bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolution of the Gekkotan Adhesive System: Does Digit Anatomy Point to One or More Origins?
Authors: Russell Anthony P , Gamble Tony 
Published: March 2019

AbstractRecently-developed, molecularly-based phylogenies of geckos have provided the basis for reassessing the number of times adhesive toe-pads have arisen within the Gekkota. At present both a single origin and multiple origin hypotheses prevail, each of which has consequences that relate to explanations about digit form and evolutionary transitions underlying the enormous variation in adhesive toe pad structure among extant, limbed geckos (pygopods lack pertinent features). These competing hypotheses result from mapping the distribution of toe pads onto a phylogenetic framework employing the simple binary expedient of whether such toe pads are present or absent. It is evident, however, that adhesive toe pads are functional complexes that consist of a suite of integrated structural components that interact to bring about adhesive contact with the substratum and release from it. We evaluated the competing hypotheses about toe pad origins using 34 features associated with digit structure (drawn from the overall form of the digits; the presence and form of adhesive scansors; the proportions and structure of the phalanges; aspects of digital muscular and tendon morphology; presence and form of paraphalangeal elements; and the presence and form of substrate compliance-enhancing structures). We mapped these onto a well-supported phylogeny to reconstruct their evolution. Nineteen of these characters proved to be informative for all extant, limbed geckos, allowing us to assess which of them exhibit co-occurrence and/or clade-specificity. We found the absence of adhesive toe pads to be the ancestral state for the extant Gekkota as a whole, and our data to be consistent with independent origins of adhesive toe pads in the Diplodactylidae, Sphaerodactylidae, Phyllodactylidae, and Gekkonidae, with a strong likelihood of multiple origins in the latter three families. These findings are consistent with recently-published evidence of the presence of adhesively-competent digits in geckos generally regarded as lacking toe pads. Based upon morphology we identify other taxa at various locations within the gekkotan tree that are promising candidates for the expression of the early phases of adhesively-assisted locomotion. Investigation of functionally transitional forms will be valuable for enhancing our understanding of what is necessary and sufficient for the transition to adhesively-assisted locomotion, and for those whose objectives are to develop simulacra of the gekkotan adhesive system for biotechnological applications.
Apurinic/apyrimidinic endonuclease 1 (APE1) is dispensable for activation-induced cytidine deaminase (AID)-dependent somatic hypermutation in the immunoglobulin gene
Authors: Islam Helena , Kobayashi Maki , Honjo Tasuku 
Published: March 2019

Abstract
Activation-induced cytidine deaminase (AID) initiates DNA breakage in the variable (V) and switch (S) regions of the immunoglobulin gene, which results in somatic hypermutation (SHM) and class switch recombination (CSR), respectively. Apurinic/apyrimidinic endonuclease 1 (APE1) has been shown to be important for CSR, and is supposed to cleave at abasic sites when AID-dependently deaminated cytidine is removed by uracil DNA glycosylase. However, APE1 is unexpectedly dispensable for SHM in the S region and translocation between immunoglobulin heavy chain (IgH) and c-myc genes in the mouse B lymphoma cell line, CH12F3-2A. This suggested that APE1 is not involved in AID-dependent DNA breakage, but rather, in DNA repair. In order to investigate detailed molecular mechanisms underlying APE1’s involvement in CSR and SHM, we measured apurinic/apyrimidinic (AP) sites via aldehyde reactive probe labeling. Results indicated that the frequencies of AP sites in the S regions were not different between APE1−/−/−CH12F3-2A and wild-type CH12F3-2A cells. To carry out similar experiments in SHM of the V region, we generated an APE1 knockout (APE1−/−) human Burkitt’s lymphoma cell line, and compared SHM between APE1-proficient and -deficient BL2 lymphoma cells. SHM frequencies in the V regions of APE1−/−BL2 and APE1-proficient cells were also similar. Taken together, we showed that AID does not induce AP sites in the S region of the IgH gene, and that APE1 is not necessary for SHM in the V and S regions; however, it is required for DNA repair following DNA breakage in CSR.
Utility of Routine Axillary Ultrasound Surveillance in Breast Cancer Survivors with Previously Diagnosed Metastatic Axillary Adenopathy
Authors: Daugherty Michael W , Niell Bethany L 
Published: March 2019

AbstractObjectiveThe purpose of this study is to evaluate the utility of routine axillary ultrasound surveillance in asymptomatic T1 or T2 breast cancer patients with 1 to 2 positive axillary nodes that did not undergo axillary lymph node dissection.MethodsA retrospective review of our institutional database identified axillary and breast ultrasound examinations performed between February 1, 2011, and August 31, 2017, in asymptomatic T1 or T2 breast cancer patients with 1 to 2 positive axillary nodes that did not undergo axillary lymph node dissection. From the electronic medical record, patient demographics, imaging data, pathology results, and surgical reports were extracted. Positive predictive values (PPVs) 2 and 3 and cancer detection rate (CDR) were calculated with exact 95% confidence intervals (CIs).ResultsAn average of 2.1 surveillance examinations was performed in 77 unique patients, yielding 160 total examinations. For 7 patients, 7 biopsies were recommended, and 5 biopsies were performed. No malignancy was diagnosed, yielding a PPV2 of 0% (0/7) (95% CI = 0% to 35%); PPV3 of 0% (0/5) (95% CI = 0% to 45%), and CDR of zero per 1000 (0/160) examinations (95% CI = 0 to 19).ConclusionGiven the low frequency of axillary recurrence, routine axillary surveillance ultrasound in women with T1 or T2 breast cancers and 1 to 2 positive lymph nodes would be expected to have a low incremental CDR compared to clinical evaluation alone. Axillary surveillance ultrasound should not be routinely recommended or performed.
Hepatitis B virus activity in untreated hepatitis B e antigen–negative human immunodeficiency virus–hepatitis B virus co-infected patients from sub-Saharan Africa
Authors: Boyd Anders , Kouamé Menan Gerard , Houghtaling Laura , Moh Raoul , Gabillard Delphine , Maylin Sarah , Abdou Chekaraou Mariama , Delaugerre Constance , Anglaret Xavier , Eholié Serge Paul , Danel Christine , Zoulim Fabien , Lacombe Karine ,   on behalf of the ANRS 12136 Temprano and ANRS 12240 VarBVA studies
Published: March 2019

Abstract

Background
In human immunodeficiency virus (HIV) and hepatitis B virus (HBV) co-infected patients from sub-Saharan Africa with hepatitis B e antigen (HBeAg)-negative status, data are limited on the evolution of HBV activity when antiretroviral treatment (ART) is absent.

Methods
A total of 43 HBeAg-negative co-infected patients not indicated for ART (per concomitant World Health Organization recommendations) were followed during participation in a randomized controlled trial in Côte d’Ivoire. Chronic HBeAg-negative phases were classified at yearly visits and defined as ‘infection’ (HBV DNA ≤10 000 copies/mL and normal alanine aminotransferase [ALT]) or ‘hepatitis’ (HBV DNA >10 000 copies/mL and/or above normal ALT). Dispersion in HBV DNA and ALT levels during follow-up was assessed using interquartile range (IQR) regression.

Results
During a median 25 months (IQR 19–31), 17 (40%) patients consistently had ‘infection’, 5 (12%) consistently had ‘hepatitis’ and 21 (48%) fluctuated between phases. Wider dispersion in HBV DNA over time was associated with higher baseline HIV RNA (p=0.02) and higher baseline HBV DNA levels (p=0.008), while wider dispersion in ALT was associated with higher baseline HIV RNA (p<0.001), higher baseline ALT levels (p=0.02) and baseline hepatitis surface antigen >4.0 log10 IU/mL (p=0.02).

Conclusions
HBV activity is common with HBeAg-negative status, whose variation is partly linked to HIV replication. Fluctuations in disease phase make it difficult to assess the risk of morbidity and mortality after ART initiation.
Melancholia as Predictor of Electroconvulsive Therapy Outcome in Later Life
Authors: Veltman Eveline M. , de Boer Alef , Dols Annemiek , van Exel Eric , Stek Max L. , Sienaert Pascal , Bouckaert Filip , van der Mast Roos , Rhebergen Didi 
Published: March 2019

Objectives
In clinical practice, particularly melancholic depression benefits from electroconvulsive therapy (ECT), albeit research melancholia criteria from the Diagnostic and Statistical Manual of Mental Disorders (DSM) is not conclusive. We compared clinical characteristics and ECT outcome of melancholic and nonmelancholic depression, here defined by psychomotor symptoms.

Methods
One hundred ten depressed older in-patients treated with ECT were included in the Mood Disorders in Elderly treated with ECT study. The CORE was used for the assessment of psychomotor symptoms, with a score of 8 or higher defining melancholic depression. Depression severity was measured before, during, and after ECT. Characteristics were compared across melancholic and nonmelancholic patients. Regression analysis was used to assess the relation between psychomotor symptoms and remission/response, and survival analysis was used to examine the difference in time.

Results
Patients with melancholic depression had higher severity, lower cognitive and overall functioning, and lower prevalence of cardiovascular disease. However, no significant relations were found between CORE scores and remission/response. Because psychotic symptoms are a positive predictor of ECT response and remission, we examined whether CORE score was a predictor of response in the nonpsychotic group (n = 49). In nonpsychotic patients, remission was 62%, and the association between CORE scores and remission almost reached significance (P = 0.057).

Discussion
Although melancholically and nonmelancholically depressed patients differed significantly on several clinical characteristics, ECT outcome did not differ. Analyses may be hampered by a high prevalence of psychotic features. In nonpsychotic patients, CORE scores neared significance as predictor of remission, suggesting that CORE scores might be a distinguishing characteristic of melancholia in nonpsychotic patients and a clinical useful predictor of ECT response.
Supramodal Sentence Processing in the Human Brain: Fmri Evidence for the Influence of Syntactic Complexity in More Than 200 Participants
Authors: Uddén Julia , Hultén Annika , Schoffelen Jan-Mathijs , Lam Nietzsche , Harbusch Karin , van den Bosch Antal , Kempen Gerard , Petersson Karl Magnus , Hagoort Peter 
Published: March 2019

ABSTRACTThis study investigated two questions. One is to which degree sentence processing beyond single words is independent of the input modality (speech vs. reading). The second question is which parts of the network recruited by both modalities is sensitive to syntactic complexity. These questions were investigated by having more than 200 participants read or listen to well-formed sentences or series of unconnected words. A largely left-hemisphere fronto-temporoparietal network was found to be supramodal in nature, i.e. independent of input modality. In addition, the left inferior frontal gyrus (LIFG) and the left posterior middle temporal gyrus (LpMTG) were most clearly associated with left-branching complexity. The left anterior middle temporal gyrus (LaMTG) showed the greatest sensitivity to sentences that differed in right-branching complexity. Moreover, activity in LIFG and LpMTG increased from sentence onset to end, in parallel with an increase of the left-branching complexity. While LIFG, bilateral anterior and posterior MTG and left inferior parietal lobe (LIPL) all contribute to the supramodal unification processes, the results suggest that these regions differ in their respective contributions to syntactic complexity related processing. The consequences of these findings for neurobiological models of language processing are discussed.
Dynamic network properties of the interictal brain determine whether seizures appear focal or generalised
Authors: Woldman Wessel , Schmidt Helmut , Abela Eugenio , Chowdhury Fahmida A. , Pawley Adam D. , Jewell Sharon , Richardson Mark P. , Terry John R. 
Published: March 2019

AbstractObjectiveCurrent explanatory concepts suggest seizures emerge from ongoing dynamics of brain networks. It is unclear how brain network properties determine focal or generalised seizure onset, or how network properties can be described in a clinically-useful manner. Understanding network properties would cast light on seizure-generating mechanisms and allow to quantify in the clinic the extent to which a seizure is focal or generalised.Methods68 people with epilepsy and 38 healthy controls underwent 19 channel scalp EEG recording. Functional brain networks were estimated in each subject using phase-locking between EEG channels in the 6-9Hz band from segments of 20s without interictal discharges. Simplified brain dynamics were simulated using a computer model. We introduce three concepts: Critical Coupling (Cc), the ability of a network to generate seizures; Onset Index (OI), the tendency of a region to generate seizures; and Participation Index (PI), the tendency of a region to become involved in seizures.ResultsCc was lower in both patient groups compared with controls. OI and PI were more variable in focal-onset than generalised-onset cases. No regions showed higher OI and PI in generalised-onset cases than in healthy controls; in focal cases, the regions with highest OI and PI corresponded to the side of seizure onset.ConclusionsProperties of interictal functional networks from scalp EEG can be estimated using a computer model and used to predict seizure likelihood and onset patterns. Our framework, consisting of three clinically-meaningful measures, could be implemented in the clinic to quantify the diagnosis and seizure onset pattern.
A HaloTag-TEV genetic cassette for mechanical phenotyping of proteins from tissues
Authors: Rivas-Pardo Jaime Andrés , Li Yong , Mártonfalvi Zsolt , Tapia-Rojo Rafael , Unger Andreas , Fernández-Trasancos Ángel , Herrero-Galán Elías , Velázquez-Carreras Diana , Fernández Julio M. , Linke Wolfgang A. , Alegre-Cebollada Jorge 
Published: March 2019

AbstractSingle-molecule methods using recombinant proteins have generated transformative hypotheses on how mechanical forces are generated and sensed in biological tissues. However, testing these mechanical hypotheses on native molecules in their natural environment remains inaccessible to conventional genetics, biophysics and molecular biology tools. To address these limitations, here we demonstrate a genetically engineered knock-in mouse model carrying a HaloTag-TEV insertion in the protein titin, the main determinant of myocyte stiffness. Using our system, we have specifically severed the titin filament by digestion with TEV protease, and found that the response of muscle fibers to length changes requires mechanical transduction through titin’s intact polypeptide chain. HaloTag-based covalent tethering has enabled directed examination of the dynamics of titin under 1-100 pN forces using recently developed magnetic tweezers. At pulling forces lower than 10 pN, titin domains are readily recruited to the unfolded state, and produce 41.5 zJ mechanical work during refolding. Our results support an active role of titin in muscle contraction in coordination with actomyosin motors. Insertion of the HaloTag-TEV cassette in proteins with mechanical roles opens new grounds to explore the molecular basis of cellular force generation, mechanosensing and mechanotransduction.
Cryo-EM structure of the human L-type amino acid transporter 1 in complex with glycoprotein CD98hc
Authors: Lee Yongchan , Wiriyasermkul Pattama , Jin Chunhuan , Quan Lili , Ohgaki Ryuichi , Okuda Suguru , Kusakizako Tsukasa , Nishizawa Tomohiro , Oda Kazumasa , Ishitani Ryuichiro , Yokoyama Takeshi , Nakane Takanori , Shirouzu Mikako , Endou Hitoshi , Nagamori Shushi , Kanai Yoshikatsu , Nureki Osamu 
Published: March 2019

SummaryThe L-type amino acid transporter 1 (LAT1) transports large neutral amino acids and drugs across the plasma membrane and is crucial for nutrient uptake, brain drug delivery and tumor growth. LAT1 is a unique solute carrier that forms a disulfide-linked heterodimer with the cell-surface glycoprotein CD98 heavy chain (CD98hc), but the mechanisms of its molecular assembly and amino acid transport are poorly understood. Here we report the cryo-EM structure of the human LAT1-CD98hc heterodimer at 3.4 Å resolution, revealing the hitherto unprecedented architecture of a solute carrier-glycoprotein heterocomplex. LAT1 features a canonical LeuT-fold while exhibiting an unusual loop structure on transmembrane helix 6, creating an extended cavity to accommodate bulky hydrophobic amino acids and drugs. CD98hc engages with LAT1 through multiple interactions, not only in the extracellular and transmembrane domains but also in the interdomain linker. The heterodimer interface features multiple sterol molecules, corroborating previous biochemical data on the role of cholesterols in heterodimer stabilization. We also visualized the binding modes of two anti-CD98 antibodies and show that they recognize distinct, multiple epitopes on CD98hc but not its glycans, explaining their robust reactivities despite the glycan heterogeneity. Furthermore, we mapped disease-causing mutations onto the structure and homology models, which rationalized some of the phenotypes of SLC3- and SLC7-related congenital disorders. Together, these results shed light on the principles of the structural assembly between a glycoprotein and a solute carrier, and provide a template for improving preclinical drugs and therapeutic antibodies targeting LAT1 and CD98.
Generation of anisotropic strain dysregulates wild-type cell division at the interface between host and oncogenic tissue
Authors: Moruzzi Megan , Nestor-Bergmann Alexander , Goddard Georgina K. , Brennan Keith , Woolner Sarah 
Published: March 2019

SUMMARYEpithelial tissues are highly sensitive to anisotropies in mechanical force, with cells altering fundamental behaviours such as cell adhesion, migration and cell division [1-5]. It is well known that in the later stages of carcinoma (epithelial cancer), the presence of tumours alters the mechanical properties of a host tissue and that these changes contribute to disease progression [6-9]. However, in the earliest stages of carcinoma, when a clonal cluster of oncogene-expressing cells first establishes in the epithelium, the extent to which mechanical changes alter cell behaviour in the tissue as a whole remains unclear. This is despite knowledge that many common oncogenes, such as oncogenic Ras, alter cell stiffness and contractility [10-13]. Here, we investigate how mechanical changes at the cellular level of an oncogenic cluster can translate into the generation of anisotropic strain across an epithelium, altering cell behaviour in neighbouring host tissue. We generated clusters of oncogene-expressing cells within otherwise normal in vivo epithelium, using Xenopus laevis embryos. We find that cells in kRasV12, but not cMYC, clusters have increased contractility, which introduces radial stress in the tissue and deforms surrounding host cells. The strain imposed by kRasV12 clusters leads to increased cell division and altered division orientation in the neighbouring host tissue, effects that can be rescued by reducing actomyosin contractility specifically in the kRasV12 cells. Our findings indicate that some oncogenes can alter the mechanical and proliferative properties of host tissue from the very earliest stages of cancer development, changes which have the potential to contribute to tumorigenesis.
Virtuality at work and social media use among dispersed workers
Authors: Tijunaitis Karolis , Jeske Debora , Shultz Kenneth S. 
Published: March 2019

PurposeTechnology and globalization of services have facilitated the digitalization of many processes at work. However, their impact on social capital is unknown. The purpose of this paper is to examine the relationships between virtuality in the workplace and social capital.Design/methodology/approachUsing an online survey, the authors recruited 152 female student workers using an opportunity sampling approach.FindingsParticipants who used social media at work (n=112) reported higher social capital overall than participants who did not use any social media to communicate with colleagues at work (n=40). This difference also presented itself in terms of the social capital subscales (network ties, shared vision and trust). Mediation analysis conducted with users of social media at work revealed that social media use was a significant mediator in the relationship between virtuality at work and social capital overall (partial mediation). Subsequent analyses with the subscales for virtuality and social capital suggested full mediation of the relationship in most instances (with the exception of work practices).Originality/valueThis is the first study to examine the relationship between virtuality, social media and social capital at work. The result of this study suggests that social media use at work between colleagues can play a significant role in promoting social capital in workplaces that are heavily reliant on technological application to support interactions at work and feature geographical and temporal dispersion.