bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-Wide Chromatin Immunoprecipitation Sequencing Analysis Shows that WhiB Is a Transcription Factor That Cocontrols Its Regulon with WhiA To Initiate Developmental Cell Division in
Streptomyces
Authors: Bush Matthew J. , Chandra Govind , Bibb Maureen J. , Findlay Kim C. , Buttner Mark J. 
Published: April 2016

ABSTRACT

WhiB is the founding member of a family of proteins (the
W
hi
B
-
l
ike [Wbl] family) that carry a [4Fe-4S] iron-sulfur cluster and play key roles in diverse aspects of the biology of actinomycetes, including pathogenesis, antibiotic resistance, and the control of development. In
Streptomyces
, WhiB is essential for the process of developmentally controlled cell division that leads to sporulation. The biochemical function of Wbl proteins has been controversial; here, we set out to determine unambiguously if WhiB functions as a transcription factor using chromatin immunoprecipitation sequencing (ChIP-seq) in
Streptomyces venezuelae
. In the first demonstration of
in vivo
genome-wide Wbl binding, we showed that WhiB regulates the expression of key genes required for sporulation by binding upstream of ~240 transcription units. Strikingly, the WhiB regulon is identical to the previously characterized WhiA regulon, providing an explanation for the identical phenotypes of
whiA
and
whiB
mutants. Using ChIP-seq, we demonstrated that
in vivo
DNA binding by WhiA depends on WhiB and vice versa, showing that WhiA and WhiB function cooperatively to control expression of a common set of WhiAB target genes. Finally, we show that mutation of the cysteine residues that coordinate the [4Fe-4S] cluster in WhiB prevents DNA binding by both WhiB and WhiA
in vivo
.

IMPORTANCE
Despite the central importance of
W
hi
B
-
l
ike (Wbl) proteins in actinomycete biology, a conclusive demonstration of their biochemical function has been elusive, and they have been difficult to study, particularly
in vitro
, largely because they carry an oxygen-sensitive [4Fe-4S] cluster. Here we used genome-wide ChIP-seq to investigate the function of
Streptomyces
WhiB, the founding member of the Wbl family. The advantage of this approach is that the oxygen sensitivity of the [4Fe-4S] cluster becomes irrelevant once the protein has been cross-linked to DNA
in vivo
. Our data provide the most compelling
in vivo
evidence to date that WhiB, and, by extension, probably all Wbl proteins, function as transcription factors. Further, we show that WhiB does not act independently but rather coregulates its regulon of sporulation genes with a partner transcription factor, WhiA.
Prehospital emergency services screening and referral to reduce falls in community-dwelling older adults: a systematic review
Authors: Zozula Alexander , Carpenter Christopher R , Lipsey Kim , Stark Susan 
Published: April 2016

BackgroundFalls represent an increasing source of geriatric morbidity and mortality. Prehospital emergency services may be uniquely suited to screen and refer subsets of high-risk older adults to fall prevention programmes. This systematic review assesses the effectiveness of such screening and referral programmes.MethodsWe searched PubMed, Embase, CINAHL, Web of Science, Scopus, the Cochrane Library and OTseeker for English-language peer-reviewed randomised trials, non-randomised trials and cohort studies evaluating prehospital fall risk screening and referral programmes for community-dwelling adults ≥60 years of age. Risk of bias was assessed using the Cochrane Collaboration's tool. Primary outcomes included the risk and rate of falling. Secondary outcomes included successful follow-up to address fall risks and adverse events.ResultsFrom 6187 unique records, 6 studies were included. Screening varied from using semistructured risk assessments to recording chief complaints. All studies were at high risk of bias. One unblinded trial of a multifactorial fall prevention programme demonstrated a 14.3% (95% CI 6.1% to 22.5%) absolute reduction in annual fall risk and a relative fall incidence of 0.45 (95% CI 0.35 to 0.58). The probability of successful follow-up varied from 9.8% to 81.0%. No studies demonstrated any attributable adverse events.ConclusionsNo high-quality evidence demonstrates that prehospital services reduce falls in community-dwelling older adults. Screening by prehospital personnel using semistructured risk assessments appears feasible, but it is unclear whether this is superior to referral based on fall-related chief complaints.Trial registration numberPROSPERO 2012:CRD42012002782.
Characterisation of amphimictic and parthenogenetic populations of Pratylenchus bolivianus Corbett, 1983 (Nematoda: Pratylenchidae) and their phylogenetic relationships with closely related species
Authors: Troccoli Alberto , Subbotin Sergei A. , Chitambar John J. , Janssen Toon , Waeyenberge Lieven , Stanley Jason D. , Duncan Larry W. , Agudelo Paula , Múnera Uribe Gladis E. , Franco Javier , Inserra Renato N. 
Published: April 2016

Amphimictic populations of root-lesion nematodes with numerous males and females having three lip annuli, a functional spermatheca and non-areolated lateral field occur on sword fern (Nephrolepis exaltata) in Florida. Identified for decades asPratylenchus penetrans, they appeared to be a morphologically separated species on the basis of a longer stylet (17.8-18.3 μm) thanP. penetrans(15-17 μm) and different lip pattern inen faceview (rectangularvsdumb-bell inP. penetrans). Morphologically similar amphimictic root-lesion nematodes have also been detected on flax lily in Costa Rica. Subsequent morphological observations indicated that these amphimictic root-lesion nematodes from fern and flax lily are closely related to the parthenogenetic speciesP. bolivianus, which has areolated lateral fields. In spite of the reproductive and morphological dissimilarities between these populations, their separation into different species was not supported by the results of molecular analyses of their DNA sequences. The populations used in these analyses included those that are amphimictic from Florida and Costa Rica and others that are parthenogenetic from the type locality in Bolivia, and geographically distant localities in Chile, China, Colombia and Europe. Phylogenetic analyses of the ITS and D2-D3 expansion segments of the 28S rRNA gene indicated that they belong to the same species,P. bolivianus, which consists of two morphotypes,P. bolivianus(am) amphimictic andP. bolivianus(pm) parthenogenetic, herein described and illustrated. Contradictory results were obtained by the analyses using a portion of thehsp90gene. The phylogenetic study, which included sequences of other root-lesion nematodes, a topotype and geographical distant populations ofP. zeae, revealed thatP. bolivianusandP. zeaeformed highly supported clades in the majority consensus trees. PCR with species-specific primers for rapid diagnostics ofP. bolivianusandP. zeaewere developed and tested.
Biomarker and Pathologic Predictors of Cutaneous Squamous Cell Carcinoma Aggressiveness
Authors: Khandelwal Alok R. , Ma Xiaohui , Egan Paige , Kaskas Nadine M. , Moore‐Medlin Tara , Caldito Gloria , Abreo Fleurette , Gu Xin , Aubrey Lurie , Milligan Edward , Nathan Cherie‐Ann O. 
Published: April 2016

ObjectiveAggressive cutaneous squamous cell carcinoma (cSCC) patients are at increased risk of metastasis. Currently, there are no accepted criteria or biomarkers for reliably predicting individuals at risk for recurrence and metastasis. Our objective is to determine if pS6 and pERK can predict cSCC aggressiveness and to identify primary tumor characteristics that may predict parotid metastasis.Study DesignRetrospective case series.SettingsTertiary care center.Subjects and MethodsAn Institutional Review Board–approved retrospective review was performed for patients with facial cSCC, with and without metastasis to the parotids. Subjects for the study were identified through the Louisiana Tumor Registry, Veterans Medical Records, and LSU Health‐Shreveport pathology database. Tumor specimens from patients with cSCC and cSCC with parotid metastasis were analyzed for pERK and pS6 expression through immunohistochemistry. To identify risk factors for tumor aggressiveness, multiple logistic regression analysis was used to evaluate patients with cSCC that was metastatic to the parotid and managed surgically.ResultscSCC with parotid metastasis specimens exhibited significantly higher average pS6 but not pERK positivity than those from cSCC without metastasis (P <. 05). Primary lesion–positive margins (P <. 01), size of the skin tumor (P <. 01) and degree of tumor differentiation (P <. 01) were significantly associated with parotid metastasis.ConclusionSurgical history of cSCC, primary lesion–positive margins, degree of differentiation, and lesion size together with pS6 positivity appear to be predictors of cSCC aggressiveness and should prompt increased monitoring or elective parotidectomy.
The Persistence of Tinnitus after Acoustic Neuroma Surgery
Authors: Bell Jason R. , Anderson‐Kim Sara J. , Low Christopher , Leonetti John P. 
Published: April 2016

ObjectiveExamine possible prognostic factors for the persistence of tinnitus after acoustic neuroma resection.Study DesignCase series with chart review.SettingTertiary academic medical center.Subjects and MethodsThe records of 166 patients who underwent acoustic neuroma resection from 2009 to 2014 were reviewed. Patients were asked to complete a survey, including the Tinnitus Handicap Inventory, 1 to 6 years postoperatively.ResultsOf the 53 patients who completed the survey, 17% reported that their tinnitus resolved; 9% reported improvement; 23% reported no change; 43% reported that their tinnitus worsened; and 8% were unsure. Respondents ≥50 years old and those with nonserviceable hearing preoperatively were more likely to report that their tinnitus resolved or improved (P <. 01 and P =. 02, respectively). Respondents <50 years old and those with serviceable hearing preoperatively were more likely to report that their tinnitus was the same or worse (P <. 001 and P =. 036, respectively). Respondents with age <50 years, serviceable hearing preoperatively, and residual tumor had a higher average Tinnitus Handicap Inventory score (P =. 016, P =. 048, and P =. 047, respectively). Sex, tumor size, surgical approach, hearing preservation, and cochlear nerve status did not correlate with the prognosis of tinnitus postoperatively. Respondents whose tinnitus resolved postoperatively were more likely to report being “very satisfied” with their care (P =. 012).ConclusionIn this study, 83% of respondents had persistent tinnitus after acoustic neuroma resection. The prognosis of tinnitus was worse for younger respondents, those with serviceable hearing preoperatively, and those with residual tumor postoperatively. Respondents’ satisfaction was higher if their tinnitus resolved.
National Behaviour in Multilateral Military Operations
Authors: Haesebrouck Tim 
Published: April 2016

What accounts for the diverging contributions to multinational military operations? Over two decades ago, Bennett, Lepgold and Unger published a seminal study that aimed to explain the division of the burdens of the Desert Storm Coalition. This article reviews four recent monographs on national behaviour in multinational operations against the backdrop of their conclusions. While the four reviewed titles suggest that the bulk of the conclusions of Bennett, Lepgold and Unger’s study hold beyond the scope of the Desert Storm Coalition, each of them also makes a distinct contribution to the literature. Baltrusaitis offers three excellent case studies on burden sharing in the 2003 Iraq War, Davidson provides essential insights on the impact of alliance value and threat and the studies of Auerswald and Saideman and Mello invoke important domestic variables that were not structurally examined by Bennett, Lepgold and Unger. Altogether, the reviewed titles provide convincing explanations for the behaviour of democratic states in US-led operations. Consequently, the article concludes by arguing that the most promising avenue for future research would be to focus on military operations in which the United States has a more limited role and on the contributions of non-democratic states to multinational operations. Auerswald DP and Saideman SM (2014) NATO in Afghanistan: Fighting Together, Fighting Alone. Princeton, NJ: Princeton University Press. Baltrusaitis DF (2010) Coalition Politics and the Iraq War: Determinants of Choice. Boulder, CO: First Forum Press. Davidson J (2011) America’s Allies and War: Kosovo, Afghanistan, and Iraq. Basingstoke: Palgrave Macmillan. Mello P (2014) Democratic Participation in Armed Conflict Military Involvement in Kosovo, Afghanistan and Iraq. Basingstoke: Palgrave Macmillan.
Epigenetic regulation of spinal cord gene expression contributes to enhanced postoperative pain and analgesic tolerance subsequent to continuous opioid exposure
Authors: Sahbaie Peyman , Liang De-Yong , Shi Xiao-You , Sun Yuan , Clark J David 
Published: April 2016

Background Opioids have become the mainstay for treatment of moderate to severe pain and are commonly used to treat surgical pain. While opioid administration has been shown to cause opioid-induced hyperalgesia and tolerance, interactions between opioid administration and surgery with respect to these problematic adaptations have scarcely been addressed. Accumulating evidence suggests opioids and nociceptive signaling may converge on epigenetic mechanisms in spinal cord to enhance or prolong neuroplastic changes. Epigenetic regulation of Bdnf (brain-derived neurotrophic factor) and Pdyn (prodynorphin) genes may be involved. Results Four days of ascending doses of morphine treatment caused opioid-induced hyperalgesia and reduced opioid analgesic efficacy in mice. Both opioid-induced hyperalgesia and the reduced opioid analgesic efficacy were enhanced in mice that received hindpaw incisions. The expression of Bdnf and Pdyn (qPCR) was increased after morphine treatment and incision. Chromatin immunoprecipitation assays demonstrated that the Pdyn and Bdnf promoters were more strongly associated with acetylated H3K9 after morphine plus incision than in the morphine or incision alone groups. Selective tropomyosin-related kinase B (ANA-12) and κ-opioid receptor (nor-binaltorphimine) antagonists were administered intrathecally, both reduced hyperalgesia one or three days after surgery. Administration of ANA-12 or nor-binaltorphimine attenuated the decreased morphine analgesic efficacy on day 1, but only nor-binaltorphimine was effective on day 3 after incision in opioid-exposed group. Coadministration of histone acetyltransferase inhibitor anacardic acid daily with morphine blocked the development of opioid-induced hyperalgesia and attenuated incision-enhanced hyperalgesia in morphine-treated mice. Anacardic acid had similar effects on analgesic tolerance, showing the involvement of histone acetylation in the interactions detected. Conclusions Spinal epigenetic changes involving Bdnf and Pdyn may contribute to the enhanced postoperative nociceptive sensitization and analgesic tolerance observed after continuous opioid exposure. Treatments blocking the epigenetically mediated up-regulation of these genes or administration of TrkB or κ-opioid receptor antagonists may improve the clinical utility of opioids, particularly after surgery.
BCR signaling inhibitors differ in their ability to overcome Mcl-1–mediated resistance of CLL B cells to ABT-199
Authors: Bojarczuk Kamil , Sasi Binu K. , Gobessi Stefania , Innocenti Idanna , Pozzato Gabriele , Laurenti Luca , Efremov Dimitar G. 
Published: April 2016

Key Points
BCR signals induce ABT-199 resistance in CLL cells by upregulating Mcl-1. SYK inhibitors prevent BCR-mediated Mcl-1 induction more effectively than BTK or PI3Kδ inhibitors.
The Effect of Intrathecal Morphine Dose on Outcomes After Elective Cesarean Delivery: A Meta-Analysis
Authors: Sultan Pervez , Halpern Stephen H. , Pushpanathan Ellile , Patel Selina , Carvalho Brendan 
Published: April 2016

BACKGROUND:
The intrathecal morphine dose achieving optimal analgesia for cesarean delivery while minimizing side effects has not yet been deduced. In this meta-analysis, our objective was to determine whether low- or high-dose intrathecal morphine provides acceptable duration and intensity of analgesia with fewer side effects.

METHODS:
A literature search (PubMed, EMBASE, MEDLINE, Scopus, Web of Science, and CINAHL) was performed to identify randomized controlled trials involving patients undergoing elective cesarean delivery under spinal anesthesia comparing low-dose (LD; 50–100 μg) morphine with higher dose (HD; >100–250 μg). The primary outcome was the time for first request for supplemental analgesia. The secondary outcomes included pain scores, morphine use, maternal side effects (vomiting and pruritus), and Apgar scores. Mean differences (MDs) and odds ratios (ORs) were calculated using random effects modeling with 95% confidence intervals (CIs).

RESULTS:
Eleven articles met our inclusion criteria. Four hundred eighty patients were recruited in all study groups (233 patients in the HD and 247 in the LD groups). The mean time to first analgesic request was longer (MD, 4.49 hours [95% CI, 1.85–7.13]; P = 0.0008) in the HD group compared with the LD group. Pain scores (0–100 scale) at 12 hours (MD, 2.54 [95% CI, −2.55 to 7.63]; P = 0.33) as well as morphine consumption at 24 hours (MD, 1.31 mg [95% CI, −3.06 to 7.31]; P = 0.42) were not significantly different. The incidence of nausea or vomiting (OR, 0.44 [95% CI, 0.27–0.73]; P = 0.002) and pruritus (OR, 0.34 [95% CI, 0.20–0.59]; P = 0.0001) was lower in the LD group. The incidence of Apgar scores <7 at 1 minute was not different between groups (OR, 1.11 [95% CI, 0.06–20.49]; P = 0.94).

CONCLUSIONS:
This meta-analysis shows that HDs of intrathecal morphine prolong analgesia after cesarean delivery compared with lower doses. The MD of 4.5 hours (95% CI, 1.9–7.1 and 99% CI, 1.0–8.2 hours) of pain relief must be balanced against the increased risk of maternal pruritus and vomiting. Results from this study can be used by clinicians to weigh the benefits and potential side effects of using HDs of intrathecal morphine for cesarean delivery.
The Effects of Fentanyl on Hepatic Mitochondrial Function
Authors: Djafarzadeh Siamak , Vuda Madhusudanarao , Jeger Victor , Takala Jukka , Jakob Stephan M. 
Published: April 2016

BACKGROUND:
Remifentanil interferes with hepatic mitochondrial function. The aim of the present study was to evaluate whether hepatic mitochondrial function is affected by fentanyl, a more widely used opioid than remifentanil.

METHODS:
Human hepatoma HepG2 cells were exposed to fentanyl or pretreated with naloxone (an opioid receptor antagonist) or 5-hydroxydecanoate (5-HD, an inhibitor of mitochondrial adenosine triphosphate (ATP)-sensitive potassium [mitoKATP] channels), followed by incubation with fentanyl. Mitochondrial function and metabolism were then analyzed.

RESULTS:
Fentanyl marginally reduced maximal mitochondrial complex–specific respiration rates using exogenous substrates (decrease in medians: 11%–18%; P = 0.003–0.001) but did not affect basal cellular respiration rates (P = 0.834). The effect on stimulated respiration was prevented by preincubation with naloxone or 5-HD. Fentanyl reduced cellular ATP content in a dose-dependent manner (P < 0.001), an effect that was not significantly prevented by 5-HD and not explained by increased total ATPase concentration. However, in vitro ATPase activity of recombinant human permeability glycoprotein (an ATP-dependent drug efflux transporter) was significantly stimulated by fentanyl (P = 0.004).

CONCLUSIONS:
Our data suggest that fentanyl reduces stimulated mitochondrial respiration of cultured human hepatocytes by a mechanism that is blocked by a mitoKATP channel antagonist. Increased energy requirements for fentanyl efflux transport may offer an explanation for the substantial decrease in cellular ATP concentration.
Epidural Volume Extension During Combined Spinal-Epidural Labor Analgesia Does Not Increase Sensory Block
Authors: Zaphiratos Valerie , George Ronald B. , Macaulay Bruce , Bolleddula Prasad , McKeen Dolores M. 
Published: April 2016

BACKGROUND:
Combined spinal-epidural (CSE) analgesia is widely used for delivering labor analgesia. Epidural volume extension (EVE) involves the injection of fluid into the epidural space compressing the dural sac, causing cephalad shift of the cerebral spinal fluid. Our hypothesis was that EVE with 10 mL normal saline during CSE would increase the sensory block height at 15 minutes after intrathecal injection. We expected EVE to decrease pain scores, decrease analgesia onset time, and decrease motor block compared with performing CSE without EVE (NEVE).

METHODS:
We randomly assigned 60 healthy term laboring nulliparous parturients with cervical dilation <5 cm to receive CSE either with EVE of 10 mL normal saline through the Tuohy needle before catheter insertion or CSE NEVE. Intrathecal analgesia consisted of 2 mg plain bupivacaine and 10 μg fentanyl (1 mL total). A blinded researcher assessed sensory dermatome level, analgesia, and motor blockade at regular intervals for 30 minutes. The primary outcome measure was the median peak sensory dermatome level at 15 minutes.

RESULTS:
Fifty-four parturients were analyzed. There was no significant difference in peak sensory dermatome levels at 15 minutes (median difference, 1 dermatome level; 95% confidence interval of median difference, 0 to 2; P = 0.22) and 30 minutes (median difference, 0 dermatome level; 95% confidence interval, −2 to 2; P = 0.76). There was no difference in the time to peak dermatome, minimum pain score, or the time to minimum pain score between groups.

CONCLUSIONS:
We found no significant difference between groups with regard to sensory dermatome level or pain scores when using EVE compared with NEVE. Our study demonstrates that addition of EVE does not offer superior analgesia when using a CSE technique for parturients requesting labor analgesia.