Mind the gap

The unmet needs of biomedical and clinical research are highlighted by reference to drug -induced liver injury(DILI), non-alcoholic fatty liver disease (NAFLD) and its severe form, non-alcoholic steatohepatitis (NASH). Examples in these areas highlight the major limitations of animal models with respect to predicting, examining and managing these clinically significant forms of liver injury. The way in which these knowledge gaps are being bridged by studies involving the use of human tissues and primary cells are described.     

Mind the gap

Nature presents plenty of examples of cellular behavior that determines the shape of an organ during development, such as epithelial polarity and cell division orientation. Little is known, however, about how organs regenerate or how cellular behavior affects regeneration. One of the most exciting aspects of regeneration biology is understanding how proliferation and patterning are coordinated, since it means that cells not only have to proliferate but also have to do so in an ordered manner so that organs are reconstructed proportionally. Drosophila wing imaginal discs and adult wings are models used in different approaches to investigate this issue; they have recently been used to reveal that, after localized cell death, neighboring cells change their cell division orientation toward the damaged zone. During this process, cell polarity and spindle orientation operate in coordination with cell proliferation to regenerate proper organ size and shape.     

Bridging the gap

Therapeutic monoclonal antibodies (mAbs) currently dominate the biologics marketplace. Development of a new therapeutic mAb candidate is a complex, multistep process and early stages of development typically begin in an academic research environment. Recently, a number of facilities and initiatives have been launched to aid researchers along this difficult path and facilitate progression of the next mAb blockbuster. Complementing this, there has been a renewed interest from the pharmaceutical industry to reconnect with academia in order to boost dwindling pipelines and encourage innovation. In this review, we examine the steps required to take a therapeutic mAb from discovery through early stage preclinical development and toward becoming a feasible clinical candidate. Discussion of the technologies used for mAb discovery, production in mammalian cells and innovations in single-use bioprocessing is included. We also examine regulatory requirements for product quality and characterization that should be considered at the earliest stages of mAb development. We provide details on the facilities available to help researchers and small-biotech build value into early stage product development, and include examples from within our own facility of how technologies are utilized and an analysis of our client base.     

The communications gap

Gap junctions are ubiquitous channels that serve a vital function in communication between cells. Vertebrates and invertebrates have gap junction proteins that are very different at the sequence level but nonetheless have much in common?     

Estimation of canopy gap size and gap shape using a hemispherical photograph

Gap size and gap shape are two important properties of forest gaps that can influence microsite conditions in a forest stand and determine the recruitment and establishment of trees. There is no universally adopted method for measuring the gap size, although several options are available. In addition, few methods have been proposed for measuring the gap shape. This paper proposes a photographic method of estimating canopy gap size and gap shape. The proposed method is based on a vertical hemispherical photograph of the gap and is thus named the hemispherical photograph method (HPM). We tested the accuracy of the HPM measure of gap size by two ground-based methods and compared the HPM with other methods. Our results indicate that the HPM measurement of the canopy gap size is accurate, but is significantly influenced by the location of the camera. Compared with the ground-based methods, the HPM is more objective and repeatable. Compared with other photographic methods, HPM is more accurate due to the more actual assumptions, but is more labor-intensive because more field measurements are necessary. We conclude that the HPM is a powerful tool for comparative and long-term studies of forest gaps.     

Mind the sustainability gap

Despite increasing efforts to reach sustainability, key global biophysical indicators such as climate change and biodiversity loss continue to deteriorate rather than improve. Ongoing failure to move towards sustainability calls into question the focus of current research and policy. We recommend two strategies for progress. First, sustainability must be conceptualized as a hierarchy of considerations, with the biophysical limits of the Earth setting the ultimate boundaries within which social and economic goals must be achieved. Second, transdisciplinary research programs must confront key normative questions facing modern consumer societies. The humanities should have a key role in such programs. Assisted by these strategies, ambitious targets that realistically reflect the biophysical limits of the life-support system of the Earth must be set and relentlessly worked towards.