for reproductive justice, and actions that support a safe, healthy, and thriving Delaware.    “As second in command for the past seven years, I’ve had the privilege of serving with […]

Attorney General Kathy Jennings this week filed a complaint against former Delaware investment adviser Elbert C. Smalls and his investment advisory firm, known as Winyah Financial Services, LLC or Winyah Financial, LLC (formerly operating in Delaware as Sun Financial Services, Inc.). The complaint is the culmination of an investigation by the Investor Protection Unit (the […]