Miracle-dz/UniFAR-FTUs huggingface dataset:
Phosphorylation-Dependent Differential Regulation of Plant Growth, Cell Death, and Innate Immunity by the Regulatory Receptor-Like Kinase BAK1

Plants rely heavily on receptor-like kinases (RLKs) for perception and integration of external and internal stimuli. The Arabidopsis regulatory leucine-rich repeat RLK (LRR-RLK) BAK1 is involved in steroid hormone responses, innate immunity, and cell death control. Here, we describe the differential regulation of three different BAK1-dependent signaling pathways by a novel allele of BAK1, bak1-5. Innate immune signaling mediated by the BAK1-dependent RKs FLS2 and EFR is severely compromised in bak1-5 mutant plants. However, bak1-5 mutants are not impaired in BR signaling or cell death control. We also show that, in contrast to the RD kinase BRI1, the non-RD kinases FLS2 and EFR have very low kinase activity, and we show that neither was able to trans-phosphorylate BAK1 in vitro. Furthermore, kinase activity for all partners is completely dispensable for the ligand-induced heteromerization of FLS2 or EFR with BAK1 in planta, revealing another pathway specific mechanistic difference. The specific suppression of FLS2- and EFR-dependent signaling in bak1-5 is not due to a differential interaction of BAK1-5 with the respective ligand-binding RK but requires BAK1-5 kinase activity. Overall our results demonstrate a phosphorylation-dependent differential control of plant growth, innate immunity, and cell death by the regulatory RLK BAK1, which may reveal key differences in the molecular mechanisms underlying the regulation of ligand-binding RD and non-RD RKs.
Hierarchical Contextual Attention Recurrent Neural Network for Map Query Suggestion

The query logs from an on-line map query system provide rich cues to understand the behaviors of human crowds. With the growing ability of collecting large scale query logs, the query suggestion has been a topic of recent interest. In general, query suggestion aims at recommending a list of relevant queries w.r. t. users’ inputs via an appropriate learning of crowds’ query logs. In this paper, we are particularly interested in map query suggestions (e.g., the predictions of location-related queries) and propose a novel model Hierarchical Contextual Attention Recurrent Neural Network (HCAR-NN) for map query suggestion in an encoding-decoding manner. Given crowds map query logs, our proposed HCAR-NN not only learns the local temporal correlation among map queries in a query session (e.g., queries in a short-term interval are relevant to accomplish a search mission), but also captures the global longer range contextual dependencies among map query sessions in query logs (e.g., how a sequence of queries within a short-term interval has an influence on another sequence of queries). We evaluate our approach over millions of queries from a commercial search engine (i.e., Baidu Map). Experimental results show that the proposed approach provides significant performance improvements over the competitive existing methods in terms of classical metrics (i.e., Recall@K and MRR) as well as the prediction of crowds’ search missions.
A New Nonenzymatic Method and Device to Obtain a Fat Tissue Derivative Highly Enriched in Pericyte-Like Elements by Mild Mechanical Forces from Human Lipoaspirates

Adipose tissue contains multipotent elements with phenotypic and gene expression profiles similar to human mesenchymal stem cells (hMSCs) and pericytes. The chance of clinical translation of the multilineage potential of these cells is delayed by the poor/negligible cell survival within cryopreserved lipoaspirates, the difficulty of ex vivo expansion, and the complexity of current Good Manufacturing Practice (cGMP) requirements for expanded cells. Hence, availability of a minimally manipulated, autologous, hMSC/pericyte-enriched fat product would have remarkable biomedical and clinical relevance. Here, we present an innovative system, named Lipogems, providing a nonexpanded, ready-to-use fat product. The system uses mild mechanical forces in a completely closed system, avoiding enzymes, additives, and other manipulations. Differently from unprocessed lipoaspirate, the nonexpanded Lipogems product encompasses a remarkably preserved vascular stroma with slit-like capillaries wedged between adipocytes and stromal stalks containing vascular channels with evident lumina. Immunohistochemistry revealed that Lipogems stromal vascular tissue included abundant cells with pericyte/hMSC identity. Flow cytometry analysis of nonexpanded, collagenase-treated Lipogems product showed that it was comprised with a significantly higher percentage of mature pericytes and hMSCs, and lower amount of hematopoietic elements, than enzymatically digested lipoaspirates. Differently from the lipoaspirate, the distinctive traits of freshly isolated Lipogems product were not altered by cryopreservation. Noteworthy, the features of fresh product were retained in the Lipogems product obtained from human cadavers, paving the way to an off-the-shelf strategy for reconstructive procedures and regenerative medicine. When placed in tissue culture medium, the Lipogems product yielded a highly homogeneous adipose tissue-derived hMSC population, exhibiting features of hMSCs isolated from other sources, including the classical commitment to osteogenic, chondrogenic, and adipogenic lineages. Moreover, the transcription of vasculogenic genes in Lipogems-derived adipose tissue hMSCs was enhanced at a significantly greater extent by a mixture of natural provasculogenic molecules, when compared to hMSCs isolated from enzymatically digested lipoaspirates.
Phage Response to CRISPR-Encoded Resistance in Streptococcus thermophilus

ABSTRACT Clustered regularly interspaced short palindromic repeats (CRISPR) and their associated genes are linked to a mechanism of acquired resistance against bacteriophages. Bacteria can integrate short stretches of phage-derived sequences (spacers) within CRISPR loci to become phage resistant. In this study, we further characterized the efficiency of CRISPR1 as a phage resistance mechanism in Streptococcus thermophilus. First, we show that CRISPR1 is distinct from previously known phage defense systems and is effective against the two main groups of S. thermophilus phages. Analyses of 30 bacteriophage-insensitive mutants of S. thermophilus indicate that the addition of one new spacer in CRISPR1 is the most frequent outcome of a phage challenge and that the iterative addition of spacers increases the overall phage resistance of the host. The added new spacers have a size of between 29 to 31 nucleotides, with 30 being by far the most frequent. Comparative analysis of 39 newly acquired spacers with the complete genomic sequences of the wild-type phages 2972, 858, and DT1 demonstrated that the newly added spacer must be identical to a region (named proto-spacer) in the phage genome to confer a phage resistance phenotype. Moreover, we found a CRISPR1-specific sequence (NNAGAAW) located downstream of the proto-spacer region that is important for the phage resistance phenotype. Finally, we show through the analyses of 20 mutant phages that virulent phages are rapidly evolving through single nucleotide mutations as well as deletions, in response to CRISPR1.
DNA-Dependent Protein Kinase Is Not Required for Efficient Lentivirus Integration

ABSTRACT How DNA is repaired after retrovirus integration is not well understood. DNA-dependent protein kinase (DNA-PK) is known to play a central role in the repair of double-stranded DNA breaks. Recently, a role for DNA-PK in retroviral DNA integration has been proposed (R. Daniel, R. A. Katz, and A. M. Skalka, Science 284:644–647, 1999). Reduced transduction efficiency and increased cell death by apoptosis were observed upon retrovirus infection of culturedscid cells. We have used a human immunodeficiency virus (HIV) type 1 (HIV-1)-derived lentivirus vector system to further investigate the role of DNA-PK during integration. We measured lentivirus transduction of scid mouse embryonic fibroblasts (MEF) and xrs-5 or xrs-6 cells. These cells are deficient in the catalytic subunit of DNA-PK and in Ku, the DNA-binding subunit of DNA-PK, respectively. At low vector titers, efficient and stable lentivirus transduction was obtained, excluding an essential role for DNA-PK in lentivirus integration. Likewise, the efficiency of transduction of HIV-derived vectors in scid mouse brain was as efficient as that in control mice, without evidence of apoptosis. We observed increased cell death in scid MEF and xrs-5 or xrs-6 cells, but only after transduction with high vector titers (multiplicity of infection [MOI], >1 transducing unit [TU]/cell) and subsequent passage of the transduced cells. At an MOI of <1 TU/cell, however, transduction efficiency was even higher in DNA-PK-deficient cells than in control cells. Taken together, the data suggest a protective role of DNA-PK against cellular toxicity induced by high levels of retrovirus integrase or integration. Another candidate cellular enzyme that has been claimed to play an important role during retrovirus integration is poly(ADP-ribose) polymerase (PARP). However, no inhibition of lentivirus vector-mediated transduction or HIV-1 replication by 3-methoxybenzamide, a known PARP inhibitor, was observed. In conclusion, DNA-PK and PARP are not essential for lentivirus integration.
Cell‐Mediated Immune Responses and Protective Efficacy against Infection with Mycobacterium tuberculosis Induced by Hsp65 and hIL‐2 Fusion Protein in Mice

Heat shock protein 65 (Hsp65) is an important immunodominant antigen against tuberculosis (TB), and interleukin‐2 (IL‐2) plays an important role in the regulation of antimycobacteria immune responses. In order to further increase the immunogenicity of Hsp65 against infection caused by Mycobacterium tuberculosis (MTB), we expressed MTB Hsp65 and human IL‐2 fusion protein, Hsp65‐hIL‐2, in Escherichia coli. The expression of Hsp65‐hIL‐2 was confirmed by Western blotting using anti‐Hsp65 MoAb and anti‐hIL‐2 MoAb, respectively. Hsp65‐IL‐2 and Hsp65 were then purified by Ni‐NTA affinity chromatography. Mice were immunized with purified Hsp65‐hIL‐2 or Hsp65 emulsified in the adjuvant combination dimethyl dioctadecylammonium bromide and monophosphoryl lipid A. Eight weeks after immunization, there was significant proliferation of spleen lymphocytes in response to both Hsp65 and Hsp65‐hIL‐2 proteins. Interestingly, Hsp65‐hIL‐2 fusion protein elicited significantly higher levels of IFN‐γ and IL‐2 in the lymphocytes culture supernatant than that of the BCG (Denmark strain) immunized group and Hsp65 group (P < 0.05). After challenging the immunized mice with MTB, the bacteria loads in the spleens and lungs of mice immunized with the fusion protein were significantly lower than Hsp65 alone group, reaching an equivalent level as BCG immunization group. Our results suggest that the Hsp65 and hIL‐2 fusion protein may serve as an alternative vaccine candidate against MTB infection.
Dental anomalies of the permanent lateral incisors and prevalence of hypodontia outside the cleft area in complete unilateral cleft lip and palate.

OBJECTIVE To determine in complete unilateral cleft lip and palate (UCLP) subjects the characteristics (location, shape) of the cleft-side lateral incisor. The presence of a supernumerary tooth at the cleft side and the prevalence of hypodontia outside the cleft area were evaluated. A comparison was made of the shape of the cleft side lateral incisor to its contralateral incisor. SETTING Hospital for Rehabilitation of Craniofacial Anomalies (HRCA), Sao Paulo, Brazil. PATIENTS Orthopantomograms of 203 subjects with UCLP and without syndromes were chronologically selected from the HRCA data bank, within an age range of 5 to 10 years. OUTCOME MEASURE Orthopantomograms were analyzed by the same observer according to established criteria. RESULTS There were no statistically significant differences between sexes for any of the criteria studied. The cleft-side lateral incisor was present in 50.2%, and it was more commonly located at the distal side (76.5%). The congenital absence of the cleft-side lateral incisor was observed in 49.8% of the sample, and its antimere was congenitally missing in 10.9%, this difference being statistically significant. The most commonly missing tooth outside the cleft area was the maxillary second premolar. CONCLUSIONS The high prevalence of hypodontia of the permanent lateral incisor in the cleft side showed that the cleft could play an important role in this absence. There were different patterns for the presence of the cleft-side lateral incisor.
Lipoxin B4 regulates human monocyte/neutrophil adherence and motility: design of stable lipoxin B4 analogs with increased biologic activity

Lipoxins are biologically active products of arachidonic acid that are formed via cell‐cell interactions, particularly those involving leukocytes. Lipoxin A4 and lipoxin B4 (LXB4), within similar concentration ranges, each inhibit human neutrophil, activate monocyte adherence and motility, and are rapidly converted by initial dehydrogenation to other inactive metabolites by human monocytes. Here, we exposed LXB4 to isolated recombinant 15‐hydroxy‐prostaglandin dehydrogenase (15‐PGDH) and found that it was a good substrate for the enzyme (Am=6.9 μM); we identified the major product as 5‐oxo‐LXB4 via physical methods including liquid chromatogra‐phy/tandem mass spectrometry. This is the first evidence of 15‐PGDH converting a substrate hydroxyl group at a position other than the ω‐6 carbon. Based on these observations, several LXB4 analogs were designed and prepared by total organic synthesis to test as stable mimetics: 5(S)‐methyl‐LXB4‐me, 5(R)‐methyl‐LXB4‐me, and 15‐epi‐LXB4‐me (the aspirin‐triggered form of LXB4). Both 5(S)‐methyl‐LXB4‐me and 5(R)‐methyl‐LXB4‐me were resistant to rapid conversion. In addition, actions of the stable analogs were evaluated separately with human mono‐cytic cells and neutrophils, and 5(S)‐methyl‐LXB4‐me was more potent (nM range) than LXB4 for both cell types. In contrast, 5(R)‐methyl‐LXB4‐me was potent in inhibiting neutrophil transmigration across endothelial monolayers, but did not stimulate monocyte adherence. These results indicate that LXB4 analogs can be designed to resist rapid transformation and retain bioactivity with both monocytes and neutrophils. Moreover, they suggest that LXB4 stable analogs are useful tools to selectively evaluate the modes of actions of LXB4 with different tis‐sues. —Maddox, J. F. , Colgan, S. P., Clish, C. B. , Petasis, N. A. , Fokin, V. V. Serhan, C. N. , Lipoxin B4 regulates human monocyte/neutrophil adherence and motility: design of stable lipoxin B4 analogs with increased biologic activity. FASEB J. 12, 487–494 (1998)
Acute and subacute ischemic stroke at high-field-strength (3.0-T) diffusion-weighted MR imaging: intraindividual comparative study.

PURPOSE To compare signal-to-noise ratios (SNRs), contrast-to-noise ratios (CNRs), image quality, and confidence in diagnosis between 1.5- and 3.0-T diffusion-weighted (DW) magnetic resonance (MR) imaging of ischemic stroke lesions. MATERIALS AND METHODS The study design was approved by the institutional review board, and all patients gave informed consent. In a prospective intraindividual study, 25 patients who had clinical symptoms consistent with ischemic stroke underwent DW MR imaging at both 1.5 T and 3.0 T. The 3.0- or 1.5-T examination was performed immediately one after the other, in random order. Two readers in consensus recorded the presence and number of ischemic lesions and rated image quality and lesion conspicuity. The image SNR and the CNR of the ischemic lesions were quantified. Paired Student t and Wilcoxon matched-pairs signed rank tests were used to test for statistical significance. RESULTS Image quality at 3.0-T DW MR imaging was consistently lower than that at 1.5-T DW MR imaging owing to greater image distortions (P < .05). Yet, overall SNR and lesion CNR at 3.0 T increased significantly; mean increases were 48.8% (P < .001) and 96.3% (P < .01), respectively. The higher overall SNR and lesion CNR translated into a significantly higher sensitivity in the detection of ischemic lesions at 3.0 T than at 1.5 T. Of the total of 48 lesions that were identified in 19 of the 25 patients, 47 (98%) were diagnosed at 3.0 T and 36 (75%) were diagnosed at 1.5 T. In addition, the conspicuity of the lesions that were visible with both systems was significantly higher at 3.0 T (P < .001). CONCLUSION Although 3.0-T DW MR imaging generates greater image distortions, it yields increased SNR and CNR compared with DW MR imaging at 1.5 T. The increased CNR at 3.0 T translates into a significantly improved diagnostic confidence in the detection of focal apparent diffusion coefficient changes in the setting of subacute and acute ischemic stroke.
Muscle after spinal cord injury

The morphological and contractile changes of muscles below the level of the lesion after spinal cord injury (SCI) are dramatic. In humans with SCI, a fiber‐type transformation away from type I begins 4–7 months post‐SCI and reaches a new steady state with predominantly fast glycolytic IIX fibers years after the injury. There is a progressive drop in the proportion of slow myosin heavy chain (MHC) isoform fibers and a rise in the proportion of fibers that coexpress both the fast and slow MHC isoforms. The oxidative enzymatic activity starts to decline after the first few months post‐SCI. Muscles from individuals with chronic SCI show less resistance to fatigue, and the speed‐related contractile properties change, becoming faster. These findings are also present in animals. Future studies should longitudinally examine changes in muscles from early SCI until steady state is reached in order to determine optimal training protocols for maintaining skeletal muscle after paralysis. Muscle Nerve, 2009
Fluid Overload in Patients With Severe Sepsis and Septic Shock Treated With Early Goal-Directed Therapy Is Associated With Increased Acute Need for Fluid-Related Medical Interventions and Hospital Death

ABSTRACT Early goal-directed therapy (EGDT) consists of early, aggressive fluid resuscitation and is known to improve survival in sepsis. It is unknown how often EGDT leads to subsequent fluid overload and whether post-EGDT fluid overload affects patients’ outcomes. Our hypothesis was that patients with sepsis treated with EGDT were at risk for fluid overload and that fluid overload would be associated with adverse outcomes. We conducted a retrospective cohort of 405 consecutive patients admitted with severe sepsis and septic shock to the medical intensive care unit of a tertiary care academic hospital from January 2008 to December 2009. Baseline demographics, daily weights, fluid status, clinical or radiographic evidence of fluid overload, and medical interventions (thoracentesis, paracentesis, diuretic use, and ultrafiltration) were abstracted, and associations explored using univariate and multivariate logistic and linear regression analyses. At day 1, 67% of patients developed evidence of fluid overload, and in 48%, fluid overload persisted to day 3. Interrater agreement for presence of fluid overload was substantial (&kgr; = 0.7). An increased trend in weight was noted in those with persistent clinical and radiologic evidence of fluid overload, but not with recorded positive fluid balance. When adjusted for baseline severity of illness, fluid overload was associated with increased use of fluid-related medical interventions (thoracentesis and diuretics) and hospital mortality (odds ratio, 1.92; confidence interval, 1.16–3.22). In patients with severe sepsis and septic shock treated with EGDT, clinical evidence of persistent fluid overload is common and is associated with increased use of medical interventions and hospital mortality.
Recurrent aphthous ulceration: a review of potential causes and novel treatments

Abstract Purpose of article: This review examines studies published between May 2012 and 2017 with a specific interest in potential recurrent aphthous ulceration (RAU) etiologies and treatment modalities/efficacy, including topical treatments, systemic regimens, vitamin repletion, and laser therapy, among others. Materials and methods: PubMed MEDLINE and Cochrane Database of Systematic Reviews were searched using various combinations of: ‘aphthous’, ‘ulcer’, and ‘treatment’. The titles and abstracts from the initial literature search were appraised to identify articles for full review and reference sections from each article were searched manually for relevant publications. Both randomized controlled trials and observational reports were included in this review, as some treatment types have not been formally examined in randomized trials. Relevant studies were reviewed, compared, and summarized. Results: RAU can result from systemic disease and trauma, but recent studies have shown a variety of potential etiologies, ranging from vitamin deficiencies, oral microbiota derangements, hematological considerations, stress, genetic polymorphisms to oxidant-antioxidant imbalances, among others. Many modalities of therapy are available and have proven efficacious. Conclusions: As the exact etiology of RAU is still unknown, therapy is based on symptomatic relief.
Testing the Predictive Power of Cognitive Atypicalities in Autistic Children: Evidence from a 3‐Year Follow‐Up Study

This follow‐up study investigated the predictive power of early cognitive atypicalities. Specifically, it examined whether early individual differences in specific cognitive skills, including theory of mind, executive function, and central coherence, could uniquely account for variation in autistic children's behaviors—social communication, repetitive behaviors, and interests and insistence on sameness—at follow‐up. Thirty‐seven cognitively able children with an autism spectrum condition were assessed on tests tapping verbal and nonverbal ability, theory of mind (false‐belief prediction), executive function (planning ability, cognitive flexibility, and inhibitory control), and central coherence (local processing) at intake and their behavioral functioning (social communication, repetitive behaviors and interests, insistence on sameness) 3 years later. Individual differences in early executive but not theory of mind skills predicted variation in children's social communication. Individual differences in children's early executive function also predicted the degree of repetitive behaviors and interests at follow‐up. There were no predictive relationships between early central coherence and children's insistence on sameness. These findings challenge the notion that distinct cognitive atypicalities map on to specific behavioral features of autism. Instead, early variation in executive function plays a key role in helping to shape autistic children's emerging behaviors, including their social communication and repetitive behaviors and interests. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.