An Improved Chromosome-scale Genome Assembly and Population Genetics resource for Populus tremula.

Aspen (Populus tremula L.) is a keystone species and a model system for forest tree genomics. We present an updated resource comprising a chromosome-scale assembly, population genetics and genomics data.

Systems genetic analysis of lignin biosynthesis in Populus tremula.

The genetic control underlying natural variation in lignin content and composition in trees is not fully understood. We performed a systems genetic analysis to uncover the genetic regulation of lignin biosynthesis in a natural 'SwAsp' population of aspen (Populus tremula) trees. We analyzed gene expression by RNA sequencing (RNA-seq) in differentiating xylem tissues, and lignin content and composition using Pyrolysis-GC-MS in mature wood of 268 trees from 99 genotypes.

Challenges for Students in the Creation, Growth, and Management of an Academic, Student-run Asylum Clinic.

Medical school asylum clinics are complex organizations that blend medical and legal expertise with service to assist individuals seeking refuge from human rights violations. The balance of power shared by the students and faculty who lead these clinics varies widely across institutions, usually in an inverse reciprocal relationship. The Weill Cornell Center for Human Rights will observe its 10th anniversary in 2020 and is notable for espousing maximal student autonomy in the organization's governance with minimal faculty control or administration participation.

Rational Design of an Orally Active Anticancer Fluoropyrimidine, Pencitabine, a Hybrid of Capecitabine and Gemcitabine.

The structure of the anticancer drug capecitabine was redesigned to prevent metabolic conversion to 5-fluorouracil and its associated potentially fatal toxicities. The resulting cytidine analogue, pencitabine, is a hybrid of capecitabine and gemcitabine, another anticancer drug in clinical use. Preliminary biological evaluation revealed that pencitabine is cytotoxic in cell culture and orally active in a human xenograft test system.

Beyond Diagnosis: Adding a Psychodynamic Dimension to the Mental Health Asylum Evaluation.

Medical-legal asylum evaluations, conducted by experienced clinicians, are one of the most important parts of an application for successfully being granted asylum. Over two-thirds of these are mental health evaluations. Customarily these evaluations are summarized and drafted as diagnostic statements, providing the attorney with clear, corroborative testimony demonstrating that the patient suffers from psychological sequalae directly related to the individual's previous experience of persecution in their home country.

Decrease in primary but not in secondary abdominal surgery for Crohn's disease: nationwide cohort study, 1990-2014.

Background: Treatment of patients with Crohn's disease has evolved in recent decades, with increasing use of immunomodulatory medication since 1990 and biologicals since 1998. In parallel, there has been increased use of active disease monitoring. To what extent these changes have influenced the incidence of primary and repeat surgical resection remains debated.

Does Smoking Cessation Reduce Surgical Recurrence After Primary Ileocolic Resection for Crohn's Disease?

Background: Tobacco smoking is a known risk factor for recurrence of Crohn's disease after surgical resection.

Objective: This study assessed the effect of smoking cessation on long-term surgical recurrence after primary ileocolic resection for Crohn's disease.

Design: A retrospective review of a prospectively maintained database was conducted.

Medical Students' Attitudes toward Torture, Revisited.

This paper reports the findings of a survey of medical students' attitudes toward torture and discusses variables that may correlate with those attitudes. In late 2016, 483 enrolled medical and MD-PhD students at the Weill Cornell Medical College received an anonymous, institutional review board-approved survey that included questions about torture and its effectiveness, demographic questions, inquiries about personal experiences of harassment or discrimination, and questions regarding engagement in human rights activities. Some questions were drawn from a 2008 University of Illinois survey of medical students' attitudes toward torture, the only prior such survey at a US medical university.

Split-care patients and their caregivers: how collaborative is collaborative care?

This study assessed the experiences of patients receiving split-care treatment, focusing on communication between the two treating professionals and its impact on patient satisfaction. Studies have documented that for more than 20% of patients, no communication occurs between providers, and the present study provides further data. Split-care patients completed a 23-item questionnaire on SurveyMonkey via Mechanical Turk, a crowd-sourcing Website, assessing patients' split-care experiences, including whether their providers had communicated and the impact of communication on patients' satisfaction with treatment.

Do psychopharmacologists speak to psychotherapists? A survey of practicing clinicians.

Background: Split-treatment, the provision of psychotherapy and psychotropic medication by two different professionals, has become prevalent in U.S. mental health care delivery, as more Americans receive prescriptions and American psychiatrists provide less psychotherapy.

Synthesis and study of cyclic pronucleotides of 5-fluoro-2'-deoxyuridine.

A one-step method for the synthesis of cyclic pronucleotide (cProTide) derivatives of 5-fluoro-2'-deoxyuridine (FdUrd), utilizing a novel phosphoramidating reagent, is described. Stereochemistry at phosphorus was established by NMR studies and modeling. Cytotoxicity data of representative cProTide derivatives of FdUrd are presented.

Do psychotherapists speak to psychopharmacologists? A survey of practicing clinicians.

While more Americans are taking psychotropic medication than ever before, psychiatrists are providing less psychotherapy, leading to the prevalence of "split-treatment" whereby two professionals provide care. Communication between clinicians treating the same patient has traditionally been an accepted principle of optimal care, however there has been no published data documenting whether or not private practice therapists actually do communicate with the psychiatrists who prescribe for their patients. A pilot study was conducted in which a nine-item anonymous survey was distributed to non-medical psychotherapists in Manhattan.

The role of phosphate in the action of thymidine phosphorylase inhibitors: Implications for the catalytic mechanism.

The design and synthesis of 5-fluoro-6-[(2-aminoimidazol-1-yl)methyl]uracil (AIFU), a potent inhibitor of thymidine phosphorylase (TP) with K(i)-values of 11nM (ecTP) and 17nM (hTP), are described. Kinetic studies established that the type of inhibition of TP by AIFU is uncompetitive with respect to inorganic phosphate (or arsenate). The results obtained suggest that AIFU and other zwitterionic thymine analog inhibitors of TP act as transition state analogs, mimicking the anionic thymine leaving group, consistent with an S(N)2-type catalytic mechanism, and anchored by their protonated side chains to the enzyme-bound phosphate by electrostatic and H-bonding interactions.

6-substituted 5-fluorouracil derivatives as transition state analogue inhibitors of thymidine phosphorylase.

A combination of mechanism-based and structure-based design strategies led to the synthesis of a series of 5- and 6-substituted uracil derivatives as potential inhibitors of thymidine phosphorlase/platelet derived endothelial cell growth factor (TP/PD-ECGF). Among those tested, 6-imidazolylmethyl-5-fluorouracil was found to be the most potent inhibitor with a Ki-value of 51 nM, representing a new class of 5-fluoropyrimidines with a novel mechanism of action.

Calorimetric studies of ligand binding in R67 dihydrofolate reductase.

R67 dihydrofolate reductase (DHFR) is a novel bacterial protein that possesses 222 symmetry and a single active site pore. Although the 222 symmetry implies that four symmetry-related binding sites must exist for each substrate as well as for each cofactor, various studies indicate only two molecules bind. Three possible combinations include two dihydrofolate molecules, two NADPH molecules, or one substrate plus one cofactor.

Synthesis of 4-formyl-4-imidazolin-2-one nucleosides, isomers of uridine and 2'-deoxyuridine.

The syntheses of the ribo- and deoxyribonucleoside derivatives of 4-formyl-4-imidazolin-2-one, isosteric isomers of uridine and 2'-deoxyuridine, respectively, were carried out by ring contraction of the corresponding 5-bromouracil nucleosides, followed by conversion of the carboxyl side-chain of the products to the respective carboxaldehyde derivatives.

Modification of Escherichia coli thymidylate synthase at tyrosine-94 by 5-imidazolylpropynyl-2'-deoxyuridine 5'-monophosphate.

Evidence is presented that 5-imidazolylpropynyl-2'-deoxyuridine 5'-monophosphate (IP-dUMP) is a mechanism-based, irreversible inactivator of Escherichia coli thymidylate synthase (TS), which covalently modifies Tyr94 at the active site of the enzyme. The inactivation of TS was time and concentration dependent and did not require the folate cofactor. Due to the rapidity of the inactivation process, accurate kinetic parameters could be determined only in the presence of saturating concentrations (1000K(M)) of the competing substrate, dUMP.

5-propynylpyrimidine nucleoside derivatives: rationally designed mechanism-based inactivators of thymidylate synthase.

A novel series of 5-propynyl-dUMP derivatives, with a variety of leaving groups on the side-chain, was designed as potential mechanism-based inhibitors of thymidylate synthase (TS), and synthesized from 5-iodo-2'-deoxyuridine by Pd(0)-catalyzed coupling, followed by direct phosphorylation with POCl3. All members of the series inhibited TS competitively with Ki-values of 0.015-18 microM.

Examination of N-hydroxylation as a prerequisite mechanism of nitric oxide synthase inactivation.

L-N5-(1-Hydroxyiminoethyl)-ornithine (L-NHIO) and L-N6-(1-hydroxyiminoethyl)-lysine (L-NHIL) were synthesized and tested as potential intermediates in the mechanism-based inactivation of nitric oxide synthase (NOS) by L-N5-iminoethylornithine (L-NIO) and L-N6-iminoethyllysine (L-NIL). Although these compounds were determined to be competitive inhibitors, mechanism-based inactivation was not observed.