bluuebunny/crossref_metadata_2025 huggingface dataset:
Radiology of the gastrointestinal tract
Authors: Freeman A.H.
Published: January 2012

The widespread introduction of endoscopic techniques has lessened the need for radiological examination of the intestinal tract, and has almost completely replaced it in the examination of the stomach. There remains, however, a major radiological role in the investigation of the small and large bowel; and clinically useful information can be obtained from thoughtful use of radiology in the diagnosis of abdominal and gastrointestinal disease in those regions of the world where facilities for endoscopy are not available....
Gastrointestinal bleeding
Authors: Rockall T.A. , Dowson H.M.P.
Published: January 2012

Gastrointestinal bleeding is a common emergency, with an incidence in the United Kingdom of about 1 per 1000 adults/year. It is subdivided into upper and lower, and acute or chronic, with acute upper gastrointestinal haemorrhage further subdivided into variceal and nonvariceal bleeding. Risk stratification in acute upper gastrointestinal haemorrhage can be performed using simple clinical and endoscopic criteria that can be used to estimate the risk of mortality, which overall is about 10% for both upper and lower gastrointestinal bleeds....
Hormones and the gastrointestinal tract
Authors: Bishop A.E. , Hammond P.J. , Polak J.M. , Bloom S.R.
Published: January 2012

The gastrointestinal tract is the largest endocrine organ in the body, with its component cells dispersed along its length rather than being clustered in glands. Gut peptides integrate gastrointestinal function by regulating the actions of the epithelium, muscles, and nerves, affect the growth and development of the gut and—as has emerged comparatively recently—they also have a major role in appetite control. There is little evidence that many gut peptides act as hormones in a classical endocrine fashion: many are autocrine, regulating the function of the cell secreting them, or paracrine, influencing the behaviour of neighbouring cells of different types....
Vascular and collagen disorders
Authors: Neale Graham
Published: January 2012

A wide range of vascular and collagen disorders may affect the gastro-intestinal tract. Most are quite uncommon but presentations are often dramatic with intestinal bleeding or gangrene.

Vascular insufficiency leading to ischaemic damage of the gut may be caused by occlusion of mesenteric vessels by either arterial thrombosis (usually with atheromatous pathology); or venous thrombosis (in thrombophilic conditions); or arterial emboli (as occurs with atrial fibrillation); or diffuse small vessel occlusion. There are four primary syndromes. (1) Acute mesenteric ischaemia—typically manifest as the sudden onset of abdominal pain, initially without marked tenderness or localizing signs. Diagnosis requires a high index of suspicion and is often delayed. Imaging serves primarily to exclude other causes of an apparent abdominal catastrophe but prompt laparotomy for embolectomy and/or arterial re-construction and/or bowel resection is required to minimize damage to the gut. (2) Chronic mesenteric ischaemia—usually due to atheroma, presents with severe cramping abdominal pain 20 to 60 min, after eating. Diagnosis requires vascular imaging and usually the condition can be relieved only by revascularization. (3) Ischaemic colitis—presents with pain and tenderness in the left iliac fossa, nausea and vomiting, followed by the passage of a loose motion containing dark blood. Contrast enema examination characteristically shows ‘thumbprinting’ of the colonic mucosa. Most cases resolve spontaneously so supportive management is usually sufficient. (4) Ischaemia–reperfusion injury—diminishes the barrier function of the gut and may lead to septicaemia in those who are already critically ill....
Gastrointestinal infections
Authors: Hamer Davidson H. , Gorbach Sherwood L.
Published: January 2012

Gastrointestinal infections, especially diarrhoea, are responsible for substantial morbidity, mortality, and socioeconomic penalties worldwide. In poor countries, the greatest burden of disease is borne by infants and young children, although older people and immunocompromised patients are also at great risk of severe and complicated disease. Poor sanitation, inadequate water supplies, and globalization of food marketing increase the risk of large epidemics of food- and water-borne outbreaks of gastrointestinal disease....
Cirrhosis and ascites
Authors: Moore Kevin
Published: January 2012

Case History—A 39 yr old man, known to have Wilson’s disease, now presenting with abdominal distension.

Ascites is the accumulation of fluid in the peritoneal cavity: 75% of cases are associated with cirrhosis, but there are many other causes, of which the commonest are malignancy and cardiac failure. The occurrence of ascites in patients with cirrhosis is associated with a poor prognosis, with survival around 50% at 1 to 2 years....
Syncope and palpitations
Authors: Rajappan K. , Rankin A.C. , McGavigan A.D. , Cobbe S.M.
Published: January 2012

Syncope is a transient episode of loss of consciousness (T-LOC) due to cerebral hypoperfusion. Its causes can be subdivided on the basis of pathophysiology, including (1) neurally mediated—or reflex—syncope; (2) orthostatic hypotension; (3) cardiac causes; and (4) cerebrovascular or psychogenic causes.

Neurocardiogenic syncope, or simple faint, is the commonest cause and is benign, but it is always important to exclude or establish the diagnosis of cardiac syncope, because this has an adverse prognosis that may be improved with appropriate treatment. Cardiac arrhythmia should be considered in all patients who have syncope associated with any of the following: (1) exertion, chest pain, or palpitations; (2) a past medical history of heart disease; (3) abnormal cardiovascular findings on examination; (4) an abnormal ECG; and (5) a family history of sudden cardiac death in people younger than 40 years old or with an inherited cardiac condition....
Pericardial disease
Authors: Henein Michael
Published: January 2012

The most common clinical presentations of pericardial disease are pericarditis, effusion, tamponade, and constriction.

The most common proven causes are viral infection or as a complication of myocardial infarction, but a wide range of other conditions including autoimmune rheumatic disorders and tuberculosis need to be considered. No firm cause is established in many cases, which are regarded as ‘idiopathic’ (presumed viral)....
Acute rheumatic fever
Authors: Carapetis Jonathan R.
Published: January 2012

Acute rheumatic fever is an immunologically mediated multisystem disease induced by recent infection with group A streptococcus. About 5% of people have the potential to develop acute rheumatic fever after infection by a strain of streptococcus with propensity to cause the condition. Most cases (97%) occur in low-income and some middle-income countries, with indigenous populations in some affluent countries also affected. Children aged 5 to 15 years are most commonly affected, and rheumatic heart disease remains the most common acquired heart disease of childhood in the world....
Tumours of the heart
Authors: Traill Thomas A.
Published: January 2012

Cardiac myxomas are rare benign tumours that grow in the lumen of the atria, usually the left. Most are sporadic, but they can be associated with the Carney complex, where unusual freckling is typically the most obvious clinical clue.

Symptoms and signs most commonly mimic those of mitral stenosis. Systemic emboli occur in about 40% of cases. Constitutional effects predominate in a few patients who present with what seems to be an obscure multisystem disorder. In many patients, specific cardiovascular signs are inconspicuous or absent: an audible ‘tumour plop’ in early diastole, analogous to a mitral opening snap, is often reported only after the diagnosis is established....
Cardiac involvement in genetic disease
Authors: Traill Thomas A.
Published: January 2012

Many clinicians find themselves faced, from time to time, with a patient who has a family history of a known disorder, such as Marfan’s syndrome, or who has noncardiac features that suggest a syndrome.

Down’s syndrome—25 to 50% have congenital heart disease, most characteristically atrioventricular canal defect....
Pulmonary oedema
Authors: Morrell Nicholas W. , Firth John D.
Published: January 2012

The formation of pulmonary oedema depends on the balance between capillary hydrostatic pressure, interstitial tissue pressure, plasma colloid osmotic pressure, endothelial permeability, and lymphatic function. The efficiency of lymphatic drainage of interstitial fluid (which can increase >10-fold) is critical in determining the onset and extent of hydrostatic oedema....
Sedation and analgesia in the critically ill
Authors: Park Gilbert , Shelly Maire P.
Published: January 2012

Nearly all critically ill patients need analgesia, anxiolysis, hypnosis, or measures to help them tolerate their tracheal tube. Although making the patient unconscious may appear the easiest way to achieve this, it is fraught with hazards.

Pain relief and tube tolerance—these are the first priority, and usually involves giving opioids. Morphine, which has both analgesic and sedative effects, is the opioid against which others are judged. Remifentanil is a relatively new agent that has properties useful in critically ill patients: fast onset of action, a predictable short half-life (10–21 min), and it is broken down by a nonspecific enzyme system present in plasma such that accumulation does not occur, and the drug wears off rapidly, even after prolonged infusions and in renal or hepatic failure....
The clinical presentation of respiratory disease
Authors: Hopkin Julian
Published: January 2012

Respiratory disease can present in many ways, with variations attributable to many factors. The clinical presentation directs diagnostic hypothesis making, the choice of diagnostically discriminating investigations, and the most appropriate management. If a detailed history is not taken, the patient not observed carefully and examined diligently, and the information from these sources is not analysed correctly, then inappropriate investigation and management is likely....
Upper respiratory tract infections
Authors: Little P.
Published: January 2012

Acute upper respiratory tract infections (URTIs) are the commonest reason for patients to seek medical advice in the United Kingdom.

Pharyngitis/tonsillitis—this is caused by both bacterial and viral organisms, with sore throat often accompanied by fever, headache, and other symptoms, with or without enlarged and tender cervical lymph nodes, tonsillar erythema, and exudate. Investigations are not generally performed or required. Antibiotics have modest benefit, so for patients who are not unwell systemically the physician should either not prescribe, or use a delayed prescribing approach, advising the patient to wait for several days before collecting or using their prescription. The antibiotic of choice is probably penicillin V, with a short acting macrolide the second-line agent. The benefits of tonsillectomy in preventing recurrent sore throat are modest....
Pneumonia in the normal host
Authors: Bartlett John G.
Published: January 2012

Pneumonia is an acute or chronic infection involving the pulmonary parenchyma and is the most important infectious disease in terms of morbidity and mortality, which is 14% for patients who are hospitalized with community-acquired pneumonia.

Aetiology—most cases are caused by microbial pathogens, the commonest being ...
Nosocomial pneumonia
Authors: Bartlett John G.
Published: January 2012

Nosocomial pneumonia is generally defined as a new pulmonary infiltrate on chest radiography, combined with evidence of infection expressed as fever, purulent respiratory secretions and/or leucocytosis, with onset at least 72 h after admission. It is the most frequent lethal nosocomial infection (overall mortality 8 to 20%)....
Upper airways obstruction
Authors: Stradling J.R. , Craig S.E.
Published: January 2012

At resting levels of ventilation, the main airway can be reduced to a diameter of 3 mm or so before respiratory distress and stridor occur. Little more narrowing is required to precipitate complete asphyxia, hence when upper airways obstruction is suspected, assessment of severity, diagnosis, and treatment is a medical emergency....
Asthma
Authors: Taylor A.J. Newman , Cullinan Paul
Published: January 2012

Case History—An obese 51 yr old woman with breathlessness and swelling.

Asthma is a chronic inflammatory disease of the bronchial airways that is characterized pathologically by a desquamative eosinophilic bronchitis and clinically by reversible airway narrowing and increased airway responsiveness to nonspecific provocative stimuli. The condition is common, frequently disabling, and can cause death. In the Western world it now affects more than 10% of children and more than 5% of adults, and in England and Wales it is the cause of more than 100 000 hospital admissions and is the certified cause of death of 1500 to 2000 people each year....
Bronchiolitis obliterans and cryptogenic organizing pneumonia
Authors: Wells A.U. , Harrison Nicholas K.
Published: January 2012

Case History—A 77 yr old woman referred because her ‘pneumonia failed to clear’.

The nomenclature of the bronchiolitides is complicated by the interchangeable use of pathological and clinical descriptions and a diversity of classification systems. The four primary histological patterns are (1) organizing pneumonia (also termed proliferative bronchiolitis and bronchiolitis obliterans organizing pneumonia); (2) bronchiolitis obliterans (also termed obliterative bronchiolitis and constrictive bronchiolitis); (3) follicular bronchiolitis; and (4) diffuse panbronchiolitis....
Extrinsic allergic alveolitis
Authors: Hendrick D.J. , Spickett G.P.
Published: January 2012

Extrinsic allergic alveolitis is an uncommon inflammatory disorder of the lungs that results from hypersensitivity responses to inhaled environmental agents. Most varieties are occupational in origin, but sporadic cases arise in domestic settings or from recreational activities. Causal agents chiefly comprise allergenic microbial spores that contaminate stored vegetable produce (e.g. farmer’s lung caused by ...
Toxic gases and aerosols
Authors: Hendrick D.J.
Published: January 2012

Acute exposure—the effects of noxious gases or aerosols on the airways and lungs are determined by (1) their solubility in water, with those that are highly soluble having their main effect on the lining of the upper respiratory tract and those with lower solubility mainly affecting the lungs, and (2) the dose of exposure, with overwhelming exposures having adverse effects throughout the respiratory tract....
Clinical presentation and diagnosis of rheumatic disease
Authors: Russell Anthony S. , Ferrari Robert
Published: January 2012

Most rheumatological diagnoses are made through effective history taking and physical examination rather than investigation.

Systemic symptoms, such as weight loss, anorexia, and fever, point to systemic diseases such as rheumatoid arthritis, other polyarthritides, systemic lupus erythematosus, polymyalgia, and vasculitides. Swelling of joints is a symptom commonly reported by patients with no objective evidence of this on examination. Inflammatory arthropathies should not be diagnosed unless the physician is able to identify objective swelling, if necessary by arranging a prompt review during an active episode. Diagnostic criteria for the systemic rheumatic diseases are useful in directing the history taking to verify a suspected diagnosis....
Crystal-related arthropathies
Authors: Roddy Edward , Doherty Michael
Published: January 2012

Many crystals have been associated with arthropathies or periarticular syndromes: only monosodium urate monohydrate (gout), calcium pyrophosphate dehydrate (pseudogout, chondrocalcinosis), and basic calcium phosphates (mainly hydroxyapatite) are common.

Crystals implicated in joint disease are stable, hard particles that exert biological effects via surface-active (activation of humoral and cell-derived mediators, interaction with cell membranes) and mechanical properties. In general, smaller particle size, marked surface irregularity, and high negative surface charge correlate with inflammatory potential....
Disorders of potassium homeostasis
Authors: Firth J
Published: January 2012

The normal range of potassium concentration in serum is 3.5 to 5.0 mmol/litre and within cells it is 150 to 160 mmol/litre, the ratio of intracellular to extracellular potassium concentration being a critical determinant of cellular resting membrane potential and thereby of the function of excitable tissues....
Clinical presentation of renal disease
Authors: Fielding Richard E , Farrington Ken
Published: January 2012

Renal disease may present in many ways, including: (1) the screening of asymptomatic individuals; (2) with symptoms and signs resulting from renal dysfunction; and (3) with symptoms and signs of an underlying disease, often systemic, which has resulted in renal dysfunction.

History and clinical signs—in many cases these are nonspecific or not apparent, and detection of renal disease relies on a combination of clinical suspicion and simple investigations, including urinalysis (by dipstick for proteinuria and haematuria, with quantification of proteinuria most conveniently performed by estimation of the albumin:creatinine ratio, ACR, or protein:creatinine ratio, PCR) and estimation of renal function (by measurement of serum creatinine, expressed as estimated glomerular filtration rate, eGFR)....
Proliferative glomerulonephritis
Authors: Mathieson Peter W.
Published: January 2012

Proliferative glomerulonephritis—which occurs in many conditions—describes the finding of increased cellularity of the glomerulus, which may be due to proliferation of intrinsic glomerular cells, infiltration of leucocytes, or both. Patients will typically have haematuria, and this may be associated with proteinuria and/or impairment of excretory renal function and/or hypertension. Different subtypes of proliferative glomerulonephritis are recognized:...
Renal involvement in genetic disease
Authors: Joly D , Grünfeld J P
Published: January 2012

There are many inherited disorders in which the kidney is affected: this chapter is concerned with the commonest inherited diseases leading to renal failure.

Autosomal dominant polycystic kidney disease—accounts for about 7% of cases of endstage renal failure in Western countries. Inheritance is autosomal dominant, with mutations in polycystin 1 responsible for 85% of cases and mutations in polycystin 2 accounting for most of the remainder, these being transmembrane proteins that are able to interact, function together as a nonselective cation channel, and also induce several distinct transduction pathways. May present with renal pain, haematuria, urinary tract infection, or hypertension, or be discovered incidentally on physical examination or abdominal imaging, or by family screening, or after routine measurement of renal function. Commonly progresses to endstage renal failure at between 40 and 60 years of age. Extrarenal manifestations include intracranial aneurysms, liver cysts, and mitral valve prolapse....
Haemopoietic stem cell disorders
Authors: Linch D.C.
Published: January 2012

The term stem-cell disorder is usually understood to imply that a disease process has begun in a primitive cell with the potential to develop into cells of different lineages. Difficulties with such a definition include (1) malignant change in a very primitive cell does not necessarily lead to the production of mature cells of multiple lineages; (2) although an immature phenotype of a malignant cell may indicate transformation of a very early cell, it is possible that transformation could arise in a later cell with subsequent dedifferentiation....
Acute lymphoblastic leukaemia
Authors: Eden Tim
Published: January 2012

Genetic changes in key progenitor cells in acute lymphoblastic leukaemia (ALL) are typically either point mutations or (more frequently) translocation of proto-oncogenes to active promoter sites, with such genetic rearrangements leading to aberrant protein production. In most childhood disease the first genetic events arise in utero...
Acute myeloid leukaemia
Authors: Kell Jonathan , Knapper Steve , Burnett Alan
Published: January 2012

It is believed that acute myeloblastic leukaemia arises in a haematopoietic stem cell as a result of mutations which promote growth or inhibit apoptosis arising in association with mutations that inhibit differentiation. In most cases there is no obvious cause, but exposure to chemical and ionizing radiation may be relevant, including previous chemotherapy for solid tumours....
Paroxysmal nocturnal haemoglobinuria
Authors: Luzzatto Lucio
Published: January 2012

Paroxysmal nocturnal haemoglobinuria (PNH) is a unique disorder in which a substantial proportion of the patient’s red cells have an abnormal susceptibility to activated complement. This results from the presence of a clone that originates from a haematopoietic stem cell bearing an acquired somatic mutation in the X-linked gene ...
The spleen and its disorders
Authors: Swirsky D.
Published: January 2012

The spleen is the single largest lymphoid organ in the body, performing important immune functions. Intrinsic disorders of the spleen are very rare: its importance in clinical practice relate to the causes of its enlargement, its hyperfunction (hypersplenism), acute rupture, and the consequences of its physical or physiological absence....
Eosinophilia
Authors: Weller Peter F.
Published: January 2012

Eosinophilia (eosinophil count >0.45 × 109/litre) is associated with some infections, some allergic diseases, and a variety of other conditions, often neoplastic.

Parasitic diseases—eosinophilia is a characteristic feature of infection by multicellular helminth parasites, e.g. Strongyloides stercoralis, with diagnosis typically based on geographical/dietary history and examination of stool for ova and larvae....
Erythrocyte enzymopathies
Authors: Beutler Ernest
Published: January 2012

Numerous enzymes, including those of the hexose monophosphate pathway and glycolysis, are active in the red cell. They are required for the generation of ATP (needed to supply energy for sodium extrusion) and the reductants NADH and NADPH, necessary to maintain haemoglobin in its active ferrous atomic state, as well as for the integrity of sulphydryl groups present on essential proteins. 2,3-diphosphoglycerate (2,3-DPG), an intermediate of ...
Glucose-6-phosphate dehydrogenase (G6PD) deficiency
Authors: Luzzatto Lucio
Published: January 2012

Deficiency of the enzyme glucose 6-phosphate dehydrogenase (G6PD) in red blood cells is an inherited abnormality due to mutations of the G6PD gene on the X chromosome that renders the cells vulnerable to oxidative damage. The condition is widespread in many populations living in or originating from tropical and ...
Inherited skin disease
Authors: Leigh Irene M. , Kelsell David P.
Published: January 2012

Most patients referred from primary care to the dermatology clinic will be seeking advice and treatment for a few common skin disorders, including psoriasis, eczema, and acne. The genetic basis of these complex conditions is being unravelled. For example, susceptibility variants have been identified in the gene for filaggrin (...
Skin and systemic diseases
Authors: Archer Clive B.
Published: January 2012

Dermatology is most interesting where it overlaps with general internal medicine. Skin lesions may be part of a systemic disease (e.g. in sarcoidosis or systemic lupus erythematosus), or they may be a manifestation of an underlying disease or process as in the case of acanthosis nigricans, which can be associated with either an underlying adenocarcinoma in older patients, or with insulin resistance and sometimes overt diabetes mellitus in younger obese patients....
Lumbar puncture
Authors: Barker Roger A. , Phillips Wendy , Rhys Davies R.
Published: January 2012

Lumbar puncture provides the means to sample cerebrospinal fluid for diagnostic purposes and to remove it for some therapeutic purposes. The procedure allows measurement of the pressure of cerebrospinal fluid, its cytological composition, biochemical content, and microbial as well as serological characteristics.

Indications—the commonest diagnostic indications are clinical suspicion of central nervous system infection (meningitis, encephalitis), subarachnoid haemorrhage, and demyelinating diseases (central and peripheral); the commonest therapeutic indications are idiopathic intracranial hypertension and for intrathecal administration of drugs....
Investigation of central motor pathways: magnetic brain stimulation
Authors: Mills K.R.
Published: January 2012

The ability to percutaneously stimulate the central nervous system of awake humans without causing pain has opened up new areas for neurophysiological investigation in the early diagnosis of neurological disease, also furthered the understanding of normal and abnormal motor control. Magnetic stimulators are now available that can excite both upper and lower limb areas of the motor cortex, as well as cranial nerves, motor roots, and deeply sited peripheral nerves....
Alzheimer’s disease and other dementias
Authors: Hodges John R.
Published: January 2012

Dementia is defined as a syndrome consisting of progressive impairment in memory and at least one other cognitive deficit (aphasia, apraxia, agnosia, or disturbance in executive function) in the absence of another explanatory central nervous system disorder, depression or delirium.

Prevalence—dementia is common, affecting about 8% of all people over 65 years, rising to around 20% of those over 85 years. It is estimated that the 18 million people with dementia worldwide will increase to 34 million by the year 2025, with this increase being most marked in the developing countries....
The genomic basis of medicine
Authors: Stankiewicz Paweł , Lupski James R.
Published: January 2012

During the last two decades it has become possible to determine the entire DNA content of living organisms—the genome. The completion of the human reference DNA sequence has provided an enormous amount of DNA sequence data and has extended our view of the genetic bases of disease....
An antiarch placoderm shows that pelvic girdles arose at the root of jawed vertebrates
Authors: Zhu Min , Yu Xiaobo , Choo Brian , Wang Junqing , Jia Liantao
Published: January 2012

Almost all gnathostomes or jawed vertebrates (including osteichthyans, chondrichthyans, ‘acanthodians’ and most placoderms) possess paired pectoral and pelvic fins. To date, it has generally been believed that antiarch placoderms (extinct armoured jawed fishes from the Silurian–Devonian periods) lacked pelvic fins. The putative absence of pelvic fins is a key character bearing on the monophyly or paraphyly of placoderms. It also has far-reaching implications for studying the sequence of origin of pelvic girdles versus that of movable jaws in the course of vertebrate evolution.Parayunnanolepis xitunensisrepresents the only example of a primitive antiarch with extensive post-thoracic preservation, and its original description has been cited as confirming the primitive lack of pelvic fins in early antiarchs. Here, we present a revised description ofParayunnanolepisand offer the first unambiguous evidence for the presence of pelvic girdles in antiarchs. As antiarchs are placed at the base of the gnathostome radiation in several recent studies, our finding shows that all jawed vertebrates (including antiarch placoderms) primitively possess both pectoral and pelvic fins and that the pelvic fins did not arise within gnathostomes at a point subsequent to the origin of jaws.
Olfactory kin recognition in a songbird
Authors: Krause E. Tobias , Krüger Oliver , Kohlmeier Philip , Caspers Barbara A.
Published: January 2012

The ability to recognize close relatives in order to cooperate or to avoid inbreeding is widespread across all taxa. One accepted mechanism for kin recognition in birds is associative learning of visual or acoustic cues. However, how could individuals ever learn to recognize unfamiliar kin? Here, we provide the first evidence for a novel mechanism of kin recognition in birds. Zebra finch (Taeniopygia guttata) fledglings are able to distinguish between kin and non-kin based on olfactory cues alone. Since olfactory cues are likely to be genetically based, this finding establishes a neglected mechanism of kin recognition in birds, particularly in songbirds, with potentially far-reaching consequences for both kin selection and inbreeding avoidance.
Identification of two voltage-dependent anion channel-like protein sequences conserved in Kinetoplastida
Authors: Flinner Nadine , Schleiff Enrico , Mirus Oliver
Published: January 2012

The eukaryotic porin superfamily consists of two families, voltage-dependent anion channel (VDAC) and Tom40, which are both located in the mitochondrial outer membrane. In
Trypanosoma brucei
, only a single member of the VDAC family has been described. We report the detection of two additional eukaryotic porin-like sequences in
T. brucei
. By bioinformatic means, we classify both as putative VDAC isoforms.
Genetic consequences of climate change for northern plants
Authors: Alsos Inger Greve , Ehrich Dorothee , Thuiller Wilfried , Eidesen Pernille Bronken , Tribsch Andreas , Schönswetter Peter , Lagaye Claire , Taberlet Pierre , Brochmann Christian
Published: January 2012

Climate change will lead to loss of range for many species, and thus to loss of genetic diversity crucial for their long-term persistence. We analysed range-wide genetic diversity (amplified fragment length polymorphisms) in 9581 samples from 1200 populations of 27 northern plant species, to assess genetic consequences of range reduction and potential association with species traits. We used species distribution modelling (SDM, eight techniques, two global circulation models and two emission scenarios) to predict loss of range and genetic diversity by 2080. Loss of genetic diversity varied considerably among species, and this variation could be explained by dispersal adaptation (up to 57%) and by genetic differentiation among populations (
F
ST
; up to 61%). Herbs lacking adaptations for long-distance dispersal were estimated to lose genetic diversity at higher rate than dwarf shrubs adapted to long-distance dispersal. The expected range reduction in these 27 northern species was larger than reported for temperate plants, and all were predicted to lose genetic diversity according to at least one scenario. SDM combined with
F
ST
estimates and/or with species trait information thus allows the prediction of species' vulnerability to climate change, aiding rational prioritization of conservation efforts.
Vertigo in Children and Adolescents: Characteristics and Outcome
Authors: Gruber Maayan , Cohen-Kerem Raanan , Kaminer Margalit , Shupak Avi
Published: January 2012

Objectives. To describe the characteristics and outcome of vertigo in a pediatric population.Patients. All children and adolescents presenting with vertigo to a tertiary otoneurology clinic between the years 2003–2010 were included in the study.Results. Thirty-seven patients with a mean age of 14 years were evaluated. The most common etiology was migraine-associated vertigo (MAV) followed by acute labyrinthitis/neuritis and psychogenic dizziness. Ten patients (27%) had pathological findings on the otoneurological examination. Abnormal findings were documented in sixteen of the twenty-three (70%) completed electronystagmography evaluations. Twenty patients (54%) were referred to treatment by other disciplines than otology/otoneurology. A follow-up questionnaire was filled by twenty six (70%) of the study participants. While all patients diagnosed with MAV had continuous symptoms, most other patients had complete resolution.Conclusions. Various etiologies of vertigo may present with similar symptoms and signs in the pediatric patient. Yet, variable clinical courses should be anticipated, depending on the specific etiology. This is the reason why treatment and follow up should be specifically tailored for each case according to the diagnosis. Close collaboration with other medical disciplines is often required to reach the correct diagnosis and treatment while avoiding unnecessary laboratory examinations.
The Effect of a Genetically Reduced Plasma Membrane Protonmotive Force on Vegetative Growth of Arabidopsis
Authors: Haruta Miyoshi , Sussman Michael R.
Published: January 2012

The plasma membrane proton gradient is an essential feature of plant cells. In Arabidopsis (Arabidopsis thaliana), this gradient is generated by the plasma membrane proton pump encoded by a family of 11 genes (abbreviated as AHA, for Arabidopsis H+-ATPase), of which AHA1 and AHA2 are the two most predominantly expressed in seedlings and adult plants. Although double knockdown mutant plants containing T-DNA insertions in both genes are embryonic lethal, under ideal laboratory growth conditions, single knockdown mutant plants with a 50% reduction in proton pump concentration complete their life cycle without any observable growth alteration. However, when grown under conditions that induce stress on the plasma membrane protonmotive force (PMF), such as high external potassium to reduce the electrical gradient or high external pH to reduce the proton chemical gradient, aha2 mutant plants show a growth retardation compared with wild-type plants. In this report, we describe the results of studies that examine in greater detail AHA2’s specific role in maintaining the PMF during seedling growth. By comparing the wild type and aha2 mutants, we have measured the effects of a reduced PMF on root and hypocotyl growth, ATP-induced skewed root growth, and rapid cytoplasmic calcium spiking. In addition, genome-wide gene expression profiling revealed the up-regulation of potassium transporters in aha2 mutants, indicating, as predicted, a close link between the PMF and potassium uptake at the plasma membrane. Overall, this characterization of aha2 mutants provides an experimental and theoretical framework for investigating growth and signaling processes that are mediated by PMF-coupled energetics at the cell membrane.
ArabidopsisUbiquitin Conjugase UBC32 Is an ERAD Component That Functions in Brassinosteroid-Mediated Salt Stress Tolerance
Authors: Cui Feng , Liu Lijing , Zhao Qingzhen , Zhang Zhonghui , Li Qingliang , Lin Baoying , Wu Yaorong , Tang Sanyuan , Xie Qi
Published: January 2012

Plants modify their growth and development to protect themselves from detrimental conditions by triggering a variety of signaling pathways, including the activation of the ubiquitin-mediated protein degradation pathway. Endoplasmic reticulum (ER)-associated protein degradation (ERAD) is an important aspect of the ubiquitin-proteasome system, but only a few of the active ERAD components have been reported in plants. Here, we report that the Arabidopsis thaliana ubiquitin-conjugating enzyme, UBC32, a stress-induced functional ubiquitin conjugation enzyme (E2) localized to the ER membrane, connects the ERAD process and brassinosteroid (BR)-mediated growth promotion and salt stress tolerance. In vivo data showed that UBC32 was a functional ERAD component that affected the stability of a known ERAD substrate, the barley (Hordeum vulgare) powdery mildew O (MLO) mutant MLO-12. UBC32 mutation caused the accumulation of bri1-5 and bri1-9, the mutant forms of the BR receptor, BRI1, and these mutant forms subsequently activated BR signal transduction. Further genetic and physiological data supported the contention that UBC32 plays a role in the BR-mediated salt stress response and that BR signaling is necessary for the plant to tolerate salt. Our data indicates a possible mechanism by which an ERAD component regulates the growth and stress response of plants.
Frontal EEG asymmetry moderates the effects of stressful life events on internalizing symptoms in children at familial risk for depression
Authors: Lopez‐Duran Nestor L. , Nusslock Robin , George Charles , Kovacs Maria
Published: January 2012

This study examined whether frontal alpha electroencephalographic (EEG) asymmetry moderates the association between stressful life events and depressive symptoms in children at familial risk for depression. Participants included 135 children ages 6 to 13, whose mothers had either a history of depression or no history of major psychiatric conditions. Frontal EEG was recorded while participants watched emotion‐eliciting films. Symptoms and stressful life events were obtained via the Child Behavior Check List and a clinical interview, respectively. High‐risk children displayed greater relative right lateral frontal activation (F7/F8) than their low‐risk peers during the films. For high‐risk children, greater relative left lateral frontal activation moderated the association between stressful life events and internalizing symptoms. Specifically, greater relative left lateral frontal activation mitigated the effects of stress in at‐risk children.
Effect of meal content on heart rate variability and cardiovascular reactivity to mental stress
Authors: Sauder Katherine A. , Johnston Elyse R. , Skulas‐Ray Ann C. , Campbell Tavis S. , West Sheila G.
Published: January 2012

Little is known about transient effects of foods and nutrients on reactivity to mental stress. In a randomized crossover study of healthy adults (n = 20), we measured heart rate variability (respiratory sinus arrhythmia), blood pressure, and other hemodynamic variables after three test meals varying in type and amount of fat. Measurements were collected at rest and during speech and cold pressor tasks. There were significant postmeal changes in resting diastolic blood pressure (−4%), cardiac output (+18%), total peripheral resistance (−17%), and interleukin‐6 (−27%). Heart rate variability and hemodynamic reactivity to stress was not affected by meal content. We recommend that future studies control for time since last meal and continue to examine effects of meal content on heart rate variability.
Participation in evolution and sustainability
Authors: Clark Thomas L , Clark Eric
Published: January 2012

The modern synthesis of genetics with evolution slanted our understanding of evolution and of ourselves by rejecting Darwin’s view of animals as participating in their own evolution. Defining evolution in terms of genetics, the modern synthesis indulges excessive individualism and distorted self‐images as self‐made. At the same time, such gene‐centred thought, evoking images of master molecules making us who we are, hollows out volition and so also moral concerns and political alternatives. Drawing on the geography of thought, we argue that stubbornly tacit preformationist biological thought reflects and anchors social processes that limit adaptability in reaching toward sustainable living. We appeal for leveraging sustainability efforts by affirming in theory and in the public square an open image of human nature that recognises the participation of our ancestors in becoming who we are, obliging people to make their history together. Achieving the collective self‐regulation sustainability requires may depend on correcting slanted reasoning about ourselves.
Fouling Mechanisms in Axial Compressors
Authors: Kurz Rainer , Brun Klaus
Published: January 2012

Fouling of compressor blades is an important mechanism leading to performance deterioration in gas turbines over time. Fouling is caused by the adherence of particles to airfoils and annulus surfaces. Particles that cause fouling are typically smaller than 2 to 10 microns. Smoke, oil mists, carbon, and sea salts are common examples. Fouling can be controlled by appropriate air filtration systems, and can often be reversed to some degree by detergent washing of components. The adherence of particles is impacted by oil or water mists. The result is a build up of material that causes increased surface roughness and to some degree changes the shape of the airfoil (if the material build up forms thicker layers of deposits), with subsequent deterioration in performance. Fouling mechanisms are evaluated based on observed data, and a discussion on fouling susceptibility is provided. A particular emphasis will be on the capabilities of modern air filtration systems.
On Validation of Extended State Observer Through Analysis and Experimentation
Authors: Zheng Qing , Gao Linda Q. , Gao Zhiqiang
Published: January 2012

This paper is concerned with the question of, for a physical plant to be controlled, whether or not its internal dynamics and external disturbances can be realistically estimated in real time from its input–output data. A positive answer would have significant implications on control system design, because it means that an accurate model of the plant is perhaps no longer required. Based on the extended state observer, it is shown that, for an nth order plant, the answer to the above question is indeed yes. In particular, it is shown that the estimation error converges to the origin asymptotically when the model of the plant is given. In face of large dynamic uncertainties, the estimation error is shown to be bounded. Furthermore, it is demonstrated that the error upper bound monotonously decreases with the bandwidth. Note that this is not another parameter estimation algorithm in the framework of adaptive control. It applies to a large class of nonlinear, time-varying processes with unknown dynamics. The solution is deceivingly simple and easy to implement. The results of analysis are further verified through simulation and hardware tests.
Inhibition of PP1 Phosphatase Activity by HBx: A Mechanism for the Activation of Hepatitis B Virus Transcription
Authors: Cougot Delphine , Allemand Eric , Rivière Lise , Benhenda Shirine , Duroure Karine , Levillayer Florence , Muchardt Christian , Buendia Marie-Annick , Neuveut Christine
Published: January 2012

A virus prolongs the activity of a host transcription factor to promote expression of viral genes.
Incoherent Feedforward Control Governs Adaptation of Activated Ras in a Eukaryotic Chemotaxis Pathway
Authors: Takeda Kosuke , Shao Danying , Adler Micha , Charest Pascale G. , Loomis William F. , Levine Herbert , Groisman Alex , Rappel Wouter-Jan , Firtel Richard A.
Published: January 2012

Rapid adaptation to changes in chemoattractant concentration involves an incoherent feedforward structure of the underlying signaling network.
Comment on “Load-Induced Modulation of Signal Transduction Networks”: Reconciling Ultrasensitivity with Bifunctionality?
Authors: Straube Ronny
Published: January 2012

Mathematical modeling of a bifunctional enzyme system fails to reproduce the experimentally observed ultrasensitivity of the system.
Response to Comment on “‘Load-Induced Modulation of Signal Transduction Networks’: Reconciling Ultrasensitivity with Bifunctionality?”
Authors: Jiang Peng , Ventura Alejandra C. , Sontag Eduardo D. , Merajver Sofia D. , Ninfa Alexander J. , Del Vecchio Domitilla
Published: January 2012

Complex biochemical and regulatory properties of a bifunctional enzyme mean that its activity cannot be modeled as a simple bifunctional system with distinct and reciprocally regulated states.
2011: Signaling Breakthroughs of the Year
Authors: Adler Elizabeth M.
Published: January 2012

Signaling breakthroughs in 2011 involved structural analyses of signaling proteins, technological advances in imaging, and insights into the mechanisms controlling gene expression, immune function, and the cellular response to stress.
Myc and Metabolism
Authors: Foley John F.
Published: January 2012

The transcription factor Myc controls the metabolic changes required for the proliferation of activated T cells.
Shifting the Antiviral Response
Authors: Gough Nancy R.
Published: January 2012

Phosphorylation by IKKε of the transcription factor STAT1 tips the balance of the antiviral response from type II to type I interferon.
Lipidation Determines Dependence
Authors: VanHook Annalisa M.
Published: January 2012

Lipid modification of Wnt ligands is required for their Wntless-mediated secretion.
Lactoferrin Inhibits Porphyromonas gingivalis Proteinases and Has Sustained Biofilm Inhibitory Activity
Authors: Dashper Stuart G. , Pan Yu , Veith Paul D. , Chen Yu-Yen , Toh Elena C. Y. , Liu Sze Wei , Cross Keith J. , Reynolds Eric C.
Published: January 2012

Porphyromonas gingivalis
is a bacterial pathogen associated with chronic periodontitis that results in destruction of the tooth's supporting tissues. The major virulence determinants of
P. gingivalis
are its cell surface Arg- and Lys-specific cysteine proteinases, RgpA/B and Kgp. Lactoferrin (LF), an 80-kDa iron-binding glycoprotein found in saliva and gingival crevicular fluid, is believed to play an important role in innate immunity. In this study, bovine milk LF displayed proteinase inhibitory activity against
P. gingivalis
whole cells, significantly inhibiting both Arg- and Lys-specific proteolytic activities. LF inhibited the Arg-specific activity of purified RgpB, which lacks adhesin domains, and also inhibited the same activity of the RgpA/Kgp proteinase-adhesin complexes in a time-dependent manner, with a first-order inactivation rate constant (
k
inact
) of 0.023 min
−1
and an inhibitor affinity constant (

K
I

) of 5.02 μM. LF inhibited
P. gingivalis
biofilm formation by >80% at concentrations above 0.625 μM. LF was relatively resistant to hydrolysis by
P. gingivalis
cells but was cleaved into two major polypeptides (53 and 33 kDa) at R
284
to S
285
, as determined by in-source decay mass spectrometry; however, these polypeptides remained associated with each other and retained inhibitory activity. The biofilm inhibitory activity of LF against
P. gingivalis
was not attributed to direct antibacterial activity, as LF displayed little growth inhibitory activity against planktonic cells. As the known RgpA/B and Kgp inhibitor
N
-α-
p
-tosyl-
l
-lysine chloromethylketone also inhibited
P. gingivalis
biofilm formation, the antibiofilm effect of LF may at least in part be attributable to its antiproteinase activity.
In Vitro
Antibacterial Activity of the Ceftazidime-Avibactam (NXL104) Combination against Pseudomonas aeruginosa Clinical Isolates
Authors: Levasseur Premavathy , Girard Anne-Marie , Claudon Monique , Goossens Herman , Black Michael T. , Coleman Kenneth , Miossec Christine
Published: January 2012

The β-lactamase inhibitor avibactam (NXL104) displays potent inhibition of both class A and C enzymes. The
in vitro
antibacterial activity of the combination ceftazidime-avibactam was evaluated against a clinical panel of
Pseudomonas aeruginosa
isolates. Avibactam offered efficient protection from hydrolysis since 94% of isolates were susceptible to ceftazidime when combined with 4 μg/ml avibactam, compared with 65% susceptible to ceftazidime alone. Ceftazidime-avibactam also demonstrated better antipseudomonal activity than imipenem (82% susceptibility), a common reference treatment.