Sensory specializations drive octopus and squid behaviour

Nature

2023 Apr 01

Kang, G;Allard, CAH;Valencia-Montoya, WA;van Giesen, L;Kim, JJ;Kilian, PB;Bai, X;Bellono, NW;Hibbs, RE;
PMID: 37045917 | DOI: 10.1038/s41586-023-05808-z

The evolution of new traits enables expansion into new ecological and behavioural niches. Nonetheless, demonstrated connections between divergence in protein structure, function and lineage-specific behaviours remain rare. Here we show that both octopus and squid use cephalopod-specific chemotactile receptors (CRs) to sense their respective marine environments, but structural adaptations in these receptors support the sensation of specific molecules suited to distinct physiological roles. We find that squid express ancient CRs that more closely resemble related nicotinic acetylcholine receptors, whereas octopuses exhibit a more recent expansion in CRs consistent with their elaborated 'taste by touch' sensory system. Using a combination of genetic profiling, physiology and behavioural analyses, we identify the founding member of squid CRs that detects soluble bitter molecules that are relevant in ambush predation. We present the cryo-electron microscopy structure of a squid CR and compare this with octopus CRs1 and nicotinic receptors2. These analyses demonstrate an evolutionary transition from an ancestral aromatic 'cage' that coordinates soluble neurotransmitters or tastants to a more recent octopus CR hydrophobic binding pocket that traps insoluble molecules to mediate contact-dependent chemosensation. Thus, our study provides a foundation for understanding how adaptation of protein structure drives the diversification of organismal traits and behaviour.

On the use of Earth Observation to support estimates of national greenhouse gas emissions and sinks for the Global stocktake process: lessons learned from ESA-CCI RECCAP2

Carbon balance and management

2022 Oct 01

Bastos, A;Ciais, P;Sitch, S;Aragão, LEOC;Chevallier, F;Fawcett, D;Rosan, TM;Saunois, M;Günther, D;Perugini, L;Robert, C;Deng, Z;Pongratz, J;Ganzenmüller, R;Fuchs, R;Winkler, K;Zaehle, S;Albergel, C;
PMID: 36183029 | DOI: 10.1186/s13021-022-00214-w

The Global Stocktake (GST), implemented by the Paris Agreement, requires rapid developments in the capabilities to quantify annual greenhouse gas (GHG) emissions and removals consistently from the global to the national scale and improvements to national GHG inventories. In particular, new capabilities are needed for accurate attribution of sources and sinks and their trends to natural and anthropogenic processes. On the one hand, this is still a major challenge as national GHG inventories follow globally harmonized methodologies based on the guidelines established by the Intergovernmental Panel on Climate Change, but these can be implemented differently for individual countries. Moreover, in many countries the capability to systematically produce detailed and annually updated GHG inventories is still lacking. On the other hand, spatially-explicit datasets quantifying sources and sinks of carbon dioxide, methane and nitrous oxide emissions from Earth Observations (EO) are still limited by many sources of uncertainty. While national GHG inventories follow diverse methodologies depending on the availability of activity data in the different countries, the proposed comparison with EO-based estimates can help improve our understanding of the comparability of the estimates

Current HIV/SIV Reservoir Assays for Preclinical and Clinical Applications: Recommendations from the Experts 2022 NIAID Workshop Summary

AIDS research and human retroviruses

2023 Apr 26

Sanders-Beer, BE;Archin, NM;Brumme, ZL;Busch, M;Deleage, C;O'Doherty, U;Hughes, SH;Jerome, K;Jones, RB;Karn, J;Kearney, MF;Keele, B;Kulpa, D;Laird, G;Li, JZ;Lichterfeld, M;Nussenzweig, MC;Persaud, D;Yukl, S;Siliciano, RF;Mellors, JW;
PMID: 37126090 | DOI: 10.1089/AID.2022.0188

Since the first HIV-cured person was reported in 2009, a strong interest in developing highly sensitive HIV and SIV reservoir assays has emerged. In particular, the question arose about the comparative value of state-of-the-art assays to measure and characterize the HIV reservoir, and how these assays can be applied to accurately detect changes in the reservoir during efforts to develop a cure for HIV infection. Secondly, it is important to consider the impact on the outcome of clinical trials if these relatively new HIV reservoir assays are incorporated into clinical trial endpoints and/or used for clinical decision-making. To understand the advantages and limitations and the regulatory implications of HIV reservoir assays, the National Institute of Allergy and Infectious Diseases (NIAID) sponsored and convened a meeting on September 16, 2022, to discuss the state of knowledge concerning these questions and best practices for selecting HIV reservoir assays for a particular research question or clinical trial protocol.

Inhibin-Positive "Cholangioblastic" Variant of Intrahepatic Cholangiocarcinoma: Report of 3 New Patients With Review of the Literature

International journal of surgical pathology

2023 Apr 18

Bakhshwin, A;Lai, KK;Ammoun, A;Friedman, K;El Hag, M;
PMID: 37073447 | DOI: 10.1177/10668969231157775

Cholangiocarcinoma is the second most common primary liver malignant neoplasm. It usually affects older individuals in their seventh decade of life with no gender predilection. Recently, a distinct subtype of cholangiocarcinoma has emerged with 2 proposed names: "cholangioblastic" and "solid tubulocystic." This variant predominantly occurs in younger women who lack the common risk factors for patients diagnosed with cholangiocarcinomas, such as older age and chronic liver disease or cirrhosis. We describe 3 new patients with a cholangioblastic variant of intrahepatic cholangiocarcinoma. At the time of diagnosis, the patients were aged 19-, 46-, and 28-year-old; 2 females and 1 male (the 46-year-old). None of our patients had a history of chronic liver disease or known predisposing factors for liver tumors. Tumor size ranged from 2.3 to 23 cm in greatest dimension. Histological examination of these tumors demonstrated reproducible morphology characterized by trabecular, nested, and multicystic patterns with micro and macro follicles filled with eosinophilic material. The immunohistochemical profile showed that the tumor cells were positive for keratin 7, inhibin, synaptophysin, and albumin in situ hybridization, while negative for HepPar1, arginase, and INSM1. All tumors lacked conventional intrahepatic cholangiocarcinoma/adenocarcinoma morphology. We also review the literature and emphasize that neuroendocrine tumors should be recognized as a major diagnostic pitfall of this variant.

Spatially resolved transcriptomics: a comprehensive review of their technological advances, applications, and challenges

Journal of genetics and genomics = Yi chuan xue bao

2023 Mar 27

Cheng, M;Jiang, Y;Xu, J;Mentis, AA;Wang, S;Zheng, H;Sahu, SK;Liu, L;Xu, X;
PMID: 36990426 | DOI: 10.1016/j.jgg.2023.03.011

The ability to explore life kingdoms is largely drive by innovations and breakthroughs in technology, from the invention of the microscope 350 years ago to the recent emergence of single cell sequencing, by which the scientific community has been able to visualize life at an unprecedented resolution. Most recently, the Spatially Resolved Transcriptomics (SRT) technologies have filled the gap in probing the spatial or even three-dimensional (3D) organization of the molecular foundation behind the molecular mysteries of life, including the origin of different cellular populations developed from totipotent cells and human diseases. In this review, we introduce recent progress and challenges on SRT from the perspectives of technologies and bioinformatic tools, as well as the representative SRT applications. With the currently fast-moving progress of the SRT technologies and promising results from early adopted research projects, we can foresee the bright future of such new tools in understanding life at the most profound analytical level.

Canonical Wnt signaling regulates soft palate development through mediating ciliary homeostasis

Development (Cambridge, England)

2023 Feb 24

Janečková, E;Feng, J;Guo, T;Han, X;Ghobadi, A;Araujo-Villalba, A;Rahman, MS;Ziaei, H;Ho, TV;Pareek, S;Alvarez, J;Chai, Y;
PMID: 36825984 | DOI: 10.1242/dev.201189

Craniofacial morphogenesis requires complex interactions involving different tissues, signaling pathways, secreted factors, and organelles. The details of these interactions remain elusive. In this study, we have analyzed the molecular mechanisms and homeostatic cellular activities governing soft palate development to improve regenerative strategies for cleft palate patients. We have identified canonical Wnt signaling as a key signaling pathway primarily active in cranial neural crest (CNC)-derived mesenchymal cells surrounding soft palatal myogenic cells. Using Osr2-Cre;β-cateninfl/fl mice, we show that Wnt signaling is indispensable for mesenchymal cell proliferation and subsequently myogenesis through mediating ciliogenesis. Specifically, we have identified that Wnt signaling directly regulates expression of the ciliary gene Ttll3. Impaired ciliary disassembly leads to differentiation defects of mesenchymal cells and indirectly disrupts myogenesis through decreased expression of Dlk1, a mesenchymal cell-derived pro-myogenesis factor. Moreover, we show that siRNA-mediated reduction of Ttll3 expression partly rescues mesenchymal cell proliferation and myogenesis in the palatal explant cultures from Osr2-Cre;β-cateninfl/fl embryos. This study highlights the role of Wnt signaling in palatogenesis through controlling ciliary homeostasis, which establishes a new mechanism for Wnt-regulated craniofacial morphogenesis.

Reversing the NK inhibitory tumor microenvironment by targeting suppressive immune effectors

NK Cells in Cancer Immunotherapy: Successes and Challenges

2023 Jan 19

Navin, I;Parihar, R;
| DOI: 10.1016/B978-0-12-822620-9.00011-2

The efficacy of natural killer (NK) cell-based therapies against solid tumors has been poor. Solid tumors generate a hostile tumor microenvironment (TME) comprising multiple cell types including inhibitory immune cells that play a key role in depressing the antitumor functions of therapeutic NK cells. Understanding how inhibitory immune effectors operate within the confines of the TME is critical to developing therapies to reverse this inhibition. In this chapter, we cover the suppressive mechanisms employed by TME-resident inhibitory immune cells and discuss methodologies to assess their composition and functionality within the TME. We also highlight novel therapeutic strategies that target inhibitory cells of the TME to improve the antitumor functions of endogenous or adoptively transferred NK cells. Multimodal approaches to overcome inhibitory immune cells within the TME will drive the development of personalized NK cell therapeutics with optimal activity, leading to improved clinical outcomes in patients with solid tumors.

Type 2 diabetes is associated with increased circulating levels of 3-hydroxydecanoate activating GPR84 and neutrophil migration

iScience

2022 Nov 01

Mikkelsen, R;Arora, T;Trošt, K;Dmytriyeva, O;Jensen, S;Meijnikman, A;Olofsson, L;Lappa, D;Aydin, Ö;Nielsen, J;Gerdes, V;Moritz, T;van de Laar, A;de Brauw, M;Nieuwdorp, M;Hjorth, S;Schwartz, T;Bäckhed, F;
| DOI: 10.1016/j.isci.2022.105683

Obesity and diabetes are associated with inflammation and altered plasma levels of several metabolites, which may be involved in disease progression. Some metabolites can activate G protein-coupled receptors (GPCRs) expressed on immune cells where they can modulate metabolic inflammation. Here we find that 3-hydroxydecanoate is enriched in the circulation of obese individuals with type 2 diabetes (T2D) compared with non-diabetic controls. Administration of 3-hydroxydecanoate to mice promotes immune cell recruitment to adipose tissue, which was associated with adipose inflammation and increased fasting insulin levels. Furthermore, we demonstrate that 3-hydroxydecanoate stimulates migration of primary human and mouse neutrophils, but not monocytes, through GPR84 and Gαi signaling in vitro. Our findings indicate that 3-hydroxydecanoate is a T2D-associated metabolite that increases inflammatory responses and may contribute to the chronic inflammation observed in diabetes.

Spatiotemporal Omics-Refining the landscape of precision medicine

Life Medicine

2022 Nov 14

Zhang, J;Yin, J;Heng, Y;Xie, K;Chen, A;Amit, I;Bian, X;Xu, X;
| DOI: 10.1093/lifemedi/lnac053

Current streamline of precision medicine uses histomorphological and molecular information to indicate individual phenotypes and genotypes to achieve optimal outcome of treatment. The knowledge of detected mutations and alteration can hardly describe molecular interaction and biological process which can finally be manifested as a disease. With molecular diagnosis revising the modalities of disease, there is a trend in precision medicine to apply multi-omic and multi-dimensional information to decode tumors, regarding heterogeneity, pathogenesis, prognosis, etc. Emerging state-of-art spatiotemporal omics provides a novel vision for in discovering clinicopathogenesis associated findings, some of which show a promising potential to be translated to facilitate clinical practice. Here, we summarize the available spatiotemporal omic technologies and algorithms, highlight the novel scientific findings and explore potential applications in the clinical scenario. Spatiotemporal omics present the ability to provide impetus to rewrite clinical pathology and to answer outstanding clinical questions. This review emphasizes the novel vision of spatiotemporal omics to refine the landscape of precision medicine in the clinic.

Nasopharyngeal Carcinoma Ecology Theory: Cancer as Multidimensional Spatiotemporal “Unity of Ecology and Evolution” Pathological Ecosystem

Preprint

2022 Oct 17

Luo, W;
| DOI: 10.20944/preprints202210.0226.v1

Nasopharyngeal carcinoma (NPC) is generally regarded as a genetic disease with diverse extent of intertumor and intratumor heterogeneity. Here we propose that, NPC is not only a genetic disease; it could be conceptualized as a multidimensional spatiotemporal “unity of ecology and evolution” pathological ecosystem. In the text, we first discuss NPC cells an invasive species and its metastasis as a multidirectional ecological dispersal, which consisting of four interdependent parts: primary ecosystem, circulating ecosystem, metastatic ecosystem and multidirectional ecosystem. We then interpreter the foundational ecological principles to understand NPC progression. The model of “mulberry-fish-ponds” can well illustrate the dynamic reciprocity of cancer ecosystem. Subsequently, we demonstrate that tumor-host interface is the ecological transition zone in cancers, and tumor buddings should be recognized as ecological islands separated from the mainland. Selection driving factors and ecological therapy including hyperthermia for NPC patients, and future perspectives of “ecological pathology”, “multidimensional spatiotemporal tumoriecology” and “integrated tumoriecology” are also pointed out. We advance that “nothing in cancer evolution or ecology makes sense except in the light of the other”. The essence of NPC and other human neoplasms should be pathological an “unity of ecology and evolution”. The establishment of “NPC ecology” might open up a new horizon, and provide a comprehensive framework for our understanding of the complex progression of this disease and development of potential preventive and therapeutic strategies for patients.

Transcriptional targets of amyotrophic lateral sclerosis/frontotemporal dementia protein TDP-43- meta-analysis and interactive graphical database

Disease models & mechanisms

2022 Sep 01

Cao, MC;Scotter, EL;
PMID: 35946434 | DOI: 10.1242/dmm.049418

TDP-43 proteinopathy is the major pathology in amyotrophic lateral sclerosis (ALS) and tau-negative frontotemporal dementia (FTD). Mounting evidence implicates loss of normal TDP-43 RNA-processing function as a key pathomechanism. However, the RNA targets of TDP-43 differ by report, and have never been formally collated or compared between models and disease, hampering understanding of TDP-43 function. Here, we conducted re-analysis and meta-analysis of publicly available RNA-sequencing datasets from six TDP-43-knockdown models, and TDP-43-immunonegative neuronal nuclei from ALS/FTD brain, to identify differentially expressed genes (DEGs) and differential exon usage (DEU) events. There was little overlap in DEGs between knockdown models, but PFKP, STMN2, CFP, KIAA1324 and TRHDE were common targets and were also differentially expressed in TDP-43-immunonegative neurons. DEG enrichment analysis revealed diverse biological pathways including immune and synaptic functions. Common DEU events in human datasets included well-known targets POLDIP3 and STMN2, and novel targets EXD3, MMAB, DLG5 and GOSR2. Our interactive database (https://www.scotterlab.auckland.ac.nz/research-themes/tdp43-lof-db/) allows further exploration of TDP-43 DEG and DEU targets. Together, these data identify TDP-43 targets that can be exploited therapeutically or used to validate loss-of-function processes. This article has an associated First Person interview with the first author of the paper.

On diabetic foot ulcer knowledge gaps, innovation, evaluation, prediction markers, and clinical needs

Journal of Diabetes and its Complications

2022 Sep 01

Schmidt, B;Holmes, C;Najarian, K;Gallagher, K;Haus, J;Shadiow, J;Ye, W;Ang, L;Burant, A;Baker, N;Katona, A;Martin, C;Pop-Busui, R;
| DOI: 10.1016/j.jdiacomp.2022.108317

Diabetic foot ulcers (DFUs) remain a very prevalent and challenging complication of diabetes worldwide due to high morbidity, high risks of lower extremity amputation and associated mortality. Despite major advances in diabetes treatment in general, there is a paucity of FDA approved technologies and therapies to promote successful healing. Furthermore, accurate biomarkers to identify patients at risk of non-healing and monitor response-to-therapy are significantly lacking. To date, research has been slowed by a lack of coordinated efforts among basic scientists and clinical researchers and confounded by non-standardized heterogenous collection of biospecimen and patient associated data. Novel technologies, especially those in the single and ‘multiomics’ arena, are being used to advance the study of diabetic foot ulcers but require pragmatic study design to ensure broad adoption following validation. These high throughput analyses offer promise to investigate potential biomarkers across wound trajectories and may support information on wound healing and pathophysiology not previously well understood. Additionally, these biomarkers may be used at the point-of-care. In combination with national scalable research efforts, which seek to address the limitations and better inform clinical practice, coordinated and integrative insights may lead to improved limb salvage rates.

Pages

	Description
sense Example: Hs-LAG3-sense	Standard probes for RNA detection are in antisense. Sense probe is reverse complent to the corresponding antisense probe.
Intron# Example: Mm-Htt-intron2	Probe targets the indicated intron in the target gene, commonly used for pre-mRNA detection
Pool/Pan Example: Hs-CD3-pool (Hs-CD3D, Hs-CD3E, Hs-CD3G)	A mixture of multiple probe sets targeting multiple genes or transcripts
No-XSp Example: Hs-PDGFB-No-XMm	Does not cross detect with the species (Sp)
XSp Example: Rn-Pde9a-XMm	designed to cross detect with the species (Sp)
O# Example: Mm-Islr-O1	Alternative design targeting different regions of the same transcript or isoforms
CDS Example: Hs-SLC31A-CDS	Probe targets the protein-coding sequence only
EnEm	Probe targets exons n and m
En-Em	Probe targets region from exon n to exon m
Retired Nomenclature
tvn Example: Hs-LEPR-tv1	Designed to target transcript variant n
ORF Example: Hs-ACVRL1-ORF	Probe targets open reading frame
UTR Example: Hs-HTT-UTR-C3	Probe targets the untranslated region (non-protein-coding region) only
5UTR Example: Hs-GNRHR-5UTR	Probe targets the 5' untranslated region only
3UTR Example: Rn-Npy1r-3UTR	Probe targets the 3' untranslated region only
Pan Example: Pool	A mixture of multiple probe sets targeting multiple genes or transcripts

Search form

Probes for INS

Content for comparison

Gene

Product

Research area

Category

Pages

Advanced Cell Diagnostics

Bio-Techne

Advanced Cell Diagnostics China