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The capacity of the brain to encode multiple types of sensory input is key to survival. Yet, how neurons integrate information from multiple sensory pathways and to what extent this influences behavior is largely unknown. Using two-photon Ca 2+ imaging, optogenetics and electrophysiology in vivo and in vitro, we report the influence of auditory input on sensory encoding in the somatosensory cortex and show its impact on goal-directed behavior. Monosynaptic input from the auditory cortex enhanced dendritic and somatic encoding of tactile stimulation in layer 2/3 (L2/3), but not layer 5 (L5), pyramidal neurons in forepaw somatosensory cortex (S1). During a tactile-based goal-directed task, auditory input increased dendritic activity and reduced reaction time, which was abolished by photoinhibition of auditory cortex projections to forepaw S1. Taken together, these results indicate that dendrites of L2/3 pyramidal neurons encode multisensory information, leading to enhanced neuronal output and reduced response latency during goal-directed behavior. Multi-sensory input can lead to dendritic integration at the single neuron level. Here the authors show that combined auditory and somatosensory input increases distal dendritic and somatic activity in layer 2/3 pyramidal neurons of the primary somatosensory cortex and decreases response latency during somatosensory-based goal-directed behaviour.

Selective enrichments enabled the recovery of moderately thermophilic isolates with copper bioleaching ability from a spent copper sulfide heap. Phylogenetic and physiological characterization revealed that the isolates were closely related to Sulfobacillus thermosulfidooxidans, Acidithiobacillus caldus and Acidimicrobium ferrooxidans. While isolates exhibited similar physiological characteristics to their corresponding type strains, in general they displayed similar or greater tolerance of high copper, zinc, nickel and cobalt concentrations. Considerable variation was found between species and between several strains related to S. thermosulfidooxidans. It is concluded that adaptation to metals present in the bioleaching heap from which they were isolated contributed to but did not entirely explain high metals tolerances. Higher metals tolerance did not confer stronger bioleaching performance, suggesting that a physical, mineralogical or chemical process is rate limiting for a specific ore or concentrate.

Cell lines are important models for drug resistance in acute lymphoblastic leukaemia (ALL), but are often criticised as being unrepresentative of primary disease. There are also doubts regarding the authenticity of many lines. We have characterised a panel of ALL cell lines for growth and drug resistance and compared data with that published for primary patient specimens. In contrast to the convention that cell lines are highly proliferative, those established in our laboratory grow at rates similar to estimates of leukaemic cells in vivo (doubling time 53–442 h). Authenticity was confirmed by genetic fingerprinting, which also demonstrated the potential stability of long-term cultures. In vitro glucocorticoid resistance correlated well with that measured ex vivo , but all lines were significantly more sensitive to vincristine than primary specimens. Sensitivity to methotrexate was inversely correlated to that of glucocorticoids and L -asparaginase, indicating possible reciprocity in resistance mechanisms. A cell line identified as highly methotrexate resistant (IC 50 >8000-fold higher than other lines) was derived from a patient receiving escalating doses of the drug, indicating in vivo selection of resistance as a cause of relapse. Many of these lines are suitable as models to study naturally occurring resistance phenotypes in paediatric ALL.

We examined the role of the glenohumeral and coracohumeral ligaments as well as the forces provided by the rotator cuff muscles, the long head of the biceps, the anterior and middle deltoids, and the pectoralis major in the stabilization of the glenohumeral joint in the posterior direction. Simulated muscle forces were mechanically applied to eight shoulder specimens. The humeroscapular position for testing simulated the 90-degree forward-flexion (humerothoracic) position used clinically for the so-called jerk test, which is the most clinically important position with regard to posterior instability of the shoulder. Experiments were performed with a variety of configurations of ligamentous and capsular cuts, humeral rotation, and levels of muscle force. Stability was investigated by measuring the force required to subluxate the humeral head a specified amount from its reduced position. Of the muscles and ligaments tested, the subscapularis muscle contributed the most to this subluxation force. The coracohumeral ligament was an effective contributor in neutral humeral rotation, and the inferior glenohumeral ligament was an effective contributor in internal humeral rotation. The long head of the biceps was found to reduce the subluxation force in certain positions. CLINICAL RELEVANCEIt is widely agreed that a complex interaction of passive and active stabilizing structures and forces is necessary for clinical stability of the shoulder. The present study identified the contributions of ligaments and muscles to posterior stability of the shoulder in the position of greatest clinical importance—posterior subluxation with the shoulder in forward flexion.

The paraesophageal hernia is an unusual disorder of the esophageal hiatus that may be associated with life-threatening mechanical problems. Elective repair is recommended at the time the condition is diagnosed, and open surgery can be accomplished with a low incidence of complications. The option of performing these repairs through a laparoscopic approach may further reduce morbidity and recovery time associated with surgical intervention. The purpose of this report was to review available options for laparoscopic repair and to present our experience with a tension-free technique for large paraesophageal hernias. Three patients with large diaphragmatic defects had laparoscopic repairs using an expanded polytetrafluorethylene (PTFE) patch secured with intracorporeal suturing techniques. One of these patients also underwent laparoscopic Toupet fundoplication in conjunction with repair of the hernia. In the other two patients, the fundus was secured to the right diaphragmatic crus to reduce the potential for recurrence and minimize postoperative reflux symptoms. All patients underwent successful repair without perioperative complications and had excellent long-term results. Laparoscopic repair of paraesophageal hernias can be accomplished by a number of different reported techniques. The use of a tension-free repair with PTFE may be particularly suitable for large diaphragmatic defects. An antireflux operation may be added selectively depending on clinical circumstances.

Fish and aquatic amphibians have evolved a unique lateral line system that detects local water displacements. Palmer et al investigated the activity of primary afferent fibers of the anterior lateral line nerve during self-induced motion n the oyster toadfish, Opsanus tau. The findings of enhanced nerve activity of the anterior lateral line during self-generated motion, indicating that perhaps mechanosensory noise is not inhibited in afferent activity.

The complete nucleotide sequence of the 16S RNA gene from the rrnB cistron of Escherichia coli has been determined by using three rapid DNA sequencing methods. Nearly all of the structure has been confirmed by two to six independent sequence determinations on both DNA strands. The length of the 16S rRNA chain inferred from the DNA sequence is 1541 nucleotides, in close agreement with previous estimates. We note discrepancies between this sequence and the most recent version of it reported from direct RNA sequencing [Ehresmann, C., Stiegler, P., Carbon, P. & Ebel, J. P. (1977) FEBS Lett. 84, 337-341]. A few of these may be explained by heterogeneity among 16S rRNA sequences from different cistrons. No nucleotide sequences were found in the 16S rRNA gene that cannot be reconciled with RNase digestion products of mature 16S rRNA.

Attempted allelic replacement of 144 Streptococcus pneumoniae open reading frames of previously uncharacterized function led to the identification of 36 genes essential for growth under laboratory conditions. Of these, 14 genes (obg, spoIIIJ2, trmU, yacA, yacM, ydiC, ydiE, yjbN, yneS, yphC, ysxC, ytaG, yloI and yxeH4) were also essential in Staphylococcus aureus and Haemophilus influenzae or Escherichia coli, 2 genes (yrrK and ydiB) were only essential in H. influenzae as well as S. pneumoniae and 8 genes were necessary for growth of S.pneumoniae and S. aureus and did not have a homolog in H. influenzae(murD2, ykqC, ylqF, yqeH, ytgP, yybQ) or were not essential in that organism (yqeL, yhcT). The proteins encoded by these genes could represent good targets for novel antibiotics covering different therapeutic profiles. The putative functions of some of these essential proteins, inferred by bioinformatic analysis, are presented. Four mutants, with deletions of loci not essential for in vitro growth, were found to be severely attenuated in a murine respiratory tract infection model, suggesting that not all targets for antibacterial therapeutics are revealed by simple in vitro essentiality testing. The results of our experiments together with those collated from previously reported studies including Bacillus subtilis, E. coli and Mycoplasma sp. demonstrate that gene conservation amongst bacteria does not necessarily indicate that essentiality in one organism can be extrapolated to others. Moreover, this study demonstrates that different experimental procedures can produce apparently contradictory results. Copyright © 2003 S. Karger AG, Basel [PUBLICATION ABSTRACT]

Forty women 30 years of age or less underwent breast biopsy at Roswell Park Cancer Institute between January 1980 and January 1989. Thirty-eight of the 40 women had a palpable breast mass. Thirty-one of these young women had self-detected breast masses, and the median duration before presentation was 6 months. Physical characteristics were described in 30 of the masses. Twenty-three were described as “fibroadenomas” or smooth, firm, and mobile. Seven masses were described as irregular. The median size of the breast mass was 1.5 cm (range: 0.5 to 9.0 cm). Mammography was performed in 20 patients, but results were reported as abnormal in only 6. Twenty of the masses were described histologically as fibroadenoma. Twelve were described histologically as “fibrocystic disease” or “stromal fibrosis.” One case (2.5%) was invasive adenocarcinoma. Probability of serious underlying breast pathology in young women is low but not nil. Noninvasive and minimally invasive techniques are proposed by some authors as cost-efficient methods that may substitute for open biopsy in these patients. Unfortunately, false-negative results persist and are particularly unacceptable in these young women. During the same time period as our study, 54 women aged 30 years or less were referred to Roswell Park Cancer Institute with a previously diagnosed invasive breast cancer. The incidence of breast cancer in this biopsy series was 2.5%. The potential costs of misdiagnosed early breast cancer in young women negate any rationalization for less invasive biopsy techniques. Following aspiration to rule out a benign cyst, and a possible period of brief observation for spontaneous resolution (2 or 3 months), excisional biopsy is recommended for young women with a breast mass.