1998 Basmajian Student Award Paper: Movement patterns after anterior cruciate ligament injury: a comparison of patients who compensate well for the injury and those who require operative stabilization

The purpose of this study was to describe kinematic and kinetic differences between a group of ACL deficient subjects who were grouped according to functional ability. Sixteen patients with complete ACL rupture were studied; eight subjects had instability with activities of daily living (non-copers) and eight subjects had returned to all pre-injury activity without limitation (copers). Three-dimensional joint kinematics and kinetics were collected from the knee and ankle during walking, jogging and going up and over a step. Results showed that both groups mitigated the force with which they contacted the floor but non-copers consistently demonstrated less knee flexion in the involved limb. The copers used joint kinematics similar to those of their uninvolved knees and similar to knee motions reported in uninjured subjects. The reduced knee motion in the involved knee of the non-copers did not correlate directly with quadriceps femoris muscle weakness.

The data suggest that the non-copers utilize a stabilization strategy which stiffens the knee joint which not only is unsuccessful but may lead to excessive joint contact forces which have the potential to damage articular structures. The copers use a strategy which permits normal knee kinematics and bodes well for joint integrity.     

Review: Helicobacter: Inflammation,immunology, and vaccines

Chronic inflammation induced by Helicobacter pylori infection is a critical factor in the development of peptic ulcer disease and gastric cancer. Central to this inflammation is the initiation of pro‐inflammatory signaling cascades within epithelial cells, in particular those mediated by two sensors of bacterial cell wall components, nucleotide‐binding oligomerization domain‐containing protein 1 (NOD1) and alpha‐protein kinase 1 (ALPK1). H pylori is, however, also highly adept at mitigating inflammation in the host, thereby restricting tissue damage and favoring bacterial persistence. H pylori modulates host immune responses by altering cytokine signaling in epithelial and myeloid cells, which results in increased proliferation of regulatory T cells and downregulation of effector T‐cell responses. H pylori vacuolating cytotoxin A (VacA) has been shown to play an important role in the dampening of immune responses and induction of immune tolerance capable of protecting against asthma. It is also possible to generate protective immune responses by immunization with various H pylori antigens or their epitopes, in combination with an adjuvant, though this for now has only been shown in mouse models. Novel non‐toxic adjuvants, consisting of modified bacterial enterotoxins or nanoparticles, have recently been developed that may not only enhance vaccine efficacy, but also help translate candidate vaccines to the clinic. This review will summarize the main discoveries in the past year regarding host immune responses to H pylori infection, as well as the design of new vaccine approaches against this infection.     

Phylogeny,classification, and biogeography of Afrotrichloris,Apochiton, Coelachyrum,Dinebra, Eleusine,Leptochloa, Schoenefeldia,and a new genus,Schoenefeldiella (Poaceae: Chloridoideae: Cynodonteae: Eleusininae)

To investigate the evolutionary relationships among species of Afrotrichloris, Apochiton, Coelachyrum, Dinebra, Eleusine, Leptochloa, and Schoenefeldia of subtribe Eleusininae, a phylogeny based on DNA sequences from nine gene regions (ITS, rps16-trnK, rps3, rps16, rpoC2, rpl32-trnL, ndhF, ndhA, ccsA) is presented. Previous molecular phylogenies indicated that Coelachyrum was polyphyletic and Schoenefeldia was paraphyletic, with Afrotrichloris embedded within it. Apochiton burttii was embedded in the Coelachyrum clade paired with C. longiglume, Coelachyrumpoiflorum was placed outside of Coelachyrum and sister to Eleusine, and Schoenefeldia is paraphyletic, with its two species forming a grade sister to Afrotrichoris. Our molecular phylogeny supports recognition of a new genus, Schoenefeldiella, and a new combination, Schoenfeldiella transiens. In addition, we provide generic emendations for Coelachyrum, which now includes five species including a new combination proposed here, Coelachyrum burttii, and Eleusine, which now includes 11 species.     

Eliciting Play: A Comparative Study: (Octodon, Octodontomys, Pediolagus, Phoca, Chocropsis, Ailuropoda)

The social play behavior of six mammalian species (Rodentia,Pinnipedia, Artiodactyla, Carnivora) is described and compared.Locomotor and Rotational Movements, e.g., jumping, running,and headshaking, occurred in all species and predominated inthe rodent play. These movements are similar in form to anti-predatorand "protective" responses and result in an immediate but temporarycessation of sensory stimulation from conspecifics. Investigation of body odors was the most important stimuluseliciting Locomotor-Rotational Movements in the rodents. Inthe larger mammals, body odor sniffing was enhanced during play,but specialized signals from other sensory modalities elicitedand maintained play interactions. The possible functions ofa heightened exchange of olfactory information during juvenilesocial development are discussed.     

Focus: A Multifaceted Battle Against Cancer: Basal Cell Carcinoma: Pathogenesis,Epidemiology, Clinical Features,Diagnosis, Histopathology,and Management

Basal cell carcinoma (BCC) is the most common malignancy. Exposure to sunlight is the most important risk factor. Most, if not all, cases of BCC demonstrate overactive Hedgehog signaling. A variety of treatment modalities exist and are selected based on recurrence risk, importance of tissue preservation, patient preference, and extent of disease. The pathogenesis, epidemiology, clinical features, diagnosis, histopathology, and management of BCC will be discussed in this review.     

Islands: stability, diversity, conservation

Islands present both a diversity and a stability paradox. They are often highly species-poor but have considerable biological interest in terms of extraordinary endemic genera and taxonomically isolated groups. They appear to be stable, as in some cases these organisms have persisted for many millions of years, and having an oceanic climate, extreme climatic events may be comparatively rare. However, when subject to extrinsic (anthropogenic) disturbance they do not appear to be stable, but often suffer catastrophic ecological change. These apparent paradoxes are resolved when it is realized that all these features are consequences of the same island characteristics: biotic isolation and oceanicity. As a result of these two characteristics, far oceanic islands are quantitatively different from continental systems in the nature of their ecological processes, which appear to give rise to an extreme punctuated equilibrium model of evolutionary change. Endemics may be ancient relict endemics displaying prolonged stasis and persistence, or products of adaptive radiation representing rapid punctuational events. A process-based definition of a relict endemic (palaeoendemic) is one whose founding lineage (i.e. the original continental source taxon) has not left any descendents. A corollary of this definition is that the time of divergence between an endemic and its continental sister-group should predate the colonization of the island by the now endemic lineage. An example is Dicksonia arborescens which has been on St Helena for at least 9 Myrs and no longer occurs in the likely source area of Africa. These relict endemics, frequent on islands, are important as the last remnants of tranches of biodiversity that have vanished elsewhere. Island conservation strategies require an integrated understanding of both sides of the diversity and stability paradox so that both island processes and island organisms can be conserved.     

Chemotaxis: Movement,direction, control

This review focuses on basic principles of motility in different cell types, formation of the specific cell structures that enable directed migration, and how external signals are transduced into cells and coupled to the motile machinery. Feedback mechanisms and their potential role in maintenance of internal chemotactic gradients and persistence of directed migration are highlighted.     

Ubiquitin: structures, functions, mechanisms

Ubiquitin is the founding member of a family of structurally conserved proteins that regulate a host of processes in eukaryotic cells. Ubiquitin and its relatives carry out their functions through covalent attachment to other cellular proteins, thereby changing the stability, localization, or activity of the target protein. This article reviews the basic biochemistry of these protein conjugation reactions, focusing on ubiquitin itself and emphasizing recent insights into mechanism and specificity.     

Biotechnology: Health care,agriculture, industry,environment

New developments in different branches of biotechnology are discussed. The production of peptide hormones, new interferons and other lymphokines by the microbial and cell cultures, and new enzyme inhibitors of microbial origin are the most important for health care and pharmacy. The main direction in research in the agriculture represents the development of the new, very effective methods of nitrogen fixation and the production of animal growth hormones by genemanipulated microorganisms. One of the most important field of application of biotechnology is the chemical industry, c.f. microbial production of polymers and biotransformation of compounds previously produced by chemical methods (acrylamide, adipic acid, naphtalen conversion, etc.). Several novel methods of degradation of the cellulosic materials are mentioned and exploitation of biotechnology in environmental protection is also discussed.     

Thioredoxin: structure, properties, function

Thioredoxin, a disulfide-containing protein having a highly conservative structure, is present in all types of organisms that are phylogenetically distant from one another. The protein possesses unique capabilities and is universal in respect of physiological functions it performs. In particular, this protein participates in nucleic acid metabolism and thus may protect cells against the lethal influence of gamma-irradiation.     

Allophycocyanin: trimers,monomers, subunits,and homodimers

Allophycocyanin is a photosynthetic light-harvesting pigment-protein complex located in the phycobilisomes of cyanobacteria and red algae. Using dynamic light scattering and circular dichroism, solutions of purified allophycocyanin were shown to consist of homogeneous trimers (alpha3beta3) with a nonspherical shape over a very wide range of protein concentrations at pH 6.0 and 20 degrees C. Deconvolutions of the visible circular dichroism spectrum of the trimer were carried out for the first determination of the individual spectra of all six-component chromophores. The chromophores were shown to be in different microenvironments that helped determine the spectrum of the trimer. Monomers (alpha beta) that were formed in either the presence of 0.50M NaSCN or at 45 degrees C were shown to be completely reversible to trimers. However, subunits (alpha and beta) that were formed in either the presence of 8M urea or at 60 degrees C, using spectroscopy and gel-filtration column chromatography, were observed to only partially reconstitute trimers. Homodimers (alpha2 and/or beta2) formed during the regeneration of trimers. The homodimer, which was detected for the first time when both subunits were present, was shown to be in equilibrium with its subunits. Unlike the trimer situation, subunits were found to fully reconstitute monomers in the presence of 0.50M NaSCN. These results suggest a route to trimer assembly from subunits with monomers serving as intermediaries and the homodimers forming in a nonproductive step that did not interfere with the overall assembly scheme.     

Focus: A Multifaceted Battle Against Cancer: Nuns,Warts, Viruses,and Cancer

It has been known for more than 150 years that the risk of carcinoma of the uterine cervix correlates with the number of sexual partners. Laboratory and epidemiological evidence demonstrated that infection with certain human papillomavirus (HPV) types initiates the vast majority of, if not all, cervical cancer, as well as a substantial fraction of other cancers, including other anogenital cancer and oropharyngeal cancer. Pap smear testing resulted in a dramatic reduction in the incidence of cervical cancer in the developed world, and HPV vaccination has the potential to eradicate HPV-associated cancer worldwide and represents a major public health breakthrough. The major current challenge is to ensure that HPV vaccines are widely administered.     

FEN nucleases: bind, bend, fray, cut

In this issue, Orans et al. (2011) and Tsutakawa et al. (2011) report exciting insights into the molecular principles governing diverse endo- and exonucleolytic cleavage specificities of members of the RAD2/FEN superfamily of nucleases, which have critical roles in DNA replication and maintenance.     

Focus: A Multifaceted Battle Against Cancer: Ashley W. Oughterson,MD: Surgeon,Soldier, Leader

Ashley W. Oughterson, MD, (1895-1956) was a longtime faculty surgeon at Yale University. He performed some of the earliest pancreatic resections in the United States. During World War II, Colonel Oughterson was the primary “Surgical Consultant” in the South Pacific and present at nearly every major battle. His meticulously kept diary is regarded as the foremost source detailing wartime surgical care. Colonel Oughterson led the initial Army team to survey Hiroshima and Nagasaki following the nuclear attacks. Thoughout his academic career at Yale, Oughterson was a key leader in several medical and surgical societies. As scientific director of the American Cancer Society, Oughterson lectured widely and guided research priorities in oncology following World War II. Oughterson also authored numerous benchmark papers in surgical oncology that continue to be cited today. These extensive contributions are examined here and demonstrate the wide-ranging impact Oughterson exerted during a formative period of American surgery.     

Behavioral genomics: A, bee, C, G, T

Honeybees, termites and ants occupy the 'pinnacle of social evolution' with societies of a complexity that rivals our own. The sequencing of the honeybee genome will provide a strong foundation for studying the genetic basis of complex social behavior.     

MicroRNAs: genomics, biogenesis, mechanism, and function

MicroRNAs (miRNAs) are endogenous approximately 22 nt RNAs that can play important regulatory roles in animals and plants by targeting mRNAs for cleavage or translational repression. Although they escaped notice until relatively recently, miRNAs comprise one of the more abundant classes of gene regulatory molecules in multicellular organisms and likely influence the output of many protein-coding genes.     

Editor's column: Planktic, nektic, benthic

The terms planktic, nektic , and benthic are taken as examples of the construction and malconstruction of biological and geological terms. Both in vernacular terminology and systematic nomenclature the formation of adjectives and compounds follows the same basic rules - keep the three concepts of stem, suffix, and connective vowel clear, and most of the serious malconstructions will be avoided.     

Hyperprolactinemia: causes, diagnosis, and treatment

The basic data on hyperprolactinemia (i.e. an excess of PRL above a reference laboratory's upper limits), the most common endocrine disorder of the hypothalamic-pituitary axis are given in this review. The following issues are discussed: regulation of prolactin (Prl) secretion, definition of hyperprolactinemia, its etiology and pathogenesis as well as its symptoms, diagnosis, and treatment (including medical and surgical therapy). It should be stressed that finding of elevated PRL serum concentrations constitute the beginning of diagnostic procedure and, after exclusion of physiologic, pharmacologic, and other organic causes of increased PRL levels, should be followed by detailed diagnosis including MRI. In patients in whom hyperprolactinemia has been confirmed the treatment with dopamine agonists (with prevalence of cabergoline, followed by quinagoline) is currently considered first-choice therapy. Surgery should be performed only in the patients resistant or intolerant to these agents, or in patients who refuse long-term therapy.     

Integrons: Past,Present, and Future

SUMMARY

Integrons are versatile gene acquisition systems commonly found in bacterial genomes. They are ancient elements that are a hot spot for genomic complexity, generating phenotypic diversity and shaping adaptive responses. In recent times, they have had a major role in the acquisition, expression, and dissemination of antibiotic resistance genes. Assessing the ongoing threats posed by integrons requires an understanding of their origins and evolutionary history. This review examines the functions and activities of integrons before the antibiotic era. It shows how antibiotic use selected particular integrons from among the environmental pool of these elements, such that integrons carrying resistance genes are now present in the majority of Gram-negative pathogens. Finally, it examines the potential consequences of widespread pollution with the novel integrons that have been assembled via the agency of human antibiotic use and speculates on the potential uses of integrons as platforms for biotechnology.