bluuebunny/crossref_metadata_2025 huggingface dataset:
GalK limits type I-F CRISPR-Cas expression in a CRP-dependent manner
Authors: Hampton Hannah G , Patterson Adrian G , Chang James T , Taylor Corinda , Fineran Peter C
Published: June 2019

CRISPR-Cas adaptive immune systems protect bacteria from phage predation, and other foreign genetic elements such as plasmids. Significant advances have been made regarding how CRISPR-Cas systems elicit immunity; however, comparatively little is known about their regulation. To study CRISPR-Cas regulation, we describe the construction of suicide lacZ-reporter plasmids with different antibiotic resistance cassettes. Through recombination into the host chromosome, single-copy expression can be achieved, thus preserving natural gene expression and maintaining a reporter expression output that reflects regulation within a normal genomic context. Previous work determined that the galactose metabolism gene galM, decreased the expression of the cas operon in Pectobacterium atrosepticum. We used the new integrative reporters to investigate galK, a gene that is located elsewhere in the genome and is responsible for the conversion of α-D-Galactose to Galactose-1-P during galactose metabolism. Deletion of galK led to elevated cas expression in a CRP-dependent manner but had no effect on CRISPR array expression. These results highlight that the metabolic status of the host cell is linked to the induction of CRISPR-Cas immunity.
Has retinal gene therapy come of age? From bench to bedside and back to bench
Authors: Trapani Ivana , Auricchio Alberto
Published: June 2019

Retinal gene therapy has advanced considerably in the past three decades. Initial efforts have been devoted to comprehensively explore and optimize the transduction abilities of gene delivery vectors, define the appropriate intraocular administration routes and obtain evidence of efficacy in animal models of inherited retinal diseases (IRDs). Successful translation in clinical trials of the initial promising proof-of-concept studies led to the important milestone of the first approved product for retinal gene therapy in both US and Europe. The unprecedented clinical development observed during the last decade in the field is however highlighting new challenges that will need to be overcome to bring gene therapy to fruition to a larger patient population within and beyond the realm of IRDs.
In situ target strength of bigeye tuna (Thunnus obesus) associated with fish aggregating devices
Authors: Boyra G , Moreno G , Orue B , Sobradillo B , Sancristobal I
Published: June 2019

Bigeye tuna (Thunnus obesus) is an important commercial fish species, which aggregates around fish aggregating devices (FADs) together with other tropical tuna species. Acoustics is the main technology used by fishers and scientists for the location and quantification of tunas at FADs. However, currently it is not possible to reliably discriminate between the different tropical tuna species that are found together at FADs using acoustic methods, which hampers the development of selective fishing needed to preserve some of the tropical tuna species for which overfishing is occurring. One of the prerequisites for species discrimination is to know the target strength (TS) of each species at different frequencies. This paper measures in situ TS values and explores the frequency response of bigeye tuna at FADs in the central Pacific Ocean using three different acoustic frequencies. For the range of body length caught (40–100 cm), the obtained b20 values were −65, −66, and −72 dB for 38, 120, and 200 kHz, respectively. The decreasing frequency response pattern obtained for this swimbladder bearing species contrasts with the opposite pattern previously observed for skipjack tuna (bladder-less), the most abundant tuna species found at FADs, hence allowing the potential for discrimination between the two species.
Interaction With Nontypeable Haemophilus influenzae Alters Progression of Streptococcus pneumoniae From Colonization to Disease in a Site-Specific Manner
Authors: Lewnard Joseph A , Givon-Lavi Noga , Dagan Ron
Published: June 2019

Background

Pneumococci and nontypeable Haemophilus influenzae (NTHi) often cocolonize children. The impact of species interactions on disease risk across the upper respiratory mucosa is not known.

Methods

We analyzed data from 4104 acute conjunctivitis (AC) cases, 11 767 otitis media (OM) cases, and 1587 nasopharyngeal specimens collected from Israeli children before pneumococcal conjugate vaccine introduction. We compared pneumococcal serotype distributions with NTHi present and absent, and compared single-species and mixed-species rates of serotype-specific progression from colonization to AC and OM.

Results

Pneumococcal serotypes causing single-species OM (NTHi absent) were less diverse than colonizing serotypes and also less diverse than those causing mixed-species OM; colonizing and OM-causing pneumococcal serotype distributions were more similar to each other with NTHi present than with NTHi absent. In contrast, serotype diversity did not differ appreciably between colonizing and AC-causing pneumococci, regardless of NTHi co-occurrence. The similarity of colonizing and AC-causing pneumococcal serotype distributions was consistent in the presence and absence of NTHi. Differences in rates that pneumococcal serotypes progressed from colonization to disease were reduced in both AC and OM when NTHi was present.

Conclusions

Interactions with NTHi may alter progression of pneumococcal serotypes to diseases of the upper respiratory mucosa in a site-specific manner.
Whistler instability based on observed flat-top two-component electron distributions in the Earth's magnetosphere
Authors: Qureshi M N S , Nasir Warda , Bruno R , Masood W
Published: June 2019

One of the fundamental features of space plasmas is the observation of non-Maxwellian particle velocity distributions. In the present study, we observe electron velocity distributions in the Earth's magnetosphere at times when the electron density is low, typical of cusp values, and when it is enhanced as a result of disturbances by the solar wind. We find that electron distributions are flat-topped and have two populations: one cold and one hot. We fit the observed electron distributions by a generalized $( {r,q} )$ distribution, and derive and plot expressions for the real frequency and growth rate using fitted and observed parameters. We show that enhancement in the density of hot electrons enhances the growth rate of whistler waves, which play an important role in energy transport in the Earth's magnetosphere.
Asymmetric Pedicle Subtraction Osteotomy for Adult Spinal Deformity with Coronal Imbalance: Complications, Radiographic and Surgical Outcomes
Authors: Chan Andrew K , Lau Darryl , Osorio Joseph A , Yue John K , Berven Sigurd H , Burch Shane , Hu Serena S , Mummaneni Praveen V , Deviren Vedat , Ames Christopher P
Published: June 2019

BACKGROUND

Asymmetric pedicle subtraction osteotomy (APSO) can be utilized for adult spinal deformity (ASD) with fixed coronal plane imbalance. There are few reports investigating outcomes following APSO and no series that include multiple revision cases.

OBJECTIVE

To detail our surgical technique and experience with APSO.

METHODS

All thoracolumbar ASD cases with a component of fixed, coronal plane deformity who underwent APSO from 2004 to 2016 at one institution were retrospectively reviewed. Preoperative and latest follow-up radiographic parameters and data on surgical outcomes and complications were obtained.

RESULTS

Fourteen patients underwent APSO with mean follow-up of 37-mo. Ten (71.4%) were revision cases. APSO involved a mean 12-levels (range 7-25) and were associated with 3.0 L blood loss (range 1.2-4.5) and 457-min of operative time (range 283-540). Surgical complications were observed in 64.3%, including durotomy (35.7%), pleural injury (14.3%), persistent neurologic deficit (14.3%), rod fracture (7.1%), and painful iliac bolt requiring removal (7.1%). Medical complications were observed in 14.3%, comprising urosepsis and 2 cases of pneumonia. Two 90-d readmissions (14.3%) and 5 reoperations (4 patients, 28.6%) occurred. Mean thoracolumbar curve and coronal vertical axis improved from 31.5 to 16.4 degrees and 7.8 to 2.9 cm, respectively. PI-LL mismatch, mean sagittal vertical axis, and pelvic tilt improved from 40.0 to 27.9-degrees, 10.7 to 3.5-cm, and 34.4 to 28.3-degrees, respectively.

CONCLUSION

The APSO, in both a revision and non-revision ASD population, provides excellent restoration of coronal balance—in addition to sagittal and pelvic parameters. Employment of APSO must be balanced with the associated surgical complication rate (64.3%).
Improved Postoperative Metrics with Modified Myofascial Closure in Fetal Myelomeningocele Repair
Authors: Flanders Tracy M , Madsen Peter J , Pisapia Jared M , Hudgins Eric D , Mackell Catherine M , Alexander Erin E , Moldenhauer Julie S , Zarnow Deborah M , Flake Alan W , Adzick N Scott , Heuer Gregory G
Published: June 2019

BACKGROUND

The effect of modifications in fetal myelomeningocele (fMMC) closure techniques has not been extensively studied.

OBJECTIVE

To study the effect of a modified closure technique on fMMC postnatal patient outcomes: hydrocephalus, hindbrain herniation, and cyst development.

METHODS

We performed single-center retrospective study of a subset of post-MOMS (Management of Myelomeningocele Study) trial patients who underwent fMMC closure. After January 2015, the fetal myofascial closure technique was modified. Needlepoint monopolar cautery was used to raise dural lined myofascial flaps to create a more robust closure. Outcomes between the pre- and postmodification groups were compared with regard to hindbrain herniation, hydrocephalus, and cyst development. Families who transitioned care to local institutions were contacted via telephone for outcome information.

RESULTS

From January 2011 to May 2016, data were reviewed from 119 fMMC closure patients. Patients without full follow-up data were excluded from the final analysis. Cerebrospinal fluid diversion was seen in 32 of 74 patients with the standard technique compared to 14 of 45 with the modified closure and was significantly decreased in postmodification when compared to that of the MOMS trial (P = .01). Hindbrain herniation resolution was significantly decreased in both the pre- and postmodification groups compared to that of the MOMS trial (P < .01). Prior to January 2015 with standard closure, 23 cysts required resection whereas no cysts required resection in the modified repair group (P < .01).

CONCLUSION

Modified myofascial closure for fMMC closure is safe and feasible. The new approach reflects a decreased rate of cyst development requiring surgical resection, and a trend for improved rates of hindbrain herniation and hydrocephalus.
Protecting Against Postoperative Dyspnea and Dysphagia After Occipitocervical Fusion
Authors: Gonda David D , Huang Meng , Briceño Valentina , Lam Sandi K , Luerssen Thomas G , Jea Andrew
Published: June 2019

BACKGROUND

Upper airway obstruction leading to dyspnea and dysphagia after occipitocervical fusion is a rare complication that has significant morbidity.

OBJECTIVE

To estimate the frequency of postoperative dyspnea and dysphagia in children after occipitocervical fusion and to identify variables associated with its occurrence.

METHODS

We retrospectively reviewed outcomes from all pediatric occipitocervical fusions at our institution between 2007 and 2014. Pre- and postoperative computed tomography (CT) scans were compared to determine differences in the clivoaxial (OC2) angles.

RESULTS

Sixty-seven pediatric patients underwent occipitocervical fusions. Median age was 9.6 yr (range 6 mo-18 yr). Fifty-six of 62 patients (90.3%) with at least 1 yr of follow-up had successful fusions. Eleven had pre-existing symptoms or otherwise compromised examination (eg, severe traumatic brain injury). None of 15 patients placed in extension (>2 degrees) relative to preoperative CT in Situ position developed new dyspnea or dysphagia. Nine of forty patients (23%) kept in Situ or flexed position developed new symptoms of dyspnea or dysphagia. Dysphagia in patients fused in the in Situ position was milder and resolved within a few weeks. No patient under age 5 (n = 20) developed symptoms of dyspnea or dysphagia regardless of head position. There were 3 cases of infection, 1 clinically silent vertebral artery injury, and 3 deaths at last follow-up.

CONCLUSION

Positioning of the child's head prior to occipitocervical fusion has considerable impact on outcomes, especially in older children. Careful measurements of the OC2 angle during surgery to ensure optimal head positioning in Situ or slightly extended position may prevent postoperative dysphagia or dyspnea.
Posterior Inferior Cerebellar Artery (PICA) Reanastomosis After Excision of a Ruptured p2-PICA Aneurysm: 2-Dimensional Operative Video
Authors: Cavallo Claudio , Labib Mohamed , Gandhi Sirin , Moreira Leandro Borba , Mascitelli Justin , Lawton Michael T
Published: June 2019

Posterior inferior cerebellar artery (PICA) aneurysms have an increased tendency towards a fusiform morphology precluding primary clip reconstruction. The management of these complex aneurysms might require cerebral revascularization to preserve flow in a distal PICA territory. This video illustrates a case of a ruptured p2-PICA aneurysm excision followed by a PICA reanastomosis. A 54-yr-old male presented with a sudden-onset severe headache, diplopia, and complete left cranial nerve six (CN VI) palsy. Neuroimaging demonstrated diffuse subarachnoid hemorrhage in basal cisterns. A catheter angiogram shows a ruptured small fusiform aneurysm in the p2-PICA segment. After obtaining consent for surgery, the patient was placed in a three-quarter prone position. After a hockey stick skin incision and C1 laminectomy, a lateral suboccipital craniotomy was performed. The aneurysm was identified within the vagoaccessory triangle. Cerebral protection consisted of propofol-induced electroencephalography burst suppression during the clamp time for the bypass, without hypothermia or hypertension. After trapping the aneurysm and excising the diseased arterial segment, the distal end of the p2-PICA was reanastomosed to the proximal parent vessel in an end-to-end fashion. Indocyanine green angiography confirmed patency of the anastomosis. Postoperatively, the patient was neurologically at his baseline. The CN VI palsy had completely resolved at a follow-up visit. Reanastomosis is an effective modality for reconstructing PICA following the excision of the fusiform aneurysm. The redundancy of the tonsillomedullary segment of PICA allows for easier distal segment reapproximation in the inferior hypoglossal triangle. An intracranial-intracranial revascularization technique eliminates the need for harvesting the occipital artery. Additionally, it prevents iatrogenic ischemic injury to contralateral PICA, if used for a PICA-PICA bypass.
1
© Barrow Neurological Institute, used with permission.
Microsurgical Resection of a Left Cerebral Peduncle Cavernous Malformation: 3-Dimensional Operative Video
Authors: Ceccato Guilherme H W , Rassi Marcio S , Borba Luis A B
Published: June 2019

Brainstem cavernous malformations are challenging lesions considering the numerous eloquent structures frequently related. Surgical resection is the preferred treatment if the patient is symptomatic and the lesion can be safely resected. We present the case of a right-handed 38-yr-old female, presenting with progressive impairment of her handwriting. Physical examination showed a right-sided grade 4/5 hemiparesis. Preoperative imaging was suggestive of a left cerebral peduncle cavernous malformation with a recent area of hemorrhage. The most superficial portion of the lesion was on the surface of the brainstem in the supratrigeminal safe entry zone of the pons. A frontotemporal craniotomy was performed, followed by a pretemporal transtentorial approach. Prior to performing brainstem incision, the area was stimulated, and no motor evoked potential was recorded. The hematoma was then evacuated, and the cavernous malformation was dissected and removed. The capsule was also dissected and removed, using neurophysiological monitoring to guide this procedure. The lesion was completely resected, and the patient was discharged on postoperative day 7 with a right-sided hemiparesis grade 3/5, which improved to grade 5/5 after 4 mo. The patient presented an improvement of her symptoms, with no new neurological deficits. Brainstem cavernomas can be safely removed in selected cases, using the adequate safe entry zone and the appropriate surgical approach. The pretemporal route can be used to reach the anterolateral aspect of the upper part of the brainstem, as it combines the advantages of both transsylvian and subtemporal approaches. An informed consent was obtained from the patient for publication of this operative video.
Absence of Ischemic Injury after Sacrificing the Superior Petrosal Vein during Microvascular Decompression
Authors: Xia Yuanxuan , Kim Timothy Y , Mashouf Leila A , Patel Kisha K , Xu Risheng , Casaos Joshua , Choi John , Kim Eileen S , Hung Alice L , Wu Adela , Garzon-Muvdi Tomas , Bender Matthew T , Jackson Christopher M , Bettegowda Chetan , Lim Michael
Published: June 2019

BACKGROUND

Sacrificing the superior petrosal vein (SPV) is controversial during a microvascular decompression (MVD). There have been multiple reports of complications including life-threatening brainstem infarction and cerebellar edema.

OBJECTIVE

To analyze the potential for vascular complications when the SPV is sacrificed during an MVD.

METHODS

Retrospective chart review was performed to identify all MVDs for trigeminal neuralgia and hemifacial spasm from 2007 to 2018 at 1 institution. Cases with ≥1 mo of follow-up were included and SPV sacrifice was noted. The primary outcome was complications related to SPV sacrifice including sinus thrombosis, cerebellar edema, and midbrain or pontine infarction. Imaging was used to confirm all potential vascular complications noted in medical records. Fisher's exact test and unpaired t-tests were used to compare between groups.

RESULTS

A total of 732 MVD cases were identified and 592 met inclusion criteria with an average follow-up of 11.8 ± 16.4 mo and a male-to-female ratio of 1:2.2. The SPV was sacrificed in 217 cases and retained in 375 cases. No SPV-related vascular complications were found in this study. Two unrelated cases of vascular complications were identified and both were in the nonsacrificed group. One case involved cerebellar bleeding while the other was an ipsilateral transverse sinus thrombosis that was present preoperatively.

CONCLUSION

In MVDs, there is no difference in the rate of vascular complications when the SPV is sacrificed compared to preserved. To best visualize a cranial nerve and optimize safe decompression, surgeons should feel free to sacrifice the SPV.
Obesity prevalence in large US cities: association with socioeconomic indicators, race/ethnicity and physical activity
Authors: Benusic Michael , Cheskin Lawrence J
Published: June 2019

Background

Obesity has a complex association with socioeconomic factors. Further clarification of this association could guide population interventions.

Methods

To determine the relationship between obesity prevalence, socioeconomic indicators, race/ethnicity, and physical activity, we performed a cross-sectional, multivariable linear regression, with data from large US cities participating in the Big Cities Health Inventory.

Results

Increased household income was significantly associated with decreased obesity prevalence, for White (−1.97% per 10 000USD), and Black (−3.02% per 10 000USD) populations, but not Hispanic. These associations remained significant when controlling for the proportion of the population meeting physical activity guidelines. Educational attainment had a co-linear relationship with income, and only a bachelor’s degree or higher was associated with a lower prevalence of obesity in White (−0.30% per percentage) and Black (−0.69% per percentage) populations. No association was found between obesity prevalence and the proportion of the population meeting physical activity guidelines for any race/ethnicity grouping.

Conclusion

At the population level of large US cities, obesity prevalence is inversely associated with median household income in White and Black populations. Strategies to increase socioeconomic status may also decrease obesity. Targeting attainment of physical activity guidelines as an obesity intervention needs further appraisal.
Feeding differing direct-fed microbials and its influence on growth and haematological parameters of growing lambs1
Authors: Antwi Christopher , Mensa Patience A , Arthur Fareed K N , Frimpong Yaw O , Baah John
Published: June 2019

A 4 mo feeding trial was conducted to ascertain the effect of direct-fed microbial (DFM) and their products, namely rumen enhancer three (RE3), Paenibacillus polymyxa (P3), and a fermentation product of RE3—RE3 Plus on the growth and haematological profile of lambs at different stages of growth (suckling, weaner, and grower phases). The lambs weighing 2.5 ± 2 kg were blocked by their weights and allotted to four dietary treatments, namely Control, RE3, RE3 Plus, and P3 in a randomized complete block design. Blood sampling of lambs to investigate the effect of the treatments on the haematological and blood biochemistry variables was done on monthly basis and analysis of variance in a repeated measures design was done using the Statistical Analysis System. Feed intake (FI) by lambs was not significantly (P > 0.05) influenced by DFM supplementation for all the phases of growth. However, feed conversion ratio (FCR) for the grower phase of the lamb was higher for T2. Similar (P > 0.05) hemoglobin (Hb), red blood cell (RBC), pack cell volume (PCV), mean corpuscular volume, mean corpuscular hemoglobin concentration (MCHC), eosinophil, lymphocyte, and basophil composition were recorded for lambs on the different experimental diets. Neutrophil and monocytes levels were, however, different (P < 0.05) for lambs fed the varying dietary treatments with lambs on RE3 Plus diets recording the lowest (P < 0.05) neutrophil levels. Monocytes levels were highest (P < 0.05) in lambs fed diets fortified with RE3. Sampling period influenced (P < 0.05) the Hb, RBC, PCV, MCHC, eosinophil, monocyte, and lymphocyte levels. The trial revealed a significant treatment × sampling period interaction (P < 0.0001) for the blood parameters examined. The inclusion of the different DFM products had no influence on the growth characteristics and blood profile of growing lambs.
New insights into the evolution of lateral compound eyes in Palaeozoic horseshoe crabs
Authors: Bicknell Russell D C , Amati Lisa , Ortega-Hernández Javier
Published: June 2019

Vision allows animals to interact with their environment. Aquatic chelicerates dominate the early record of lateral compound eyes among non-biomineralizing crown-group euarthropods. Although the conservative morphology of lateral eyes in Xiphosura is potentially plesiomorphic for Euarthropoda, synziphosurine eye organization has received little attention despite their early diverging phylogenetic position. Here, we re-evaluate the fossil evidence for lateral compound eyes in the synziphosurines Bunodes sp., Cyamocephalus loganensis, Legrandella lombardii, Limuloides limuloides, Pseudoniscus clarkei, Pseudoniscus falcatus and Pseudoniscus roosevelti. We compare these data with lateral eyes in the euchelicerates Houia yueya, Kasibelinurus amicorum and Lunataspis aurora. We find no convincing evidence for lateral eyes in most studied taxa, and Pseudoniscus roosevelti and Legrandella lombardii are the only synziphosurines with this feature. Our findings support two scenarios for euchelicerate lateral eye evolution. The elongate-crescentic lateral eyes of Legrandella lombardii might represent the ancestral organization, as suggested by the phylogenetic position of this taxon in stem-group Euchelicerata. Alternatively, the widespread occurrence of kidney-shaped lateral eyes in stem-group Xiphosura and stem-group Arachnida could represent the plesiomorphic condition; Legrandella lombardii eyes would therefore be derived. Both evolutionary scenarios support the interpretation that kidney-shaped lateral eyes are ancestral for crown-group Euchelicerata and morphologically conserved in extant Limulus polyphemus.
Adolescents and loot boxes: links with problem gambling and motivations for purchase
Authors: Zendle David , Meyer Rachel , Over Harriet
Published: June 2019

Loot boxes are items in video games that can be paid for with real-world money but contain randomized contents. Many games that feature loot boxes are played by adolescents. Similarities between loot boxes and gambling have led to concern that they are linked to the development of problem gambling in adolescents. Previous research has shown links between loot boxes and problem gambling in adult populations. However, thus far, there is no empirical evidence of either the size or existence of a link between loot box spending and problem gambling in adolescents. A large-scale survey of 16- to 18-year-olds (
n
= 1155) found evidence for such a link (
η
2
= 0.120). The link between loot box spending and problem gambling among these older adolescents was of moderate to large magnitude. It was stronger than relationships previously observed in adults. Qualitative analysis of text data showed that gamers bought loot boxes for a variety of reasons. Several of these motivations were similar to common reasons for engaging in gambling. Overall, these results suggest that loot boxes either cause problem gambling among older adolescents, allow game companies to profit from adolescents with gambling problems for massive monetary rewards, or both of the above. Possible strategies for regulation and restriction are given.
Pleistocene climate change and the formation of regional species pools
Authors: Calatayud Joaquín , Rodríguez Miguel Ángel , Molina-Venegas Rafael , Leo María , Horreo Jose Luis , Hortal Joaquín
Published: June 2019

Although the description of bioregions dates back to the origin of biogeography, the processes originating their associated species pools have been seldom studied. Ancient historical events are thought to play a fundamental role in configuring bioregions, but the effects of more recent events on these regional biotas are largely unknown. We used a network approach to identify regional and sub-regional faunas of European
Carabus
beetles and developed a method to explore the relative contribution of dispersal barriers, niche similarities and phylogenetic history on their configuration. We identify a transition zone matching the limit of the ice sheets at the Last Glacial Maximum. While southern species pools are mostly separated by dispersal barriers, in the north species are mainly sorted by their environmental niches. Strikingly, most phylogenetic structuration of
Carabus
faunas occurred during the Pleistocene. Our results show how extreme recent historical events—such as Pleistocene climate cooling, rather than just deep-time evolutionary processes—can profoundly modify the composition and structure of geographical species pools.
Do metrics of sexual selection conform to Bateman's principles in a wind-pollinated plant?
Authors: Tonnabel Jeanne , David Patrice , Pannell John R.
Published: June 2019

Bateman's principles posit that male fitness varies more, and relies more on mate acquisition, than female fitness. While Bateman's principles should apply to any organism producing gametes of variable sizes, their application to plants is potentially complicated by the high levels of polyandry suspected for plants, and by variation in the spatial distribution of prospective mates. Here we quantify the intensity of sexual selection by classical Bateman metrics using two common gardens of the wind-pollinated dioecious plant
Mercurialis annua
. Consistent with Bateman's principles, males displayed significantly positive Bateman gradients (a regression of fitness on mate number), whereas the reproductive success of females was independent of their ability to access mates. A large part of male fitness was explained by their mate number, which in turn was associated with males' abilities to disperse pollen. Our results suggest that sexual selection can act in plant species in much the same way as in many animals, increasing the number of mates through traits that promote pollen dispersal.
The preference and costs of sleeping under light at night in forest and urban great tits
Authors: Ulgezen Zeynep N. , Käpylä Teemu , Meerlo Peter , Spoelstra Kamiel , Visser Marcel E. , Dominoni Davide M.
Published: June 2019

Artificial light at night (ALAN) is an increasing phenomenon associated with worldwide urbanization. In birds, broad-spectrum white ALAN can have disruptive effects on activity patterns, metabolism, stress response and immune function. There has been growing research on whether the use of alternative light spectra can reduce these negative effects, but surprisingly, there has been no study to determine which light spectrum birds prefer. To test such a preference, we gave urban and forest great tits
(Parus major)
the choice where to roost using pairwise combinations of darkness, white light or green dim light at night (1.5 lux). Birds preferred to sleep under artificial light instead of darkness, and green was preferred over white light. In a subsequent experiment, we investigated the consequence of sleeping under a particular light condition, and measured birds' daily activity levels, daily energy expenditure (DEE), oxalic acid as a biomarker for sleep debt and cognitive abilities. White light affected activity patterns more than green light. Moreover, there was an origin-dependent response to spectral composition: in urban birds, the total daily activity and night activity did not differ between white and green light, while forest birds were more active under white than green light. We also found that individuals who slept under white and green light had higher DEE. However, there were no differences in oxalic acid levels or cognitive abilities between light treatments. Thus, we argue that in naive birds that had never encountered light at night, white light might disrupt circadian rhythms more than green light. However, it is possible that the negative effects of ALAN on sleep and cognition might be observed only under intensities higher than 1.5 lux. These results suggest that reducing the intensity of light pollution as well as tuning the spectrum towards long wavelengths may considerably reduce its impact.
Community turnover by composition and climatic affinity across scales in an alpine system
Authors: Smithers Brian V. , Oldfather Meagan F. , Koontz Michael J. , Bishop Jim , Bishop Catie , Nachlinger Jan , Sheth Seema N.
Published: June 2019

Premise of the study

Examining community turnover across climate gradients at multiple scales is vital to understanding biogeographic response to climate change. This approach is especially important for alpine plants in which the relative roles of topographic complexity and non-climatic or stochastic factors vary across spatial scales.

Methods

We examined the structure of alpine plant communities across elevation gradients in the White Mountains, California. Using community climatic niche means (CCNMs) and measures of community dissimilarity, we explored the relationship between community composition and elevation gradients at three scales: the mountain range, individual peaks, and within elevation contours.

Key Results

At the mountain range scale, community turnover and CCNMs showed strongly significant relationships with elevation, with an increase in the abundance of cooler and wetter-adapted species at higher elevations. At the scale of a single peaks, we found weak and inconsistent relationships between CCNMs and elevation, but variation in community composition explained by elevation increased. Within the elevation contours, the range of CCNMs was weakly positively correlated with turnover in species identity, likely driven by microclimate and other site-specific factors.

Conclusions

Our results suggest that there is strong environmental sorting of alpine plant communities at broad scales, but microclimatic and site-specific, non-climatic factors together shape community turnover at finer scales. In the context of climate change, our results imply that community-climate relationships are scale-dependent, and predictions of local alpine plant range shifts are limited by a lack of topoclimatic and habitat information.
Endothelial-derived exosomes demonstrate a link between endothelial innate inflammation and brain dysfunction and injury in aging
Authors: Elahi F.M. , Harvey D. , Altendahl M. , Casaletto K.B. , Fernandes N. , Staffaroni A.M. , Maillard P. , Hinman J.D. , Miller B.L. , DeCarli C. , Kramer J.H. , Goetzl E.J.
Published: June 2019

We test the hypothesis that endothelial cells take on an inflammatory phenotype in functionally intact human subjects with radiographic evidence of white matter injury. Markers within all three complement effector pathways and regulatory proteins were quantified from endothelial-derived exosomes (EDE) of subjects (age 70-82) with (n=11) and without (n=16) evidence of white matter hyperintensity on MRI. Group differences and associations with systemic markers of immune activation (IL6, ICAM1), cognition and neuroimaging were calculated via regression modelling.

EDE complement factors within the alternative and classical pathways were found to be higher and regulatory proteins lower in subjects with WMH. EDE levels of several factors demonstrated significant associations with cognitive slowing and systolic blood pressure. The inhibitor of the membrane attack complex, CD46, showed a significant positive association with cerebral grey matter volume. Systemic inflammatory markers, IL6 and ICAM1, were positively associated with EDE levels of several factors.

These findings provide the first in vivo evidence of the association of endothelial cell inflammation with white matter injury, cognition, and brain degeneration in functionally normal older individuals, and form the basis for future biomarker development in early or preclinical stages of vascular cognitive impairment and dementia.
Impact of herbivore preference on the benefit of plant trait variability
Authors: Thiel Tatjana , Gaschler Sarah , Mody Karsten , Blüthgen Nico , Drossel Barbara
Published: June 2019

We explore the hypothesis that intraspecific trait variability can beper sebeneficial for the plant when the curvature of the herbivore response to this trait is concave downwards. This hypothesis is based on a mathematical relation for non-linear averaging (Jensen’s inequality), leading to reduced herbivory when the trait distribution becomes broader. Our study introduces and investigates a model for plants and their insect herbivores that includes an unequal distribution of nutrient content between leaves. In contrast to earlier publications, we take into account the ability of herbivores to choose leaves, and the associated costs. By performing computer simulations and analytic calculations, we find that this herbivore preference can considerably alter the conclusion cited above. In particular, we demonstrate that herbivore populations that show preference for leaves on which they grow well can benefit from large nutrient level variability independently of the curvature of the herbivore response function, and despite the cost for preference.
A novel Mendelian randomization method identifies causal relationships between gene expression and low-density lipoprotein cholesterol levels
Authors: van der Graaf Adriaan , Claringbould Annique , Rimbert Antoine ,   BIOS consortium, Westra Harm-Jan , Li Yang , Wijmenga Cisca , Sanna Serena
Published: June 2019

Robust inference of causal relationships between gene expression and complex traits using Mendelian Randomization (MR) approaches is confounded by pleiotropy and linkage disequilibrium (LD) between gene expression quantitative loci (eQTLs). Here we propose a new MR method, MR-link, that accounts for unobserved pleiotropy and LD by leveraging information from individual-level data. In simulations, MR-link shows false positive rates close to expectation (median 0.05) and high power (up to 0.89), outperforming all other MR methods we tested, even when only one eQTL variant is present. Application of MR-link to low-density lipoprotein cholesterol (LDL-C) measurements in 12,449 individuals and eQTLs summary statistics from whole blood and liver identified 19 genes causally linked to LDL-C. These include the previously functionally validatedSORT1gene, and thePVRL2gene, located in theAPOElocus, for which a causal role in liver was yet unknown. Our results showcase the strength of MR-link for transcriptome-wide causal inferences.
The histopathological staging of tau, but not amyloid, corresponds to antemortem cognitive status, dementia stage, functional abilities, and neuropsychiatric symptoms
Authors: Malpas Charles B , Sharmin Sifat , Kalincik Tomas
Published: June 2019

Objective

Alzheimer’s disease (AD) is characterised by two cardinal pathologies, namely the extracellular accumulation amyloid-related aggregates, and the intracellular formation of taurelated neurofibrillary tangles (NFTs). While both pathologies disrupt cognitive function, a large body of evidence suggests that tau-pathology has a stronger relationship with the clinical manifestation of the disease compared to amyloid. Given the ordinal nature of histopathological staging systems, however, it is possible that the effect of amyloid pathology has been underestimated in clinicopathological studies.

Method

We investigated this possibility using data from the National Alzheimer’s Coordinating Center (NACC) database. Bayesian ordinal models were used to directly investigate the relative contribution of Braak NFT, diffuse plaque, and neuritic plaque staging to the severity of antemortem clinical impairment.

Results

Data from 144 participants were included in the final analysis. Bayesian ordinal models revealed that Braak NFT stage was the only predictor of global cognitive status, clinical dementia stage, functional abilities, and neuropsychiatric symptoms. When compared directly, Braak NFT stage was a stronger predictor than diffuse or neuritic plaques across these domains.

Conclusions

These findings confirm that tau-related pathology is more strongly related to clinical status than amyloid pathology. This suggests that conventional clinical markers of disease progression might be insensitive to amyloid-pathology, and hence might be inappropriate for use as outcome measures in therapeutic trials that directly target amyloid.
Mechanics of allostery: contrasting the induced fit and population shift scenarios
Authors: Ravasio Riccardo , Flatt Solange , Yan Le , Zamuner Stefano , Brito Carolina , Wyart Matthieu
Published: June 2019

In allosteric proteins, binding a ligand can affect function at a distant location, for example by changing the binding affinity of a substrate at the active site. The induced fit and population shift models, which differ by the assumed number of stable configurations, explain such cooperative binding from a thermodynamic viewpoint. Yet, understanding what mechanical principles constrain these models remains a challenge. Here we provide an empirical study on 34 proteins supporting the idea that allosteric conformational change generally occurs along a soft elastic mode presenting extended regions of high shear. We argue, based on a detailed analysis of how the energy profile along such a mode depends on binding, that in the induced fit scenario there is an optimal stiffness for cooperative binding, where N is the number of residues involved in the allosteric response. We find that the population shift scenario is more robust to mutation affecting stiffness, as binding becomes more and more cooperative with stiffness up to the same characteristic value , beyond which cooperativity saturates instead of decaying. We confirm numerically these findings in a non-linear mechanical model. Dynamical considerations suggest that a stiffness of order is favorable in that scenario as well, supporting that for proper function proteins must evolve a functional elastic mode that is softer as their size increases. In consistency with this view, we find a significant anticorrelation between the stiffness of the allosteric response and protein size in our data set.
Older adults demonstrate interlimb transfer of reactive gait adaptations to repeated unpredictable gait perturbations
Authors: McCrum Christopher , Karamanidis Kiros , Grevendonk Lotte , Zijlstra Wiebren , Meijer Kenneth
Published: June 2019

The ability to rapidly adjust gait to cope with unexpected mechanical perturbations declines with ageing. Previous studies however, have not ensured that pre-perturbation gait stability was equivalent, meaning that differences in unperturbed gait stability may have influenced the outcomes, which this study addresses. We also examine if interlimb transfer of gait adaptations are observed in healthy older adults, potentially driven by the increased motor error experienced due to their reduced ability to cope with the perturbations. 30 young and 28 older healthy adults experienced ten unpredictable treadmill belt accelerations (the first and last applied to the right leg, the others to the left) during walking at their stability-normalised walking speeds (young: 1.32±0.07m/s; older: 1.31±0.13m/s). Using kinematic data, we assessed the margins of stability during unperturbed walking and the first eight post-perturbation recovery steps. Older adults required three more steps to recover during the first perturbation to each leg than the young adults. Yet, after repeated perturbations of the left leg, older adults required only one more step to recover. Interestingly, for the untrained right leg, we found an improvement of three steps in the recovery of the older adults, indicating interlimb transfer of the improvements. Age differences in reactive gait stability remain even when participants’ walk with equivalent stability. Furthermore, we show that healthy older adults can transfer improvements in balance recovery made during repeated perturbations to one limb to their recovery following a perturbation to the untrained limb.
Meaningful patterns of information in the brain revealed through analysis of errors
Authors: Woolgar Alexandra , Dermody Nadene , Afshar Soheil , Williams Mark A. , Rich Anina N.
Published: June 2019

Great excitement has surrounded our ability to decode task information from human brain activity patterns, reinforcing the dominant view of the brain as an information processor. We tested a fundamental but overlooked assumption: that such decodable information is actually used by the brain to generate cognition and behaviour. Participants performed a challenging stimulus-response task during fMRI. Our novel analyses trained a pattern classifier on data from correct trials, and used it to examine stimulus and rule coding on error trials. There was a striking interaction in which frontoparietal cortex systematically representedincorrectrule but correct stimulus information when participants used the wrong rule, andincorrectstimulus but correct rule information on other types of errors. Visual cortex, by contrast, did not code correct or incorrect information on error. Thus behaviour was tightly linked to coding in frontoparietal cortex and only weakly linked to coding in visual cortex. Human behaviour may indeed result from information-like patterns of activity in the brain, but this relationship is stronger in some brain regions than in others. Testing for information coding on error can help establish which patterns constitute behaviourally-meaningful information.
Somatic aging pathways regulate reproductive plasticity inCaenorhabditis elegans
Authors: Ow Maria C. , Nichitean Alexandra M. , Hall Sarah E.
Published: June 2019

Early life stress of an animal often results in changes in gene expression that correspond with changes in their adult phenotype. In the nematodeC. elegans, starvation during early larval stages promotes entry into a non-feeding, stress-resistant stage named dauer until environmental conditions improve. Here we show that the endocrine signaling attributed to the somatic aging pathways inC. elegansadults lacking a functional germline also regulate the reproductive phenotypes of adults that have experienced dauer as a result of early life starvation. Postdauer adults modulate their fatty acid metabolism in order to re-allocate fat reserves in a manner benefitting their progeny at the expense of the parental somatic fat reservoir. Our results also show that the metabolic plasticity in postdauer animals and the inheritance of ancestral starvation memory in the progeny are a result of crosstalk between somatic and reproductive tissues mediated by the HRDE-1 nuclear RNAi Argonaute.
Mechanoreceptor-mediated circuit regulates cold tolerance in Caenorhabditis elegans
Authors: Takagaki Natsune , Ohta Akane , Ohnishi Kohei , Minakuchi Yohei , Toyoda Atsushi , Fujiwara Yuichiro , Kuhara Atsushi
Published: June 2019

C. elegans mechanoreceptors located in the ASG sensoryneuron have been found to sense temperature — a key trait for animal survival. Experimental loss of xanthine dehydrogenase (XDH-1) function in the AIN and AVJ interneurons resulted in reduced cold tolerance and atypical neuronal response to changes in temperature. These interneurons are synapse with upstream neurons such as the mechanoreceptor-expressing ASG. Ca2+ imaging revealed that ASG responsiveness to temperature change via mechanoreceptor DEG-1, a Degenerin/Epithelial Sodium Channel (DEG/ENaC), affects downstream AIN and AVJ circuits. Ectopic expression of DEG-1 in the ASE gustatory neuron resulted in acquisition of thermosensitivity, while electrophysiological analysis revealed that DEG-1 was involved in temperature sensation. Together, these results suggest that cold tolerance is regulated by mechanoreceptor-mediated circuit calculation.
Critiquing Protein Family Classification Models Using Sufficient Input Subsets
Authors: Carter Brandon , Bileschi Maxwell L. , Smith Jamie , Sanderson Theo , Bryant Drew , Belanger David , Colwell Lucy J.
Published: June 2019

In many application domains, neural networks are highly accurate and have been deployed at large scale. However, users often do not have good tools for understanding how these models arrive at their predictions. This has hindered adoption in fields such as the life and medical sciences, where researchers require that models base their decisions on underlying biological phenomena rather than peculiarities of the dataset introduced. In response, we propose a set of methods for critiquing deep learning models and demonstrate their application for protein family classification, a task for which high-accuracy models have considerable potential impact. Our methods extend the sufficient input subsets technique, which we use to identify subsets of features (SIS) in each protein sequence that are alone sufficient for classification. Our suite of tools analyzes these subsets to shed light on the decision-making criteria employed by models trained on this task. These tools expose that while deep models may perform classification for biologically-relevant reasons, their behavior varies considerably across choice of network architecture and parameter initialization. While the techniques that we develop are specific to the protein sequence classification task, the approach taken generalizes to a broad set of scientific contexts in which model interpretability is essential.