Recent advances in sensing the inter-biomolecular interactions at the nanoscale – A comprehensive review of AFM-based force spectroscopy

Biomolecular interactions underpin most processes inside the cell. Hence, a precise and quantitative understanding of molecular association and dissociation events is crucial, not only from a fundamental perspective, but also for the rational design of biomolecular platforms for state-of-the-art biomedical and industrial applications. In this context, atomic force microscopy (AFM) appears as an invaluable experimental technique, allowing the measurement of the mechanical strength of biomolecular complexes to provide a quantitative characterization of their interaction properties from a single molecule perspective. In the present review, the most recent methodological advances in this field are presented with special focus on bioconjugation, immobilization and AFM tip functionalization, dynamic force spectroscopy measurements, molecular recognition imaging and theoretical modeling. We expect this work to significantly aid in grasping the principles of AFM-based force spectroscopy (AFM-FS) technique and provide the necessary tools to acquaint the type of data that can be achieved from this type of experiments. Furthermore, a critical assessment is done with other nanotechnology techniques to better visualize the future prospects of AFM-FS

A Receptor of the Immunoglobulin Superfamily Regulates Adaptive Thermogenesis

Exquisite regulation of energy homeostasis protects from nutrient deprivation but causes metabolic dysfunction upon nutrient excess. In human and murine adipose tissue, the accumulation of ligands of the receptor for advanced glycation end products (RAGE) accompanies obesity, implicating this receptor in energy metabolism. Here, we demonstrate that mice bearing global- or adipocyte-specific deletion of Ager, the gene encoding RAGE, display superior metabolic recovery after fasting, a cold challenge, or high-fat feeding. The RAGE-dependent mechanisms were traced to suppression of protein kinase A (PKA)-mediated phosphorylation of its key targets, hormone-sensitive lipase and p38 mitogen-activated protein kinase, upon beta-adrenergic receptor stimulation-processes that dampen the expression and activity of uncoupling protein 1 (UCP1) and thermogenic programs. This work identifies the innate role of RAGE as a key node in the immunometabolic networks that control responses to nutrient supply and cold challenges, and it unveils opportunities to harness energy expenditure in environmental and metabolic stress

Program Corporate Social Responsibility Dalam Perspektif Indeks Kepuasan Publik Di Riau

Program Corporate Social Reponsibility (CSR) merupakan salah satu kebutuhan dan di Indonesia merupakan suatu kewajiban dan ditetapkan melalui Undang-Undang Nomor 40 Tahun 2007 tentang Perseroan Terbatas. Dimana pada pasal 74 menjelaskan bahwa tanggung jawab sosial merupakan suatu kegiatan yang diwajibkan dan dilaksanakan berdasarkan pada kepatutan dan kewajaran sesuai dengan peraturan pemerintahan. Pelaksanaan tanggung jawab sosial dikenal dengan istilah CSR oleh Perusahaan merupakan suatu bentuk komitmen Perusahaan untuk membangun kualitas kehidupan yang lebih baik bersama stakeholders terkait, terutama masyarakat disekitar Perusahaan tersebut berada. Karena peran CSR ternyata saat ini semakin penting bagi masyarakat di sekitar Perusahaan dalam upaya menyeimbangkan pembangunan, baik ekonomi, sosial dan lingkungan. Penelitian ini dilaksanakan secara komprehensif mengenai implementasi dan prioritas program CSR di PT. Pertamina (Persero) RU II Dumai dan PT. Cevron Pasific Indonesia (CPI) di Tapung, Minas dan Rumbai Provinsi Riau. Metode penelitian dilakukan dengan metode campuran (mixed methods) yaitu mengkombinasikan pendekatan kuantitatif dan pendekatan kualitatif. Pengumpulan data dilakukan dengan penyebaran angket, in-dept interview dan observasi terhadap multistakeholders. Hasil penelitian yang ditemukan implementasi program CSR oleh PT. Pertamina (Persero) RU II Dumai dan PT. Cevron Pasific Indonesia (CPI) di Provinsi Riau masih berjalan dengan kurang baik. Sedangkan prioritas program CSR yang dibutuhkan berdasarkan indeks kepuasan publik di PT. Pertamina (Persero) RU II Dumai dan PT. Cevron Pasific Indonesia (CPI) di Tapung, Minas dan Rumbai Provinsi Riau adalah program yang berbasis pemberdayaan ekonomi masyarakat.Kata Kunci: pemberdayaan, program Corporate Social Reponsibility, indeks kepuasan publik. Corporate Social Reponsibility program (CSR) is seen as an urgent thing on social development. Its supported by regulation that stated in Act No. 40 year 2007 about Limited Company. In the article number 74 stated that social responsibility is one among activities that should be conducted by the companies. The companies should have committed for surround people quality of life, in terms of social and economic perspective. The sample of this research covers the implementation of the priority programmes and corporate social responsibility (CSR) PT. Pertamina (Persero) RU II Dumai and PT. Cevron Pacific Indonesia (CPI) at Tapung, Minas and Rumbai Riau Province. Data has been collected by questionnaire, in-depth interview and observation. Results of the study found implementation of programs of corporate social responsibility by PT. Pertamina (Persero) RU II Dumai and PT Cevron Pacific Indonesia (CPI) in Riau Province is still inadequate. The CSR program of the sample have been emphasized on social-economy empowerment

Rethinking of Optical Transport Network Design for 5G/6G Mobile Communication

Driven by the increasing use of emerging smart mobile applications, mobile technology is continuously and rapidly advancing towards the next generation communication systems such as 5G and 6G. However, the transport network, which needs to provide low latency and reliable connectivity between hundreds of thousands of cell sites and the network core, has not advanced at the same pace. This article provides insight into how we can solve the fundamental challenges of implementing cost-optimal transport and 5G and beyond mobile networks simultaneously while satisfying the network and user requirements irrespective of the radio access network\u27s architecture

Molecular Determinants of the Intrinsic Efficacy of the Antipsychotic Aripiprazole

Partial agonists of the dopamine D2 receptor (D2R) have been developed to treat the symptoms of schizophrenia without causing the side effects elicited by antagonists. The receptor-ligand interactions that determine the intrinsic efficacy of such drugs, however, are poorly understood. Aripiprazole has an extended structure comprising a phenylpiperazine primary pharmacophore and a 1,2,3,4-tetrahydroquinolin-2-one secondary pharmacophore. We combined site-directed mutagenesis, analytical pharmacology, ligand fragments and molecular dynamics simulations to identify the D2R-aripiprazole interactions that contribute to affinity and efficacy. We reveal that an interaction between the secondary pharmacophore of aripiprazole and a secondary binding pocket defined by residues at the extracellular portions of transmembrane segments 1, 2 and 7 determine the intrinsic efficacy of aripiprazole. Our findings reveal a hitherto unappreciated mechanism through which to fine-tune the intrinsic efficacy of D2R agonists

Effectiveness of the 23-valent pneumococcal polysaccharide vaccine against vaccine serotype pneumococcal pneumonia in adults: A case-control test-negative design study.

BACKGROUND: Vaccination with the 23-valent pneumococcal polysaccharide vaccine (PPV23) is available in the United Kingdom to adults aged 65 years or older and those in defined clinical risk groups. We evaluated the vaccine effectiveness (VE) of PPV23 against vaccine-type pneumococcal pneumonia in a cohort of adults hospitalised with community-acquired pneumonia (CAP). METHODS AND FINDINGS: Using a case-control test-negative design, a secondary analysis of data was conducted from a prospective cohort study of adults (aged ≥16 years) with CAP hospitalised at 2 university teaching hospitals in Nottingham, England, from September 2013 to August 2018. The exposure of interest was PPV23 vaccination at any time point prior to the index admission. A case was defined as PPV23 serotype-specific pneumococcal pneumonia and a control as non-PPV23 serotype pneumococcal pneumonia or nonpneumococcal pneumonia. Pneumococcal serotypes were identified from urine samples using a multiplex immunoassay or from positive blood cultures. Multivariable logistic regression was used to derive adjusted odds of case status between vaccinated and unvaccinated individuals; VE estimates were calculated as (1 - odds ratio) × 100%. Of 2,357 patients, there were 717 PPV23 cases (48% vaccinated) and 1,640 controls (54.5% vaccinated). The adjusted VE (aVE) estimate against PPV23 serotype disease was 24% (95% CI 5%-40%, p = 0.02). Estimates were similar in analyses restricted to vaccine-eligible patients (n = 1,768, aVE 23%, 95% CI 1%-40%) and patients aged ≥65 years (n = 1,407, aVE 20%, 95% CI -5% to 40%), but not in patients aged ≥75 years (n = 905, aVE 5%, 95% CI -37% to 35%). The aVE estimate in relation to PPV23/non-13-valent pneumococcal conjugate vaccine (PCV13) serotype pneumonia (n = 417 cases, 43.7% vaccinated) was 29% (95% CI 6%-46%). Key limitations of this study are that, due to high vaccination rates, there was a lack of power to reject the null hypothesis of no vaccine effect, and that the study was not large enough to allow robust subgroup analysis in the older age groups. CONCLUSIONS: In the setting of an established national childhood PCV13 vaccination programme, PPV23 vaccination of clinical at-risk patient groups and adults aged ≥65 years provided moderate long-term protection against hospitalisation with PPV23 serotype pneumonia. These findings suggest that PPV23 vaccination may continue to have an important role in adult pneumococcal vaccine policy, including the possibility of revaccination of older adults