Exploring the Specific Role of Iron Center in the Catalytic Activity of Human Serum Transferrin: CTAB-Induced Conformational Changes and Sequestration by Mixed Micelles.

Conformational changes play a seminal role in modulating the activity of proteins. This concept becomes all the more relevant in the context of metalloproteins, owing to the formation of specific conformation(s) induced by internal perturbations (like a change in pH, ligand binding, or receptor binding), which may carry out the binding and release of the metal ion/ions from the metal binding center of the protein. Herein, we investigated the conformational changes of an iron-binding protein, monoferric human serum transferrin (Fe-hTF), using several spectroscopic approaches. We could reversibly tune the cetyltrimethylammonium bromide (CTAB)-induced conformation of the protein, exploiting the concept of mixed micelles formed by three sequestrating agents: (3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate) hydrate (CHAPS) and two bile salts, namely, sodium cholate (NaC) and sodium deoxycholate (NaDC). The formation of mixed micelles between CTAB and these reagents (CHAPS/NaC/NaDC) results in the sequestration of CTAB molecules from the protein environment and aids the protein in reattaining its native-like structure. However, the guanidinium hydrochloride-induced denatured Fe-hTF did not acquire its native-like structure using these sequestrating agents, which substantiates the exclusive role of mixed micelles in the present study. Apart from this, we found that the conformation of transferrin (adopted in the presence of CTAB) displays pronounced esterase-like activity toward the para-nitrophenyl acetate (PNPA) substrate as compared to native transferrin. We also outlined the impact of the iron center and amino acids surrounding the iron center on the effective catalytic activity in the CTAB medium. We estimated ∼3 times higher specific catalytic efficiency for the iron-depleted Apo-hTF compared to the fully iron-saturated Fe2-hTF in the presence of CTAB.

Macrocyclic Cavitand ß-Cyclodextrin Inhibits the Alcohol-Induced Trypsin Aggregation.

Trypsin, the most abundant pancreatic protein, aids in protein digestion by hydrolysis and exhibits aggregation propensity in presence of alcohol, which can further lead to pancreatitis and eventually pancreatic cancer. Herein, by several experimental and theoretical approaches, we unearth the inhibition of alcohol-induced aggregation of Trypsin by macrocyclic cavitand, ß-cyclodextrin (ß-CD). ß-CD interacts with the native protein and shows inhibitory effect in a dose dependent manner. Moreover, the secondary structures and morphologies of Trypsin in presence of ß-CD also clearly emphasize the inhibition of fibril formation. From Fluorescence Correlation Spectroscopy, we observed an enhancement in diffusion time of Nile Red with ∼2.5 times increase in hydrodynamic radius, substantiating the presence of fibrillar structure. Trypsin also shows reduction in its functional activity due to alcohol-induced aggregation. Our simulation data reports the probable residues responsible for fibril formation, which was validated by molecular docking studies.

Structure and Transition Dynamics of Intrinsically Disordered Proteins Probed by Single-Molecule Spectroscopy.

Intrinsically disordered proteins (IDPs) are a class of proteins that do not follow the unanimated perspective of the structure-function paradigm. IDPs enunciate the dynamics of motions which are often difficult to characterize by a particular experimental or theoretical approach. The chameleon nature of the IDPs is a result of an alteration or transition in their conformation upon binding with ligands. Experimental investigations via ensemble-average approaches to probe this randomness are often difficult to synchronize. Thus, to sense the substates of different conformational ensembles of IDPs, researchers have often targeted approaches based on single-molecule measurements. In this Perspective, we will discuss various single-molecule approaches to explore the conformational transitions of IDPs in different scenarios, the outcome, challenges, and future prospects.

Exploring the Nucleobase-Specific Hydrophobic Interaction of Cryptolepine Hydrate with RNA and Its Subsequent Sequestration.

The study of the interactions of drug molecules with genetic materials plays a key role underlying the development of new drugs for many life-threatening diseases in pharmaceutical industries. Understanding their fundamental base-specific and/or groove-binding interaction is crucial to target the genetic material with an external drug, which can pave the way to curing diseases related to the genetic material. Here, we studied the interaction of cryptolepine hydrate (CRYP) with RNA under physiological conditions knowing the antimalarial and anticancer activities of the drug. Our experiments explicitly demonstrate that CRYP interacts with the guanine- and adenine-rich region within the RNA duplex. The pivotal role of the hydrophobic interaction governing the interaction is substantiated by temperature-dependent isothermal titration calorimetry experiments and spectroscopic studies. Circular dichroism study underpins a principally intercalative mode of binding of CRYP with RNA. This interaction is found to be drastically affected in the presence of magnesium salt, which has a strong propensity to coordinate with RNA nucleobases, which can in turn modulate the interaction of the drug with RNA. The temperature-dependent calorimetric results substantiate the occurrence of entropy-enthalpy compensation, which enabled us to rule out the possibility of groove binding of the drug with RNA. Furthermore, our results also show the application of host-guest chemistry in sequestering the RNA-bound drug, which is crucial to the development of safer therapeutic applications.

Protein-templated gold nanoclusters as specific bio-imaging probes for the detection of Hg(ii) ions in in vivo and in vitro systems: discriminating between MDA-MB-231 and MCF10A cells.

Gold nanoclusters (AuNCs) synthesized within a protein (Human Serum Albumin, HSA) template exhibited intense red luminescence accompanied by a quantum yield >10% and remarkable photo and cluster-core stability for a prolonged period (more than a year). These photoluminescent nanoclusters (NCs) were resistant to chemical and thermal perturbations but break down selectively and highly sensitively in the presence of mercury, Hg(ii), ions. The AuNCs were efficient in quantifying Hg(ii) ions in solution as well as bound to the hormone insulin. By exploiting the auto-fluorescence of these AuNCs, we demonstrated that our AuNCs were able to sense Hg(ii) ions at single-molecule sensitivity using Fluorescence Correlation Spectroscopy (FCS), highlighting a detection limit in the sub-nanomolar regime. The translational diffusion time of the AuNCs decreased significantly upon the interaction with Hg(ii) ions and resulted in the formation of smaller sized clusters. A cell viability study reveals the non-toxic nature of these nano-probes, which thus can be used for cell imaging. Interestingly, a cell line-based study reveals that the fluorescence intensity of AuNCs could be detected in cancerous MDA-MB-231 cells but not in non-cancerous breast-derived MCF10A cells. Further, time lapse fixed cell imaging by confocal microscopy revealed that the fluorescence of AuNCs could be quenched by Hg(ii) ions inside the MDA-MB-231 cells. Thus the objective of our study is to appraise the sensitive in vivo as well as in vitro detection of Hg(ii) ions using AuNCs as a probe.

Contrasting Thermodynamics Governs the Interaction of 3-Hydroxyflavone with the N-Isoform and B-Isoform of Human Serum Albumin.

Herein we report the interaction of 3-hydroxyflavone (3HF) with various isomeric forms of Human Serum Albumin (HSA), namely, the N-isoform (or native HSA at pH 7.4) and the B-isoform (at pH 9.2). Spectroscopic signatures of 3HF reveal that the interaction of 3HF with the N-isoform of HSA results in significant lowering of absorbance of the neutral species (λabs ∼ 345 nm) with concomitant increase of the anionic species (λabs ∼ 416 nm) whereas interaction with the B-isoform of HSA leads to selective enhancement of absorbance of the anionic species. The fluorescence profile of 3HF displays marked increase of intensity of the proton transferred tautomer (λem ∼ 538 nm) as well as the anionic species (λem ∼ 501 nm) for both the forms of the protein. However, analyses of the associated thermodynamics through temperature-dependent isothermal titration calorimetric (ITC) indicate that the interaction of 3HF with the N-isoform of HSA is more enthalpic in the lower temperature limit while the entropy contribution predominates in the higher temperature limit. Consequently, the 3HF-HSA (N-isoform at pH 7.4) interaction reveals an unusual thermodynamic signature of a positive heat capacity change (ΔCp = 3.84 kJ mol-1K-1) suggesting the instrumental role of hydrophobic hydration. On the contrary, the 3HF-HSA (B-isoform at pH 9.2) interaction shows qualitatively reverse effect. Consequently, the interaction is found to be characterized by an enthalpy-dominated hydrophobic effect (negative heat capacity change, ΔCp = -1.15 kJ mol-1K-1) which is rationalized on the basis of the nonclassical hydrophobic effect.

Optical properties and magnetic flux-induced electronic band tuning of a T-graphene sheet and nanoribbon.

Tetragonal graphene (T-graphene) is a theoretically proposed dynamically stable, metallic allotrope of graphene. In this theoretical investigation, a tight binding (TB) model is used to unravel the metal to semiconductor transition of this 2D sheet under the influence of an external magnetic flux. In addition, the environment under which the sheet exposes an appreciable direct band gap of 1.41 ± 0.01 eV is examined. Similarly, the electronic band structure of the narrowest armchair T-graphene nanoribbon (NATGNR) also gets modified with different combinations of magnetic fluxes through the elementary rings. The band tuning parameters are critically identified for both systems. It is observed that the induced band gaps vary remarkably with the tuning parameters. We have also introduced an exact analytical approach to address the band structure of the NATGNR in the absence of any magnetic flux. Finally, the optical properties of the sheet and NATGNR are also critically analysed for both parallel and perpendicular polarizations with the help of density functional theory (DFT). Our study predicts that this material and its nanoribbons can be used in optoelectronic devices.

A Bioinspired Light Harvesting System in Aqueous Medium: Highly Efficient Energy Transfer through the Self Assembly of ß-Sheet Nanostructures of Poly-d-Lysine.

Nature has beautifully assembled its light harvesting pigments within protein scaffolds, which ensures a very high energy transfer. Designing a highly efficient artificial bioinspired light harvesting system (LHS) thus requires the nanoscale spatial orientation and electronic control of the associated chromophores. Although DNA has been used as a scaffold to organize chromophores, proteins or polypeptides, however, are very rarely explored. Here, we have developed a highly efficient, artificial, bioinspired LHS using polypeptide (poly-d-lysine, PDL) nanostructures making use of their ß-sheet structure in an aqueous alkaline medium. The chromophores used herein are compatible for an energy transfer process and are nonfluorescent in an aqueous medium but exhibit high fluorescence intensity when bound to the nanostructure of PDL. The close proximity of the chromophores results in an energy transfer efficiency of ∼92% besides generating white light emission at a particular molar ratio between the chromophores.

DNA-Templated Modulation in the Photophysical Properties of a Fluorescent Molecular Rotor Auramine O by Varying the DNA Composition.

This work delineates an integrative approach combining spectroscopic and computational studies to decipher the association-induced fluorescence properties of a fluorescent molecular rotor, viz., auramine O (AuO), after interacting with 20-mer duplex DNA having diverse well-matched base pairs. While exploring the scarcely explored sequence-dependent interaction mechanism of AuO and DNA, we observed that DNA could act as a conducive scaffold to the formation of AuO dimer through noncovalent interactions at lower molecular density. The photophysical properties of AuO depend on the nucleotide compositions as described from sequence-dependent shifting in the emission and absorption maxima. Furthermore, we explored such DNA base pair-dependent fluorescence spectral characteristics of AuO toward discriminating the thermodynamically most stable single nucleotide mismatch in a 20-mer sequence. Our results are interesting and could be useful in developing analogues with further enhanced emission properties toward mismatched DNA sequences.

Engineering topological phase transition and Aharonov-Bohm caging in a flux-staggered lattice.

A tight binding network of diamond shaped unit cells trapping a staggered magnetic flux distribution is shown to exhibit a topological phase transition under a controlled variation of the flux trapped in a cell. A simple real space decimation technique maps a binary flux staggered network into an equivalent Su-Shrieffer-Heeger (SSH) model. In this way, dealing with a subspace of the full degrees of freedom, we show that a topological phase transition can be initiated by tuning the applied magnetic field that eventually simulates an engineering of the numerical values of the overlap integrals in the paradigmatic SSH model. Thus one can use an external agent, rather than monitoring the intrinsic property of a lattice to control the topological properties. This is advantageous from an experimental point of view. We also provide an in-depth description and analysis of the topologically protected edge states, and discuss how, by tuning the flux from outside one can enhance the spatial extent of the Aharonov-Bohm caging of single particle states for any arbitrary period of staggering. This feature can be useful for the study of transport of quantum information. Our results are exact.

Preferential Binding of Thioflavin T to AT-Rich DNA: White Light Emission through Intramolecular Förster Resonance Energy Transfer.

Herein we report the effect of different nucleobase pair compositions on the association-induced fluorescence enhancement property of Thioflavin T (ThT), upon binding with 20 base pair long double-stranded DNA (dsDNA). Analysis of binding and decay constants along with the association (Kass) and dissociation (Kdiss) rate constants obtained from the fluctuation in the fluorescence intensity of ThT after binding with different DNA revealed selective affinity of ThT toward AT-rich dsDNA. Molecular docking also substantiates the experimental results. We also observed that addition of orange-emitting ethidium bromide (EtBr) to cyan-emitting ThT-DNA complexes leads to bright white light emission (WLE) through Förster resonance energy transfer. Additionally, the emission of white light is far greater in the case of intra-DNA strands. Besides endorsing the binding insights of ThT to AT-rich dsDNA, the present investigations open a new perspective for realizing promising WLE from two biomarkers without labeling the DNA.

Spectroscopic probing of the refolding of an unfolded protein through the formation of mixed-micelles.

We report the unfolding of the globular protein, Bovine Serum Albumin (BSA) induced by anionic surfactant sodium dodecyl sulfate (SDS) and subsequently monitored the refolding of this denatured BSA using triblock copolymers F127 and P123 through the formation of mixed micelles. Our study exclusively represents the reversibility of this unfolding-refolding process using pluronic triblock copolymers F127/P123 as refolding agents. We confirm the recovery of its native state from its denatured state estimating the α-helical structure of the denatured protein from the CD data which support our steady state fluorescence spectra monitoring the fluorescence of the intrinsic Trp molecules present in BSA. Time resolved study also corroborates the stepwise recovery of the denatured BSA as well as the reversibility of the processes. Isothermal Titration Calorimetry (ITC) data explain the negligible interactions between the triblock copolymers and the native state of BSA. The high binding constant of SDS and triblock copolymers probably play the crucial role in the stepwise recovery of the unfolded BSA followed by reversibility of the refolding processes through the formation of the mixed micelles. The mechanism of mixed-micelle formation has been substantiated by the fact that the Guanidine Hydrochloride denatured BSA does not react with F127/P123 whereby no recovery of the protein was observed.

Structure, Activity, and Dynamics of Human Serum Albumin in a Crowded Pluronic F127 Hydrogel.

Structure, activity, and dynamics of a plasma protein, human serum albumin (HSA), inside a crowded environment of F127 gel are studied by circular dichroism (CD), fluorescence correlation spectroscopy (FCS), and picosecond time-resolved fluorescence spectroscopy. For this purpose, the protein is covalently labeled by a maleimide dye, 7-(diethylamino)-3-(4-maleimidylphenyl)-4-methyl-coumarin (CPM). The circular dichroism (CD) spectra suggest that the protein is more structured in the gel reflecting about the biological activities of the protein. FCS results demonstrate that compared to that in bulk water (buffer solution), translational diffusion is about 59 times slower inside the F127 gel. This indicates higher translational friction (viscosity) sensed by the probe (CPM). On the contrary, rotational relaxation (and hence, rotational friction) is more or less similar in F127 gel and in bulk water. FCS results further indicate that the time scales of conformational relaxation of the protein are substantially slow inside the crowded environment of F127 gel. The fast component of conformational relaxation is retarded by ∼55 times, and the slow component by ∼20 times. Fluorescence maximum of CPM bound to HSA show a ∼5 nm red shift, implying that the microenvironment of the probe, CPM, is more polar inside the gel. Solvation dynamics of CPM-labeled HSA inside the gel (⟨τs⟩ ∼ 300 ps) is faster compared to that for the protein in bulk water (⟨τs⟩ ∼ 600 ps).

Procrastination among basic science undergraduate medical students in a Caribbean medical school.

This article was migrated. The article was marked as recommended. PURPOSE: The study was conducted to study procrastination behavior among basic science undergraduate medical students using the previously validated procrastination assessment scale students (PASS). Frequency of and reasons for procrastination were compared among different subgroups of respondents. METHODS: The study was conducted during the first two weeks of February 2017 using PASS. Gender, nationality and semester of study of the respondents were noted. PASS explores areas of and frequency of procrastination, reasons for procrastination and interest in changing the behavior. The frequency of procrastination, fear of failure, risk aversiveness, laziness and rebellion against control scores were compared among different subgroups using appropriate statistical tests. RESULTS: A total of 107 students (84.9%) participated in the study. The mean frequency of procrastination score was 32.9 (maximum score 60). The score was significantly correlated with the respondents' gender. With regard to the percentage of students who nearly always or always procrastinated on a task, the percentages with regard to completing assignments, studying for exams, completing reading assignments, academic administrative tasks, attendance tasks and school activities in general were 25.2, 19.7, 25.2, 19.6, 18.7 and 17.7. The mean score for 'fear of failure' and 'aversiveness of task' as described by Solomon and Rothblum was 2.29 and 2.83. The mean scores for fear of failure, risk taking, and laziness were 26.17, 13.76 and 14.32. The median rebellion against control score was 6. Risk taking score was higher among respondents of other nationalities compared to Americans. CONCLUSIONS: Procrastination was regarded as a greater problem with regard to studying for exams and completing reading assignments and preparing for problem-based learning sessions. Only 42% of students were interested in attending a program to overcome procrastination. Similar studies among students during the clinical years are required. A study correlating self-reported procrastination with behavior can be carried out. Procrastination can also be studied in other offshore, Caribbean medical schools.

Using Movies to Strengthen Learning of the Humanistic Aspects of Medicine.

INTRODUCTION: Movie screening and activities have been used during the last two semesters (spring and summer 2015) to strengthen the learning of communication skills, empathy, professionalism, and greater understanding of the process and death and dying at the Xavier University School of Medicine. AIM: The present manuscript describes the movie screening and activities. Student feedback regarding the sessions is also mentioned. SETTINGS AND DESIGN: The activity was conducted among basic science undergraduate medical students and student feedback was obtained. A cross-sectional study design was used. MATERIALS AND METHODS: Feedback was obtained towards the end of June 2015 using a questionnaire designed by the authors. Participants were asked to rate their degree of agreement with the set of statements and provide an overall rating for the sessions. No demographic information was collected. STATISTICAL ANALYSIS: Cronbach's alpha was calculated as a measure of internal consistency. The normality of distribution of the scores of individual statements and of the overall rating was determined using one sample Kolmogorov-Smirnov test. The average scores were calculated. Free text comments were tabulated. RESULTS: Forty-nine of the 63 students (77.8%) participated in the study. Cronbach's alpha was 0.868 indicating a high level of internal consistency. The median scores indicating the degree of agreement with most statements ranged from 3 to 5. The mean participant rating of the sessions was 7.10 (maximum possible score 10). A few participants provided free text comments regarding the sessions. CONCLUSION: Student feedback about the session was positive. Impact of the session on humanistic issues, professionalism and death and dying should be studied in future.

Flat band analogues and flux driven extended electronic states in a class of geometrically frustrated fractal networks.

We demonstrate, by explicit construction, that a single band tight binding Hamiltonian defined on a class of deterministic fractals of the b = 3N Sierpinski type can give rise to an infinity of dispersionless, flat-band like states which can be worked out analytically using the scale invariance of the underlying lattice. The states are localized over clusters of increasing sizes, displaying the existence of a multitude of localization areas. The onset of localization can, in principle, be 'delayed' in space by an appropriate choice of the energy of the electron. A uniform magnetic field threading the elementary plaquettes of the network is shown to destroy this staggered localization and generate absolutely continuous sub-bands in the energy spectrum of these non-translationally invariant networks.

Attitude of Basic Science Medical Students Toward Interprofessional Collaboration.

PURPOSE: Interprofessional collaboration (IPC) and interprofessional education (IPE) are increasingly emphasized in the education of health professions. Xavier University School of Medicine, a Caribbean medical school admits students from the United States, Canada, and other countries to the undergraduate medical course. The present study was carried out to obtain information about the attitude toward IPC among basic science medical students and note differences, if any, among different subgroups. METHODS: The study was conducted among first to fifth semester students during July 2015 using the previously validated Jefferson Scale of Attitudes Toward Interprofessional Collaboration (JeffSATIC). Gender, age, semester, and nationality were noted. Participants' agreement with a set of 20 statements was studied. Mean total scores, working relationship, and accountability scores were calculated and compared among different subgroups of respondents (p<0.05). RESULTS: Sixty-seven of the 71 students (94.4%) participated. Cronbach's alpha value of the questionnaire was 0.827, indicating good internal consistency. The mean total score was 104.48 (maximum score 140) while the working relationship and accountability scores were 63.51 (maximum score 84) and 40.97 (maximum score 56), respectively. Total scores were significantly higher among third-semester students and students of Canadian nationality. Working relationship and accountability scores were higher among first and third-semester students. CONCLUSION: The total working relationship and accountability scores were lower compared to those obtained in a previous study. Opportunities for IPE and IPC during the basic science years should be strengthened. Longitudinal studies in the institution may be helpful. Similar studies in other Caribbean medical schools are required.

Student feedback on problem-based learning processes.

BACKGROUND: Problem-based learning (PBL) sessions consist of a brainstorming phase, search phase, individual study, and reporting phase. At the Xavier University School of Medicine, Aruba, PBL is a new learning modality first introduced in May 2013. AIMS: PBL processes have not been studied previously at the Xavier University School of Medicine, hence the present study was carried out to obtain information about the PBL processes and note differences, if any, among different groups of students. METHOD: The study was conducted among first- to fourth-semester undergraduate medical students during July 2014 using a previously validated PBL processes instrument developed by van den Hurk et al. Information about gender, semester, weekly hours of study, and learning resources used was obtained. Respondents' agreement with a set of 23 statements was noted using a Likert-type scale, which was scored as 1=totally disagree with the statement, 2=disagree, 3=neutral, 4=agree, and 5=totally agree with the statement. Mean scores were compared among different groups of respondents. RESULTS: Fifty-one of the 58 students (87.9 per cent) participated. The weekly average study time was 29.9 hours. Lecture handouts and textbooks were commonly used information sources. The mean scores (scale 1 to 5) for learning-issue-driven searching, and extensiveness of searching were 3.49 and 3.45, respectively. The score for explanation-oriented preparation was 3.94, while those for breadth and depth of discussion were 3.75 and 3.62, respectively. Most scores were higher among second-semester students, but the difference was not significant. CONCLUSION: The self-reported scores were comparable to those reported in previous studies done using the same PBL processes instrument in other medical schools. At Xavier University School of Medicine interactive lectures are the major teaching method and topics covered during PBL are also likely to be covered during lectures, which could influence the scores. The findings of our study providing information about how students function during PBL brainstorming and presentation sessions and how they use different learning resources would be of interest to other medical schools worldwide following a hybrid curriculum. Further studies are required.

Small group effectiveness in a Caribbean medical school's problem-based learning sessions.

PURPOSE: The Tutorial Group Effectiveness Instrument was developed to provide objective information on the effectiveness of small groups. Student perception of small group effectiveness during the problem base learning (PBL) process has not been previously studied in Xavier University School of Medicine (Aruba, Kingdom of the Netherlands); hence, the present study was carried out. METHODS: The study was conducted among second and third semester undergraduate medical students during the last week of September 2013, at Xavier University School of Medicine of the Netherlands. Students were informed about the objectives of the study and invited to participate after obtaining written, informed consent. Demographic information like gender, age, nationality, and whether the respondent had been exposed to PBL before joining the institution was noted. Student perception about small group effectiveness was studied by noting their degree of agreement with a set of 19 statements using a Likert-type scale. RESULTS: Thirty-four of the 37 (91.9%) second and third semester medical students participated in the study. The mean cognitive score was 3.76 while the mean motivational and de-motivational scores were 3.65 and 2.51, respectively. The median cognitive category score was 27 (maximum score 35) while the motivation score was 26 (maximum score 35) and the de-motivational score was 12 (maximum score25). There was no significant difference in scores according to respondents' demographic characteristics. CONCLUSION: Student perception about small group effectiveness was positive. Since most medical schools worldwide already have or are introducing PBL as a learning modality, the Tutorial Group Effectiveness Instrument can provide valuable information about small group functioning during PBL sessions.

Student perception about working in rural United States/Canada after graduation: a study in an offshore Caribbean medical school.

INTRODUCTION: Rural residents of the United States (US) and Canada face problems in accessing healthcare. International medical graduates (IMGs) play an important role in delivering rural healthcare. IMGs from Caribbean medical schools have the highest proportion of physicians in primary care.  Xavier University School of Medicines admits students from the US, Canada and other countries to the undergraduate medical (MD) course and also offers a premedical program. The present study was conducted to obtain student perception about working in rural US/Canada after graduation.   METHODS: The study was conducted among premedical and preclinical undergraduate medical (MD) students during October 2014. The questionnaire used was modified from a previous study. Semester of study, gender, nationality, place of residence and occupation of parents were noted. Information about whether students plan to work in rural US/Canada after graduation, possible reasons why doctors are reluctant to work in rural areas, how the government can encourage rural practice, possible problems respondents anticipate while working in rural areas were among the topics studied. RESULTS: Ninety nine of the 108 students (91.7%) participated. Forty respondents were in favor of working in rural US/Canada after graduation. Respondents mentioned good housing, regular electricity, water supply, telecommunication facilities, and schools for education of children as important conditions to be fulfilled. The government should provide higher salaries to rural doctors, help with loan repayment, and provide opportunities for professional growth.  Potential problems mentioned were difficulty in being accepted by the rural community, problems in convincing patients to follow medical advice, lack of exposure to rural life among the respondents, and cultural issues. CONCLUSIONS: About 40% of respondents would consider working in rural US/Canada. Conditions required to be fulfilled have been mentioned above. Graduates from Caribbean medical schools have a role in addressing rural physician shortage. Similar studies in other offshore Caribbean medical schools are required as Caribbean IMGs make an important contribution to the rural US and Canadian health workforce.