Mechanisms of kinetic trapping in self-assembly and phase transformation

In self-assembly processes, kinetic trapping effects often hinder the formation of thermodynamically stable ordered states. In a model of viral capsid assembly and in the phase transformation of a lattice gas, we show how simulations in a self-assembling steady state can be used to identify two distinct mechanisms of kinetic trapping. We argue that one of these mechanisms can be adequately captured by kinetic rate equations, while the other involves a breakdown of theories that rely on cluster size as a reaction coordinate. We discuss how these observations might be useful in designing and optimising self-assembly reactions

True-color 3D surface metrology for additive manufacturing using interference microscopy

Coherence scanning interferometry (CSI) is widely used for surface topography characterisation. With the ability to measure both rough surfaces with the high slopes and optical finishes, CSI has made contibutions in fields from industrial machining to optical fabrication and polishing [1,2]. While the low coherence sources for CSI are typically broadband and suitable for color imaging, the metrology is usually performed without regards for the color information [3]. We present color surface topography measurements from a CSI instrument designed to provide true color images in addition to areal surface topography of additive manufactired samples. The addition of color measurements enables contamination and defect detection along with blemish and discoloration identification

Earthworm functioning in soil ecosystem services in relation to land use intensity

The FP7 EcoFINDERS project aimed to assess the relationship between soil biodiversity and ecosystem service provision. We studied functional responses for earthworms and fungi on soil formation and water regulation under different agricultural land uses representing a range in land use intensity. The aim was to establish and quantify these functional relationships by literature and field studies

Physical environmental factors that invite older adults to walk for transportation

Knowledge on the physical environmental factors that invite older adults to walk for transportation is limited. The current study aimed to investigate the relationships between environmental factors and invitingness to walk for transportation and the potential moderating effects of gender, functional limitations and current walking for transportation behavior. Sixty older participants evaluated 40 panoramic photographs on their invitingness in two ways: a forced choice (first impressions) and a rating task (more deliberate evaluation). Presence of vegetation, benches, and surveillance significantly positively related to both invitingness-measures. Upkeep and presence of historic elements significantly positively related to the assigned invitingness-ratings. For the forced choice task, significant positive relationships emerged for land use and separation between sidewalk and cycling path, but only in functionally limited participants. Environments offering comfort, safety from crime, and pleasantness may attract older adults to walk for transportation. Experimental and on-site studies are needed to elaborate on current findings

MICU2, a Paralog of MICU1, Resides within the Mitochondrial Uniporter Complex to Regulate Calcium Handling

Mitochondrial calcium uptake is present in nearly all vertebrate tissues and is believed to be critical in shaping calcium signaling, regulating ATP synthesis and controlling cell death. Calcium uptake occurs through a channel called the uniporter that resides in the inner mitochondrial membrane. Recently, we used comparative genomics to identify MICU1 and MCU as the key regulatory and putative pore-forming subunits of this channel, respectively. Using bioinformatics, we now report that the human genome encodes two additional paralogs of MICU1, which we call MICU2 and MICU3, each of which likely arose by gene duplication and exhibits distinct patterns of organ expression. We demonstrate that MICU1 and MICU2 are expressed in HeLa and HEK293T cells, and provide multiple lines of biochemical evidence that MCU, MICU1 and MICU2 reside within a complex and cross-stabilize each other's protein expression in a cell-type dependent manner. Using in vivo RNAi technology to silence MICU1, MICU2 or both proteins in mouse liver, we observe an additive impairment in calcium handling without adversely impacting mitochondrial respiration or membrane potential. The results identify MICU2 as a new component of the uniporter complex that may contribute to the tissue-specific regulation of this channel.National Institutes of Health (U.S.) (GM0077465)National Institutes of Health (U.S.) (DK080261

Macrophages in inflammatory multiple sclerosis lesions have an intermediate activation status

BACKGROUND: Macrophages play a dual role in multiple sclerosis (MS) pathology. They can exert neuroprotective and growth promoting effects but also contribute to tissue damage by production of inflammatory mediators. The effector function of macrophages is determined by the way they are activated. Stimulation of monocyte-derived macrophages in vitro with interferon-γ and lipopolysaccharide results in classically activated (CA/M1) macrophages, and activation with interleukin 4 induces alternatively activated (AA/M2) macrophages. METHODS: For this study, the expression of a panel of typical M1 and M2 markers on human monocyte derived M1 and M2 macrophages was analyzed using flow cytometry. This revealed that CD40 and mannose receptor (MR) were the most distinctive markers for human M1 and M2 macrophages, respectively. Using a panel of M1 and M2 markers we next examined the activation status of macrophages/microglia in MS lesions, normal appearing white matter and healthy control samples. RESULTS: Our data show that M1 markers, including CD40, CD86, CD64 and CD32 were abundantly expressed by microglia in normal appearing white matter and by activated microglia and macrophages throughout active demyelinating MS lesions. M2 markers, such as MR and CD163 were expressed by myelin-laden macrophages in active lesions and perivascular macrophages. Double staining with anti-CD40 and anti-MR revealed that approximately 70% of the CD40-positive macrophages in MS lesions also expressed MR, indicating that the majority of infiltrating macrophages and activated microglial cells display an intermediate activation status. CONCLUSIONS: Our findings show that, although macrophages in active MS lesions predominantly display M1 characteristics, a major subset of macrophages have an intermediate activation status

Impact of DNA damage repair defects and aggressive variant features on response to carboplatin-based chemotherapy in metastatic castration-resistant prostate cancer

Platinum-based chemotherapy is not standard of care for unselected or genetically selected metastatic castration-resistant prostate cancer (mCRPC) patients. A retrospective assessment of 71 patients was performed on platinum use in the Netherlands. Genetically unselected patients yielded low response rates. For a predefined subanalysis of all patients with comprehensive next-generation sequencing, 30 patients were grouped based on the presence of pathogenic aberrations in genes associated with DNA damage repair (DDR) or aggressive variant prostate cancer (AVPC). Fourteen patients (47%) were DDR deficient (DDRd), of which seven with inactivated BRCA2 (BRCA2mut). Six patients classified as AVPC. DDRd patients showed beneficial biochemical response to carboplatin, largely driven by all BRCA2mut patients having >50% prostate-speci