Progressive multifocal leukoencephalopathy with gastrointestinal disease in a pediatric kidney transplant recipient.

PML is a demyelinating disease of the central nervous system caused by infection with JCV. Several cases of PML in bone marrow and solid organ transplant recipients have been reported in recent years. JCV has been isolated from the gastrointestinal mucosa of immunocompromised patients, but there are no published reports of PML associated with symptomatic gastrointestinal involvement in kidney transplant recipients. We report a case of a nine-yr-old girl with a kidney transplant who developed a severe gastrointestinal illness causing pseudo-obstruction in association with PML. JCV was suspected as the causative agent in this patient by the detection of high JCV titer through PCR analysis of the cerebrospinal fluid and blood and positive staining for simian virus 40 in the colon. JCV intestinal infection should be considered in kidney transplant recipients presenting with intestinal pseudo-obstruction.

The Haw River syndrome: dentatorubropallidoluysian atrophy (DRPLA) in an African-American family.

Haw River Syndrome (HRS) is a dominant neurodegenerative disease that has affected five generations of an African-American family in rural North Carolina. The disorder represents a unique spectrum of multiple system degenerations resembling Huntington's disease, spinocerebellar atrophy and dentatorubropallidoluysian atrophy (DRPLA), a neurodegenerative disease that has been primarily reported in Japan. Recently, DRPLA has been shown to be due to an expanded trinucleotide repeat located on chromosome 12pter-p12. We have genotyped this family and found HRS to be tightly linked to the DRPLA region. Further examination demonstrates that, despite their distinct cultural origins and clinical and pathological differences, HRS is caused by the same expanded CTG-B37 repeat as DRPLA.

The effect of anaesthetic use on healing in sub cutaneous abscess management: a retrospective before and after cohort study.

INTRODUCTION: There is wide variation in the management of simple subcutaneous abscesses in the UK and no national guidelines describing best practice. During the SARS-CoV-2 pandemic, regional or local anaesthesia (LA) use was recommended instead of general anaesthesia. This study aimed to assess the effect of anaesthetic use on outcomes following incision and drainage (I&D) of simple subcutaneous abscesses. METHODS: Two cohorts of patients undergoing abscess incision and drainage at St. James' University Hospital in Leeds were identified retrospectively over a 14-week period before (P1) and after (P2) the introduction of the COVID-19 anaesthetic guidelines. The number of follow-up appointments for repacking and representation to healthcare services 30 days after I&D were used as surrogate endpoints for wound healing. RESULTS: A total of 133 patients were included (n=70, P1 and n=63, P2). Significantly more procedures were performed under LA after the intervention (84.1% vs 5.7%; p<0.0001) with a significant reduction in wound packing (68.3% vs 87.1%; p=0.00473). Follow-up analysis found no significant difference in the median number of follow-up appointments (7.46 vs 5.11; p=0.0731) and the number of patients who required ongoing treatment after 30 days (n=14, P1 vs n=14, P2; p=0.921). CONCLUSIONS: Drainage of simple subcutaneous abscess under 5cm in diameter is safe under LA, with no significant difference in surrogate endpoints of wound healing observed in this patient cohort. Recurrent packing may not be required. Future work should explore patient-reported outcomes, including pain management, cosmesis and the cost and sustainability implications of a change in this common procedure.

Huntingtin and DRPLA proteins selectively interact with the enzyme GAPDH.

At least five adult-onset neurodegenerative diseases, including Huntingtin disease (HD), and dentatorubral-pallidoluysian atrophy (DRPLA) are produced by genes containing a variably increased CAG repeat within the coding region. The size range of the repeats is similar in all diseases; unaffected individuals have fewer than 30 CAG repeats, whereas affected patients usually have more than 40 repeats. The size of the inherited CAG repeat correlates with the severity and age of disease onset. The CAG triplet repeat produces a polyglutamine domain in the expressed proteins. All of these diseases are inherited in a dominant fashion, and a pathologic gain of function in gene carriers has been proposed. We sought to identify proteins in the brain that selectively interact with polyglutamine-domain proteins, hypothesizing that the polyglutamine domain may determine protein-protein interactions.

Delay to surgery in acute perforated and ischaemic gastrointestinal pathology: a systematic review.

BACKGROUND: Patients with acute abdominal pathology requiring emergency laparotomy who experience a delay to theatre have an increased risk of morbidity, mortality and complications. The timeline between symptom onset and operation is ill defined with international variance in assessment and management. This systematic review aims to define where delays to surgery occur and assess the evidence for interventions trialled across Europe. METHODS: A systematic review was performed searching MEDLINE and EMBASE databases (1 January 2005 to 6 May 2020). All studies assessing the impact of time to theatre in patients with acute abdominal pathology requiring emergency laparotomy were considered. RESULTS: Sixteen papers, involving 50 653 patients, were included in the analysis. Fifteen unique timepoints were identified in the patient pathway between symptom onset and operation which are classified into four distinct phases. Time from admission to theatre (1-72 hours) and mortality rate (10.6-74.5 per cent) varied greatly between studies. Mean time to surgery was significantly higher in deceased patients compared with that in survivors. Delays were related to imaging, diagnosis, decision making, theatre availability and staffing. Four of five interventional studies showed a reduced mortality rate following introduction of an acute laparotomy pathway. CONCLUSION: Given the heterogeneous nature of the patient population and pathologies, an assessment and management framework from onset of symptoms to operation is proposed. This could be incorporated into mortality prediction and audit tools and assist in the assessment of interventions.

Gender representation in editorial boards of international general surgery journals.

BACKGROUND: Despite women constituting over half of new doctors, gender disparity remains an issue. Surgery has shown particularly slow progress towards gender parity. This study aimed to quantify gender representation within editorial boards of the highest ranking international general surgery journals. METHODS: Surgical journals were collated using two indices: SCImago Journal Rank (SJR) and Journal Impact Factor (JIF). Non-general surgery journals were excluded. Journals were contacted, requesting gender editorial team demographics. Editorial board data were collected via journal websites on 28 November 2019. RESULTS: The top 25 general surgery journals according to SJR and JIF ranking methods were determined, identifying 28 unique journals. Editorial board data were publicly available for 27 of these 28 surgical journals, and were examined. Women accounted for 20.2 per cent (568 of 2816) of total editorial board positions. Women constituted 11 per cent (4 of 36) of editor-in-chief positions, 32 per cent (29 of 92) of deputy editors, and 19.1 per cent (369 of 1935) of general editorial board positions. CONCLUSION: The findings demonstrate gender disparity within editorial boards of the most prominent general surgery journals.

The quantitative impact of COVID-19 on surgical training in the United Kingdom.

BACKGROUND: COVID-19 has had a global impact on all aspects of healthcare including surgical training. This study aimed to quantify the impact of COVID-19 on operative case numbers recorded by surgeons in training, and annual review of competency progression (ARCP) outcomes in the UK. METHODS: Anonymized operative logbook numbers were collated from electronic logbook and ARCP outcome data from the Intercollegiate Surgical Curriculum Programme database for trainees in the 10 surgical specialty training specialties.Operative logbook numbers and awarded ARCP outcomes were compared between predefined dates. Effect sizes are reported as incident rate ratios (IRR) with 95 per cent confidence intervals. RESULTS: Some 5599 surgical trainees in 2019, and 5310 in surgical specialty training in 2020 were included. The IRR was reduced across all specialties as a result of the COVID-19 pandemic (0.62; 95 per cent c.i. 0.60 to 0.64). Elective surgery (0.53; 95 per cent c.i. 0.50 to 0.56) was affected more than emergency surgery (0.85; 95 per cent c.i. 0.84 to 0.87). Regional variation indicating reduced operative activity was demonstrated across all specialties. More than 1 in 8 trainees in the final year of training have had their training extended and more than a quarter of trainees entering their final year of training are behind their expected training trajectory. CONCLUSION: The COVID-19 pandemic has had a major effect on surgical training in the UK. Urgent, coordinated action is required to minimize the impacts from the reduction in training in 2020.

Tumour growth rate of carcinoma of the colon and rectum: retrospective cohort study.

BACKGROUND: The growth pattern of colorectal cancer is seldom investigated. This cohort study aimed to explore tumour growth rate in colorectal cancers managed non-surgically or deemed not resectable, and to determine its implication for prognosis. METHODS: Consecutive patients with colonic or rectal adenocarcinoma were identified through the colorectal multidisciplinary team database at Leeds Teaching Hospitals NHS Trust over a 2-year interval. Patients who received no treatment (surgery, stenting, colonic defunctioning procedures, chemotherapy, radiotherapy) and who underwent CT twice more than 5 weeks apart were included. Multidetector CT/three-dimensional image analysis was performed independently by three experienced radiologists. RESULTS: Of 804 patients reviewed, 43 colorectal cancers were included in the final analysis. Median age at first CT was 80 (73-85) years and the median interval between scans was 150 (i.q.r. 72-471) days. An increase in T category was demonstrated in 31 of 43 tumours, with a median doubling time of 211 (112-404) days. The median percentage increase in tumour volume was 34·1 (13·3-53·9) per cent per 62 days. The all-cause 3-year mortality rate was 81 per cent (35 of 43) with a median survival time of 1·1 (0·4-2·2) years after the initial diagnostic scan. In those obstructed, the relative risk of death from subsequent perforation was 1·26 (95 per cent c.i. 1·07 to 1·49; P = 0·005). CONCLUSION: This study documented a median doubling time of 211 days, with a concerning suggestion of tumour progression, which has implications for the current management standard.

ANTECEDENTES: El patrón de crecimiento del CRC (colorectal cancer, CRC) ha sido poco investigado. El objetivo de este estudio de cohortes fue explorar la tasa de crecimiento tumoral en los pacientes con CRC no tratados quirúrgicamente o con tumores irresecables para determinar su valor pronóstico. MÉTODOS: Los pacientes consecutivos con adenocarcinoma de colon o recto se identificaron a partir de la base de datos del equipo multidisciplinario colorrectal del "Leeds Teaching Hospitals NHS Trust" durante un período de 2 años. Se incluyeron los pacientes que no recibieron tratamiento (cirugía, colocación de endoprótesis, procedimientos de desfuncionalización del colon, quimioterapia, radioterapia), en los que se obtuvieron tomografías computarizadas con > 5 semanas de diferencia. El análisis de imágenes TC/3D multidetector fue realizado de forma independiente por tres radiólogos expertos. RESULTADOS: De los 804 pacientes revisados, 43 CRCs se incluyeron en el análisis final con una mediana de 150 días (rango intercuartílico, interquartile range, IQR: 72-471) entre los escáners. La mediana de edad en el primer escáner era de 80 años (IQR: 73-85). En 31 (72%) casos, se demostró un aumento del estadio TNM del tumor, con un tiempo medio de duplicación del tamaño tumoral de 211 días (IQR: 112-404). La mediana de aumento porcentual del volumen del tumor era de un 34% cada 62 días (IQR: 13,3-53,9). La mortalidad por cualquier causa a los 3 años fue del 81% (35/43), con una mediana de supervivencia de 1,1 años (IQR: 0,4-2,2) desde el escáner inicial diagnóstico. El riesgo relativo de mortalidad como resultado de la obstrucción intestinal y perforación subsiguiente era de 1,26 (i.c. del 95% 1,07-1,49, P < 0,01). CONCLUSIÓN: Este estudio documentó una mediana de tiempo de duplicación del tamaño del tumor de 211 días, así como datos preocupantes de la progresión del tumor que podrían tener repercusión en el tratamiento estándar actual.

A High-Throughput BRET Cellular Target Engagement Assay Links Biochemical to Cellular Activity for Bruton's Tyrosine Kinase.

Protein kinases are intensely studied mediators of cellular signaling. While traditional biochemical screens are capable of identifying compounds that modulate kinase activity, these assays are limited in their capability of predicting compound behavior in a cellular environment. Here, we aim to bridge target engagement and compound-cellular phenotypic behavior by utilizing a bioluminescence resonance energy transfer (BRET) assay to characterize target occupancy within living cells for Bruton's tyrosine kinase (BTK). Using a diverse chemical set of BTK inhibitors, we determine intracellular engagement affinity profiles and successfully correlate these measurements with BTK cellular functional readouts. In addition, we leveraged the kinetic capability of this technology to gain insight into in-cell target residence time and the duration of target engagement, and to explore a structural hypothesis.

Twin pairs discordant for neuropathologically confirmed Lewy body dementia.

AIM: Little is known about the concordance rate in twins for dementia with Lewy bodies (DLB). The rate of agreement between clinical and pathological diagnoses for DLB is typically low, necessitating confirmation of the diagnosis neuropathologically. METHODS: Participants were 17 twin pairs enrolled in the Duke Twins Study of Memory in Aging in which at least one member of the pair had an autopsy confirmed diagnosis of DLB, Alzheimer's disease (AD) with Lewy bodies or frontotemporal dementia with Lewy bodies. The characteristics of those with dementia were assessed and rates of concordance for pathological confirmed dementia were examined. RESULTS: Four monozygotic twin pairs had a proband with neuropathologically confirmed pure DLB; all remained discordant for dementia for periods up to 16 years or more. Five of 13 pairs in which the proband had AD plus DLB were concordant for dementia but only one pair was concordant for AD plus DLB, while the co-twins in the other four pairs had other types of dementia. CONCLUSIONS: The present study indicates that even among twins, a diagnosis of DLB in one twin does not predict the same diagnosis in the other twin. Neuropathological discordance in type of dementia among monozygotic pairs hints at environmental or epigenetic factors playing a role in Lewy body pathology.

Prevalence of dementia in the United States: the aging, demographics, and memory study.

AIM: To estimate the prevalence of Alzheimer's disease (AD) and other dementias in the USA using a nationally representative sample. METHODS: The Aging, Demographics, and Memory Study sample was composed of 856 individuals aged 71 years and older from the nationally representative Health and Retirement Study (HRS) who were evaluated for dementia using a comprehensive in-home assessment. An expert consensus panel used this information to assign a diagnosis of normal cognition, cognitive impairment but not demented, or dementia (and dementia subtype). Using sampling weights derived from the HRS, we estimated the national prevalence of dementia, AD and vascular dementia by age and gender. RESULTS: The prevalence of dementia among individuals aged 71 and older was 13.9%, comprising about 3.4 million individuals in the USA in 2002. The corresponding values for AD were 9.7% and 2.4 million individuals. Dementia prevalence increased with age, from 5.0% of those aged 71-79 years to 37.4% of those aged 90 and older. CONCLUSIONS: Dementia prevalence estimates from this first nationally representative population-based study of dementia in the USA to include subjects from all regions of the country can provide essential information for effective planning for the impending healthcare needs of the large and increasing number of individuals at risk for dementia as our population ages.

Identification of imidazo[1,2-b]pyridazine TYK2 pseudokinase ligands as potent and selective allosteric inhibitors of TYK2 signalling.

As a member of the Janus (JAK) family of non-receptor tyrosine kinases, TYK2 mediates the signaling of pro-inflammatory cytokines including IL-12, IL-23 and type 1 interferon (IFN), and therefore represents an attractive potential target for treating the various immuno-inflammatory diseases in which these cytokines have been shown to play a role. Following up on our previous report that ligands to the pseudokinase domain (JH2) of TYK2 suppress cytokine-mediated receptor activation of the catalytic (JH1) domain, the imidazo[1,2-b]pyridazine (IZP) 7 was identified as a promising hit compound. Through iterative modification of each of the substituents of the IZP scaffold, the cellular potency was improved while maintaining selectivity over the JH1 domain. These studies led to the discovery of the JH2-selective TYK2 inhibitor 29, which provided encouraging systemic exposures after oral dosing in mice. Phosphodiesterase 4 (PDE4) was identified as an off-target and potential liability of the IZP ligands, and selectivity for TYK2 JH2 over this enzyme was obtained by elaborating along selectivity vectors determined from analyses of X-ray co-crystal structures of representative ligands of the IZP class bound to both proteins.

Disrupted spermine homeostasis: a novel mechanism in polyglutamine-mediated aggregation and cell death.

Our data suggest a novel mechanism whereby pathological-length polyglutamine (polyQ) proteins promote the spermine synthetic pathway, increasing polyQ-aggregation and cell death. As detected in a cell-free turbidity assay, spermine promotes aggregation of thio-polyQ62 in a dose-dependent manner. Using a stable neuronal cell line expressing pathological-length [polyQ57-yellow fluorescent protein (YFP) (Q57)] or non-pathological-length [polyQ19-YFP (Q19)] polyglutamine protein, we show that multiple steps in the production of polyamines are affected in Q57 cells, suggesting dysfunctional spermine homeostasis. As the building block for spermine synthesis, arginine transport is significantly increased in neuronal cell lines stably expressing Q57. Q57 lines displayed upregulated basal and inducible arginase I activities that were not seen in polyQ19-YFP lines. Normal induction of spermidine/spermine N-acetyltransferase in Q19 lines regulating back-conversion of spermine, thereby reducing spermine levels, however, was not observed in Q57 lines. Pharmacological activation of ornithine decarboxylase (ODC), a key enzyme of the polyamine synthetic pathway, increased cellular aggregates and increased cell death in Q57 cells not observed in Q19 cells. Inhibition of ODC by difluoromethylornithine prevented basal and induced cell death in Q57 cells, demonstrating a central role for polyamines in this process.

Leukotriene B4 stimulates the release of arachidonate in human neutrophils via the action of cytosolic phospholipase A2.

Leukotriene B4 (LTB4) is a potent lipid mediator of inflammation and is involved in the receptor-mediated activation of a number of leukocyte responses including degranulation, superoxide formation, and chemotaxis. In the present research, stimulation of unprimed polymorphonuclear leukocytes (neutrophils) with LTB4 results in the transient release of arachidonate as measured by mass. This release of arachidonate was maximal at an LTB4 concentration of 50-75 nM and peaked at 45 s after stimulation with LTB4. The transient nature of this release can be attributed, in part, to a fast (< 60 s) metabolism of the added LTB4. Moreover, the inhibition of the reacylation of the released arachidonate with thimerosal results in greater than 4-times as much arachidonate released. Thus, a rapid reacylation of the released arachidonate also contributes to the transient nature of its measured release. Multiple additions of LTB4, which would be expected to more closely resemble the situation in vivo where the cell may come into contact with an environment where LTB4 is in near constant supply, yielded a more sustained release of arachidonate. No release of [3H]arachidonate was observed when using [3H]arachidonate-labeled cells. This indicates that the release of arachidonate as measured by mass is most probably the result of hydrolysis of arachidonate-containing phosphatidylethanolamine within the cell since the radiolabeled arachidonate is almost exclusively incorporated into phosphatidylcholine and phosphatidylinositol pools under the non-equilibrium radiolabeling conditions used. Consistent with the role of cytosolic phospholipase A2 (cPLA2) in the release of arachidonate, potent inhibition of the LTB4-stimulated release was observed with methylarachidonylfluorophosphonate, an inhibitor of cPLA2 (IC50 of 1 microM). The bromoenol lactone of the calcium-independent phosphospholipase A2. failed to affect LTB4-stimulated release of arachidonate in these cells.

Studies on the function of the non-primer tRNAs associated with the 70 S RNA of avian myeloblastosis virus.

Significant amounts of three tRNAs are associated with the 70 S RNA of avian myeloblastosis virus (AMV). The temperatures at which they are half dissociated from the 70 S RNA in 50 mM NaCl and their respective quantities relative to 35 S RNA are: tRNAArg, 51 degree C, 1.6; tRNALys, 57 degree C, 0.7 and tRNATrp, 76 degree C, 1.0. Possible functions for the non-primer tRNAs (tRNAArg and tRNALys) were evaluated by determining the effect of their thermal dissociation on: (a) conversion of 70 S to 35 S RNA, (b) capacity of 70 S and/or 35 S RNA to be translated in vitro, and (c) capacity of 70 S and/or 35 S RNA to be reverse transcribed in vitro. Conversion of 70 S to 35 S RNA occurred with a tm of 56 degree C and is consistent with the hypothesis that tRNALys might be involved in joining two 35 S RNA subunits to form the 70 S RNA complex. There was no indication that the association of either tRNAArg or tRNALys influenced the rate or quality of translation of 70 S or 35 S RNA. A decrease in the rate at which 70 S RNA is transcribed occurs in parallel with the dissociation of tRNAArg and tRNALys.

Phosphorylation and calcium influx are not sufficient for the activation of cytosolic phospholipase A2 in U937 cells: requirement for a Gi alpha-type G-protein.

Differentiation with dibutyryl cyclic AMP (dBcAMP) of the human, premonocytic U937 cell line toward a monocyte/granulocyte-like cell results in the cell acquiring an ability to release arachidonate upon stimulation. In contrast, the calcium ionophore ionomycin was able to stimulate phospholipase C, as measured by inositol 1,4,5-trisphosphate formation, to equal extents in both undifferentiated and dBcAMP-differentiated U937 cells. The role and regulation of cytosolic phospholipase A2 (cPLA2) in the production of arachidonate in these cells when either the chemotactic peptide fMLP or ionomycin are used as stimulus were investigated. The ionomycin- and fMLP-stimulated release of arachidonate were sensitive to the cPLA2 inhibitor arachidonyl trifluoromethylketone (IC50 values of 32 and 18 microM, respectively), but were not inhibited by E-6-(bromomethylene)-tetrahydro-3-(1-naphthalenyl)-2 H-pyran-2-one, a bromoenol lactone inhibitor of the calcium-independent phospholipase A2. These results, coupled with the inhibition of ionomycin-induced arachidonate production by electroporation of differentiated cells to introduce an anti-cPLA2, demonstrate that the cPLA2 is the enzyme responsible for arachidonate release in differentiated cells. SDS-PAGE and immunoblot analysis of differentiated cells showed the cells to contain both phosphorylated and unphosphorylated forms of cPLA2 (ratio of about 2: 3). Surprisingly, undifferentiated cells contain 30% more enzyme than differentiated cells and contain a higher percentage (approximately 75%) of the phosphorylated in the absence of stimulation. The inability of undifferentiated cells to produce arachidonate is not due to insufficient intracellular calcium concentrations since ionomycin induces large (820-940 nM) influxes of intracellular calcium in both differentiated and undifferentiated cells. This demonstrates that phosphorylation of cPLA2 andan influx of intracellular calcium are not sufficient to activate the enzyme to produce arachidonate. Instead, activation of a pertussis toxin-sensitive Gi alpha-type G-protein is required as evidenced by the production of arachidonate in undifferentiated cells stimulated with mastoparan, an activator of Gi alpha subunits, in combination with ionomycin. This activation of a Gi alpha-type G-protein is independent of modulations of adenylyl cyclase activity since cellular cAMP levels were not modulated upon treatment with mastoparan and ionomycin.

Modulation of the tibial nerve H-reflex by mechanical stimulation of afferents in the lumbar spine.

The purpose of this study was to describe the convergence of afferent discharges from the ligament-muscular system of the lumbar spine to the segmentally-related gastrocnemius muscle. The subjects were 32 healthy, young volunteers recruited from a college student population. Afferent discharges from the ligament-muscular system of the lumbar spine were evoked by manually moving the trunk into either flexion (n = 16) or left lateral bending (n = 16) using a multi-directional adjustable treatment table (Zenith Cox Flexion Table). Using linear potentiometers affixed to the treatment table and interfaced with a computer data acquisition system, manual movements of the table were visually guided to generate passive trunk movements at velocities of 10 degrees, 20 degrees, and 40 degrees per second. Tibial nerve H-reflex responses were recorded from the right gastrocnemius muscle as the trunk approached its end range of motion. Regardless of velocity for the flexion movement, the H/M(Max) ratio significantly decreased from 28.0% to 20.9% (p < .05). During lateral bending, the H/M(Max) ratio significantly decreased from 27.4% to 24.0% at velocities of 10 degrees and 20 degrees per second (p < .05) with a subsequent decrease to 20.5% at a velocity of 40 degrees per second (p < .05). The nature of these decreases in the H/M(Max) ratios across the different velocities during lateral bending significantly departed from linearity (p < .05). These data provide sufficient evidence to suggest that heteronymous conditioning effects from the ligament-muscular system of the lumbar spine during passive trunk movements attenuate alpha motoneuronal activity of the segmentally-related gastrocnemius muscle.

Comparison of stretch reflex responses evoked during drop jumping in highly skilled atheles versus untrained subjects.

AIM: The purpose of the study was to describe changes in the excitability of the stretch reflex response (SRR) during different drop jumps as a function of training background and as an adaptation to a preseason sport-specific resistance training program. METHODS: Twelve collegiate field event athletes (discus, hammer, javelin, shot put, and weight; 9 males and 3 females) and 12 college-aged control subjects performed the following three jumps: (1) countermovement jump (CMJ); (2) countermovement drop jump; and (3) bounce-drop jump (BDJ). Neuromechanical changes in the performance of drop jumps by athletes were measured during the sport-specific resistance training program. Pre-post testing of drop jump performance by control subjects was included for comparison. For each jump trial, ground reaction forces (GRF), electromyograms (EMG) and cinematographic data were collected. RESULTS: There were no training adaptations. However, jump heights were greater for the athletes than the controls among the different jumps with the jump heights for all subjects being less during the BDJ than CMJ and CDJ. In athletes only, there was a differential modulation of the SRR from the gastrocnemius muscle with different levels of background muscle activity for the CDJ and BDJ. CONCLUSION: There were changes in excitability of SRR from the gastrocnemius muscle as a function of training background. Interrelated neuromechanical mechanisms to include landing biomechanics, intrinsic musculotendinous tissue properties of the ankle, and centrally regulated motor commands may underlie the facilitation of the SRR from the gastrocnemius muscle in athletes as compared to controls.

Toxicity of expanded polyglutamine-domain proteins in Escherichia coli.

Five neurodegenerative diseases are caused by proteins with expanded polyglutamine domains. Toxicity of these proteins has been previously identified only in mammals, and no simple model systems are available. In this paper, we demonstrate in E. coli that long polyglutamine domains (59-81 residues) as GST-fusion proteins inhibit growth while smaller glutamine (10-35 residues) or polyalanine (61 residues) domains have no effect. Analogously in humans, polyglutamine repeats less than 35-40 glutamines produce a normal phenotype, while expansion greater than 40 glutamines is always associated with disease. Expression of polyglutamine proteins in E. coli may help identify the molecular mechanism of pathogenesis of CAG trinucleotide repeat diseases and be a useful screen to identify potential therapeutic compound.