The current biodiversity extinction event: Scenarios for mitigation and recovery

The current massive degradation of habitat and extinction of species is taking place on a catastrophically short timescale, and their effects will fundamentally reset the future evolution of the planet's biota. The fossil record suggests that recovery of global ecosystems has required millions or even tens of millions of years. Thus, intervention by humans, the very agents of the current environmental crisis, is required for any possibility of short-term recovery or maintenance of the biota. Many current recovery efforts have deficiencies, including insufficient information on the diversity and distribution of species, ecological processes, and magnitude and interaction of threats to biodiversity (pollution, overharvesting, climate change, disruption of biogeochemical cycles, introduced or invasive species, habitat loss and fragmentation through land use, disruption of community structure in habitats, and others). A much greater and more urgently applied investment to address these deficiencies is obviously warranted. Conservation and restoration in human-dominated ecosystems must strengthen connections between human activities, such as agricultural or harvesting practices, and relevant research generated in the biological, earth, and atmospheric sciences. Certain threats to biodiversity require intensive international cooperation and input from the scientific community to mitigate their harmful effects, including climate change and alteration of global biogeochemical cycles. In a world already transformed by human activity, the connection between humans and the ecosystems they depend on must frame any strategy for the recovery of the biota.

Intervention of carbohydrate recognition by proteins and nucleic acids.

Carbohydrates in biological systems are often associated with specific recognition and signaling processes leading to important biological functions and diseases. Considerable efforts have been directed toward understanding and mimicking the recognition processes and developing effective agents to control the processes. The pace of discovery research in glycobiology and development of carbohydrate-based therapeutics, however, has been relatively slow due to the lack of appropriate strategies and methods available for carbohydrate-related research. This review summarizes some of the most recent developments in the field, with particular emphasis on work from our laboratories regarding the use of chemoenzymatic strategies to tackle the carbohydrate recognition problem. Highlights include the study of selectin-carbohydrate and aminoglycoside-RNA interactions and development of agents for the intervention of these recognition processes.

Induction of microsatellite instability by oxidative DNA damage

Instability of repetitive sequences, both in intronic sequences and within coding regions, has been demonstrated to be a hallmark of genomic instability in human cancer. Understanding how these mutational events arise may provide an opportunity for prevention or early intervention in cancer development. To study the source of this instability, we have identified a region of the β-lactamase gene that is tolerant to the insertion of fragments of exogenous DNA as large as 1,614 bp with minimal loss of enzyme activity, as determined by antibiotic resistance. Fragments inserted out-of-frame render Escherichia coli sensitive to antibiotic, and compensatory frameshift mutations that restore the reading frame of β-lactamase can be selected on the basis of antibiotic resistance. We have utilized this site to insert a synthetic microsatellite sequence within the β-lactamase gene and selected for mutations yielding frameshifts. This assay provides for detection of one frameshift mutation in a background of 106 wild-type sequences. Mismatch repair deficiency increased the observed frameshift frequency ≈300-fold. Exposure of plasmid containing microsatellite sequences to hydrogen peroxide resulted in frameshift mutations that were localized exclusively to the microsatellite sequences, whereas DNA damage by UV or N-methyl-N′-nitro-N-nitrosoguanidine did not result in enhanced mutagenesis. We postulate that in tumor cells, endogenous production of oxygen free radicals may be a major factor in promoting instability of microsatellite sequences. This β-lactamase assay may provide a sensitive methodology for the detection and quantitation of mutations associated with the development of cancer.

Composite fermions and bosons: An invitation to electron masquerade in Quantum Hall

The two-dimensional electron gas formed at the semiconductor heterointerface is a theater for many intriguing plays of physics. The fractional quantum Hall effect (FQHE), which occurs in strong magnetic fields and low temperatures, is the most fascinating of them. The concept of composite fermions and bosons not only is beautiful by itself but also has proved highly successful in providing pictorial interpretation of the phenomena associated with the FQHE.

Structural recovery in lesioned adult mammalian spinal cord by x-irradiation of the lesion site.

Mechanical injury to the adult mammalian spinal cord results in permanent morphological disintegration including severance/laceration of brain-cord axons at the lesion site. We report here that some of the structural consequences of injury can be averted by altering the cellular components of the lesion site with x-irradiation. We observed that localized irradiation of the unilaterally transected adult rat spinal cord when delivered during a defined time-window (third week) postinjury prevented cavitation, enabled establishment of structural integrity, and resulted in regrowth of severed corticospinal axons through the lesion site and into the distal stump. In addition, we examined the natural course of degeneration and cavitation at the site of lesion with time after injury, noting that through the third week postinjury recovery processes are in progress and only at the fourth week do the destructive processes take over. Our data suggest that the adult mammalian spinal cord has innate mechanisms required for recovery from injury and that timed intervention in certain cellular events by x-irradiation prevents the onset of degeneration and thus enables structural regenerative processes to proceed unhindered. We postulate that a radiation-sensitive subgroup of cells triggers the delayed degenerative processes. The identity of these intrusive cells and the mechanisms for triggering tissue degeneration are still unknown.

High fat diet-induced hyperglycemia: prevention by low level expression of a glucose transporter (GLUT4) minigene in transgenic mice.

High-fat intake leading to obesity contributes to the development of non-insulin-dependent diabetes mellitus (NIDDM, type 2). Similarly, mice fed a high-fat (safflower oil) diet develop defective glycemic control, hyperglycemia, and obesity. To assess the effect of a modest increase in the expression of GLUT4 (the insulin-responsive glucose transporter) on impaired glycemic control caused by fat feeding, transgenic mice harboring a GLUT4 minigene were fed a high-fat diet. Low-level tissue-specific (heart, skeletal muscle, and adipose tissue) expression of the GLUT4 minigene in transgenic mice prevented the impairment of glycemic control and accompanying hyperglycemia, but not obesity, caused by fat feeding. Thus, a small increase (< or = 2-fold) in the tissue level of GLUT4 prevents a primary symptom of the diabetic state in a mouse model, suggesting a possible target for intervention in the treatment of NIDDM.