Lung function in our aging population

<p>Abstract</p> <p>Aims of investigation</p> <p>The chronological age of the Caucasian population and their anthropometrical data have significantly changed within the last five decades. Therefore the question arises whether or not the commonly used reference values of the European Community (ECCS) for lung function may still be accepted today. Since these values were obtained in the 1960s from subjects in a limited age range. For the elderly, the measured values are deduced by extrapolation beyond the range of reference equations which had been obtained in a different population. Therefore decisions concerning elderly and smaller subjects concerning remuneration due to impaired lung function after industrial exposure on the basis of EGKS values are questionable.</p> <p>Methods</p> <p>Lung function tests were performed by pneumotachography, recording static lung volumes and flow-volume-curves in 262 asymptomatic non smoking males, aged 20 to 90 years. Measurements were performed with the MasterLab, or Pneumo-Screen systems (CareFusion, Höchberg). Results were compared to the reference values of ECCS, SAPALDIA and LuftiBus.</p> <p>Results</p> <p>For simplicity analysis of age and height dependence of investigated respiratory parameters (VC, FVC, FEV₁, FEV₁%FVC, PEF, MEF_75,50,25) can be described by linear functions (y = a * height - b * age + c). The forced expiratory vital capacity, FVC, was calculated by FVC = 0.0615*H - 0.0308*A - 4.673; r = 0.78. Mean FVC for younger subjects was found to be 104.7 ± 10.7% of the ECCS reference values and 96.5 ± 11.8% in older subjects. For most parameters investigated linear regressions on age were steeper than described by the ECCS reference values. The regression of lung function to height largely follows the ECCS prescriptions.</p> <p>Summary</p> <p>Bochum lung function values of younger healthy subjects were higher compared to the reference values of the ECCS and showed a steeper age descent. The alternatively discussed reference values of the SAPALDIA-, or LuftiBus-Study are higher, but do not cover all necessary parameters and/or the age range. A multi centre study for contemporary reference values is recommended.</p

Frustrated flexibility in metal-organic frameworks

Stimuli-responsive flexible metal-organic frameworks (MOFs) remain at the forefront of porous materials research due to their enormous potential for various technological applications. Here, we introduce the concept of frustrated flexibility in MOFs, which arises from an incompatibility of intra-framework dispersion forces with the geometrical constraints of the inorganic building units. Controlled by appropriate linker functionalization with dispersion energy donating alkoxy groups, this approach results in a series of MOFs exhibiting a new type of guest- and temperature-responsive structural flexibility characterized by reversible loss and recovery of crystalline order under full retention of framework connectivity and topology. The stimuli-dependent phase change of the frustrated MOFs involves non-correlated deformations of their inorganic building unit, as probed by a combination of global and local structure techniques together with computer simulations. Frustrated flexibility may be a common phenomenon in MOF structures, which are commonly regarded as rigid, and thus may be of crucial importance for the performance of these materials in various applications

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Hypertonicity counteracts MCL 1 and renders BCL XL a synthetic lethal target in head and neck cancer

Head and neck squamous cell carcinoma (HNSCC) is an aggressive and difficult‐to‐treat cancer entity. Current therapies ultimately aim to activate the mitochondria‐controlled (intrinsic) apoptosis pathway, but complex alterations in intracellular signaling cascades and the extracellular microenvironment hamper treatment response. On the one hand, proteins of the BCL‐2 family set the threshold for cell death induction and prevent accidental cellular suicide. On the other hand, controlling a cell's readiness to die also determines whether malignant cells are sensitive or resistant to anticancer treatments. Here, we show that HNSCC cells upregulate the proapoptotic BH3‐only protein NOXA in response to hyperosmotic stress. Induction of NOXA is sufficient to counteract the antiapoptotic properties of MCL‐1 and switches HNSCC cells from dual BCL‐XL/MCL‐1 protection to exclusive BCL‐XL addiction. Hypertonicity‐induced functional loss of MCL‐1 renders BCL‐XL a synthetically lethal target in HNSCC, and inhibition of BCL‐XL efficiently kills HNSCC cells that poorly respond to conventional therapies. We identify hypertonicity‐induced upregulation of NOXA as link between osmotic pressure in the tumor environment and mitochondrial priming, which could perspectively be exploited to boost efficacy of anticancer drugs

Aromatic Foldamer Helices as α‐Helix Extended Surface Mimetics

Helically folded aromatic oligoamide foldamers have a size and geometrical parameters very distinct from those of α‐helices and are not obvious candidates for α‐helix mimicry. Nevertheless, they offer multiple sites for attaching side chains. It was found that some arrays of side chains at the surface of an aromatic helix make it possible to mimic extended α‐helical surfaces. Synthetic methods were developed to produce quinoline monomers suitably functionalized for solid phase synthesis. A dodecamer was prepared. Its crystal structure validated the initial design and showed helix bundling involving the α‐helix‐like interface. These results open up new uses of aromatic helices to recognize protein surfaces and to program helix bundling in water